Contribuciones para el aprendizaje de las Ciencias de la Tierra, desde un espacio de educación no formal

El presente trabajo da a conocer una serie de actividades planificadas y realizadas desde un espacio de Educación no formal como es el Museo de Ciencias Naturales y Antropológicas "Prof. Antonio Serrano", en la Ciudad de Paraná Entre Ríos, con el objetivo de promover el conocimiento de las Ciencias de la Tierra. Las mismas son proyectadas con el fin de contribuir a acortar la distancia existente entre el conocimiento geológico producido por los científicos y el conocimiento de la sociedad. Se clasifican en cuatro ejes interrelacionados entre sí; el eje Investigación y sus productos, agrupa acciones destinadas a la producción del conocimiento geológico provincial y su sociabilización, publicadas en revistas, libros, jornadas y congresos; el eje didáctico presenta actividades relacionadas con la enseñanza de las Ciencias de la Tierra, efectuando trabajos interdisciplinarios entre el Museo y las instituciones educativas; el eje académico y de extensión concentra tareas de capacitación y extensión con entidades culturales y educativas; por último el eje infraestructura destinado a fomentar la creación de espacios dinámicos, dentro y fuera ámbito del Museo. Evaluadores externos e internos, nos motivan a generar acciones de mejora continua, dirigidas a mantener la calidad en los distintos ejes, como también a proyectar nuevas propuestas. La creciente demanda de las actividades didácticas, reflejan que los objetivos planteados están siendo alcanzados y en algunos casos superados; respondiendo así el Museo Serrano a las necesidades de la comunidad.Trabajos del área Ciencias NaturalesDepartamento de Ciencias Exactas y Naturale

Whole-genome microarrays of fission yeast: characteristics, accuracy, reproducibility, and processing of array data

Background: The genome of the fission yeast Schizosaccharomyces pombe has recently been sequenced, setting the stage for the post-genomic era of this increasingly popular model organism. We have built fission yeast microarrays, optimised protocols to improve array performance, and carried out experiments to assess various characteristics of microarrays.|Results: We designed PCR primers to amplify specific probes (180-500 bp) for all known and predicted fission yeast genes, which are printed in duplicate onto separate regions of glass slides together with control elements (similar to13,000 spots/slide). Fluorescence signal intensities depended on the size and intragenic position of the array elements, whereas the signal ratios were largely independent of element properties. Only the coding strand is covalently linked to the slides, and our array elements can discriminate transcriptional direction. The microarrays can distinguish sequences with up to 70% identity, above which cross-hybridisation contributes to the signal intensity. We tested the accuracy of signal ratios and measured the reproducibility of array data caused by biological and technical factors. Because the technical variability is lower, it is best to use samples prepared from independent biological experiments to obtain repeated measurements with swapping of fluorochromes to prevent dye bias. We also developed a script that discards unreliable data and performs a normalization to correct spatial artefacts.|Conclusions: This paper provides data for several microarray properties that are rarely measured. The results define critical parameters for microarray design and experiments and provide a framework to optimise and interpret array data. Our arrays give reproducible and accurate expression ratios with high sensitivity. The scripts for primer design and initial data processing as well as primer sequences and detailed protocols are available from our website

Optimisation of the Schizosaccharomyces pombe urg1 expression system

The ability to study protein function in vivo often relies on systems that regulate the presence and absence of the protein of interest. Two limitations for previously described transcriptional control systems that are used to regulate protein expression in fission yeast are: the time taken for inducing conditions to initiate transcription and the ability to achieve very low basal transcription in the "OFF-state". In previous work, we described a Cre recombination-mediated system that allows the rapid and efficient regulation of any gene of interest by the urg1 promoter, which has a dynamic range of approximately 75-fold and which is induced within 30-60 minutes of uracil addition. In this report we describe easy-to-use and versatile modules that can be exploited to significantly tune down P urg1 "OFF-levels" while maintaining an equivalent dynamic range. We also provide plasmids and tools for combining P urg1 transcriptional control with the auxin degron tag to help maintain a null-like phenotype. We demonstrate the utility of this system by improved regulation of HO-dependent site-specific DSB formation, by the regulation Rtf1-dependent replication fork arrest and by controlling Rhp18(Rad18)-dependent post replication repair

FYPO: the fission yeast phenotype ontology.

MOTIVATION: To provide consistent computable descriptions of phenotype data, PomBase is developing a formal ontology of phenotypes observed in fission yeast. RESULTS: The fission yeast phenotype ontology (FYPO) is a modular ontology that uses several existing ontologies from the open biological and biomedical ontologies (OBO) collection as building blocks, including the phenotypic quality ontology PATO, the Gene Ontology and Chemical Entities of Biological Interest. Modular ontology development facilitates partially automated effective organization of detailed phenotype descriptions with complex relationships to each other and to underlying biological phenomena. As a result, FYPO supports sophisticated querying, computational analysis and comparison between different experiments and even between species. AVAILABILITY: FYPO releases are available from the Subversion repository at the PomBase SourceForge project page (https://sourceforge.net/p/pombase/code/HEAD/tree/phenotype_ontology/). The current version of FYPO is also available on the OBO Foundry Web site (http://obofoundry.org/)

Recovery for all in the community:Position paper on principles and key elements of community-based mental health care

Backgroud:Service providers throughout Europe have identified the need to define how high-quality community-based mental health care looks to organize their own services and to inform governments, commissioners and funders. In 2016, representatives of mental health care service providers, networks, umbrella organizations and knowledge institutes in Europe came together to establish the European Community Mental Health Services Provider (EUCOMS) Network. This network developed a shared vision on the principles and key elements of community mental health care in different contexts. The result is a comprehensive consensus paper, of which this position paper is an outline. With this paper the network wants to contribute to the discussion on how to improve structures in mental healthcare, and to narrow the gap between evidence, policy and practice in Europe.Main text:The development of the consensus paper started with an expert workshop in April 2016. An assigned writing group representing the workshop participants built upon the outcomes of this meeting and developed the consensus paper with the input from 100 European counterparts through two additional work groups, and two structured feedback rounds via email. High quality community-based mental health care: 1) protects human rights; 2) has a public health focus; 3) supports service users in their recovery journey; 4) makes use of effective interventions based on evidence and client goals; 5) promotes a wide network of support in the community and; 6) makes use of peer expertise in service design and delivery. Each principle is illustrated with good practices from European service providers that are members of the EUCOMS Network.Conclusions:Discussion among EUCOMS network members resulted in a blueprint for a regional model of integrated mental health care based upon six principles.</p

LaSSO, a strategy for genome-wide mapping of intronic lariats and branch points using RNA-seq

Both canonical and alternative splicing of RNAs are governed by intronic sequence elements and produce transient lariat structures fastened by branch points within introns. To map precisely the location of branch points on a genomic scale, we developed LaSSO (Lariat Sequence Site Origin), a data-driven algorithm which utilizes RNA-seq data. Using fission yeast cells lacking the debranching enzyme Dbr1, LaSSO not only accurately identified canonical splicing events, but also pinpointed novel, but rare, exon-skipping events, which may reflect aberrantly spliced transcripts. Compromised intron turnover perturbed gene regulation at multiple levels, including splicing and protein translation. Notably, Dbr1 function was also critical for the expression of mitochondrial genes and for the processing of self-spliced mitochondrial introns. LaSSO showed better sensitivity and accuracy than algorithms used for computational branch-point prediction or for empirical branch-point determination. Even when applied to a human data set acquired in the presence of debranching activity, LaSSO identified both canonical and exon-skipping branch points. LaSSO thus provides an effective approach for defining high-resolution maps of branch-site sequences and intronic elements on a genomic scale. LaSSO should be useful to validate introns and uncover branch-point sequences in any eukaryote, and it could be integrated into RNA-seq pipelines

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects

Background: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. Methods: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. Results: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 μmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). Conclusions: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus

Virtual Mutagenesis of the Yeast Cyclins Genetic Network Reveals Complex Dynamics of Transcriptional Control Networks

Study of genetic networks has moved from qualitative description of interactions between regulators and regulated genes to the analysis of the interaction dynamics. This paper focuses on the analysis of dynamics of one particular network – the yeast cyclins network. Using a dedicated mathematical model of gene expression and a procedure for computation of the parameters of the model from experimental data, a complete numerical model of the dynamics of the cyclins genetic network was attained. The model allowed for performing virtual experiments on the network and observing their influence on the expression dynamics of the genes downstream in the regulatory cascade. Results show that when the network structure is more complicated, and the regulatory interactions are indirect, results of gene deletion are highly unpredictable. As a consequence of quantitative behavior of the genes and their connections within the network, causal relationship between a regulator and target gene may not be discovered by gene deletion. Without including the dynamics of the system into the network, its functional properties cannot be studied and interpreted correctly

Antibody Vh Repertoire Differences between Resolving and Chronically Evolving Hepatitis C Virus Infections

Despite the production of neutralizing antibodies to hepatitis C virus (HCV), many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(D)J region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR), 9 patients with a newly diagnosed chronically evolving infection (CE), and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naïve B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naïve B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion