Transcriptional feedback in the insulin signalling pathway modulates ageing in both Caenorhabditis elegans and Drosophila melanogaster.

Several components have been previously identified, that modulate longevity in several species, including the target of rapamycin (TOR) and the Insulin/IGF-1 (IIS) signalling pathways. In order to infer paths and transcriptional feedback loops that are likely to modulate ageing, we manually built a comprehensive and computationally efficient signalling network model of the IIS and TOR pathways in worms. The core insulin transduction is signalling from the sole insulin receptor daf-2 to ultimately inhibit the translocation of the transcription factor daf-16 into the nucleus. Reduction in this core signalling is thought to increase longevity in several species. In addition to this core insulin signalling, we have also recorded in our worm model the transcription factors skn-1 and hif-1, those are also thought to modulate ageing in a daf-16 independent manner. Several paths that are likely to modulate ageing were inferred via a web-based service NetEffects, by utilising perturbed components (rheb-1, let-363, aak-2, daf-2;daf-16 and InR;foxo in worms and flies respectively) from freely available gene expression microarrays. These included "routes" from TOR pathway to transcription factors daf-16, skn-1, hif-1 and daf-16 independent paths via skn-1/hif-1. Paths that could be tested by experimental hypotheses, with respect to relative contribution to longevity, are also discussed. Direct comparison of the IIS and TOR pathways in both worm and fly suggest a remarkable similarity. While similarities in the paths that could modulate ageing in both organisms were noted, differences are also discussed. This approach can also be extended to other pathways and processes

Tourism sustainability methodologies: A critical assessment

In an era of economic crisis and serious environmental constraints, the transition to sustainability enters dynamically the debate over long-term preservation and welfare at a systemic level. Tourism is a resource- (capital, human and natural) demanding sector; this paper explores the variety and diversity of methodological approaches and tools employed in the evaluation of tourism, and their potential to support sustainability-oriented assessments and practices. Ranging from traditional economics-oriented frameworks to assessments of impact and ecological footprint, this paper discusses the prevailing assessment frameworks of specific tourism dimensions heading towards the integrative approaches for Tourism Sustainability Assessment. The review highlights that despite the widespread acceptance of the concept and the international consensus on the importance of its operationalization, the transition towards tourism sustainability remains still a complicated and rather problematic endeavour. © 2014 IEEE

Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing.

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects

Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling

FoxO transcription factors, inhibited by insulin/insulin-like growth factor signalling (IIS), are crucial players in numerous organismal processes including lifespan. Using genomic tools, we uncover over 700 direct dFOXO targets in adult female Drosophila. dFOXO is directly required for transcription of several IIS components and interacting pathways, such as TOR, in the wild-type fly. The genomic locations occupied by dFOXO in adults are different from those observed in larvae or cultured cells. These locations remain unchanged upon activation by stresses or reduced IIS, but the binding is increased and additional targets activated upon genetic reduction in IIS. We identify the part of the IIS transcriptional response directly controlled by dFOXO and the indirect effects and show that parts of the transcriptional response to IIS reduction do not require dfoxo. Promoter analyses revealed GATA and other forkhead factors as candidate mediators of the indirect and dfoxoindependent effects. We demonstrate genome-wide evolutionary conservation of dFOXO targets between the fly and the worm Caenorhabditis elegans, enriched for a second tier of regulators including the dHR96/daf-12 nuclear hormone receptor. Molecular Systems Biology 7: 502; published online 21 June 2011; doi:10.1038/msb.2011.3

RECENT SEDIMENTARY PROCESSES IN THE WESTERN GULF OF CORINTH, GREECE: SEISMIC AND ASEISMIC TURBITIDES

Η παρούσα εργασία στοχεύει στην μελέτη και ανάδειξη των σύγχρονων διεργασιών ιζηματογένεσης στον δυτικό Κορινθιακό κόλπο μέσα από μια σειρά εργαστηριακών αναλύσεων σε ιζήματα πυρήνων ιζήματος. Δύο πυρήνες βαρύτητας μήκους περίπου 1μ. από την περιοχή ενός υποθαλάσσιου καναλιού μεταφοράς ιζημάτων επιλέχθηκαν προς ανάλυση. Σε αυτούς μελετήθηκαν οι ιζηματογενείς ιστολογικές δομές μέσω οπτικών παρατηρήσεων και ακτινογραφήσεων (Χ rays), η κοκκομετρική κατανομή και η ορυκτολογική σύσταση των ιζημάτων τους, ενώ πραγματοποιήθηκαν επίσης χημικές αναλύσεις προσδιορισμού της φυσικής ραδιενέργειας (226Ra, 232Th, 40K ) και ραδιοχρονολογήσεις (14C). Η σύνθεση όλων των παραπάνω, φανερώνει το μοντέλο ιζηματογένεσης του καναλιού κατά το οποίο, ημιπελαγικές ακολουθίες διακόπτονται από αμμώδεις τουρβιδίτες οι οποίοι ενίοτε αποτελούν συνέπεια κάποιου σεισμικού γεγονότος (σεισμικοί τουρβιδίτες). Τα θαλάσσια ρεύματα της περιοχής, ο τεκτονισμός, και οι παροχές των ποταμών που εκβάλουν στον δυτικό Κορινθιακό κόλπο, επηρεάζουν καθοριστικά τις διεργασίες και τον ρυθμό ιζηματογένεσης ο οποίος μειώνεται προς τα ανατολικά κατά μήκος του καναλιού από 2.57 mm/yr σε 0.67 mm/yr.The Corinth rift is counted among the most active tectonic grabens in the world, with extension rates up to 15 mm/yr (Western part). These high extension rates are associated with very strong seismic events that are, occasionally, responsible for submarine mass movements. These movements, their consequential bottom currents, and the differential river-discharging sediment accumulation in the whole gulf, strongly affect the modern marine sedimentary processes. The definition and understanding of these processes is the main aim of this project. This is attempted through via sedimentological, mineral and geochemical analyses on sediment samples from two ~1.1 m long, sediment cores from a WE submarine canyon (10 km long, 3 km wide) that lies in the Western tip of the gulf. The general sedimentation motif reveals the presence of hemipelagic deposits which are occasionally interrupted by sandy turbidites. Occasionally, these turbidites seem to have seismic origin. The sedimentation rates range between 2.57 mm/yr in the western part and 0.67 mm/yr in the eastern part

Gramene 2018: unifying comparative genomics and pathway resources for plant research

Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramene's Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene-gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces

A call for public archives for biological image data

Public data archives are the backbone of modern biological and biomedical research. While archives for biological molecules and structures are well-established, resources for imaging data do not yet cover the full range of spatial and temporal scales or application domains used by the scientific community. In the last few years, the technical barriers to building such resources have been solved and the first examples of scientific outputs from public image data resources, often through linkage to existing molecular resources, have been published. Using the successes of existing biomolecular resources as a guide, we present the rationale and principles for the construction of image data archives and databases that will be the foundation of the next revolution in biological and biomedical informatics and discovery.Comment: 13 pages, 1 figur

Early childhood pedagogies: spaces for young children to flourish

This paper introduces the Special Issue of Early Child Development and Care focused on Early Childhood Pedagogy. It opens by considering past and present discourses concerning early childhood pedagogy, and focus is given to established philosophical underpinnings in the field and their translation to contemporary guidance, alongside research and policy. It is argued that early childhood pedagogy is a contested, complex and diverse space, yet these factors are entirely appropriate for supporting young children to flourish as valued individuals in different contexts. Building on this argument, it is posited that it may be more appropriate to discuss early childhood pedagogies rather than early childhood pedagogy. The paper goes on to critique a range of established early childhood pedagogies, before introducing 18 papers from across the world that make exciting new contributions to the discourse. It is intended that this collection will inspire new debates and fresh endeavours concerning early childhood pedagogies

Clostridium difficile infection.

Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota