An XML transfer schema for exchange of genomic and genetic mapping data: implementation as a web service in a Taverna workflow

<p>Abstract</p> <p>Background</p> <p>Genomic analysis, particularly for less well-characterized organisms, is greatly assisted by performing comparative analyses between different types of genome maps and across species boundaries. Various providers publish a plethora of on-line resources collating genome mapping data from a multitude of species. Datasources range in scale and scope from small bespoke resources for particular organisms, through larger web-resources containing data from multiple species, to large-scale bioinformatics resources providing access to data derived from genome projects for model and non-model organisms. The heterogeneity of information held in these resources reflects both the technologies used to generate the data and the target users of each resource. Currently there is no common information exchange standard or protocol to enable access and integration of these disparate resources. Consequently data integration and comparison must be performed in an <it>ad hoc </it>manner.</p> <p>Results</p> <p>We have developed a simple generic XML schema (GenomicMappingData.xsd – GMD) to allow export and exchange of mapping data in a common lightweight XML document format. This schema represents the various types of data objects commonly described across mapping datasources and provides a mechanism for recording relationships between data objects. The schema is sufficiently generic to allow representation of any map type (for example genetic linkage maps, radiation hybrid maps, sequence maps and physical maps). It also provides mechanisms for recording data provenance and for cross referencing external datasources (including for example ENSEMBL, PubMed and Genbank.). The schema is extensible via the inclusion of additional datatypes, which can be achieved by importing further schemas, e.g. a schema defining relationship types. We have built demonstration web services that export data from our ArkDB database according to the GMD schema, facilitating the integration of data retrieval into Taverna workflows.</p> <p>Conclusion</p> <p>The data exchange standard we present here provides a useful generic format for transfer and integration of genomic and genetic mapping data. The extensibility of our schema allows for inclusion of additional data and provides a mechanism for typing mapping objects via third party standards. Web services retrieving GMD-compliant mapping data demonstrate that use of this exchange standard provides a practical mechanism for achieving data integration, by facilitating syntactically and semantically-controlled access to the data.</p

Purple sulfur bacteria fix N-2 via molybdenum-nitrogenase in a low molybdenum Proterozoic ocean analogue

Biological N-2 fixation was key to the expansion of life on early Earth. The N-2-fixing microorganisms and the nitrogenase type used in the Proterozoic are unknown, although it has been proposed that the canonical molybdenum-nitrogenase was not used due to low molybdenum availability. We investigate N-2 fixation in Lake Cadagno, an analogue system to the sulfidic Proterozoic continental margins, using a combination of biogeochemical, molecular and single cell techniques. In Lake Cadagno, purple sulfur bacteria (PSB) are responsible for high N-2 fixation rates, to our knowledge providing the first direct evidence for PSB in situ N-2 fixation. Surprisingly, no alternative nitrogenases are detectable, and N-2 fixation is exclusively catalyzed by molybdenum-nitrogenase. Our results show that molybdenum-nitrogenase is functional at low molybdenum conditions in situ and that in contrast to previous beliefs, PSB may have driven N-2 fixation in the Proterozoic ocean. N-2 fixation was key to the expansion of life on Earth, but which organisms fixed N-2 and if Mo-nitrogenase was functional in the low Mo early ocean is unknown. Here, the authors show that purple sulfur bacteria fix N-2 using Mo-nitrogenase in a Proterozoic ocean analogue, despite low Mo conditions

PHI-base update: additions to the pathogen–host interaction database

The pathogen–host interaction database (PHI-base) is a web-accessible database that catalogues experimentally verified pathogenicity, virulence and effector genes from bacterial, fungal and Oomycete pathogens, which infect human, animal, plant, insect, fish and fungal hosts. Plant endophytes are also included. PHI-base is therefore an invaluable resource for the discovery of genes in medically and agronomically important pathogens, which may be potential targets for chemical intervention. The database is freely accessible to both academic and non-academic users. This publication describes recent additions to the database and both current and future applications. The number of fields that characterize PHI-base entries has almost doubled. Important additional fields deal with new experimental methods, strain information, pathogenicity islands and external references that link the database to external resources, for example, gene ontology terms and Locus IDs. Another important addition is the inclusion of anti-infectives and their target genes that makes it possible to predict the compounds, that may interact with newly identified virulence factors. In parallel, the curation process has been improved and now involves several external experts. On the technical side, several new search tools have been provided and the database is also now distributed in XML format. PHI-base is available at: http://www.phi-base.org/

Data-driven campaigning and democratic disruption : evidence from six advanced democracies

Data-driven campaigning has become one of the key foci for academic and non-academic audiences interested in political communication. Widely seen to have transformed political practice, it is often argued that data-driven campaigning is a force of significant democratic disruption because it contributes to a fragmentation of political discourse, undermines prevailing systems of electoral accountability and subverts ‘free’ and ‘fair’ elections. In this article, we present one of the very first cross-national analyses of data-driven campaigning by political parties. Drawing on empirical research conducted by experts in six advanced democracies, we show that the data-driven campaign practices seen to threaten democracy are often not manifest in party campaigns. Instead, we see a set of practices that build on pre-existing techniques and which are far less sophisticated than is often assumed. Indeed, we present evidence that most political parties lack the capacity to execute the hyper-intensive practices often associated with data-driven campaigning. Hence, while there is reason to remain alert to the challenges data-driven campaigning produces for democratic norms, we argue that this practice is not inherently disruptive, but rather exemplifies the evolving nature of political campaigning in the 21st century

Biofunctional Nanodot Arrays in Living Cells Uncover Synergistic Co-Condensation of Wnt Signalodroplets

Qualitative and quantitative analysis of transient signaling platforms in the plasma membrane has remained a key experimental challenge. Here, biofunctional nanodot arrays (bNDAs) are developed to spatially control dimerization and clustering of cell surface receptors at the nanoscale. High-contrast bNDAs with spot diameters of ≈300 nm are obtained by capillary nanostamping of bovine serum albumin bioconjugates, which are subsequently biofunctionalized by reaction with tandem anti-green fluorescence protein (GFP) clamp fusions. Spatially controlled assembly of active Wnt signalosomes is achieved at the nanoscale in the plasma membrane of live cells by capturing the co-receptor Lrp6 into bNDAs via an extracellular GFP tag. Strikingly, co-recruitment is observed of co-receptor Frizzled-8 as well as the cytosolic scaffold proteins Axin-1 and Disheveled-2 into Lrp6 nanodots in the absence of ligand. Density variation and the high dynamics of effector proteins uncover highly cooperative liquid-liquid phase separation (LLPS)-driven assembly of Wnt "signalodroplets" at the plasma membrane, pinpointing the synergistic effects of LLPS for Wnt signaling amplification. These insights highlight the potential of bNDAs for systematically interrogating nanoscale signaling platforms and condensation at the plasma membrane of live cells

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

MPHASYS: a mouse phenotype analysis system

<p>Abstract</p> <p>Background</p> <p>Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery.</p> <p>Results</p> <p>Here we introduce a Mouse Phenotype Analysis System (MPHASYS), a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd.</p> <p>Conclusion</p> <p>MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p

Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.</p> <p>Methods</p> <p>Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.</p> <p>Results</p> <p>The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both <it>in vitro </it>and <it>in vivo </it>after transplantation into regenerating muscle of immunodeficient mice.</p> <p>Conclusions</p> <p>Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess <it>in vivo </it>the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.</p