EuroPhenome: a repository for high-throughput mouse phenotyping data.

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.

ViralZone: recent updates to the virus knowledge resource.

ViralZone (http://viralzone.expasy.org) is a knowledge repository that allows users to learn about viruses including their virion structure, replication cycle and host-virus interactions. The information is divided into viral fact sheets that describe virion shape, molecular biology and epidemiology for each viral genus, with links to the corresponding annotated proteomes of UniProtKB. Each viral genus page contains detailed illustrations, text and PubMed references. This new update provides a linked view of viral molecular biology through 133 new viral ontology pages that describe common steps of viral replication cycles shared by several viral genera. This viral cell-cycle ontology is also represented in UniProtKB in the form of annotated keywords. In this way, users can navigate from the description of a replication-cycle event, to the viral genus concerned, and the associated UniProtKB protein records.

The branch-site test of positive selection is surprisingly robust but lacks power under synonymous substitution saturation and variation in GC

Positive selection is widely estimated from protein coding sequence alignments by the nonsynonymous-to-synonymous ratio omega. Increasingly elaborate codon models are used in a likelihood framework for this estimation. Although there is widespread concern about the robustness of the estimation of the omega ratio, more efforts are needed to estimate this robustness, especially in the context of complex models. Here, we focused on the branch-site codon model. We investigated its robustness on a large set of simulated data. First, we investigated the impact of sequence divergence. We found evidence of underestimation of the synonymous substitution rate for values as small as 0.5, with a slight increase in false positives for the branch-site test. When dS increases further, underestimation of dS is worse, but false positives decrease. Interestingly, the detection of true positives follows a similar distribution, with a maximum for intermediary values of dS. Thus, high dS is more of a concern for a loss of power (false negatives) than for false positives of the test. Second, we investigated the impact of GC content. We showed that there is no significant difference of false positives between high GC (up to similar to 80%) and low GC (similar to 30%) genes. Moreover, neither shifts of GC content on a specific branch nor major shifts in GC along the gene sequence generate many false positives. Our results confirm that the branch-site is a very conservative test.

Rhea-a manually curated resource of biochemical reactions.

Rhea (http://www.ebi.ac.uk/rhea) is a comprehensive resource of expert-curated biochemical reactions. Rhea provides a non-redundant set of chemical transformations for use in a broad spectrum of applications, including metabolic network reconstruction and pathway inference. Rhea includes enzyme-catalyzed reactions (covering the IUBMB Enzyme Nomenclature list), transport reactions and spontaneously occurring reactions. Rhea reactions are described using chemical species from the Chemical Entities of Biological Interest ontology (ChEBI) and are stoichiometrically balanced for mass and charge. They are extensively manually curated with links to source literature and other public resources on metabolism including enzyme and pathway databases. This cross-referencing facilitates the mapping and reconciliation of common reactions and compounds between distinct resources, which is a common first step in the reconstruction of genome scale metabolic networks and models.

Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines.

Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients.

T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension.

This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10,000 residues and is available from both http://www.tcoffee.org and its main mirror http://tcoffee.crg.cat.

Unification of multi-species vertebrate anatomy ontologies for comparative biology in Uberon.

BACKGROUND: Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent 'natural' phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes. RESULTS: Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued. CONCLUSIONS: The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. THE ONTOLOGY RELEASE FILES ASSOCIATED WITH THE ONTOLOGY MERGE DESCRIBED IN THIS MANUSCRIPT ARE AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ CURRENT ONTOLOGY RELEASE FILES ARE AVAILABLE ALWAYS AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/

Local alignment refinement using structural assessment.

Homology modeling is the most commonly used technique to build a three-dimensional model for a protein sequence. It heavily relies on the quality of the sequence alignment between the protein to model and related proteins with a known three dimensional structure. Alignment quality can be assessed according to the physico-chemical properties of the three dimensional models it produces.In this work, we introduce fifteen predictors designed to evaluate the properties of the models obtained for various alignments. They consist of an energy value obtained from different force fields (CHARMM, ProsaII or ANOLEA) computed on residue selected around misaligned regions. These predictors were evaluated on ten challenging test cases. For each target, all possible ungapped alignments are generated and their corresponding models are computed and evaluated.The best predictor, retrieving the structural alignment for 9 out of 10 test cases, is based on the ANOLEA atomistic mean force potential and takes into account residues around misaligned secondary structure elements. The performance of the other predictors is significantly lower. This work shows that substantial improvement in local alignments can be obtained by careful assessment of the local structure of the resulting models.

La flexibilité du temps de travail: entre autonomie et contraintes. Une étude de cas en Suisse.

Flexitime : between autonomy and constraints. A case study in SwitzerlandBy looking at how a new regulation is translated into everyday practices, this dissertation explores through a specific case study the degree of autonomy gained by wage-earners with the introduction of flexible working schedules. The guiding hypothesis is that by introducing procedural rules, flexitime opens the space for more daily negotiations, therefore reinforcing the effects of power relations inherent to employment relationships. The goal is to understand, through a sociological approach, how employees experience a form of working time that transfers responsibility for time management to them, and howthey integrate work-related constraints with their life outside the workplace. The first part of the dissertation sets up the context of the case study. It offers a definition of flexibility by situating it in the broader history of work time, as well as in relation to various organizational forms and cultural transformations. An international literature review and a focus on the Swiss case are offered. In the second part, the focus is narrowed to a specificSwiss firm specialized in mail-order, where a system of individualized management of annual work time has been introduced. By combining a quantitative and qualitative approach, it is possible to analyze determinants of the practices internal to the firm anddeterminants related to employees themselves, as well as the way in which employees articulate these two orders of constraints. The results show that the implementation of flexible working time is not affecting daily negotiation practices so much as it is creating a set of informal rules. The autonomy ofwage-earners is expressed first and foremost through their capacity to produce, negotiate, and legitimate these rules. The intraindividual level has proven to be central for the social regulation of flexible working time. It is not so much a question of legitimation, but rather the process of institutionalization nurtured by the energy invested by wage-earners in their personal quest for a compromise between their various roles, identities, and aspirations. It is this individualized regulation that is ensuring the success of the system under study.

Climate Change, Neutrality and the Harm Principle

This paper aims at evaluating the compatibility of coercive climate policies with liberal neutrality. More precisely, it focuses on the doctrine of state neutrality as associated with the "harm principle". It argues that given the difficulty of attributing causal responsibilities for climate harms to individuals, the harm principle doesn't work in this case, at least if one endorses a liberal atomistic ontology. Furthermore, the definition of what constitutes climate harms implies making moral assumptions, which makes it impossible to justify climate policies in a neutral way. Finally, the paper shows another consequence of applying neutrality to the case of climate change, that is the risk of a shift from political forms of decision-making to technocracy. Focusing too much on liberty of choice may (paradoxically) be to the detriment of political freedom. The paper concludes that climate change is an intrinsically moral issue and that it should be the occasion of a political debate about our current values and lifestyles. It should not be reduced to a mere question of carbon metric.

Peatlands and plantations in Sumatra, Indonesia : Complex realities for resource governance, rural development and climate change mitigation

Peatlands play a crucial role in Indonesia's economic development, and in its stated goal of reducing greenhouse gas emissions. Improved peatland management - including a national moratorium on the granting of any new conversion licenses - forms a cornerstone of Indonesia's climate change mitigation commitment. At the same time, rapid expansion of the plantation sector is driving wide-scale drainage and conversion of peat swamp ecosystems. The province of Riau, in central Sumatra, finds itself at the crossroads of these conflicting agendas. This essay presents a case study of three islands on Riau's east coast affected by industrial timber plantation concessions. It examines the divergent experiences, perceptions and responses of communities on the islands. A mix of dramatic protests, localised everyday actions and constructive dialogue has succeeded in delaying or perhaps halting one of the concessions, while negotiations and contestation with the other two continue. With the support of regional and national non-governmental organisations and local government, communities are pursuing alternative development strategies, including the cultivation of sago, which requires no peat drainage. While a powerful political economy of state and corporate actors shapes the contours of socio-environmental change, local social movements can alter trajectories of change, promoting incremental improvements and alternative pathways.

Interdependency management in universities: a case study

There remains uncertainty in scientific discussions regarding the governance of universities in new public management regimes in terms of who actually 'rules' in the university. Apparently, a strengthened management leadership is confronted with continuing elements of academic self-regulation and professional autonomy in knowledge production and diffusion. Organisational and academic rationales coexist in today's management of universities. This article endeavours to clarify some of the ambiguities pertaining to the coexistence of two authorities by demonstrating the working of 'interdependency management' that is taking place within universities. For this purpose, the authors have scrutinised research, teaching and recruitment policies in one Swiss university that is subject to such ambiguities. The study confirms existing research in that a command-and-control system is not applied. Policymaking in universities is instead based on a mix of negotiations in faculties that are taking place in the 'shadow of hierarchy', negotiated bargaining between faculties and leaders and occasional unilateral decisions of leaders. This mitigates latent conflicts between management and the academic community: strategic orientations of the university are generally accepted by the academic community while the academic community has influence on policy formulation and maintains defining powers over policy substance.

Comparison of differential gene expression to water stress among bacteria with relevant pollutant-degradation properties.

Resistance to semi-dry environments has been considered a crucial trait for superior growth and survival of strains used for bioaugmentation in contaminated soils. In order to compare water stress programmes, we analyse differential gene expression among three phylogenetically different strains capable of aromatic compound degradation: Arthrobacter chlorophenolicus A6, Sphingomonas wittichii RW1 and Pseudomonas veronii 1YdBTEX2. Standardized laboratory-induced water stress was imposed by shock exposure of liquid cultures to water potential decrease, induced either by addition of solutes (NaCl, solute stress) or by addition of polyethylene glycol (matric stress), both at absolute similar stress magnitudes and at those causing approximately similar decrease of growth rates. Genome-wide differential gene expression was recorded by micro-array hybridizations. Growth of P. veronii 1YdBTEX2 was the most sensitive to water potential decrease, followed by S. wittichii RW1 and A. chlorophenolicus A6. The number of genes differentially expressed under decreasing water potential was lowest for A. chlorophenolicus A6, increasing with increasing magnitude of the stress, followed by S. wittichii RW1 and P. veronii 1YdBTEX2. Gene inspection and gene ontology analysis under stress conditions causing similar growth rate reduction indicated that common reactions among the three strains included diminished expression of flagellar motility and increased expression of compatible solutes (which were strain-specific). Furthermore, a set of common genes with ill-defined function was found between all strains, including ABC transporters and aldehyde dehydrogenases, which may constitute a core conserved response to water stress. The data further suggest that stronger reduction of growth rate of P. veronii 1YdBTEX2 under water stress may be an indirect result of the response demanding heavy NADPH investment, rather than the presence or absence of a suitable stress defence mechanism per se.