Economic interests cloud hazard reductions in the European regulation of substances of very high concern

Here we investigate how the conflicts between hazard reduction and economic interests have shaped the regulation of substances of very high concern (SVHCs) under the Authorization program of the European chemical regulation Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH). Since regulation starts with listing SVHCs on the Candidate List, we analyze the relative importance of toxicological properties, economic motivations, and available scientific knowledge on the probability of inclusion on the Candidate List. We find that the most important factor in whether a substance is listed is whether it is being produced in, or imported into, the European Economic Area (EEA), with the regulators less likely to place a substance on the list if it is currently being produced or imported in the EEA. This evidence suggests that regulators have listed chemicals of secondary importance leading to lesser than anticipated hazard reductions, either because production and imports had already ceased before the listing, or because the compound has never been produced or imported in the EEA at all

Statistical evaluation of methods for identification of differentially abundant genes in comparative metagenomics

Background: Metagenomics is the study of microbial communities by sequencing of genetic material directly from environmental or clinical samples. The genes present in the metagenomes are quantified by annotating and counting the generated DNA fragments. Identification of differentially abundant genes between metagenomes can provide important information about differences in community structure, diversity and biological function. Metagenomic data is however high-dimensional, contain high levels of biological and technical noise and have typically few biological replicates. The statistical analysis is therefore challenging and many approaches have been suggested to date. Results: In this article we perform a comprehensive evaluation of 14 methods for identification of differentially abundant genes between metagenomes. The methods are compared based on the power to detect differentially abundant genes and their ability to correctly estimate the type I error rate and the false discovery rate. We show that sample size, effect size, and gene abundance greatly affect the performance of all methods. Several of the methods also show non-optimal model assumptions and biased false discovery rate estimates, which can result in too large numbers of false positives. We also demonstrate that the performance of several of the methods differs substantially between metagenomic data sequenced by different technologies. Conclusions: Two methods, primarily designed for the analysis of RNA sequencing data (edgeR and DESeq2) together with a generalized linear model based on an overdispersed Poisson distribution were found to have best overall performance. The results presented in this study may serve as a guide for selecting suitable statistical methods for identification of differentially abundant genes in metagenomes

A framework for identifying the recent origins of mobile antibiotic resistance genes

Since the introduction of antibiotics as therapeutic agents, many bacterial pathogens have developed resistance to antibiotics. Mobile resistance genes, acquired through horizontal gene transfer, play an important role in this process. Understanding from which bacterial taxa these genes were mobilized, and whether their origin taxa share common traits, is critical for predicting which environments and conditions contribute to the emergence of novel resistance genes. This knowledge may prove valuable for limiting or delaying future transfer of novel resistance genes into pathogens. The literature on the origins of mobile resistance genes is scattered and based on evidence of variable quality. Here, we summarize, amend and scrutinize the evidence for 37 proposed origins of mobile resistance genes. Using state-of-the-art genomic analyses, we supplement and evaluate the evidence based on well-defined criteria. Nineteen percent of reported origins did not fulfill the criteria to confidently assign the respective origin. Of the curated origin taxa, >90% have been associated with infection in humans or domestic animals, some taxa being the origin of several different resistance genes. The clinical emergence of these resistance genes appears to be a consequence of antibiotic selection pressure on taxa that are permanently or transiently associated with the human/domestic animal microbiome

Characterization of the Zoarces viviparus liver transcriptome using massively parallel pyrosequencing

<p>Abstract</p> <p>Background</p> <p>The teleost <it>Zoarces viviparus </it>(eelpout) lives along the coasts of Northern Europe and has long been an established model organism for marine ecology and environmental monitoring. The scarce information about this species genome has however restrained the use of efficient molecular-level assays, such as gene expression microarrays.</p> <p>Results</p> <p>In the present study we present the first comprehensive characterization of the <it>Zoarces viviparus </it>liver transcriptome. From 400,000 reads generated by massively parallel pyrosequencing, more than 50,000 pieces of putative transcripts were assembled, annotated and functionally classified. The data was estimated to cover roughly 40% of the total transcriptome and homologues for about half of the genes of <it>Gasterosteus aculeatus </it>(stickleback) were identified. The sequence data was consequently used to design an oligonucleotide microarray for large-scale gene expression analysis.</p> <p>Conclusion</p> <p>Our results show that one run using a Genome Sequencer FLX from 454 Life Science/Roche generates enough genomic information for adequate <it>de novo </it>assembly of a large number of genes in a higher vertebrate. The generated sequence data, including the validated microarray probes, are publicly available to promote genome-wide research in <it>Zoarces viviparus</it>.</p

Does the scientific knowledge reflect the chemical diversity of environmental pollution? – A twenty-year perspective

Environmental policymaking relies heavily on the knowledge of the toxicological properties of chemical pollutants. The ecotoxicological research community is an important contributor to this knowledge, which together with data from standardized tests supports policy-makers in taking the decisions required to reach an appropriate level of protection of the environment. The chemosphere is, however, massive and contains thousands of chemicals that can constitute a risk if present in the environment at sufficiently high concentrations. The scientific ecotoxicological knowledge is growing but it is not clear to what extent the research community manages to cover the large chemical diversity of environmental pollution. In this study, we aimed to provide an overview of the scientific knowledge generated within the field of ecotoxicology during the last twenty years. By using text mining of over 130,000 scientific papers we established time-trends describing the yearly publication frequency of over 3500 chemicals. Our results show that ecotoxicological research is highly focused and that as few as 65 chemicals corresponded to half of all occurrences in the scientific literature. We, furthermore, demonstrate that the last decades have seen substantial changes in research direction, where the interest in pharmaceuticals has grown while the interest in biocides has declined. Several individual chemicals showed an especially rapid increase (e.g. ciprofloxacin, diclofenac) or decrease (e.g. lindane and atrazine) in occurrence in the literature. We also show that university- and corporate-based research exhibit distinct publication patterns and that for some chemicals the scientific knowledge is dominated by publications associated with the industry. This study paints a unique picture and provides quantitative estimates of the scientific knowledge of environmental chemical pollution generated during the last two decades. We conclude that there is a large number of chemicals with little, or no, scientific knowledge and that a continued expansion of the field of ecotoxicology will be necessary to catch up with the constantly increasing diversity of chemicals used within the society

Approaching the taxonomic affiliation of unidentified sequences in public databases – an example from the mycorrhizal fungi

BACKGROUND: During the last few years, DNA sequence analysis has become one of the primary means of taxonomic identification of species, particularly so for species that are minute or otherwise lack distinct, readily obtainable morphological characters. Although the number of sequences available for comparison in public databases such as GenBank increases exponentially, only a minuscule fraction of all organisms have been sequenced, leaving taxon sampling a momentous problem for sequence-based taxonomic identification. When querying GenBank with a set of unidentified sequences, a considerable proportion typically lack fully identified matches, forming an ever-mounting pile of sequences that the researcher will have to monitor manually in the hope that new, clarifying sequences have been submitted by other researchers. To alleviate these concerns, a project to automatically monitor select unidentified sequences in GenBank for taxonomic progress through repeated local BLAST searches was initiated. Mycorrhizal fungi – a field where species identification often is prohibitively complex – and the much used ITS locus were chosen as test bed. RESULTS: A Perl script package called emerencia is presented. On a regular basis, it downloads select sequences from GenBank, separates the identified sequences from those insufficiently identified, and performs BLAST searches between these two datasets, storing all results in an SQL database. On the accompanying web-service , users can monitor the taxonomic progress of insufficiently identified sequences over time, either through active searches or by signing up for e-mail notification upon disclosure of better matches. Other search categories, such as listing all insufficiently identified sequences (and their present best fully identified matches) publication-wise, are also available. DISCUSSION: The ever-increasing use of DNA sequences for identification purposes largely falls back on the assumption that public sequence databases contain a thorough sampling of taxonomically well-annotated sequences. Taxonomy, held by some to be an old-fashioned trade, has accordingly never been more important. emerencia does not automate the taxonomic process, but it does allow researchers to focus their efforts elsewhere than countless manual BLAST runs and arduous sieving of BLAST hit lists. The emerencia system is available on an open source basis for local installation with any organism and gene group as targets

Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge

The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where such\ua0initial mobilization\ua0events of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes

The Association between Insertion Sequences and Antibiotic Resistance Genes

Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could be a first step toward discovering novel ARGs through predictive or experimental strategies. This could be valuable, as early identification of ARGs in pathogens could facilitate surveillance, confinement actions, molecular diagnostics, and drug development. Here, we present a comprehensive analysis of the association of specific ISs with known ARGs. A large collection of bacterial genomes was used to characterize the immediate context of 2,437 known ARGs and 3,768 ISs. While many ARGs were consistently found close to specific ISs, the contexts around all ISs were more variable. Nevertheless, a subset of individual ISs, as well as tentative composite transposons, showed significant associations with ARGs. These included, e.g., insertion sequences classified as IS6, Tn3, IS4, and IS1 that were not only strongly associated with diverse ARGs but also highly abundant in pathogens. Therefore, we conclude that the context of this subset of ISs and tentative composite transposons would be particularly valuable to discover novel ARGs through modeling or empirical approaches. A set of 1,891 metagenomes were analyzed to identify environments where those ISs commonly associated with ARGs were particularly abundant. The associations found in metagenomes were similar to those found in genomes.IMPORTANCE The emergence and spread of antibiotic resistance genes (ARGs) among pathogens threaten the prevention and treatment of bacterial infections as well as our food production chains. Early knowledge about mobile ARGs that are present in pathogens or that have the potential to become clinically relevant could help mitigate potential negative consequences. Recently, exploring integron gene cassettes was shown to be successful for identifying novel mobilized ARGs, some of which were already circulating in pathogens. Still, only a subset of ARGs is mobilized by integrons, and the contexts of other mobile genetic elements associated with ARGs remain unexplored. This includes insertion sequences (ISs) responsible for the mobilization of many ARGs. Our analyses identified ISs, species, and environments where ARG-IS relationships are particularly strong. This could be a first step to guide the discovery of novel ARGs, while also providing insights into mechanisms involved in the mobilization and transfer of ARGs

The structure and diversity of human, animal and environmental resistomes

Background:Antibiotic resistance genes (ARGs) are widespread but cause problems only when present in pathogens. Environments where selection and transmission of antibiotic resistance frequently take place are likely to be characterized by high abundance and diversity of horizontally transferable ARGs. Large-scale quantitative data on ARGs is, however, lacking for most types of environments, including humans and animals, as is data on resistance genes to potential co-selective agents, such as biocides and metals. This paucity prevents efficient identification of risk environments.Results:We provide a comprehensive characterization of resistance genes, mobile genetic elements (MGEs) and bacterial taxonomic compositions for 864 metagenomes from humans (n = 350), animals (n = 145) and external environments (n = 369), all deeply sequenced using Illumina technology. Environment types showed clear differences in both resistance profiles and bacterial community compositions. Human and animal microbial communities were characterized by limited taxonomic diversity and low abundance and diversity of biocide/metal resistance genes and MGEs but a relatively high abundance of ARGs. In contrast, external environments showed consistently high taxonomic diversity which in turn was linked to high diversity of both biocide/metal resistance genes and MGEs. Water, sediment and soil generally carried low relative abundance and few varieties of known ARGs, whereas wastewater/sludge was on par with the human gut. The environments with the largest relative abundance and/or diversity of ARGs, including genes encoding resistance to last resort antibiotics, were those subjected to industrial antibiotic pollution and a limited set of deeply sequenced air samples from a Beijing smog event.Conclusions:Our study identifies air and antibiotic-polluted environments as under-investigated transmission routes and reservoirs for antibiotic resistance. The high taxonomic and genetic diversity of external environments supports the hypothesis that these also form vast sources of unknown resistance genes, with potential to be transferred to pathogens in the future

Les exposicions del Guernica de Picasso

Aproximació al procés de creació del Guernica de Pablo Picasso i a la seva presentació pública, a través de les exposicions de caràcter temporal i les corresponents a les col·leccions dels museus en les quals es va dipositar, per a poder reconstruir la història d’una de les icones mundials de l’art modern universal. El treball atent a la creació, contingut simbòlic i característiques principals de l’obra, a les circumstàncies històriques que la van envoltar, als itineraris expositius, els discursos museogràfics i les condicions de la seva presentació pública: al Pavelló espanyol de l’Exposició Internacional de París de 1937, al Museu d’Art Modern de New York (MoMA), al Museo Nacional del Prado i al Museu Nacional Centre de Artes Reina Sofía de Madrid, institució que acull actualment l’obra. Al llarg del treball es descriu el procés de transformació de la seva significació en funció del context en el qual s’insereix en cada moment, des d’un instrument de propaganda política, icona de l’art modern occidental, fins a la seva consideració com a obra mestra en la articulació de l’art espanyol modern i contemporani