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We simulate the combined natural and pollutant-induced survival of early life stages of NEA cod and haddock, and the impact on the adult populations in response to the time of a major oil spill in a single year. Our simulations reveal how dynamic ocean processes, controlling both oil transport and fate and the frequency of interactions of oil with drifting fish eggs and larvae, mediate the magnitude of population losses due to an oil spill. The largest impacts on fish early life stages occurred for spills initiated in Feb–Mar, concomitant with the initial rise in marine productivity and the earliest phase of the spawning season. The reproductive health of the adult fish populations was maintained in all scenarios. The study demonstrates the application of a simulation system that provides managers with information for the planning of development activities and for the protection of fisheries resources from potential impacts. An annual profile of the impacts of simulated oil spills on the Northeast Arctic cod and haddock fisherie

The plastid phosphate translocators evolved in algae but diversified into several groups, which adopted different physiological functions by extensive gene duplications and losses in Streptophyta. The plastid phosphate translocators (pPT) are a family of transporters involved in the exchange of metabolites and inorganic phosphate between stroma and cytosol. Based on their substrate specificities, they were divided into four subfamilies named TPT, PPT, GPT and XPT. To analyse the occurrence of these transporters in different algae and land plant species, we identified 652 pPT genes in 101 sequenced genomes for phylogenetic analysis. The first three subfamilies are found in all species and evolved before the split of red and green algae while the XPTs were derived from the duplication of a GPT gene at the base of Streptophyta. The analysis of the intron-exon structures of the pPTs corroborated these findings. While the number and positions of introns are conserved within each subfamily, they differ between the subfamilies suggesting an insertion of the introns shortly after the three subfamilies evolved. During angiosperm evolution, the subfamilies further split into different groups (TPT1-2, PPT1-3, GPT1-6). Angiosperm species differ significantly in the total number of pPTs, with many species having only a few, while several plants, especially crops, have a higher number, pointing to the importance of these transporters for improved source-sink strength and yield. The differences in the number of pPTs can be explained by several small-scale gene duplications and losses in plant families or single species, but also by whole genome duplications, for example, in grasses. This work could be the basis for a comprehensive analysis of the molecular and physiological functions of this important family of transporters.

Summary Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling., Graphical Abstract, Highlights • G3BPs act non-redundantly in the TSC-mTORC1 signaling axis • G3BPs reside at the lysosomal surface and inhibit mTORC1 • The TSC complex requires G3BPs as its lysosomal tether • G3BP1 deficiency phenocopies TSC complex loss in cancer cells and neurons, Distinct from their contributions to stress granules, G3BPs regulate mTORC1 activity through spatial control of the TSC complex.

SummaryG3BP1 (Ras GTPase-activating protein-binding protein 1) is widely recognized as a core component of stress granules (SG), non-membranous RNA-protein-assemblies required for cellular survival under stress. We report that in the absence of SG, G3BP1 acts as lysosomal anchor of the Tuberous Sclerosis Complex (TSC) protein complex. By tethering the TSC complex to lysosomes, G3BP1 suppresses signaling through the metabolic master regulator mTORC1 (mechanistic target of rapamycin complex 1). Like the known TSC complex subunits, G3BP1 suppresses phenotypes related to mTORC1 hyperactivity in the context of tumors and neuronal dysfunction. Thus, G3BP1 is not only a core component of SG but also a key element of lysosomal TSC-mTORC1 signaling.HighlightsThebona fidestress granule component G3BP1is a key element of the TSC-mTORC1 signaling axis.tethers the TSC complex to lysosomes.prevents mTORC1 hyperactivation by metabolic stimuli.suppresses mTORC1-driven cancer cell motility and epileptiform activity.Graphical Abstract

Background Systems Biology Markup Language (SBML) is the standard model representation and description language in systems biology. Enriching and analysing systems biology models by integrating the multitude of available data, increases the predictive power of these models. This may be a daunting task, which commonly requires bioinformatic competence and scripting. Results We present SBMLmod, a Python-based web application and service, that automates integration of high throughput data into SBML models. Subsequent steady state analysis is readily accessible via the web service COPASIWS. We illustrate the utility of SBMLmod by integrating gene expression data from different healthy tissues as well as from a cancer dataset into a previously published model of mammalian tryptophan metabolism. Conclusion SBMLmod is a user-friendly platform for model modification and simulation. The web application is available at http://sbmlmod.uit.no, whereas the WSDL definition file for the web service is accessible via http://sbmlmod.uit.no/SBMLmod.wsdl. Furthermore, the entire package can be downloaded from https://github.com/MolecularBioinformatics/sbml-mod-ws. We envision that SBMLmod will make automated model modification and simulation available to a broader research community. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1722-9) contains supplementary material, which is available to authorized users.

Nicotinamide adenine dinucleotide (NAD) provides an important link between metabolism and signal transduction and has emerged as central hub between bioenergetics and all major cellular events. NAD-dependent signaling (e.g., by sirtuins and poly–adenosine diphosphate [ADP] ribose polymerases [PARPs]) consumes considerable amounts of NAD. To maintain physiological functions, NAD consumption and biosynthesis need to be carefully balanced. Using extensive phylogenetic analyses, mathematical modeling of NAD metabolism, and experimental verification, we show that the diversification of NAD-dependent signaling in vertebrates depended on 3 critical evolutionary events: 1) the transition of NAD biosynthesis to exclusive usage of nicotinamide phosphoribosyltransferase (NamPT); 2) the occurrence of nicotinamide N-methyltransferase (NNMT), which diverts nicotinamide (Nam) from recycling into NAD, preventing Nam accumulation and inhibition of NAD-dependent signaling reactions; and 3) structural adaptation of NamPT, providing an unusually high affinity toward Nam, necessary to maintain NAD levels. Our results reveal an unexpected coevolution and kinetic interplay between NNMT and NamPT that enables extensive NAD signaling. This has implications for therapeutic strategies of NAD supplementation and the use of NNMT or NamPT inhibitors in disease treatment.

Source at https://doi.org/10.3389/fevo.2018.00203. It is well established that GC content varies across the genome in many species and that GC biased gene conversion, one form of meiotic recombination, is likely to contribute to this heterogeneity. Bird genomes provide an extraordinary system to study the impact of GC biased gene conversion owed to their specific genomic features. They are characterized by a high karyotype conservation with substantial heterogeneity in chromosome sizes, with up to a dozen large macrochromosomes and many smaller microchromosomes common across all bird species. This heterogeneity in chromosome morphology is also reflected by other genomic features, such as smaller chromosomes being gene denser, more compact and more GC rich relative to their macrochromosomal counterparts - illustrating that the intensity of GC biased gene conversion varies across the genome. Here we study whether it is possible to infer heterogeneity in GC biased gene conversion rates across the genome using a recently published method that accounts for GC biased gene conversion when estimating branch lengths in a phylogenetic context. To infer the strength of GC biased gene conversion we contrast branch length estimates across the genome both taking and not taking non-stationary GC composition into account. Using simulations we show that this approach works well when GC fixation bias is strong and note that the number of substitutions along a branch is consistently overestimated when GC biased gene conversion is not accounted for. We use this predictable feature to infer the strength of GC dynamics across the great tit genome by applying our new pipeline to data at 4-fold degenerate sites from three bird species—great tit, zebra finch and chicken—three species that are among the best annotated bird genomes to date. We show that using a simple one-dimensional binning we fail to capture a signal of fixation bias as observed in our simulations. However, using a multidimensional binning strategy, we find evidence for heterogeneity in the strength of fixation bias, including AT fixation bias. This highlights the difficulties when combining sequence data across different regions in the genome.

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species, it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here, we address this question by investigating the evolutionary pattern of more than 6600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a priori knowledge of disordered protein regions, and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs fourfold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts.

Publisher's version, source http://doi.org/10.1099/mgen.0.000066 The faecal microbiota of muskoxen (n=3) pasturing on Ryøya (69° 33′ N 18° 43′ E), Norway, in late September was characterized using high-throughput sequencing of partial 16S rRNA gene regions. A total of 16 209 high-quality sequence reads from bacterial domains and 19 462 from archaea were generated. Preliminary taxonomic classifications of 806 bacterial operational taxonomic units (OTUs) resulted in 53.7–59.3 % of the total sequences being without designations beyond the family level. Firmicutes (70.7–81.1 % of the total sequences) and Bacteroidetes (16.8–25.3 %) constituted the two major bacterial phyla, with uncharacterized members within the family Ruminococcaceae (28.9–40.9 %) as the major phylotype. Multiple-library comparisons between muskoxen and other ruminants indicated a higher similarity for muskoxen faeces and reindeer caecum (P>0.05) and some samples from cattle faeces. The archaeal sequences clustered into 37 OTUs, with dominating phylotypes affiliated to the methane-producing genus Methanobrevibacter (80–92 % of the total sequences). UniFrac analysis demonstrated heterogeneity between muskoxen archaeal libraries and those from reindeer and roe deer (P=1.0e-02, Bonferroni corrected), but not with foregut fermenters. The high proportion of cellulose-degrading Ruminococcus-affiliated bacteria agrees with the ingestion of a highly fibrous diet. Further experiments are required to elucidate the role played by these novel bacteria in the digestion of this fibrous Artic diet eaten by muskoxen.