An integrated approach to assess the impacts of zinc pyrithione at different levels of biological organization in marine mussels.

The mechanisms of sublethal toxicity of the antifouling biocide, zinc pyrithione (ZnPT), have not been well-studied. This investigation demonstrates that 14-d sublethal exposure to ZnPT (0.2 or 2 μM, alongside inorganic Zn and sea water controls) is genotoxic to mussel haemocytes but suggests that this is not caused by oxidative DNA damage as no significant induction of oxidised purines was detected by Fpg-modified comet assay. More ecologically relevant endpoints, including decreased clearance rate (CR), cessation of attachment and decreased tolerance of stress on stress (SoS), also showed significant response to ZnPT exposure. Our integrated approach was underpinned by molecular analyses (qRT-PCR of stress-related genes, 2D gel electrophoresis of proteins) that indicated ZnPT causes a decrease in phosphoenolpyruvate carboxykinase (PEPCK) expression in mussel digestive glands, and that metallothionein genes are upregulated; PEPCK downregulation suggests that altered energy metabolism may also be related to the effects of ZnPT. Significant relationships were found between % tail DNA (comet assay) and all higher level responses (CR, attachment, SoS) in addition to PEPCK expression. Principal component analyses suggested that expression of selected genes described more variability within groups whereas % tail DNA reflected different ZnPT concentrations

Exposure to tritiated water at an elevated temperature: Genotoxic and transcriptomic effects in marine mussels (M. galloprovincialis).

Temperature is an abiotic factor of particular concern for assessing the potential impacts of radionuclides on marine species. This is particularly true for tritium, which is discharged as tritiated water (HTO) in the process of cooling nuclear institutions. Additionally, with sea surface temperatures forecast to rise 0.5 - 3.5 C in the next 30-100 years, determining the interaction of elevated temperature with radiological exposure has never been more relevant. We assessed the tissue-specific accumulation, transcriptional expression of key genes, and genotoxicity of tritiated water to marine mussels at either 15 or 25 C, over a 7 day time course with sampling after 1 h, 12 h, 3 d and 7d. The activity concentration used (15 MBq L-1) resulted in tritium accumulation that varied with both time and temperature, but consistently produced dose rates (calculated using the ERICA tool) of <20 Gy h-1, i.e. considerably below the recommended guidelines of the IAEA and EURATOM. Despite this, there was significant induction of DNA strand breaks (as measured by the comet assay), which also showed a temperature-dependent time shift. At 15 C, DNA damage was only significantly elevated after 7 d, in contrast to 25 C where a similar response was observed after only 3 d. The transcription profiles of two isoforms of hsp70, hsp90, mt20, p53 and rad51 indicated potential mechanisms behind this temperature-induced acceleration of genotoxicity, which may be the result of compromised defence. Specifically, genes involved in protein folding, DNA double strand break repair and cell cycle checkpoint control were upregulated after 3 d HTO exposure at 15 C, but significantly downregulated when the same exposure occurred at 25 C. This study is the first to investigate temperature efects on radiation-induced genotoxicity in an ecologically relevant marine invertebrate, Mytilus galloprovincialis. From an ecological perspective, our study suggests that mussels (or similar marine species) exposed to increased temperature and HTO may have a compromised ability to defend against genotoxic stress. Abbreviations: HTO, tritiated water; Fpg, formamidopyrimidine glyco- sylase; GoI, gene of interest; LSC, liquid scintillation counting; tDAC, tissue dry activity concentration; TFWT, tissue free water tritium; tTAC, tissue total activity concentration; woTAC, whole organism total activity concentration

DNA adducts in fish following an oil spill exposure

On 12 December 1999, one third of the load of the Erika tanker, amounting to about 10,000 t crude oil flowed into sea waters close to the French Atlantic Coast. This oil contained polycyclic aromatic compounds (PAC) that are known to be genotoxic. Genotoxic effects induce DNA adducts formation, which can thus be used as pollution biomarkers. Here, we assessed the genotoxic impact of the “Erika” oil spill by DNA adducts detection in the liver of immature fishes (Solea solea) from four locations of the French Brittany coasts. Two months after the spill, a high amount of DNA adducts was found in samples from all locations, amounting to 92–290 DNA adduct per 109 nucleotides. Then total DNA adduct levels decreased to reach about 50 adducts per 109 nucleotides nine months after the spill. In vitro experiments using human cell cultures and fish liver microsomes evidence the genotoxicity of the Erika fuel. They also prove the formation of reactive species able to create DNA adducts. Furthermore, in vitro and in vivo DNA adducts fingerprints are similar, thus confirming that DNA adducts are a result of the oil spill

Towards a System Level Understanding of Non-Model Organisms Sampled from the Environment: A Network Biology Approach

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations

Extreme sensitivity in Snowball Earth formation to mountains on PaleoProterozoic supercontinents

During the PaleoProterozoic 2.45 to 2.2 billion years ago, several glaciations may have produced Snowball Earths. These glacial cycles occurred during large environmental change when atmospheric oxygen was increasing, a supercontinent was assembled from numerous landmasses, and collisions between these landmasses formed mountain ranges. Despite uncertainties in the composition of the atmosphere and reconstruction of the landmasses, paleoclimate model simulations can test the sensitivity of the climate to producing a Snowball Earth. Here we present a series of simulations that vary the atmospheric methane concentration and latitudes of west–east-oriented mountain ranges on an idealised supercontinent. For a given methane concentration, the latitudes of mountains control whether a Snowball Earth forms or not. Significantly, mountains in middle latitudes inhibited Snowball Earth formation, and mountains in low latitudes promoted Snowball Earth formation, with the supercontinent with mountains at ±30° being most conducive to forming a Snowball Earth because of reduced albedo at low latitudes. We propose that the extreme sensitivity of a Snowball Earth to reconstructions of the paleogeography and paleoatmospheric composition may explain the observed glaciations, demonstrating the importance of high-quality reconstructions to improved understanding of this early period in Earth’s history

Fluoxetine Counteracts the Cognitive and Cellular Effects of 5-Fluorouracil in the Rat Hippocampus by a Mechanism of Prevention Rather than Recovery

5-Fluorouracil (5-FU) is a cytostatic drug associated with chemotherapy-induced cognitive impairments that many cancer patients experience after treatment. Previous work in rodents has shown that 5-FU reduces hippocampal cell proliferation, a possible mechanism for the observed cognitive impairment, and that both effects can be reversed by co-administration of the antidepressant, fluoxetine. In the present study we investigate the optimum time for administration of fluoxetine to reverse or prevent the cognitive and cellular effects of 5-FU

Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.

A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events

Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.

A Measurement of the Tau Hadronic Branching Ratios

The exclusive and semi-exclusive branching ratios of the tau lepton hadronic decay modes (h- v_t, h- pi0 v_t, h- pi0 pi0 v_t, h- \geq 2pi0 v_t, h- \geq 3pi0 v_t, 2h- h+ v_t, 2h- h+ pi0 v_t, 2h- h+ \geq 2pi0 v_t, 3h- 2h+ v_t and 3h- 2h+ \geq 1pi0 v_t) were measured with data from the DELPHI detector at LEP.Comment: 53 pages, 18 figures, Accepted by Eur. Phys. J.