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Eduarda M. Santos
Centre for Sustainable Aquaculture Futures, University of Exeter, Exeter EX4 4QD, UK

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Journal article
Published: 13 June 2021 in Viruses
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White Spot Disease (WSD) presents a major barrier to penaeid shrimp production. Mechanisms underlying White Spot Syndrome Virus (WSSV) susceptibility in penaeids are poorly understood due to limited information related to early infection. We investigated mRNA and miRNA transcription in Penaeus vannamei over 36 h following infection. Over this time course, 6192 transcripts and 27 miRNAs were differentially expressed—with limited differential expression from 3–12 h post injection (hpi) and a more significant transcriptional response associated with the onset of disease symptoms (24 hpi). During early infection, regulated processes included cytoskeletal remodelling and alterations in phagocytic activity that may assist WSSV entry and translocation, novel miRNA-induced metabolic shifts, and the downregulation of ATP-dependent proton transporter subunits that may impair cellular recycling. During later infection, uncoupling of the electron transport chain may drive cellular dysfunction and lead to high mortalities in infected penaeids. We propose that post-transcriptional silencing of the immune priming gene Dscam (downregulated following infections) by a novel shrimp miRNA (Pva-pmiR-78; upregulated) as a potential mechanism preventing future recognition of WSSV that may be suppressed in surviving shrimp. Our findings improve our understanding of WSD pathogenesis in P. vannamei and provide potential avenues for future development of prophylactics and treatments.

ACS Style

Rebecca Millard; Lisa Bickley; Kelly Bateman; Audrey Farbos; Diana Minardi; Karen Moore; Stuart Ross; Grant Stentiford; Charles Tyler; Ronny van Aerle; Eduarda Santos. Global mRNA and miRNA Analysis Reveal Key Processes in the Initial Response to Infection with WSSV in the Pacific Whiteleg Shrimp. Viruses 2021, 13, 1140 .

AMA Style

Rebecca Millard, Lisa Bickley, Kelly Bateman, Audrey Farbos, Diana Minardi, Karen Moore, Stuart Ross, Grant Stentiford, Charles Tyler, Ronny van Aerle, Eduarda Santos. Global mRNA and miRNA Analysis Reveal Key Processes in the Initial Response to Infection with WSSV in the Pacific Whiteleg Shrimp. Viruses. 2021; 13 (6):1140.

Chicago/Turabian Style

Rebecca Millard; Lisa Bickley; Kelly Bateman; Audrey Farbos; Diana Minardi; Karen Moore; Stuart Ross; Grant Stentiford; Charles Tyler; Ronny van Aerle; Eduarda Santos. 2021. "Global mRNA and miRNA Analysis Reveal Key Processes in the Initial Response to Infection with WSSV in the Pacific Whiteleg Shrimp." Viruses 13, no. 6: 1140.

Journal article
Published: 11 June 2021 in Viruses
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The basis of pathogenicity of viral haemorrhagic septicaemia virus (VHSV) was analysed in the transcriptome of a rainbow trout cell line inoculated with pathogenic and non-pathogenic VHSV isolates. Although both VHSV isolates showed similar viral replication patterns, the number of differentially expressed genes was 42-fold higher in cells inoculated with the non-pathogenic VHSV at 3 h post inoculation (hpi). Infection with the non-pathogenic isolate resulted in Gene Ontologies (GO) enrichment of terms such as immune response, cytokine-mediated signalling pathway, regulation of translational initiation, unfolded protein binding, and protein folding, and induced an over-representation of the p53, PPAR, and TGF-β signalling pathways. Inoculation with the pathogenic isolate resulted in the GO enrichment of terms related to lipid metabolism and the salmonella infection KEGG pathway involved in the rearrangement of the cytoskeleton. Antiviral response was evident at 12hpi in cells infected with the pathogenic isolate. Overall, the data showed a delay in the response of genes involved in immune responses and viral sensing in cells inoculated with the pathogenic isolate and suggest transcriptional shutoff and immune avoidance as a critical mechanism of pathogenicity in VHSV. These pathways offer opportunities to further understand and manage VHSV pathogenicity in rainbow trout.

ACS Style

Irene Cano; Eduarda Santos; Karen Moore; Audrey Farbos; Ronny van Aerle. Evidence of Transcriptional Shutoff by Pathogenic Viral Haemorrhagic Septicaemia Virus in Rainbow Trout. Viruses 2021, 13, 1129 .

AMA Style

Irene Cano, Eduarda Santos, Karen Moore, Audrey Farbos, Ronny van Aerle. Evidence of Transcriptional Shutoff by Pathogenic Viral Haemorrhagic Septicaemia Virus in Rainbow Trout. Viruses. 2021; 13 (6):1129.

Chicago/Turabian Style

Irene Cano; Eduarda Santos; Karen Moore; Audrey Farbos; Ronny van Aerle. 2021. "Evidence of Transcriptional Shutoff by Pathogenic Viral Haemorrhagic Septicaemia Virus in Rainbow Trout." Viruses 13, no. 6: 1129.

Preprint content
Published: 02 March 2021
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For non-kin cooperation to be maintained, individuals need to respond adaptively to the cooperative behaviour of their social partners. Currently, however, little is known about the biological responses of individuals to experiencing cooperation. Here, we quantify the neuroregulatory response of Trinidadian guppies (Poecilia reticulata) experiencing cooperation or defection by examining the transcriptional response of the oxytocin gene (oxt; also known as isotocin), which has been implicated in cooperative decision-making. We exposed wild-caught females to social environments where partners either cooperated or defected during predator inspection, or to a control (non-predator inspection) context, and quantified the relative transcription of the oxt gene. We tested an experimental group, originating from a site where individuals are under high predation threat and have previous experience of large aquatic predators (HP), and a control group, where individuals are under low predation threat and naïve to large aquatic predators (LP). In HP, but not LP, fish brain mid-section oxt relative transcription varied depending on social partner behaviour. HP fish experiencing cooperation during predator inspection had lower oxt transcription than those experiencing defection. This effect was not present in the control population or in the control context, where the behaviour of social partners did not affect oxt transcription. Our findings provide insight into the neuromodulation underpinning behavioural responses to social experiences, and ultimately to the proximate mechanisms underlying social decision-making.

ACS Style

Sylvia Dimitriadou; Eduarda M. Santos; Darren P. Croft; Ronny van Aerle; Indar W. Ramnarine; Amy L. Filby; Safi K. Darden. Social partner cooperativeness influences brain oxytocin transcription in Trinidadian guppies (Poecilia reticulata). 2021, 1 .

AMA Style

Sylvia Dimitriadou, Eduarda M. Santos, Darren P. Croft, Ronny van Aerle, Indar W. Ramnarine, Amy L. Filby, Safi K. Darden. Social partner cooperativeness influences brain oxytocin transcription in Trinidadian guppies (Poecilia reticulata). . 2021; ():1.

Chicago/Turabian Style

Sylvia Dimitriadou; Eduarda M. Santos; Darren P. Croft; Ronny van Aerle; Indar W. Ramnarine; Amy L. Filby; Safi K. Darden. 2021. "Social partner cooperativeness influences brain oxytocin transcription in Trinidadian guppies (Poecilia reticulata)." , no. : 1.

Journal article
Published: 21 October 2020
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Silver is a non-essential, toxic metal widespread in freshwaters and capable of causing adverse effects to wildlife. Its toxic effects have been studied in detail but less is known about how sensitivity varies during development and whether pre-exposures affect tolerance upon re-exposure. We address these knowledge gaps using the zebrafish embryo (Danio rerio) model to investigate whether exposures encompassing stages of development prior to mid-blastula transition, when chorion hardening and epigenetic reprogramming occur, result in greater toxicity compared to those initiated after this period. We conducted exposures to silver initiated at 0.5 h post fertilisation (hpf) and 4 hpf to determine if toxicity differed. In parallel, we exposed embryos to the methylation inhibitor 5-azacytidine as a positive control. Toxicity increased when exposures started from 0.5 hpf compared to 4 hpf and LC50 were significantly lower by 1.2 and 7.6 times for silver and 5-azacyitidine, respectively. We then investigated whether pre-exposure to silver during early development (from 0.5 or 4 hpf) affected the outcome of subsequent exposures during the larvae stage, and found no alterations in toxicity compared to naïve larvae. Together, these data demonstrate that during early development zebrafish embryos are more sensitive to silver when experiments are initiated at the one-cell stage, but that pre-exposures do not influence the outcome of subsequent exposures, suggesting that no long-lasting memory capable of influencing future susceptibility was maintained under our experimental conditions. The finding that toxicity is greater for exposures initiated at the one-cell stage has implications for designing testing systems to assess chemical toxicity.

ACS Style

Paige C. Robinson; Hannah R. Littler; Anke Lange; Eduarda M. Santos. Developmental exposure window influences silver toxicity but does not affect the susceptibility to subsequent exposures in zebrafish embryos. 2020, 154, 579 -595.

AMA Style

Paige C. Robinson, Hannah R. Littler, Anke Lange, Eduarda M. Santos. Developmental exposure window influences silver toxicity but does not affect the susceptibility to subsequent exposures in zebrafish embryos. . 2020; 154 (5):579-595.

Chicago/Turabian Style

Paige C. Robinson; Hannah R. Littler; Anke Lange; Eduarda M. Santos. 2020. "Developmental exposure window influences silver toxicity but does not affect the susceptibility to subsequent exposures in zebrafish embryos." 154, no. 5: 579-595.

Original paper
Published: 21 October 2020 in Histochemistry and Cell Biology
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Silver is a non-essential, toxic metal widespread in freshwaters and capable of causing adverse effects to wildlife. Its toxic effects have been studied in detail but less is known about how sensitivity varies during development and whether pre-exposures affect tolerance upon re-exposure. We address these knowledge gaps using the zebrafish embryo (Danio rerio) model to investigate whether exposures encompassing stages of development prior to mid-blastula transition, when chorion hardening and epigenetic reprogramming occur, result in greater toxicity compared to those initiated after this period. We conducted exposures to silver initiated at 0.5 h post fertilisation (hpf) and 4 hpf to determine if toxicity differed. In parallel, we exposed embryos to the methylation inhibitor 5-azacytidine as a positive control. Toxicity increased when exposures started from 0.5 hpf compared to 4 hpf and LC50 were significantly lower by 1.2 and 7.6 times for silver and 5-azacyitidine, respectively. We then investigated whether pre-exposure to silver during early development (from 0.5 or 4 hpf) affected the outcome of subsequent exposures during the larvae stage, and found no alterations in toxicity compared to naïve larvae. Together, these data demonstrate that during early development zebrafish embryos are more sensitive to silver when experiments are initiated at the one-cell stage, but that pre-exposures do not influence the outcome of subsequent exposures, suggesting that no long-lasting memory capable of influencing future susceptibility was maintained under our experimental conditions. The finding that toxicity is greater for exposures initiated at the one-cell stage has implications for designing testing systems to assess chemical toxicity.

ACS Style

Paige C. Robinson; Hannah R. Littler; Anke Lange; Eduarda M. Santos. Developmental exposure window influences silver toxicity but does not affect the susceptibility to subsequent exposures in zebrafish embryos. Histochemistry and Cell Biology 2020, 154, 579 -595.

AMA Style

Paige C. Robinson, Hannah R. Littler, Anke Lange, Eduarda M. Santos. Developmental exposure window influences silver toxicity but does not affect the susceptibility to subsequent exposures in zebrafish embryos. Histochemistry and Cell Biology. 2020; 154 (5):579-595.

Chicago/Turabian Style

Paige C. Robinson; Hannah R. Littler; Anke Lange; Eduarda M. Santos. 2020. "Developmental exposure window influences silver toxicity but does not affect the susceptibility to subsequent exposures in zebrafish embryos." Histochemistry and Cell Biology 154, no. 5: 579-595.

Perspective
Published: 03 August 2020 in Nature Food
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Aquaculture is predicted to supply the majority of aquatic dietary protein by 2050. For aquaculture to deliver significantly enhanced volumes of food in a sustainable manner, appropriate account needs to be taken of its impacts on environmental integrity, farmed organism health and welfare, and human health. Here, we explore increased aquaculture production through the One Health lens and define a set of success metrics — underpinned by evidence, policy and legislation — that must be embedded into aquaculture sustainability. We provide a framework for defining, monitoring and averting potential negative impacts of enhanced production — and consider interactions with land-based food systems. These metrics will inform national and international science and policy strategies to support improved aquatic food system design.

ACS Style

G. D. Stentiford; I. J. Bateman; S. J. Hinchliffe; D. Bass; R. Hartnell; E. M. Santos; M. J. Devlin; S. W. Feist; N. G. H. Taylor; D. W. Verner-Jeffreys; R. Van Aerle; E. J. Peeler; W. A. Higman; L. Smith; R. Baines; D. C. Behringer; I. Katsiadaki; H. E. Froehlich; C. R. Tyler. Sustainable aquaculture through the One Health lens. Nature Food 2020, 1, 468 -474.

AMA Style

G. D. Stentiford, I. J. Bateman, S. J. Hinchliffe, D. Bass, R. Hartnell, E. M. Santos, M. J. Devlin, S. W. Feist, N. G. H. Taylor, D. W. Verner-Jeffreys, R. Van Aerle, E. J. Peeler, W. A. Higman, L. Smith, R. Baines, D. C. Behringer, I. Katsiadaki, H. E. Froehlich, C. R. Tyler. Sustainable aquaculture through the One Health lens. Nature Food. 2020; 1 (8):468-474.

Chicago/Turabian Style

G. D. Stentiford; I. J. Bateman; S. J. Hinchliffe; D. Bass; R. Hartnell; E. M. Santos; M. J. Devlin; S. W. Feist; N. G. H. Taylor; D. W. Verner-Jeffreys; R. Van Aerle; E. J. Peeler; W. A. Higman; L. Smith; R. Baines; D. C. Behringer; I. Katsiadaki; H. E. Froehlich; C. R. Tyler. 2020. "Sustainable aquaculture through the One Health lens." Nature Food 1, no. 8: 468-474.

Review article
Published: 16 April 2020 in Nature Reviews Microbiology
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Aquaculture is the fastest-growing farmed food sector and will soon become the primary source of fish and shellfish for human diets. In contrast to crop and livestock production, aquaculture production is derived from numerous, exceptionally diverse species that are typically in the early stages of domestication. Genetic improvement of production traits via well-designed, managed breeding programmes has great potential to help meet the rising seafood demand driven by human population growth. Supported by continuous advances in sequencing and bioinformatics, genomics is increasingly being applied across the broad range of aquaculture species and at all stages of the domestication process to optimize selective breeding. In the future, combining genomic selection with biotechnological innovations, such as genome editing and surrogate broodstock technologies, may further expedite genetic improvement in aquaculture.

ACS Style

Ross D. Houston; Tim P. Bean; Daniel J. MacQueen; Manu Kumar Gundappa; Ye Hwa Jin; Tom L. Jenkins; Sarah Louise C. Selly; Samuel A. M. Martin; Jamie R. Stevens; Eduarda M. Santos; Andrew Davie; Diego Robledo. Harnessing genomics to fast-track genetic improvement in aquaculture. Nature Reviews Microbiology 2020, 21, 389 -409.

AMA Style

Ross D. Houston, Tim P. Bean, Daniel J. MacQueen, Manu Kumar Gundappa, Ye Hwa Jin, Tom L. Jenkins, Sarah Louise C. Selly, Samuel A. M. Martin, Jamie R. Stevens, Eduarda M. Santos, Andrew Davie, Diego Robledo. Harnessing genomics to fast-track genetic improvement in aquaculture. Nature Reviews Microbiology. 2020; 21 (7):389-409.

Chicago/Turabian Style

Ross D. Houston; Tim P. Bean; Daniel J. MacQueen; Manu Kumar Gundappa; Ye Hwa Jin; Tom L. Jenkins; Sarah Louise C. Selly; Samuel A. M. Martin; Jamie R. Stevens; Eduarda M. Santos; Andrew Davie; Diego Robledo. 2020. "Harnessing genomics to fast-track genetic improvement in aquaculture." Nature Reviews Microbiology 21, no. 7: 389-409.

Review
Published: 01 April 2020 in Journal of Invertebrate Pathology
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White Spot Syndrome Virus (WSSV) causes White Spot Disease (WSD) and is historically the most devastating disease in the shrimp industry. Global losses from this disease have previously exceeded $3 bn annually, having a major impact on a global industry worth US$19 bn per annum. Shrimp are cultured predominantly in enclosed ponds that are subject to considerable fluctuations in abiotic conditions and WSD outbreaks are increasingly linked to periods of extreme weather, which may cause major fluctuations in pond culture conditions. Combined with the intensity of production in these systems, the resulting suboptimal physicochemical conditions have a major bearing on the susceptibility of shrimp to infection and disease. Current knowledge indicates that pond temperature and salinity are major factors determining outbreak severity. WSSV appears to be most virulent in water temperatures between 25 and 28 °C and salinities far removed from the isoosmotic point of shrimp. Elevated temperatures (>30 °C) may protect against WSD, depending on the stage of infection, however the mechanisms mediating this effect have not been well established. Other factors relating to water quality that may play key roles in determining outbreak severity include dissolved oxygen concentration, nitrogenous compound concentration, partial pressure of carbon dioxide and pH, but data on their impacts on WSSV susceptibility in cultured shrimps is scarce. This illustrates a major research gap in our understanding of the influence of environmental conditions on disease. For example, it is not clear whether temperature manipulations can be used effectively to prevent or mitigate WSD in cultured shrimp. Therefore, developing our understanding of the impact of environmental conditions on shrimp susceptibility to WSSV may provide insight for WSD mitigation when, even after decades of research, there is no effective practical prophylaxis or treatment.

ACS Style

Rebecca S. Millard; Robert P. Ellis; Kelly S. Bateman; Lisa K. Bickley; Charles R. Tyler; Ronny van Aerle; Eduarda M. Santos. How do abiotic environmental conditions influence shrimp susceptibility to disease? A critical analysis focussed on White Spot Disease. Journal of Invertebrate Pathology 2020, 107369 .

AMA Style

Rebecca S. Millard, Robert P. Ellis, Kelly S. Bateman, Lisa K. Bickley, Charles R. Tyler, Ronny van Aerle, Eduarda M. Santos. How do abiotic environmental conditions influence shrimp susceptibility to disease? A critical analysis focussed on White Spot Disease. Journal of Invertebrate Pathology. 2020; ():107369.

Chicago/Turabian Style

Rebecca S. Millard; Robert P. Ellis; Kelly S. Bateman; Lisa K. Bickley; Charles R. Tyler; Ronny van Aerle; Eduarda M. Santos. 2020. "How do abiotic environmental conditions influence shrimp susceptibility to disease? A critical analysis focussed on White Spot Disease." Journal of Invertebrate Pathology , no. : 107369.

Journal article
Published: 06 March 2020 in Environmental Pollution
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Hypoxia is a major stressor in aquatic environments and it is frequently linked with excess nutrients resulting from sewage effluent discharges and agricultural runoff, which often also contain complex mixtures of chemicals. Despite this, interactions between hypoxia and chemical toxicity are poorly understood. We exposed male three-spined stickleback during the onset of sexual maturation to a model anti-androgen (flutamide; 250 μg/L) and a pesticide with anti-androgenic activity (linuron; 250 μg/L), under either 97% or 56% air saturation (AS). We assessed the effects of each chemical, alone and in combination with reduced oxygen concentration, by measuring the transcription of spiggin in the kidney, as a marker of androgen signalling, and 11 genes in the liver involved in some of the molecular pathways hypothesised to be affected by the exposures. Spiggin transcription was strongly inhibited by flutamide under both AS conditions. In contrast, for linuron, a strong inhibition of spiggin was observed under 97% AS, but this effect was supressed under reduced air saturation, likely due to interactions between the hypoxia inducible factor and the aryl hydrocarbon receptor (AhR) pathways. In the liver, hypoxia inducible factor 1α was induced following exposure to both flutamide and linuron, however this was independent of the level of air saturation. This work illustrates the potential for interactions between hypoxia and pollutants with endocrine or AhR agonist activity to occur, with implications for risk assessment and management.

ACS Style

Jennifer A. Fitzgerald; Maciej Trznadel; Ioanna Katsiadaki; Eduarda M. Santos. Hypoxia modifies the response to flutamide and linuron in male three-spined stickleback (Gasterosteus aculeatus). Environmental Pollution 2020, 263, 114326 .

AMA Style

Jennifer A. Fitzgerald, Maciej Trznadel, Ioanna Katsiadaki, Eduarda M. Santos. Hypoxia modifies the response to flutamide and linuron in male three-spined stickleback (Gasterosteus aculeatus). Environmental Pollution. 2020; 263 ():114326.

Chicago/Turabian Style

Jennifer A. Fitzgerald; Maciej Trznadel; Ioanna Katsiadaki; Eduarda M. Santos. 2020. "Hypoxia modifies the response to flutamide and linuron in male three-spined stickleback (Gasterosteus aculeatus)." Environmental Pollution 263, no. : 114326.

Journal article
Published: 03 February 2020 in npj Schizophrenia
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Clozapine is an atypical antipsychotic medication that is used to treat schizophrenia patients who are resistant to other antipsychotic drugs. The molecular mechanisms mediating the effects of clozapine are not well understood and its use is often associated with severe side-effects. In this study, we exposed groups of wild-type zebrafish to two doses of clozapine (‘low’ (20 µg/L) and ‘high’ (70 µg/L)) over a 72-h period, observing dose-dependent effects on behaviour. Using RNA sequencing (RNA-seq) we identified multiple genes differentially expressed in the zebrafish brain following exposure to clozapine. Network analysis identified co-expression modules characterised by striking changes in module connectivity in response to clozapine, and these were enriched for regulatory pathways relevant to the etiology of schizophrenia. Our study highlights the utility of zebrafish as a model for assessing the molecular consequences of antipsychotic medications and identifies genomic networks potentially involved in schizophrenia.

ACS Style

Joana Viana; Nick Wildman; Eilis Hannon; Audrey Farbos; Paul O’ Neill; Karen Moore; Ronny Van Aerle; Greg Paull; Eduarda Santos; Jonathan Mill. Clozapine-induced transcriptional changes in the zebrafish brain. npj Schizophrenia 2020, 6, 1 -11.

AMA Style

Joana Viana, Nick Wildman, Eilis Hannon, Audrey Farbos, Paul O’ Neill, Karen Moore, Ronny Van Aerle, Greg Paull, Eduarda Santos, Jonathan Mill. Clozapine-induced transcriptional changes in the zebrafish brain. npj Schizophrenia. 2020; 6 (1):1-11.

Chicago/Turabian Style

Joana Viana; Nick Wildman; Eilis Hannon; Audrey Farbos; Paul O’ Neill; Karen Moore; Ronny Van Aerle; Greg Paull; Eduarda Santos; Jonathan Mill. 2020. "Clozapine-induced transcriptional changes in the zebrafish brain." npj Schizophrenia 6, no. 1: 1-11.

Journal article
Published: 06 October 2019 in Aquatic Toxicology
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Hypoxia is one of the major threats to biodiversity in aquatic systems. The association of hypoxia with nutrient-rich effluent input into aquatic systems results in scenarios where hypoxic waters could be contaminated with a wide range of chemicals, including metals. Despite this, little is known about the ability of fish to respond to hypoxia when exposures occur in the presence of environmental toxicants. We address this knowledge gap by investigating the effects of exposures to different levels of oxygen in the presence or absence of copper using the three-spined sticklebacks (Gasterosteus aculeatus) model. Fish were exposed to different air saturations (AS; 100%, 75% and 50%) in combination with copper (20 μg/L) over a 4 day period. The critical oxygen level (Pcrit), an indicator of acute hypoxia tolerance, was 54.64 ± 2.51% AS under control conditions, and 36.21 ± 2.14% when fish were chronically exposed to hypoxia (50% AS) for 4 days, revealing the ability of fish to acclimate to low oxygen conditions. Importantly, the additional exposure to copper (20 μg/L) prevented this improvement in Pcrit, impairing hypoxia acclimation. In addition, an increase in ventilation rate was observed for combined copper and hypoxia exposure, compared to the single stressors or the controls. Interestingly, in the groups exposed to copper, a large increase in variation in the measured Pcrit was observed between individuals, both under normoxic and hypoxic conditions. This variation, if observed in wild populations, may lead to selection for a tolerant phenotype and alterations in the gene pool of the populations, with consequences for their sustainability. Our findings provide strong evidence that copper reduces the capacity of fish to respond to hypoxia by preventing acclimation and will inform predictions of the consequences of global increases of hypoxia in water systems affected by other pollutants worldwide.

ACS Style

Jennifer A. Fitzgerald; Mauricio G. Urbina; Nicholas J. Rogers; Nic R. Bury; Ioanna Katsiadaki; Rod W. Wilson; Eduarda M. Santos. Sublethal exposure to copper supresses the ability to acclimate to hypoxia in a model fish species. Aquatic Toxicology 2019, 217, 105325 .

AMA Style

Jennifer A. Fitzgerald, Mauricio G. Urbina, Nicholas J. Rogers, Nic R. Bury, Ioanna Katsiadaki, Rod W. Wilson, Eduarda M. Santos. Sublethal exposure to copper supresses the ability to acclimate to hypoxia in a model fish species. Aquatic Toxicology. 2019; 217 ():105325.

Chicago/Turabian Style

Jennifer A. Fitzgerald; Mauricio G. Urbina; Nicholas J. Rogers; Nic R. Bury; Ioanna Katsiadaki; Rod W. Wilson; Eduarda M. Santos. 2019. "Sublethal exposure to copper supresses the ability to acclimate to hypoxia in a model fish species." Aquatic Toxicology 217, no. : 105325.

Journal article
Published: 01 August 2018 in Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
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Reproduction is an essential process for life and is regulated by complex hormone networks and environmental factors. To date, little is known about the contribution of epigenetic mechanisms to the regulation of reproduction, particularly in lower vertebrates. We used the zebrafish (Danio rerio) model to investigate the sex-specific transcription and DNA methylation profiles for genes involved in the regulation of reproduction and in epigenetic signalling in the livers and gonads. We found evidence for associations between DNA promotor methylation and transcription for esr1 (gonads and female livers), amh (gonads) and dnmt1 (livers). In the liver, esr1 was shown to be significantly over-expressed in females compared to males, and its promoter was significantly hypo-methylated in females compared to males. In the gonads, genes involved in epigenetic processes including dnmt1, dnmt3 and hdac1 were over-expressed in the ovary compared to the testis. In addition, dnmt1 and dnmt3 transcription in the testis was found to be strongly correlated with global DNA methylation. These data provide evidence of the sex-specific epigenetic regulation and transcription of genes involved in reproduction and epigenetic signalling in a commonly used vertebrate model.

ACS Style

L.V. Laing; J. Viana; Emma Dempster; Tamsyn Uren Webster; R. van Aerle; Jonathan Mill; E.M. Santos. Sex-specific transcription and DNA methylation profiles of reproductive and epigenetic associated genes in the gonads and livers of breeding zebrafish. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 2018, 222, 16 -25.

AMA Style

L.V. Laing, J. Viana, Emma Dempster, Tamsyn Uren Webster, R. van Aerle, Jonathan Mill, E.M. Santos. Sex-specific transcription and DNA methylation profiles of reproductive and epigenetic associated genes in the gonads and livers of breeding zebrafish. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology. 2018; 222 ():16-25.

Chicago/Turabian Style

L.V. Laing; J. Viana; Emma Dempster; Tamsyn Uren Webster; R. van Aerle; Jonathan Mill; E.M. Santos. 2018. "Sex-specific transcription and DNA methylation profiles of reproductive and epigenetic associated genes in the gonads and livers of breeding zebrafish." Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 222, no. : 16-25.

Journal article
Published: 23 July 2018 in Nature Climate Change
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Survival of marine fishes that are exposed to elevated near-future CO2 levels is threatened by their altered responses to sensory cues. Here we demonstrate a physiological and molecular mechanism in the olfactory system that helps to explain altered behaviour under elevated CO2. We combine electrophysiology measurements and transcriptomics with behavioural experiments to investigate how elevated CO2 affects the olfactory system of European sea bass (Dicentrarchus labrax). When exposed to elevated CO2 (approximately 1,000 µatm), fish must be up to 42% closer to an odour source for detection, compared with current CO2 levels (around 400 µatm), decreasing their chances of detecting food or predators. Compromised olfaction correlated with the suppression of the transcription of genes involved in synaptic strength, cell excitability and wiring of the olfactory system in response to sustained exposure to elevated CO2 levels. Our findings complement the previously proposed impairment of γ-aminobutyric acid receptors, and indicate that both the olfactory system and central brain function are compromised by elevated CO2 levels.

ACS Style

Cosima S. Porteus; Peter C. Hubbard; Tamsyn M. Uren Webster; Ronny Van Aerle; Adelino V. M. Canário; Eduarda M. Santos; Rod W. Wilson. Near-future CO2 levels impair the olfactory system of a marine fish. Nature Climate Change 2018, 8, 737 -743.

AMA Style

Cosima S. Porteus, Peter C. Hubbard, Tamsyn M. Uren Webster, Ronny Van Aerle, Adelino V. M. Canário, Eduarda M. Santos, Rod W. Wilson. Near-future CO2 levels impair the olfactory system of a marine fish. Nature Climate Change. 2018; 8 (8):737-743.

Chicago/Turabian Style

Cosima S. Porteus; Peter C. Hubbard; Tamsyn M. Uren Webster; Ronny Van Aerle; Adelino V. M. Canário; Eduarda M. Santos; Rod W. Wilson. 2018. "Near-future CO2 levels impair the olfactory system of a marine fish." Nature Climate Change 8, no. 8: 737-743.

Review
Published: 01 July 2017 in Journal of Invertebrate Pathology
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Over the last decade, advances in high-throughput sequencing technologies have revolutionised biological research, making it possible for DNA/RNA sequencing of any organism of interest to be undertaken. Sequencing approaches are now routinely used in the detection and characterisation of (novel) viruses, investigation of host-pathogen interactions, and effective development of disease treatment strategies. For the sequencing and identification of viruses of interest, metagenomics approaches using infected host tissue are frequently used, as it is not always possible to culture and isolate these pathogens. High-throughput sequencing can also be used to investigate host-pathogen interactions by investigating (temporal) transcriptomic responses of both the host and virus, potentially leading to the discovery of novel opportunities for treatment and drug targets. In addition, viruses in environmental samples (e.g. water or soil samples) can be identified using eDNA/metagenomics approaches. The promise that recent developments in sequencing brings to the field of invertebrate virology are not devoid of technical challenges, including the need for better laboratory and bioinformatics strategies to sequence and assemble virus genomes within complex tissue or environmental samples, and the difficulties associated with the annotation of the large number of novel viruses being discovered.

ACS Style

R. van Aerle; E.M. Santos. Advances in the application of high-throughput sequencing in invertebrate virology. Journal of Invertebrate Pathology 2017, 147, 145 -156.

AMA Style

R. van Aerle, E.M. Santos. Advances in the application of high-throughput sequencing in invertebrate virology. Journal of Invertebrate Pathology. 2017; 147 ():145-156.

Chicago/Turabian Style

R. van Aerle; E.M. Santos. 2017. "Advances in the application of high-throughput sequencing in invertebrate virology." Journal of Invertebrate Pathology 147, no. : 145-156.

Journal article
Published: 01 March 2017 in Environmental Pollution
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Hypoxia is a global problem in aquatic systems and often co-occurs with pollutants. Despite this, little is known about the combined effects of these stressors on aquatic organisms. The objective of this study was to investigate the combined effects of hypoxia and copper, a toxic metal widespread in the aquatic environment. We used the three-spined stickleback (Gasterosteus aculeatus) as a model because of its environmental relevance and amenability for environmental toxicology studies. We focused on embryonic development as this is considered to be a sensitive life stage to environmental pollution. We first investigated the effects of hypoxia alone on stickleback development to generate the information required to design subsequent studies. Our data showed that exposure to low oxygen concentrations (24.7 ± 0.9% air saturation; AS) resulted in strong developmental delays and increased mortalities, whereas a small decrease in oxygen (75.0 ± 0.5%AS) resulted in premature hatching. Stickleback embryos were then exposed to a range of copper concentrations under hypoxia (56.1 ± 0.2%AS) or normoxia (97.6 ± 0.1%AS), continuously, from fertilisation to free swimming larvae. Hypoxia caused significant changes in copper toxicity throughout embryonic development. Prior to hatching, hypoxia suppressed the occurrence of mortalities, but after hatching hypoxia significantly increased copper toxicity. Interestingly, when exposures were conducted only after hatching, the onset of copper-induced mortalities was delayed under hypoxia compared to normoxia, but after 48 h, copper was more toxic to hatched embryos under hypoxia. This is the second species for which the protective effect of hypoxia on copper toxicity prior to hatching, followed by its exacerbating effect after hatching is demonstrated, suggesting the hypothesis that this pattern may be common for teleost species. Our research highlights the importance of considering the interactions between multiple stressors, as understanding these interactions is essential to facilitate the accurate prediction of the consequences of exposure to complex stressors in a rapidly changing environment.

ACS Style

Jennifer A. Fitzgerald; Ioanna Katsiadaki; Eduarda M. Santos. Contrasting effects of hypoxia on copper toxicity during development in the three-spined stickleback (Gasterosteus aculeatus). Environmental Pollution 2017, 222, 433 -443.

AMA Style

Jennifer A. Fitzgerald, Ioanna Katsiadaki, Eduarda M. Santos. Contrasting effects of hypoxia on copper toxicity during development in the three-spined stickleback (Gasterosteus aculeatus). Environmental Pollution. 2017; 222 ():433-443.

Chicago/Turabian Style

Jennifer A. Fitzgerald; Ioanna Katsiadaki; Eduarda M. Santos. 2017. "Contrasting effects of hypoxia on copper toxicity during development in the three-spined stickleback (Gasterosteus aculeatus)." Environmental Pollution 222, no. : 433-443.

Journal article
Published: 01 March 2017 in Aquatic Toxicology
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Some fish populations inhabiting contaminated environments show evidence of increased chemical tolerance, however the mechanisms contributing to this tolerance, and whether this is heritable, are poorly understood. We investigated the responses of two populations of wild three-spined stickleback (Gasterosteus aculeatus) with different histories of contaminant exposure to an oestrogen and copper, two widespread aquatic pollutants. Male stickleback originating from two sites, the River Aire, with a history of complex pollution discharges, and Siblyback Lake, with a history of metal contamination, were depurated and then exposed to copper (46μg/L) and the synthetic oestrogen ethinyloestradiol (22ng/L). The hepatic transcriptomic response was compared between the two populations and to a reference population with no known history of exposure (Houghton Springs, Dorset). Gene responses included those typical for both copper and oestrogen, with no discernable difference in response to oestrogen between populations. There was, however, some difference in the magnitude of response to copper between populations. Siblyback fish showed an elevated baseline transcription of genes encoding metallothioneins and a lower level of metallothionein induction following copper exposure, compared to those from the River Aire. Similarly, a further experiment with an F1 generation of Siblyback fish bred in the laboratory found evidence for elevated transcription of genes encoding metallothioneins in unexposed fish, together with an altered transcriptional response to 125μg/L copper, compared with F1 fish originating from the clean reference population exposed to the same copper concentration. These data suggest that the stickleback from Siblyback Lake have a differential response to copper, which is inherited by the F1 generation in laboratory conditions, and for which the underlying mechanism may include an elevation of baseline transcription of genes encoding metallothioneins. The genetic and/or epigenetic mechanisms contributing to this inherited alteration of metallothionein transcription have yet to be established.

ACS Style

Tamsyn M. Uren Webster; Tim D. Williams; Ioanna Katsiadaki; Anke Lange; Ceri Lewis; Janice A. Shears; Charles R. Tyler; Eduarda M. Santos. Hepatic transcriptional responses to copper in the three-spined stickleback are affected by their pollution exposure history. Aquatic Toxicology 2017, 184, 26 -36.

AMA Style

Tamsyn M. Uren Webster, Tim D. Williams, Ioanna Katsiadaki, Anke Lange, Ceri Lewis, Janice A. Shears, Charles R. Tyler, Eduarda M. Santos. Hepatic transcriptional responses to copper in the three-spined stickleback are affected by their pollution exposure history. Aquatic Toxicology. 2017; 184 ():26-36.

Chicago/Turabian Style

Tamsyn M. Uren Webster; Tim D. Williams; Ioanna Katsiadaki; Anke Lange; Ceri Lewis; Janice A. Shears; Charles R. Tyler; Eduarda M. Santos. 2017. "Hepatic transcriptional responses to copper in the three-spined stickleback are affected by their pollution exposure history." Aquatic Toxicology 184, no. : 26-36.

Journal article
Published: 26 January 2017 in Environmental Science & Technology
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This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Diclofenac is one of the most widely prescribed nonsteroidal anti-inflammatory drugs worldwide. It is frequently detected in surface waters; however, whether this pharmaceutical poses a risk to aquatic organisms is debated. Here we quantified the uptake of diclofenac by the fathead minnow (Pimephales promelas) following aqueous exposure (0.2-25.0 μg L(-1)) for 21 days, and evaluated the tissue and biomolecular responses in the kidney. Diclofenac accumulated in a concentration- and time-dependent manner in the plasma of exposed fish. The highest plasma concentration observed (for fish exposed to 25 μg L(-1) diclofenac) was within the therapeutic range for humans. There was a strong positive correlation between exposure concentration and the number of developing nephrons observed in the posterior kidney. Diclofenac was not found to modulate the expression of genes in the kidney associated with its primary mode of action in mammals (prostaglandin-endoperoxide synthases) but modulated genes associated with kidney repair and regeneration. There were no significant adverse effects following 21 days exposure to concentrations typical of surface waters. The combination of diclofenac's uptake potential, effects on kidney nephrons and relatively small safety margin for some surface waters may warrant a longer term chronic health effects analysis for diclofenac in fish.This work was funded by Knowledge Transfer Partnership (KTP): Use of ‘omic’ technologies in the environmental risk assessment of pharmaceuticals (KTP007650) and AstraZeneca’s Safety, Health and Environment (SHE) Research Programme. We thank Lina Gunnarsson, Matt Winter and James Cresswell (Exeter University), and former members of the Brixham Environmental Laboratory for their advice and assistance. Authors declare no competing financial interest

ACS Style

Lisa K. Bickley; Ronny van Aerle; A. Ross Brown; Adam Hargreaves; Russell Huby; Victoria Cammack; Richard Jackson; Eduarda M. Santos; Charles R. Tyler. Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas). Environmental Science & Technology 2017, 51, 1764 -1774.

AMA Style

Lisa K. Bickley, Ronny van Aerle, A. Ross Brown, Adam Hargreaves, Russell Huby, Victoria Cammack, Richard Jackson, Eduarda M. Santos, Charles R. Tyler. Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas). Environmental Science & Technology. 2017; 51 (3):1764-1774.

Chicago/Turabian Style

Lisa K. Bickley; Ronny van Aerle; A. Ross Brown; Adam Hargreaves; Russell Huby; Victoria Cammack; Richard Jackson; Eduarda M. Santos; Charles R. Tyler. 2017. "Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas)." Environmental Science & Technology 51, no. 3: 1764-1774.

Journal article
Published: 22 August 2016 in Reproduction Abstracts
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Eduarda M. Santos; Webster Tamsyn M. Uren; Lauren V. Laing; Jennifer A. Fitzgerald. Molecular mechanisms of reproductive disruption in fish. Reproduction Abstracts 2016, 1 .

AMA Style

Eduarda M. Santos, Webster Tamsyn M. Uren, Lauren V. Laing, Jennifer A. Fitzgerald. Molecular mechanisms of reproductive disruption in fish. Reproduction Abstracts. 2016; ():1.

Chicago/Turabian Style

Eduarda M. Santos; Webster Tamsyn M. Uren; Lauren V. Laing; Jennifer A. Fitzgerald. 2016. "Molecular mechanisms of reproductive disruption in fish." Reproduction Abstracts , no. : 1.

Research paper
Published: 17 June 2016 in Epigenetics
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Bisphenol A (BPA) is a commercially important high production chemical widely used in epoxy resins and polycarbonate plastics, and is ubiquitous in the environment. Previous studies demonstrated that BPA activates estrogenic signaling pathways associated with adverse effects on reproduction in vertebrates and that exposure can induce epigenetic changes. We aimed to investigate the reproductive effects of BPA in a fish model and to document its mechanisms of toxicity. We exposed breeding groups of zebrafish (Danio rerio) to 0.01, 0.1, and 1 mg/L BPA for 15 d. We observed a significant increase in egg production, together with a reduced rate of fertilization in fish exposed to 1 mg/L BPA, associated with significant alterations in the transcription of genes involved in reproductive function and epigenetic processes in both liver and gonad tissue at concentrations representing hotspots of environmental contamination (0.1 mg/L) and above. Of note, we observed reduced expression of DNA methyltransferase 1 (dnmt1) at environmentally relevant concentrations of BPA, along with a significant reduction in global DNA methylation, in testes and ovaries following exposure to 1 mg/L BPA. Our findings demonstrate that BPA disrupts reproductive processes in zebrafish, likely via estrogenic mechanisms, and that environmentally relevant concentrations of BPA are associated with altered transcription of key enzymes involved in DNA methylation maintenance. These findings provide evidence of the mechanisms of action of BPA in a model vertebrate and advocate for its reduction in the environment.

ACS Style

Lauren Laing; Joana Viana; Emma Dempster; M. Trznadel; L. A. Trunkfield; Tamsyn Uren Webster; Ronny van Aerle; G. C. Paull; Robert Wilson; Jonathan Mill; E. M. Santos. Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio). Epigenetics 2016, 11, 526 -538.

AMA Style

Lauren Laing, Joana Viana, Emma Dempster, M. Trznadel, L. A. Trunkfield, Tamsyn Uren Webster, Ronny van Aerle, G. C. Paull, Robert Wilson, Jonathan Mill, E. M. Santos. Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio). Epigenetics. 2016; 11 (7):526-538.

Chicago/Turabian Style

Lauren Laing; Joana Viana; Emma Dempster; M. Trznadel; L. A. Trunkfield; Tamsyn Uren Webster; Ronny van Aerle; G. C. Paull; Robert Wilson; Jonathan Mill; E. M. Santos. 2016. "Bisphenol A causes reproductive toxicity, decreases dnmt1 transcription, and reduces global DNA methylation in breeding zebrafish (Danio rerio)." Epigenetics 11, no. 7: 526-538.

Research article
Published: 11 April 2016 in Environmental Science & Technology
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Hypoxia is a global and increasingly important stressor in aquatic ecosystems, with major impacts on biodiversity worldwide. Hypoxic waters are often contaminated with a wide range of chemicals but little is known about the interactions between these stressors. We investigated the effects of hypoxia on the responses of zebrafish (Danio rerio) embryos to copper, a widespread aquatic contaminant. We showed that during continuous exposures copper toxicity was reduced by over 2-fold under hypoxia compared to normoxia. When exposures were conducted during 24h windows, hypoxia reduced copper toxicity during early development and increased its toxicity in hatched larvae. In order to investigate the role of the hypoxia signalling pathway on the suppression of copper toxicity during early development, we stabilised the hypoxia inducible factor (HIF) pathway under normoxia using a prolyl-4-hydroxylase inhibitor, dimethyloxalylglycine (DMOG) and demonstrated that HIF activation results in a strong reduction in copper toxicity. We also established that the reduction in copper toxicity during early development was independent of copper uptake, while after hatching, copper uptake was increased under hypoxia, corresponding to an increase in copper toxicity. These findings change our understanding of the current and future impacts of world-wide oxygen depletion on fish communities challenged by anthropogenic toxicants.

ACS Style

Jennifer A. Fitzgerald; Hannah M. Jameson; Victoria H. Dewar Fowler; Georgia L. Bond; Lisa K. Bickley; Tamsyn Uren Webster; Nicolas Bury; Robert Wilson; Eduarda Santos. Hypoxia Suppressed Copper Toxicity during Early Development in Zebrafish Embryos in a Process Mediated by the Activation of the HIF Signaling Pathway. Environmental Science & Technology 2016, 50, 4502 -4512.

AMA Style

Jennifer A. Fitzgerald, Hannah M. Jameson, Victoria H. Dewar Fowler, Georgia L. Bond, Lisa K. Bickley, Tamsyn Uren Webster, Nicolas Bury, Robert Wilson, Eduarda Santos. Hypoxia Suppressed Copper Toxicity during Early Development in Zebrafish Embryos in a Process Mediated by the Activation of the HIF Signaling Pathway. Environmental Science & Technology. 2016; 50 (8):4502-4512.

Chicago/Turabian Style

Jennifer A. Fitzgerald; Hannah M. Jameson; Victoria H. Dewar Fowler; Georgia L. Bond; Lisa K. Bickley; Tamsyn Uren Webster; Nicolas Bury; Robert Wilson; Eduarda Santos. 2016. "Hypoxia Suppressed Copper Toxicity during Early Development in Zebrafish Embryos in a Process Mediated by the Activation of the HIF Signaling Pathway." Environmental Science & Technology 50, no. 8: 4502-4512.