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The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU. © 2013 Bergman et al.; licensee BioMed Central Ltd.

BackgroundFacilitated by the inability to vaccinate, and an immature immune system, COVID-19 remains a leading cause of death among children. Vaccinated lactating mothers produce specific SARS-CoV-2 antibodies in their milk, capable of neutralizing the virus in vitro. Our objective for this study is to assess the effect of COVID-19 booster dose on SARS-CoV-2 antibody concentration and viral neutralization in milk, plasma, and infant stool.MethodsThirty-nine mothers and 25 infants were enrolled from December 2020 to May 2022. Milk, maternal plasma, and infants' stool were collected at various time-points up to 12 months following mRNA COVID-19 vaccination. A subgroup of 14 mothers received a booster dose. SARS-CoV-2 antibody levels and their neutralization capacities were assessed.ResultsBooster vaccination led to significantly higher IgG levels within human milk and breastfed infants' stool. In vitro neutralization of VSV-gfp-SARS-CoV-2-S-gp, a laboratory safe SARS-CoV-2 like pseudovirus, improved following the booster, with a 90% increase in plasma neutralization and a 60% increase in milk neutralization. We found that post-booster neutralization by human milk was highly correlated to SARS-CoV-2 IgG level. In support of our correlation result, Protein G column depletion of IgG in milk yielded a significant reduction in viral neutralization (p = 0.04).DiscussionThe substantial increase in neutralizing IgG levels in milk and breastfed infants' stool post-booster, coupled with the decrease in milk neutralization capabilities upon IgG depletion, underscores the efficacy of booster doses in augmenting the immune response against SARS-CoV-2 in human milk.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory—e.g., the amygdala and hippocampus—are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing β-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.

Abstract Background Identifying ineffective practices that have been used in oncology is important in reducing wasted resources and harm. We sought to examine the prevalence of practices that are being used but have been shown in RCTs to be ineffective (medical reversals) in published oncology studies. Methods We cross-sectionally analyzed studies published in three high-impact oncology medical journals (2009–2018). We abstracted data relating to the frequency and characterization of medical reversals. Results Of the 64 oncology reversals, medications (44%) represented the most common intervention type (39% were targeted). Fourteen (22%) were funded by pharmaceutical/industry only and 56% were funded by an organization other than pharmaceutical/industry. The median number of years that the practice had been in use prior to the reversal study was 9 years (range 1–50 years). Conclusion Here we show that oncology reversals most often involve the administration of medications, have been practiced for years, and are often identified through studies funded by non-industry organizations.

We present a 26-year-old female with HbSC disease who presented to the emergency department multiple times with pain and shortness of breath, eventually developing unresponsiveness and a brief episode of pulseless electrical activity. She was admitted to the intensive care unit with multisystem organ failure and found to have diffuse ischemic strokes. Infectious workup revealed disseminated anaplasmosis and babesiosis, which had likely caused sickle cell crisis, atypical hemolytic-uremic syndrome, and ischemic brain injury. She was started on eculizumab therapy as well as antimicrobial therapy with doxycycline, clindamycin, and atovaquone. The patient was given tracheostomy and a percutaneous feeding tube. Unfortunately, she did not have significant neurologic recovery after prolonged hospital stay and was discharged to a skilled nursing facility with significant neurologic burden.

The ability to identify medical reversals and other low-value medical practices is an essential prerequisite for efforts to reduce spending on such practices. Through an analysis of more than 3000 randomized controlled trials (RCTs) published in three leading medical journals (the Journal of the American Medical Association, the Lancet, and the New England Journal of Medicine), we have identified 396 medical reversals. Most of the studies (92%) were conducted on populations in high-income countries, cardiovascular disease was the most common medical category (20%), and medication was the most common type of intervention (33%).

Connectivity conservation is an emergent approach to counteracting landscape fragmentation and enhancing resilience to climate change at local, national, and global scales. While policy that promotes connectivity is advancing, there has been no systematic, evidence-based study that assesses whether connectivity conservation plans (CCPs) resulted in conservation outcomes, and identifies specific plan attributes that may favor successful implementation. To fill this gap, we gathered 263 terrestrial CCPs from around the world, characterized attributes of 109 plans by surveying plan authors, and conducted semi-structured interviews with authors and implementers of 77 CCPs. The production of CCPs started around 1990 and has increased markedly in all parts of the world, most notably in the United States (led by NGOs and a few states, with little federal involvement), Europe (led by the EU and national policies and implemented at local levels), and the Republic of South Africa (where national legislation mandates each municipality to map corridors and zone all land by 2020). All of the 109 plans that we examined in detail were followed by implementation actions such as crossing structures, ecological restoration, land purchases or easements, recognition of corridors through zoning or government designation, and public engagement. Interviewees emphasized the importance of initial buy-in from key government stakeholders, stakeholder involvement beyond initial buy-in, minimizing staff turnover, and transparent and repeatable procedures. Our quantitative and qualitative analyses similarly suggested that implementation of a CCP was enhanced by enduring partnerships among stakeholders, continuity of leadership, specific recommendations in the CCP using tools appropriately selected from a large toolbox, the existence of enabling legislation and policy, a transparent and repeatable scientific approach, adequate funding, and public outreach.

When it comes to smart cities, one of the most important components is data. To enable smart city applications, data needs to be collected, stored, and processed to accomplish intelligent tasks. In this paper we discuss smart cities and the use of new and existing technologies to improve multiple aspects of these cities. There are also social and environmental aspects that have become important in smart cities that create concerns regarding ethics and ethical conduct. Thus we discuss various issues relating to the appropriate and ethical use of smart city applications and their data. Many smart city projects are being implemented and here we showcase several examples to provide context for our ethical analysis. Law enforcement, structure efficiency, utility efficiency, and traffic flow control applications are some areas that could have the most gains in smart cities; yet, they are the most pervasive as the applications performing these activities must collect and process the most private data about the citizens. The secure and ethical use of this data must be a top priority within every project. The paper also provides a list of challenges for smart city applications pertaining in some ways to ethics. These challenges are drawn from the studied examples of smart city projects to bring attention to ethical issues and raise awareness of the need to address and regulate such use of data.

Medial patellar instability, though infrequently recognized, can be a disabling complication of a lateral retinacular release. Patients with persistent anterior knee pain and instability after lateral release should be evaluated closely. If evidence of increased medial patellar translation is identified on physical examination, a trial of reverse McConnell taping should be prescribed. If there is noted improvement in symptoms after this taping trial, reconstruction of the lateral patellotibial ligament should be considered. This article details our technique for lateral patellotibial ligament reconstruction using iliotibial band and patellar tendon autografts.

Environmental DNA (eDNA) is a technique increasingly used for monitoring organisms in the natural environment including riverine macroinvertebrates. However, the effectiveness of eDNA for monitoring riverine macroinvertebrates compared with the more traditional method of sampling the organisms directly and identifying them via morphological analysis, has not been well established. Furthermore, the ability of the various gene markers and PCR primer sets to detect the full range of riverine invertebrate taxa has not been quantified. Here we conducted a meta-analysis of the available literature, to assess the effectiveness of eDNA sampling for detecting riverine macroinvertebrates compared with sampling for the organisms directly and applying morphological analysis. We found, on average, eDNA sampling, irrespective of the gene marker used, detected fewer riverine invertebrates than morphological sampling. The most effective PCR primer set for identifying taxa was mlCOIintF/jgHCO2198, (mlCOIintF- forward primer, jgHCO2198, - reverse primer). Regardless of the gene marker or primer sets used, however, many taxa were not detected by eDNA metabarcoding that were detected by sampling directly for these invertebrates, including over 100 members of Arthropoda. eDNA sampling failed to detect any species belonging to Nematoda, Platyhelminthes, Cnidaria or Nematomorpha and these markers applied for eDNA sampling in terrestrial systems also do not detect members of Nematoda. In addition to these issues, uncertainties relating to false positives from upstream DNA sources, the stability of DNA from different species, differences in the propensity for DNA release into the environment for different organisms, and lack of available sequence information for numerous taxa illustrates the use of eDNA is not yet applicable as a robust stand-alone method for the monitoring of riverine invertebrates. As a primary consideration, further methodological developments are needed to ensure eDNA captures some of the key freshwater taxa, notably taxa belonging to the phyla Arthropoda, Nematoda, Platyhelminthes, Cnidaria and Nematomorpha., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Imogen Poyntz-Wright reports financial support was provided by Natural Environment Research Council. Imogen Poyntz-Wright reports financial support was provided by United Kingdom Department for Environment Food and Rural Affairs., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Climate heating has the potential to drive changes in ecosystems at multiple levels of biological organization. Temperature directly affects the inherent physiology of plants and animals, resulting in changes in rates of photosynthesis and respiration, and trophic interactions. Predicting temperature-dependent changes in physiological and trophic processes, however, is challenging because environmental conditions and ecosystem structure vary across biogeographical regions of the globe. To realistically predict the effects of projected climate heating on wildlife populations, mechanistic tools are required to incorporate the inherent physiological effects of temperature changes, as well as the associated effects on food availability within and across comparable ecosystems. Here we applied an agent-based bioenergetics model to explore the combined effects of projected temperature increases for 2100 (1.4, 2.7, and 4.4°C), and associated changes in prey availability, on three-spined stickleback (Gasterosteus aculeatus) populations representing latitudes 50, 55, and 60°N. Our results showed a decline in population density after a simulated 1.4°C temperature increase at 50°N. In all other modeled scenarios there was an increase (inflation) in population density and biomass (per unit area) with climate heating, and this inflation increased with increasing latitude. We conclude that agent-based bioenergetics models are valuable tools in discerning the impacts of climate change on wild fish populations, which play important roles in aquatic food webs., (© 2024 The Author(s). Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Antidepressants are one of the most globally prescribed classes of pharmaceuticals, and drug target conservation across phyla means that nontarget organisms may be at risk from the effects of exposure. Here, we address the knowledge gap for the effects of chronic exposure (28 days) to the tricyclic antidepressant amitriptyline (AMI) on fish, including for concentrations with environmental relevance, using zebrafish ( Danio rerio ) as our experimental model. AMI was found to bioconcentrate in zebrafish, was readily transformed to its major active metabolite nortriptyline, and induced a pharmacological effect (downregulation of the gene encoding the serotonin transporter; slc6a4a ) at environmentally relevant concentrations (0.03 μg/L and above). Exposures to AMI at higher concentrations accelerated the hatch rate and reduced locomotor activity, the latter of which was abolished after a 14 day period of depuration. The lack of any response on the features of physiology and behavior we measured at concentrations found in the environment would indicate that AMI poses a relatively low level of risk to fish populations. The pseudopersistence and likely presence of multiple drugs acting via the same mechanism of action, however, together with a global trend for increased prescription rates, mean that this risk may be underestimated using current ecotoxicological assessment paradigms.

Viral outbreaks are a constant threat to aquaculture, limiting production for better global food security. A lack of diagnostic testing and monitoring in resource-limited areas hinders the capacity to respond rapidly to disease outbreaks and to prevent viral pathogens becoming endemic in fisheries productive waters. Recent developments in diagnostic testing for emerging viruses, however, offers a solution for rapid in situ monitoring of viral outbreaks. Genomic epidemiology has furthermore proven highly effective in detecting viral mutations involved in pathogenesis and assisting in resolving chains of transmission. Here, we demonstrate the application of an in-field epidemiological tool kit to track viral outbreaks in aquaculture on farms with reduced access to diagnostic labs, and with non-destructive sampling. Inspired by the "lab in a suitcase" approach used for genomic surveillance of human viral pathogens and wastewater monitoring of COVID19, we evaluated the feasibility of real-time genome sequencing surveillance of the fish pathogen, Infectious spleen and kidney necrosis virus (ISKNV) in Lake Volta. Viral fractions from water samples collected from cages holding Nile tilapia ( Oreochromis niloticus ) with suspected ongoing ISKNV infections were concentrated and used as a template for whole genome sequencing, using a previously developed tiled PCR method for ISKNV. Mutations in ISKNV in samples collected from the water surrounding the cages matched those collected from infected caged fish, illustrating that water samples can be used for detecting predominant ISKNV variants in an ongoing outbreak. This approach allows for the detection of ISKNV and tracking of the dynamics of variant frequencies, and may thus assist in guiding control measures for the rapid isolation and quarantine of infected farms and facilities., Competing Interests: The authors declare there are no competing interests., (©2024 Alathari et al.)

There is growing evidence that rising global temperatures resulting from climate change may exacerbate the toxic effect of pollutants and heterotherms, including fish, in which homestatic mechanisms are directly influenced by environmental temperature will be most affected. Pharmaceuticals discharged into the environment are potentially harmful to wildlife as many of their drug targets are conserved across divergent phyla. Oxidative stress (OS) is a major mechanism by which many pharmaceutical contaminants can induce toxicity but this has received little consideration in the context of effects in wildlife. Further, these mechanisms are relatively poorly understood, particularly regarding multiple stressor interactions. We used transgenic TG(EpRE:mCherry) zebrafish, developed in our laboratory for detecting OS, as our experimental model. We show that the oxidative effects of high concentrations of pharmaceuticals from three different therapeutic classes (paracetamol, diclofenac and doxorubicin) are increased at temperatures elevated by 2-5 °C above those for zebrafish standard husbandry and relevant to their current natural environment (and predicted under the IPCC 2023 scenarios for intermediate to very high greenhouse gas emissions). These OS responses were primarily seen in the pronephros, liver, and gastrointestinal tract. The increase in OS at the increased water temperature may have resulted from the elevated temperature acting as a direct additive physiological stressor to the OS imposed by the drugs and/or via the temperature increasing the chemicals oxidative effect. For paracetamol, it appeared that the elevated responses at the higher temperature of 33 °C were in part due to an increase in uptake of the drug. Our data illustrate that risk assessments for chemicals inducing OS in fish (and likely other heterotherms) should consider the influence of temperature to ensure environmental protection in future environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Small-scale carp polyculture plays a key role in food supply in Bangladesh. However, factors including water pollution, limited infrastructure, and inadequate disease management hinder its sustainability. This paper reports on a survey of 231 farmers across the six major carp producing regions in Bangladesh, analyzing factors including farmers' social aspects, farm characteristics, information on disease and approaches adopted to combat them, and biosecurity practices. Almost half (46.8%) of the farms surveyed experienced disease in carp species, with clear regional variations. Eighty-four percent of farms reported carp mortalities during disease outbreaks, with an average mortality level of 10.23 ± 11.81%. Clinical signs during outbreaks lasted between a week and a month, with a peak in disease outbreaks occurring in two seasonal periods between June and July and October and December. Disease incidence was related to a range of factors including the farmer's experience, ponds/farm type, stocked species, and biosecurity practice. A combination of disinfecting measures during pond preparation and measures during stocking, including discarding fingerling transport water away from the farm, fingerling disinfection, and checking the health of fingerlings before stocking, significantly reduced disease occurrence. Treatments involving antibiotics, ciprofloxacin, erythromycin, and azithromycin were reported as ineffective, raising concerns about their non-prudent use, inadequate dosing (perhaps without appropriate veterinary guidance), and the potential for driving antimicrobial resistance in the environment. The research unveils a concerning pattern of high disease incidence across small-scale carp farms in Bangladesh, and the significant potential for disease spread highlights the need for responsible disposal practices. The study emphasizes the need for improving training and awareness programs for addressing biosecurity and disease management challenges, ensuring sustainable aquaculture and community well-being.

Globally, riverine system biodiversity is threatened by a range of stressors, spanning pollution, sedimentation, alterations to water flow, and climate change. Pesticides have been associated with population level impacts on freshwater invertebrates for acute high-level exposures, but far less is known about the chronic impact of episodic exposure to specific classes of pesticides or their mixtures. Here we employed the use of the UK Environment Agency's monitoring datasets over 40 years (covering years 1980 to 2019) to assess the impacts of AChE (acetylcholinesterase) and GABA (gamma-aminobutyric acid) receptor targeting pesticides on invertebrate family richness at English river sites. Concentrations of AChE and GABA pesticides toxic to freshwater invertebrates occurred (measured) across 18 of the 66 river sites assessed. For one of the three river sites (all found in the Midlands region of England) where data recorded over the past 40 years were sufficient for robust modelling studies, both AChE and GABA pesticides associated with invertebrate family richness. Here, where AChE total pesticide concentrations were classified as high, 46 of 64 invertebrate families were absent, and where GABA total pesticide concentration were classified as high, 16 of 64 invertebrate families were absent. Using a combination of field evidence and laboratory toxicity thresholds for population relevant endpoints we identify families of invertebrates most at risk in the selected English rivers to AChE and GABA pesticides. We, furthermore, provide strong evidence that the absence of the invertebrate family Polycentropodidae (caddisfly) from one field site is due to exposure effects to AChE pesticides., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Imogen Poyntz-Wright reports financial support was provided by Natural Environment Research Council. Imogen Poyntz-Wright reports financial support was provided by United Kingdom Department for Environment Food and Rural Affairs. Susan Zappala reports a relationship with JNCC Support Co that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The skin of fish contains a diverse microbiota that has symbiotic functions with the host, facilitating pathogen exclusion, immune system priming, and nutrient degradation. The composition of fish skin microbiomes varies across species and in response to a variety of stressors, however, there has been no systematic analysis across these studies to evaluate how these factors shape fish skin microbiomes. Here, we examined 1922 fish skin microbiomes from 36 studies that included 98 species and nine rearing conditions to investigate associations between fish skin microbiome, fish species, and water physiochemical factors. Proteobacteria, particularly the class Gammaproteobacteria, were present in all marine and freshwater fish skin microbiomes. Acinetobacter, Aeromonas, Ralstonia, Sphingomonas and Flavobacterium were the most abundant genera within freshwater fish skin microbiomes, and Alteromonas, Photobacterium, Pseudoalteromonas, Psychrobacter and Vibrio were the most abundant in saltwater fish. Our results show that different culturing (rearing) environments have a small but significant effect on the skin bacterial community compositions. Water temperature, pH, dissolved oxygen concentration, and salinity significantly correlated with differences in beta-diversity but not necessarily alpha-diversity. To improve study comparability on fish skin microbiomes, we provide recommendations for approaches to the analyses of sequencing data and improve study reproducibility., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Reproducibility in animal research is impacted by the environment, by husbandry practices in the laboratory and by the animals' provenance. These factors, however, are often not adequately considered by researchers. A disconnect between researchers and animal care staff can result in inappropriate housing and husbandry decisions for scientific studies with those animals. This is especially the case for the research in neuro-behaviour, epigenetics, and the impact of climate change, as heritable phenotypic, behavioural or physiological changes are known to result from the animals' environmental housing, husbandry, provenance and prior experience. This can lead to greater variation (even major differences) in data outcomes among studies, driving scientific uncertainties. Herein, we illustrate some of the endpoints measured in fish studies known to be intrinsically linked to the environment and husbandry conditions and assess the significance of housing and husbandry practice decisions for research adopting these endpoints for different fish species. We highlight the different priorities and challenges faced by researchers and animal care staff and how harmonising their activities and building greater understanding of how husbandry practices affect the fish will improve reproducibility in research outcomes. We furthermore illustrate how improving engagement between stakeholders, including regulatory bodies, can better underpin fish husbandry decisions and where researchers could help to drive best husbandry practices through their own research with fish models., (© 2023 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

The mode of sex determination in vertebrates can be categorized as genotypic or environmental. In the case of genotypic sex determination (GSD), the sexual fate of an organism is determined by the chromosome composition with some having dominant genes, named sex-determining genes, that drive the sex phenotypes. By contrast, many reptiles exhibit environmental sex determination (ESD), whereby environmental stimuli drive sex determination, and most notably temperature. To date, temperature-dependent sex determination (TSD) has been found in most turtles, some lizards, and all crocodylians, but commonalities in the controlling processes are not well established. Recent innovative sequencing technology has enabled investigations into gonadal transcriptomic profiles during temperature-sensitive periods (TSP) in various TSD species which can help elucidate the controlling mechanisms. In this study, we conducted a time-course analysis of the gonadal transcriptome during the male-producing temperature (26℃) of the Reeve's turtle (Chinese three-keeled pond turtle) Mauremys reevesii. We then compared the transcriptome profiles for this turtle species during the TSP with that for the American alligator Alligator mississippiensis to identify conserved reptilian TSD-related genes. Our transcriptome-based findings provide an opportunity to retrieve the candidate molecular cues that are activated during TSP and compare these target responses between TSD and GSD turtle species, and between TSD species., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Globally freshwater biodiversity has experienced major decline and chemical pollutants are believed to have played a significant role in this decline, but this has not been well quantified for most riverine invertebrate populations. Here we applied a biogeographically independent trait-based bioindicator, SPEAR pesticides across sites across five regions (Northern, Midlands and Western, Anglian, Southeast, and Southwest) in England to investigate for associations specifically between pesticide use/pollution and riverine invertebrate communities over a 55-year period (1965-2019). Both spatially and temporally post-1990, the Anglian and Thames regions consistently showed the lowest SPEAR pesticides scores, illustrating the presence of fewer pesticide sensitive species. The Anglian region had the highest pesticide use compared to all other regions from 1990 to 2018 and there were negative relationships between the level of pesticide/insecticide use and the regional SPEAR pesticides score. Biochemical Oxygen Demand and ammonia, as measures of general water quality, were also negatively correlated with the SPEAR pesticides scores across the regions, but these factors were not the driver for the lower SPEAR pesticides scores seen in the Anglian region. Based on SPEAR pesticides scores, riverine invertebrate communities in England have been most impacted in the Anglian region and we evidence chronic insecticide exposure is likely a significant factor in shaping the status of those invertebrate communities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Imogen Poyntz-Wright reports financial support was provided by Natural Environment Research Council. Imogen Poyntz-Wright reports financial support was provided by United Kingdom Department for Environment Food and Rural Affairs. Susan Zappala reports a relationship with JNCC Support Co that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

New tools and refined frameworks for identifying and regulating endocrine-disrupting chemicals (EDCs) are being developed as our scientific understanding of how they work advances. Although focus has largely been on organic chemicals, the potential for metals to act as EDCs in aquatic systems is receiving increasing attention. Metal interactions with the endocrine system are complicated because some metals are essential to physiological systems, including the endocrine system, and nonessential metals can have similar physiochemical attributes that allow substitution into or interference with these systems. Consequently, elevated metal exposure could potentially cause endocrine disruption (ED) but can also cause indirect effects on the endocrine system via multiple pathways or elicit physiologically appropriate compensatory endocrine-mediated responses (endocrine modulation). These latter two effects can be confused with, but are clearly not, ED. In the present study, we provide several case studies that exemplify the challenges encountered in evaluating the endocrine-disrupting (ED) potential of metals, followed by recommendations on how to meet them. Given that metals have multiple modes of action (MOAs), we recommend that assessments use metal-specific adverse outcome pathway networks to ensure that accurate causal links are made between MOAs and effects on the endocrine system. We recommend more focus on establishing molecular initiating events for chronic metal toxicity because these are poorly understood and would reduce uncertainty regarding the potential for metals to be EDCs. Finally, more generalized MOAs such as oxidative stress could be involved in metal interactions with the endocrine system, and we suggest it may be experimentally efficient to evaluate these MOAs when ED is inferred. These experiments, however, must provide explicit linkage to the ED endpoints of interest. Environ Toxicol Chem 2023;42:2564-2579. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

Zinc (Zn) is an essential metal present in numerous enzymes throughout the body, playing a vital role in animal and human health. However, the increasing use of zinc oxide nanomaterials (ZnONPs) in a diverse range of products has raised concerns regarding their potential impacts on health and the environment. Despite these concerns, the toxicity of ZnONP exposure on animal health remain poorly understood. To help address this knowledge gap, we have developed a highly sensitive oxidative stress (OS) biosensor zebrafish capable of detecting cell/tissue-specific OS responses to low doses of various oxidative stressors, including Zn, in a live fish embryo. Using live-imaging analysis with this biosensor zebrafish embryo, we discovered that the olfactory sensory neurons in the brain are especially sensitive to ZnOP exposure. Furthermore, through studies monitoring neutrophil migration and neuronal activation in the embryonic brain and via behaviour analysis, we have found that sub-lethal doses of ZnONPs (ranging from 0.033 to 1 mg/L nominal concentrations), which had no visible effect on embryo growth or morphology, cause significant localised inflammation, disrupting the neurophysiology of olfactory brain tissues and ultimately impaired olfaction-mediated behaviour. Collectively, these findings establish a potent and important effect mechanism for ZnONP toxicity, indicating the olfactory sensory system as the primary target for ZnONPs as an environmental toxicant in aquatic environments. Our result also highlights that even low doses of ZnONPs can have detrimental effects on the olfactory sensory system, surpassing previous expectations. The importance of olfaction in environment sensing, sex behaviours and overall fitness across species raises concerns about the potential impact of ZnONPs on olfaction-mediated brain function and behaviour in animals and humans. Our study emphasises the need for greater consideration of the potential risks associated with these nanomaterials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Endocrine disruption of wild fish, primarily resulting in the feminization of males, has been reported in English river sites for several decades. Estrogenic activity emanating from wastewater treatment works (WwTW) has been conclusively demonstrated to be the main driver of these feminized phenotypes. Here, we revisit 10 English river sites previously surveyed in the late 1990s and early 2000s to assess how the frequency and severity of feminization now compare with the historical surveys. In the contemporary assessment, 60% of the sites revisited still showed endocrine disruption at the tissue organization level (oocytes present in otherwise male gonads; intersex) and 90% of sites had average male plasma vitellogenin concentrations (female-specific yolk protein; a sensitive biomarker of estrogen exposure) above natural baseline levels. In contrast to the historic surveys, none of the males sampled in the contemporary survey had ovarian cavities. At one of the larger WwTW, improvements to treatment technology may have driven a significant reduction in intersex induction, whereas at several of the smaller WwTW sites, the frequencies of feminization did not differ from those observed in the late 1990s. In conclusion, we show that although the severity of feminization is now reduced at many of the revisited sites, endocrine-disrupting chemicals are still impacting wild fish living downstream of WwTW in England.

This study assessed the oxidative stress impacts of Ag NPs and ZnO NPs and their mixtures in zebrafish (Danio rerio). Zebrafish were exposed to sublethal concentrations of each NP and a mixture for 28 days followed by a 28-day recovery period (without NP exposure) and measurements made on hepatic levels of antioxidant enzymes (CAT, SOD, and GPx), MDA levels, expression of the genes for the Hsp70 and Hsp90, and MT, blood biochemical parameters (total protein, globulin, albumin, AST, ALT, ALP, and LDH), and genotoxicity in erythrocytes (via measurement of micronuclei (MN) and nuclear (NA) abnormalities). There was a tendency for an increase in the variation in the responses of antioxidant defense systems and there were higher MDA levels with increasing exposure concentration of Ag NPs and with increasing exposure time. Total protein, globulin, and albumin decreased during the exposure period, especially on the days of 28. Moreover, levels of AST and LDH increased significantly in the NPs co-exposure treatments, while levels of ALT and ALP significantly decreased. The highest expression levels for these genes occurred on day 14 and in the NPs co-exposure treatments. For exposure to both NPs individually and as a mixture, the frequency of MN and other NA were significantly increased (p < 0.05). During the recovery periods, most of the effects seen were reduced, most notably in the individual NPs treatments. The overall results suggest that the toxic effects of Ag NPs and ZnO NPs in combination significantly increase their toxicity in zebrafish., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest related to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Gold nanoparticles (AuNPs) are widely used in biomedicine and their specific properties including, size, geometrics, and surface coating, will affect their fate and behaviour in biological systems. These properties are well studied for their intended biological targets, but there is a lack of understanding on the mechanisms by which AuNPs interact in non-target organisms when they enter the environment. We investigated the effects of size and surface chemistry of AuNPs on their bioavailability, tissue distribution and potential toxicity using zebrafish (Danio rerio) as an experimental model. Larval zebrafish were exposed to fluorescently tagged AuNPs of different sizes (10-100 nm) and surface modifications (TNFα, NHS/PAMAM and PEG), and uptake, tissue distribution and depuration rates were measured using selective-plane illumination microscopy (SPIM). The gut and pronephric tubules were found to contain detectable levels of AuNPs, and the concentration-dependent accumulation was related to the particle size. Surface addition of PEG and TNFα appeared to enhance particle accumulation in the pronephric tubules compared to uncoated particles. Depuration studies showed a gradual removal of particles from the gut and pronephric tubules, although fluorescence indicating the presence of the AuNPs remained in the pronephros 96 h after exposure. Toxicity assessment using two transgenic zebrafish reporter lines, however, revealed no AuNP-related renal injury or cellular oxidative stress. Collectively, our data show that AuNPs used in medical applications across the size range 40-80 nm, are bioavailable to larval zebrafish and some may persist in renal tissue, although their presence did not result in measurable toxicity with respect to pronephric organ function or cellular oxidative stress for short term exposures., Competing Interests: Declaration of Competing Interest SFO is an employee and shareholder of AstraZeneca PLC. All other authors declare no potentially competing interests., (Copyright © 2023. Published by Elsevier Inc.)

The presence of endocrine-active chemicals (EACs) in the environment continues to cause concern for wildlife given their potential for adverse effects on organisms. However, there is a significant lack of understanding about the potential effects of EACs on populations. This has real-world limitations for EAC management and regulation, where the aim in environmental risk assessment is to protect populations. We propose a methodological approach for the application of modeling in addressing the population relevance of EAC exposure in fish. We provide a case study with the fungicide prochloraz to illustrate how this approach could be applied. We used two population models, one for brown trout (Salmo trutta; inSTREAM) and the other for three-spined stickleback (Gasterosteus aculeatus) that met regulatory requirements for development and validation. Effects data extracted from the literature were combined with environmentally realistic exposure profiles generated with the FOCUS SW software. Population-level effects for prochloraz were observed in some modeling scenarios (hazard-threshold [HT]) but not others (dose-response), demonstrating the repercussions of making different decisions on implementation of exposure and effects. The population responses, defined through changes in abundance and biomass, of both trout and stickleback exposed to prochloraz were similar, indicating that the use of conservative effects/exposure decisions in model parameterization may be of greater significance in determining population-level adverse effects to EAC exposure than life-history characteristics. Our study supports the use of models as an effective approach to evaluate the adverse effects of EACs on fish populations. In particular, our HT parameterization is proposed for the use of population modeling in a regulatory context in accordance with Commission Regulation (EU) 2018/605. Environ Toxicol Chem 2023;42:1624-1640. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

With an ever-growing human population, the need for sustainable production of nutritional food sources has never been greater. Aquaculture is a key industry engaged in active development to increase production in line with this need while remaining sustainable in terms of environmental impact and promoting good welfare and health in farmed species. Microbiomes fundamentally underpin animal health, being a key part of their digestive, metabolic and defense systems, in the latter case protecting against opportunistic pathogens in the environment. The potential to manipulate the microbiome to the advantage of enhancing health, welfare and production is an intriguing prospect that has gained considerable traction in recent years. In this review we first set out what is known about the role of the microbiome in aquaculture production systems across the phylogenetic spectrum of cultured animals, from invertebrates to finfish. With a view to reducing environmental footprint and tightening biological and physical control, investment in "closed" aquaculture systems is on the rise, but little is known about how the microbial systems of these closed systems affect the health of cultured organisms. Through comparisons of the microbiomes and their dynamics across phylogenetically distinct animals and different aquaculture systems, we focus on microbial communities in terms of their functionality in order to identify what features within these microbiomes need to be harnessed for optimizing healthy intensified production in support of a sustainable future for aquaculture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lorgen-Ritchie, Uren Webster, McMurtrie, Bass, Tyler, Rowley and Martin.)

In anuran amphibians (frogs and toads), evidence linking pollution to population declines is limited, in particular through impaired reproduction. Here we review the evidence for pollutant-induced alterations on reproductive endpoints in wild anurans with a particular focus on the application of non-destructive endpoints including on sex ratios, male reproductive phenotypes (data are too scarce for females) and reproductive outputs (reflective of mating success). Data evidencing alterations in sex ratio in wild anurans are scarce, however, both feminisation and masculinisation in response to pollution have been reported (seven studies). Male nuptial pad morphology and calling behaviour display high sensitivity to pollutant-exposure and are important features determining male breeding success, however there is considerable variation in these endpoints and inconsistencies in the responses of them to pollution are reported in wild anurans. Data for clutch size are insufficient to assess sensitivity to pollutants (five studies only). However, hatch success and offspring fitness (tadpole survival/development) are sensitive to pollution, with clear linkages to population stability. In conclusion, there are a wide range of non destructive measures with good potential for application to assess/monitor reproductive health in wild anurans, however, a greater understanding of pollutant effects on these endpoints is needed. There measures deserve wider application as they are relatively simple and inexpensive to implement, and as they can be applied non-destructively are widely applicable to our declining anuran populations., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Frances Orton reports financial support was provided by Department of Environment, Food and Rural Affairs., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The increasing levels and frequencies at which active pharmaceutical ingredients (APIs) are being detected in the environment are of significant concern, especially considering the potential adverse effects they may have on nontarget species such as fish. With many pharmaceuticals lacking environmental risk assessments, there is a need to better define and understand the potential risks that APIs and their biotransformation products pose to fish, while still minimizing the use of experimental animals. There are both extrinsic (environment- and drug-related) and intrinsic (fish-related) factors that make fish potentially vulnerable to the effects of human drugs, but which are not necessarily captured in nonfish tests. This critical review explores these factors, particularly focusing on the distinctive physiological processes in fish that underlie drug absorption, distribution, metabolism, excretion and toxicity (ADMET). Focal points include the impact of fish life stage and species on drug absorption (A) via multiple routes; the potential implications of fish's unique blood pH and plasma composition on the distribution (D) of drug molecules throughout the body; how fish's endothermic nature and the varied expression and activity of drug-metabolizing enzymes in their tissues may affect drug metabolism (M); and how their distinctive physiologies may impact the relative contribution of different excretory organs to the excretion (E) of APIs and metabolites. These discussions give insight into where existing data on drug properties, pharmacokinetics and pharmacodynamics from mammalian and clinical studies may or may not help to inform on environmental risks of APIs in fish.

Tilapia farming is one of the most important sectors in aquaculture worldwide and of major importance to global food security. Infectious spleen and kidney necrosis virus (ISKNV) has been identified as an agent of high morbidity and mortality, threatening tilapia aquaculture. ISKNV was detected in Lake Volta, Ghana, in September 2018 and spread rapidly, with mortality rates between 60 and 90% and losses of more than 10 tonnes of fish per day. Understanding the spread and evolution of viral pathogens is important for control strategies. Here, we developed a tiled-PCR sequencing approach for the whole-genome sequencing of ISKNV, using long read sequencing to enable field-based, real-time genomic surveillance. This work represents the first use of tiled-PCR for whole genome recovery of viruses in aquaculture, with the longest genome target (>110 kb dsDNA) to date. Our protocol was applied to field samples collected from the ISKNV outbreaks from four intensive tilapia cage culture systems across Lake Volta, between October 2018 and May 2022. Despite the low mutation rate of dsDNA viruses, 20 single nucleotide polymorphisms accumulated during the sampling period. Droplet digital PCR identified a minimum requirement of template in a sample to recover 50% of an ISKNV genome at 275 femtograms (2410 viral templates per 5 µL sequencing reaction). Overall, tiled-PCR sequencing of ISKNV provides an informative tool to assist in disease control in aquaculture.

Natural capital accounting provides a systematic framework through which to quantify the benefits of natural assets. National-scale applications have demonstrated the feasibility of developing such accounts and their value as a tool to support environmental policy and management decisions. Building on that success, there have been increasing calls for sub-national organisations (for example, protected area authorities and water companies) to develop their own natural capital accounts. As we document in this paper, recent efforts by local organisations in the UK to produce such accounts have tended to rely on a set of 'standard practice' methods, many borrowed directly from national natural capital accounting exercises. In this paper, we review those methods and apply them in producing natural capital accounts for two UK National Parks. Working with the National Park Authorities, we critically assess the usefulness of those accounts to inform local land management. On account of data gaps and significant sensitivity to methodological assumptions, our research shows that these local accounts are considered of limited practical use for land management decision making at a local scale. Through specific illustrative examples, we show that natural capital accounts for local decision-making can be improved through: the inclusion of fit-for-purpose data and valuation methods, the consideration of uncertainties, and the incorporation of ecological information and spatial aspects. We also highlight the need for the development of both standardised guidelines and readily-available tools to quantify and value ecosystem services., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

There was no regulatory requirement for ecotoxicological testing of human pharmaceuticals authorized before 2006, and many of these have little or no data available to assess their environmental risk. Motivated by animal welfare considerations, we developed a decision tree to minimize in vivo fish testing for such legacy active pharmaceutical ingredients (APIs). The minimum no observed effect concentration (NOEC min , the lowest NOEC from chronic Daphnia and algal toxicity studies), the theoretical therapeutic water concentration (TWC, calculated using the fish plasma model), and the predicted environmental concentration (PEC) were used to derive API risk quotients (PEC/NOEC min and PEC/TWC). Based on a verification data set of 96 APIs, we show that by setting a threshold value of 0.001 for both risk quotients, the need for in vivo fish testing could potentially be reduced by around 35% without lowering the level of environmental protection. Hence, for most APIs, applying an assessment factor of 1000 (equivalent to the threshold of 0.001) to NOEC min substituted reliably for NOEC fish , and TWC acted as an effective safety net for the others. In silico and in vitro data and mammalian toxicity data may further support the final decision on the need for fish testing.

Seaweed farming in Europe is growing and may provide environmental benefits, including habitat provisioning, coastal protection, and bioremediation. Habitat provisioning by seaweed farms remains largely unquantified, with previous research focused primarily on the detrimental effects of epibionts, rather than their roles in ecological functioning and ecosystem service provision. We monitored the development and diversity of epibiont assemblages on cultivated sugar kelp (Saccharina latissima) at a farm in Cornwall, southwest UK, and compared the effects of different harvesting techniques on epibiont assemblage structure. Increases in epibiont abundance (PERMANOVA, F4,25 = 100.56, p < 0.001) and diversity (PERMANOVA, F4,25 = 27.25, p < 0.001) were found on cultivated kelps over and beyond the growing season, reaching an average abundance of >6000 individuals per kelp plant with a taxonomic richness of ~9 phyla per kelp by late summer (August). Assemblages were dominated by crustaceans (mainly amphipods), molluscs (principally bivalves) and bryozoans, which provide important ecological roles, despite reducing crop quality. Partial harvesting techniques maintained, or increased, epibiont abundance and diversity beyond the farming season; however, these kelp plants were significantly fouled and would not be commercially viable in most markets. This paper improves understanding of epibiont assemblage development at European kelp farms, which can inform sustainable, ecosystem-based approaches to aquaculture.

Thyroid-hormone-disrupting chemicals are increasingly attracting attention because of their potential harmful effects on animal health, including on fishes. Here, we investigated the effects of exposure to the thyroid-hormone-disrupting chemicals 6-propyl-2-thiouracil (PTU) and tetrabromobisphenol A (TBBPA) on swim bladder inflation, eye development, growth, swimming performance, and the expression of thyroid-related genes in Japanese medaka (Oryzias latipes). PTU exposure resulted in reductions in eye size, growth, and swim bladder inflation, and these effects led to poorer swimming performance. These phenotypic effects were accompanied by increased expression of the thyroid-stimulating hormone subunit beta (tshβ) paralog tshβ-like, but there were no significant changes in expression for tshβ, deiodinase 1 (dio1), deiodinase 2 (dio2), and thyroid hormone receptor alpha (trα) and beta (trβ). For PTU exposure, we identified the key event (swim bladder inflation reduction) and an adverse outcome (swimming performance reduction). No significant effects from TBBPA exposure were seen on swim bladder inflation, eye development, growth, or swimming performance. However, expression of tshβ-like and tshβ (significantly enhanced) and trα and trβ (significantly reduced) were affected by TBBPA exposure albeit not in dose-dependent manners. There were no effects of TBBPA on the expression of dio1 and dio2. We thus show that the two thyroid-hormone-disrupting chemicals PTU and TBBPA differ in their effect profiles with comparable effects on the studied phenotypes and thyroid-related gene expression to those reported in zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We assessed the acute toxicity effects (96 h) of silver nanoparticles (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) and chronic (28 d) exposure to Ag NPs, including in combination with ZnO NPs. In the chronic studies, we further assessed the toxicokinetics and bioaccumulation of Ag and the resulting histopathological effects in the gill, intestine, and liver of zebrafish. Co-exposures with ZnO NPs reduced the toxicity of Ag NPs for acute (lethality) but enhanced the toxicity effects (tissue histopathology) for chronic exposures. The histological lesions for both NPs exposures in the gill included necrosis and fusion of lamellae, for the intestine necrosis and degeneration, and in the liver, mainly necrosis. The severity of the histological lesions induced by the Ag NPs was related to the amount of accumulated Ag in the zebrafish organs. The Ag accumulation in different organs was higher in the presence of ZnO NPs in the order of the gill > intestine > liver. Depuration kinetics illustrated the lowest half-life for Ag occurred in the gill and for the combined exposure of Ag with ZnO NPs. Our findings illustrate that in addition to tissue, time, and exposure concentration dependencies, the Ag NPs toxicity can also be influenced by the co-exposure to other NPs (here ZnO NPs), emphasizing the need for more combination exposure effects studies for NPs to more fully understand their potential environmental health risks., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: All decapod crustaceans are considered potentially susceptible to White Spot Syndrome Virus (WSSV) infection, but the degree of White Spot Disease (WSD) susceptibility varies widely between species. The European shore crab Carcinus maenas can be infected with the virus for long periods of time without signs of disease. Given the high mortality rate of susceptible species, the differential susceptibility of these resistant hosts offers an opportunity to investigate mechanisms of disease resistance., Methods: Here, the temporal transcriptional responses (mRNA and miRNA) of C. maenas following WSSV injection were analysed and compared to a previously published dataset for the highly WSSV susceptible Penaeus vannamei to identify key genes, processes and pathways contributing to increased WSD resistance., Results: We show that, in contrast to P. vannamei , the transcriptional response during the first 2 days following WSSV injection in C. maenas is limited. During the later time points (7 days onwards), two groups of crabs were identified, a recalcitrant group where no replication of the virus occurred, and a group where significant viral replication occurred, with the transcriptional profiles of the latter group resembling those of WSSV-susceptible species. We identify key differences in the molecular responses of these groups to WSSV injection., Discussion: We propose that increased WSD resistance in C. maenas may result from impaired WSSV endocytosis due to the inhibition of internal vesicle budding by dynamin-1, and a delay in movement to the nucleus caused by the downregulation of cytoskeletal transcripts required for WSSV cytoskeleton docking, during early stages of the infection. This response allows resistant hosts greater time to fine-tune immune responses associated with miRNA expression, apoptosis and the melanisation cascade to defend against, and clear, invading WSSV. These findings suggest that the initial stages of infection are key to resistance to WSSV in the crab and highlight possible pathways that could be targeted in farmed crustacean to enhance resistance to WSD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Millard, Bickley, Bateman, Verbruggen, Farbos, Lange, Moore, Stentiford, Tyler, van Aerle and Santos.)

In many vertebrate societies dominant individuals breed at substantially higher rates than subordinates, but whether this hastens ageing remains poorly understood. While frequent reproduction may trade off against somatic maintenance, the extraordinary fecundity and longevity of some social insect queens highlight that breeders need not always suffer more rapid somatic deterioration than their nonbreeding subordinates. Here, we used extensive longitudinal assessments of telomere dynamics to investigate the impact of dominance status on within-individual age-related changes in somatic integrity in a wild social bird, the white-browed sparrow-weaver (Plocepasser mahali). Dominant birds, who monopolise reproduction, had neither shorter telomeres nor faster telomere attrition rates over the long-term (1-5 years) than their subordinates. However, over shorter (half-year) time intervals dominants with shorter telomeres showed lower rates of telomere attrition (and evidence suggestive of telomere lengthening), while the same was not true among subordinates. Dominants may therefore invest more heavily in telomere length regulation (and/or somatic maintenance more broadly); a strategy that could mitigate the long-term costs of reproductive effort, leaving their long-term telomere dynamics comparable to those of subordinates. Consistent with the expectation that reproduction entails short-term costs to somatic integrity, telomere attrition rates were most severe for all birds during the breeding seasons of wetter years (rainfall is the key driver of reproductive activity in this arid-zone species). Our findings suggest that, even in vertebrate societies in which dominants monopolise reproduction, dominants may experience long-term somatic integrity trajectories indistinguishable from those of their nonreproductive subordinates., (© 2021 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Food production environments in low- and middle-income countries (LMICs) are recognized as posing significant and increasing risks to antimicrobial resistance (AMR), one of the greatest threats to global public health and food security systems. In order to maximize and expedite action in mitigating AMR, the World Bank and AMR Global Leaders Group have recommended that AMR is integrated into wider sustainable development strategies. Thus, there is an urgent need for tools to support decision makers in unravelling the complex social and environmental factors driving AMR in LMIC food-producing environments and in demonstrating meaningful connectivity with other sustainable development issues. Here, we applied the Driver-Pressure-State-Impact-Response (DPSIR) conceptual framework to an aquaculture case study site in rural Bangladesh, through the analysis of distinct social, microbiological, and metagenomic data sets. We show how the DPSIR framework supports the integration of these diverse data sets, first to systematically characterize the complex network of societal drivers of AMR in these environments and second to delineate the connectivity between AMR and wider sustainable development issues. Our study illustrates the complexity and challenges of addressing AMR in rural aquaculture environments and supports efforts to implement global policy aimed at mitigating AMR in aquaculture and other rural LMIC food-producing environments.

Experimental exposures aimed at assessing the risks posed by estrogens in waste-water treatment work (WwTW) effluents to fish populations have rarely considered whether populations differ in their sensitivity to estrogenic compounds. This is despite evidence that selection at genes involved in the estrogen response has occurred in wild populations, and evidence that genotype can influence estrogen-response. In this study we compare the effects of a two-year exposure to a low measured concentration (1.3 ng/L) of ethinylestradiol (EE2) on the sexual development of roach (Rutilus rutilus) whose parental generation was sampled from two river stretches heavily contaminated with WwTW effluent and from two without any known WwTW effluent contamination. Exposure to EE2 significantly reduced the proportion of genetic males and induced a range of feminized phenotypes in males. Significantly, exposure also increased the proportion of genetic females with vitellogenic oocytes from 51 to 96%, raising the possibility that estrogen pollution could impact populations of annually spawning fish species through advancing female reproduction by at least a year. However, there was no evidence that river origin affected sensitivity to estrogens in either sex. Thus, we conclude that chronic exposure to low level EE2 has reproductive health outcomes for both male and female roach, but we find no evidence that the nature or magnitude of the response is affected by the population origin., (Copyright © 2022. Published by Elsevier B.V.)

Animal behaviour is remarkably sensitive to disruption by chemical pollution, with widespread implications for ecological and evolutionary processes in contaminated wildlife populations. However, conventional approaches applied to study the impacts of chemical pollutants on wildlife behaviour seldom address the complexity of natural environments in which contamination occurs. The aim of this review is to guide the rapidly developing field of behavioural ecotoxicology towards increased environmental realism, ecological complexity, and mechanistic understanding. We identify research areas in ecology that to date have been largely overlooked within behavioural ecotoxicology but which promise to yield valuable insights, including within- and among-individual variation, social networks and collective behaviour, and multi-stressor interactions. Further, we feature methodological and technological innovations that enable the collection of data on pollutant-induced behavioural changes at an unprecedented resolution and scale in the laboratory and the field. In an era of rapid environmental change, there is an urgent need to advance our understanding of the real-world impacts of chemical pollution on wildlife behaviour. This review therefore provides a roadmap of the major outstanding questions in behavioural ecotoxicology and highlights the need for increased cross-talk with other disciplines in order to find the answers., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

In this Quick guide, Bertram et al. discuss the environmental sources of endocrine-disrupting chemicals and their effects on biological systems., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Globally, millions of zebrafish (Danio rerio) are used for scientific laboratory experiments for which researchers have a duty of care, with legal obligations to consider their welfare. Considering the growing use of the zebrafish as a vertebrate model for addressing a diverse range of scientific questions, optimising their laboratory conditions is of major importance for both welfare and improving scientific research. However, most guidelines for the care and breeding of zebrafish for research are concerned primarily with maximising production and minimising costs and pay little attention to the effects on welfare of the environments in which the fish are maintained, or how those conditions affect their scientific research. Here we review the physical and social conditions in which laboratory zebrafish are kept, identifying and drawing attention to factors likely to affect their welfare and experimental science. We also identify a fundamental lack knowledge of how zebrafish interact with many biotic and abiotic features in their natural environment to support ways to optimise zebrafish health and well-being in the laboratory, and in turn the quality of scientific data produced. We advocate that the conditions under which zebrafish are maintained need to become a more integral part of research and that we understand more fully how they influence experimental outcome and in turn interpretations of the data generated., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

The clinical heterogeneity of heart failure has challenged our understanding of the underlying genetic mechanisms of this disease. In this respect, large-scale patient DNA sequencing studies have become an invaluable strategy for identifying potential genetic contributing factors. The complex aetiology of heart failure, however, also means that in vivo models are vital to understand the links between genetic perturbations and functional impacts as part of the process for validating potential new drug targets. Traditional approaches (e.g., genetically-modified mice) are optimal for assessing small numbers of genes, but less practical when multiple genes are identified. The zebrafish, in contrast, offers great potential for higher throughput in vivo gene functional assessment to aid target prioritisation, by providing more confidence in target relevance and facilitating gene selection for definitive loss of function studies undertaken in mice. Here we used whole-exome sequencing and bioinformatics on human patient data to identify 3 genes ( API5 , HSPB7 , and LMO2 ) suggestively associated with heart failure that were also predicted to play a broader role in disease aetiology. The role of these genes in cardiovascular system development and function was then further investigated using in vivo CRISPR/Cas9-mediated gene mutation analysis in zebrafish. We observed multiple impacts in F0 knockout zebrafish embryos (crispants) following effective somatic mutation, including changes in ventricle size, pericardial oedema, and chamber malformation. In the case of lmo2 , there was also a significant impact on cardiovascular function as well as an expected reduction in erythropoiesis. The data generated from both the human in silico and zebrafish in vivo assessments undertaken supports further investigation of the potential roles of API5 , HSPB7 , and LMO2 in human cardiovascular disease. The data presented also supports the use of human in silico genetic variant analysis, in combination with zebrafish crispant phenotyping, as a powerful approach for assessing gene function as part of an integrated multi-level drug target validation strategy., Competing Interests: Authors SR, MB-Y, AW, and EM are employees of AstraZeneca PLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Winter, Ono, Ball, Walentinsson, Michaelsson, Tochwin, Scholpp, Tyler, Rees, Hetheridge and Bohlooly-Y.)

Zinc oxide nanoparticles (ZnO NPs) and multi-layer graphenes (MLGs) are widely used, and due to the lack of appropriate wastewater treatment may end up in the aquatic environment, with unknown consequences to biota. The main purpose of this study was to assess the acute toxicity, histopathological and behavioural changes caused by the exposure of ZnO NPs and MLGs, alone and combined, to the blackfish Capoeta fusca. The estimated mean 96 h-LC 50 for ZnO NPs was 4.9 mg L -1 and 68.4 mg L -1 for MLGs. In combination, MLGs increased the acute toxicity of the ZnO NPs. The effects of the different NPs on the gills included hyperplasia, aneurisms, and fusion of the lamellae. In the intestine, exposure to the NPs resulted in an increase in the number and swelling of goblet cells and tissue degeneration. Loss of balance, restlessness, erratic and abnormal swimming patterns were the most common behavioural changes seen in the ZnO NPs' exposed blackfish. In contrast with the acute toxicity findings, MLGs decreased the histopathological and behavioural effects of the ZnO NPs on both gills and intestinal tissues as well as fish behaviour. Our experimental results illustrated insights into the simultaneous exposure assessment of metal-based NPs and carbon nanomaterials, although further research is needed on the interactions exposure of these substances to interpreting the toxicological effects of metal-based nanomaterials seen in exposed organisms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)