Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach

The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals-the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417-421. © 2015 SETAC

Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback

 This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe effects of toxicant exposure on individuals captured in standard environmental risk assessments (ERA) do not necessarily translate proportionally into effects at the population-level. Population models can incorporate population resilience, physiological susceptibility, and likelihood of exposure, and can therefore be employed to extrapolate from individual- to population-level effects in ERA. Here, we present the development of an individual-based model (IBM) for the three-spined stickleback (Gasterosteus aculeatus) and its application in assessing population-level effects of disrupted male breeding behaviour after exposure to the anti-androgenic pesticide, fenitrothion. The stickleback is abundant in marine, brackish, and freshwater systems throughout Europe and their complex breeding strategy makes wild populations potentially vulnerable to the effects of endocrine disrupting chemicals (EDCs). Modelled population dynamics matched those of a UK field population and the IBM is therefore considered to be representative of a natural population. Literature derived dose-response relationships of fenitrothion-induced disruption of male breeding behaviours were applied in the IBM to assess population-level impacts. The modelled population was exposed to fenitrothion under both continuous (worst-case) and intermittent (realistic) exposure patterns and population recovery was assessed. The results suggest that disruption of male breeding behaviours at the individual-level cause impacts on population abundance under both fenitrothion exposure regimes; however, density-dependent processes can compensate for some of these effects, particularly for an intermittent exposure scenario. Our findings further demonstrate the importance of understanding life-history traits, including reproductive strategies and behaviours, and their density-dependence, when assessing the potential population-level risks of EDCs.Syngenta LtdBiotechnology and Biological Sciences Research Council (BBSRC

Engineered nanomaterials: toward effective safety management in research laboratories

It is still unknown which types of nanomaterials and associated doses represent an actual danger to humans and environment. Meanwhile, there is consensus on applying the precautionary principle to these novel materials until more information is available. To deal with the rapid evolution of research, including the fast turnover of collaborators, a user-friendly and easy-to-apply risk assessment tool offering adequate preventive and protective measures has to be provided.Results: Based on new information concerning the hazards of engineered nanomaterials, we improved a previously developed risk assessment tool by following a simple scheme to gain in efficiency. In the first step, using a logical decision tree, one of the three hazard levels, from H1 to H3, is assigned to the nanomaterial. Using a combination of decision trees and matrices, the second step links the hazard with the emission and exposure potential to assign one of the three nanorisk levels (Nano 3 highest risk; Nano 1 lowest risk) to the activity. These operations are repeated at each process step, leading to the laboratory classification. The third step provides detailed preventive and protective measures for the determined level of nanorisk.Conclusions: We developed an adapted simple and intuitive method for nanomaterial risk management in research laboratories. It allows classifying the nanoactivities into three levels, additionally proposing concrete preventive and protective measures and associated actions. This method is a valuable tool for all the participants in nanomaterial safety. The users experience an essential learning opportunity and increase their safety awareness. Laboratory managers have a reliable tool to obtain an overview of the operations involving nanomaterials in their laboratories; this is essential, as they are responsible for the employee safety, but are sometimes unaware of the works performed. Bringing this risk to a three-band scale (like other types of risks such as biological, radiation, chemical, etc.) facilitates the management for occupational health and safety specialists. Institutes and school managers can obtain the necessary information to implement an adequate safety management system. Having an easy-to-use tool enables a dialog between all these partners, whose semantic and priorities in terms of safety are often different

Comparison of the Effectiveness of Low Carbohydrate Versus Low Fat Diets, in Type 2 Diabetes: Systematic Review and Meta-Analysis of Randomized Controlled Trials

The clinical benefit of low carbohydrate (LC) diets compared with low fat (LF) diets for people with type 2 diabetes (T2D) remains uncertain. We conducted a meta-analysis of randomized controlled trials (RCTs) to compare their efficacy and safety in people with T2D. RCTs comparing both diets in participants with T2D were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies. Mean differences and relative risks with 95% CIs were pooled for measures of glycaemia, cardiometabolic parameters, and adverse events using the following time points: short-term (3 months), intermediate term (6 and 12 months) and long-term (24 months). Twenty-two RCTs comprising 1391 mostly obese participants with T2D were included. At 3 months, a LC vs. LF diet significantly reduced HbA1c levels, mean difference (95% CI) of −0.41% (−0.62, −0.20). LC diet significantly reduced body weight, BMI, fasting insulin and triglycerides and increased total cholesterol and HDL-C levels at the short-to-intermediate term, with a decrease in the requirement for antiglycaemic medications at intermediate-to-long term. There were no significant differences in other parameters and adverse events. Except for reducing HbA1c levels and adiposity parameters at short-to-intermediate terms, a LC diet appears to be equally effective as a LF diet in terms of control of cardiometabolic markers and the risk of adverse events in obese patients with T2D

Qualidade de alface crespa cultivada em sistema orgânico, convencional e hidropônico.

O objetivo deste trabalho foi avaliar a qualidade da alface do grupo crespa, cv. Vera, em sistemas de cultivo orgânico, convencional e hidropônico em Rio Branco-AC. O experimento foi conduzido em julho de 2009. As amostras dos sistemas, convencional e hidropônico (3 marcas comerciais), foram escolhidas aleatoriamente nos supermercados do município de Rio Branco, no mesmo dia de coleta da alface produzida em sistema orgânico. A alface orgânica, produzida na área experimental do Setor de Agricultura Ecológica da Universidade Federal do Acre (UFAC), em Rio Branco, foi cultivada em estufa, sob plantio direto utilizando folhas de bambu como cobertura do solo, e adubada com composto orgânico (17 t ha-1 em base seca). O delineamento utilizado foi o inteiramente casualizado, com cinco tratamentos e quatro repetições compostas por três plantas. As amostras foram lavadas, cortadas e processadas com folha e caule, para obter o suco. Logo após foram determinados os teores de sólidos solúveis e a concentração de nitrato e ácido ascórbico. As três marcas de alface hidropônica apresentaram maior teor de nitrato e menor concentração de sólidos solúveis e ácidos ascórbico, enquanto a alface orgânica apresentou qualidade superior, com baixa concentração de nitrato e maior teor de ácido ascórbico

CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8αα T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8αα T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8αα colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system

Predicting population-level impacts of projected climate heating on a temperate freshwater fish

Data Availability Statement: The NetLogo model and associated input files are available as a supplement to this study. The supporting information is available online at: https://onlinelibrary.wiley.com/doi/10.1111/jfb.15889#support-information-section .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

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress

The interpretations and uses of fitness landscapes in the social sciences

__Abstract__ This working paper precedes our full article entitled “The evolution of Wright’s (1932) adaptive field to contemporary interpretations and uses of fitness landscapes in the social sciences” as published in the journal Biology & Philosophy (http://link.springer.com/article/10.1007/s10539-014-9450-2). The working paper features an extended literature overview of the ways in which fitness landscapes have been interpreted and used in the social sciences, for which there was not enough space in the full article. The article features an in-depth philosophical discussion about the added value of the various ways in which fitness landscapes are used in the social sciences. This discussion is absent in the current working paper. Th