Bumblebee nest departures under low light conditions at sunrise and sunset.

Only a few diurnal animals, such as bumblebees, extend their activity into the time around sunrise and sunset when illumination levels are low. Low light impairs viewing conditions and increases sensory costs, but whether diurnal insects use low light as a cue to make behavioural decisions is uncertain. To investigate how they decide to initiate foraging at these times of day, we observed bumblebee nest-departure behaviours inside a flight net, under naturally changing light conditions.

An integrated in vitro carcinogenicity test that distinguishes between genotoxic carcinogens, non-genotoxic carcinogens, and non-carcinogens.

Chemical safety testing plays a crucial role in product and pharmacological development, as well as chemoprevention; however, in vitro genotoxicity safety tests do not always accurately predict the chemicals that will be in vivo carcinogens. If chemicals test positive in vitro for genotoxicity but negative in vivo, this can contribute to unnecessary testing in animals used to confirm erroneous in vitro positive results. Current in vitro tests typically evaluate only genotoxicity endpoints, which limits their potential to detect non-genotoxic carcinogens.

Multi-endpoint analysis of cadmium chloride-induced genotoxicity shows role for reactive oxygen species and p53 activation in DNA damage induction, cell cycle irregularities, and cell size aberrations.

Cadmium chloride (CdCl2) is a known genotoxic carcinogen, with a mechanism of action thought to partly involve the generation of reactive oxygen species (ROS). We applied here a multi-endpoint approach in vitro to explore the impact of CdCl2 on both the genome and on wider cell biology pathways relevant to cancer. Multi-endpoint approaches are believed to offer greater promise in terms of understanding the holistic effects of carcinogens in vitro.

Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review.

Mitochondrial DNA mutation and toxicity have been linked to several inherited and acquired diseases; however, these are challenging to diagnose and characterize due to clinical and genetic heterogeneity. This review investigates current techniques for the analysis of mitochondrial perturbations, and novel, emerging endpoints for routine application within the clinical setting. Particular focus is given to the biochemistry of the mitochondria influencing each endpoint and the relation of these to toxicity.

Limiting motorboat noise on coral reefs boosts fish reproductive success.

Anthropogenic noise impacts are pervasive across taxa, ecosystems and the world. Here, we experimentally test the hypothesis that protecting vulnerable habitats from noise pollution can improve animal reproductive success. Using a season-long field manipulation with an established model system on the Great Barrier Reef, we demonstrate that limiting motorboat activity on reefs leads to the survival of more fish offspring compared to reefs experiencing busy motorboat traffic.

Deducing the cellular mechanisms associated with the potential genotoxic impact of gold and silver engineered nanoparticles upon different lung epithelial cell lines .

Human ENP exposure is inevitable and the novel, size-dependent physicochemical properties that enable ENPs to be beneficial in innovative technologies are concomitantly causing heightened public concerns as to their potential adverse effects upon human health. This study aims to deduce the mechanisms associated with potential ENP mediated (geno)toxicity and impact upon telomere integrity, if any, of varying concentrations of both ∼16 nm (4.34 × 10 to 17.

Attack behaviour in naive gyrfalcons is modelled by the same guidance law as in peregrine falcons, but at a lower guidance gain.

The aerial hunting behaviours of birds are strongly influenced by flight morphology and ecology, but little is known of how this relates to the behavioural algorithms guiding flight. Here, we used GPS loggers to record the attack trajectories of captive-bred gyrfalcons () during their maiden flights against robotic aerial targets, which we compared with existing flight data from peregrine falcons (). The attack trajectories of both species were well modelled by a proportional navigation (PN) guidance law, which commands turning in proportion to the angular rate of the line-of-sight to target, at a guidance gain However, naive gyrfalcons operate at significantly lower values of than peregrine falcons, producing slower turning and a longer path to intercept.

The effect of chronic dosing and p53 status on the genotoxicity of pro-oxidant chemicals in vitro.

In this study, we have studied the cytotoxicity and genotoxic potency of 3 pro-oxidants; H2O2, menadione and KBrO3 in different dosing scenarios, namely acute (1-day dosing) and chronic (5-days). For this purpose, relative population doubling (RPD%) and mononucleated micronucleus (MN) test were used. TK6 cells and NH32 were employed in in vitro experiments.

Detection of urethane-induced genotoxicity in vitro using metabolically competent human 2D and 3D spheroid culture models.

In vitro genotoxicity studies are a quick and high throughput approach to assess the genotoxic potential of chemicals; however, the reliability of these tests and their relevance to in vivo effects depends on the choice of representative cell line and optimisation of assay conditions. For chemicals like urethane that require specific metabolic activation to cause genotoxicity, it is important that in vitro tests are conducted using cell lines exhibiting the activity and induction of CYP450 enzymes, including CYP2E1 enzyme that is important in the metabolism of urethane, at a concentration representing actual or perceived chemical exposure. We compared 2D MCL-5 cells and HepG2 cells with 3D HepG2 hanging drop spheroids to determine the genotoxicity of urethane using the micronucleus assay.

Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action.

Current in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound's subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential.

Assessing and mitigating impacts of motorboat noise on nesting damselfish.

Motorboats are a pervasive, growing source of anthropogenic noise in marine environments, with known impacts on fish physiology and behaviour. However, empirical evidence for the disruption of parental care remains scarce and stems predominantly from playback studies. Additionally, there is a paucity of experimental studies examining noise-mitigation strategies.

Comparison of passive-dosed and solvent spiked exposures of pro-carcinogen, benzo[a]pyrene, to human lymphoblastoid cell line, MCL-5.

Genotoxicity testing methods in vitro provide a means to predict the DNA damaging effects of chemicals on human cells. This is hindered in the case of hydrophobic test compounds, however, which will partition to in vitro components such as plastic-ware and medium proteins, in preference to the aqueous phase of the exposure medium. This affects the freely available test chemical concentration, and as this freely dissolved aqueous concentration is that bioavailable to cells, it is important to define and maintain this exposure.

Reprint of: A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies.

The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative.

A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies.

The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative.

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells.

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70-90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis.

Investigation of J-shaped dose-responses induced by exposure to the alkylating agent N-methyl-N-nitrosourea.

Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade.

Genetic toxicity assessment of engineered nanoparticles using a 3D in vitro skin model (EpiDerm™).

Background: The rapid production and incorporation of engineered nanomaterials into consumer products alongside research suggesting nanomaterials can cause cell death and DNA damage (genotoxicity) makes in vitro assays desirable for nanosafety screening. However, conflicting outcomes are often observed when in vitro and in vivo study results are compared, suggesting more physiologically representative in vitro models are required to minimise reliance on animal testing.

Method: BASF Levasil® silica nanoparticles (16 and 85 nm) were used to adapt the 3D reconstructed skin micronucleus (RSMN) assay for nanomaterials administered topically or into the growth medium.

Acute dosing and p53-deficiency promote cellular sensitivity to DNA methylating agents.

Risk assessment of human exposure to chemicals is crucial for understanding whether such agents can cause cancer. The current emphasis on avoidance of animal testing has placed greater importance on in vitro tests for the identification of genotoxicants. Selection of an appropriate in vitro dosing regime is imperative in determining the genotoxic effects of test chemicals.

Recommendations, evaluation and validation of a semi-automated, fluorescent-based scoring protocol for micronucleus testing in human cells.

Micronucleus (MN) induction is an established cytogenetic end point for evaluating structural and numerical chromosomal alterations in genotoxicity testing. A semi-automated scoring protocol for the assessment of MN preparations from human cell lines and a 3D skin cell model has been developed and validated. Following exposure to a range of test agents, slides were stained with 4'-6-diamidino-2-phenylindole (DAPI) and scanned by use of the MicroNuc module of metafer 4, after the development of a modified classifier for selecting MN in binucleate cells.