The last decade has seen substantial advances in the capacity to record behaviour and neural activity in humans in real-world settings, to simulate real-world situations in laboratory settings and to apply sophisticated analyses to large-scale data. Along with these developments, a growing number of groups has begun to advocate for real-world neuroscience and cognitive science. Here, we review the arguments and the available methods for real-world research and outline an overarching framework that embeds key ideas proposed in the literature integrating them into a cyclic process of 'bringing the lab to the real world' (recording behavioural and neural activity in real-world settings) and 'bringing the real-world to the lab' (manipulating the environments in which behaviours occur in the laboratory) that combines exploratory and confirmatory research and is interdisciplinary (including those sciences concerned with the natural, built or virtual environment).
View Article and Find Full Text PDFProtein A (PA) is a bacterial cell wall component of Staphylococcus aureus whose function is to bind to Immunoglobulin G (IgG). Given its ability to bind IgG as well as its stability and resistance to harsh acidic and basic cleaning conditions, it is commonly used in the affinity chromotography purification of biotherapeutics. This use can result in levels of PA being present in a drug product and subsequent patient exposure.
View Article and Find Full Text PDFCounting growth layers in dentine and/or secondary cementum is widely used for age determination in wild mammals but the underlying seasonal changes in the structure and degree of mineralisation of dental tissue have not been well characterised. We embedded first (m1) and second (m2) mandibular permanent molar teeth from a 12-year-old female Svalbard reindeer (Rangifer tarandus platyrhynchus) in PolyMethylMethAcrylate (PMMA), prepared cut and polished surfaces coated with evaporated carbon and used 20 kV back-scattered electron imaging in a scanning electron microscope (BSE-SEM) to study aspects of dental tissue structure which depend on the degree of mineralisation at the micron and sub-micron scale. BSE-SEM revealed differences between the mineral content of growth layers (annulations) in the secondary cementum and the primary and secondary dentine, the latter, incidentally, still forming at death in m1.
View Article and Find Full Text PDFWiley Interdiscip Rev Nanomed Nanobiotechnol
September 2021
The Adverse Outcome Pathway (AOP) framework is serving as a basis to integrate new data streams in order to enhance the power of predictive toxicology. AOP development for engineered nanomaterials (ENM), including silver nanoparticles (AgNP), is currently lagging behind other chemicals of regulatory interest due to our limited understanding of the mechanism by which underlying genetics or diseases directly modify host response to AgNP exposures. This also highlights the importance of considering the Aggregate Exposure Pathway (AEP) framework, which precedes the AOP framework and outlines source to target site exposure.
View Article and Find Full Text PDFSilver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. Previous studies have identified AgNP toxicity in airway epithelial cells, but no studies to date have used organotypic cultures as a high-content model of the conducting airway to characterize the effects of interactions between host genetic and acquired factors, or gene × phenotype interactions (G × P), on AgNP toxicity. In the present study, we derived organotypic cultures from primary murine tracheal epithelial cells (MTEC) to characterize nominal and dosimetric dose-response relationships for AgNPs with a gold core on barrier dysfunction, glutathione (GSH) depletion, reactive oxygen species (ROS) production, lipid peroxidation, and cytotoxicity across two genotypes (A/J and C57BL/6J mice), two phenotypes ('Normal' and 'Type 2 [T2]-Skewed'), and two exposures (an acute exposure of 24 h and a subacute exposure of 4 h, every other day, over 5 days [5 × 4 h]).
View Article and Find Full Text PDFThe airway epithelium is critical for maintaining innate and adaptive immune responses, and occupational exposures that disrupt its immune homeostasis may initiate and amplify airway inflammation. In our previous study, we demonstrated that silver nanoparticles (AgNP), which are engineered nanomaterials used in multiple applications but primarily in the manufacturing of many antimicrobial products, induce toxicity in organotypic cultures derived from murine tracheal epithelial cells (MTEC), and those differentiated toward a "Type 2 [T2]-Skewed" phenotype experienced an increased sensitivity to AgNP toxicity, suggesting that asthmatics could be a sensitive population to AgNP exposures in occupational settings. However, the mechanistic basis for this genotype × phenotype (G × P) interaction has yet to be defined.
View Article and Find Full Text PDFThe evidence that diel patterns of physiology and behaviour in mammals are governed by circadian 'clocks' is based almost entirely on studies of nocturnal rodents. The emergent circadian paradigm, however, neglects the roles of energy metabolism and alimentary function (feeding and digestion) as determinants of activity pattern. The temporal control of activity varies widely across taxa, and ungulates, microtine rodents, and insectivores provide examples in which circadian timekeeping is vestigial.
View Article and Find Full Text PDFSilver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. AgNP toxicity in the respiratory system is well characterized, but few in vitro or in vivo studies have evaluated the effects of interactions between host genetic and acquired factors or gene × environment interactions (G × E) on AgNP toxicity in the respiratory system. The primary goal of this article is to review host genetic and acquired factors identified across in vitro and in vivo studies and prioritize those necessary for defining exposure limits to protect all populations.
View Article and Find Full Text PDFExposure estimates that do not account for time in-transit may underestimate exposure to traffic-related air pollution, but exact contributions have not been studied directly. We conducted a 2-week monitoring, including novel in-vehicle sampling, in a subset of the Multi-Ethnic Study of Atherosclerosis and Air Pollution cohort in two cities. Participants spent the majority of their time indoors and only 4.
View Article and Find Full Text PDFOccurrence of 24-h rhythms in species apparently lacking functional molecular clockwork indicates that strong circadian mechanisms are not essential prerequisites of robust timing, and that rhythmical patterns may arise instead as passive responses to periodically changing environmental stimuli. Thus, in a new synthesis of grazing in a ruminant (MINDY), crepuscular peaks of activity emerge from interactions between internal and external stimuli that influence motivation to feed, and the influence of the light/dark cycle is mediated through the effect of low nocturnal levels of food intake on gastric function. Drawing on risk allocation theory, we hypothesized that the timing of behavior in ruminants is influenced by the independent effects of light on motivation to feed and perceived risk of predation.
View Article and Find Full Text PDFSeasonally breeding mammals use the annual change in the photoperiod cycle to drive rhythmic nocturnal melatonin signals from the pineal gland, providing a critical cue to time seasonal reproduction. Paradoxically, species resident at high latitudes achieve tight regulation of the temporal pattern of growth and reproduction despite the absence of photoperiodic information for most of the year. In this study, we show that the melatonin rhythm of reindeer (Rangifer tarandus) is acutely responsive to the light/dark cycle but not to circadian phase, and also that two key clock genes monitored in reindeer fibroblast cells display little, if any, circadian rhythmicity.
View Article and Find Full Text PDFAt the close of the Fourth International Polar Year, we take stock of the ecological consequences of recent climate change in the Arctic, focusing on effects at population, community, and ecosystem scales. Despite the buffering effect of landscape heterogeneity, Arctic ecosystems and the trophic relationships that structure them have been severely perturbed. These rapid changes may be a bellwether of changes to come at lower latitudes and have the potential to affect ecosystem services related to natural resources, food production, climate regulation, and cultural integrity.
View Article and Find Full Text PDFNonlinear and irregular population dynamics may arise as a result of phase dependence and coexistence of multiple attractors. Here we explore effects of climate and density in the dynamics of a highly fluctuating population of wild reindeer (Rangifer tarandus platyrhynchus) on Svalbard observed over a period of 29 years. Time series analyses revealed that density dependence and the effects of local climate (measured as the degree of ablation [melting] of snow during winter) on numbers were both highly nonlinear: direct negative density dependence was found when the population was growing (Rt > 0) and during phases of the North Atlantic Oscillation (NAO) characterized by winters with generally high (1979-1995) and low (1996-2007) indices, respectively.
View Article and Find Full Text PDFIn reindeer Rangifer tarandus, a high latitude species, the rhythmic production of melatonin periodically dissipates under natural photoperiods when, in mid-winter, there is near permanent darkness and again, in summer, when there is permanent light. In spring and autumn, as expected, melatonin production reflects the ambient light:dark (LD) cycle. We investigated the expression of circadian mechanisms on blood levels of melatonin in reindeer.
View Article and Find Full Text PDFBiological rhythms are a result of interplay between endogenous clocks and the ambient light-dark (LD) cycle. Biological timing in resident polar organisms presents a conundrum because these experience distinct daily LD cycles for only a few weeks each year. We measured locomotor activity in reindeer, Rangifer tarandus platyrhynchus (SR, n = 5 and 6) and R.
View Article and Find Full Text PDFThe light/dark cycle of day and night synchronizes an internal 'biological clock' that governs daily rhythms in behaviour, but this form of regulation is denied to polar animals for most of the year. Here we demonstrate that the continuous lighting conditions of summer and of winter at high latitudes cause a loss in daily rhythmic activity in reindeer living far above the Arctic Circle. This seasonal absence of circadian rhythmicity may be a ubiquitous trait among resident polar vertebrates.
View Article and Find Full Text PDFThe vulnerability framework of the Research and Assessment Systems for Sustainability Program explicitly recognizes the coupled human-environment system and accounts for interactions in the coupling affecting the system's responses to hazards and its vulnerability. This paper illustrates the usefulness of the vulnerability framework through three case studies: the tropical southern Yucatán, the arid Yaqui Valley of northwest Mexico, and the pan-Arctic. Together, these examples illustrate the role of external forces in reshaping the systems in question and their vulnerability to environmental hazards, as well as the different capacities of stakeholders, based on their access to social and biophysical capital, to respond to the changes and hazards.
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