Thyroid hormone links environmental signals to DNA methylation.

Environmental conditions experienced within and across generations can impact individual phenotypes via so-called 'epigenetic' processes. Here we suggest that endocrine signalling acts as a 'sensor' linking environmental inputs to epigenetic modifications. We focus on thyroid hormone signalling and DNA methylation, but other mechanisms are likely to act in a similar manner. DNA methylation is one of the most important epigenetic mechanisms, which alters gene expression patterns by methylating cytosine bases via DNA methyltransferase enzymes. Thyroid hormone is mechanistically linked to DNA methylation, at least partly by regulating the activity of DNA methyltransferase 3a, which is the principal enzyme that mediates epigenetic responses to environmental change. Thyroid signalling is sensitive to natural and anthropogenic environmental impacts (e.g. light, temperature, endocrine-disrupting pollution), and here we propose that thyroid hormone acts as an environmental sensor to mediate epigenetic modifications. The nexus between thyroid hormone signalling and DNA methylation can integrate multiple environmental signals to modify phenotypes, and coordinate phenotypic plasticity at different time scales, such as within and across generations. These dynamics can have wide-ranging effects on health and fitness of animals, because they influence the time course of phenotypic adjustments and potentially the range of environmental stimuli that can elicit epigenetic responses. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Endocrine responses to environmental variation.

Hormones regulate most physiological functions and life history from embryonic development to reproduction. In addition to their roles in growth and development, hormones also mediate responses to the abiotic, social and nutritional environments. Hormone signalling is responsive to environmental changes to adjust phenotypes to prevailing conditions. Both hormone levels and receptor densities can change to provide a flexible system of regulation. Endocrine flexibility connects the environment to organismal function, and it is central to understanding environmental impacts and their effect on individuals and populations. Hormones may also act as a 'sensor' to link environmental signals to epigenetic processes and thereby effect phenotypic plasticity within and across generations. Many environmental parameters are now changing in unprecedented ways as a result of human activity. The knowledge base of organism-environmental interactions was established in environments that differ in many ways from current conditions as a result of ongoing human impacts. It is an urgent contemporary challenge to understand how evolved endocrine responses will modulate phenotypes in response to anthropogenic environmental impacts including climate change, light-at-night and chemical pollution. Endocrine responses play a central role in ecology, and their integration into conservation can lead to more effective outcomes. This article is part of the theme issue 'Endocrine responses to environmental variation: conceptual approaches and recent developments'.

Impacts of sequential salinity and heat stress are recovery time-specific in freshwater crustacean, Daphnia pulicaria.

Stressors can interact to affect animal fitness, but we have limited knowledge about how temporal variation in stressors may impact their combined effect. This limits our ability to predict the outcomes of pollutants and future dynamic environmental changes. Elevated salinity in freshwater ecosystems has been observed worldwide. Meanwhile, heatwaves have become more frequent and intensified as an outcome of climate change. These two stressors can jointly affect organisms; however, their interaction has rarely been explored in the context of freshwater ecosystems. We conducted lab experiments using Daphnia pulicaria, a key species in lakes, to investigate how elevated salinity and heatwave conditions collectively affect freshwater organisms. We also monitored the impacts of various recovery times between the two stressors. Daphnia physiological conditions (metabolic rate, Na+-K+-ATPase (NKA) activity, and lipid peroxidation level) and life history traits (survival, fecundity, and growth) in response to salt stress as well as mortality in heat treatment were examined. We found that Daphnia responded to elevated salinity by upregulating NKA activity and increasing metabolic rate, causing a high lipid peroxidation level. Survival, fecundity, and growth were all negatively affected by this stressor. These impacts on physiological conditions and life history traits persisted for a few days after the end of the exposure. Heat treatments caused mortality in Daphnia, which increased with rising temperature. Results also showed that individuals that experienced salt exposure were more susceptible to subsequent heat stress, but this effect decreased with increasing recovery time between stressors. Findings from this work suggest that the legacy effects from a previous stressor can reduce individual resistance to a subsequent stressor, adding great difficulties to the prediction of outcomes of multiple stressors. Our work also demonstrates that cross-tolerance/susceptibility and the associated mechanisms remain unclear, necessitating further investigation.

Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration.

Respiratory reductases enable microorganisms to use molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae and Erysipelotrichaceae) that encode large arsenals of tens to hundreds of respiratory-like reductases per genome. Screening species from each family (Sutterella wadsworthensis, Eggerthella lenta and Holdemania filiformis), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner. Identified reactions transform multiple classes of dietary- and host-derived metabolites, including bioactive molecules resveratrol and itaconate. Products of identified respiratory metabolisms highlight poorly characterized compounds, such as the itaconate-derived 2-methylsuccinate. Reductase substrate profiling defines enzyme-substrate pairs and reveals a complex picture of reductase evolution, providing evidence that reductases with specificities for related cinnamate substrates independently emerged at least four times. These studies thus establish an exceptionally versatile form of anaerobic respiration that directly links microbial energy metabolism to the gut metabolome.

Low Glycolysis Is Neuroprotective during Anoxic Spreading Depolarization (SD) and Reoxygenation in Locusts.

Migratory locusts enter a reversible hypometabolic coma to survive environmental anoxia, wherein the cessation of CNS activity is driven by spreading depolarization (SD). While glycolysis is recognized as a crucial anaerobic energy source contributing to animal anoxia tolerance, its influence on the anoxic SD trajectory and recovery outcomes remains poorly understood. We investigated the effects of varying glycolytic capacity on adult female locust anoxic SD parameters, using glucose or the glycolytic inhibitors 2-deoxy-d-glucose (2DG) or monosodium iodoacetate (MIA). Surprisingly, 2DG treatment shared similarities with glucose yet had opposite effects compared with MIA. Specifically, although SD onset was not affected, both glucose and 2DG expedited the recovery of CNS electrical activity during reoxygenation, whereas MIA delayed it. Additionally, glucose and MIA, but not 2DG, increased tissue damage and neural cell death following anoxia-reoxygenation. Notably, glucose-induced injuries were associated with heightened CO2 output during the early phase of reoxygenation. Conversely, 2DG resulted in a bimodal response, initially dampening CO2 output and gradually increasing it throughout the recovery period. Given the discrepancies between effects of 2DG and MIA, the current results require cautious interpretations. Nonetheless, our findings present evidence that glycolysis is not a critical metabolic component in either anoxic SD onset or recovery and that heightened glycolysis during reoxygenation may exacerbate CNS injuries. Furthermore, we suggest that locust anoxic recovery is not solely dependent on energy availability, and the regulation of metabolic flux during early reoxygenation may constitute a strategy to mitigate damage.

Future increased risk from extratropical windstorms in northern Europe.

European windstorms cause socioeconomic losses due to wind damage. Projections of future losses from such storms are subject to uncertainties from the frequency and tracks of the storms, their intensities and definitions thereof, and socio-economic scenarios. We use two storm severity indices applied to objectively identified extratropical cyclone footprints from a multi-model ensemble of state-of-the-art climate models under different future socio-economic scenarios. Here we show storm frequency increases across northern and central Europe, where the meteorological storm severity index more than doubles. The population-weighted storm severity index more than triples, due to projected population increases. Adapting to the increasing wind speeds using future damage thresholds, the population weighted storm severity index increases are only partially offset, despite a reduction in the meteorological storm severity through adaptation. Through following lower emissions scenarios, the future increase in risk is reduced, with the population-weighted storm severity index increase more than halved.

Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes.

Cellular behaviors emerge from layers of molecular interactions: proteins interact to form complexes, pathways, and phenotypes. We show that hierarchical networks of protein interactions can be defined from the statistical pattern of proteome variation measured across thousands of diverse bacteria and that these networks reflect the emergence of complex bacterial phenotypes. Our results are validated through gene-set enrichment analysis and comparison to existing experimentally derived databases. We demonstrate the biological utility of our approach by creating a model of motility in Pseudomonas aeruginosa and using it to identify a protein that affects pilus-mediated motility. Our method, SCALES (Spectral Correlation Analysis of Layered Evolutionary Signals), may be useful for interrogating genotype-phenotype relationships in bacteria.

Physiological Performance Curves: When Are They Useful?

This review serves as an introduction to a special issue of Frontiers in Physiology, focused on the importance of physiological performance curves across phylogenetic and functional boundaries. Biologists have used performance curves to describe the effects of changing environmental conditions on animal physiology since the late 1800s (at least). Animal physiologists have studied performance curves extensively over the past decades, and there is a good foundation to understanding how the environment affects physiological functions of individuals. Our goal here was to build upon this research and address outstanding questions regarding the mutability and applicability of performance curves across taxonomic groups and levels of biological organization. Performance curves are not fixed at a taxonomic, population, or individual level - rather they are dynamic and can shift in response to evolutionary pressures (e.g., selection) and epigenetic programming (e.g., plasticity). The mechanisms underlying these shifts are being increasingly used to predict the efficacy with which plasticity and heritability of performance curves can render individuals and populations less vulnerable to climate change. Individual differences in physiological performance curves (and plasticity of performance curves) can also have cascading effects at higher levels of biological organization. For instance, individual physiology likely influences group behaviors in non-additive ways. There is a need therefore to extend the concept of performance curves to social interactions and sociality. Collectively, this special issue emphasizes the power of how within- and between-individual shifts in performance curves might scale up to the population-, species-, and community-level dynamics that inform conservation management strategies.

Plasticity of Performance Curves in Ectotherms: Individual Variation Modulates Population Responses to Environmental Change.

Many ectothermic animals can respond to changes in their environment by altering the sensitivities of physiological rates, given sufficient time to do so. In other words, thermal acclimation and developmental plasticity can shift thermal performance curves so that performance may be completely or partially buffered against the effects of environmental temperature changes. Plastic responses can thereby increase the resilience to temperature change. However, there may be pronounced differences between individuals in their capacity for plasticity, and these differences are not necessarily reflected in population means. In a bet-hedging strategy, only a subsection of the population may persist under environmental conditions that favour either plasticity or fixed phenotypes. Thus, experimental approaches that measure means across individuals can not necessarily predict population responses to temperature change. Here, we collated published data of 608 mosquitofish (Gambusia holbrooki) each acclimated twice, to a cool and a warm temperature in random order, to model how diversity in individual capacity for plasticity can affect populations under different temperature regimes. The persistence of both plastic and fixed phenotypes indicates that on average, neither phenotype is selectively more advantageous. Fish with low acclimation capacity had greater maximal swimming performance in warm conditions, but their performance decreased to a greater extent with decreasing temperature in variable environments. In contrast, the performance of fish with high acclimation capacity decreased to a lesser extent with a decrease in temperature. Hence, even though fish with low acclimation capacity had greater maximal performance, high acclimation capacity may be advantageous when ecologically relevant behaviour requires submaximal locomotor performance. Trade-offs, developmental effects and the advantages of plastic phenotypes together are likely to explain the observed population variation.

Utilizing comparative models in biomedical research.

This review serves as an introduction to a Special Issue of Comparative Biochemistry and Physiology, focused on using non-human models to study biomedical physiology. The concept of a model differs across disciplines. For example, several models are used primarily to gain an understanding of specific human pathologies and disease states, whereas other models may be focused on gaining insight into developmental or evolutionary mechanisms. It is often the case that animals initially used to gain knowledge of some unique biochemical or physiological process finds foothold in the biomedical community and becomes an established model. The choice of a particular model for biomedical research is an ongoing process and model validation must keep pace with existing and emerging technologies. While the importance of non-mammalian models, such as Caenorhabditis elegans, Drosophila melanogaster, Danio rerio and Xenopus laevis, is well known, we also seek to bring attention to emerging alternative models of both invertebrates and vertebrates, which are less established but of interest to the comparative biochemistry and physiology community.

WITHDRAWN: Utilizing comparative models in biomedical research.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, Volume 255, 2021, 110593, https://doi.org/10.1016/j.cbpb.2021.110593. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

DNA methyltransferase 3a mediates developmental thermal plasticity.

BACKGROUND: Thermal plasticity is pivotal for evolution in changing climates and in mediating resilience to its potentially negative effects. The efficacy to respond to environmental change depends on underlying mechanisms. DNA methylation induced by DNA methyltransferase 3 enzymes in the germline or during early embryonic development may be correlated with responses to environmental change. This developmental plasticity can interact with reversible acclimation within adult organisms, which would increase the speed of response and could alleviate potential mismatches between parental or early embryonic environments and those experienced at later life stages. Our aim was to determine whether there is a causative relationship between DNMT3 enzyme and developmental thermal plasticity and whether either or both interact with short-term acclimation to alter fitness and thermal responses in zebrafish (Danio rerio). RESULTS: We developed a novel DNMT3a knock-out model to show that sequential knock-out of DNA methyltransferase 3a isoforms (DNMT3aa-/- and DNMT3aa-/-ab-/-) additively decreased survival and increased deformities when cold developmental temperatures in zebrafish offspring mismatched warm temperatures experienced by parents. Interestingly, short-term cold acclimation of parents before breeding rescued DNMT3a knock-out offspring by restoring survival at cold temperatures. DNMT3a knock-out genotype interacted with developmental temperatures to modify thermal performance curves in offspring, where at least one DNMT3a isoform was necessary to buffer locomotion from increasing temperatures. The thermal sensitivity of citrate synthase activity, an indicator of mitochondrial density, was less severely affected by DNMT3a knock-out, but there was nonetheless a significant interaction between genotype and developmental temperatures. CONCLUSIONS: Our results show that DNMT3a regulates developmental thermal plasticity and that the phenotypic effects of different DNMT3a isoforms are additive. However, DNMT3a interacts with other mechanisms, such as histone (de)acetylation, induced during short-term acclimation to buffer phenotypes from environmental change. Interactions between these mechanisms make phenotypic compensation for climate change more efficient and make it less likely that thermal plasticity incurs a cost resulting from environmental mismatches.

Sex differences in the association between tumor growth and T cell response in a melanoma mouse model.

Epidemiological evidence suggests that females have an advantage over males in cases of melanoma incidence, progression, and survival. However, the biological mechanisms underlying these sex differences remain unclear. With the knowledge that females generally have a more robust immune system than males, we investigated sex differences in melanoma progression in a B16-F10/BL6 syngeneic mouse model. We observed significantly less tumor volume and growth rate over 14 days in female mice compared to male mice. Furthermore, higher populations of CD4+ and CD8+ T cells, which indicate adaptive immune responses, were found in the circulating blood and tumors of females and corresponded with less tumor growth, and vice versa in males. Our results highlight a mouse model that represents melanoma progression in the human population and displays a higher immune response to melanoma in females compared to males. These findings suggest that the immune system may be one of the mechanisms responsible for sex differences in melanoma.

Behavioral and physiological evidence that increasing group size ameliorates the impacts of social disturbance.

Intra-group social stability is important for the long-term productivity and health of social organisms. We evaluated the effect of group size on group stability in the face of repeated social perturbations using a cooperatively breeding fish, Neolamprologus pulcher In a laboratory study, we compared both the social and physiological responses of individuals from small versus large groups to the repeated removal and replacement of the most dominant group member (the breeder male), either with a new male (treatment condition) or with the same male (control condition). Individuals living in large groups were overall more resistant to instability but were seemingly slower to recover from perturbation. Members of small groups were more vulnerable to instability but recovered faster. Breeder females in smaller groups also showed greater physiological preparedness for instability following social perturbations. In sum, we discover both behavioral and physiological evidence that living in larger groups helps to dampen the impacts of social instability in this system.

What do warming waters mean for fish physiology and fisheries?

Environmental signals act primarily on physiological systems, which then influence higher-level functions such as movement patterns and population dynamics. Increases in average temperature and temperature variability associated with global climate change are likely to have strong effects on fish physiology and thereby on populations and fisheries. Here we review the principal mechanisms that transduce temperature signals and the physiological responses to those signals in fish. Temperature has a direct, thermodynamic effect on biochemical reaction rates. Nonetheless, plastic responses to longer-term thermal signals mean that fishes can modulate their acute thermal responses to compensate at least partially for thermodynamic effects. Energetics are particularly relevant for growth and movement, and therefore for fisheries, and temperature can have pronounced effects on energy metabolism. All energy (ATP) production is ultimately linked to mitochondria, and temperature has pronounced effects on mitochondrial efficiency and maximal capacities. Mitochondria are dependent on oxygen as the ultimate electron acceptor so that cardiovascular function and oxygen delivery link environmental inputs with energy metabolism. Growth efficiency, that is the conversion of food into tissue, changes with temperature, and there are indications that warmer water leads to decreased conversion efficiencies. Moreover, movement and migration of fish relies on muscle function, which is partially dependent on ATP production but also on intracellular calcium cycling within the myocyte. Neuroendocrine processes link environmental signals to regulated responses at the level of different tissues, including muscle. These physiological processes within individuals can scale up to population responses to climate change. A mechanistic understanding of thermal responses is essential to predict the vulnerability of species and populations to climate change.

Maxed Out: Optimizing Accuracy, Precision, and Power for Field Measures of Maximum Metabolic Rate in Fishes.

Both laboratory and field respirometry are rapidly growing techniques to determine animal performance thresholds. However, replicating protocols to estimate maximum metabolic rate (MMR) between species, populations, and individuals can be difficult, especially in the field. We therefore evaluated seven different exercise treatments-four laboratory methods involving a swim tunnel (critical swim speed [Ucrit], Ucrit postswim fatigue, maximum swim speed [Umax], and Umax postswim fatigue) and three field-based chasing methods (3-min chase with 1-min air exposure, 3-min chase with no air exposure, and chase to exhaustion)-in adult coho salmon (Oncorhynchus kisutch) as a case study to determine best general practices for measuring and quantifying MMR in fish. We found that all seven methods were highly comparable and that chase treatments represent a valuable field alternative to swim tunnels. Moreover, we caution that the type of test and duration of measurement windows used to calculate MMR can have significant effects on estimates of MMR and statistical power for each approach.

Population differences in aggression are shaped by tropical cyclone-induced selection.

Extreme events, such as tropical cyclones, are destructive and influential forces. However, observing and recording the ecological effects of these statistically improbable, yet profound 'black swan' weather events is logistically difficult. By anticipating the trajectory of tropical cyclones, and sampling populations before and after they make landfall, we show that these extreme events select for more aggressive colony phenotypes in the group-living spider Anelosimus studiosus. This selection is great enough to drive regional variation in colony phenotypes, despite the fact that tropical cyclone strikes are irregular, occurring only every few years, even in particularly prone regions. These data provide compelling evidence for tropical cyclone-induced selection driving the evolution of an important functional trait and show that black swan events contribute to within-species diversity and local adaptation.