This review explores the remarkable metabolic adaptations of species that thrive in extreme environments, providing insights into their resilience, flexibility and disease resistance. Species such as hibernating brown bears, migratory birds, cavefish, Greenland sharks and naked mole rats exhibit unique metabolic traits that challenge conventional paradigms of metabolic regulation. These adaptations, including resistance to hypoxia and metabolic ageing, offer potential solutions to human metabolic disorders, including obesity, type 2 diabetes and CVD. Insights from comparative physiology, particularly the mechanisms by which animals cope with food scarcity, extreme temperatures and hypoxia, could help identify novel therapeutic targets for advancing human health. For example, hibernation can serve as a model for understanding metabolic diseases, providing insights into reversible insulin resistance and energy homeostasis. This review also highlights the impact of environmental stressors, including climate change, on these species, which may jeopardise their survival despite their resilience. Accelerating anthropogenic environmental change threatens even the most resilient animal species. We call for a holistic approach to conservation and environmental protection to preserve these species and the valuable lessons they offer for managing our metabolic health.

Abstract Variable chlorophyll a (Chl a ) fluorescence, a standard tool for assessing phytoplankton physiology, offers a wealth of information on photosynthetic performance and primary productivity through noninvasive means. However, a better understanding of diurnal patterns in photosynthesis is critically important as advanced fluorescence techniques are increasingly used to monitor coastal and oceanic primary productivity rates in situ. In this study, we coupled a custom‐made, Fast Repetition Rate Chl a fluorometer to an algal culture system (photobioreactor) to monitor the photosynthetic response of two strains of the green alga, Micromonas commoda , under highly regulated light and CO 2 conditions. When comparing diel profiles, our results reveal notable differences in the quantum yield of PSII and reoxidation kinetics across light patterns despite exposure to the same integrated photon dose per day. Specifically, CCMP2709 experienced a larger reduction in the quantum yield of PSII during the dark period, likely reflecting elevated chlororespiratory activity. This suggests that diel light patterns with rapid shifts in irradiance can bias phytoplankton toward the use of alternative electron pathways; such shifts can alter energetic budgets thereby leading to physiological changes. Our results also indicate a light‐profile dependent response to elevated CO 2 conditions, as reductions in cell size, relative Chl a fluorescence per cell, and side scatter are observed under the gradual, but not rapid changes in light intensity. These findings emphasize the utility of high‐resolution tools for monitoring photosynthetic performance in algal research, and the need to account for diel light patterns when comparing physiology among species and/or experimental conditions.

This study presents the design and development of a portable iontophoresis device intended to address excessive sweating and its physiological implications in both humans and animals. Hyperhidrosis, characterized by uncontrollable sweating, can interfere with thermoregulation and lead to significant emotional and social distress. While iontophoresis is a proven treatment for this condition, traditional devices are often bulky, reliant on AC power, and pose risks of electric shock. To address these limitations, a compact, rechargeable iontophoresis apparatus was developed. It features a USB-supported power system that allows for safe operation via DC sources such as power banks or vehicle USB ports but is still compatible with conventional AC chargers. The device includes a controller, prongs, removable electrodes, a foldable case, and a safety barrier to prevent direct skin contact during treatment. In addition to human therapy, this study explores the potential applications of these devices in animal ecophysiology. This study is limited to the engineering and design phases; no experimental or clinical testing was conducted on humans or animals. As such, while the device shows promise as a field-deployable, therapeutic tool, its efficacy and safety remain to be validated through future clinical and veterinary trials. The design also opens avenues for research into sweat-related responses in animals—such as dogs, cats, and horses—within the context of environmental and comparative physiology.

The pancreas is a vital organ with both endocrine and exocrine functions in mammalian species. This report presents a comparative study of the ultrastructural characteristics of pancreatic tissue in the rabbit (Oryctolagus cuniculus) and guinea pig (Cavia porcellus) using scanning electron microscopy (SEM). Pancreas specimens were obtained from healthy adult animals on the University of Muthanna and processed for SEM using standard techniques for SEM processing. This study has documented different sizes of acinar cells, ductal structure, and organization of islets between the two species. The rabbit pancreas exhibited larger acini than guinea pig pancreas with more larger zymogen granules than that in the guinea pig. In contrast, the guinea pig pancreas exhibited more acinar units more densely packed with smaller acinar and cellular dimensions. Additionally, the ductal system of the rabbit pancreas exhibited more branching than that of the guinea pig pancreas. The current study adds to our knowledge of comparative pancreatic morphology to different species, regardless of physiological functional similarities, which has intrinsic importance in future studies involving comparative physiology or as an experimental model.

Exploring Comparative Physiology and Evolution: Understanding Homologous Structures with Students

Comparative biochemistry and physiology, part C combined Zn and Mn affect osmoregulation of the freshwater teleost Prochilodus lineatus in distinct ways from isolated metals.

Iron toxicity, predominantly stemming from excessive levels of ferrous iron (Fe2+) in acidic soils, poses a considerable challenge for crop production. Hypoxic conditions induced by waterlogging can exacerbate Fe2+ availability, which significantly impacts the cultivation and productivity of rice (Oryza sativa), a staple food for millions worldwide. In several regions across South America, Africa, and Asia, the prevalence of acidic soils results in elevated Fe2+ levels leading to iron toxicity, thereby hindering rice yield. Some regional rice varieties demonstrate a notable adaptation to high iron conditions, offering insights into the tolerance mechanisms through comparative physiology and transcriptomic studies. This review synthesizes the various strategies employed by rice plants to mitigate iron toxicity stress, with a focus on the regulation of essential genes and genetic pathways associated with iron transport and homeostasis. We place particular emphasis on the co-expression networks and predicted subcellular localization of the proteins encoded by these genes. A meta-analysis of differential gene expression data gathered from studies involving six distinct rice lines-either tolerant or sensitive-reveals significant influences of plant genotype, developmental stage, and treatment type on the expression patterns, leading to the identification of robust marker genes associated with the iron excess response. Our comprehensive literature review uncovers several critical knowledge gaps, establishing a framework for developing novel approaches aimed at elucidating the molecular mechanisms underpinning iron stress tolerance. These insights are vital for enhancing rice yield in iron-rich, acidic soils, ultimately contributing to improved food security in affected regions.

Aging poses one of the greatest biomedical challenges of our time, with rising rates of frailty, sarcopenia, and cognitive decline globally. Preserving muscle and brain health is central to maintaining independence and quality of life in aging populations. This commentary explores how hibernation research, rooted in comparative physiology, offers unprecedented opportunities for drug discovery and therapeutic innovation. Hibernating animals exhibit remarkable abilities to regulate metabolism, protect the brain and muscles from atrophy, and prevent cellular damage under extreme conditions. These adaptations could inform new strategies for muscle preservation during inactivity, neuroprotection, and targeted temperature management, as well as critical needs in aging, neurocritical care, and space medicine. The bidirectional relationship between muscle and brain health underscores the potential for hibernation-inspired therapies to address both sarcopenia and cognitive decline. Applying these insights to space medicine and critical care settings could lead to groundbreaking solutions for unmet medical needs. Just as GLP-1 agonists emerged from the study of Gila monster venom, focusing on nature's extreme survivors may reveal overlooked molecular targets for drug development. By harnessing these adaptations, we can advance biomimicry in medical research and inspire sustainable solutions for healthy aging, critical care, and space exploration-offering new hope for patients, clinicians, and policymakers.

Development and application of a targeted phosphoproteomics method for analysing the mTOR pathway dynamics in zebrafish PAC2 cell line.

The deposition of pre-peer-reviewed scientific articles in repositories as preprints has been practised for over 50 years. Recently, the popularity of this practice has surged, particularly in chemistry and physics disciplines. In the life sciences, bioRxiv is a popular preprint server; however, its usage varies greatly between fields. Preprinting is not common practice within comparative physiology, with the number of manuscripts submitted lagging far behind that seen in other fields. In this Perspective, we dig into the possible explanations for this difference. We explore common concerns regarding the deposition and use of preprints and highlight some relevant reasons why preprints are helpful to the field of comparative physiology. We strongly believe that use of preprints can help to improve transparency in the scientific publishing process and will be an important component of publishing for all fields of science in the future.

ECR Spotlight is a series of interviews with early-career authors from a selection of papers published in Journal of Experimental Biology and aims to promote not only the diversity of early-career researchers (ECRs) working in experimental biology but also the huge variety of animals and physiological systems that are essential for the ‘comparative’ approach. Patrícia Ferreira is an author on ‘ A second look at the stomach – a fishy perspective’, published in JEB. Patrícia conducted the research described in this article while a PhD candidate in Dr Jonathan M. Wilson's lab at Department of Biology, Wilfrid Laurier University, Canada. Patrícia is now a post-doctoral researcher in the lab of Dr Kathleen Gilmour at Department of Biology, University of Ottawa, Canada, investigating comparative vertebrate physiology, ion regulation and gastrointestinal physiology.

To efficiently digest food resources that may vary spatially and temporally, animals maintain physiological flexibility across levels of organization. For example, in response to dietary shifts, animals may exhibit changes in the expression of digestive enzymes, the size of digestive organs or the structure of their gut microbiome. A 'Grand Challenge' in comparative physiology is to understand how components of flexibility across organizational levels may scale to cumulatively determine organismal performance. Here, we conducted feeding trials on three rodent species with disparate feeding strategies: herbivorous montane voles (Microtus montanus), omnivorous white-footed mice (Peromyscus leucopus) and carnivorous grasshopper mice (Onychomys torridus). For each species, four groups of individuals were presented with diets that varied in carbohydrate, fiber and protein content. After 4-5 weeks, we measured organismal performance in the form of nutrient digestibility (dry matter, nitrogen, fiber). We also measured gut anatomy and organ size, and conducted enzyme assays on various tissues to measure activities of carbohydrases and peptidases. We found some shared physiological responses, e.g. fiber generally increased gut size across species. However, the specifics of these responses were distinct across species, suggesting different capacities for flexibility. Thus, in the context of digestion, we still lack an understanding of how flexibility across organizational levels may scale to determine whole-animal performance.

Marine SAR116 bacterioplankton are ubiquitous in surface waters across global oceans and form their own order, Puniceispirillales, within the Alphaproteobacteria. To date no comparative physiology among diverse SAR116 isolates has been performed to capture the functional diversity within the clade, and further, diversity through the lens of metabolic potential and environmental preferences via clade-wide pangenomics continues to evolve with the addition of new genomes. Using high-throughput dilution-to-extinction cultivation, we isolated and genome sequenced five new and diverse SAR116 isolates from the northern Gulf of Mexico. Here we present a comparative physiological analysis of these SAR116 isolates, along with a pangenomic investigation of the SAR116 clade using a combination of metagenome-assembled genomes (MAGs, n = 258), single-amplified genomes (n = 84), previously existing (n = 2), and new isolate genomes (n = 5), totaling 349 SAR116 genomes. Phylogenomic investigation supported the division of SAR116 into three distinct subclades, each with additional structure totaling 15 monophyletic groups. Our SAR116 isolates belonged to three groups within subclade I representing distinct genera with different morphologies and varied phenotypic responses to salinity and temperature. Overall, SAR116 genomes encoded differences in vitamin and amino acid synthesis, trace metal transport, and osmolyte synthesis and transport. They also had genetic potential for diverse sulfur oxidation metabolisms, placing SAR116 at the confluence of the organic and inorganic sulfur pools. SAR116 subclades showed distinct patterns in habitat preferences across open ocean, coastal, and estuarine environments, and three of our isolates represented the most abundant coastal and estuarine subclade. This investigation provides the most comprehensive exploration of SAR116 to date anchored by new culture genomes and physiology.

Field guide to Nath's research work on ATP synthesis and hydrolysis.

Hypothesis: Venous occlusion impairs cardiac ventricle filling to end-diastolic volume (EDV). As EDV preload is reduced, ejected stroke volume (SV) is simultaneously lowered. The EDV mediation of SV output reflects the Frank-Starling Mechanism and compels a presented hypothesis that ejection fraction ratio EF=SV/EDV might remain constant during preload adjustment. Methods: Pressure volume (PV) loop datasets (n=34) recorded from female swine left ventricles 1 were provided for studied post-processing. Each dataset was analyzed to compute EF in the natural steady-state. Following EF measurement, inferior vena-cava occlusion (IVCO) measures of EDV i were noted at each IVCO beat i and EF constancy was applied to estimate each beat i stroke volume as SV i ~ EF x EDV i . Results: SV estimates were computed during early IVCO (beats 1 ≥ 5) and during a second phase of beats (beats 6 ≥10). Shown in Table 1, SV predictions exhibited near-unity slopes of proportion to direct SV measures. [Table: see text] Conclusions: A normal left ventricle appears to preserve EF during a preload reduction. This result highlights a possibility to quantify contractile mechanism aberrations if adjustment causes EF to change. For purposes of functional computation and modeling, the SV prediction also facilitates a useful forecast 2 of each IVCO beat i end-systolic volume as ESV i = EDV i - SV i ~ EDV i x (1- EF). 1. Habigt, M., et al., Nonlinearity of end-systolic pressure–volume relation in afterload increases is caused by an overlay of shortening deactivation and the Frank–Starling mechanism. Nature-Scientific Reports 2021. 11(3353): p. 1-11. 2. Marcus, E., A Study of Mechanisms Influencing Left-Ventricle End-Systolic Pressure Volume Relationship Measures, in COMPARATIVE PHYSIOLOGY: From Organisms to Omics in an Uncertain World, A.P. Society, Editor. 2022, American Physiology Society: San Diego EM's salary is supported by the Boston Children's Hospital Cardiology Department This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: We apply ejection fraction (EF) as a fundamental constant to predict end-systolic volume (ESV) and end-systolic pressure (ESP) trends of the end-systolic pressure volume relationship (ESPVR). Methods: As described previously (1), ejection fraction (EF) predicts [ ESV i , ESP i ] data based on end-diastolic volume (EDV i ) of beat i during ESPVR measurement. ESV i = EDV i x (1- EF) ESP i = K conduit x EDV i x EF + DBP Constant K conduit is the effective, beat–synchronized elastic modulus of the arterial load, and constant DBP is diastolic arterial blood pressure. When differentiated, ESP and ESP equations formulate the following expression of ESPVR slope during a one-beat perturbation from steady state. ESPVR Beat 1 : α slope = K conduit x EF / (1-EF) Slope α is therefore the ESPVR curve’s expected tangent when functioning near natural preload. As EDV adjustment proceeds beyond beat 1 , ESPVR data gradually forms a curved pattern with different slopes through the pressure-volume diagram; this curve generally trends towards volume V= 0 as the chamber pressure is fully relaxed to P=0. Starting from this equilibrium [V=0, P= 0], a Bezier curve's construction ending at the steady-state end-systolic sample [ESV, ESP] can therefore apply α slope as a Bezier end-point slope constraint to estimate ESPVR. Results: Applying Bezier construction to 36 studied pressure-volume loop datasets (2), we approximate end-systolic elastance (Ees) of ESPVR with a similarly computed linear regression slope through Bezier curve points. Within the upper 50% of each ESPVR pressure range, computed end-systolic elastance (Ees’) exhibits a robust and unity-proportioned correlation to direct Ees measurement. Ees’ =.98 x Ees -.01 mmHg/mL (R 2 =.97) Conclusion: In addition to indicating the contractile mechanism elastance magnitude, natural range ESPVR data reflects the outcome of arterial load coupling to characteristic ejection fraction functionality maintained during preload adjustment. 1. Marcus, E., A Study of Mechanisms Influencing Left-Ventricle End-Systolic Pressure Volume Relationship Measures, in COMPARATIVE PHYSIOLOGY: From Organisms to Omics in an Uncertain World, A.P. Society, Editor. 2022, American Physiology Society: San Diego 2. Marcus, E., Ejection Fraction is Maintained during Preload Adjustment, Proceedings of the American Physiology Society Annual Summit, A.P. Society, Editor. 2025, American Physiology Society: Baltimore. Mr. Marcus is a salary-supported Principal Research Software Engineer This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

George Mackie was a comparative physiologist who explored how behaviour can arise from interactions between nerves and excitable epithelia. Reading about colonial marine life as a student at Oxford, he wondered how a colony of individual ‘jellyfish’ could coordinate to perform ‘loop-the-loop’ swimming. This led to studies on a wide range of invertebrates such as ctenophores, glass sponges, hydromedusae and tunicates, all animals where behaviour can be approached at a cellular level and from an evolutionary point of view. Mackie’s training as a neuroanatomist was the key to his many discoveries, of which perhaps best known is the role of non-neural signalling pathways in generating behaviour. This, together with electrical signalling in sponges and dual threshold signalling in the jellyfish Aglantha digitale , are among the many fields that Mackie either initiated or promoted. His ingenuity, patience, persistence, curiosity and independence of thought made him a brilliant innovator. He spent most of his career at the University of Victoria, British Columbia, but retained a lifelong affection for UK and Continental European culture. He and his wife, Gillian, were creative potters and warm and generous hosts. Their five children survive them, all highly innovative in their different fields.

Abstracts from the 46<sup>th</sup> Annual Meeting of the Japanese Society for Comparative Physiology and Biochemistry

Fish models to explore epigenetic determinants of hypoxia-tolerance.

Diversity drives innovation and creativity, directly contributing to scientific excellence. However, achieving equity in academia, including in experimental biology fields such as biomechanics and comparative physiology, remains a significant challenge, with women and other historically marginalized groups underrepresented, especially in more senior roles. When considering gender, the disparity is often linked to difficulties in balancing family responsibilities with demanding careers, along with lower 'academic visibility', as evidenced by fewer professional awards for women scientists. Many successful women who balance career and family keep their family lives private, making these aspects invisible to early career scholars, and thus depriving them of role models. To help close the gender gap, in this Perspective, we propose 10 actionable strategies for scholars at all career stages to promote gender diversity and inclusion through active allyship. Although we focus on gender diversity, these strategies can be broadly applied to harness the benefits of other diversity dimensions (e.g. age or ethnicity). We argue that embracing allyship benefits individual scientists, their research groups, the quality of their research, the broader research community and society at large by enhancing collective scientific output and inspiring the next generation of scientists.