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Futile cycles in metabolic flexibility: The energetic cost of regulatory precision
Item type: Review Article
Khandelwal, Radhika; Ding, Lianggong; Sharma, Anand Kumar (2026)
Futile cycles (FCs), also known as substrate cycles, are a pair of opposing biochemical reactions that continually convert a substrate into a product and back. In doing so, FCs waste ATP without producing a tangible metabolic output (thus termed ‘futile’). Because ATP hydrolysis is exothermic, recent studies have extensively focused on the thermogenic function of various FCs, particularly in adipose tissue. However, the function of FCs on other target organs and their primary biological functions remain poorly defined. In this forward-looking minireview/perspective, we discuss a few underexplored functions of FCs that underpin metabolic flexibility and systemic metabolic health. We propose an integrative model in which discrete FCs across metabolic organs act in concert to regulate cellular energetics and organismal metabolic physiology. We postulate that FCs sense and integrate metabolic status, redox balance, and metabolite signaling, with mitochondria serving as the central hub where energetic and signaling cues converge to generate a calibrated cellular response. Given the broad regulatory role of FCs, including in metabolic flexibility, future studies should aim to define the wider functions vis-à-vis metabolic homeostasis in health and disease.
Seeding a landscape for biocultural stewardship: fertile grounds to nurture diverse relational values
Item type: Review Article
Chapman, Mollie (2026)
A cornerstone of biocultural stewardship is the connections people and communities have with places, ecosystems, and species — or in other words, their relational values. There has been recent excitement about the potential for plural values (including relational values) to underlie sustainability transformations. Yet what do relational values need to thrive? I offer three suggestions for ‘fertile grounds’ that might nurture relational values for food system transformation. Each centers the idea of biocultural stewardship. One: foster agency to enable stewardship practices and the relational values they embody. Two: create spaces for receiving reciprocal contributions. Three: weave together the connections needed to sustain and grow reciprocal practices. I end by pointing to new forms of research that center on reciprocity and relationality.
Letter to the editor: Exploring the role of drug interactions in lithium-associated bradycardia: A network analysis of Vigibase
Item type: Other Journal Item
Schoretsanitis, Georgios; Raschi, Emanuel; Weiler, Stefan; et al. (2026)
Long-term major histocompatibility complex class I suppression in astronauts and clinical implications
Item type: Review Article
LeRoy, Erik; Kim, JangKeun; Ruland, Helena; et al. (2026)
Spaceflight can disrupt astronaut immunity, including sustained downregulation of Major Histocompatibility Complex (MHC) class I genes across missions ranging from the three-day Inspiration4 flight to long-duration International Space Station stays. MHC class I downregulation is a known mechanism of immune evasion in cancer and viral infection, potentially increasing health risks during and after spaceflight. The underlying mechanisms, clinical implications and therapeutic options remain underexplored. This Perspective discusses long-term risks associated with astronaut MHC class I suppression, proposes future research directions and outlines therapeutic approaches with broader relevance to related health challenges on Earth.
Thermophilization: Concepts, Methods, and Implications of Changes in Community Composition due to Global Warming
Item type: Review Article
Feeley, Kenneth J.; Iseli, Evelin; Bektaş, Billur; et al. (2026)
With global warming, many species will shift their geographic ranges coldward (i.e., towards higher latitudes and elevations) to remain within suitable thermal conditions. At the community level, these range shifts result in "thermophilization"-the increasing relative abundance of warm-adapted ("thermophilic") species and the concomitant decrease of cold-adapted species over time. Quantifying rates of thermophilization provides a powerful approach to assessing responses to rising temperatures at the community level, particularly in high-diversity systems where the detailed spatial data needed to calculate species-level responses to warming for thousands of individual species are often unavailable. This review synthesizes our current understanding of thermophilization across terrestrial, marine, and aquatic systems. We detail the most common methods used to quantify thermophilization, primarily through the calculation of the Community Temperature Index (CTI, °C), which aggregates species' thermal affiliations into a single community-level metric that can then be tracked through time to calculate an annualized thermophilization rate (TR, °C year-1). We evaluate the advantages of this approach, such as its ability to partition the contributions of underlying demographic processes (i.e., recruitment vs. growth vs. mortality, or colonization vs. extinction) and/or individual species and species groups, its flexibility in using diverse data sources like herbarium records and citizen science, and its ability to test relationships between TR and site-specific conditions such as elevation, landcover, and anthropogenic disturbances. We also discuss some of the standing challenges and limitations of the thermophilization approach, including a lack of standardization that hinders large-scale synthetic analyses, the challenge of propagating estimation errors from the species- to community-level, and difficulties in interpreting and communicating results. We then discuss the implications of thermophilization for ecosystem stability and function, including the potential for biodiversity losses and altered ecosystem services. Finally, we highlight several important and exciting avenues for future research on climate-driven shifts in community composition.