Within many species, and particularly fish, fecundity does not scale with mass linearly; instead, it scales disproportionately. Disproportionate intraspecific size–reproduction relationships contradict most theories of biological growth and present challenges for the management of biological systems. Yet the drivers of reproductive scaling remain obscure and systematic predictors of how and why reproduction scaling varies are lacking. Here, we parameterise life history optimisation model to predict global patterns in the life histories of marine fishes. Our model predict latitudinal trends in life histories: Polar fish should reproduce at a later age and show steeper reproductive scaling than tropical fish. We tested and confirmed these predictions using a new, global dataset of marine fish life histories, demonstrating that the risks of mortality shape maturation and reproductive scaling. Our model also predicts that global warming will profoundly reshape fish life histories, favouring earlier reproduction, smaller body sizes, and lower mass-specific reproductive outputs, with worrying consequences for population persistence.

The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England’s mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta’s emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.

Viruses, the diseases they can trigger, and the possible associated societal disaster represent different entities. To engage with the complexities of viral pandemics, we need to recognize each entity by using a distinctive name.

Pollinators are currently facing dramatic declines in abundance and richness across the globe. This can have profound impacts on agriculture, as 75% of globally common food crops benefit from pollination services. As many native bee species require natural areas for nesting, restoration efforts within croplands may be beneficial to support pollinators and enhance agricultural yields. Yet, restoration can be challenging to implement due to large upfront costs and the removal of land from production. Designing sustainable landscapes will require planning approaches that include the complex spatiotemporal dynamics of pollination services flowing from (restored) vegetation into crops. We present a novel planning framework to determine the best spatial arrangement for restoration in agricultural landscapes while accounting for yield improvements over 40 years following restoration. We explored a range of production and conservation goals using a coffee production landscape in Costa Rica as a case study. Our results show that strategic restoration can increase forest cover by approximately 20% while doubling collective landholder profits over 40 years, even when accounting for land taken out of production. We show that restoration can provide immense economic benefits in the long run, which may be pivotal to motivating local landholders to undertake conservation endeavours in pollinator-dependent croplands.

There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence in cultured cells and extends lifespan in yeast, nematodes, and fruit flies. Here, we asked whether chronic continuous hypoxia is beneficial in mammalian aging. We utilized the Ercc1 Δ/- mouse model of accelerated aging given that these mice are born developmentally normal but exhibit anatomic, physiological, and biochemical features of aging across multiple organs. Importantly, they exhibit a shortened lifespan that is extended by dietary restriction, the most potent aging intervention across many organisms. We report that chronic continuous 11% oxygen commenced at 4 weeks of age extends lifespan by 50% and delays the onset of neurological debility in Ercc1 Δ/- mice. Chronic continuous hypoxia did not impact food intake and did not significantly affect markers of DNA damage or senescence, suggesting that hypoxia did not simply alleviate the proximal effects of the Ercc1 mutation, but rather acted downstream via unknown mechanisms. To the best of our knowledge, this is the first study to demonstrate that “oxygen restriction” can extend lifespan in a mammalian model of aging.

Phage therapy is a medical form of biological control of bacterial infections, one that uses naturally occurring viruses, called bacteriophages or phages, as antibacterial agents. Pioneered over 100 years ago, phage therapy nonetheless is currently experiencing a resurgence in interest, with growing numbers of clinical case studies being published. This renewed enthusiasm is due in large part to phage therapy holding promise for providing safe and effective cures for bacterial infections that traditional antibiotics acting alone have been unable to clear. This Essay introduces basic phage biology, provides an outline of the long history of phage therapy, highlights some advantages of using phages as antibacterial agents, and provides an overview of recent phage therapy clinical successes. Although phage therapy has clear clinical potential, it faces biological, regulatory, and economic challenges to its further implementation and more mainstream acceptance.

Necrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie NEC is lacking. This study aimed at filling in this gap. We combine single-cell RNA sequencing (scRNAseq), T-cell receptor beta (TCRβ) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions, and zonal changes in NEC. We find an abundance of proinflammatory macrophages, fibroblasts, endothelial cells as well as T cells that exhibit increased TCRβ clonal expansion. Villus tip epithelial cells are reduced in NEC and the remaining epithelial cells up-regulate proinflammatory genes. We establish a detailed map of aberrant epithelial–mesenchymal–immune interactions that are associated with inflammation in NEC mucosa. Our analyses highlight the cellular dysregulations of NEC-associated intestinal tissue and identify potential targets for biomarker discovery and therapeutics.

Human gut bacteria perform diverse metabolic functions with consequences for host health. The prevalent and disease-linked Actinobacterium Eggerthella lenta performs several unusual chemical transformations, but it does not metabolize sugars and its core growth strategy remains unclear. To obtain a comprehensive view of the metabolic network of E. lenta, we generated several complementary resources: defined culture media, metabolomics profiles of strain isolates, and a curated genome-scale metabolic reconstruction. Stable isotope-resolved metabolomics revealed that E. lenta uses acetate as a key carbon source while catabolizing arginine to generate ATP, traits which could be recapitulated in silico by our updated metabolic model. We compared these in vitro findings with metabolite shifts observed in E. lenta-colonized gnotobiotic mice, identifying shared signatures across environments and highlighting catabolism of the host signaling metabolite agmatine as an alternative energy pathway. Together, our results elucidate a distinctive metabolic niche filled by E. lenta in the gut ecosystem. Our culture media formulations, atlas of metabolomics data, and genome-scale metabolic reconstructions form a freely available collection of resources to support further study of the biology of this prevalent gut bacterium.

Candida albicans is a frequent colonizer of human mucosal surfaces as well as an opportunistic pathogen. C. albicans is remarkably versatile in its ability to colonize diverse host sites with differences in oxygen and nutrient availability, pH, immune responses, and resident microbes, among other cues. It is unclear how the genetic background of a commensal colonizing population can influence the shift to pathogenicity. Therefore, we examined 910 commensal isolates from 35 healthy donors to identify host niche-specific adaptations. We demonstrate that healthy people are reservoirs for genotypically and phenotypically diverse C. albicans strains. Using limited diversity exploitation, we identified a single nucleotide change in the uncharacterized ZMS1 transcription factor that was sufficient to drive hyper invasion into agar. We found that SC5314 was significantly different from the majority of both commensal and bloodstream isolates in its ability to induce host cell death. However, our commensal strains retained the capacity to cause disease in the Galleria model of systemic infection, including outcompeting the SC5314 reference strain during systemic competition assays. This study provides a global view of commensal strain variation and within-host strain diversity of C. albicans and suggests that selection for commensalism in humans does not result in a fitness cost for invasive disease.

The superior colliculus (SC), a conserved midbrain node with extensive long-range connectivity throughout the brain, is a key structure for innate behaviors. Descending cortical pathways are increasingly recognized as central control points for SC-mediated behaviors, but how cortico-collicular pathways coordinate SC activity at the cellular level is poorly understood. Moreover, despite the known role of the SC as a multisensory integrator, the involvement of the SC in the somatosensory system is largely unexplored in comparison to its involvement in the visual and auditory systems. Here, we mapped the connectivity of the whisker-sensitive region of the SC in mice with trans-synaptic and intersectional tracing tools and in vivo electrophysiology. The results reveal a novel trans-collicular connectivity motif in which neurons in motor- and somatosensory cortices impinge onto the brainstem-SC-brainstem sensory-motor arc and onto SC-midbrain output pathways via only one synapse in the SC. Intersectional approaches and optogenetically assisted connectivity quantifications in vivo reveal convergence of motor and somatosensory cortical input on individual SC neurons, providing a new framework for sensory-motor integration in the SC. More than a third of the cortical recipient neurons in the whisker SC are GABAergic neurons, which include a hitherto unknown population of GABAergic projection neurons targeting thalamic nuclei and the zona incerta. These results pinpoint a whisker region in the SC of mice as a node for the integration of somatosensory and motor cortical signals via parallel excitatory and inhibitory trans-collicular pathways, which link cortical and subcortical whisker circuits for somato-motor integration.