<p>by Lillith C. Zijmers, Katie L. Abson, Jarrod D. Hadfield, Adam Eyre-Walker</p>
A population’s ability to adapt is determined by its levels of additive genetic variance (<i>V</i><sub>A</sub>), and while it is agreed that most organisms have genetic variation for most traits, the extent to which it varies between species is poorly characterized. Here, we investigate this question by compiling 3,209 and 1,852 estimates of heritability and evolvability (the additive genetic variance divided by the square of the mean), respectively, for a variety of traits from 220 and 172 multicellular eukaryotic species. Using phylogenetic generalized linear mixed models, we find substantial and highly significant interspecific variation in evolvability. Much of the variation is explained by phylogenetic relatedness, with plants in our data having substantially higher evolvability than animals. While heritability also varies between species, the differences are more subtle, and plants are not exceptional. We investigate whether the variation in evolvability and heritability between species is due to variation in the mutation rate, effective population size, genome size, ploidy, and recombination rate, but find little evidence of any factor being important. However, the confidence intervals are large suggesting that we have little power to detect any associations between these factors and our estimates of <i>V</i><sub>A</sub>.
Science Journals
<p>by Alberto Docampo-Seara, Mehmet Ilyas Cosacak, Kim Heilemann, Friederike Kessel, Ana-Maria Oprişoreanu, Markus Westphal, Özge Çark, Daniela Zöller, Josi Arnold, Anja Bretschneider, Alisa Hnatiuk, Nikolay Ninov, Catherina G. Becker, Thomas Becker</p>
Zebrafish, in contrast to mammals, regenerate neurons after spinal cord injury, but little is known about the control mechanisms of this process. Here we use scRNA-seq and in vivo experiments to show that <i>sema4ab</i>, mainly expressed by lesion-reactive microglia, attenuates regenerative neurogenesis by changing the complex lesion environment. After spinal injury, disruption of <i>sema4ab</i> doubles the number of newly generated progenitor cells and neurons but attenuates axon regrowth and recovery of swimming function. Disruption of the <i>plxnb1a/b</i> receptors, selectively expressed by neural progenitor cells, increases regenerative neurogenesis. In addition, disruption of <i>sema4ab</i> alters activation state and cytokine expression of microglia, such that fibroblasts increase expression of the cytokine <i>tgfb3</i>, which strongly promotes regenerative neurogenesis. Hence, we propose that <i>sema4ab</i> expression in microglia attenuates regenerative neurogenesis in multiple ways, likely directly through <i>plxnb1a/b</i> receptors and indirectly, by controlling the inflammatory milieu and <i>tgfb3</i> levels<i>.</i> Targeting Sema4A-dependent signaling in non-regenerating vertebrates may be a future strategy to improve regenerative outcomes.
<p>by Guillermina Griffa, Marco Palombo, Abraham Yeffal, Hong-Hsi Lee, Agustin Solano, Susie Y. Huang, Valeria Della-Maggiore</p>
Structural neuroplasticity supports learning, development, and shapes vulnerability to brain disorders, making it a central priority in neuroscience research. However, progress in humans has remained limited by the inability to probe cellular processes in vivo, leaving mechanistic insight largely dependent on animal models. To address this gap, here we combined the sub-voxel sensitivity of ultra–high-gradient diffusion MRI with the cell-compartment specificity of the Soma and Neurite Density Imaging (SANDI) model to probe structural plasticity directly in the living human brain. By tracking how learning modulates the temporal dynamics of cell bodies and cell processes, we aimed to distinguish plastic from nonplastic biological processes driving changes in microstructure. We found that learning a motor skill triggered two distinct temporal responses: a transient expansion of cell bodies across all brain regions engaged by the task, consistent with a short-lived homeostatic mechanism, and a sustained increase in cell-process density restricted to key motor regions, consistent with structural plasticity. Our approach provides a mechanistic window into human neuroplasticity and marks a significant step toward bridging the gap between animal and human neuroscience.
<p>by Dario Pasquale Anobile, Layla Barbar, Emile Maucotel, Alexis Cornec, Valeria Manriquez, Wilfrid Richer, Jordan Denizeau, Christine Sedlik, Charlie Bories, Elodie Couderc, Renaud Leclere, Judith Sobas, Emeline Papillon, Rafael Mena Osuna, Jimena Tosello-Boari, Marianne Burbage, Eliane Piaggio, Enzo Z. Poirier</p>
One of the first-line treatments for advanced non-small cell lung cancer (NSCLC) are immune checkpoint inhibitors (ICI), which activate the antitumor immune response. Despite their success, ICI remain ineffective in many patients, highlighting the need for strategies to overcome resistance. Most efforts have focused on promoting immune cell infiltration into refractory tumors to improve ICI efficacy. In this work, we mobilize this approach by focusing on Argonaute 2 (Ago2), a pivotal member of the RNA interference pathway. Using two murine models of immunorefractory NSCLC, we demonstrate that tumoral Ago2 suppresses interferon signaling, leading to poor immunogenicity and failure of ICI therapy. Genetic deletion of Ago2 in cancer cells restores interferon signaling and supports immune infiltration of the tumor. Consequently, whereas wild-type tumors are resistant to ICI, tumors devoid of Ago2 become sensitive to treatment. In NSCLC patients treated with ICI, high Ago2 expression and a low interferon signature in tumors correlates with reduced survival. Ago2 is thus a driver of the immunorefractory phenotype observed in NSCLC and may represent a therapeutic target when aiming to sensitize patients to ICI.
<p>by Yoshiko M. Ikushima, Kuan-Chan Chen, Richard J. Sulston, Domenico Mattiucci, Eleanor J. Brain, Stefanie A. Fung Xin Zi, Karla J. Suchacki, Benjamin J. Thomas, Andrea Lovdel, Matthew Bennett, Hiroshi Kobayashi, Phillip D. Whitfield, Keiyo Takubo, Andrew H. Baker, Nicholas M. Morton, Robert K. Semple, William P. Cawthorn</p>
Adiponectin is the most abundant hormone in the circulation. Plasma adiponectin decreases in obesity but increases in leanness, including during caloric restriction (CR) in animals and humans. In obesity, adiponectin deficiency promotes cardiometabolic dysfunction. In contrast, the roles of adiponectin in CR, when it is at its highest, are largely unknown. To address this, we studied global adiponectin knockout (KO) in male and female mice fed either <i>ad libitum</i> (AL) or a 30% CR diet from 9–13 weeks of age. We show that adiponectin KO did not alter CR effects on body mass, body composition, or energy expenditure. However, KO unexpectedly decreased blood glucose levels during CR, both with fasting and following an oral glucose challenge. This is opposite to the effects of adiponectin deficiency during AL feeding or obesity and occurred without changes in insulin concentrations or sensitivity. Moreover, adiponectin KO augmented CR-induced increases in plasma fatty acids in both sexes and, in males only, impaired systemic triglyceride clearance on both AL and CR diets. These effects on lipid metabolism were associated with sex- and diet-specific KO effects on white adipose tissue, including altered adipocyte size and expression of key regulators of adipocyte lipid metabolism. Indirect calorimetry further revealed that adiponectin KO alters the shifts between carbohydrate and lipid utilization that occur during transitions between fed and fasted states. To determine potential molecular mechanisms, we investigated effects of adiponectin KO on the liver, a major adiponectin target that plays key roles entraining metabolism to nutritional…
Multicellularity has emerged in the three branches of the tree of life. The formation of simple multicellular entities can either result from cells aggregating or staying together after mitosis. However, it is not yet fully understood how, once formed, these simple multicellular entities could be maintained or even selected for. Here, using the <i>ace2</i> yeast snowflake model of simple multicellularity, we aimed at identifying genetic conditions favoring its maintenance. Growth-competition experiments revealed that, while the <i>ace2</i> mutation by itself does not provide any fitness advantage or disadvantage, the <i>ace2</i> snowflakes were strongly selected when combined with conditions affecting regulators of the G1/S transition of the cell cycle, such as Cln3 or Whi5. We show that this selection results from a faster exit from quiescence of the <i>ace2</i> snowflake cells. Importantly, this advantage is not dependent on the multicellular phenotype, but rather on the <i>ace2</i> genotype itself. We found that the <i>ace2</i> selective advantage in the <i>cln3</i> background fully depends on the <i>KSS1</i> gene, a target of the Ace2 transcription factor. Finally, we show that phenotypes observed for <i>ace2</i> mutants are phenocopied by the <i>AMN1<sup>368D</sup></i> allelic form found in ‘non-laboratory’ yeast strains, hence adding physiological relevance to these observations. Altogether, our results support the hypothesis that simple multicellularity could, in some cases, persist, not because it provides a direct selective advantage due to multicellularity itself, but rather as a ‘passenger’ phenotype that is maintained alongside other selected traits.
When <i>Escherichia coli</i> ribosomes are assembled in vitro, manipulation of incubation temperature and magnesium ion concentration has been an essential procedure, which is a crucial step for the assembly of active large subunits. The present study tackles this issue to develop a single-step procedure, which can be performed in near-physiological conditions, where cell-free protein synthesis is active. We found that GTPase factors EngA and ObgE can complement the changes in temperature and magnesium ion concentrations. In the presence of these factors, both the ribosome assembly and translation processes were successfully integrated in the reconstituted cell-free protein synthesis system. Furthermore, we found that these GTPase factors can reassemble the ribosomes to an active state, whose structure was disrupted by EDTA chelation of magnesium ions, indicating that these two factors can reversibly induce the ribosome structure to an intact state. The findings are essential for the bottom-up construction of synthetic cells.
Chen H, Xiong T, Guan B, Huang J, Zhao D, Chen Y, Liang H, Li Y, Wu J, Ye S, Li T, Shu W, Li J-T, Wang Y. 2025. Exogenous myristate fuels the growth of symbiotic arbuscular mycorrhizal fungi but disrupts their carbon-phosphorus exchange with host plants. eLife 14:RP109524. doi: 10.7554/eLife.109524.
Published 19 December 2025
We are retracting the eLife paper cited above, which proposed the uptake of external myristate by symbiotic arbuscular mycorrhizal fungi (AMF) and its subsequent disruption of carbon-phosphorus exchange in arbuscular mycorrhiza (AM) symbiosis. Following publication, the editorial office raised concerns regarding the presentation and analysis of a small portion of data — specifically, instances of potentially duplicated values, the inappropriate use of shared controls, and incorrect statistical analyses.
Upon a thorough internal review by the authors, we identified several errors resulting from unintentional oversights. Specifically,
In Figure 1C, background (control) 13C levels in R. irregularis Trial 2 and R. diaphanus extrardical hyphae were combined as a single non-labelled control group, which was displayed in a misleading manner. Regarding the concerns of three pairs of seemingly identical 13C abundance values in the raw data file, we confirm that these values are indeed very close, as is common for 13C background measurements, but are not identical. We have provided the original raw outputs from the EA-IRMS instrument in our communication with the editorial office to substantiate this clarification.
We acknowledge that several statistical analyses in Figures 2c, 3f, 5d, 6e, and Supplementary Figures S1-2 were performed incorrectly. This resulted in inaccurate statistical significance labels, although the impact on the primary conclusions of this study is minimal.
In the supplementary material, the measurement precision of the EA-IRMS device was incorrectly stated as ±0.2‰. The actual precision for the 13C:12C ratio of CO2 from combuste…
Synchronized spontaneous neural activity is a fundamental feature of developing central nervous systems and is thought to be essential for proper brain development. However, the mechanisms that regulate this synchronization and its long-term impact on brain function remain unclear. Here, we identify a previously unrecognized role of oligodendrocytes in orchestrating synchronized spontaneous activity during a critical developmental window, with lasting consequences for adult behavior. Using oligodendrocyte-specific genetic manipulation in the mouse cerebellum, we demonstrate that oligodendrocyte deficiency during early postnatal development, but not after weaning, disrupts the synchronization of Purkinje cell activity both during development and in adulthood. The early disruption produced persistent deficits in cerebellar-dependent behaviors, including anxiety, sociality, and motor function. Optogenetic re-synchronization in adulthood restored motor and social functions but not anxiety-like behavior, demonstrating that reduced Purkinje cell synchrony specifically drives the motor and social impairments. Our findings establish a causal link between developmental oligodendrocyte-regulated neural synchrony and the emergence of complex brain functions, which depend on the proper developmental trajectory necessary for driving brain function.
Enterovirus D68 (EV-D68) is an important pathogen associated with acute flaccid myelitis (AFM). The pathogenesis of AFM involves infection of spinal motor neurons and motor neuron death; however, the mechanisms linking EV-D68 infection to selective neurotoxicity are not well understood. Dysfunction of the nuclear pore complex (NPC) has been implicated in motor neuron injury in neurodegenerative diseases such as amyotrophic lateral sclerosis, and the NPC is also modified by picornavirus proteases during infection. We therefore sought to determine the impact of EV-D68 proteases on NPC composition and function. We demonstrate widespread disruption of NPC composition by EV-D68 2A and 3C proteases via direct cleavage of a relatively small number of nucleoporins, notably Nup98 and POM121, by 2A<sup>pro</sup>. Using reporter systems, we demonstrate that 2A<sup>pro</sup> inhibits nuclear transport of protein cargoes and disrupts the permeability barrier of the NPC, while having no apparent effect on RNA export. Independently, we show 2A<sup>pro</sup> is toxic to induced pluripotent stem cell-derived motor neurons by demonstrating a rescue of toxicity with the 2A<sup>pro</sup> inhibitor telaprevir at concentrations insufficient to inhibit viral replication. These findings expand our understanding of EV-D68 neuropathogenesis and provide a rationale for studying the NPC or 2A<sup>pro</sup> as therapeutic targets in AFM.
<p>by Marlis Reich</p>
Marine fungi were assumed to have a minor role in carbon cycling, unable to compete with bacteria. A new PLOS Biology study challenges this dogma, showing fungi can dominate labile dissolved organic matter assimilation, reshaping our understanding of ocean carbon retention and storage.
Marine fungi were assumed to have a minor role in the carbon cycling, unable to compete with bacteria. A new PLOS Biology study challenges this dogma, showing fungi can dominate labile dissolved organic matter assimilation, reshaping our understanding of ocean carbon retention and storage.
Li T, Yang L, Tu J, Hao Y, Zhu Z, Xiong Y, Gao Q, Zhou L, Xie G, Zhang D, Li X, Jin Y, Zhang Y, Zhao B, Li N, Wang X, Jia J-M. 2025. The myeloid cell-driven transdifferentiation of endothelial cells into pericytes promotes the restoration of BBB function and brain self-repair after stroke. eLife 14:RP105593. doi: 10.7554/eLife.105593.
Published 16 July 2025
We have identified errors in the chart legend in Figure 9D of our published eLife article. One of the groups is incorrectly labelled. The order of the groups in the chart legend is incorrect and inconsistent with the other charts in Figure 9.
How the correction was made:
1. Group designation error (incorrect group names):
The experimental group (red) was incorrectly labelled “iECs”. The label has now been corrected to “iECs:Tgfbr2fl/fl”.
2. Incorrect placement of group positions:
The control group “Tgfbr2fl/fl” was incorrectly placed at the bottom of the chart legend, we have corrected this to place this at the top. In turn the experimental group “iECs:Tgfbr2fl/fl” was incorrectly placed at the top, we have corrected this to place this group at the bottom.
We have carefully rechecked the published eLife article. Importantly, these corrections do not affect the data presented in Figure 9, nor do they alter the results or conclusions of the study. All authors have reviewed and agreed to the changes.
The corrected Figure 9 (updated for panel D) is shown here:
The originally published Figure 9 is shown for reference:
The article has been corrected accordingly.
Author details
© 2026, Li et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
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Respiratory organs must balance their primary function of gas exchange with the constant threat of inhaled pathogens. In the <i>Drosophila</i> tracheal system, gas exchange occurs at the tracheal terminal cells (TTCs), the functional equivalents of mammalian alveoli. While bacterial infection triggers a robust innate immune response throughout the broader airway epithelium, we reveal that TTCs are uniquely exempt from this reaction. Mechanistically, TTCs lack expression of the membrane-associated peptidoglycan recognition receptor PGRP-LC. This absence protects these highly susceptible cells from immune deficiency (Imd) pathway activation and subsequent JNK-mediated cell death, establishing TTCs as a distinct, immune-privileged niche. Ectopic immune activation via targeted <i>PGRP-LCx</i> overexpression in TTCs caused a severe reduction in branching, cellular damage, and ultimately cell death, phenotypes that were fully rescued by the depletion of AP-1 or <i>foxo</i>. Because both structural plasticity (in response to nutritional cues and hypoxia) and innate immune responses strictly require the transcription factor FoxO, we demonstrate that potent immune signaling is fundamentally incompatible with dynamic TTC remodeling. Ultimately, the immune-privileged status of TTCs represents an essential evolutionary trade-off, restricting local inflammation to preserve <i>foxo</i>-dependent structural plasticity and vital respiratory function.
The mechanotransduction process relies on the interaction of mechanical and biochemical cues, transmitting cellular forces to intracellular organelles to activate biochemical pathways and elicit responses. This involves mechanoresponsive components like actin filaments, microtubules (MTs), and the lamin meshwork. Fluidic force microscopy (FluidFM), a force-controlled micropipette, allows for the manipulation of intact cells mechanically and chemically, providing a novel approach to study mechanotransmission in cells in situ. FluidFM combined with fluorescence lifetime imaging microscopy (FLIM) enables high-resolution mapping of intracellular tension dynamics. Here, we used cells with varying nuclear lamina compositions to explore the lamina’s role in initiating mechanoresponse to external cues. We found that A- and B-type lamins trigger nuclear mechanoresponse distinctly, with A-type lamins contributing to nuclear elasticity, whereas B-type lamins influence viscous response. Moreover, MTs underwent mechanical adaptation and assisted in releasing the tension in lamin A/C knockout (KO) cells, contrasting with healthy cells where MTs aid in preserving the tension locally rather than transferring it. This research provides insights into the dynamic mechanoresponse of cellular components and supports targeted therapies for mechanical stress-related diseases.
In presynaptic nerve terminals, the endocytic apparatus rapidly restores synaptic vesicles after neurotransmitter release. Many endocytic proteins localize to the periactive zone, a loosely defined area adjacent to active zones. A prevailing model posits that recruitment of these endocytic proteins to the periactive zone is activity-dependent. We show that periactive zone targeting of endocytic proteins is largely independent of active zone machinery and synaptic activity. At mouse hippocampal synapses and <i>Drosophila</i> neuromuscular junctions, pharmacological or genetic silencing resulted in unchanged or increased levels of endocytic proteins including Dynamin, Amphiphysin, Nervous Wreck, Endophilin A, Dap160/Intersectin, PIPK1γ, and AP-180. Similarly, disruption of active zone assembly via genetic ablation of active zone scaffolds at each synapse did not impair the localization of endocytic proteins. Overall, our work indicates that endocytic proteins are constitutively deployed to the periactive zone and supports the existence of independent assembly pathways for active zones and periactive zones.
<p>by Juan Carlos Trejos-Espeleta, James A. Bradley, Ömer K. Coskun, Laura M. Wehrmann, Gonzalo V. Gomez-Saez, William D. Orsi</p>
Fungi serve as critical biological carbon storage reservoirs in soil ecosystems, but whether this fungal trait is also important for marine sediment carbon storage processes is poorly understood. Here, we quantify for the first time assimilation of dissolved free amino acids by fungi in marine sediments from a high Arctic fjord and show that a distinct community of marine fungi promoted the stabilization of assimilated carbon via a relatively high metabolic efficiency. This corresponded to higher in situ ratios of fungi:prokaryote biomass in the fjord benthos, indicating efficient fungal metabolism promotes increased retention of microbial biomass at the seafloor. Quantitative stable isotope probing linked this efficient assimilation of amino acids to more than 80 fungal taxa in the fjord sediments, primarily associated with aquatic hyphomycetes. An efficient assimilation of amino acids is shown here to be a trait of marine fungi that plays a role in retaining labile dissolved organic matter as microbial biomass in Arctic fjord benthic ecosystems, hotspots for carbon sequestration that are currently experiencing rapid change due to climate warming. Our results indicate that fungal metabolism and biomass in marine sediment should be considered as an important contributor to seafloor carbon storage.
<p>by Hongtao Zhang, Wenqing Liang, Meng Li, Yuejun Yang, Lei He, Wencong Nan, Guoteng Liu, Bin Wang, Ye Hong</p>
Crossover (CO) formation ensures accurate segregation of homologous chromosomes during the first meiotic division. The pro-crossover proteins are essential for crossover formation and undergo dynamic changes during meiotic prophase I, although the underlying regulatory mechanism is largely unknown. Here, we found that the ubiquitin-proteasome system (UPS) plays a pivotal role in orchestrating pro-crossover protein dynamics and crossover patterning during meiosis in <i>Caenorhabditis elegans</i>. Knockdown of either the ubiquitin-activating enzyme E1 or the proteasome resulted in elevated pro-crossover protein levels and crossover designation. Impairing ubiquitination, but not proteasome activity, led to persistent association of pro-crossover proteins on meiotic chromosomes, a process mediated by the CDC-48<sup>UFD-1/NPL-4</sup> segregase. Utilizing a hypomorphic allele of <i>cosa-1</i>, a well-characterized pro-crossover protein-encoding gene, we further demonstrate that the UPS restricts crossover formation. Collectively, our findings reveal a multilayered UPS-mediated regulatory network that maintains proper pro-crossover protein dynamics, thereby coordinating crossover formation with meiotic chromosome segregation.
This population-based screening study examines early-stage (stage 1 or 2) type 1 diabetes prevalence and disease progression to clinical (stage 3) type 1 diabetes in children.
Value-based decision making is regulated by a delicate interplay of instrumental and Pavlovian controllers. Here, we assessed the role of catecholamines in this interplay. We investigated the effects of the catecholamine reuptake inhibitor methylphenidate (MPH) in 100 healthy subjects using a combined appetitive and aversive Pavlovian-to-instrumental transfer (PIT) paradigm, including approach and withdrawal actions. By administering the drug after learning, our design allowed us to establish that MPH can also bias action outside a learning context by directly modulating the interaction of Pavlovian cues with instrumental action. Previously we showed that the effect of MPH on bias varied across these individuals as a function of their working memory (WM) span capacity (Swart et al., 2017). Here, we show by assessing both approach and withdrawal actions that MPH enhanced not only the invigorating effect of appetitive cues on active approach but also the inhibitory effect of appetitive Pavlovian cues on active withdrawal and the invigorating effect of aversive cues on active withdrawal. Thus, in participants with high WM capacity, MPH boosted both approach and withdrawal PIT. Taken together, this pattern of effects is most consistent with the hypothesis that MPH modulates the <i>cognitive control of Pavlovian biasing</i> in a baseline-state-dependent manner, in line with the well-established inverted U-shaped relationship between catecholamine receptor stimulation in prefrontal cortex and cognitive control.
Cortical circuits produce time-varying patterns of population and single-neuron activity that play a fundamental role in perceptual and behavioral processes. However, the functional contributions of individual neuron activity to population dynamics and behavior remain unclear. Here, we addressed this issue focusing on the mouse gustatory cortex (GC) and using a taste mixture-based decision-making task, high-density electrophysiology, and computational modeling. GC population dynamics represented stimuli linearly during taste sampling, and choices categorically before decisions. Single neurons were classified by their linear and categorical activity patterns, revealing sub-populations encoding sensory, perceptual, and decisional variables. To test their functional role, we built a recurrent neural network model of GC. Model perturbations showed linear and categorical neurons were essential for driving normal population dynamics and behavioral performance, whereas many units with other activity patterns could be silenced without consequence. These results have implications that extend beyond GC and demonstrate the role of linear and categorical coding neurons in cortical dynamics and behavior during perceptual decision-making.
Cancer progression involves extensive alterations in epigenetic and gene expression programs, but the accompanying changes in higher-order genome organization remain less well understood. Using high-resolution Micro-C mapping in the MCF10 cell model of breast cancer, we profiled chromatin compartments, topologically associated domains, and chromatin loops. We find large-scale compartmental shifts occur predominantly in early stages of cancer development, with more fine-scale structural changes in topologically associating domains and loops accumulating during the later transition to metastasis. Relating these chromatin features to gene expression and enhancer-associated histone marks revealed that many differentially expressed genes are physically connected to distal regulatory elements. While enhancer–promoter contact frequency and distal enhancer activity correlated with gene expression, strong changes in chromatin looping were relatively infrequent during progression, suggesting that alterations in chromatin contacts are not globally necessary, but may facilitate gene regulation at a subset of genes. These results elucidate the connection between gene regulation and genome remodeling in a cell-based cancer progression model.
The Faroe Islands are home to descendants of a North Atlantic founder population with a unique history shaped by both migration and periods of relative isolation. Here, we investigate the genetic diversity, population structure, and demographic history of the islands by analyzing whole genome sequencing data from 40 participants in the Faroe Genome Project. This represents the first whole genome sequencing panel of this size from the Faroe Islands. We observed numerous putatively functional private alleles, including stop gain variants and high impact missense variants in the cohort. Faroese individuals had a higher proportion of their genomes contained in long runs of homozygosity than other European groups, including Finnish, suggesting a more recent or stronger bottleneck in the Faroese population. Signals of positive selection were identified at loci containing genes that play roles in vitamin D and dietary fat absorption and DNA repair, while increased diversity on lactase persistence haplotypes was observed. Fine-scale analysis of haplotype structure in present-day and ancient European genomes revealed genetic affinities with ancient Iron Age individuals from the North and West of Europe, providing evidence for potential contributions to the Faroese gene pool from Celtic and Viking populations as well as information about the temporal order in which these events happened. This study highlights the impact of evolutionary processes, such as ancient admixture, founder events, and positive selection, on the present-day genetic architecture of North Atlantic founder populations like the Faroe Islands.
Classically, type 1 diabetes has been diagnosed only after patients have lost a critical threshold of beta cell mass, resulting in symptoms of hyperglycemia due to insulin deficiency. Despite advances in glycemic monitoring and insulin delivery, patients with clinical type 1 diabetes experience enormous mental burden and health care costs and are at risk of developing complications from chronic hyper or hypoglycemia. Natural history studies have shown that type 1 diabetes can be diagnosed in presymptomatic stages via detection of 2 or more islet autoantibodies. Stage 1 is defined by the presence of 2 or more islet autoantibodies with normoglycemia and stage 2 by the presence of 2 or more islet autoantibodies and abnormal glucose metabolism. Stage 3 marks the clinical diagnosis of type 1 diabetes, characterized by hyperglycemia. Options for disease modification to intervene in the presymptomatic stages and delay insulin requirements are becoming available clinically or through prevention trials testing agents shown to have efficacy in stage 3 disease (NCT07222137 and NCT07216391). As these advances in prediction and disease modification evolve, the long sought–after possibility of prevention of clinical type 1 diabetes is now approaching reality. With this possibility for intervention, screening for presymptomatic type 1 diabetes begins to meet the criteria for the principles and practice of screening by Wilson and Jungner, which state that screening programs should target health conditions that are detectable at an early stage, have an effective intervention when applied early, and have a valid, reliable, and acceptable test available. In addition, Wilson and Junger outline the importance of cost-effectiveness and the existence of intrastructure and systems to support diagnosis, treatment, and follow-up to ensure that benefits outweigh potential harm.
A common question asked when encountering a patient presenting with pain is “How would you describe your pain?” Although some descriptors are routinely taught during training (the 0 to 10 pain scale) or heard more frequently in clinic visits (stabbing, burning, or gnawing), pain remains a deeply personal experience. Despite medicine’s interest in patients characterizing their pain, quantitative scales and checkbox adjectives are too often insufficient. Hence, patients turn toward the arts, such as poetry, to help them best narrate their experiences of pain. While offering pharmacological or interventional treatments to alleviate pain, clinicians might also better help patients by validating and listening to their unique experiences of pain when expressed creatively. In the poem “Pain,” the speaker does just this, describing an unusual and even refreshing personification of pain. Featuring metaphors at once humorous and yet biting, pain is depicted not as necessarily punitive or adversarial, but as something to engage. It is “a clown,” both “misbehaving” and “scour[ing],” a persona that is certainly annoying but also almost comical. The speaker’s physiological pain becomes a metaphorically pestering pain, doing exactly what it should not be doing—it is “parading” and “screech[ing]”—always persistently “there.” Yet articulating what exactly is so irksome in these novel ways leads to a certain empowerment, especially when using metaphors that make pain seem more like an unruly friend than a malevolent presence. Perhaps, while pain might ultimately feel like something that cannot be shared, how it is named exerts a kind of control that the afflicted can still hold over it.