eLife Assessment

This important study examines the benefits of spatial cognition in a wild population of mountain chickadees. Using robust genetic analyses and experimental design, the authors show with compelling evidence that females seeking out extra-pair copulations prefer males with strong spatial cognition, and that these males have a reproductive advantage over other males. This work is of broad interest to evolutionary and behavioural biologists.

eLife Assessment

This important study provides evidence that plateau pikas, at moderate densities, can facilitate yak nutrition by suppressing a poisonous plant, offering a helpful perspective on reciprocal interactions between small mammal ecosystem engineers and large herbivores. The evidence is solid, supported by a manipulative field experiment and appropriate measurements of intermediary ecological processes, although some claims about density dependence, competition, and stress-gradient mechanisms are not fully supported by the experimental design. The work will be of interest to ecologists, conservation biologists, and rangeland managers, particularly those studying grassland herbivore interactions and livestock management on the Qinghai-Tibetan Plateau.

eLife Assessment

The authors combine a modeling approach, using a digital twin, with electrophysiological evidence in two species to assess the role of inhibition in shaping selectivity in the visual cortex. The results provide a fundamental advance beyond the classic view of sensory coding by proving compelling evidence that many neurons in visual areas exhibit dual-feature selectivity. Overall, the work compellingly showcases how in silico experiments can generate concrete hypotheses about neuronal coding that are difficult to discover experimentally.

eLife Assessment

This fundamental work substantially advances our understanding of tissue deformation and growth patterns during the earliest stages of mammalian heart development. One of the strengths of the work is the compelling quantitative approach to analyzing time-lapse imaging data using an original computational pipeline, which goes beyond the current state of the art and provides new insights into heart tube formation. Overall, this rigorous study will be of broad interest to computational and developmental biologists studying tissue dynamics.

eLife Assessment

This study presents valuable findings on the differential effects of RNA on the phase separation, aggregation dynamics, and bioactivity of PSMα3 and LL-37. The authors provide solid evidence from complementary biophysical and cell-based experiments that RNA influences peptide assembly and associated in vitro activities. The study is of interest for understanding interactions between amyloidogenic peptides and nucleic acids.

eLife Assessment

This fundamental study provides compelling evidence for the functional segregation of the sensorimotor cortex into precisely delineated areas, and highlights a rapid transition in functional properties at the boundaries between these areas. This result further confirms and extends recent work on the diversity of neural response specificities across cortical areas in the context of complex behavioral tasks. This work will be of interest to neuroscientists studying sensory-motor functions.

eLife Assessment

This study makes a valuable contribution to the understanding of meta-learning and its neural mechanisms by distinguishing two timescales of learning rate adaptation: rapid, within-block reductions and slower, location-specific, meta-learned adjustments. Behavioural data and computational modelling provide convincing evidence that individuals adjust learning rates both rapidly in response to uncertainty and more gradually through meta-learning of environmental statistics. Neuroimaging results indicate that meta-learned learning rates are represented in orbitofrontal cortex, and that prediction errors are encoded across a distributed network including the ventral striatum, where they are modulated by expectations about error magnitude. The manuscript is timely and clearly written and opens the door to future work on how these signals contribute to adaptive behaviour.

eLife Assessment

This important study provides solid novel evidence for a role of ripples in the hippocampus in visual short-term memory. The work is strong in employing state-of-the-art intracranial electrophysiology in epilepsy patients with multivariate pattern classifiers in the context of an elegant experiment, but several aspects of the theoretical framing, mechanistic interpretation, and analysis strategy are incomplete.

eLife Assessment

This valuable study combines sub-millimeter 7T fMRI, EEG, representational similarity analysis, and deep neural network modeling to investigate layer-specific spatiotemporal dynamics underlying human object processing in early visual cortex and lateral occipital cortex; the authors report temporally distinct signatures in superficial layers of LOC that are interpreted as reflecting sequential feedforward and feedback processing during visual recognition. The multimodal methodological approach and empirical dataset are substantial and will be of broad interest to researchers in visual neuroscience, layer-fMRI methodology, and computational vision. However, the evidence supporting the central interpretation of interareal feedback remains incomplete, as the observed dynamics could also be explained by alternative mechanisms such as within-area recurrent processing, and there are additional concerns regarding several methodological and modeling choices underlying claims about increasing representational complexity at later time points. Overall, the study provides solid evidence for layer- and time-specific neural dynamics during object processing, while the interpretation of these signals as feedback-related remains provisional.

eLife Assessment

This foundational and valuable study expands our understanding of circadian clock work in non-model taxa in wider environmental niches, using solid methods for protein and RNA detection to describe the expression pattern of PDH, cry2, and per in the central nervous system of Euphausia superba. While the anatomical annotation is extensive, support for the identification of the clock network is incomplete.

eLife Assessment

This important study reveals distinct representations of task-related information in the dendrites and somata of cortical neurons during sensorimotor learning and behavioral adaptation. The evidence is compelling, combining simultaneous imaging of dendritic and somatic activity during behavior to demonstrate compartment-specific encoding of sensory cues, motor actions, and corrective signals. The work will be of broad interest to neuroscientists studying dendritic computation, motor learning, and the cellular mechanisms underlying adaptive behavior.

eLife Assessment

This valuable study examines whether reduced cooperation is driven by betrayal aversion beyond nonsocial loss aversion, using matched social and nonsocial risky decision-making tasks combined with computational modeling and EEG. The authors provide solid empirical evidence that social risk is processed differently from matched nonsocial risk, offering a meaningful contribution to the study of cooperation and decision-making under uncertainty. However, further justification of the computational modeling approach would strengthen some of the conclusions. This work will be of interest to researchers studying social decision-making, cooperation, trust, and the neural and computational mechanisms underlying risk and betrayal aversion.

eLife Assessment

This important study demonstrates that extrachromosomal circular DNA and chromatin-associated proteins are components of stress granules. The data from a range of cellular and microscopy approaches are convincing, but the main conclusions would be further strengthened by demonstrating functional relevance and by extending the analysis to additional cell types. This paper will be of broad interest to cell biologists and those studying stress granule formation.

eLife Assessment

This useful study examines how the swimming of a lab strain of Escherichia coli changes under laboratory conditions designed to mimic disordered, porous environments: a setting that is biologically relevant and less understood than chemotaxis in bulk liquid. By combining experimental evolution in soft agar, inducible control of run duration, visualization of flagella, and theoretical modeling, the authors demonstrate that the optimal mean run duration for migration in semisolid agar is substantially shorter than in liquid and decreases with increasing agar concentration. The authors provide incomplete evidence regarding optimal chemotaxis in porous media as emerging through evolution from tradeoffs that involve newly discovered trapped states.

eLife Assessment

The nematode C. elegans is an ideal model in which to achieve the ambitious goal of having a genome-wide atlas of protein expression and localization. In this paper, the authors develop a rational strategy for at-scale tagging of all protein coding genes with fluorescent markers, providing solid evidence that it would be a feasible foundation for a community-based, genome-wide effort. This work should serve as an important springboard for discussions about how to achieve this worthy and impactful goal.

eLife Assessment

This study uses the yeast two-hybrid assay to identify proteins that may interact with yeast Set1 and other subunits of COMPASS/Set1C, the histone H3K4 methyltransferase, providing also some evidence for Set1 sumoylation and a role of SET1C methylating other factors in vitro. The results are valuable and they should contribute to understanding the functions of the conserved SET1C complex, as they suggest potential functional connections with RNA biogenesis, chromatin remodeling, and non-histone methylation whose implications would yet need to be explored. Nevertheless, apart from the fact that only a small subset of the Y2H interactions is further examined, the validating experiments are only partial or inconclusive, the strength of evidence being incomplete at this point, although with improvements over the previous version.

eLife Assessment

This study presents an important finding regarding the role of oxytocin neurons in thermogenesis and behavioral thermoregulation. The use of numerous converging methods, including behavior, fiber photometry, optogenetics, thermal recordings, metabolic analyses, and more, produces a multi-dimensional dataset delivering findings that provide solid support for the conclusions. The conclusions could be further strengthen by more extensive analyses of behavior and determining whether it is the release of oxytocin (rather than co-release of glutamate) from the PVN that is critical for the transition between behavioral states, nevertheless, the manuscript had many strengths, the findings are novel, and this work opens new doors for understanding the role of the PVT in thermoregulation. This work will be of strong interest to the thermoregulation, social behavior, and oxytocin signaling communities.

eLife Assessment

The authors describe the important finding that the Legionella-containing vacuole is surrounded by a dense ubiquitin "cloud" that is highly resistant to detergent extraction. The study provides compelling evidence that this structure is generated through a combination of canonical ubiquitination mediated by the SidC Legionella ligase and phosphoribosyl-ubiquitination mediated by the SidE family of Legionella ligases. These findings provide important insight into how Legionella remodels the host vacuolar environment through complex ubiquitin modifications.

eLife Assessment

In this study, the authors found that a species of aphid that is a known agricultural pest salivated longer and produced more honeydew when feeding at night. The authors identified aphid genes with diurnal expression patterns, including potential salivation-related genes. Silencing these genes reduced aphid performance only on plants and not on artificial diet, suggesting a specific role in plant feeding. This study is valuable for understanding plant-insect interactions in agriculture and presents solid evidence of diurnal rhythmicity in aphid activity and performance, although further research is needed to elucidate the function of the identified genes.

eLife Assessment

Huang and colleagues examined neural responses in mouse anterior cingulate cortex (ACC) during a discrimination-avoidance task. The authors present valuable findings that ACC neurons encode primarily "action content" over extended periods. The methodological approach is sound and the evidence in support of action state encoding is solid, though it is not conclusive to what extent ACC primarily encodes post-action events.

eLife Assessment

This study presents valuable findings on the neuromodulatory underpinnings of adaptive learning in dynamic, probabilistic environments. Solid evidence for these claims comes from showing spatial correlations between model-derived fMRI responses and PET-based receptor density maps. The work will be of interest to cognitive and systems neuroscientists working on decision-making.

eLife Assessment

This valuable study uses naturalistic movie-viewing fMRI and stacked encoding models to investigate sensory feature representations in autistic and non-autistic youth, showing a relative shift toward low-level visual representations in higher-order social cortical regions in autism. The evidence is solid overall, supported by preregistration, a relatively large open dataset, and sophisticated encoding-model analyses, although several methodological and interpretive issues require further clarification and validation. The work will interest researchers in developmental cognitive neuroscience and naturalistic neuroimaging.

eLife Assessment

This valuable study uses an elegant visual-anagram approach to test whether perceived animacy structures visual working memory and attention while controlling for many low-level image properties. The evidence is solid, with converging results across seven preregistered experiments, but the central claim that animacy itself is represented independently of visual features should be tempered, as residual mid-level configural cues, ensemble or category structure, and broader semantic differences may also contribute to the effects. The work will be of interest to researchers studying high-level visual representation, attention, and working memory.

eLife Assessment

This useful study combines behavioral reports, EEG decoding, and computational modeling to address an interesting question: how delay-period distractors bias working-memory representations, and how these effects depend on target relevance, distractor location, and the strength of memory maintenance and distractor encoding. However, the supporting evidence is incomplete, as several key claims require clearer statistical tests, better integration of the behavioral and neural results, and more careful consideration of alternative explanations. Stronger engagement with prior literature would also substantially strengthen the manuscript and increase its potential interest to researchers in systems, cognitive, and computational neuroscience.

eLife Assessment

This revised manuscript retreats from the original claim of establishing a causal link between cardiolipin deficiency and the progression from steatotic liver disease to steatohepatitis and instead advances a more limited mechanistic conclusion: that cardiolipin deficiency perturbs electron transport and promotes electron leak from the mitochondrial respiratory chain. The experimental evidence supporting this revised claim is now solid, and the potential for increased electron leak to contribute to liver pathophysiology is demonstrated. However, absent evidence that cardiolipin deficiency is causally upstream of disease progression, the overall significance of the work remains limited. While the study provides a convincing analysis of mitochondrial bioenergetics, the narrowing of its central claim diminishes its impact relative to that proposed in the original submission.

eLife Assessment

This important study assesses the portability of epigenetic clocks across ancestries, including in the context of accelerated aging in Alzheimer's Disease patients. It provides convincing evidence for population differences in age estimation accuracy across a variety of epigenetic clocks, driven in large part by continuous variation in ancestry. Given the accelerating use of epigenetic clocks across fields, this study is likely to be of interest to researchers working on human genetic and epigenetic variation or who apply epigenetic clocks to diverse human populations.

eLife Assessment

This study presents a comparison of the efficiency and precision of two prime editing methods to introduce single-nucleotide variants and longer exogenous DNA sequences into the zebrafish genome. Convincing data support the conclusion that the PE2 prime editor Nickase is more effective at introducing single-nucleotide variants, while the PEn prime editor nuclease is more effective at integrating sequences from 3 up to 46 base pairs, for both somatic and germline editing. The results will be valuable for the zebrafish community, in particular to model human disease variants in this model organism.

eLife Assessment

This important study used five metrics to compare the cost-effectiveness of intramural and extramural research funded by the National Institutes of Health in the United States between 2009 and 2019. They found that each type of research had its own set of strengths: extramural research was more cost-effective in terms of publications, whereas intramural research was more cost-effective in terms of influencing clinical work. The evidence supporting these findings is solid.

eLife Assessment

Du et al. present a valuable study examining neural activation in medial prefrontal cortex (mPFC) subpopulations projecting to the basolateral amygdala (BLA) and nucleus accumbens (NAc) during behavioral tasks assessing anxiety, social preference, and social dominance. The strength of the evidence linking in vivo neural physiology to behavioral outcomes was considered solid. Overall, the reviewers felt that the revised work provides insight into how distinct mPFC→BLA and mPFC→NAc pathways influence anxiety, exploration, and social behaviors.

eLife Assessment

This multimodal neuroimaging study leverages fMRI, PET, and deep learning to predict memory performance. The authors introduce the brain-cognition gap to link these different imaging modalities to cognition and evaluate their results in two independent cohorts. The results are solid and provide an important contribution to the literature and will be of interest to neuroscientists working at the interface of cognition, neuroimaging.

eLife Assessment

This important study used whole-genome data to investigate Beefalo ancestry for the first time, providing insight into the genetics of Beefalo cattle and challenging the long-held claim of 37.5% bison ancestry reported by the American Beefalo Association. Despite some limitations regarding sequencing depth and sampling, the expert use of a comprehensive set of population-genomic methods allowed the authors to demonstrate convincingly that Beefalo and bison hybrid ancestry profiles are consistent with repeated backcrossing to either parental species. The work will be of significant interest to evolutionary biologists, population geneticists, animal breeders, and those involved in the conservation genetics of bovine species.

eLife Assessment

This study provides a detailed anatomical and functional framework for understanding CO₂ processing and behavioral flexibility in Drosophila. The significance of the work is important, as it identifies how specific neural circuits, such as LN23, modulate innately aversive signals across different contexts. The strength of the evidence is convincing, supported by a robust combination of connectomics, anatomical reconstructions, and targeted behavioral manipulations.

eLife Assessment

This study presents analyses of single neuron activity in the subthalamic nucleus (STN) of monkeys performing a decision-making task that manipulates both perceptual evidence and reward. The study shows convincing evidence of distinct subpopulations of neurons in STN that differ in their representations of key quantities related to decision formation. These findings reveal important functional heterogeneity within the STN that helps provide new insights into its contributions to decision processing.

eLife Assessment

This manuscript represents a valuable contribution to understanding motion processing in the visual cortex. Based on a heterogeneous collection of previous empirical findings, the authors show that the diversity of tuning curves in the middle temporal (MT) area, in response to moving center-surround images, can be explained by Bayesian inference combined with neural sampling. The model rests on strong and solid assumptions about the prior and likelihood; independent evidence that neither of these factors is misspecified would strengthen the work.

eLife Assessment

This valuable study raises the intriguing possibility that crickets use bat-associated odors as cues of predation risk, extending the classic bat-insect arms race beyond its usual acoustic framework. The authors combine fecal metabarcoding, behavioral assays, electrophysiology, chemical analyses, and field observations to show that Loxoblemmus equestris avoids the odor of the insectivorous bat Scotophilus kuhlii, and that synthetic (-)-limonene can elicit antennal responses, avoidance in the laboratory, and reduced calling activity in the field. However, the evidence is currently incomplete because the identity, biological source, natural concentration, and ecological specificity of limonene as a bat-derived predator cue require stronger support, including clearer quantification, contamination controls, individual-level odor data, and evidence that crickets can distinguish bat-associated limonene from common environmental sources. The work will be of interest to researchers in sensory ecology, chemical ecology, predator-prey interactions, and bat-insect coevolution.

eLife Assessment

The authors use convincing methodology to investigate the detachment and reattachment kinetics of kinesin-1, 2 and 3 motors against loads oriented parallel to the microtubule. The conclusions drawn from the valuable experiments as well as the overall interpretation of the results are fully supported by the presented data.

eLife Assessment

This study characterizes a potentially targetable mechanism by which phosphate scarcity drives polymyxin B resistance in Enterobacteriaceae. The findings are important. While some aspects of the approach are very strong, particularly the diversity of techniques, it is recommended to include genetic controls and antibiotic resistance experiments in order to strengthen the evidence, which is currently solid. The clarity and presentation of the findings could also be improved.

eLife Assessment

This study used pupillometry to provide an objective assessment of a form of synesthesia in which people see additional color when reading numbers. It provides convincing evidence that subjective color ratings are matched by changes in pupil size that recapitulate brightness-mediated changes when exposed to the real color. The work provides a valuable contribution to the literature on both synesthetic perception and the use of pupillometry to probe perception and related psychological processes.

eLife Assessment

This study presents valuable findings on the high prevalence of pain in women with polycystic ovary syndrome and its association with distinct future health risks across different racial groups. The evidence supporting the conclusions is compelling, utilizing a massive global dataset and rigorous propensity score matching to identify pain as a critical, yet underexplored, clinical marker. The work will be of interest to reproductive endocrinologists, medical biologists, and clinicians involved in the diagnosis and management of polycystic ovary syndrome.

eLife Assessment

Rickert and colleagues demonstrate that the host peptidoglycan-binding protein PGLYRP1 has both beneficial and detrimental effects on Bordetella pertussis infection in mice. Using a solid array of techniques, the study provides useful insights into how the peptidoglycan fragment tracheal cytotoxin alters host immune responses, dampening inflammatory responses later in B. pertussis infection. These studies indicate that release of peptidoglycan fragments with particular structures can be used by bacteria to modulate NOD1 versus NOD2 responses to their advantage.

eLife Assessment

This study provides a fundamental finding regarding the context-dependent roles of the JAK-STAT pathway (JSP) across different cellular compartments within the breast cancer microenvironment, supported by convincing evidence. The comments of the reviewers were sufficiently addressed.

eLife Assessment

This study presents a valuable framework for the rational design of bacterial probiotics to protect against respiratory infections. The evidence supporting the central claim - that metabolic niche overlap predicts probiotic efficacy - is solid, combining innovative in vitro modeling with in vivo validation, though the model appears less effective for probiotics that rely on antimicrobial metabolite production.

eLife Assessment

This study identifies apoptotic retinal ganglion cells as a potential source of ATP-mediated activation of PANX1 channels that initiate developmental retinal Ca²⁺ waves and coordinate microglial activation and vascular outgrowth with postnatal maturation. The work is important because it proposed an integrative framework linking programmed cell death, spontaneous neural activity, immune responses, and angiogenesis into a self-regulating developmental loop. The multimodal data are solid, but the mechanistic conclusions would be strengthened by complementary genetic approaches, such as PANX1 or BAX knockout models, to establish direct causality.

eLife Assessment

This important study deepens our understanding of how populations of a given species may diverge in their molecular and physiological patterns as a result of adaptation to different thermal regimes. By approaching this question from multiple directions, the authors provide convincing evidence for adaptive changes in three strains of the diamondback moth after only three years of experimental evolution. This work will be of interest to anyone working on the response of pest species to environmental change and to workers on adaptive evolution in general.

eLife Assessment

This fundamental work demonstrates that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner. The evidence in this study is compelling. This study will be of interest to readers in the field of synaptic transmission.

eLife Assessment

This is an important study that establishes a zebrafish model of PIK3CA-related overgrowth syndrome. The imaging characterization of the mesodermal, particularly vascular, lesions of the model is compelling. The scRNA-Seq analysis is convincing, revealing key perturbations in the PIK3CA-mutation model, although deeper investigation of the exact mechanism leading to the lesions, as well as validation at different time points, could further strengthen the findings. This work will be of interest to medical biologists working on PROS, and potentially to a broader audience interested in non-cell-autonomous signaling of PIK3CA and its implications in other diseases.

eLife Assessment

This work presents important findings on quantifying gene coexpression from spatial omics. These quantification methods have been applied to gastruloid to describe how genes are spatialised. The description of the quantifying tools might be incomplete, which also weakens the biological message. Clearer formalization and justification of quantification will improve the study.

eLife Assessment

This valuable study provides the first broad cross-species evolutionary analysis of the pir multigene family in malaria parasites, showing that the family evolved through rapid duplication and loss while retaining a small number of conserved orthologs with essential functions. The authors identify pirC1 as a key determinant of parasite growth across multiple Plasmodium species. However, the work remains incomplete because the mechanistic role of PIRCl and its precise subcellular localization are not directly resolved.

eLife Assessment

This important study by Bi and colleagues employed a clever genetics screen to uncover the role of the GidB rRNA methylase in translation fidelity, under certain conditions, in Mycobacterium smegmatis. The findings are solid, supporting the findings that the loss of GidB results in mistranslation. The work contributes to a more in-depth understanding of mycobacterial translation fidelity and will be of interest to microbiologists.

eLife Assessment

This valuable work addresses a longstanding question of how the extant genetic code came to be selected and conserved almost universally across life. Using a mutational approach and a small set of reporters, the authors demonstrate that the mutational impact was similar for non-standard genetic codes. The data provide solid support for the claim of having provided experimental verification of the error minimization theory.

eLife Assessment

This study reports important advances in our understanding of how enteropathogenic E. coli (EPEC) interacts at the intestinal interface. Compelling data describe a novel model of spatially coordinated calcium signaling to modulate NF-kB activation. These findings, which integrate imaging, genetics, and computational modeling, provide a new way to consider host-pathogen interactions in EPEC infections that may lead to improved therapies.

eLife Assessment

This valuable study advances our understanding of best practices for analyzing population-level data using advanced functional alignment methods. It provides convincing evidence that demographic-specific functional templates improve functional neuroimaging studies that use hyperalignment. This study will be of interest to cognitive neuroscientists, neuroimaging methodologists, and computational researchers with an interest in the human brain.

eLife Assessment

This important study substantially advances the imaging toolbox available to neuroscientists by presenting a tunable Bessel (tBessel-TPFM) platform that enables high-speed volumetric two-photon imaging. The evidence supporting the novel methodology is convincing, with rigorous benchmarking and demonstrations of a wide range of neuroimaging applications covering vascular dynamics, neurovascular coupling, optogenetic perturbation, and microglial responses. The work will be of broad interest to neuroscientists and imaging system tool developers.

eLife Assessment

This important study links allelic expression imbalance with replication timing, suggesting a stochastic model for haploinsufficiency in dosage-sensitive disease. The integration of allele-specific RNA-seq and replication timing in clonal systems provides solid evidence for an association between asynchronous replication and allelic imbalance, although the scope and generality should be addressed in future work. This study will interest epigeneticists and genome regulation researchers studying replication timing and monoallelic expression, as well as developmental biologists and human geneticists concerned with clonal heterogeneity, haploinsufficiency, and variable disease penetrance.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This valuable study uses technically compelling long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The authors further propose the provocative model that post-translational mechanisms, rather than the transcriptional-translational processes, may contribute to circadian regulation of neuronal excitability. However, the evidence for circadian firing in these neurons, and for post-translational modification of Orco as the underlying mechanism, remains incomplete. In contrast, the study does provide strong evidence that the application of cyclic nucleotides can modulate Orco-dependent activity at a single time point, and reports that the temporal pattern of Orco transcript abundance is not circadian.

eLife Assessment

This well-designed, valuable study uses isotope tracing to analyse how iron limitation alters TCA cycle metabolism in Mycobacterium tuberculosis, revealing potential antibiotic targets for non-replicating bacteria in the host. The evidence is solid, providing insights into metabolic remodelling under iron-limited conditions.

eLife Assessment

This paper provides a novel and valuable method improve the accuracy of predictions of the impact of insecticide-treated net (ITN)-based strategies for malaria control and elimination by using sub-national estimates of the duration of ITN access and use over time from cross-sectional survey data and annual country ITNs received. The authors propose a sophisticated methodological framework that accounts for many sources of uncertainty, providing compelling evidence.

eLife Assessment

In this manuscript, the authors investigate programmed DNA elimination (PDE) across nematodes using a large-scale cytological approach. This work is potentially significant because it expands PDE beyond a few known nematodes to a much broader set of Rhabditidae species, providing an important resource for investigating PDE's evolutionary origins and functions. The strength of evidence, however, is incomplete; the technique used to evaluate PDE is insufficient to provide unambiguous support for the phenomenon, so additional methods, such as genomic sequencing from a few species spanning the range of elimination levels, would be required to confirm these findings. This research would be of interest to geneticists, evolutionary biologists, and those working on the regulation of genome integrity.

eLife Assessment

This is a fundamental study of individual variation and the contribution of learning to behavioural individuality. The experimental design of massively parallel behavioural phenotypes is outstanding and the conclusions are supported by a compelling and rigorous analysis across a large number of experiments in thousands of individuals across genotypes and conditions. The dataset further represents an advance in studying visual associative learning thanks to the ability to make longitudinal measurements of many behavioural decisions within the same animals. These results are a major contribution to the understanding of the sources of behavioural individuality.

eLife Assessment

This paper presents a valuable methodology for genetic manipulation of Blastocystis. Although some imaging data are compelling, higher-quality figures together with more rigorous biochemical assays would strengthen support for the authors' claims. With the experimental evidence and graphics improved, the study would be of interest both to researchers investigating mitochondrial evolution under anaerobic conditions and to medical biologists studying human pathogens.

eLife Assessment

This manuscript presents a useful computational framework for systematically characterising how heterogeneity in initial conditions or biophysical parameters shapes the dynamic behaviour of protein signalling networks, with potential relevance to understanding adaptive drug resistance. While the approach represents a significant methodological contribution, the extent to which its conclusions are biologically informative remains debated, as the model is only qualitatively compared with experimental data and lacks quantitative validation. As a result, the strength of evidence supporting the mechanistic claims is viewed as incomplete.

eLife Assessment

This study represents an important contribution to the study of decision-making under risk, bringing an interdisciplinary approach spanning economic theory, behavioral neuroscience, and computational modeling to test how choice preference is influenced by rare and extreme events. The authors aim to test whether rats are indeed sensitive to these rare and extreme events despite their infrequent occurrence, and to isolate behavioral evidence for avoidance of "Black Swans" - rare and extreme losses. The evidence for specific sensitivity to rare and extreme events however remains incomplete, owing in part to the difficulty of isolating the effect of these events beyond that arising from risk preferences more generally in both task design and in the computational modeling of the choice behavior. Despite this, and given the approach here brings a relatively novel and highly interdisciplinary perspective, this paper will be of broad interest to those seeking to understand animal behavior through the lens of economic choice and decision theory.

eLife Assessment

Insects can act as vectors of plant diseases, hence the study of insect-pathogen interactions is relevant for agriculture. This important study identifies in Diaphorina citri a dopamine receptor responsive to 'Candidatus Liberibacter asiaticus' infection, demonstrate direct regulation of this receptor by a microRNA, and integrate dopamine signaling into an established insect reproductive hormone framework. Multiple complementary experimental approaches convincingly support for the findings, although key conclusions rely on correlative data and the mechanistic evidence for the proposed linear signaling cascade is limited. This work will be of interest for insect physiology and vector-pathogen biology, and more broadly for citrus agriculture.

eLife Assessment

This fundamental manuscript presents a novel application of the SANDI (Soma and Neurite Density Imaging) model to study microstructural alterations in the basal ganglia of individuals with Huntington's disease (HD). The compelling methods are, to our understanding, the first application of SANDI to neurodegenerative diseases, provide strong evidence for HD-related neurodegeneration in the striatum, account significantly for striatal atrophy, and correlate with motor impairments. The integration of novel diffusion acquisition and modelling methods with multimodal behavioural data are both of high value in their own right, and create a framework for future studies.

eLife Assessment

Using fMRI-based pRF mapping, this important study presents a novel method for estimating visual field (VF) loss and potential restoration by analyzing contrast-sensitivity patterns in early visual cortex. The evidence supporting the main claims is convincing. This work will be of broad interest to researchers in vision and clinical vision, neuroscience, and brain imaging.

eLife Assessment

This important study utilizes behavioral data and computational modeling to show that spatial properties of visual attention affect human planning. The methodology and statistical analyses are convincing, though the way attention is conceptualized and modeled could be refined. The findings of this study will interest cognitive scientists studying attention, perception, and decision-making.

eLife Assessment

This study offers a valuable analysis of how moment-to-moment fluctuations in arousal are associated with structured, non-uniform patterns of brain-wide functional connectivity during wakefulness. Using data-driven analyses of resting-state and naturalistic fMRI with eye tracking, the authors present convincing evidence that arousal is a dynamic, continuous process that shapes brain activity in a structured way beyond a simple global effect. This paper sheds light on the link between brain activity and ongoing fluctuations in arousal and will be of interest to researchers studying large-scale brain functional organization and links between the brain and body.

eLife Assessment

The importance of uterine natural killer (NK) cells in reproductive success has been demonstrated in mice and humans; however, it is still unclear how uterine NK cells are developed. In this important manuscript, the authors provide convincing evidence that TGF-b signaling in NK cells supports normal pregnancy in mice by the conversion of conventional NK cells into uterine tissue-resident NK cells. Previous concerns have been addressed in this revised version.

eLife Assessment

This manuscript provides important insights into how U2AF2-dependent intron retention regulates the localization and function of long noncoding RNAs, with evidence supported by multiple complementary approaches. The work is notable for linking intron retention to nuclear speckle localization and cellular phenotypes, including proliferation and migration, although the mechanistic basis remains incompletely resolved. Overall, the study presents a compelling dataset with clear biological implications but would benefit from additional analyses to strengthen mechanistic interpretation and generality.

eLife Assessment

This important study establishes the first vertebrate models of DeSanto-Shinawi Syndrome, revealing conserved craniofacial and social and behavioral phenotypes across mouse and zebrafish that mirror key clinical features. The convincing evidence is supported by behavioral, anatomical, and molecular analyses of Wac animal mutants. This study sets a baseline for future mechanistic studies and reports a platform to test approaches to reverse phenotypes.

eLife Assessment

This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This work provides convincing evidence, supported by pharmacological perturbations and numerical simulations using the vertex model, that the principle of "high heterotypic interfacial tension" that appears to drive cell sorting and tissue segregation in embryonic models similarly applies to cancer cell behaviour.

eLife Assessment

This study presents valuable findings on phase-separated condensate formation by the MUT-16 protein, which plays a key role in small RNA biogenesis. A detailed analysis of the interactions governing condensate formation was carried out using coarse-grained and all-atom molecular dynamics simulations, complemented by in vitro phase separation experiments. While many of the results appear solid, a number of technical details are lacking, the computational part appears incomplete and would benefit from additional analyses and clarifications, and the novelty of the study should also be clarified, particularly in comparison with the authors' previous work on MUT-16. Overall, the work will be of interest to biophysicists and molecular biologists studying phase separation and biomolecular condensates.

eLife Assessment

Overall, this is a manuscript with solid evidence that delivers an important community resource for those performing experimental research in amyotrophic lateral sclerosis. The authors address the lack of validated tools for the detection and quantification of proteins associated with amyotrophic lateral sclerosis (ALS) through an extensive screening of 303 commercially available antibodies to 33 protein targets. The effort invested in generating the knockout lines for validation experiments is a clear strength of the study.

eLife Assessment

Non-essential amino acids such as glutamine have been known to be required for T cell general activation through sustaining basic biosynthetic processes, including nucleotide biosynthesis, ATP generation, and protein synthesis. In this important study, the authors found that extracellular asparagine (Asn) is required not only for T cells to generally refuel metabolic reprogramming, but to produce helper T cell lineage-specific cytokine, for instance, IL17. In particular, the importance of Asn in IL17 production was convincingly demonstrated in the mouse experimental autoimmune encephalomyelitei (EAE) model, mimicking human multiple sclerosis disease.

eLife Assessment

This important study demonstrates that nutrient stress engenders metabolic vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). By combining cell line and mouse models, the authors provide compelling evidence showing that arginine depletion from the microenvironment disrupts lipid homeostasis in PDAC resulting in ferroptosis upon exposure of tumors to polyunsaturated fatty acids. This report is likely to be of broad interest to researchers interested in studying cancer biology, metabolic adaptations and stress responses.

eLife Assessment

This important study provides a quantitative comparison of how zebrafish and medaka larvae process visual motion, revealing clear differences in how they integrate information across space and time. The evidence is convincing, combining a broad set of behavioral assays with response decomposition and mechanistic modeling that together support the central conclusions. Some aspects remain incomplete, particularly the link between the spatial and temporal findings, the extent to which the model accounts for the full range of behavioral results, and the framing of broader evolutionary or social interpretations. Overall, the work offers a careful and informative analysis that should be of broad interest to researchers studying visual processing, sensorimotor computation, and comparative neuroscience.

eLife Assessment

This study presents a large-scale characterization of single-neuron responses during reading and listening, enabling examination of both 'low-level' (orthographic/phonological) and 'higher-level' (syntactic) features, as well as links between single-neuron activity and multi-scale field potentials, making it a valuable resource for bridging micro- and macroscale accounts of language processing. The analyses identify modality-specific and putatively modality-independent responses across distributed brain regions, offering an intriguing framework for understanding how sensory-specific and abstract representations may relate. However, the evidence supporting the central claims is currently incomplete, due to limited population-level quantification, insufficient statistical characterization of how many neurons encode the relevant features, ambiguity in the interpretation of encoding model results, and a lack of rigorous tests of cross-modal generalization and alternative accounts, which together weaken the conclusions about amodal representations and hierarchical processing.

eLife assessment

This is a valuable survey of movements and locomotor patterns produced by circuits in the medial reticular formation (MRF) of the brainstem. The authors provide solid evidence that activation of GABAergic MRF neurons slowed down walking, activation of glutamatergic neurons induced a specific "shuffle" limb trajectory, and the activation of serotonergic neurons increased locomotor speed without affecting walking signature. This study adds to the growing body of knowledge about the effects of brainstem circuits on specific aspects of locomotor function.

eLife Assessment

This study provides valuable mechanistic insight into the mutually exclusive distributions of the histone variant H2A.Z and DNA methylation by testing two hypotheses: (i) that DNA methylation suppresses H2A.Z deposition by ATP-dependent chromatin remodelling complexes, and (ii) that DNA methylation destabilizes H2A.Z nucleosomes, thereby preventing H2A.Z retention. Through a series of well-designed and carefully executed experiments, solid support is presented for the first hypothesis. The evidence supporting the second hypothesis is less complete, and the extent to which either mechanism is responsible for H2A.Z exclusion from methylated DNA remains not entirely clear. This work will be of broad interest to researchers in chromatin biology and epigenetics.

eLife Assessment

This study reports on the development and characterization of chickens with genetic deficiencies in type I or type III interferon receptors, which is an important contribution to the field of avian immunology. The data reflecting the development of the new interferon-receptor-deficient chickens is compelling. The initial characterization of IFN biology and infection responses in these knockout chickens provides a solid foundation for future studies on the distinct contributions of type I and type III interferon signaling to antiviral responses.

eLife Assessment

This important study implicates that changes in cell regulation may contribute to the evolution of multicellularity. The evidence supporting the conclusions is convincing, with rigorous methods used to test alternative hypotheses. The work will be of broad interest to cell and evolutionary biologists and those studying the cell cycle and cancer.

eLife Assessment

This important study demonstrates that paternal diet influences not only testicular morphology but also placental and fetal development, supporting a role for paternal contributions to offspring health. The study also considers potential links between the microbiome and male reproductive health. By combining transcriptomic and histological analyses across multiple tissues, the evidence supporting the central conclusions of the study is convincing.

eLife Assessment

The work by van der Pijl presents important findings on the role of titin-associated muscle ankyrin repeat proteins (MARPs) on hypertrophy via mTOR signalling. The study presents rigourous data using in vivo loss-of-function and pharmacological approaches to investigate effects on hypertrophy. While the evidence supporting the role of MARPs on hypertrophy is solid, there are limitations. For example, the use of Rapamycin only inhibits some aspects of mTORC1 signalling and the study is limited to analysis of the diaphragm and thus it is not clear if the mechanisms are conserved across other muscle types.

eLife Assessment

This potentially valuable study investigates the anti-senescence effects of red light exposure, proposing that reduced SIRT4 levels enhance fatty acid metabolism and H3K9ac, thereby attenuating ageing-related phenotypes. The authors use multiple approaches, including cultured cells, animal models, and molecular analyses, to support their conclusions. However, the evidence remains incomplete, as additional controls and stronger mechanistic data are needed to fully support the proposed pathway, particularly how red light exposure reduces SIRT4 levels.

eLife Assessment

The study presents valuable findings regarding the impact of ARHGEF6 deletion, a RhoGTPase regulator linked to X-linked intellectual disability (XLID46), in the development of interneurons. The evidence supporting the observed cellular and developmental phenotypes collected in both mouse and human iPSC models is convincing, although further work would strengthen the mechanistic interpretation and clarify the specificity of the findings. This work offers new insights into ARHGEF6 function and the potential contribution of its dysfunction to neurodevelopmental disorders.

eLife Assessment

This important study examines the effects of diet and exercise on brain structure and behaviour in the 3xTg mouse model of Alzheimer's disease. They show that combined access to a low-fat diet and exercise improves regional brain volume and behaviour in transgenic and wild-type control mice in a sex-specific manner, with analyses linking functional improvements to glucose homeostasis. Although some claims are well supported, the overall strength of the evidence is incomplete and hampered by a lack of clarity regarding the statistical analyses chosen. The work may be of interest to researchers studying neurodegenerative disease, particularly in preclinical contexts.

eLife Assessment

The manuscript by Rotsides et al. reports the design and validation of SMART-MR1, a miniaturized MR1 metabolite-display platform in which the α1/α2 ligand-binding domain is stabilized by a synthetic helical domain in place of the α3 domain and β2-microglobulin. Supported by biochemical, biophysical, and structural approaches, including ITC, NMR, and cryo-EM, the work provides solid evidence that SMART-MR1 retains native-like ligand binding and A-F7 TCR recognition while enabling experimental approaches for ligand screening that are difficult with conventional MR1 constructs. The study is valuable for the MR1 and MAIT-cell fields, particularly as a tool for ligand screening and mechanistic studies of MR1-restricted antigen presentation. There are several suggestions to further strengthen the study's impact, including clearer benchmarking against existing MR1 platforms, broader validation across ligands and TCRs, and functional evidence from MAIT-cell staining or activation assays.

eLife Assessment

The study by Izquierdo and colleagues provides important insights into the field of genomic and transcriptomic prediction of traits across multiple environments. The rationale and analyses conducted to integrate the two types of ~omics datasets across two environments are solid. However, some clarification would be appreciated in the presentation of the results, and adding some statistical control to clarify how the predictors were selected, or assessing their importance using the SHAP framework, would further consolidate the findings.

eLife Assessment

This Review Article provides an overview of circadian findings obtained using the zebrafish model and will be of particular interest to researchers working with zebrafish in chronobiology and behavioural neuroscience. The article would benefit from a broader conceptual framework that more clearly positions zebrafish within the wider landscape of animal models used in circadian biology, including comparisons with other extensively studied systems. In addition, several citation inaccuracies and interpretational issues identified during peer review should be carefully addressed to strengthen the accuracy and impact of the review.

eLife Assessment

This important study demonstrates that a perinuclear actomyosin network, present in some types of human cells, facilitates kinetochore-spindle attachment of chromosomes in unfavorable locations, thereby reducing their missegregation rate. This actomyosin network and its general role have been studied previously, but this study convincingly clarifies the underlying mechanism and expands the investigation to additional cell lines. The results are relevant to understanding chromosome missegregation in cancer cells.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This potentially useful paper presents an intriguing hypothesis about the evolutionary origins of the SLC25 family of mitochondrial carrier proteins common to all eukaryotic life, proposing that all members originated from the ADP/ATP carrier (AAC) and that AAC itself may have emerged from bacterial homologs such as CysZ and YihY. While the phylogenetic analyses and structural searches are reasonable methodologies to explore ancient evolutionary events, the evidence provided here is deemed to provide incomplete support for the conclusion that the mitochondrial ATP transporter is related to CysZ and Yih.

eLife Assessment

This valuable study uses a computer vision pipeline to infer the motor control of cephalopod skin, revealing that individual chromatophores exhibit anisotropic deformations and can be associated with multiple putative motor units. The evidence supporting these claims is convincing, and the authors present some limited electrophysiological validation of the findings from their computational analysis. This work will be of significant interest to biologists studying cephalopod behavior and motor control.

eLife Assessment

The paper presents a valuable finding that the human brain and models that incorporate sentence structures can capture sentence-level semantics beyond word meaning, while large language models behave differently. The evidence supporting the authors' claims is solid, though the stimuli are highly controlled and some analyses could be more thorough. This work will be of interest to researchers in language neuroscience and those developing language models.

eLife Assessment

This study addresses an important question in aging biology by combining metabolic, genetic, and functional approaches to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast. The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in shaping distinct aging-associated phenotypes is convincing overall, with the engineered A2A strain providing a particularly elegant demonstration of coordinated metabolic regulation. However, several conclusions would benefit from clarification or moderation, particularly regarding the relationship between late-life fitness and replicative lifespan, the interpretation of "senescence," the proposed existence of distinct aging subpopulations, and the extent to which the data support mechanistic claims about lipid starvation, acetyl-CoA excess, and chromatin-based aging pathways.

eLife Assessment

This important study provides convincing data suggesting that subcellular localization of the spatial regulator of cell division, MinD, is an intrinsic feature of the protein's ability to associate with the membrane as both a dimer and a monomer. These findings distinguish the behavior of MinD in B. subtilis from its counterpart in E. coli and suggest that there is not a need to invoke additional localization factors. The reviewers felt that the revisions, particularly the additional experiments and changes to the text to make the experimental design and conclusions clearer, improve the quality of the manuscript.

eLife Assessment

This important study provides novel information on multi-enzyme complexes, known as metabolons, that form between sequential enzymes in a metabolic pathway. Using an innovative NanoBiT split-luciferase system, the authors present compelling evidence that malate dehydrogenase (MDH1) and citrate synthase (CIT1) dynamically associate under different metabolic conditions in Saccharomyces cerevisiae. The findings suggest the dynamic MDH1-CIT1 interaction facilitates control of TCA pathway flux rate.

eLife Assessment

This important study utilizes behavioral data and computational modeling to show that spatial properties of visual attention affect human planning. The methodology and statistical analyses are solid, though the way attention is conceptualized and modeled could be refined. The findings of this study will interest cognitive scientists studying attention, perception, and decision-making.

eLife Assessment

This manuscript presents a useful mean-field model for a network of Hodgkin-Huxley neurons retaining the equations for ion exchange between the intracellular and extracellular space. The mean-field model derived in this work relies on approximations and heuristic arguments that, on the one hand, allow a closed-form derivation of the mean-field equations, but also raise questions about their justifications and the degree to which the results agree with experiments as well as direct numerical simulations. While the revised manuscript is much improved, reviewers continue to question the methodology for reducing model dimensionality and therefore the evidence for the utility of this approach remains incomplete at present.

eLife Assessment

This work by Pyne and Pandey et al. addresses DNase X (DNase1L1) activity at the macrophage phagocytic cup, using an innovative imaging approach that couples visualization of cup formation to spatially resolve DNA degradation. The methodology is technically sound, and the central finding that DNA digestion begins prior to phagolysosomal maturation is considered well supported, though some mechanistic claims may benefit from further evidence and more cautious framing. Overall, the study is solid and provides a valuable framework for investigating early events at the phagocytic cup that may shape responses to pathogens and inflammatory disease.

eLife Assessment

This important study combines single-molecule imaging and CUT&TAG to address the molecular mechanism underlying the differentiation process that initiates the formation of red blood cells in the bone marrow. The authors provide evidence that the transcription factor GATA2 transiently associates with a new set of genomic loci early in the differentiation process before it is replaced by GATA1. Together, the experiments across three biological systems are solid, but they could benefit from additional details and controls to strengthen the conclusions.

eLife Assessment

This manuscript presents a valuable and timely contribution by incorporating desolvation barriers into coarse-grained models of biomolecular condensates. The findings are convincing, supported by a clear physical model and systematic simulations showing effects on phase behavior, packing, and dynamics. Some clarification and broader context would improve the manuscript, but it provides a foundation that will be of use for developing more realistic coarse-grained interaction schemes.

eLife Assessment

This study presents a valuable framework that uses anticipatory eye movements to track how expectations are formed and revised during implicit probabilistic sequence learning. The evidence supporting a behavioural dissociation between errors arising from environmental noise and errors reflecting an inaccurate internal model is solid, but the oculomotor data describe behaviour rather than explain the underlying computational mechanisms, and the stronger mechanistic claims - that learning is more repetition-based than error-driven - remain incomplete without formal comparison against computational models of error-driven learning. The emerging reaction-time difference between conditions appears driven by slowing to low-probability stimuli rather than facilitation of high-probability ones, an asymmetry that requires decomposition and consideration of alternative explanations. The potential contamination of the anticipatory measure by starting gaze position should be addressed through control analyses, and the "process-pure" framing should be tempered, given that oculomotor behaviour is itself subject to motor learning.

eLife Assessment

This valuable study uses large-scale 7T naturalistic fMRI data and nonlinear pRF modeling to map the tonotopic organization of the human auditory cortex, linking spectral tuning to speech selectivity and cortical hierarchy. The evidence is solid, demonstrating that movie-based stimuli can recover robust population-level auditory maps and offering tools for leveraging existing datasets, although there is room for improvement in relating static tonotopy to dynamic speech processing and in presentation clarity. The study will be of interest to a broad audience working on auditory cortex organization and mapping.

eLife Assessment

This important study identifies two pairs of dopaminergic neurons (DA-WED) in Drosophila that coordinate cardiac deceleration and locomotor responses to a mechanical threat. The evidence is convincing, supported by comprehensive optogenetic, physiological, and behavioral experiments showing that these neurons are required for and sufficient to drive threat-associated cardiac slowing. The proposed role of cardiac deceleration as an interoceptive contributor to locomotion is intriguing, but should be presented more cautiously, as the causal relationship between heartbeat changes and locomotor output remains less directly established. The work will be of broad interest to those interested in neural circuits, neuromodulation, and the integration of physiological and behavioral responses.

eLife Assessment

This study proposes that fitness level influences exercise-induced hypoalgesia in women. However, the evidence to support this claim is incomplete: the conclusions rely on a small interaction that emerges only under specific conditions and are incongruent with the title, the findings are inconsistent across pain modalities and stimulus intensities, the analysis approach does not fully exploit the continuous pain ratings collected, and the absence of a baseline condition limits the interpretability of results as reflecting true hypoalgesia. Additionally, the methods by which fitness level was categorized across cohorts can be questioned, and the results and figures do not clearly illustrate how between-group comparisons were conducted. With a proper revision, it could be useful for sports medicine practitioners to consider how they administer exercise protocols to help those experiencing pain.

eLife Assessment

This study presents important findings on the relationship between nutrient availability and NAD/NADH levels, which in turn regulate biomass production in cancer cells. The authors provide convincing evidence to support their claims, offering insight into why it is difficult to predict which nutrients limit cancer cell growth: both cell type and nutrient availability together determine the oxidative capacity that constrains the synthesis of various metabolic intermediates. The manuscript will be of broad interest to researchers working in cancer and cell metabolism.

eLife Assessment

This study addresses an important gap in drug discovery by delivering a rigorous, large-scale evaluation of widely used co-folding methods for predicting ligand-bound protein complexes and virtual screening. A key strength is the comprehensive benchmarking framework, which leverages structures and chemical compounds that were absent from the AI models training set, thereby providing particularly compelling and unbiased evidence of co-folding performance. The findings clearly delineate the complementary roles of deep learning-based co-folding and physics-based docking, offering practical guidance for their rational integration into drug discovery workflows. Overall, the conclusions are well supported by thorough analyses across a representative set of cases and are highly convincing.

eLife Assessment

The nematode C. elegans is an ideal model in which to achieve the ambitious goal of a genome-wide atlas of protein expression and localization. In this paper, the authors develop a rational and useful strategy for at-scale tagging of all protein coding genes with fluorescent markers, providing solid evidence that it could be a feasible foundation for a large-scale, community-wide project.

eLife Assessment

This important paper substantially advances our understanding of how Molidustat may work, beyond its canonical role, by identifying its therapeutic targets in cancer. This study presents a compelling and well-structured investigation into the therapeutic vulnerabilities of APC-mutant colorectal cancer. This work will be of broad interest to the cancer community in studying small molecules and their therapeutic targets.

eLife Assessment

This study used pupillometry to provide an objective assessment of a form of synesthesia in which people see additional color when reading numbers. It provides convincing evidence that subjective color ratings are matched by changes in pupil size that recapitulate brightness-mediated changes when exposed to the real color. The work provides a valuable contribution to the literature on both synesthetic perception and the use of pupillometry to probe perception and related psychological processes.

eLife Assessment

This study presents a large, systematically curated catalog of non-canonical open reading frames (ncORFs) in human and mouse through the reanalysis of nearly 400 Ribo-seq datasets using a standardized pipeline; the resulting atlas consolidates ncORF annotations across tissues and provides a valuable resource for investigating non-canonical translation and ORF emergence. The main conclusions are supported by consistent data processing and multiple computational measures of translation and conservation. While the pipeline is transparent and technically robust, some analytical criteria and dataset limitations could be described more explicitly, and several downstream conclusions would benefit from more cautious interpretation, some evolutionary inferences are primarily correlative; dataset heterogeneity, uneven tissue representation, and limited experimental validation also constrain the strength of a subset of the findings. Overall, the evidence is solid, and the resource is likely to be broadly beneficial to the community.

eLife Assessment

This study offers an important contribution to our understanding of the role of layer 6b cortical neurons in sleep-wake regulation, providing new insight into how this understudied neural population may regulate cortical arousal via orexin signaling. The evidence supporting these findings is solid, although somewhat constrained by limitations in the specificity of the genetic targeting strategy. Nonetheless, the work introduces new avenues for uncovering how the classical wake-promoting peptide, orexin, exerts its effects on the cortex.

eLife Assessment

In this potentially valuable computational study, the authors conducted extensive atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating temperature-responsive structural and condensation behavior. Despite considerable improvements in the revised manuscript, the level of evidence is considered incomplete, since several of the supplementary observables introduced to support the revised claim indicate that the variants studied are not statistically distinguishable within the reported replicate uncertainty.

eLife Assessment

This is an important study describing 'SPEx', a broadly accessible method that combines cell expansion, laser microdissection, and mass spectrometry to enable subcellular proteomic profiling. The authors provide convincing evidence that this flexible integration of established techniques provides a robust and practical approach for compartment-resolved spatial proteomics. The authors support their main claims with appropriate validation across multiple subcellular compartments and show that the method can recover known markers while also identifying previously uncharacterized components. Overall, the work is likely to be of broad interest to cell and molecular biologists, particularly those seeking scalable and cost-effective strategies for mapping organelle composition.

eLife Assessment

This valuable study investigates whether high-level physical reasoning is grounded in real-time bodily and vestibular signals using an innovative combination of virtual tool-use tasks and galvanic vestibular stimulation. The evidence is incomplete, as the main claims rely on limited and partially exploratory effects, including uncorrected multiple comparisons and cross-study comparisons that weaken the strength of the conclusions. The work, if it can be supported by clearer statistical support and more cautious interpretation, will be of interest to researchers in embodied cognition and physical reasoning.

eLife Assessment

In this solid work, Fukui et al. re-examined the ATP hydrolysis mechanism in GHKL ATPases, revealing a cooperative role for two conserved acidic residues rather than a single one. This useful study used a range of biochemical and structural techniques on various mutants from different members of the GHKL ATPase family to test and validate their proposed mechanism. An updated and extended mechanistic model of ATP hydrolysis by this class of enzymes is proposed.