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    1. eLife Assessment

      The results of this study are important and the approach to dissect the developmental contribution of RIF1 function is convincing. The finding that replication timing and gene expression may be independently controlled is intriguing and provides a strong foundation for future research. The work will be of interest for researchers both in the transcription and the replication field, especially for scientists investigating the interplay between the two processes.

    1. eLife Assessment

      In this manuscript, the authors analyse the nanoscale localisation of α5β1 and αVβ3 integrins in integrin adhesion complexes (IAC) by dual-colour STORM and DNA-Paint and assess the spatial organisation at the nano and mesoscale of their main adaptors (paxillin, talin and vinculin). This is an important work that provides detailed analyses that reveal how elements of these complex structures are really organised at the nanoscale, an essential perspective for a better understanding of how IACs function and regulate mechanotransduction processes. The evidence presented is convincing, using complementary super-resolution imaging techniques and subsequent computational modelling that enabled a quantitative assessment of the resulting data.

    1. eLife Assessment

      This important study presents a convincing methodological approach to probe the structural features of the full-length human Hv1 channel as a purified protein. The method is supported by rigorous biochemical assays and spectral FRET analysis, which will interest biophysicists and physiologists studying Hv1 and other ion channels and membrane proteins. Overall, the work introduces an interesting labeling strategy and provides a methodology that is of value in investigating hHV1 in particular and can be extended to other ion channels. The authors also provide preliminary observations regarding conformational changes induced by zinc.

    1. eLife Assessment

      This important study compares how different classes of drugs act on the SARS-CoV-2 main protease, a key antiviral target, and shows that many of them work by controlling whether the enzyme assembles into its active dimeric form. The evidence, based on a range of complementary biophysical methods, is convincing and points to the interface between the two protein protomers, including a newly found binding site, as a promising target for broad-spectrum antiviral drugs. This work will be of interest to biochemists and virologists working on treatments for coronaviruses.

    1. eLife Assessment

      This is a fundamental study on the sensory roles of cerebrospinal-fluid-contacting neurons (CSF-cNs) in mammals, revealing how the apical extension is used as an amplifier of chemical changes in content of the CSF. Specifically, the authors show compelling evidence that PKD2L1 is predominantly a pH-sensing channel in CSF-cNs and link its apical localization to dual phasic and sustained responses underlying CSF chemosensation.

    1. eLife Assessment

      This important study reports that neural activity in the auditory cortex (field L) of singing male zebra finches can be modulated by the presence of a female conspecific. These findings extend recent work showing that the activity of dopaminergic neurons in songbirds is also affected by an audience. Solid evidence is presented for the importance of singing context in modulating auditory processing during vocal production, but the study does not yet fully establish that these effects arise specifically from audience-dependent modulation of auditory feedback, as opposed to possible acoustic, temporal, or recording-related confounds. This work should be of interest to researchers studying the context dependence of sensory processing, the role of auditory feedback, and vocal communication during courtship behavior.

    1. eLife Assessment

      In this fundamental manuscript, Richter et al. present a thorough anatomical characterization of the Drosophila melanogaster larval pharyngeal sensory system, which is involved in taste-guided behaviors. This study fills a major gap in the larval sensory map, providing a compelling neuroanatomical foundation for future investigations into sensory circuits and behavior. The exceptional data will significantly enrich the field of Drosophila neurobiology.

    1. eLife Assessment

      This important study provides mechanistic evidence for how the tea-adapted Kanzawa spider mite, Tetranychus kanzawai, overcomes the catechin-based defenses of green tea plants. The work identifies the horizontally transferred dioxygenase DOG15 as a key contributor to host adaptation and supports a two-step model involving evolutionary modification of enzyme activity together with strong inducible upregulation upon feeding on tea. The evidence is convincing because comparative behavioral and toxicological assays, transcriptomic and proteomic analyses, RNAi-mediated functional validation, and recombinant enzyme assays converge to link DOG15 activity and expression with improved performance on tea. The revised manuscript appropriately acknowledges that the products of catechin cleavage have not yet been characterized and that additional detoxification pathways may contribute to tea adaptation, providing a balanced interpretation of the otherwise strong mechanistic evidence.

    1. eLife Assessment

      This valuable study presents a real-time system for identifying multiple unrestrained marmosets in a home cage setting using a combination of facial features and color-coded beads. While there is solid evidence that the system has a precision comparable to human experimenters in the tested scenarios, there is limited evidence that this would generalize to unconstrained multi-animal environments

    1. eLife Assessment

      This important study investigates how distinct honeybee viruses differentially alter flight performance through interactions with octopamine signaling pathways. The combination of behavioral flight assays, pharmacological perturbation, and transcriptomic analyses provides solid evidence that virus-specific effects on flight are associated with octopamine signaling. The data presented also establish a framework for additional analyses that may strengthen the proposed mechanistic model, including quantification of endogenous octopamine levels and receptor specificity studies.

    1. eLife Assessment

      This manuscript reports an important study in which the authors apply smFRET imaging to probe HIV-1 Env conformational dynamics in the presence of antibodies. Previous implementations of smFRET imaging of HIV-1 Env, which focus on gp120 conformation, have yielded limited information on antibodies that target gp41. Through the cutting-edge application of smFRET imaging, the study provides convincing insights into the mechanisms of action of relevant antibodies.

    1. eLife Assessment

      This important study investigates the role of Nav1.7 voltage-gated sodium channels in regulating excitability of human dorsal root ganglion (hDRG) neurons. The authors characterize a previously identified Nav1.7 channel inhibitor using recombinant channels and human neurons. The study convincingly shows that inhibition of Nav1.7 channels with AM-2099 causes a modest decrease in neuronal excitability and prolongs the refractory period. This work offers new insights into the mechanism of clinically relevant pharmacological targets for pain relief.

    1. eLife Assessment

      A computational model potentially provides important new insights into the circuit mechanisms underlying navigational control in insects. The authors compare high speed video recordings of ants with detailed predictions from a new computational model. The similarities between model and behavioral data are striking and convincingly suggest how complex behavioral motifs can emerge from a simple neural circuit.

    1. eLife Assessment

      This valuable study advances our understanding of habituation and related potentiation behavior in a single-celled organism, Stentor. The authors provide convincing evidence for their claims in the form of extensive data on habituation behavior. The work will be of interest to cell biologists, neuroscientists, and also scientists broadly interested in behavior in non-neural organisms.

    1. eLife Assessment

      This valuable work discusses the phylogenetic conservation of the hippocampal region and primary sensory cortical regions in mammalian species. The authors propose that species-specific differences in behavior and mnemonic functions may be due to differences in cortico-hippocampal connectivity patterns. However, the manuscript, in its present form, is speculative, and the strength of evidence for this proposition is incomplete.

      [Editors’ note: the final version of this work has been published in the journal Hippocampus (https://doi.org/10.1002/hipo.70119)]

    1. eLife Assessment

      In this study, electroencephalography was recorded during a binocular-rivalry paradigm in which participants viewed a target and a distractor stimulus. The stimuli were independently frequency-tagged, allowing the researchers to track target and distractor processing over time. The findings suggest that parietal alpha oscillations initially segregate competing inputs, followed by frontal theta activity associated with suppression of distractor representations. The significance of these findings is valuable, although the strength of the evidence remains incomplete, because of specific experiment design choices and methodological limitations.

    1. eLife Assessment

      This important study introduces a method, based on active control, for determining the functional connectivity between neurons or groups of neurons. While the theory is derived for a linear model with a perfectly observed control signal, the authors present compelling evidence that their method will work even when the system is nonlinear and the control signal is not fully observed. Furthermore, they provide a practical recipe for doing so.

    1. eLife Assessment

      This work presents a software and hardware suite for targeted photostimulation that can be used in vivo. The package is a well-designed and documented hardware/software suite with a comprehensive build guide. This tool will likely promote important neuroscience advances through targeted real-time perturbation of the cerebral cortex. Overall, this manuscript makes a compelling case on how to design and make available power tools for the research community.

    1. eLife Assessment

      Mechanical transduction channels of sensory hair cells possess lipid scramblase activity. Membrane lipid disruption resulting from mechanical transduction is thought to be restored by flippase activities. This fundamental study provides compelling evidence that ATP8B1, a P4-ATP flippase and its subunit TMEM30B, are key in mediating this restorative function in outer hair cells of the mammalian cochlea.

      [Editors’ note, September 9, 2026: There is a potential confound with the findings shown in Figure 7 suggesting that specific targeting of ATP8B1 and TMEM30B subunits to the hair cell stereocilia is dependent on mechanoelectrical transduction channel activity. This does not affect the central findings or conclusions, but readers should be aware that a revised version of the paper is being prepared.]

    1. eLife Assessment

      This study used several approaches (computational modeling, neuronal cultures, rodent epilepsy model, and human intracranial recordings) to address a significant question in epilepsy research, with additional relevance to EEG studies more broadly: Are high frequency oscillations (or "fast ripples", defined as >200 Hz by the authors) distinct from randomly occurring clustering of spikes? The results suggest fast ripples can occur by chance and how this may occur. The significance was considered important and the strength of evidence convincing, with minor limitations related to the need to address behavioral state, explaining the results in relation to epileptiform activity described by others, and discussing implications.

    1. eLife Assessment

      This valuable study demonstrates molecular changes associated with age related impairment in oligodendrocyte differentiation and ability to myelinate. The identification of particular genes that are associated with this decline will provide potential future targets for therapeutic interventions. The reviewers felt that the quality of the evidence was convincing while identifying some minor weaknesses that were largely addressed in the review process.

    1. eLife Assessment

      This important work sets out to identify the neural substrates of associative fear responses in adult zebrafish. Through a compelling and innovative paradigm and analysis, the authors identify brain regions associated with individual differences in fear memory expression. While most findings are well supported, there is limited evidence that the four behavioral clusters represent discrete forms of associative fear-memory expression and the related interpretations would benefit from additional analysis or more cautious framing. Nonetheless, this study showcases the strength of zebrafish for systems-level neuroscience and will be of broad interest to the neuroscience community.

    1. eLife Assessment

      This study provides useful information for the Drosophila ageing community by characterising the auxin-based gene expression system (AGES) and identifying caveats associated with its use in adult flies. The authors provide solid evidence for sex-, age-, tissue- and dose-dependent variability in transgene induction, as well as effects of auxin feeding and AGES activation on stress resistance, metabolism, and lifespan. While the study would benefit from a broader characterisation of some of these limitations, the findings provide a helpful benchmark for researchers using AGES in ageing studies.

    1. eLife Assessment

      This important study integrates mouse genetics with sequencing, electrophysiological and behavioral tools to uncover the behavioral role and molecular profile of a developmentally defined subpopulation in the lateral septum. The data collected and analyzed are convincing, highlighting the role of this subpopulation in threat avoidance and stress, providing a framework by which developmental origin is linked to mature neuronal function. The work will be of interest to biologists and neuroscientists working on development and behavior.

    1. eLife Assessment

      This study examines how prefrontal population dynamics tune social behaviors, providing important findings that oxytocin receptor-expressing interneurons support sociosexual choice in female mice. The multidisciplinary evidence is convincing and could be strengthened by more comprehensive reporting of the methodology and a clearer distinction between inferential and directly tested insights from modelling. This work will be of interest to those interested in prefrontal cortex, oxytocin, and/or social behavior.

    1. eLife Assessment

      This important paper provides evidence that visual representations, as observed through drawing, preferentially preserve topological features over metric features. Across three experiments with different age groups and creative converging methods, they demonstrate that holes and T-junctions are relatively preserved as compared to topologically irrelevant L-junctions, and Euclidian features like length or precise angle. Together, these data provide convincing evidence for topology as an organizing principle for spatial representation, but the work would be strengthened by considering a broader range of topological features, or by ruling out alternative accounts, like preserved memory for complex features, motor production limitations, or noisy compression, that may produce a similar pattern without a topological prior.

    1. eLife Assessment

      This important study introduces a Bayesian method to determine bacterial counts that accounts for the experimental noise inherent to dilution and plating methods and distinguishes it from biological uncertainty. The evidence supporting the conclusions is compelling, combining simulated data and experimental data. The method will be of interest to microbial ecologists, and potentially to the broader community interested in inference from biological data, even more so if the domain of application and the limitations are further clarified.

    1. eLife Assessment

      This valuable study examines how the prelimbic cortex represents learned and generalized threat over time and identifies potentially distinct stable and dynamic subnetworks that may support these functions. The work is conceptually interesting and is strengthened by the longitudinal calcium imaging approach and the inclusion of key control groups. However, the evidence supporting the claims is incomplete, particularly because the interpretations regarding inference, time-dependent representational change, and the dissociation of neural activity from freezing behavior extend beyond what is currently established by the data.

    1. eLife Assessment

      This work provides a fundamental advance through a detailed, integrative analysis of how the tsetse fly feeds on blood, demonstrating that successful penetration depends on subtle structural adaptations rather than extreme forces or unusual anatomy. By combining high-resolution imaging, innovative biomechanical measurements, and experiments on artificial skin, the study offers complementary and compelling evidence, with clear data supporting a robust mechanistic interpretation. These findings have broad significance, as they clarify the biomechanics of vector feeding and have implications for the transmission of diseases such as African trypanosomiasis across diverse hosts.

    1. eLife Assessment

      This important work addresses a very relevant biological question: what is the cellular basis of wound healing? Using the Drosophila pupal notum as a model, the paper provides an elegant, thorough, descriptive characterization of syncytia-driven wound closure using state-of-the-art confocal live imaging of the pupal notum. The authors meticulously characterize the cell-cell fusion events during wound healing and inhibit cell fusion to show to that it is necessary to speed wound closure. This study provides convincing evidence that cell fusion allows actin resources at be partitioned to the leading edge.

    1. eLife Assessment

      This valuable study addresses the effects of selection for aggression on fitness and life-history trade-offs in Drosophila melanogaster. The evidence presented is overall solid, however, the data as they are do not completely support the claims of increased survival of highly aggressive males at the expense of reproductive success. The main limitation is the choice to use males from only one aggressive Drosophila line, that do not allow disambiguation between nonaggression-related factors and aggression-related factors influencing lifespan.

    1. 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. Following revision, many of the concerns previously raised by the reviewers have been addressed. The evidence is solid, whereas additional controls and stronger mechanistic data are still needed to fully substantiate the proposed pathway, particularly the mechanism by which red light exposure leads to reduced SIRT4 levels.

    1. eLife Assessment

      This study presents valuable findings on the role of specific dopamine neurons for aversive learning and modulation of innate behavior in Drosophila larvae. The authors present convincing evidence backed up by detailed behavioral quantification and rigorous testing. Their data confirms previous findings and will be of interest to the learning and memory community.

    1. 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 valuable 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.

    1. eLife Assessment

      This study offers valuable insights into brain responses to somatosensory and visual temporal and spatial tasks in the auditory cortex of Deaf and hearing individuals. The evidence for a sensorily-bound representation in the deprived cortex -- rather than abstract -- is solid; however, the study will benefit from some additional analyses to better clarify and contextualise the results. This work will be of broad interest to neuroscientists investigating brain plasticity and development.

    1. eLife Assessment

      This study provides a useful investigation of machine learning approaches that can lessen potential gaps in the prediction of behaviour from brain imaging data across majority and minority samples. The authors provide incomplete evidence to suggest that domain adaptation methods can mitigate these gaps. The analysis would benefit from further testing of model generalisability and the inclusion of recommended workflows for how the tested approaches can be used in future research. This work will be of interest to scientists using machine learning in brain imaging.

    1. eLife Assessment

      This study presents a useful finding on using diverse experimental systems to understand how neuromodulatory signals shape glial inflammatory signaling; however, the strength of evidence is inadequate. The astrocyte-enrichment method used may permit contamination by microglia, oligodendrocyte-lineage cells, or neurons, complicating attribution of TNF expression specifically to astrocytes. This concern is compounded by the strong microglial response to Gi manipulation and the lack of quantitative validation of chemogenetic cell-type specificity in vivo. These weaknesses have hindered further evaluation of the claims.

    1. eLife Assessment

      This study addresses a fundamental question about how large-scale brain networks interact, and specifically how the default mode network exchanges information with sensory cortex. The analyses provide solid evidence for the claims made in the paper. The findings should be of broad interest to researchers studying brain network organization and dynamics.

    1. eLife Assessment

      This important study combines chromatin accessibility and genomic DNA sequence conservation data from low-coverage genome sequencing of related species (without assembly), for the in-silico identification of cis-regulatory elements in large genomes. The approach and results are compelling and well supported by the experimental validations. The work will be of interest to researchers working in the field of gene regulation and evolution, particularly because the methodology proposed can be applied to a large variety of experimental organisms.

    1. eLife Assessment

      The report by Liu and colleagues reports on an analysis of environmental adaptation across diverse lineages of the grass Phragmites australis differing by their level of ploidy. These results represent important findings for understanding the environmental adaptation of species complexes with mixed ploidy and the analysis reports solid evidence that lineages with distinct levels of ploidy occupy different climate niches. The use of regional survey in tandem with common garden experiment represents a convincing approach to suggest a correlation between ploidy and climate adaptation. This manuscript will be of interest to a broad community of ecological genomicists interested in how structural variation in gene dosage potentially affects the pattern of adaptation.

    1. eLife Assessment

      This study provides valuable insights into the cellular dynamics underlying accelerated tooth regeneration in a vertebrate model. Using single-nucleus RNA sequencing across multiple time points, the authors present a well-structured analysis of cell populations, trajectories, and intercellular signaling events associated with this process. The strength of evidence is solid but only partially supported, as the conclusions are primarily supported by computational inference, without experimental validation of key findings.

    1. eLife Assessment

      This manuscript provides an important contribution to the field of platelet biogenesis, and the convincing evidence will advance our understanding of signal transduction driving the development of late megakaryopoiesis and platelet reactivity that results in bleeding diathesis. The paper is noteworthy for analyzing two related tyrosine phosphatases, using single or combined conditional gene knockouts at different developmental stages. Because SHP1 is a negative regulator and SHP2 is an activator, the synergistic effects found in the double knockout were surprising.

    1. eLife Assessment

      This important study demonstrates how ablation or silencing of hilar mossy cells in the mouse influences the primary location where the mossy cells project, the inner molecular layer of the dentate gyrus. The anatomical findings are convincing and include altered adult-born granule cells and the shrinkage of the inner molecular layer following mossy cell ablation. However, the mechanisms and their functional significance are unclear, so more of these types of experiments/analyses would strengthen the study, especially the support for the broader conclusions.

    1. eLife Assessment

      This important study proposes a framework in which tutor-song memorization and performance-error computation arise from a shared predictive-cancellation circuit. The approach is solid, but the choice of learning rules, circuit architecture, and sparsity assumptions is not always sufficiently justified, and the model would benefit from a clearer mechanistic derivation and more concrete experimental predictions. This study would be relevant for researchers studying vocal learning and motor learning in general.

    1. eLife Assessment

      This valuable study analyzes how recurrent neural network can flexibly switch between multiple tasks. The evidence is solid, but reviewers have raised questions about the impacts of transient dynamics, whether the activity is actually chaotic, can inputs be used to switch between tasks, what determines overlap between tasks and others. In addition, there were more minor questions pertaining to whether the analyses are actually analytic or primarily based on numerical simulations, as well as the relationship to prior studies where the same network was optimized to perform multiple tasks simultaneously with different readouts.

  2. Sep 2026
    1. eLife Assessment

      The manuscript presents a compelling application of the microfluidic mother machine as a "selection" machine. While individual elements of the work have existed for many years across various research communities, the simplicity and elegance of this particular application should make it readily implementable and therefore a useful contribution. The proposed plans for revision are sound, particularly in light of the senior author's stated logistical constraints.

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

    1. eLife Assessment

      This study uses convincing analyses of publicly available connectomic and transcriptomic datasets to survey the anatomy and connectivity of neurosecretory cells in the Drosophila brain. The systems-level description of the neurosecretory system is complemented by selected functional experiments and predictions for circuit function and paracrine signaling networks that can now be tested in future studies. This important work will be of interest to neuroscientists working on hormonal signaling in Drosophila and other animals.

    1. eLife Assessment

      This study reports results characterizing two boundaries (homie and nhomie) flanking the TAD of a developmental gene. The study's thorough and mechanistic characterization of these boundaries provides useful information to the field, and the conclusions are well supported by convincing evidence. The novelty of the work is somewhat limited because the major conclusion is confirmatory in nature.

    1. eLife Assessment

      This study presents important evidence showing that the high susceptibility to sepsis of Kit-mutant mice is not due to mast cell deficiency. The revised manuscript, with solid data, focuses on refuting the notion that mast cells play a major role in sepsis. This paper would be of interest to researchers in mast cell biology and mucosal immunology.

    1. eLife Assessment

      This study presents a systematic analysis of interactions involving components of the outer membrane protein biogenesis machinery in Escherichia coli. The authors identify interactions between Bam-associated proteins and several pathways. The evidence supporting the principal conclusions is convincing, including several newly identified interactions as well as findings that reinforce previously proposed connections described in the literature. The resulting dataset provides a useful resource for future investigations of bacterial envelope homeostasis and the functions of poorly characterized genes.

    1. eLife Assessment

      This valuable study presents findings on how prokaryotic antibiotics affect translation in mitochondrial ribosomes. Using mitoribosome profiling, the authors provide solid evidence that most tested antibiotics act similarly on bacterial and mitochondrial translation. Additionally, this work shows that alternative translation initiation events exist in two specific mt-mRNAs (MT-ND1 and MT-ND5).

    1. eLife Assessment

      This study provides important insights into the crosstalk between ATG2A and components of the early secretory pathway. The authors employ an elegant proximity-labelling approach to identify two ER-Golgi intermediate compartment (ERGIC)-localized proteins. They further identify ARFGAP1 and Rab1A as components of early autophagic membranes, which accumulate at the periphery of pre-autophagosomal structures induced by loss of ATG2. Overall, the study is well executed, and the evidence supporting the claims is convincing.

    1. eLife Assessment

      These results add to a growing body of literature demonstrating a role for IL-21 in T follicular helper cell expansion and differentiation, as well as in germinal center formation and maintenance. The authors use an IL21R ENU-induced mutant, together with complementary in vitro and in vivo experiments, to investigate the roles of STAT1 and STAT3 signaling downstream of IL-21R. The experimental approach is valuable, but the main conclusion is incompletely supported by the evidence, as the mutant exhibits a broad reduction in STAT signaling rather than a selective impairment of STAT1 signaling.

    1. eLife Assessment

      This important study reports that Sox17 is key to the formation and function of the Sertoli valve, a transition region between the rete testis and seminiferous tubules that remains an understudied domain of testicular biology. The supporting data are solid and convincing. This work will be of interest to developmental and reproductive biologists, as well as andrologists who work on male fertility and men's health.

    1. eLife Assessment

      The study investigates how CD1c-restricted T cells respond to Mtb-infected APCs, leading to increased cytokine production and cytotoxic activity that may help control Mtb infection. The work is important and will interest researchers in the field. The supporting evidence is solid.

    1. eLife Assessment

      By using a combination of patch clamp recordings, calcium imaging and computer modeling, the authors analyze the spatial distribution of voltage gated calcium channels at glutamatergic synapses formed between layer 5 pyramidal neurons (L5PNs) and between layer 2/3 and L5PNs in the prefrontal cortex (PFC) and primary somatosensory cortex (S1); they conclude that the calcium channel-vesicle coupling is looser in the PFC compared to S1, and future ultrastructural studies may directly confirm the proposed differences in the spatial organization of voltage-gated calcium channels and vesicular release sites. Overall, these findings are important because they have implications for shaping synaptic plasticity and neural circuit function across brain regions. They are convincing because they are based on the use of a multi-pronged approach, although the presentation would benefit from stronger integration of the current findings with the existing literature and a more explicit discussion of potential limitations and confounding factors for data interpretation.

    1. eLife Assessment

      This is a valuable contribution to influenza surveillance. After revisions, addressing methodological and reporting issues, the claims of providing an early warning tool now align more with the reported study results, and ultimately, the evidence presented provide a solid addition to the evidence base.

    1. eLife Assessment

      This study explores the phylogeny and macroevolutionary patterns of water striders, linking sexual conflict-driven morphological traits to species diversification. It provides robust and compelling evidence for ILS, introgression, and differential evolutionary rates of male and female antagonistic traits, offering valuable insights into sexual conflict and speciation.

    1. eLife Assessment

      This important study elucidates the roles of two lytic transglycosylase (LTG) enzymes in the progression of spore formation in the research model species Myxococcus xanthus. Consistent with previous work indicating loss of peptidoglycan during the laboratory-induced rapid spore formation process, the new data demonstrate a similar loss of peptidoglycan during the normal, slow sporulation process. Solid evidence is provided for the roles of the two LTGs in spore formation and for interplay between the functions of these enzymes and peptidoglycan synthetic systems. These findings may have broader implications for understanding PG metabolism across a range of bacterial species.

    1. eLife Assessment

      This valuable paper describes the regulation of the association of meiotic chromosome axis proteins on chromosome ends with sub-telomeric elements in budding yeast. The genome-wide analyses of binding of chromosome components as well as chromatin regulators, complemented with the mapping of meiotic DNA double-strand breaks on chromosome ends, provided solid evidence to support the authors' conclusion. The results in the paper are of interest to researchers studying meiotic recombination and the structure of genomes and chromosomes.

    1. eLife Assessment

      This work provides a reassessment of VBIT-4, a compound previously proposed to inhibit oligomerization of the crucial protein known as the mitochondrial voltage-dependent anion channel. Combining complementary experimental approaches with molecular dynamics simulations, the authors provide compelling evidence that VBIT-4 primarily disrupts lipid membranes and induces channel-independent cytotoxicity. The study has fundamental implications for interpreting previous work using VBIT-4 as a probe of channel function and highlights the need to consider membrane-disruptive effects when evaluating drug mechanisms.

    1. eLife Assessment

      The study provides important insight into the development of CD8 T cell virtual memory cells by identifying a dose-sensitive role for Bcl11b. The authors define the developmental stages affected by reduced Bcl11b expression and establish its role in promoting the virtual memory fate. The evidence is compelling, supported by multiple genetic models and complementary approaches.

    1. eLife Assessment

      This fundamental study advances our understanding of the neural substrate of planning trajectories towards a goal by using recurrent neural networks. The manuscript provides compelling evidence for the proposed mechanism by linking a computational model to previous findings in neural data, designing a hand-crafted implementation of the mechanism, and showing that trained recurrent networks converge to computational principles consistent with the proposed mechanism. The work will be of broad interest to theoretical and systems neuroscientists and to cognitive scientists.

    1. eLife Assessment

      This is an important work, using preclinical models and reporting that a shared inflammatory and vascular leakage response following Treg depletion, UVB irradiation, and DNFB contact hypersensitivity facilitates outgrowth of premalignant melanocytes. However, some of the work to support the claims is incomplete; this pertains particularly to the quantification of melanocyte expansion and sample size inconsistencies. With some additional supporting evidence to strengthen the claims, the study will be of broad interest to cancer biologists and immunologists.

    1. eLife Assessment

      This useful study reports the application of targeted RNA-probe hybridization-capture metagenomic sequencing to characterize Klebsiella pneumoniae detected in post-mortem lung tissue from infants and young children who died from respiratory illness in Lusaka, Zambia. The findings provide a convincing proof-of-concept for the use of targeted sequencing to recover clinically relevant genomic information from archived post-mortem tissue specimens. However, the evidence supporting broader epidemiological and public health conclusions should be interpreted with caution given the small number of cases, the limitations inherent to culture-independent sequencing, and the fact that the study was not designed to determine the source or setting of acquisition.

    1. eLife Assessment

      Using the clownfish model, this study examines how growth, feeding, and agonistic behavior result in socially dominant or subordinate states in size- and age-matched individuals of the clownfish, Amphiprion percula. The authors complement this work with whole-body transcriptomics and find significant variation in genes and gene co-expression modules related to growth and satiety-related pathways, as well as ossification-related genes. They provide solid evidence that emerging dominants grow more, eat more, and behave more aggressively than subordinate or solitary individuals; these phenotypic differences are accompanied by distinct gene expression profiles, including variation in growth- and satiety-related pathways. The work is valuable in advancing our understanding of how the social environment regulates phenotypic change; however, claims regarding the mechanistic role of gene expression are only partially supported by the current analyses.

    1. eLife Assessment

      This study presents valuable evidence that activating a lysosomal signaling pathway lowers blood glucose in diabetic mice, pointing to a potential new strategy for treating metabolic disease. However, the evidence for the proposed mechanism is inadequate: the glucose transporter's movement and glucose uptake were not measured in the physiologically relevant tissue, and the measurement that was performed used an unconventional technique. As a result, whether this transporter-dependent pathway explains the glucose-lowering effect has not yet been established.

    1. eLife Assessment

      In their important study, Beaudet, Berger and Hendricks provide a mechanistic link between disease-associated tau hyperphosphorylation, loss of cooperative tau envelope formation on microtubules, and dysregulation of axonal transport prior to aggregation. Using complementary in vitro reconstitution and human iPSC-derived neuronal assays with phosphodeficient and phosphomimetic tau constructs targeting 14 disease-relevant sites, the authors convincingly show that phosphorylation state alters tau organization on microtubules and differentially impacts kinesin- and lysosome-based transport. The evidence is solid and well aligned with the conclusions and will be of interest to the biophysical, cell biology and neurodegenerative communities.

    1. eLife Assessment

      This valuable study presents a promising framework for automated spike sorting in high-density extracellular electrophysiology. The core evidence is solid, but could be strengthened with extended simulations, broader benchmarking against existing sorters, and validation via expert curation. It will be of interest to the systems neuroscience community.

    1. eLife Assessment

      This important study investigated the effects of the nutrient microenvironment on key elements of cellular morphology, function, and metabolism in both human iPSC-derived and human fetal RPE cultures. The analysis compared commonly used iPSC-RPE media formulations (MEMα, DMEM-HG/F12 basal media), alongside human plasma-like medium (HPLM) in an effort to model a more physiologically relevant culture environment. The authors provide compelling evidence that standard culture media differ significantly in key aspects of retinal pigment epithelium biology, particularly regarding metabolic profiles. Further clarification of the biological replicates and data normalization methods will help maximize the impact of this manuscript.

    1. eLife Assessment

      This study reports high-resolution cryo-EM structures of Paracoccus trimethylamine N-oxide demethylase and advances the intriguing hypothesis that the enzyme may be bifunctional, coupling TMAO demethylation to formaldehyde capture at a distal tetrahydrofolate-binding site through an enclosed intramolecular tunnel. Supported by biochemical assays and molecular dynamics simulations, the structural findings are important and potentially of broad interest, particularly the unusual oligomeric architecture and the proposed conduit for a reactive intermediate. However, evidence that the conduit mediates formaldehyde channeling remains incomplete, because the current HCHO-THF measurements do not demonstrate enzyme-dependent transfer or distinguish downstream HCHO consumption from indirect effects of THF on enzyme activity.

    1. eLife Assessment

      In this valuable study, Robben et al. describe a 3D beta-cell spheroid culture platform, that allows high-throughput monitoring of cytoplasmic calcium concentrations and insulin secretion. The authors demonstrate measurements of calcium signals comparable to those recorded in primary pancreatic islets. The authors validate the method by culturing MIN6 cells in a 3D-culture system, and show solid evidence of its utility by recording calcium signals in a high-throughput format and characterizing these calcium signals using pharmacological tools. This methodology demonstrates the utility of the 3D beta-cell spheroids for screening pharmacological modulators of pancreatic beta-cell function.

    1. eLife Assessment

      This potentially valuable work finds that exposure to the odor diacetyl in the worm C. elegans leads to changes in metabolic nutrient-responsive programs, inducing expression of genes that act in the DHAP-glycerol shunt followed by induction of the flavin-containing monooxygenase fmo-2. The genetic and multi-omic evidence is solid and is based on an extensive set of experiments; however, mechanistic support for underlying metabolic and redox changes remains incomplete without more comprehensive metabolic profiling. The mechanism through which diacetyl or its breakdown products is sensed did not involve known receptors of diacetyl, so it remains unknown whether sensory neurons are involved in these responses.

    1. eLife Assessment

      This valuable study examines how abstraction and metacognition relate to transdiagnostic dimensions of psychopathology. It combines a reward-learning task, computational modelling and a large questionnaire. The evidence linking reduced metacognitive sensitivity to a compulsive hypersensitivity dimension is solid, but the evidence for the abstraction findings is currently incomplete. This work will be of interest to researchers studying metacognition and computational approaches to psychiatry.

    1. eLife Assessment

      This valuable study compares the anti-HIV activity of human natural killer cell subsets and identifies CD56<sup>dim</sup>CD16<sup>dim</sup> cells as a potentially key effector population against HIV-infected autologous T cells. The evidence supporting the central conclusions seems incomplete because the interpretation may be substantially confounded by activation-induced CD16 downregulation, making it difficult to distinguish intrinsic functional differences from phenotypic changes that occur during target-cell engagement. Additional experiments using purified NK-cell subsets and appropriate controls would substantially strengthen the evidence supporting the major conclusions.

    1. eLife Assessment

      The cell wall and plasma membrane are tightly associated in plant cells, and even after plasmolysis, sites of strong contact remain between the plasma membrane and cell wall. Here, the authors provide solid data to implicate an Arabidopsis lectin-like receptor kinase in plasma-membrane-to-cell-wall contact sites, and propose that these attachment sites are of importance for plant resistance to hyperosmotic stress, yet the evidence remains incomplete without key controls. These important results broaden our view on dynamic modulation of plasma membrane topology and its physiological consequences.

    1. eLife Assessment

      This study presents a valuable metagenomic analysis of the gut microbiome in sickle cell disease (SCD) patients, revealing associations between bacteriophage, host immunity, and SCD pathophysiology. This solid dataset and in-depth analysis will be of broad interest to researchers studying SCD, immunology, phage biology, and the microbiome, adding to the small but growing literature suggesting a microbial component to SCD.

    1. eLife Assessment

      This valuable study leveraged high-definition transcranial direct current stimulation to the left dorsolateral prefrontal cortex to provide strikingly large effects on procrastination behavior over an extended time span. The cross-sectional, longitudinal study and testing of competing models provided solid evidence for how stimulating dlPFC impacts reveal-world procrastination behavior. Whether these results generalize to a larger population will be a significant future direction. This work will be of interest to those interested in cortical function, procrastination, and related states.

    1. eLife Assessment

      This manuscript examines how overexpression of sphingosine 1-phosphate receptor 1 in a mouse model affects neutrophil distribution, metabolism and function. Given the significance of S1PR1 in inflammatory mechanisms, this work is valuable for uncovering novel aspects of S1PR1 signaling in neutrophil dynamics and function. The evidence provided is solid as it integrates single-cell transcriptomics, flow cytometry, and multiple in vivo studies. This work also raises key questions about distinct physiological and pathophysiological roles of S1PR1 signaling in neutrophils that could become therapeutic targets.

    1. eLife Assessment

      This paper demonstrates that relocating the MreB-Rod complex to the poles of E. coli can reprogram cell-wall synthesis, causing cells to elongate through peptidoglycan incorporation at the poles rather than along the cell length. This is a valuable finding for understanding how bacterial growth can be spatially reprogrammed and provides insight into how distinct modes of bacterial growth might arise. However, the evidence is currently incomplete, particularly regarding the nature of the polar structures, their relationship to cell shape and growth, and the requirement for a pre-existing pole.

    1. eLife Assessment

      This important study leverages a large global dataset of tens of thousands of tuberculosis samples to place recurrent protein-coding mutations into their three-dimensional structural context, offering an expanded view of how antibiotic resistance emerges compared to traditional genetic analyses alone. The strength of evidence is compelling, supported by the scale and breadth of the dataset and the systematic structural analysis, although some of the assumptions made in the modeling approach are only partially supported. Overall, the work will be of broad interest to researchers studying microbial evolution, antibiotic resistance, and structure-function relationships in pathogens.

    1. eLife Assessment

      This study modeled vocal learning in zebra finches with a network of three components: a pathway with delayed/slow Hebbian learning that mimics the HVC-RA projection, a pathway with reinforcement learning that mimics the HVC-BG-RA projection, and a motor unit that mimics the syrinx and produces song output. The model convincingly reproduces key features of song learning and is a valuable step towards understanding how vocal learning is substantiated in the song system. The generic and simplified nature of the model limits its generalization to other forms of motor learning. Further examination of model assumptions and presentation of testable predictions would increase the impact of the study.

    1. eLife Assessment

      The authors investigate how dominance hierarchy shapes defensive strategies in mice under two naturalistic threats: a transient visual looming stimulus and a sustained live rat. This study provides important insights into how social context and dominance hierarchy modulate innate defensive behaviors across distinct naturalistic threats. The strength of evidence is convincing, with detailed classification and analysis of behaviors.

    1. eLife Assessment

      This fundamental work substantially advances our understanding of short-term plasticity mechanisms by providing evidence for release-independent low-frequency synaptic depression that reflects a model that proposes a redistribution of vesicles within the readily releasable pool, via a reduction in docking site occupancy due to vesicle undocking. The evidence supporting this model is convincing, with rigorous modeling, electrophysiological data and computational analysis. The work will be of broad interest to cellular neuroscientists and synaptic physiologists.

    1. eLife Assessment

      This valuable study compares auditory cortex responses to sounds and cochlear implant stimulation measured with surface electrode grids in rats. Beyond the reduced frequency resolution of cochlear implants observed previously, this study suggests further discrepancies between neuronal representations of cochlear stimulations and natural sounds. The evidence for this result is solid. This study is of interest to researchers in the auditory neuroscience field and clinicians implementing treatments with cochlear implants.

    1. eLife Assessment

      These are valuable findings for those interested in how neural signals reflect auditory speech streams, and in understanding the roles of prediction, attention, and eye movements in this tracking. The evidence is solid, as the revised analyses broadly support the main claims and address the key methodological concerns raised during review. Remaining limitations concern the interpretation of some sensor-level and eye-movement effects, but these do not substantially undermine the overall conclusions.

    1. eLife Assessment

      This study presents a useful alternate labeling-based approach to identify or profile bioenergetic changes between cells. Overall, the approaches and data are solid, but have limitations in interpretation and so are as yet incomplete. The method itself can be of interest to a variety of biochemists, cell and systems-biologists interested in quantitative cellular metabolism.

    1. eLife Assessment

      This valuable pharmacological MEG study implicates GABA-A receptors in the shaping of intrinsic neuronal timescales in the human brain. While the authors provide solid evidence for the claims that (i) GABAergic neuronal inhibition prolongs timescales in specific cortical networks and (ii) NMDA receptor manipulations have no detectable effect, the manuscript could be further strengthened by resolving some apparent discrepancies in the results as well as additional validation of the network analysis used. This work will be of interest for experimental and theoretical neuroscientists studying brain-wide network dynamics and the large-scale organization of neurotransmitter systems.

    1. eLife Assessment

      This study presents a valuable investigation of how inhibition of the WNK-SPAK/OSR1 pathway influences neuronal chloride homeostasis and seizure-like activity in organotypic hippocampal slice cultures. The evidence supporting the principal mechanistic conclusions is incomplete because several proposed mechanisms are inferred from changes in chloride dynamics rather than directly demonstrated. The work will be of interest to researchers studying chloride homeostasis, inhibitory neurotransmission, and epilepsy.

    1. eLife Assessment

      This valuable study combines free-flight kinematics, aerodynamic modeling, optogenetics, and connectomics to ask how Drosophila stabilize roll perturbations during flight. The kinematic and modeling methods are solid, but the evidence for redundant motor control of roll stabilization is incomplete: optogenetic silencing experiments lack a positive control, and no experiment directly tests the central claim that redundant motor pathways drive robust roll control. This work will interest researchers studying insect flight and robust motor control.

    1. eLife Assessment

      This important study provides solid evidence that, in an α-synucleinoathy model, brain atrophy and associated functional decline generalize across host genotype and fibril species, while being strongly shaped by the site of seeding and regional vulnerability. With an unusually large longitudinal in vivo MRI dataset combined with behavioural and computational modelling, the study offers a comprehensive characterization of neurodegeneration across multiple biological and experimental conditions. The openly shared imaging dataset and analysis pipeline are an excellent resource, and the scale, longitudinal design, methodological breadth, and openness of the study make it a substantial contribution to the field. This work will be of interest to scientists in synucleinopathy- and network- neurodegeneration communities.

    1. eLife Assessment

      This is a valuable study that contributes to our understanding of transcriptomic responses in microglia to HIV infection in the human brain. The evidence provided remains incomplete, and further analyses are required (i.e., a bigger sample size) to eliminate confounding factors so that the study can unequivocally ascertain the persistent inflammatory state of microglia in HIV-suppressed brains.

  3. Aug 2026
    1. eLife Assessment

      This valuable study characterizes the population structure and ancestry of Helicobacter pylori in Cabo Verde. Using a carefully sampled population-based cohort and paired host-bacterial genomic data, the authors identify distinct local lineages but with limited concordance between human and bacterial ancestry. The evidence is solid for the principal findings concerning bacterial diversity, ancestry and recent lineage expansion, while the support for the claim that this reflects host adaptation, enhanced transmission, reduced virulence or a mix thereof is weaker. The work has particular relevance for researchers interested in microbial population genomics, host-pathogen coevolution and the genetic consequences of human migration and admixture.

    1. eLife Assessment

      In this fundamental study, the authors argue that the most widely used behavioral measure of the ability to stop an action is largely determined by the time it takes for visual signals to reach the brain and for movements to be executed, rather than by the control processes it is assumed to index. The evidence is convincing, combining reanalyses of seven existing datasets with a preregistered new experiment, and its force comes from the authors doing three things at once: identifying the problem, showing that it is present wherever it can be measured, and offering remedies applicable to both archived and future data. Various concerns were raised as to the interpretation of the data and their robustness to experimental manipulations, but if these were properly addressed, the implications of the work could extend across psychology, psychiatry and neuroscience.

    1. eLife Assessment

      Winter months with short days are commonly associated with seasonal depression and hypersomnolence; the mechanisms behind this hypersomnolence however, remain unclear. Chen and colleagues identify a genetic basis for this phenomenon in the fly Drosophila - mutations in the circadian photoreceptor cryptochrome resulted in increased sleep under short photoperiods. These findings are valuable insights into the genetic mechanisms regulating sleep under short days. There is solid evidence that cryptochrome acts in GABAergic neurons, but only limited evidence for the proposed site of action. Further work with better techniques will be needed to identify the precise site of action of cryptochrome.

    1. eLife Assessment

      This important study reports dynamic reprogramming of global H3K4me2 during the oocyte-to-embryo transition in mice. The data presented support the main conclusion and are generally convincing. The work will be of interest to researchers working on epigenetic reprogramming during embryonic development.

    1. eLife Assessment

      This important study provides new insights into how extracellular-domain disulfide configurations regulate ligand binding and endocytosis of the natural killer cell receptor KIR2DL4, identifying a conformational switch that provides a mechanistic framework for receptor trafficking. The evidence supporting the main conclusions is solid, with complementary biochemical, structural, and functional approaches providing strong support for alternative disulfide configurations and their role in regulating receptor behavior. The work will be of interest to researchers studying natural killer cell biology, immune receptor signaling, and protein disulfide regulation.

    1. eLife Assessment

      This study attempts to predict spatial patterns of genetic diversity among coral reef dwellers, estimated with a computationally efficient, standardized k-mer pipeline, from satellite-derived seascape variables. The curated dataset of 18 coral reef taxa across 173 reefs is valuable, but the evidence for the central ecological claims is in its current form incomplete: pairwise genetic distances are modelled as independent observations, the reef-level random effects used as the response in the environmental analysis likely conflate species composition with environmental signal, and , and the coverage is likely too sparse to robustly support conclusions about loss of inter-and intra-specific within-reef diversity over time. The work will be of interest to conservation geneticists, marine biologists, and researchers developing Earth-observation approaches to biodiversity monitoring.

    1. eLife Assessment

      This study presents a valuable analysis of the TARA oceans dataset, advancing genome- and ecosystem-scale metabolic modeling. The authors present convincing evidence for the factors that shape microbial ecology at the molecular scale. The work will be of broad interest to oceanographers and scientists in other areas where metabolic interactions in diverse communities are of importance.

    1. eLife Assessment

      This is a valuable manuscript that leverages information already being collected in mosquito surveillance, but that is currently discarded, building on ideas developed during the SARS-CoV-2 pandemic. The work is mostly rigorous, involving ample data from real-world surveillance, independent laboratory testing, and simulation modeling to validate the inference method. The evidence is solid for demonstrating feasibility and biological plausibility, although some conclusions would be strengthened by additional sensitivity analyses on key assumptions.

    1. eLife Assessment

      An intriguing set of electrophysiological and analytical results suggests that adult rat neurons in the medulla oblongata crucial for mediating descending pain modulation are embedded in a network that generates a specific pattern of oscillatory activity. These valuable findings may broaden our understanding of how descending pain modulation is achieved. The supporting evidence is incomplete, and the authors need to provide several methodological clarifications and additional data interpretations to strengthen the manuscript.

    1. eLife Assessment

      This important technical study introduces SCOPE, an optics-free spatial reconstruction method based on bidirectional sender and receiver oligonucleotides on barcoded hydrogel beads. By sequencing proximity-encoded chimeric molecules, the authors computationally reconstruct 2D and 3D spatial information at an impressive scale. The technical demonstrations in synthetic bead systems are convincing and establish proof-of-principle that large spatial domains can be reconstructed without microscopy. The methodological advance is clear and the scale is impressive. This work will be of interest to those working on spatial mapping.

    1. eLife Assessment

      This important study investigates how sleep loss and circadian disruption affect whole-organ metabolism in flies (Drosophila melanogaster) and reports that wild-type flies align metabolism in anticipation of diurnal rhythm, while mutant flies with impaired sleep or circadian function shift to reactive or misaligned metabolism. The integration of chamber-based flow-through respirometry with LC-MS metabolomics is innovative, and the significance of the findings is significant. The strength of evidence needed to support the conclusions is generally convincing, although the absence of direct measures of locomotor activity makes it difficult to separate intrinsic metabolic changes from potential behavioral differences in mutants.

    1. eLife Assessment

      This study presents fundamental results on questions related to the presence/absence of the Entner-Doudoroff pathway in cyanobacteria. In contrast to an earlier study, compelling evidence is given that Synechocystis PCC 6803 lacks both an Entner-Doudoroff pathway and a related bypass but contains a promiscuous aldolase. This study successfully reconciles data from different studies and lessons learned from a previous misconception.

    1. eLife Assessment

      This study applies a relatively novel method, ABR (Automated Behavioural Response system), to an arboreal small mammal, providing some valuable results on the responses of these small primates to both natural predators and human stimuli. However, the study in its current form is incomplete in its framing and methodology and could be improved to appeal more broadly to behavioural biologists.

    1. eLife Assessment

      This valuable study identifies an upstream repressive region in the Saccharomyces cerevisiae DDI2/3 promoter and shows that chemical stress induced by cyanamide or MMS is accompanied by reduced histone abundance and decreased nucleosome occupancy across the DDI2/3 locus. Genetic histone depletion is sufficient to enhance DDI2/3 expression, while MNase-seq and genetic analyses support a model in which the transcription factor Fzf1 both activates transcription through its established promoter-binding function and promotes chromatin changes that relieve nucleosome-mediated repression, helping to explain the unusually strong induction of DDI2/3 relative to other Fzf1 targets. The study is significant, as it provides a conceptually interesting extension of Fzf1-mediated stress regulation. The strength of the evidence is solid, although additional controls and a more cautious treatment of whether Fzf1 directly drives nucleosome eviction versus acting indirectly through transcriptional recruitment or chromatin-remodeling factors would further strengthen the mechanistic conclusions.

    1. eLife Assessment

      The study addresses a timely problem that is of importance in the cfRNA field, and it provides a potentially valuable resource. The use of a common processing pipeline, publicly available code, and variance-partition analyses are notable strengths. However, several central conclusions, particularly those concerning protocol-level effects, the dominance of technical over biological variation, and the proposed universal QC criteria remain more general than the study design and available data can support. Therefore the evidence is currently incomplete and needs to be improved through the revision process.

    1. eLife Assessment

      This study presents a valuable patient-derived human cell platform for investigating LMNA-associated cardiomyopathy and identifies cyproheptadine as a compound that improves abnormal calcium handling across multiple LMNA variants in vitro. The experimental approaches are generally rigorous and establish reproducible disease-associated cellular phenotypes; however, the evidence remains incomplete because the mechanistic basis of the observed rescue is not established, and the translational conclusions substantially exceed the presented data.

    1. eLife Assessment

      This study presents a valuable finding on impacts of the common driver mutations APC, KRAS G12D, and TP53 in murine colorectal organoids. In particular, the authors examine how the order of APC and TP53 acquisition influences tumor phenotype. The evidence supporting the claims of the authors is solid. The work will be of interest to scientists working in the field of breast cancer.

    1. eLife Assessment

      This important study shows that prenatal alcohol exposure produces lasting changes in amyloid precursor protein processing, including altered APP C-terminal fragments and Notch intracellular domain levels, that persist into adulthood and track with progressive spatial learning and memory deficits, in both wild-type and 3xTg-AD mice. The convincing study was carefully designed and combined biochemical, histological, and behavioral approaches across multiple ages. The work will interest researchers studying fetal alcohol spectrum disorders, Alzheimer's disease risk, and the developmental origins of neurodegeneration. Nonetheless, reviewers identified opportunities to strengthen the conclusions with additional samples and controls.

    1. eLife Assessment

      This fundamental work significantly advances our understanding of the circuit-level implementation of predictive processing by elucidating the functional influence between putative prediction error neurons in layer 2/3 and putative internal representation neurons in layer 5. The evidence demonstrating that neither the hierarchical nor the non-hierarchical variant of predictive processing fully accounts for the presented data is convincing. Moving forward, this line of work would benefit from explicitly comparing different theories, thereby clearly articulating the points raised in this paper.

    1. eLife Assessment

      This important study provides new insights into the patterns of organelle inheritance in the protozoan parasite Toxoplasma gondii. The authors introduce an innovative dual-labeling approach to distinguish maternally inherited from de novo synthesized organelles, representing convincing evidence that different organelles follow distinct inheritance fates during parasite replication. Future studies will be needed to determine whether the residual body functions as a central recycling hub, as the current data are also consistent with alternative models.

    1. eLife Assessment

      This study presents fundamental and significant findings that bovine mammary epithelial cells can be infected with both avian and human influenza A viruses, providing a potential site for viral reassortment. The evidence to support these claims is compelling. The work will be of interest to virologists and evolutionary biologists working on cross-species transmission of viruses and pandemic preparedness.

    1. eLife Assessment

      This article provides a computational study to understand how evolutionary selection could introduce structural priors into neural networks to improve learning. This useful investigation provides incomplete evidence that such joint learning is possible and has some counterintuitive features. However, the extent to which the models studied are distinct from those studied in the literature previously remains unclear.

    1. eLife Assessment

      This valuable study examines whether neurally-derived non-decision time estimates can guide decision models to more reliable parameter estimates. Convincing evidence for their value is obtained from state-of-the-art model-fitting methods applied to two empirical datasets. However, the premise relies on very strong assumptions regarding the degree to which the neural metrics directly index non-decision time and comparisons across models that appear to differ in more ways than just the non-decision time constraint.

    1. eLife Assessment

      This important study investigates the peptide-binding principles by promiscuous chicken MHC molecules. The data from crystallography, mass-spec, and modeling are compelling. This paper will be of broad interest to immunologists and those interested in vaccine development.

    1. eLife Assessment

      This study makes a valuable contribution by broadening the range of eukaryotic model systems and establishing Blastocystis, the most prevalent microeukaryote in the human gut, tractable for reverse-genetics investigations. The presented imaging data are convincing and informative. The work should interest readers studying host-microbe interactions in the human gut, as well as those developing new systems for eukaryotic research.

    1. eLife Assessment

      This is a fundamental study on the sensory roles of cerebrospinal-fluid-contacting neurons (CSF-cNs) in mammals, revealing how the apical extension is used as an amplifier of chemical changes in content of the CSF. Specifically, the authors show compelling evidence that PKD2L1 is predominantly a pH-sensing channel in CSF-cNs and link its apical localization to dual phasic and sustained responses underlying CSF chemosensation.

    1. eLife Assessment

      This valuable work introduces HSSM, a flexible and modular Python toolbox for hierarchical Bayesian estimation of sequential sampling models. By combining model simulation, neural likelihood approximation, established inference backends, formula-based regression, and support for trial-level covariates, HSSM could become a widely used resource in cognitive and computational neuroscience. Evidence for the framework's scope and core functionality is convincing, but support for its usability, computational performance, and reliability is incomplete. The contribution would be substantially strengthened by an executable end-to-end analysis, clearer exposition for non-specialists, parameter and model recovery demonstrations, guidance on diagnostics and model comparison, quantitative benchmarks, and a clearer delineation of HSSM's scope relative to broader claims about neurocognitive modelling.

    1. eLife Assessment

      This study provides a useful single-cell atlas of the Clytia hemisphaerica planula, complemented by an updated medusa dataset, ultrastructural analyses and in situ validation of expression patterns. The cross-stage comparison and cluster-similarity framework offer a promising basis for investigating cellular diversification across the life cycle. The evidence is currently incomplete due to documentation deficits and insufficient cross-referencing with prior work. It should be relatively easy to address these issues, which should make this a valued resource for cnidarian researchers and for colleagues studying cell-type evolution.

    1. eLife Assessment

      This important study presents an ultrastructural atlas of extracellular vesicles and non-vesicular particles in Drosophila olfactory sensilla, using cryofixation-based serial block-face electron microscopy to catalogue roughly 7,800 particles across four antennal regions. The evidence is compelling: the cryofixation minimizes fixation artifacts, and the rigorous, well-validated methodology and morphometric analyses provide strong support for the structural classifications and spatial distributions, though some conclusions require moderation or additional evidence. The work provides a potentially foundational resource for researchers studying extracellular-particle signaling in sensory organs.

    1. eLife Assessment

      The authors investigate the activation mechanism of a gasdermin pore-forming effector of Callorhinchus milii, which is a shark that is one of the most basal members of the cartilaginous fishes. The valuable findings show that GSDMA/B can be cleaved by a lipopolysaccharide-activated caspase here termed CmiCASP1, analogous to the cytosolic LPS detection pathway already established in mammals. The strength of evidence supporting these conclusions is solid; however, the data indicating the functional consequences of these proteins remain incomplete.

    1. eLife Assessment

      This important study presents a new approach to individualised functional brain mapping using multi-task batteries, and introduces a toolbox to support its implementation. Convincing evidence from simulations and empirical analyses across multiple datasets demonstrates clear advantages over traditional single-task approaches and provides practical guidance on task selection. The extent to which these improvements translate into more accurate recovery of individual-specific functional boundaries beyond well-characterised systems remains to be established.

    1. eLife Assessment

      This useful study builds on the previously identified terminal Schwann cell (tSC) marker Col20a1 to generate a novel Col20a1-CreERT2 knock-in mouse line that enables the selective genetic labelling and ablation of tSCs at the neuromuscular junction. This model represents a new tool for distinguishing tSCs from myelinating Schwann cells. The authors conclude that loss of tSCs does not cause major alterations in the overall structure of the neuromuscular junction, but that tSC ablation intrinsically compromises the presynaptic reserve pool. However, the study remains incomplete because the evidence provided does not adequately support these conclusions.

    1. eLife assessment

      The findings documented here are interesting and valuable with respect to revealing genetic players that may underlie AD. However, there are concerns related to the analysis pipeline and the basic assumptions underlying the modelling. There is an overarching lack of controls in terms of comparator diseases and/or positive and negative control findings; hence, the main claims are only partially supported, and the study is incomplete.

    1. eLife Assessment

      This important study shows how hunger alters avoidance of harmful heat in C. elegans by reconfiguring the activity of key sensory neurons. The evidence is convincing, with well-designed behavioural, genetic, and imaging experiments that support the main conclusions. The work will be of interest to neuroscientists studying how internal states shape sensory processing and behaviour across species.

    1. eLife Assessment

      This important study shows that an odorant that is typically thought of as a repellant actually activates both attractant and repellant olfactory neurons in C. elegans. Convincing evidence is provided that nematode worms can integrate signals in different sensory pathways to drive different behavioral responses to the same cue. These findings will be of interest to scientists interested in combinatorial coding in sensory systems.

    1. eLife Assessment

      Feeding, the circadian rhythm, and the gut microbiota are all intimately linked, motivating new approaches to identify causal relationships while minimizing confounding factors. The authors employ an innovative combination of the osmotic laxative lactulose and a defined 3-member gut microbiota to acutely induce gut bacterial metabolism in mice during the daytime, resulting in changes in the ileal expression of clock genes and altered feeding behavior. Together, this study utilizes convincing methods to provide important new insights into the role of gut microbiota in the circadian rhythm, setting the stage for follow-on studies aimed at better understanding the mechanisms responsible.

    1. eLife Assessment

      This paper introduces a valuable optical method for simultaneous in vivo multiphoton imaging of the mouse brain combined with DMD-based one-photon patterned photostimulation in different axial planes. The evidence for effective optical separation of excitation and imaging is convincing, although the in vivo data in the olfactory bulb suggest potential confounding factors arising if stimulation not only affects cell bodies but also neuronal processes. The work will be of broad interest to neurobiologists working in circuit and systems neuroscience, as well as to specialists in optical microscopy.

    1. eLife Assessment

      This study presents a valuable finding on the spatio-temporal neural dynamics of language processing modulated by story context and presentation speed. The presentation of evidence in the version of the original submission is solid, as providing further clarifications on methodological details and addressing potential confounds would strengthen the study. The work will be of interest to cognitive neuroscientists working on reading and language comprehension.

    1. eLife Assessment

      Chen and colleagues use in vivo electrophysiology in rats to characterize distance-encoding neurons in the retrosplenial cortex during both random foraging and goal-oriented navigation. This valuable work identifies a subset of retrosplenial neurons that encode distance to a hidden goal, and it reports that head-direction coding is enhanced during goal-directed navigation relative to foraging. Although the analytical framework aims to isolate the unique contribution of goal distance to retrosplenial firing patterns, strongly covarying self-motion and spatial signals leave the main claims about distance coding incompletely supported.

    1. eLife Assessment

      This valuable study is a rigorous and comprehensive anatomical description of populations of spinal-projecting neurons in the brain of the larval zebrafish. The manuscript consists of compelling data that reveal a far more complete and robust visualization of these populations than past work. The scholarship is also notable, featuring thoughtful contextualization of the findings with respect to both non-mammalian and mammalian literature.

    1. eLife Assessment

      This important study introduces EvoDiff, an order-agnostic diffusion foundation model for protein sequence generation, and demonstrates its potential across unconditional generation, motif scaffolding, MSA-conditioned design, and IDR inpainting. The evidence supporting the principal claims is solid, combining computational evaluation with experimental validation, although the comparative advantages and generality of some applications would benefit from further clarification and calibration.

    1. eLife Assessment

      This study examines how adolescent adversity influences maternal caregiving and social development across generations. The findings are potentially valuable, but several conclusions currently extend beyond what is directly supported by the data, rendering the strength of the evidence incomplete. Key mechanistic claims are limited by the communal reassuring design, and by several unresolved questions regarding causality and interpretation.

    1. Exchange value

      Exchange value appears as the property of a commodity that is exchangeable for other commodities. It also presupposes societies who produce commodities and exchange them. While all societies have things with use values, exchange value is relative to a specific time and place.

      Additionally, exchanging commodities must also presuppose a way to determine proportionality between different commodities, so that they can be exchanged in the first place.

      Exchange therefore requires some other measure that stands above the two commodities meant to be exchanged. If there were no ways in which iron and corn were found similar to a society, for example, then we would not exchange them and they would have no exchange value.

      Marx will contend that what each commodity must contain crystalized within it is value (formally) and that the substance of value is labor (viz. the common factor of both iron and corn is labor). Marx will call this kind of labor abstract labor.

    1. eLife Assessment

      This is a valuable study of the effects of selective or broadband amyloid deposition in medial septum (MS) cholinergic neurons on neuropathology, cognition, sleep, and hyperexcitability in aging mice carrying risk factors for Alzheimer's disease (AD). The investigation is still incomplete, with some weaknesses related to conceptualization and methodology that need to be addressed.

    1. eLife Assessment

      This important study investigates how viral macrodomains in dual-host viruses functionally contribute to their infection in the vector, which was previously understudied. The findings that chikungunya virus (CHIKV) macrodomain mutants have unique impacts on virus replication in mammalian cells and in live mosquitoes are convincing and significant; however, the study can be strengthened by further investigating the role of ADP-ribose binding and potential other compensatory mutations. The work will be of interest to virologists and biologists who study macrodomains and ADP-ribosylation.

    1. eLife Assessment

      This important study identifies and characterizes a set of amino acid states that can rescue protein function in the presence of substantially deleterious mutations. Some of these super-compensatory substitutions also confer substantial mutational robustness, with broader implications for understanding epistasis, protein evolution, and protein engineering. The evidence is convincing, supported by a creative reanalysis of a large deep-mutational-scanning dataset, statistically rigorous treatment of anticipated error rates, experimental validation, and analyses of additional proteins, although clearer presentation and deeper investigation of the evolutionary implications and structural mechanisms would further strengthen the study.

    1. eLife Assessment

      This important study investigated whether the adoption of different explicit strategies influences implicit recalibration during visuomotor adaptation. Through a series of increasingly controlled experiments, the authors demonstrated that implicit recalibration is relatively insensitive to the specific type of explicit strategy employed but is influenced by the variability of strategic motor plans. However, the evidence supporting these conclusions is currently incomplete. The findings will be of interest to cognitive scientists studying motor control and its relationship to higher-level cognitive processes, provided that the key claims are supported by more rigorous analyses and experimental approaches.

    1. eLife Assessment

      This study presents valuable findings implicating Xkr and its newly identified binding partners in regulating the exposure of apoptotic signal for phagocytosis, suggesting that Xkr might facilitate phosphatidylserine transfer at the ER-plasma membrane contact sites. However, several conclusions, including caspase-independent activity of Xkr and its role at the ER-PM contact sites, are not well supported by experimental data. Furthermore, some key controls are missing, and in numerous places the authors' discussion has extended far beyond what the data support. The findings presented are currently incomplete and do not fully support key mechanistic claims of the study.

    1. eLife Assessment

      Shin et al present significant new observations highlighting a novel oscillatory window during REM sleep that impacts neuronal dynamics and cross-regional communication and could have implications for our understanding of sleep's role in memory consolidation. This important study identifies and characterizes high-frequency oscillations (HFOs) in the prefrontal cortex (PFC) during REM sleep, reporting their temporal dynamics and coordination with hippocampal area CA1, and an intriguing dissociation between activation of CA1 neurons during REM HFOs and non-REM ripples that may impact sleep-dependent firing rate decreases. The main claims are supported with convincing evidence including an impressive range of analyses.

    1. eLife Assessment

      This study presents a useful combined analysis of human behavior, pupillometry and EEG measures to probe differences in ambiguity assessment between individuals during value-based decision-making. Using computational models, the authors aim to test for distinct groups of participants that differ in the relationship between evidence accumulation, arousal, and neural decision-making computations. However, at present, the evidence for group differences in the physiological, neural, and behavioral profile of decision-making under uncertainty is incomplete, lacking an appropriate statistical test for group differences, and a more complete assessment of the modeling results on evidence accumulation in decision-making in this study is required to robustly characterize and interpret the results.

    1. eLife Assessment

      This valuable study advances our understanding of the physiological conditions that promote the formation of mitochondrial-derived compartments (MDCs). The genetically amenable yeast system allowed the authors to generate convincing data showing the rapid formation of MDCs under physiologically relevant conditions where the mitochondrial proteome needs to be expanded during metabolic remodeling. The identification of a key role for a yeast AMPK-related protein called Snf1 will be of interest for cell biologists and biochemists.

    1. eLife Assessment

      This important study uses dual-color super-resolution microscopy, quantitative clustering analyses and simulations, as well as biochemical approaches to investigate the nanoscale organization of mucins and trans-sialidases on the surface of Trypanosoma cruzi, the causative agent of Chagas disease. The evidence supporting a non-uniform distribution of these molecules into segregated nanoclusters and a more ordered non-clustered population is solid. Overall, this work provides a generalizable analytical framework that can help understand how parasite surface proteins are spatially organized. The main remaining limitations concern the mechanistic basis of the proposed organization and the need to exclude possible effects of sample preparation before fixation.

    1. eLife Assessment

      A regulated cell death pathway that intentionally causes ferroptosis has not been previously described. The authors describe a useful finding that the ferroptosis inducers ML162 and erastin induce caspase-5-mediated cleavage of GSDME in mesenchymal-like ovarian cancer cells, resulting in pore formation. The data supporting the main claims are incomplete. This work will be of interest to researchers who study regulated cell death.

    1. eLife Assessment

      This study presents an important empirical analysis of the acoustic space of vocal repertoires across primates and humans, providing new data that challenge the widely held hypothesis that the expansion of the human vocal space, driven by modifications of the vocal tract, was a key prerequisite for the evolution of spoken language. The evidence is convincing in its technical implementation and acoustic measurements, offering helpful comparative insights into voiced vocalizations. However, the theoretical framing and interpretation would benefit from further discussion.

    1. eLife Assessment

      The ability to measure autophagic flux in vivo in response to physiological stresses remains a challenge for investigators in the field; the novel mouse model present in this work is significant and should prove valuable to investigators in addressing shortcomings of existing models. In addition, the development of the microplate reader approach to permit semi-high-throughput analysis of samples is convincing and a significant advance. The application of these approaches to measuring autophagy in multiple tissues is appreciated but raises some questions that need to be answered and highlighted, including what new biological insight has been generated for tissues under study, how overall autophagy versus rates of flux are determined, and how the sex of the animal affects outcomes. The neuronal populations under study should be reassessed.

    1. eLife Assessment

      This manuscript presents valuable experimental results describing the localisation and regulation of casein kinase CK1δ during the cell cycle. During the G2 phase of the cell cycle, the autophosphorylation of the C-terminal tail stabilises and inhibits the kinase which might protect CK1δ in the subsequent G1 phase. The results may be of interest to researchers working on casein kinase function and regulation but due to lack of some controls remain incomplete.

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

    1. eLife Assessment

      This important study identifies a non-canonical essential role for acyl carrier protein in maintaining apicoplast metabolism and blood-stage survival in Plasmodium falciparum. The main conclusions are compelling, and supported by strong genetic and biochemical evidence, while function of fatty acid synthesis pathways in low-lipid conditions will require future studies to fully resolve. The work provides novel mechanistic insight into ACP-mediated stabilization of pyruvate kinase II and will be of broad interest to the malaria and apicoplast biology communities.

    1. eLife Assessment

      This important work identifies phlda2 as a specific marker for primordial cardiomyocytes in the adult zebrafish heart and demonstrates their essential role in myocardial morphogenesis and coronary vascularization, but not in heart regeneration. The conclusions are well supported by single-cell transcriptomics, new genetic tools, and cell-specific ablation experiments. The revised version strengthens these findings with analyses of the epicardium, long-term time points showing that the developmental defects persist, and a control confirming that loss of primordial cardiomyocytes alone does not trigger a regenerative response. Overall, the evidence is solid and provides insight into the difference between developmental and regenerative cardiac programs, and this work will be of interest for those studying cardiac development and regeneration.

    1. eLife Assessment

      This important study identifies PRRT2 as an auxiliary regulator of Nav channel slow inactivation in vitro and in vivo, demonstrating that PRRT2 facilitates entry into, and delays recovery from, the slow-inactivated state. The revised manuscript has been substantially strengthened, providing compelling evidence that PRRT2 is relevant to normal brain physiology and disease pathophysiology, providing a mechanistic link between PRRT2 mutations and episodic neurological phenotypes. Overall, this study will be of interest to ion channel biophysicists and neurophysiologists, particularly those studying channelopathies.

    1. eLife Assessment

      The authors describe the results of a longitudinal study of pertussis infection in mother/infant dyads in Lusaka, Zambia. This work represents an important contribution to our understanding of the global burden of pertussis. The evidence presented is compelling, with strengths including routine sampling irrespective of symptoms and rigorous qPCR methodology. The study is a significant and much-needed contribution, which sheds light on an often-overlooked dimension of pertussis transmission and opens avenues for future research and policy consideration.

    1. eLife Assessment

      This study offers valuable insights into the genetic and evolutionary basis of the starvation response by confirming the hypothesis about the mito-nuclear etiology of this trait. The level of evidence is currently incomplete but could be improved if controls were designed better, particularly by including analysis of variation in the initial, common population prior to all treatments. Overall, this work would be interesting to a broad audience, beyond the Drosophila community, if the analysis of the candidate genes against Human ortholog loci were to be conducted with more careful controls.

    1. eLife Assessment

      This valuable study combines a chromosome-level genome assembly with population resequencing and demographic modelling to reassess the status of the Formosan landlocked salmon, a critically endangered salmonid at the southern edge of the genus. The assembly and the evidence for extensive lineage-specific chromosomal fusions are genuinely well done, and the discovery of an overlooked, genetically distinct population in Hehuan Creek is sound and of clear management relevance. Evidence for the headline claims is incomplete: species rank is asserted but nowhere argued, and gene flow is excluded using a coalescent model that contains no migration parameter. Support for the population-viability conclusions is also not complete, as the demographic mechanisms invoked in the discussion are not borne out by the supplementary tables.

    1. eLife Assessment

      This important study combines cryo-EM, biochemical, and cell-based assays to examine how Gβγ interacts with and potentiates PLCβ3. The authors present evidence for multiple Gβγ interaction surfaces and argue that Gβγ primarily enhances PLCβ3 activity after membrane recruitment rather than serving mainly as a membrane-recruitment factor. Following additional experimental support, the evidence in support of their conclusions is convincing.

    1. eLife Assessment

      This fundamental work uncovers an unexpected lysosomal function for NINJ2 and links it to ferroptosis and cancer biology. The evidence supporting the conclusions appears to be convincing. This work will be of general interest to the community of ferroptosis and cancer biology.

    1. eLife Assessment

      This valuable study uses genetic, behavioural, neuronal activity and cell-based assays to show that the Drosophila ionotropic receptor IR20a contributes to the detection of arginine and low-sodium salt, and suggests that peripheral receptor combinations may help integrate these nutrient cues. The evidence for a role for IR20a and associated co-receptors in these responses is solid, but the evidence that distinct receptor assemblies mediate receptor-level multimodal integration is incomplete, as this central model is inferred from functional data and leaves some discrepancies between behaviour, physiology and prior work unresolved. The study will be of interest to sensory neuroscientists and chemosensory biologists.

    1. eLife Assessment

      This Review delineates postmenopausal age-related lobular involution (ARLI) in the breast that remains only partially resolved. In contrast to the conventional view of persistent lobules as passive residual structures, this work defines them as an actively maintained senescence-immune reserve niche. Inclusion of operational definitions for the reserve state in human breast tissue would strengthen the article. The work will be of interest to scientists working in the fields of breast disorders.

    1. eLife Assessment

      This important study provides new insights into the regulation of cell organization and division in Trypanosoma brucei through the phosphorylation-dependent control of a kinesin motor protein by a polo-like kinase. The authors present convincing evidence, combining rigorous biochemical, cell biological, and imaging analyses, demonstrating that phosphorylation modulates kinesin localization and function, thereby influencing cellular organization and cytokinesis. The findings advance our understanding of the molecular mechanisms governing trypanosome cell division and will be of broad interest to researchers studying trypanosomes, cytoskeletal regulation, and eukaryotic cell division.

    1. eLife Assessment

      This study provides an important contribution to retinal regeneration research by using overexpression of pro-neural factors to reprogram fetal human RPE cells into retinal neurons. The authors provide solid evidence of fetal RPE reprogramming into neural and photoreceptor-like states using scRNA-seq and imaging validation; however, there are concerns regarding comparisons between the effectiveness of different combinatorial transcription factor codes.

    1. eLife Assessment

      This study addresses a valuable question with implications for the development of EEG-based neurofeedback interventions for pain. However, the strength of evidence is incomplete because the principal conclusions rely on post hoc responder analyses and methodological ambiguities that weaken the support for the claimed causal relationship between gamma modulation and pain reduction.

    1. eLife Assessment

      This study provides important evidence that crickets use bat-associated odors as cues of predation risk, extending the classic bat-insect arms race beyond its traditional 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. Together, the multidisciplinary results provide a coherent and convincing chain of evidence for an olfactory component of predator detection in this bat-insect system. The work will be of broad interest to researchers in sensory ecology, chemical ecology, predator-prey interactions, and bat-insect coevolution.

    1. eLife Assessment

      This important study systematically investigates repeat expansion in the plant Arabidopsis thaliana using a new k-mer-based method, expanding on previous smaller studies, to comprehensively identify cis- and trans-acting loci associated with repeat dynamics. The approach is methodologically sound, and the exploration of different k-mer lengths and use of a more complete reference assembly strengthen confidence in the analysis while clarifying its limitations and the method is broadly applicable to large-scale short-read datasets for assessing copy-number variation and genomic repeat content. The findings are convincing in their scope and novelty for A. thaliana. It will be of interest to learn in future how the approach generalizes to species with substantially greater or lower repeat content.

    1. eLife Assessment

      This important study presents an innovative combination of experimental evolution and CRISPR screening to study the genetic basis of a polygenic trait, resistance against octanoic acid in Drosophila. The evidence supporting the authors claims is solid. The work will be of interest to the Drosophila community and researchers interested in functional testing of polygenic traits.

    1. eLife Assessment

      This study presents valuable findings on the functional consequences of nuclear envelope rupture caused by the depletion of nuclear pore complex subunits on the behaviour and organisation of chromosomes during mitosis in C. elegans embryos. The experiments are generally well-designed and executed; however, the evidence for some of the main conclusions is incomplete. This work is of potential interest to cell biologists working on cell division.

    1. eLife Assessment

      This useful study employs an innovative chemoproteomic and multi-modal experimental approach to support VDAC2 as a key functional mediator of STX effects on mitochondrial bioenergetics. However, concerns remain regarding the physiological and disease relevance, including the reliance on cell lines, lack of loss-of-function validation, unresolved binding specificity, and limited justification for focusing on POMC neurons in the context of Alzheimer's disease. As a result, the evidence is incomplete for a link between VDAC2 and Alzheimer's pathogenesis, and aspects of the binding data raise alternative interpretations, including a potential role for other VDAC isoforms.

    1. eLife Assessment

      This revised study offers valuable insights into how nuclear export influences protein condensates and TDP-43 phase behaviour. The findings are solid and highlight several noteworthy observations for the field, such as RNA-dependent stabilisation of TDP-43 condensates and the inhibition of nuclear export in an ALS organoid model. The work suggests a possible mechanistic link between nuclear export and TDP-43 aggregation in ALS/FTD; however, the exact mechanistic connection remains unclear, as much of the evidence is based on indirect observations within sensitised model systems. Although the authors carefully acknowledge these limitations and moderate their conclusions, further validation in more physiologically relevant models will be necessary to demonstrate a direct causal role of nuclear export in regulating pathological TDP-43 aggregation.

    1. eLife Assessment

      The study presents valuable findings of a new E. coli cell-free protein synthesis (eCFPS) system that has been simplified by reducing the number of core components from 35 to 7; furthermore, the findings communicate a simplified 'fast lysate' preparation that eliminates the need for traditional runoff and dialysis steps. The system's robustness is exhibited by its applicability to nanoluc, an ubiquitous protein and to more challenging proteins like vimentin and the active restriction endonuclease Bsal. The evidence is convincing and supports the main claims on efficiency backed up by investigations on the mechanisms. The paper will be of interest to scientists in cell and molecular biology, microbiology, biotechnology and protein synthesis.

    1. eLife Assessment

      This is an important study that comprehensively determines the consequences of DNMT3A mutations on human neuronal development in culture. The data derived from multiple different mutations in iPSC and hESC derived neurons and organoids are convincing and well controlled. This work will be of interest to researchers who study chromatin mechanisms of brain development and to those interested in DMNT3A mutations in Tatton-Brown-Rahman Syndrome.

    1. eLife Assessment

      This important work presents a novel computational framework for modeling macroscopic traveling waves in the mouse cortex by integrating open-source connectomic and transcriptomic data into a spiking network model. This approach allows the computational model to assign excitatory/inhibitory connections based on neurotransmitter profiles and extends simulations to the 3D domain. The authors present results that demonstrate how spatiotemporal dynamics such as slow oscillations (0.5-4 Hz) emerge and self-organize at the whole-brain scale. This study provides convincing initial insights into the structural basis of traveling waves at the whole-brain scale, and allows future links between connectome-driven spiking neural networks and whole-hemisphere imaging in the mouse.

    1. eLife Assessment

      This study shows that combining forced cell cycle re-entry with Rbpj deletion enhances Müller glia dedifferentiation and promotes their conversion into retinal neuron-like cells in the uninjured mouse retina. It provides a valuable strategy for improving Müller glia-mediated neurogenesis and advancing regenerative potential in the mammalian retina. Overall, the data are convincing. The authors have also addressed concerns regarding Müller glia function, cell survival, and the limitations of neuronal maturation and integration, further strengthening the conclusions of the study.

    1. eLife Assessment

      This study investigates the role of the Z-disc protein Zasp52 in Drosophila flight muscles and provides evidence that an intrinsically disordered region (IDR) helps to stabilize and promote the localization of the protein to the Z-disc. Overall, this represents an important study that provides insights into Z-disc function and maintenance. The data are convincing, supported by strong genetic evidence and behavioral tests, well-controlled experiments, and detailed statistical analyses. Characterization of a new actin-binding motif mutant and FRAP analysis further support the functional importance of the Zasp52 IDR.

    1. eLife Assessment

      This study reports important findings regarding social influence on charitable donations, showing that giving is shaped by the statistical properties of others' donations in a manner that can be captured by a reinforcement learning model. The evidence for the conclusions is solid, although the computational modelling could be better motivated and described, the individual differences analyses could be more robust, and some design choices could be better motivated. Overall, the core effect appears robust and is supported by multiple well-designed experiments, but the conclusions that rely upon computational modelling and individual differences may require further support.

    1. eLife Assessment

      In this important study, Lau et al. identify non-conserved nucleotides within the common binding motifs of BLIMP1 and IRF4 that provide a molecular mechanism for their distinct roles as crucial transcription factors during the antibody-secreting cell differentiation. The major strength of this manuscript is the solid and detailed characterization of human in vitro plasma cell differentiation. However, several overstatements exist, therefore requiring careful revision to improve the manuscript.

    1. eLife Assessment

      This important study shows that cave-adapted Astyanax mexicanus have shifted from avoiding alarm and decay odors to being attracted by them, alongside sex-specific responses to social odors. The evidence for the behavioral and heritability claims is convincing, supported by analyses of different cave populations and F2 hybrids, as well as starvation-induced plasticity experiments. Whole-brain pERK mapping offers suggestive mechanistic insight, although uncertainties in anatomical assignments and aspects of statistical and ethogram reporting temper the strength of the neurobiological conclusions. The work will be of interest to anyone working on the evolution of behavior.

    1. eLife Assessment

      Using sci-L3-Strand-seq, this study shows genome-wide, single-cell evidence that DSBs triggered by CRISPR/Cas9 are frequently resolved through sister chromatid exchange (SCE), which is undetectable with conventional whole-genome sequencing approaches. This important work provides helpful metrics quantifying the occurrence of SCE events at targeted and repetitive genomic loci that are of particular interest to those working in gene editing, DNA repair, genome instability, or repetitive genomic loci. However, the evidence supporting the proposed involvement of under-replicated region/replication-termination-zone resolution and TRAIP/URR-like pathways is currently incomplete and could be strengthened with an increased number of reciprocal daughter-cell pairs and by genetic or molecular perturbation, or alternatively, this can be addressed by changing the discussion.

    1. eLife Assessment

      This valuable study provides insights into the developmental regulation of the unusual form of holometabolous metamorphosis that occurs in the black soldier fly, in which a distinct prepupal stage is interposed between the final larval instar and pupation. This type of life history strategy is similar to what is seen in insects at the hemimetabolous-holometabolous boundary, but, given the phylogenetic position of dipterans, it is likely to be a derived trait. The combination of developmental characterization, gene expression profiling, and RNAi-mediated functional analyses provides solid evidence supporting the authors' conclusions and will be of interest to researchers studying insect development and the evolution of metamorphosis.

    1. eLife Assessment

      What can a neural network trained to imitate animal behavior tell us about biology? This valuable work uses deep reinforcement learning to train an artificial neural network to transform the dynamics of a recurrent neural network based on the C. elegans connectome into an adult Drosophila walking program in a physical model of the fly body, demonstrating that achieving plausible output dynamics does not in and of itself imply biologically meaningful simulation. Evidence for this basic claim is solid, but more extensive analyses, better methodological description, and a discussion of deeper challenges in the undertaking of biological brain modeling would strengthen the study. This result demands the attention of the practitioners of the growing field of connectome simulation for the purpose of gaining mechanistic understanding of nervous system function.

    1. eLife Assessment

      This study provides valuable insights into the role of the bile acid receptor TGR5 in regulating bone marrow adipose tissue. This revised manuscript has additional characterization of TGR5 expression in hematopoietic and stromal populations, and phenotypic differences observed between sexes, during aging, and under high-fat diet conditions. Although the scope of the study has expanded, the mechanism of how TGR5 in the microenvironment regulates hematopoietic recovery is still incomplete.

    1. eLife Assessment

      This important study partially fills the gap in the knowledge of olfaction at the level of the Anterior Olfactory Nucleus (AON) and Piriform Cortex with functional magnetic resonance imaging, electrophysiology, and modeling. The methods used are convincing. Some of the findings confirm ongoing hypotheses, such as the behavioral importance of AON for odor source discrimination, while other results shed light on the dynamics of the connection between the olfactory system and the rest of the brain. However, the lack of access to raw data hampers the assessment of data quality.

    1. eLife Assessment

      This valuable study addresses two debates about how confidence is computed: whether it continues the accumulation process that produced the initial choice or reflects a separate one, and whether that accumulation stops at a time limit or an evidence boundary. The evidence is solid, combining systematic model comparison with an independent neural marker of evidence accumulation to adjudicate between models that behaviour alone cannot separate. Support for the boundary-based stopping rule is stronger than for the single-process account, as the neural comparison is qualitative rather than quantified and the alternatives tested cover only a narrow range of plausible two-stage architectures. The work will be of interest to researchers studying decision-making and metacognition.

    1. eLife Assessment

      The work presented represents important new evidence linking the cascade of neural processes triggered by memory-based prediction errors. The study uses an impressive collection of approaches and methods to characterize and measure cognitive control, arousal, and memory changes as a function of memory-based violations. Analyses are technically sophisticated and rigorous and, taken together, provide solid evidence that there are multiple processes accompanying prediction errors, and that they differentially relate to successful encoding.

    1. eLife Assessment

      This valuable study uses the Cntnap2 mouse model of autism to investigate how reduced activity in the dorsal CA1 region of the hippocampus contributes to impaired temporal binding and memory flexibility. The authors combined trace conditioning and radial maze assays with fibre photometry, optogenetic rescue, and brain-wide c-Fos mapping to provide solid evidence that dorsal CA1 hypoactivity limits the retention of temporally separated associations and biases learning towards less flexible strategies. The work advances understanding of hippocampal contributions to cognitive alterations associated with autism and will be of broad interest to researchers studying memory, hippocampal function, and neurodevelopmental disorders.

    1. eLife Assessment

      This fundamental study reveals a new downstream mechanism that mediates mTOR's effect on lifespan in C. elegans. Using a combination of genetic, genomic, and functional analyses, the authors uncovered that a bile acid-like hormone, dafachronic acid (DA), acts downstream of mTOR to modulate lifespan. The reviewers found the evidence provided to be compelling.

    1. eLife Assessment

      This important study combines crystallographic fragment-based screening with fluorescence-polarization competition assays to demonstrate that the SARS-CoV-2 accessory protein ORF9b, and its interface with the mitochondrial import receptor TOM70, is accessible to small-molecule binding. This is a result with practical implications beyond coronavirus biology for efforts to restore interferon signalling and the antiviral response. The structural evidence is convincing, resting on an unusually large body of ligand-bound crystal structures whose fragment hotspots are independently corroborated by orthogonal biophysical approaches including fluorescence polarization and SPR. This work would benefit from additional information regarding the use of CHAI-1 and other attempts to determine the interactions between hit compounds and Tom70.

    1. eLife Assessment

      This important manuscript proposes a dual behavioral/computational approach to assess emotional regulation in humans. The authors present convincing evidence for the idea that emotional distancing (as routinely used in clinical interventions for e.g. mood and anxiety disorders) enhances emotional control.

    1. Editors Assessment:

      Here is a Data Release article sharing the reference genome of the Pacific herring (Clupea pallasii), a species with broad ecological, economic, and cultural importance. This specimen coming from the eastern Bering Sea which are genetically quite different from those from the Gulf of Alaska. This high-quality chromosome-scale reference was built from Hi-C and PacBio Hifi reads, creating a 795MB assembly anchoring to 26 chromosomes. There was initially a mixup with the data availability but after review this was resolved and all data is publicly available. This data allows study of cryptic diversity in Clupea and its evolutionary history in the subarctic.

      This evaluation refers to version 1 of the preprint

    1. eLife Assessment

      This important study on multisensory learning examines the effect of integrating color vision and olfaction in the center for learning and memory (the mushroom body) in the fruit fly brain, and finds that memory performance is improved, with neurons otherwise selective for color being recruited into odor memories via interneuron interactions. The combination of carefully controlled behavioural experiments, neurogenetic manipulations of individual neurons and detailed analyses of synaptic connectivity in the fly brain connectome convincingly supports the findings. The circuit- and receptor-level demonstration of interactions across sensory modalities in memory performance will be of interest to the broader neuroscience field.

    1. eLife Assessment

      This valuable study provides key insights into the role of the G protein-coupled receptor GPR34 in an Alzheimer's disease (AD) model. Notably, its findings differ, at least in part, from those of previous studies, although the underlying reasons for these discrepancies are not investigated or discussed. The data show that GPR34 deficiency enhances the transcriptional disease-associated microglia signature in microglia and provide solid evidence that myelin is a GPR34 ligand, although the relevance of myelin engulfment in AD is unclear. This study would be of interest for neuro-immunologists and AD clinicians.

    1. 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.

    1. eLife Assessment

      This short report is an important study that visual acuity declines nonlinearly with cone dropout, while eye motion partially compensates by improving sampling from remaining cones. The method for experimentally simulating cone dropout is compelling, leveraging state-of-the-art imaging and testing in human subjects.

    1. 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 convincing, supported by a manipulative field experiment and appropriate measurements of intermediary ecological processes. The work will be of interest to ecologists, conservation biologists, and rangeland managers, particularly those studying grassland herbivore interactions and livestock management.

    1. eLife Assessment

      This important study provides new insights into the regulation of cell organization and division in Trypanosoma brucei through the phosphorylation-dependent control of a kinesin motor protein by a polo-like kinase. The authors present convincing evidence, combining rigorous biochemical, cell biological, and imaging analyses, demonstrating that phosphorylation modulates kinesin localization and function, thereby influencing cellular organization and cytokinesis. The findings advance our understanding of the molecular mechanisms governing trypanosome cell division and will be of broad interest to researchers studying trypanosomes, cytoskeletal regulation, and eukaryotic cell division.

    1. eLife Assessment

      This important study demonstrates that nutrient resorption efficiency in the widespread wetland grass Phragmites australis is largely canalized by phylogeographic lineage, ecotype and geographic origin, rather than responding plastically to short-term salt stress. The findings have implications beyond plant ecophysiology because they suggest that predictions of wetland nutrient cycling under increasing salinization should account for the genetic composition of plant populations. The evidence supporting the central conclusions is compelling, based on a well-designed common-garden experiment involving 110 genotypes, paired control and salinity treatments, and convergent metabolomic, ionomic and whole-plant evidence confirming that the treatment imposed substantial physiological stress. The interpretation is nevertheless limited to one growing season and a single, moderate salinity treatment, leaving open whether chronic, more severe or multigenerational exposure might induce plastic or transgenerational responses; further clarification of the relationships among phylogeographic lineage, ecotype and latitude, and a more cautious interpretation of the variance explained by latitude, would strengthen the manuscript.

    1. eLife Assessment

      This important study introduces an open-source software package that improves the computational efficiency of whole-brain modelling and facilitates individualised model fitting in large neuroimaging cohorts. The evidence is convincing for the main computational and practical claims, supported by evaluations across multiple optimisation strategies, speed benchmarks, and demonstrations using human neuroimaging data. Its modular design and documentation should make it a resource that is of value to researchers interested in scalable and individualised brain network modelling.

    1. eLife Assessment

      This is a valuable study addressing a debated question in brain repair research by testing whether NeuroD1 can convert brain immune cells into nerve cells using a virus-free genetic approach and live imaging. The solid evidence presented here supports that, under the conditions tested, NeuroD1-expressing cells do not become nerve cells and instead retain their original identity; however, some aspects of expression level, injury timing, and cell-type composition would benefit from further clarification. This work will be of interest to neuro-immunologists.

    1. eLife Assessment

      This study uses a technically challenging long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The study provides solid evidence that ORNs have a circadian pattern of spontaneous firing that is Orco-dependent and yet that Orco transcript abundance does express a circadian rhythmicity and that cAMP can modulate all Orco-dependent activity. Together with computational work, the work is valuable in proposing a provocative hypothesis that an Orco-centred post-translational feedback loop generates the circadian rhythm.

    1. eLife Assessment

      This fundamental work significantly advances our understanding of how contact-dependent antagonism enables keystone bacteria to establish and maintain their niche over time. The evidence obtained is convincing, supporting most of the conclusions drawn. This work will be of significant interest to the microbiome research community.

    1. eLife Assessment

      This study presents a valuable insight into the mechanism of action of With-No-lysine (K) kinases (WNK) in the insulin-dependent signaling in the context of learning and memory. The study uses solid methodological approaches that align with the current standards in the field. The revised manuscript, which includes diverse models ranging from mouse to cell systems assessed by a broad range of complementary techniques, convincingly argues that WNK signaling contributes to neuronal function in insulin-sensitive brain regions such as the hippocampus through its effects on GLUT4 trafficking.

    1. eLife Assessment

      This manuscript presents a valuable computational tool for identifying 3-5 gene regulatory network topologies capable of generating oscillatory dynamics. The application of Monte Carlo Tree Search to circuit design is novel and effectively expands the scale at which non-linear behaviours can be explored in silico. The efficiency of the proposed algorithm is convincing, and the work will be of interest to the systems and synthetic biology communities. While the generality of the identified circuit properties is constrained by the simplifying modelling assumptions and parameter choices, the methodological contribution represents a significant advance in the field.