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.

eLife Assessment

This important study elucidates the roles of two lytic transglycosylase (LTG) enzymes in the progression of spore formation in the important 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.

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.

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.

eLife Assessment

This valuable 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 incomplete lineage sorting (ILS), introgression, and differential evolutionary rates of male and female antagonistic traits, offering valuable insights into sexual conflict and speciation.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

eLife Assessment

This valuable study compares the anti-HIV activity of human natural killer cell subsets and identifies CD56^dimCD16^dim 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.]

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.]

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.