eLife Assessment

This fundamental study identifies GVIN as a previously unrecognized interferon-induced antimicrobial GTPase and establishes its role in cell-autonomous immunity against intracellular Burkholderia. The compelling data demonstrate that GVIN assembles into coat-like structures on the bacterial surface and restricts BimA-dependent actin-based motility through a mechanism independent of GBP1. These findings expand our understanding of interferon-induced host defense mechanisms and reveal a distinct pathway by which human cells restrict the intracellular spread of bacterial pathogens.

eLife Assessment

This study represents an important contribution to the study of decision-making under risk, bringing an interdisciplinary approach spanning economic theory, behavioral neuroscience, and computational modeling to test how choice preference is influenced by rare and extreme events. Using a novel experimental design, the authors present evidence that rats are indeed sensitive to these rare and extreme events despite their infrequent occurrence, driven primarily by an almost complete avoidance of "Black Swans" - rare and extreme losses. Motivated by economic theory, computational models of the choice behavior provide solid evidence of a distinct distributional effect, in which rare outcomes are treated as a differently-weighed contributor to the overall expectation associated with each option. Noting the inevitable difficulty in empirically testing the impact of rare events in animal tasks, these results bring a novel interdisciplinary perspective to a question of broad interest for understanding decision-making in complex probabilistic environments through the lens of economic choice.

eLife Assessment

The study provides an important advance towards understanding how spatial and temporal transcriptional programs are integrated to regulate lineage-specific chromatin and enhancer activation. The functional evidence is currently based on limited evidence, but the current data provide a solid correlative and conceptual foundation. Functional experiments directly linking Gsb occupancy to chromatin state and regulation of some lineage-specific targets would further strengthen the causal interpretation of the model. Clarifying the scope of conclusions and explicitly acknowledging the technical limitations of current chromatin assays would provide a more balanced interpretation of the manuscript.

eLife Assessment

This useful manuscript presents evidence that the major contribution of the lysine methyltransferase KMT2A to ribosomal gene transcription regulation is through promoting histone acetylation rather than H3K4 methylation, in part through interactions of KMT2A with PCAF. Some of the claims in the paper are unsupported by the evidence and therefore viewed as incomplete. Additional experiments demonstrating a more direct and causal link between PCAF and KMT2A would elevate the key conceptual advance that this new axis influences epigenetic pathways through an unconventional histone acetylation pathway. This work will be of interest to those studying transcriptional regulation and chromatin remodeling.

eLife Assessment

This study provides invaluable insights into the field of genomic prediction of traits by demonstrating how machine learning algorithms can integrate genomic and transcriptomic data and handle nonlinearity, providing important comparative prediction results across environments. The rationale and analyses conducted to integrate the two types of ~omics datasets in two environments are solid. The work will be of interest to plant geneticists and breeders, especially those interested in the genetics of environmental adaptation.

eLife Assessment

This useful study shows that loss of Samp1, a protein at the boundary of the cell nucleus, disrupts muscle cell development and is accompanied by changes in gene activity and genome organization. Some of the evidence is solid, but data to support the overall claims is judged to be incomplete. Controlled experiments and mutants to establish whether the changes in organization contribute to impaired development or follow from it would elevate the work. This work will be of interest to those in the genome organization and developmental fields.

eLife Assessment

In this potentially useful study, the authors explored the conformational dynamics of the intrinsically disordered protein p53-TAD and a cancer-associated variant by examining its conformation-dependent block of conductance through a MspA nanopore, in conjunction with molecular dynamics simulations. In principle, this combination of single-molecule recordings, hidden Markov modeling, and molecular dynamics simulations can provide a generally applicable platform for studying disordered proteins. While the experimental observations could be described as compelling, there are also issues regarding the apparently low statistics for the observed long-lived pore-blockage events and limited differences between WT and mutant simulations. Therefore, in the current form, the level of evidence is deemed incomplete and requires further validation.

eLife Assessment

This study offers an important set of findings on a previously unrecognised mechanism by which integrin-dependent trafficking, notably the recycling of CD98hc from endosomes to the plasma membrane, controls the abundance of a major amino acid transporter at the cell surface, with implications for a stable amino acid supply and metabolic homeostasis. The approach and results are convincing in showing the trafficking steps involved, although the experimental analysis is in places incomplete and would benefit from more rigorous approaches, deeper mechanistic characterisation, and stronger links to metabolic homeostasis. With these aspects strengthened, the work would be of interest to cell biologists working on trafficking and amino acid metabolism, as well as to the cancer cell metabolism community.

eLife Assessment

The authors make the valuable observation that directional memory during epithelial cell migration is enhanced in collective contexts compared to single-cell migration. While there is solid evidence for some parts of the work, the evidence linking directional memory to adherens junctions and vinculin dimerization remains limited. Key issues are that the Y1065E mutant may affect vinculin beyond its ability to dimerize, and focal adhesions were not directly compared across migration contexts.

eLife Assessment

This valuable study compares hippocampal-cortical functional connectivity to various other brain measures and examines their development across youth. It uses sophisticated analyses replicated in multiple datasets, but provides incomplete evidence to support the primary claim that hippocampal-cortical connectivity relates to cognitive maturation. The manuscript would benefit from a more nuanced consideration of the biological basis of some of the derived imaging measures and the limitations of the cross-sectional design. This work will be of interest to neuroimaging specialists and cognitive neuroscientists.

eLife Assessment

This study investigates the temporal dynamics of neural activity preceding self-initiated movements and makes a valuable contribution to this field. To overcome methodological and analytical limitations in previous work the authors introduce a matched control condition in which no response is required to assess when neural activity is predictive of self-initiated movement (using electro- and magnetoencephalography). Applying solid methods and machine-learning analyses, the authors show that a late-stage neural event is most predictive of upcoming movements (~100 ms before the response), whereas earlier neural activity is less informative. This finding contradicts previous work that suggested that earlier build-up of neural activity (e.g., starting 500 ms before the response) reflects the planning and preparation of movement.

eLife Assessment

Nui and colleagues tackle several questions concerning the assembly of the heterotetrameric kinesin-1 complex, examining intermolecular interactions between KHC and KLC and KHC with the cargo adaptor TRAK2. Aspects of the study using computational models and biopysical/biochemical analysis to examine the interaction between KHC and KLC and KHC and TRAK2 are useful, alongside an interesting new model for modulation of TRAK2 binding by KLC. The study will be of great interest to the community, but currently it is incomplete, with some claims partially supported.

eLife Assessment

The authors use a modeling approach to examine the effects of local and global perturbations on the electrophysiological properties of astrocytes: their modeling results suggest that local ionic changes associated with synaptic activity alter the membrane potential in fine distal processes but not in the soma. The work is valuable because it addresses a long-standing question in the field regarding key electrophysiological properties of astrocytes. The conclusions are convincing, but the manuscript would benefit from providing more details about the assumptions underlying the model and from incorporating more realistic astrocyte morphologies into the simulations.

eLife Assessment

This important study advances the HIV-1 vaccine development field by establishing six humanized immunoglobulin knock-in mouse models to facilitate the design and evaluation of HIV-1 vaccines. The evidence supporting the claims is compelling, with robust genetic engineering and rigorous baseline sequencing data, while additional assessment of BCR pairing, expression, and repertoire diversity would round out the characterization of these models. These mice offer the field a rich resource to evaluate vaccine candidates that induce broadly neutralizing antibodies against major epitopes of the HIV-1 envelope protein.

eLife Assessment

This useful study examines the role of Dynamin-2 in regulating neural progenitor behavior and fate by regulating Notch ligand and receptor function. Whilst the study is of interest because of the importance of these questions, the analyses are incomplete, and there are significant areas requiring additional experimentation in order to provide full confidence in the findings.

eLife Assessment

This valuable study provides a comprehensive metabolic and multi-omics characterization of the Ts66Yah mouse model of Down syndrome, identifying widespread metabolic, inflammatory, and molecular alterations that may help explain metabolic features observed in individuals with Down syndrome. The evidence supporting the authors' conclusions is solid, based on extensive physiological, molecular, and systems-level analyses in both male and female mice, although interpretations of sex-specific metabolic phenotypes and cross-model comparisons would benefit from additional clarification. The work will be of interest to researchers studying Down syndrome biology, metabolism, and the development and application of preclinical disease models.

eLife Assessment

This study provides a valuable analysis of T cell receptor repertoire organization in paired primary melanomas and sentinel lymph nodes from treatment-naive patients. The evidence for differences in repertoire architecture between these compartments is solid, but the evidence linking TCR sequence features and sequence-based communities to specific tumor antigens, particularly neoantigens, is incomplete. Additional benchmarking and robustness analyses of the community-based approach, together with more cautious interpretation of antigen specificity, would strengthen the study.

eLife Assessment

This important study investigates how the hippocampus distinguishes between reactive escape and anticipatory withdrawal during approach-avoidance conflict in rats performing a naturalistic decision-making task. Solid evidence supports the main finding that hippocampal neuronal representations differ during different types of defensive behaviors. The study will be of interest to researchers studying memory, navigation, and decision-making in the presence of competing rewards and threats.

eLife Assessment

This study provides important findings on the neural circuits underlying dishabituation of the olfactory avoidance response in Drosophila. The data as presented provide convincing evidence that the dishabituation involves distinct pathways from habituation. They show that reward-activated dopaminergic neurons provide input for within-modal dishabituation, while punishment-activated dopaminergic neurons provide input for cross-modal dishabituation. The work will interest neuroscientists, particularly behavioral neuroscientists working on habituation, neural circuits, and the dopaminergic system.

eLife Assessment

The authors study global neuropeptide changes in C. elegans mutants lacking functional BMP, using this as a viable and fertile animal model that exhibits consistent dyspepsia and chronic dietary restriction. The findings of this study are valuable as they provide a global picture of neuropeptide responses to starvation and detail a circuit from a sensory neuron to lipid metabolism in the gut. This work provides evidence that nutrient stress resulting from impaired food processing engages NLP-10-, NPR-35-, FLP-18-, and NPR-4-dependent signalling to promote fat utilization. However, the evidence is incomplete, as the order of action of the neuropeptides is weak.

eLife Assessment

This important study records basal ganglia output neurons in the substantia nigra pars reticulata of head-fixed mice performing self-timed reaching and licking tasks. Contrary to simple predictions of action selection and inhibitory gating by basal ganglia output, the authors report that most substantia nigra pars reticulata neurons modulate congruently across reaching, licking, and reaches to different targets. Optogenetic identification of substantia nigra pars reticulata neurons projecting to the central and lateral, orofacial superior colliculus shows that these congruent signals are routed to both output zones. Evidence from the recordings is convincing, while that from the projection-specific experiments is solid but rests on few animals and would be strengthened by increased power and clearer criteria for unit identification.

eLife Assessment

The study makes a valuable contribution to understanding the development of reflexes responsible for gaze stabilization. Using a combination of behavioural, electrophysiological and imaging approaches and analyses in developing Xenopus tadpoles, the findings provide a convincing demonstration that maturation of the angular vestibulo-ocular reflex in larval tadpoles involved increased modulation of silent but not spontaneously firing abudens motor units during horizontal semicircular canal activation, as well as increased myelination and innervation of the lateral rectus motor nerve. The findings will set the stage for future investigations to uncover the mechanistic underpinnings of the current observation.

eLife Assessment

This important study characterizes wing flicking in sexually immature Drosophila melanogaster females as a rejection response behavior that produces patterned acoustic signals and suppresses male courtship. The authors combine behavioral and acoustic measurements with manipulations of sensory input and targeted neuronal populations to provide solid evidence for how sexual maturation is signaled. With some clarification, additional information, and a more cautious interpretation of the findings in the discussion, this study will be of interest to neurobiologists and ethologists studying sexual maturation and behavior and will open up opportunities to address questions across several distinct areas, including sexual dimorphism, sexual maturation, and even the evolution of sexual signals.

eLife Assessment

This work presents a computational resource for identifying and classifying chloroplast outer envelope membrane β-barrel proteins (COB) across a broad range of plant species. By substantially expanding the available sequence space for this proteome, the COB database will serve as a potentially important resource for researchers working in diverse areas, including chloroplast protein import, outer envelope membrane biology, and membrane protein evolution. Although the computational framework and broad comparative analyses are generally solid, the limitations of the negative training set and the similarity-based sequence expansion approach may require further implementation. In addition, some of the broader biological implications need to be more carefully addressed, as they remain to be validated experimentally.

eLife Assessment

This valuable study presents a computational model of meta-learning that bridges two known neural mechanisms of learning: through activation dynamics and through synaptic plasticity. The evidence that the model is a good match to data from a mouse perceptual decision-making task is convincing, but the evidence that it also matches data from a widely studied human multistep decision-making task is incomplete. This work will be of broad interest to neuroscientists and cognitive scientists studying reinforcement learning and decision making.

eLife Assessment

This important study provides an accessible comparative atlas of gene activity in sensory hair cells across four vertebrate species. The evidence is convincing, supported by comparative analyses and experimental validation, although technical differences between datasets and unclear definitions of cell maturity limit some interpretations. The resource will be of interest to researchers studying hearing, balance, sensory cell development and regeneration, and evolutionary biology.

eLife Assessment

This important study presents an efficient approach to storing and retrieving memories in large language models based on complementary learning systems theory, and highlights the gap between storing information and using it flexibly. The presented evidence for the efficacy of the technical implementation of the memory system is convincing. However, support for the proposed parallels with certain aspects of complementary learning systems theory and with biological memory systems more generally remains incomplete. This work will be of broad interest to cognitive and computational neuroscientists studying memory, as well as researchers developing memory systems for artificial intelligence.

eLife Assessment

Loss of POLQ function is synthetically lethal with BRCA1 or BRCA2 deficiency, as is pharmacological inhibition of its motor (ATPase) or polymerase activity. This important manuscript validates an inhibitor of the DNA polymerase theta (POLθ) motor domain in biochemical and cell-based assays and provides evidence of its efficacy against homologous recombination-deficient tumors in preclinical and clinical settings, particularly in combination with PARP inhibitors. The experiments are rigorous, the evidence is convincing, and the results are appropriately interpreted. This work will be of considerable interest to the ovarian cancer research community.

eLife Assessment

This study provides a valuable mapping of how genomic variation from a large collection of Klebsiella pneumoniae clinical isolates shapes bacterial fitness across 214 conditions. Solid data describe that fitness is strongly condition-dependent and that features can be advantageous under selection. Though the predictive, plasmid causality and GWAS association findings would be further strengthened by additional analyses ruling out population-structure confounding, these findings are of value for our understanding of the power of genotype to predict phenotype for this human pathogen.

eLife Assessment

This important study provides a 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. There remains concerns regarding comparisons between the effectiveness of different combinatorial transcription factor codes.

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 study will be of interest to the broad readership of eLife, spanning structural biology, drug discovery, and coronavirus communities.

eLife Assessment

By combining previously established mathematical models, this valuable study demonstrates that the opposite direction of surface contraction waves in Xenopus embryos and starfish oocytes can in principle arise from the same underlying mechanism. The modeling results, showing the effect of nuclear size and position, cell size, and nuclear Cdk1 concentration, are convincing and plausible but have not yet been experimentally verified.

eLife Assessment

Using genome databases, the authors performed solid bioinformatic analyses to trace the genomic history of the clinically relevant Staphylococcus aureus tetracycline resistance plasmid pT181 over the last seven decades. They discovered that this element has transitioned from a multicopy plasmid to a chromosomally integrated element, and the work represents a valuable demonstration of the use of publicly available data to investigate plasmid biology and inform clinical epidemiology. This work will appeal to researchers interested in staphylococcal evolution, plasmid biology, antimicrobial resistance and bacterial genome structure.

eLife Assessment

This important manuscript reports exceptionally preserved, millimeter-scale segmented bilaterian microfossils from the early Cambrian Fortunian Kuanchuanpu Formation in South China. The authors propose that these non-biomineralized animals were preserved through microbial pseudomorphs rather than direct phosphatization, filling a critical taphonomic and evolutionary gap in early animal evolution. The physical preservation and high-resolution imaging of the fossils are convincing, but the theoretical grounds for establishing "true segmentation" versus superficial annulation/homonomy remain underdeveloped and need revision and further context. The new fossils and their taphonomy will be of broad interest to the paleontology community and those interested in early animal evolution.

eLife Assessment

This study provides valuable insights into the architecture of the tripartite attachment complex in Trypanosoma brucei and how it may preserve mitochondrial genome anchoring during basal body movement. Cryo-electron tomography and structural modelling provide solid support for the observed variability in filament length and basal body positioning, although the proposed mechanism involving p197 repeat orientation awaits direct molecular validation. These findings will interest researchers studying mitochondrial DNA inheritance, organelle organization, and the cell biology of kinetoplastid parasites.

eLife Assessment

This study reveals valuable links between cell-penetrating peptide uptake and the cell cycle, membrane voltage and an endogenous potassium channel. The evidence is solid, and further experiments would strengthen the proposed mechanism and the degree of the mechanism's generalization. The findings will interest researchers working on delivery of therapeutic molecules into cells.

eLife Assessment

The study reports on the relative lipid permeabilities of different ribonucleotide isomers. The findings are valuable for prebiotic chemistry and protocell research because they offer an additional possible explanation for how the canonical ribonucleotide isomers were selected. The strength of the evidence is solid, being supported by experimental and computational approaches, although the step from differential permeability to selection is less firmly supported.

eLife Assessment

This valuable study compares hippocampal-cortical functional connectivity to various other brain measures and examines their development across youth. It uses sophisticated analyses replicated in multiple datasets, providing solid, albeit cross-sectional, evidence to support the primary claim that hippocampal-cortical connectivity relates to cognitive maturation. The manuscript would benefit from a more nuanced consideration of the biological basis of some of the derived imaging measures and the limitations of the cross-sectional design. This work will be of interest to neuroimaging specialists and cognitive neuroscientists.

eLife Assessment

This study provides a valuable resource describing the size, density, and synaptic proximity of mitochondria across thousands of neurons in the Drosophila brain, drawn from a well-annotated electron microscopy dataset. The evidence supporting the main descriptive findings is mostly solid, though some measured parameters contain internal inconsistencies and the proposed links between mitochondrial properties and neural activity or energy use remain speculative. The work will interest neuroscientists studying mitochondrial biology, energetics, and connectomics, and lays a foundation for future studies connecting mitochondrial organization to neural circuit function.

eLife Assessment

This is a valuable study that uses several operant paradigms to test Drosophila for the appetitive or aversive behavioral effects of self-activation of specific dopaminergic neuron (DAN) populations. The work provides solid data, although the range of paradigms and genetic driver lines will require more specific future evidence in case-by-case assays. The results suggest that a more nuanced view of the role of these neurons in ongoing behaviour and learning is necessary. The results will be of broad interest to the neuroscience community.

eLife Assessment

This important study provides a detailed analysis of the transcriptional landscape of the mouse hippocampus in the context of various physiological states. The main conclusions are convincingly supported: that most transcriptional targets are generally stable, with notable exceptions in the dentate gyrus and with regard to circadian changes. The authors comprehensively addressed the concerns raised in the first round of review.

eLife Assessment

This important study combines cortex-wide activity imaging and optogenetics to characterize large-scale changes in functional connectivity following administration of the psychedelic DOI, as well as the circuit mechanisms underlying them. It provides solid evidence that DOI reduces the modularity of cortical networks and has concurrent effects on both cortico-cortical and cortico-thalamic functional connectivity. The study will be of broad interest to basic scientists working on the circuit mechanisms of psychedelics, as well as to researchers studying humans who may wish to reverse-translate their findings into mice.

eLife Assessment

This study provides valuable insights into how the timing of dopamine signals can influence associative learning and memory in fruit fly larvae at the single-cell level. Combining optogenetic manipulation of individual dopaminergic neurons and computational modeling of circuit computations provides some convincing evidence for the underlying circuit-level mechanisms. However, there are also aspects of incomplete evidence that require key control and validation experiments. The work will be of interest to researchers studying the neural mechanisms of learning and memory.'

eLife Assessment

This paper provides fundamental data on the ultrastructural signatures of neuromodulatory axons in mouse cortex obtained from exceptionally high-quality correlated light- and volume electron microscopy. They report unique vesicle and synapse configurations of cholinergic and serotonergic axons, providing compelling structural support for volume transmission.

eLife Assessment

This important study examines the relationship between climatic niche limits and extinction risk across more than 23,000 terrestrial vertebrate species. The large comparative dataset and phylogenetic analyses indicate solid evidence that species with lower upper thermal niche limits are more likely to be classified as threatened, whereas associations with aridity limits are less consistent. However, the treatment of data-deficient species and unclear definitions of niche metrics warrant further scrutiny, and the analyses do not establish that climate or land-use change drives the observed patterns. The findings will interest researchers in macroecology, global change biology, and conservation.

eLife Assessment

This work provides an important set of findings using sensory preconditioning procedures that advance our understanding of the circumstances that influence the integration of discrete learning experiences. The evidence supporting the conclusions is solid, as the study used multiple different conditions to differentiate between different theories of memory integration. Moreover, the findings should be of broader interest to the learning and memory field for considering the role of the medial temporal lobe in how separate experiences are integrated.

eLife Assessment

This study makes an important 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 creative and timely study uses an innovative cybrid approach to provide convincing evidence that mitochondrial variation influences telomere maintenance. Although the proposed molecular mechanism requires further validation and the evidence for telomere-length inheritance in humans remains preliminary, the work represents an important advance at the intersection of mitochondrial and telomere biology, with broad implications for aging and genome stability.

eLife Assessment

This study presents an important 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 solid, although the proposed regulation of chloride transporters is inferred rather than directly demonstrated in this model. The work will be of interest to researchers studying chloride homeostasis, inhibitory neurotransmission, and epilepsy.

eLife Assessment

This is an important study establishing the mechanistic principles on how NUP98-KDM5A phase separates together with H3K4me3 chromatin in leukemia. Methods are sound and results are convincing, providing a framework to understand gene expression changes in leukemia patients.

eLife Assessment

This valuable manuscript contains exciting data that has the potential to advances understanding of how psilocybin acutely alters decision making by modulating the impact of outcomes on future choices and altering how prefrontal cortex neurons encode outcomes. While the experimental paradigm, behavioral and neural analysis are elegant, the strength of evidence is, at present, incomplete given the lack of a saline treated comparison. This work will be of interest to behavioral and computational neuroscientists studying decision making, flexibility, or psychedelics.

eLife Assessment

This study provides valuable insights into humans' ability to generalize learned structural knowledge to new experiences that share underlying graph components but involve different stimuli. The behavioral and MEG evidence is solid, broadly supporting the transfer of abstract structural knowledge across contexts, although the findings speak more directly to the reuse of individual structural components than to their recombination. This study will be of interest to cognitive neuroscientists studying structure learning, abstract representations, and the generalization of knowledge across contexts.

eLife Assessment

This study provided useful information regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, while some behavior and imaging data are compelling, limitations in the motor-learning task design and data analysis make it difficult to support the central conclusions.

eLife Assessment

This paper presents a collection of analyses relating structure and function in the whole-brain Drosophila EM connectome and whole-brain calcium imaging data. The linkage of detailed anatomical structure with population activity is of broad interest in circuit neuroscience in light of increasingly detailed brain maps, but the methods used made the evidence incomplete due to indirect consideration of biological detail such as neurotransmitter identity and assumptions about the relationship between structural correlations and functional correlations. The conclusions are useful for specific network observations, but a more thorough analysis of the anatomical and functional data is needed to support the overall claims.

eLife Assessment

This valuable study compares orthogonal approaches for detecting RNA chemical modifications and provides a helpful framework for improving the reliability of RNA modification identification by direct RNA sequencing. The evidence supporting the technical benchmarking claims is solid, with multiple complementary controls, including in vitro-transcribed RNA, chemical inhibition of METTL3, and orthogonal m6A mapping. However, claims regarding relative method accuracy and cell-type- and isoform-specific biological differences remain less well supported due to limited biological replication and validation.

eLife Assessment

This study reports the relative importance of Tie1 and Tie2 signaling for atrial versus ventricular trabeculation. It is an important study and is one of the few works to date that have carefully and simultaneously analyzed these two processes. In line with a previous study in zebrafish, the authors demonstrate key differences between atrial and ventricular trabeculation. While the imaging and quantitative analyses are conducted using solid and validated methodologies throughout the manuscript, future studies using additional experimental approaches will be invaluable to further establish the underlying mechanisms.

eLife Assessment

This valuable study relating brain anatomy to reading ability in children studied longitudinally finds that a difference in sulcal anatomy is more predictive of reading ability than cognitive measures. The evidence that this anatomical difference is predictive and confers some benefit in the connectivity between brain areas is based on careful analyses and is solid. The findings would be of interest to researchers studying brain and cognitive development.

eLife Assessment

This study shows that the compound Yoda potentiates the function of the PIEZO2 channel, challenging the assumption that they selectively activate PIEZO1. This is an important finding and the evidence supporting this claim is solid. The authors have addressed the methodological and conceptual issues raised during review. Overall, this work will be of broad interest to researchers working with PIEZO channels across various biological scales.

eLife Assessment

The study investigates, from multiple angles, the still-debated function of insect rhodopsin-7 (Rh7). The authors present compelling results for its ancient phylogenetic origin across pan-arthropods, a non-visual role based on expression analyses in the fly brain, an unusual G-protein signalling pathway, and - using behavioural genetics - that Rh7 affects how Drosophila melanogaster interprets and responds to light-dark transitions. Through this, the work provides fundamental new insights into the evolution and function of non-visual opsins.

eLife Assessment

This study provides important information on the role of ErbB4 expression in parvalbumin-positive cells in relation to olfactory behaviour and circuit dynamics in the olfactory bulb. The central question is both timely and novel, and the findings could shed light on the critical role that ErbB4 may play in modulating olfactory bulb cell function and olfactory perception. The authors conducted a comprehensive set of experiments which provide solid evidence in support of their conclusions. However, some concerns remain regarding the technical approaches used, such as spike sorting and control/baseline comparisons.

Editors Assessment:

This Technical Release (software) presents a serverless cloud workflow for the computationally intensive alignment step of single-cell RNA-seq processing, extending the authors’ earlier serverless approach for bulk RNA-seq. Hung et al. built on the Piscem-Alevin-Fry pipeline and implemented it with AWS Lambda functions, working around their memory, storage and runtime limits by splitting large FASTQ files into four-million-read shards, streaming inputs from S3 straight into the aligner, and merging shard outputs as they complete. Because every stage overlaps, alignment adds only seconds beyond the cost of splitting and uploading. Compared with an optimized 32-thread on-server run on identical EC2 hardware, the serverless workflow was faster for all three datasets tested (two 10x Genomics PBMC datasets and a 450 GB, 13-sample MorPhiC pancreatic differentiation knockout dataset). The speedup grew with dataset size, from 1.27× to 1.93× to 7.01× for the largest, cutting about 2.4 hours of alignment to under 21 minutes, with outputs validated as identical to the conventional pipeline. The authors are transparent that this speed comes at a cost: the serverless runs were more expensive at list prices, though the premium shrank to about 13% for the largest dataset, and gains for small datasets are limited by driver-side preprocessing. With open-source code under an MIT license, an automated orchestration script, and deposited reference index and count matrices, this is a useful and reproducible template for processing large single-cell datasets, and for applying serverless computing to other bioinformatics workflows.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This Technical Release (software/workflow paper) presents Poly Pipeline, an open-source spatial transcriptomics workflow designed to handle the data sparsity, fragmented proprietary formats and duplicated-gene complexity that make polyploid plant genomes difficult to analyze. Carvalho et al. combine a converter that turns h5ad and GEM files into the GEF format used by Stereopy, quality filtering, Louvain, Leiden and Spatial Leiden clustering, a user-defined “anchoring” step for assigning regions, and highly variable and marker gene detection. Optional hdWGCNA co-expression networks are built on KNN-derived metacells, intended to retain low-expressed duplicated genes that would otherwise be discarded as dropouts. The pipeline was developed on a hexaploid wheat seed Stereo-seq dataset and benchmarked on rice, Arabidopsis and mouse data in different formats. Spatial Leiden gave more cohesive tissue domains than standard Leiden (15 versus 26 clusters in wheat), and the largest dataset (40,248 cells, 70,766 genes) ran in about 23.5 minutes using a peak of 31.8 GB of RAM. The benchmarking mainly shows that the workflow runs reliably and produces spatially coherent domains across organisms and formats. It does not directly test the claim that hdWGCNA better preserves duplicated-gene signatures, so that remains largely supported by argument rather than comparison with other methods. Nonetheless, with the code available on GitHub under an MIT license (with Zenodo, WorkflowHub, RRID and bio.tools entries), this provides a reproducible, HPC-ready framework that should help plant researchers working with complex genomes and multi-platform spatial datasets.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This Data Release presents shotgun metagenomic sequencing data from the oral microbiome of patients with oral squamous cell carcinoma (OSCC), a setting where most previous studies have used 16S rRNA amplicon sequencing with limited species-level resolution. The authors sequenced dental plaque, saliva and tumor tissue from 10 OSCC patients, alongside plaque and saliva from 10 healthy controls, on the Illumina MiSeq platform. After three control saliva samples failed quality control, 46 samples remained, with roughly 75,000-100,000 reads per sample after filtering. Reads were classified with Kraken2 and Bracken, and the sequencing data are deposited in NCBI, with supporting data in GigaDB and a Conda-based pipeline on GitHub. The authors report that dental plaque had the highest diversity, that saliva was more homogeneous, and that tumor tissue had a distinct profile dominated by taxa such as Sellimonas catena, Escherichia coli and Lacrimispora sp. HJ-01. The plaque of OSCC patients was enriched in Pyramidobacter piscolens and Parvimonas parva, compared with Streptococcus koreensis in controls. The authors are open about the limitations of this small, convenience-sampled exploratory cohort: oral hygiene differs markedly between patients and controls, 90% of participants are female, and no negative extraction controls or mock communities were included. The taxonomic differences should therefore be read as hypothesis-generating rather than disease-specific. Even so, the matched multi-niche sampling, open data and reproducible workflow make this a useful resource for integration with other metagenomic datasets and for follow-up functional studies of the oral microbiome in OSCC.

This evaluation refers to version 1 of the preprint

eLife Assessment

This work presents valuable new data on the role of D-Serine and how it competes with its stereoisomer L-Serine to influence metabolism. The work presents a variety of convincing experimental data combined with simulated results to investigate the mechanisms focused on one-carbon metabolism, which is relevant for several research fields. However, some claims are only partially supported by data, and critical areas comparing L- vs D-Serine and further mechanistic studies are required. Furthermore, while the work has potential for various fields, the work has only been studied in a neural context.

eLife Assessment

This important study identifies two pairs of dopaminergic neurons (DA-WED) in Drosophila that coordinate cardiac deceleration and locomotor responses to a mechanical threat. The conclusions are supported by convincing evidence from a combination of optogenetic, physiological, and behavioral experiments. The work provides invaluable insights into the neural coordination of behavioral and cardiac responses to threat and will be broad interest to neuroscientists, physiologists, and researchers studying brain-body interactions.

eLife Assessment

This study utilizes a two-choice assay to examine how groups of Drosophila melanogaster respond to temperature changes. The findings are useful, offering focused importance for the collective decision-making community. However, the strength of the evidence is incomplete, as the current data only partially support the primary claims and the work lacks the necessary integration into the existing literature to contextualize the findings.

eLife Assessment

This fundamental paper describes the role of the Pre-rRNA in meiotic sex chromosome inactivation in mouse spermatocytes. The cytological and genome-wide analyses on components of the nucleolus and chemical inhibition of RNA polymerase I for rDNA transcription provided solid evidence to support the authors' conclusion. The results shown in the paper are of interest to researchers in meiotic chromosome structure and the nucleolus.

eLife Assessment

This study presents an important examination of the role of cis-acting versus trans-acting genetic variation in DNA methylation divergence between humans and chimpanzees and its relationship to gene expression. By differentiating fused interspecies tetraploid cell lines into multiple cell types, the study provides compelling evidence that cis-acting changes predominate in DNA methylation divergence. The evidence linking directional methylation divergence to lineage-specific selection and, particularly, to adaptive human phenotypes is less clear. This work will be of interest to biologists and evolutionary anthropologists studying the evolution and genetics of gene regulation, particularly in primates.

eLife Assessment

The authors established a novel three-dimensional culture system for stratified epithelia that allows epithelial cells to undergo epithelial-to-mesenchymal transition (EMT) and subsequent mesenchymal-to-epithelial transition (MET) while migrating through a membrane with 3.0-µm micropores, and, thus, provides a highly valuable tool to study EMT and possibly wound regeneration or metastasis. Furthermore, a set of experiments provides compelling data suggesting that TGF beta signaling and actin polymerization promote movement of epithelial cells into the pores, while Piezo1 and Keratin 6 prevent keratinocyte migration and EMT.

eLife Assessment

This important study describes computationally designed proteins that bind to the chemokine CCL25. The authors present evidence that some binders simply prevent chemokine binding to the CCR9 receptor, while one binder changes the downstream signaling triggered by chemokine binding. The evidence is convincing, showing a degree of selectivity between chemokine ligands that could be further improved. The study will be of interest to pharmacologists, cell biologists studying chemokine function, and protein engineers.

eLife Assessment

This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents an important addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. The experimental evidence supporting the core ideas is solid and provides mechanistic insight into how ITK deficiency promotes a tissue-protective Treg phenotype, although additional studies will be needed to further define the molecular pathways involved.

eLife Assessment

This manuscript seeks to understand the hierarchical temporal representation of social actions in the lateral visual pathway in the human brain. It introduces a potentially valuable methodological approach for characterizing the spatiotemporal dynamics of social-interaction representations, with the data supporting the hypothesis that the anterior portion of the superior temporal sulcus responds to communicative actions, and providing a temporal estimate of when it begins responding. However, the failure to recover several previously reported effects regarding mid-level representations in this and other visual brain regions, combined with unresolved concerns about the correspondence between EEG, fMRI, and stimulus-feature measures, limits confidence in the method's sensitivity and validity, rendering the current empirical evidence against a hierarchical feedforward architecture incomplete.

eLife Assessment

This valuable study identifies Gcn5 as a regulator of blood cell development in the Drosophila lymph gland, with links to autophagy and nutrient-sensing mTORC1 signalling. While the mechanistic ordering between Gcn5, mTORC1 and TFEB/autophagy remains less fully resolved, the evidence is solid that perturbing Gcn5, autophagy genes and mTORC1 activity affects blood cell homeostasis. The work will be of interest to researchers studying developmental haematopoiesis, metabolic regulation and autophagy.

eLife Assessment

This important study extends a model of cortical normalization (ORGaNICs) to interacting cortical areas and shows that communication through coherence and communication subspaces can arise from a single set of dynamics. The evidence is convincing, showing analytically that contrast-dependent gamma dynamics and a low-dimensional inter-areal communication subspace arise from one parameter set. The work will interest neuroscientists and theorists concerned with inter-areal communication, cortical oscillations, and divisive normalization.

eLife Assessment

Using their unique Fish-On-Chips optofluidics platform, the authors make three important findings: the presence of precise coupling between saccades and tail flips can be used to discriminate between turning or gliding behaviours; aversive and appetitive chemosensory cues differentially modulate these behaviours; transformation from cue valence to behaviour is encoded by the pallium. The evidence supporting these findings is solid. The work advances our understanding of the ancient interplay between chemosensation and motor output through the modulation of eye-body coordination.

eLife Assessment

This study presents a valuable contribution to comparative cognitive neuroscience by directly mapping functional homologues of the human multiple-demand network in macaques using a matched spatial maze task. It provides solid evidence for functional correspondence between human and macaque cognitive control networks in dorsomedial frontal cortex and insula. However, given only two animals and no cross-animal convergence in parietal or ventrolateral prefrontal regions, claims that these regions form part of a macaque MD network should be read as provisional. The work will be of interest to researchers studying the evolution of cognitive control and cross-species neuroimaging.

eLife Assessment

This work has much novelty, supportive data, and the potential for changing thinking about melanoma biology with the discovery of MRGPRX4 as a relatively melanoma-specific G protein-coupled receptor. MRGPRX4 is normally restricted to peripheral sensory neurons, but it is aberrantly expressed in human melanomas; melanomas with neural-crest-like/invasive features were most likely affected. When ectopically expressed in murine melanocytes, MRGPRX4 drives melanoma development with metastasis; the mechanism appears to involve ligand-independent receptor signaling. Overall, the text presents this as a novel model of oncogenesis driven by re-expression of a sensory GPCR - this is an important study with compelling data.

eLife Assessment

This important study presents a cell-based screen for small-molecule activators of GCN2, an eIF2α kinase that regulates the Integrated Stress Response under diverse stress conditions. The authors identify a compound as a potent GCN2 activator with GCN1-independent activity under the tested conditions, providing a new pharmacological tool for probing GCN2 regulation. The revised manuscript provides compelling support for the central conclusions through a clearer description of the screening workflow, extended kinetic analyses, and demonstration that the identified compound causes a GCN2-dependent reduction in protein synthesis.

eLife Assessment

This valuable study investigates the cleavage-independent functions of Gasdermins in keratinocytes. The data collected using advanced microscopy methods and Western blotting are solid, but the main conclusions from these experiments remain partially supported. This paper is relevant to those studying cell-type specific inflammatory responses and client/cargo specificities of Gasdermins.

eLife Assessment

This study provides valuable insights into the role of thalamic nuclei in associative threat and extinction learning, underpinned by a large dataset and rigorous, multipronged analyses. The evidence provided is solid, supporting the main conclusions. The manuscript will be of broad interest to researchers in learning and memory, fear, thalamic circuitry, and related mental health conditions.

eLife Assessment

This valuable study uses single-cell profiling, lineage barcoding, and functional assays to examine drug-tolerant persisters in a BRAF-inhibited melanoma cell line. The data provide solid evidence that persisters arise from many lineages and have altered calcium handling and increased sensitivity to ferroptosis, although the lineage result is difficult to interpret without knowing how many cells survived treatment. The broader claim that these cells represent substates within a single persister state is less well supported, as it rests largely on transcriptomic projections, lacks time-resolved data, and has been examined in only one cell line.

eLife Assessment

This important study provides convincing novel evidence for a role of ripples in the hippocampus in visual short-term memory. The work is strong in employing state-of-the-art intracranial electrophysiology in epilepsy patients with multivariate pattern classifiers in the context of an elegant experiment, though some reviewers had concerns about interpretation of the ripple activity. The work will be of interest to researchers studying working memory and hippocampal ripples.

eLife Assessment

This is a very helpful study that presents an easy to use and reliable alternative to conventional and UV-based tetramers for the identification of antigen-specific CD8 T cells. The authors demonstrate that tetramers for a number of HLA alleles can be subjected to specific temperatures that facilitate peptide exchange whilst maintaining structural integrity, thereby generating detection reagents. They provide convincing evidence for this method, and the approach is likely to provide a useful alternative to generating reagents for examining T cell specificities.

eLife Assessment

This valuable study compares orthogonal approaches for detecting RNA chemical modifications and provides a helpful framework for improving the reliability of RNA modification identification by direct RNA sequencing. The evidence supporting the technical benchmarking claims is solid, with multiple complementary controls, including in vitro-transcribed RNA, chemical inhibition of METTL3, and orthogonal m6A mapping. However, claims regarding relative method accuracy and cell-type- and isoform-specific biological differences remain less well supported due to limited biological replication and validation.

eLife Assessment

In this important study, the authors demonstrate that generative AI techniques (restricted Boltzmann machine) can be used effectively to design and characterize mutational pathways of WW domains with different binding specificities. The computational studies are complemented by experimental validations, and the results provide convincing evidence supporting the idea that sequence landscape holds significance in understanding protein evolution from a transition path perspective. The minor weakness of the study has been largely addressed in the revision. The work will likely have a major impact on research aimed at understanding how evolution navigates fitness landscapes as well as reconstructing ancestral sequences.

eLife Assessment

In this manuscript the authors established a novel three-dimensional culture system for stratified epithelia that allows epithelial cells to undergo epithelial-to-mesenchymal transition (EMT) and subsequent mesenchymal-to-epithelial transition (MET) while migrating through a membrane with 3.0-µm micropores, and, thus, provides a highly valuable tool to study EMT and possibly wound regeneration or metastasis. Furthermore, a set of experiments provides compelling data suggesting that TGF beta signaling and actin polymerization promote movement of epithelial cells into the pores, while Piezo1 and Keratin 6 prevent keratinocyte migration and EMT.

eLife Assessment

This important study presents convincing findings on creating an exhaustive library of new enhancer-AAVs targeting astrocytes and oligodendrocytes with high potential for both basic and translational work, which will be of value to a large and growing community. The revisions appropriately addressed some of the previous concerns by updating description of glial biology in the Introduction and modifying text on experimental results and approaches. Overall, these amendments have strengthened the claims. The work will be of interest to neuroscientists working on glial cell biology.

eLife Assessment

The study provides an important empirical assessment of a non-adaptive hypothesis on transposable element evolution grounded in population genetics principles. The results suggest that the impact of genetic drift on transposable element amplification is not global, but depends on the phylogenetic scale being considered and can be overwhelmed by lineage-specific dynamics. The analyses are mostly appropriate, but currently incomplete in some aspects. Former conclusions will require additional crosschecks.

eLife Assessment

This important study tackles the challenge of analyzing genome integrity and instability in unicellular pathogens by introducing a novel single-cell genomics approach. It presents compelling evidence that this new tool outperforms standard whole-genome amplification techniques and describes a method that shows promise for probing questions regarding the biology of Leishmania and other microbial eukaryotes.

eLife Assessment

This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents an important addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. The experimental evidence supporting the core ideas is solid, but there is additional work needed to define the underlying mechanisms.

eLife Assessment

This important study presents evidence that the human brain encodes perceptual absence and numerical absence through distinct neural codes, while confirming that symbolic and non-symbolic forms of zero share a common representation. The evidence supporting this dissociation is convincing, although the tasks differ substantially, and it remains unclear whether the result reflects a divide between numerical and non-numerical absence or between perception and abstract concepts. The work will be of interest to neuroscientists and psychologists studying numerical cognition and the boundary between perception and higher-level cognition.

eLife Assessment

The authors provide valuable findings showing that GM-CSF prevents the loss of ILC3 populations during gut inflammation and inhibits pro-inflammatory cytokine production. They combine a preclinical model of gut inflammation in zebrafish with spatial transcriptomic analysis of samples from Crohn's disease patients. Although the data provided are clear and point to an anti-inflammatory role of GM-CSF, the strength of evidence remains incomplete especially on the nature of the cells involved. This work will be of interest to immunologists.

eLife Assessment

This study presents a useful inventory of genes that are up- and down-regulated in the mouse small intestine (duodenum and ileum) during the first postnatal month, along with a comparison to the human intestine and organoids; the data were collected and analyzed using solid and validated methodology and can be used as a starting point for additional validation of specific markers and for follow-up functional studies.

eLife Assessment

This is an important study that establishes a novel and enabling 3D super-resolution imaging approach for visualizing the nanoscale organization of AMPA receptors in thick mouse brain tissue. The biological findings are of importance and interest to the neuroscience field, with potential implications for neurodegenerative disease research. However, the evidence remains incomplete and some of the biological conclusions would benefit from strengthened quantitative analysis and revisions to the manuscript to ensure that the interpretations are appropriately aligned with what is supported by the analysis.

eLife Assessment

This important study shows that induced expression of transglutaminase 2 (TG2) fused to an antigenic peptide in mouse intestinal epithelial cells can trigger an anti-TG2 autoantibody response similar to that seen in celiac disease. The conclusions are supported by convincing evidence from a well-designed mouse model, although some additional experiments would strengthen the study. The work will be of interest to researchers studying celiac disease, other autoimmune conditions, and mucosal immunologists.

eLife Assessment

This study presents a valuable finding on the condition dependence of autophagy-mediated lifespan regulation in C. elegans. The evidence is solid, as the data broadly support the main claims, although variability between biological replicates in several of the performed experiments and mechanistic exploration with only a limited set of experimental techniques leave some conclusions less firmly established. The work will be of interest to researchers studying autophagy, ageing, and intracellular trafficking.

eLife Assessment

This study provides useful data on oscillatory coupling during speech planning, particularly suggesting that theta-band phase coupling may differentiate networks involved in object recognition and semantic-lexical retrieval. However, the strength of the evidence is incomplete because the absence of a linguistic manipulation and key confounds between the naming and control conditions limit the ability to attribute the reported effects specifically to word production, leaving the main mechanistic conclusions only partially supported.

eLife Assessment

This valuable study reports the architectural reorganization of the uterine luminal epithelium during the implantation period. Solid data are presented to support the main conclusion. This work is of interest to reproductive biologists and physicians practicing reproductive medicine.

eLife Assessment

This work presents valuable findings that identify ergosterol binding by the human ABC transporter ABCG5/G8 and show that ergosterol stimulates its ATPase activity more strongly than cholesterol, advancing understanding of sterol recognition and transport. The evidence from single-particle cryo-EM, molecular dynamics simulations, and biochemical assays is convincing, although additional structures and mutational studies would strengthen the proposed mechanism. These results provide key insight into the molecular basis of sterol recognition and regulation of ABCG5/G8 and will be of interest to researchers studying sterol transport and ABC transporter function.

eLife Assessment

This study presents an open-source reinforcement learning framework for the real-time, closed-loop optimization of spatiotemporal electrical stimulation in engineered neuronal networks. Using single-spike-resolution activity as continuous feedback, the authors provide solid evidence that their platform can identify stimulation patterns that drive specific activity motifs within a structurally constrained four-node circuit. While this reproducible system offers a valuable and accessible tool for interacting with biological neural networks in an adaptive manner, further validation is needed to determine how well these stimulation strategies generalize to larger, unstructured, or more conventional network architectures.

eLife Assessment

In this valuable study, the authors build on previous work demonstrating that the microtubule-associated protein CKAP2 functions at the mitotic spindle to regulate microtubule dynamics for proper chromosome segregation. Here, the authors show that CKAP2 and its paralog CKAP2L also function at the cilium to regulate cilium formation and Hedgehog signaling. The writing is clear, the experiments and data are generally convincing, and the proper data analysis is carried out; however, the evidence supporting the proposal that CKAP2 and CKAP2L compensate for each other is incomplete. Overall, the findings advance the field in our knowledge of microtubule-associated proteins with roles in both the mitotic spindle and the cilium.

eLife Assessment

This valuable study shows first that yeast strains potentially associated with the [MRPL10+] prion state strongly influence Drosophila cold tolerance and locomotor behavior, and it goes on to exploit natural variation to identify host pathways contributing to these responses. The evidence for host physiology and genetics is solid, but the evidence for MRPL10 prion causality is incomplete because the prion state has not been directly validated in the yeast strains used. The study would be substantially strengthened either by establishing the presence of the MRPL10 prion state, or by tempering the prion-specific causal claims and framing involvement of MPRL10 or other prions in the yeast strains as a plausible but unproven mechanism. The work will be of interest to many fields, including quantitative genetics, insect physiology and microbe-host interactions.

eLife Assessment

This valuable study presents a comparative framework for quantifying adaptation in SARS-CoV-2 and influenza H3N2 from changes in clade frequencies, enabling comparison of rates of adaptation across the two viruses on a common per-generation scale and showing that a simple count of mutations performs as well as much more sophisticated protein language models in predicting variant fitness. The evidence supporting the quantitative estimates of fitness flux is currently incomplete because the analysis assumes a single, time-independent fitness for each clade; for antigenically evolving viruses, clade fitness changes with population immunity, and it remains unclear how this assumption affects the estimated fitness flux. The interpretation of cumulative fitness flux in relation to changes in absolute fitness over time also requires clarification.

eLife Assessment

This important study investigates how retinoic acid signaling and retinal support cells called Müller glia might contribute to regional differences in the morphology and function of cone photoreceptors - light-sensitive neurons in the zebrafish retina - and may have broader implications for understanding how non-neuronal cells such as glia shape neuronal cell specialization in other regions of the nervous system. Despite well-executed imaging and pharmacological experiments, the evidence remains incomplete because the proposed mechanism is not established as specific to Müller glia, and broader effects on retinal development, cell growth, maturation, and/or differentiation could explain the observed shortening of light-sensitive structures. The work will interest researchers studying vision, nervous system development, and interactions between neurons and their supporting cells.

eLife Assessment

This valuable study examines excitation/inhibition (E/I) balance in the CA3-CA1 circuit of the hippocampus, yielding results that suggest a way in which CA1 neurons can perform mismatch detection. A combination of experimental and computational modeling results are presented and supported by solid evidence. The results are likely to be of interest to researchers who study computations in the hippocampal circuit.

eLife Assessment

This valuable study employs an innovative chemoproteomic and multi-modal experimental approach to support VDAC2 as a key functional mediator of STX effects on mitochondrial bioenergetics. The authors assimilated convincing evidence for targeting VDAC2 within POMC neurons to demonstrate neuroprotective therapies against Alzheimer's disease and menopause-associated neurodegeneration, with the potential to minimize adverse off-target side effects.

eLife Assessment

This important study investigates whether high-level physical reasoning is grounded in real-time bodily and vestibular signals using an innovative combination of virtual tool-use tasks and galvanic vestibular stimulation. The evidence is solid for the specific conclusion that ongoing vestibular information can influence selected aspects of physical reasoning in a context-dependent manner, while is incomplete for the broader mechanistic interpretations.

eLife Assessment

This important study shows that long-range somatostatin-expressing neurons in the ventrolateral periaqueductal grey that project to the rostral ventromedial medulla selectively suppress pain responses during conditioned fear. The evidence supporting these conclusions is exceptional, with methods spanning a novel cued fear-conditioned analgesia paradigm, cell-type-specific optogenetic activation and inhibition, anatomical circuit tracing, and in vivo spinal cord electrophysiology. These results will be of broad interest to systems and behavioral neuroscientists studying fear, pain, and descending pain-control circuitry.

eLife Assessment

This valuable study builds a novel auditory-motor paradigm to investigate how the brain learns associations between movements and their auditory consequences. Solid evidence is provided for early ERPs (50-100 ms latency) reflecting violations of established key-pitch mappings. The study is of potential interest to researchers studying audition, sensorimotor integration, or predictive coding, but some statistical analyses, however, could still be improved.

eLife Assessment

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

eLife Assessment

This important study examines how temporal and spatial discrepancies between an action and its visual feedback are combined in judgments related to the sense of agency. Using a virtual-reality reaching task and computational modeling, the authors show that both discrepancies influence self-attribution and that a multiplicative model outperforms the prespecified alternatives, a result reproduced in a preregistered replication. The evidence is convincing for the conclusion that temporal and spatial information is integrated. Other models - beyond multiplication - may in principle account equally well for the observed data; sharpening these claims and situating the findings more clearly within Bayesian accounts of cue integration would further strengthen this key contribution.

eLife Assessment

This valuable study evaluates how different learning curricula in a complex planning task impact performance. The authors provide convincing evidence across eight behavioral studies that practicing increasingly difficult examples of a concept before moving to the next concept benefits immediate performance, despite participants having a preference for the reverse - learning new concepts before practicing. However, there is incomplete evidence for claims about relevance to real-world learning settings, as the curriculum effects did not persist across a delay or support transfer to new problem types. The paper will be of interest to researchers studying learning curricula, problem solving, planning, and education.

eLife Assessment

The primary aim of this study is to measure the different dimensions of executive function in non-human primates and the classification of animals into distinct cognitive phenotypes. To achieve this, it uses a multi-task touchscreen battery for six rhesus macaques with repeated measurements to examine how performance across inhibitory control, shifting/learning, working memory, and updating covaries within and across individuals. Overall, this is an important finding with relevance for anyone interested in behavioural assessment of cognitive functions in non-human primates or dimensionality of executive functions. The strength of evidence is overall convincing, with some minor methodological weaknesses that should be addressable in future versions.

eLife Assessment

This valuable study uses chemogenetic inactivation techniques in behaving macaque monkeys to ask whether the locus coeruleus (LC), an area that is involved in the control of arousal, is also involved in regulating access to mental resources for a task that requires working memory. The data show that moderate locus coeruleus inhibition impairs foraging efficiency without affecting response times, total rewards accrued, or overall motivation. However, the evidence supporting the more specific claim that the locus coeruleus regulates cognitive and/or working memory function is currently incomplete, as the experimental design is confounded by elapsed time, lacks formal statistical interaction tests, and relies on behavioral measures that cannot cleanly separate effort allocation from working memory capacity or strategy shifts. These limitations may be ameliorated with further analyses.

eLife Assessment

This study suggests that caspases strengthen the antiviral response by cleaving Drp1, which otherwise restrains mitochondria-mediated type I interferon signaling. The authors report an important finding supported by solid evidence. However, further mechanistic work is needed to firmly establish whether apoptotic caspases are indeed required for Drp1 depletion in virus-infected cells.

eLife Assessment

This manuscript addresses an important and conceptually ambitious question by using a synthetic biology strategy to perturb ATP homeostasis in yeast and examine its relationship with replicative lifespan. While the lifespan phenotype is robust and the experimental approach is generally solid, the current evidence is limited to establish intracellular ATP abundance as the causal determinant of lifespan, particularly given the apparent uncoupling from NTT1-dependent ATP import and single-cell ATP levels, as well as the possibility of extracellular ATP-induced stress responses. Further clarification of the mechanistic interpretation, including more cautious treatment of Snf1/AMPK signaling and NTT1 transport directionality, will be needed before the biological significance of the findings can be fully assessed.