eLife Assessment

This study provides an important advance in understanding how disordered proteins interact with cell membranes by identifying the sequence rules that enable aromatic residues to penetrate deeply into the membrane interior. The integration of complementary computational approaches, including molecular simulations, large-scale sequence analysis, and the development of an online prediction server, makes the work potentially impactful for the membrane protein and intrinsically disordered protein communities. The evidence supporting the main conclusions is generally convincing.

eLife Assessment

This is an important study on the role of Slap in restricting Src activity and proliferation of colonic cells in vivo. The authors present solid evidence that an EPHB2-SRC signaling axis stimulates the proliferation of colon precursors and is controlled by the Src-binding protein SLAP, whose loss promotes tumorigenesis.

eLife Assessment

This useful study describes a physical mechanism for the emergence of spiral patterns in the outer epithelial layer of the mammalian cornea independent of pre-patterning or guidance cues, using an agent-based model of self-propelled particles with alignment. The well constructed model show that spiral patterns can emerge from the interaction between the limbus position, cell division, extrusion, and collective cell migration. While the conclusions are solid, some significant questions related to the importance of topological defect remain, and the comparison between the model and data are so far mostly qualitative.

eLife Assessment

This important study contributes to our understanding of how epithelial cells establish polarity by identifying a hierarchy in which Par3 acts upstream of centrosome positioning and apical membrane initiation. The evidence supporting the main conclusions is convincing, and the authors addressed the unresolved questions about microtubule organization and the need for clearer integration of quantitative and conceptual points raised in review. The work will be of interest to cell and developmental biologists.

eLife Assessment

The authors show that innate defensive behavior in mice is shaped by threat intensity, reward value, and social hierarchy, highlighting how value and social context influence instinctive decisions. The authors provide a valuable characterization of escape behavior which approximates naturalistic conditions. Despite minor methodological limitations, the work provides a solid foundation for future investigation of how reward and social context interact to influence behavior.

eLife Assessment

This important study addresses a discrepancy between population-level growth laws and single-cell correlations. It shows, for flagellar and synthetic genes in E. coli, that while gene expression of certain genes reduces population-average growth, expression levels positively correlate with growth at the single-cell level. The measurements are convincing, and the proposed mechanism - inheritance of growth factors such as ribosomes during asymmetric division - is consistent with the data.

eLife Assessment

This fundamental study demonstrates that polarized second-harmonic generation microscopy can be used to probe the ON/OFF states of myosin in both permeabilized and intact muscle, making this key measurement accessible to a greater number of labs. This has the potential to help with the study of disease-causing mutations and our understanding of drug function. The methodology is well defined, and the results are convincing; however, there are some limitations to the interpretation of the data.

eLife Assessment

This useful study uses creative scalp EEG decoding methods to demonstrate that two forms of learned associations in a Stroop task are dissociable, despite sharing similar temporal dynamics. The evidence supporting the conclusions is solid, although it could be further strengthened with a modified experimental design. This paper would be of interest to researchers studying cognitive control and adaptive behavior.

eLife Assessment

This work of fundamental significance introduces a novel statistical model of spiking activity that incorporates continuous-time gain modulation. The authors provide exceptional evidence that the model outperforms earlier approaches and alternative candidates in capturing spiking responses across multiple visual areas in the macaque. Beyond its methodological contribution, the study offers new insights into how stimulus-driven variability and internally generated gain fluctuations evolve over time and between brain areas. The framework is likely to find broad application beyond the datasets examined here.

eLife Assessment

This valuable study uses repeated experience sampling to track the relationship between depressive symptoms and perceptual confidence. The central claim that depression impairs the integration of momentary confidence into a global sense of confidence is supported by solid, robust evidence. However, the largely subclinical, highly compliant sample with limited mood variability restricts the generalisability of the conclusions. This study will be of interest to researchers studying mood disorders and metacognition, as it suggests more ecologically valid ways to investigate how mental health influences metacognition.

eLife Assessment

This valuable 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, drawing on neural decoding techniques and Bayesian analyses, although some concerns remain about task design and decoding method, which could partly explain the lack of shared representation. The work will be of interest to neuroscientists and psychologists studying numerical cognition and the boundary between perception and higher-level cognition.

eLife Assessment

This valuable study presents a comparative dataset on crab locomotion to investigate the evolution of sideways walking. The evidence supporting the authors' claims is convincing. This work will be of broad interest to researchers in animal locomotion and evolutionary biology.

eLife Assessment

This important study investigates how the size of an LLM may influence its ability to model the human neural response to language recorded by ECoG. Overall, solid evidence is provided that larger language models can better predict the human ECoG response. This study will be of interest to both neuroscientists and psychologists who work on language comprehension and computer scientists working on LLMs.

eLife Assessment

This study demonstrates that toll-like receptor 4 in non-myeloid cells is a central regulator of leptomeningeal inflammation in the context of neonatal E. coli meningitis. The data, derived from conditional gene deletions in mice, and from cultured endothelial cells, are convincing and support the authors' conclusions. This work is important because it advances our understanding of the host cellular and molecular factors underlying meningitis pathogenesis, especially in the context of the vascular barrier breakdown.

eLife Assessment

This study employs state-of-the-art quantitative imaging and genomics approaches to address a fundamental question regarding the establishment of Polycomb domains during Drosophila embryogenesis. The authors identify the maternal-to-zygotic transition, rather than earlier developmental stages, as the critical window for Polycomb domain establishment, providing significant clarification of the timing of this process and they further investigate the roles of Zelda and GAGA factor, demonstrating that Zelda, but not GAGA factor, contributes to Polycomb domain establishment. Overall, the conclusions are well supported by the experimental evidence presented. These compelling findings advance our understanding of how Polycomb domains are established during early embryogenesis and have broad implications for chromatin regulation and developmental biology.

eLife Assessment

The study presents valuable findings on early behavioral phenotypes that arise in an ADHD-associated adgrl3.1 mutant zebrafish, using a new behavioral approach with a closed-loop OMR assay. The evidence supporting the claims of the authors is solid; however, the validation of the method and analysis is incomplete and would benefit from more rigorous approaches and validation practices. This work will be of broad interest to developmental biologists and behavioral neuroscientists.

eLife Assessment

This valuable cross-sectional longitudinal study leverages high-definition transcranial direct current stimulation to the left dorsolateral prefrontal cortex to examine its effect on procrastination behavior over an extended time span. The cross-sectional longitudinal study a 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 study presents a valuable human organoid platform for investigating neuron-immune interactions in Alzheimer's disease and modeling the interplay between innate and adaptive immunity in the context of amyloid pathology. The system has the potential to advance the field by enabling the study of human-specific neuroimmune interactions that are difficult to recapitulate in rodent models; however, the evidence supporting several central conclusions remains incomplete. Key claims, including the causal role of microglia-derived chemokines in T cell recruitment and the existence of a neuroinflammatory feedback loop, rely primarily on correlative observations and lack the mechanistic experiments necessary to establish causality; in addition, a major confounding factor, the non-autologous nature of the cellular components, is not adequately addressed. Despite these limitations, the study will be of considerable interest to researchers in neuroimmunology and Alzheimer's disease.

eLife Assessment

This valuable study presents a comparative analysis of the transcriptomic features underlying C. elegans longevity, providing insights into how different changes in gene expression can promote longevity. The authors present solid evidence with analysis and selected functional validation showing that some long-lived animals share common changes while others appear to use opposing strategies. The datasets and analyses contained within and the user-friendly website developed will be of interest to researchers interested in complicated transcriptomic analyses and/or the biology of aging.

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

eLife Assessment

This important study uses an elegant visual-anagram approach to test whether perceived animacy shapes visual working memory and guides visual attention while tightly controlling for lower- and mid-level image properties. The evidence is convincing and provides a rigorous demonstration that perceived animacy influences visual cognition beyond the contribution of its typical visual correlates. The findings will be of broad interest to researchers studying high-level vision, attention, and working memory.

eLife Assessment

This study provides important insights into the neural mechanisms linking sleep and long-term memory consolidation. By combining behavioural, genetic, imaging, and connectomic approaches in Drosophila, it identifies a target neural circuit that will be of broad interest to researchers studying sleep, memory, and neural circuits. The evidence supporting the involvement of the identified circuit in the regulation of sleep and memory is solid and represents a substantial advance in the field. Nevertheless, there is limited evidence to support the mechanistic claim that this circuit directly links sleep and memory consolidation within the available data, and some results should therefore be interpreted with appropriate caution.

eLife Assessment

This important work examines the effects of gaze on valuation signals in the human brain as participants choose between bundles of sequentially presented items food items. The paper provides convincing analyses of how gaze affects participants choice behaviour and how this varies across time. The work will be of interest to neuroscientists working on attention and decision-making.

eLife Assessment

This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.

eLife Assessment

This revised paper provides solid evidence for HGF-induced trafficking of the HGF receptor, MET, together with metalloprotease MT1-MMP into invadopodia and the role of this trafficking in triple-negative breast cancer (TNBC) cell invasion in vitro. The evidence could be improved with additional experimental controls and analysis, but the findings will be valuable for cancer cell biologists investigating TNBC.

eLife Assessment

This work establishes a valuable theoretical finding about how the spike timing dependence of inhibitory plasticity shapes recurrent network connectivity. The combination of theoretical analysis and simulations provides convincing evidence that effective inhibitory connectivity forms a so-called Mexican-hat profile when multiple inhibitory neuron types follow distinct learning rules. These mechanisms are thought to be implicated in the contextual modulation of neuronal responses to stimuli.

eLife Assessment

This set of studies provides important knowledge for the role of zona incerta neurons in motivation and food-seeking in mice. The evidence supporting the findings is convincing, with the use of multiple approaches and nice behavioral procedures to provide converging lines of evidence. Additional analyses and data from the current studies would further strengthen the evidence. This work will be of interest to those interested in motivation and its brain substrates.

eLife Assessment

This valuable paper reports on a measure of flexible brain state engagement, derived from fMRI, as a predictor of cognitive control. One strength of the study is the use of external datasets for validation and replication. The results are solid, although some may benefit from further explanation.

eLife Assessment

This valuable study aimed to explore whether sensory representations in the cortex reorganize on the same timescale over which behavioral changes first emerge. Convincing evidence is presented to show that reward-dependent plasticity takes place in the mouse barrel cortex within a single recording session as mice learn a whisker detection task. However, the evidence supporting the authors' proposal that this rapid reorganization may involve spontaneous reactivation of neurons that gain stimulus responsiveness during training is incomplete. The work will be of interest to systems neuroscientists studying cortical circuits and learning.

eLife Assessment

This valuable study describes a simple and robust approach for estimating information-limiting noise by splitting neural populations and comparing estimator values. The authors report more accurate and robust results compared to previous methods. The evidence for the robustness of the method is currently incomplete; some concerns regarding bias need to be resolved, and additional tests need to be provided on how the number of trials and neurons affect performance.

eLife Assessment

This valuable study establishes a novel genetic model for chronic, in vivo visualization of protein engulfment in brain macrophages from the naturally short-lived African turquoise killifish. The solid data presented here show that brain phagocytes exhibit transcriptional features resembling mammalian border associated macrophages and monocyte derived macrophages rather than classical microglia and that their engulfment capacity declines with age, providing a resource for future studies on brain immune cells in teleosts. This research will interest a broad audience across developmental biology, genetics, neuroimmunology, aging research, and evolutionary biology.

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

Editors Assessment:

The paper presents high-quality reference genome assemblies for two closely related widow spider species, the Australian redback (Latrodectus hasselti) and the New Zealand endemic katipō (L. katipo), providing an important genomic resource for studies of venom evolution, adaptation, and conservation biology. Rather than simply reporting assembly statistics, the authors compare the genomic architecture of the two species, showing that both genomes are highly complete (BUSCO scores >94%) and share similar repeat content, while differing in overall genome size, scaffold continuity, and predicted gene numbers. The chromosome-level assembly achieved for L. katipo enables more detailed comparative analyses than previously possible, whereas the more fragmented L. hasselti assembly still captures a highly complete gene repertoire. Ortholog analyses reveal substantial conservation between the species but also indicate lineage-specific differences, with evidence suggesting either gene duplication in L. hasselti or gene loss in L. katipo, providing insight into their divergent evolutionary histories despite their close relationship and contrasting ecological distributions. Beyond generating sequence data, the study establishes foundational genomic resources that will facilitate future investigations into venom gene evolution, population genomics, species divergence, and the conservation of these ecologically and medically significant spiders.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This Data Release presents a multilingual dataset collected from a survey of participants and community members at the 2025 DBCLS BioHackathon, with the goal of understanding how AIis being used in bioinformatics and related scientific fields. The survey, available in English, Japanese, and Thai, gathered responses from 105 participants about AI usage frequency, applications, challenges, institutional support, satisfaction, concerns, and demographic information. The released dataset includes anonymized raw responses, a cleaned English-language version for quantitative analysis, the original questionnaire, a data dictionary, and a translation lookup table to support reproducible research. To protect participant privacy, the authors carefully removed personally identifiable information. This openly available resource provides researchers with valuable data for studying AI adoption, evaluating policy and institutional support, and developing methods for analyzing survey data related to AI use in scientific research. Overall, this work contributes a well-documented, reusable dataset that can help inform future research on the evolving role of artificial intelligence in genomics, bioinformatics, software development, and the broader scientific community.

This evaluation refers to version 1 of the preprint

eLife Assessment

This important study builds on previous work from the same authors to present a conceptually distinct workflow for cryo-EM reconstruction that uses 2D template matching to enable high-resolution structure determination of small (sub-50 kDa) protein targets. The paper provides convincing evidence that the density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template, and it provides an insightful quantification of the level of model bias that remains in the resulting reconstructions. The convenient visualisation of small molecules bound to protein targets of a known structure will be relevant for the pharmaceutical industry.

eLife Assessment

This study demonstrates a critical role of the glycolipid membrane protein insertase (MPIase) in the twin-arginine translocation (Tat) pathway, a protein translocation system that is conserved across all domains of life. The successful reconstitution of the bacterial Tat system in both bacteria-derived and artificial liposomes provides solid experimental evidence that MPIase has a broader role in membrane protein translocation than previously recognized. By revealing the essential function of a nonproteinaceous membrane component in catalyzing a core cellular process, this work offers fundamental insights into the molecular mechanisms of protein translocation.

eLife Assessment

The authors provide convincing evidence that, during early mouse embryogenesis, distal visceral endoderm cells migrate in a coordinated, intermittent start-and-stop manner along an axis that correlates with the asymmetric morphology of the ectoplacental cone. This fundamental finding is supported by high-quality live imaging and quantitative image analysis, while computational modelling suggests that the observed intermittent behavior may be explained by the movement of a cohesive cell group through a viscoelastic tissue, rather than by fluctuations in DVE migration velocity itself.

eLife Assessment

This valuable study provides fMRI evidence for a hierarchical representation of sequence, arranged along the anterior-posterior axis of the entorhinal cortex, as well as evidence from human single-unit recordings for sequence position coding in the hippocampus and entorhinal cortex. Weaknesses include tenuous links between the single-unit and fMRI datasets, incomplete evidence for some claims, lack of discussion of relevant hippocampal literature, and potential over-interpretation of the findings in relation to rodent grid coding. This work will be of interest to researchers studying memory, sequence representations, and spatial coding in the medial temporal lobe.

eLife Assessment

This study provides valuable evidence that glycogen phosphorylase is unlikely to represent an effective insecticidal target in Plutella xylostella and that diflubenzuron does not directly inhibit this enzyme. The combination of biochemical, molecular and physiological approaches provides convincing data to support these conclusions, although the proposed metabolic compensation mechanism is supported primarily by indirect evidence and would benefit from direct demonstration.

eLife Assessment

This important study provides convincing evidence that envelope-carrying Ty3/gypsy retrotransposons (errantiviruses) are ancient and widespread across nearly all major animal phyla, with distribution in many lineages that are consistent with recent or ongoing genomic expansion. Using comprehensive phylogenetic and AlphaFold2-based structural analyses, together with new host-taxonomy concordance tests, the authors show that these elements independently acquired membrane fusion proteins early in metazoan evolution, likely predating the bilaterian-non-bilaterian split. The work offers significant insights into the deep evolutionary roots of retroelement-envelope associations and the origins of retroviruses.

eLife Assessment

In this important study, the authors have performed a zebrafish drug screen to identify suppressors of atherogenic lipoproteins. They utilize a well-established LipoGlo assay to find molecules that modulate these lipoproteins, identifying 49 potential hits and they perform validation experiments, including studies linking enoxolone to its likely inhibitory effect on a specific transcription factor, HNF4alpha. Overall, the results are convincing and robust, and will open up new areas of exploration for those investigators interested in in vivo lipid biology.

eLife Assessment

This study provides important insights into how researchers can use perceptual metamers to formally explore the limits of visual representations at different processing stages. The framework is compelling and the data support the claims.

eLife Assessment

This is an important study establishing the mechanistic principles 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

In this important study, the authors describe the mechanisms by which CDK4/6 overexpression mediates resistance to Osimertinib in EGFR mutant lung cancer models. Their data show that CD4/6 overexpressing cells had increased replicative stress and genomic instability. The evidence is solid, but inclusion of some additional experiments would make this stronger.

eLife Assessment

This study presents a potentially important structure-interaction model describing recognition of polymyxin antibiotics by the human transporter hPepT2 and applies these insights to guide the rational design of potent polymyxin B analogues with reduced nephrotoxicity. The conclusions are supported by compelling evidence, integrating molecular dynamics simulations, transporter mutagenesis, uptake assays, protein expression analyses, antibacterial testing, and mouse nephrotoxicity studies, although some mechanistic interpretations remain limited by altered transporter expression and the absence of direct structural validation.

possible conclusion

possible evidence for topic/subtopic

possible topic/subtopic

eLife Assessment

This valuable study provides solid evidence that N6 methylation of A74 by METTL3 is required for efficient translation directed by the SARS-CoV-2 5′UTR in uninfected cells, likely by limiting access of protein factors to the 5′UTR that are necessary for efficient translation. These findings advance our understanding of the role of RNA modification in coronavirus replication and m6A-mediated regulation of gene expression more broadly, while further supporting METTL3 as a potential anticoronaviral therapeutic target. However, the evidence that m6A acts by destabilizing the third stem-loop (SL3) of the 5′UTR remains incomplete. The impact of the study would be strengthened by biochemical analyses directly assessing structural changes in the 5′UTR induced by A74 methylation.

Most African Americans were living in the south as slaves in what is the U.S. now, around the late 1700's slaves could not learn to read or write because of harsh laws. Most of the African American literary traditions became oral and not written around that time. Their literature started to get past down to many people, and generations using the oral tradition.

eLife assessment

In this manuscript, Rademacher and colleagues examined the effect of a chemogenetic approach on the integrity of the dopamine system in mice with chronically stimulating dopamine neurons. These findings are important: (1) This approach led to an axon-first degeneration over a time course (2–4 weeks) that is suitable for experimental investigation; (2) The finding that direct excitation of dopaminergic neurons causes differential degeneration sheds light on dopaminergic neuron selective vulnerability mechanisms. Overall, the strength of the evidence is solid, but the behavior experiments that do not include a CNO control provide incomplete support for the findings.

eLife Assessment

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

eLife Assessment

This study identifies apoptotic retinal ganglion cells as a potential source of ATP-mediated activation of PANX1 channels that initiates developmental retinal Ca²⁺ waves and coordinates microglial activation and vascular outgrowth during postnatal maturation. The work is important because it proposes an integrative framework linking programmed cell death, spontaneous neural activity, immune responses, and angiogenesis into a self-regulating developmental loop. Although the mechanistic conclusions would benefit from complementary genetic validation, the study provides a convincing foundation for future investigations into the coordination of neural circuit development and tissue remodeling.

eLife Assessment

This convincing contribution addresses a question of practical importance: when collecting tilt-series data, what is the optimal angular step size between successive tilt images? The work provides valuable practical insights into cryo-ET data acquisition by demonstrating that balancing two competing demands - sufficient dose per individual tilt image and fine angular sampling - is essential to achieve high-quality tomographic reconstructions. They demonstrate that tilt-series acquired with finer increments (1-3 degrees) yield superior alignment accuracy and improved template-matching performance.

eLife Assessment

This is a valuable study on the metabolic adaptations upon succinate dehydrogenase loss in cancer cells. If confirmed, this study will offer some therapeutic vulnerabilities in treating SDH-deficient cancer. However, the evidence supporting the authors' claim is incomplete and would benefit from additional experimental evidence. This study will be of broad interest for cancer biologists focusing on metabolism.

eLife Assessment

This valuable study documents, for the first time, the degree of preference for contralateral versus ipsilateral forelimb movements in the motor cortex of mice, revealing subtly distinct profiles across cortical areas, with the orofacial region showing comparatively little limb selectivity relative to the forelimb motor areas. The experiments and analyses are, in general, solid and well-designed, and the data support the paper's conclusions.

eLife Assessment

This manuscript employs cryo-EM, mutational analysis, and biochemical assays to explore the molecular basis by which glutamine promotes filamentation and regulates the activity of human glutamine synthetase (hGS) by stabilizing interactions between hGS decamers. The combined structural and biochemical data supporting the proposed mechanism are solid, although the evidence for a higher-order filamentous architecture and the precise assignment of the interface density would benefit from additional support. This work will be of particular interest and useful to groups interested in understanding the molecular basis of nutrient sensing, cellular metabolism, and structural regulation of enzyme activity.

eLife Assessment

This work presents important findings on quantifying gene coexpression from spatial omics. These quantification methods have been applied to gastruloid to describe how genes are spatialised. The description of the quantifying tools is characterized by exceptional evidence after a thorough revision.

eLife Assessment

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

eLife Assessment

This study explores how complement protein C3 and its signalling may modulate immune training in alveolar macrophages. The findings are an important contribution to the field of trained immunity. The findings are convincingly supported by in vivo and ex vivo experiments, encompassing both pharmacological and genetic-based approaches.

eLife Assessment

This valuable study presents an analysis of the gene regulatory networks that contribute to tumour heterogeneity and tumor plasticity in Ewing sarcoma, with key implications for other fusion-driven sarcomas. The authors employed compelling orthogonal approaches, including single-cell sequencing and xenografts, to reveal the existence and plasticity of specific gene regulatory networks (e.g., TGF-beta signaling) within Ewing sarcoma, as well as significant differences that exist between cell lines and patient tumors.

Bias can cause students who speak Black English to be though of as less intelligent, when they aren't

Teachers need to make sure to respect others' cultures and dialects and prepare students for the real world by teaching Standard English.

Getting farther in society means that you have to speak the way that other, "dominant" people do.

We should change the way standard English is being taught in schools so that it focuses more on diversity.

Requiring standardized English makes it harder for some people to get education, jobs, and talk to people in conversations and actively telling students to not use their home language at school.

eLife Assessment

This manuscript reports an important new statistical method for calculating the significance of correlations between two time-series, which provides more accuracy than other methods when the data has few replicates. The proposed method solves a real-life problem that is frequently encountered and is broadly applicable to many realistic datasets in many experimental contexts. The technique is supported with compelling mathematical derivations as well as analysis of both computer-generated and previously published experimental data.

eLife Assessment

This important study by Otgonbaatar and colleagues employs advanced live microscopy, optogenetics, and an endogenous fluorescent timer system to investigate short- and long-term stabilization dynamics of β-catenin/Armadillo (Arm) during Drosophila development. The authors identify an unexpected and functionally relevant enrichment of stabilized junctional Arm in leading-edge cells during dorsal closure, providing evidence for a stabilization mechanism that appears independent of canonical Wingless signaling. These findings are significant because they expand current understanding of β-catenin/Arm beyond its canonical signaling functions and suggest a role in tissue mechanics and force transmission during dorsal closure. The proposed model represents a key advance in the field, but the strength of evidence is currently incomplete: the main conclusions regarding Wingless independence, JNK-mediated regulation, and the mechanical role of stabilized Arm are only partially supported by the available data and would benefit from further experimental testing and corroboration.

eLife Assessment

This study presents a valuable RNA velocity solution which integrates cell differentiation and gene regulation, with a balance between neuralODE and raw gene space. The evidence supporting the claims of the authors is solid, although inclusion of discussion on the challenges in capturing cell cycle transitions would have strengthened the study. The work will be of interest to scientists working in the field of computational biology and gene regulation.

eLife Assessment

This study demonstrates that endothelial toll-like receptor 4 is a central regulator of leptomeningeal inflammation in neonatal E. coli meningitis. The data are derived from cell-type-specific gene knockouts in mice and cultured endothelial cells and are convincing. This work is important as it advances our understanding of host cellular processes and molecular pathways underlying meningitis pathogenesis and specifically expands the knowledge of how breakdown of the blood brain barrier contributes to the pathogenesis.

eLife Assessment

This important study addresses how the molecular identity of a single neuron specifies its hard-wired synaptic connectivity, using repeated single-cell RNA sequencing of identified Drosophila sensory neurons together with functional perturbation of candidate cell-surface molecules. It demonstrates remarkably low transcriptomic variability across animals for the same identified neuron, defines a tractable set of differentially expressed cell-surface molecules that distinguish mechanosensory from chemosensory neurons, and links several of these molecules to axonal targeting and circuit function. The evidence is solid, with the single-neuron transcriptomic datasets and Dscam isoform repertoires offering a lasting resource for the field, though clearer articulation of the experimental logic, additional controls in the RNAi screen, and a more complete characterization of the neuronal re-wiring would further strengthen the central claims.

eLife Assessment

This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury? The authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival after a variety of chemical and surgical liver injury models. The authors provide evidence that some zones mount tailored stress responses, which ultimately promote regeneration and liver healing; however, the "mid-zone" changes with different injury models, making it difficult to conclude that the ATF4-CHOP response is specific to this zone in all injury contexts. In addition, it is possible that Atf4 and Btg2 overexpression could lead to Cyp2e1 suppression, which could reduce the extent of injury after CCl4 or APAP. To some extent, these points make the strength of the evidence incomplete, but do not entirely detract from the significance of the study, which is underscored by the helpful observation that there are zone-specific stress responses that mediate liver regeneration and survival.

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 a valuable addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. However, the experimental evidence supporting the underlying cellular and molecular mechanisms and the integration of foundational background literature to provide the necessary context are incomplete.

eLife assessment

The authors present a valuable open-source tool for three-dimensional analysis of dissected slices of human brains including 3D reconstruction and high-resolution 3D segmentation. Convincing evidence is provided based on experiments on both real and synthetic data. This tool would be of use to researchers in the neuropathology and neuroimaging field.

eLife assessment

The study presents a tool for searching molecular dynamics simulation data, making such data sets accessible for open science. The authors provide convincing evidence that it is possible to identify noteworthy molecular dynamics simulation data sets and their analysis can produce valuable information.

eLife Assessment

This valuable manuscript by Alonso-Caraballo et al is a novel piece of work that examines the impact of oxycodone self-administration on neural plasticity within paraventricular thalamic (PVT) to nucleus accumbens shell (Shell) pathway - two regions shown to play a key role in cue-induced drug seeking on their own - and whether this plasticity varies based on abstinence period and biological sex. Data show that a clinically relevant long-access model of self-administration promotes dependence in both male and female rats and provide compelling data that when compared to current literature indicate that craving-induced relapse for opioids may develop faster and may be more pronounced in females compared to males. In addition to these behavioral findings, the authors provide the first evidence that glutamate signaling within the PVT-to-Shell pathway is selectively strengthened at the output medium spiny neurons by opioids following protracted, but not acute abstinence. These data highlight a potential role for these adaptations in relapse behavior and identify a potential therapeutic target during abstinence to reduce relapse risk in abstaining individuals.

eLife Assessment

This important study addresses the role of sphingolipid metabolism in maintaining endolysosomal membrane integrity and its impact on tau pathology in Caenorhabditis elegans and human cell culture models. The findings are convincing, and the proposed mechanisms are conceivable. The experimental evidence supports the conclusions of the study. The work will be of broad interest to cell biologists and biologists working on Alzheimer's disease and related proteinopathies.

eLife Assessment

This study presents a fundamental finding that the JAK-STAT pathway (JSP) exerts context-dependent roles across distinct cellular compartments within the breast cancer microenvironment. The conclusions are supported by convincing evidence from multi-omics analyses. This study may inspire future studies to explore specific factors that selectively modulate JAK-STAT activity in immune cells to achieve favorable therapeutic outcomes.

eLife Assessment

In this valuable study, the authors performed cell-specific ribosome pulldown to identify gene expression (translatome) differences in the anterior (NT1) vs middle & posterior (NT2-9) cells of the C. elegans intestine, under fed, starved, or refeeding conditions. The data generated will be very helpful to the C. elegans community, and the evidence supporting the conclusions of the study is assessed to be solid. Some methodological caveats remain and are discussed.

eLife Assessment

This study investigated mitochondrial dysfunction and the impairment of the ciliary Sonic Hedgehog signaling in Lowe syndrome (LS), a timely topic given the limited research in this area. The data obtained from patient-derived iPSC neurons and a mouse model are solid. Although the main claims of the study are only partially supported by the current evidence, it provides a useful starting point for future functional studies investigating the link between mitochondrial defects and primary cilia in neural development.

eLife Assessment

This study introduces an artificial-intelligence tool that estimates fat in skull bone marrow from routine brain scans, enabling large studies that were previously impractical. The evidence for the method's repeatability and for identifying genetic links is convincing overall. The authors identify genes, diseases, and other biological characteristics that are linked to skull marrow fat, which represents an important advance. The work will be of most interest to researchers using large imaging biobanks and those studying ageing-related changes across bone, blood, and brain.

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 limited cell type and context.

eLife Assessment

This useful study investigates how plasticity and homeostatic adaptation can lead to the emergence of synchronization patterns associated with different sleep phases. The ideas are novel and interesting, but the evidence at present remains incomplete. Further work is needed to determine whether the reported states persist for larger system sizes, longer integration times, and how robust the results are to different initial conditions.

eLife Assessment

This important study introduces a non-perturbative pulse-labeling strategy for yeast nuclear pore complexes (NPCs), employing a nanobody-based approach in order to selectively capture Nup84-containing complexes for imaging and biochemical analysis. The data convincingly demonstrate that a short induction period (20 minutes to 1 hour) yields a strong and sustained signal, enabling affinity purification that faithfully recapitulates the endogenous Nup84 interactome. This tool offers a powerful framework for investigating NPC dynamics and associated interactomes through both imaging and biochemical assays.

eLife Assessment

This valuable study presents a comparative analysis of the transcriptomic features underlying C. elegans longevity, providing insights into how different changes in gene expression can promote longevity. The authors present solid evidence with analysis and selected functional validation showing that some long-lived animals share common changes while others appear to use opposing strategies. The datasets and analyses contained within and the user-friendly website developed will be of interest to researchers interested in complicated transcriptomic analyses and/or the biology of aging.

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

eLife Assessment

This valuable study provides insights into the role of MATR3 in oocyte maturation and folliculogenesis, using conditional knockout mice and in vitro follicle culture systems to show that MATR3 is required for oocyte growth and gene transcription, with downstream effects on follicle development. The evidence is solid, but some minor inadequacies in replication of key methods and independent validation reduce confidence in the conclusions. The work will be of interest to researchers in reproductive biology and fertility.

eLife Assessment

One-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this valuable study, the authors employ a solid genetics-based approach to demonstrate that three distinct metabolic pathways are essential for synthesising 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence.

eLife Assessment

This is a detailed and well-designed simulation study of the utility of replication metrics in animal-to-human study translations in bridging the gap between laboratory discoveries and health practice, a critical consideration in turning laboratory scientific research findings into tangible, real-world applications, to directly help human health. The study approaches are convincing, and the findings are important, as they offer insights into clinical research translations to advance health decision-making.

eLife Assessment

This fundamental study uses simultaneous EEG and fMRI recordings to shed light on the relationship between alpha and gamma oscillations and specific cortical layers. The sophisticated methodology provides compelling evidence for correlations between oscillatory power and the strength and contents of fMRI signals in different cortical layers. This paper will be of interest to neuroscientists studying the role and mechanisms of alpha and gamma oscillations.

eLife Assessment

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

eLife Assessment

This important study combines peptide engineering, molecular docking, and functional assays to define the molecular basis of ligand recognition and activation of the human Y4 receptor and to identify three novel small-molecule agonists. The evidence supporting the conclusions is convincing, with complementary experimental and computational approaches providing strong support for the proposed receptor-ligand interactions. While concentration-response analyses of the small-molecule agonists and additional structural or mutagenesis studies would further strengthen the work, these are not essential to support the main conclusions. The work will be of interest to researchers studying GPCR pharmacology, structural biology, and ligand discovery.

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. While these data are interesting and helpful for hypothesis generation, they are deemed incomplete; additional experiments would be needed to test causality and to provide mechanistic insight. Despite these limitations, this work 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 is an important study that applies a new chromatin profiling technique to the study of cellular responses to low oxygen. The authors provide convincing evidence for distinct kinetic phases of the response and identify many new putative regulators of the response. This work will be of broad interest to those studying low oxygen responses and transcriptional regulation.

eLife Assessment

The manuscript concerns a fundamental and controversial question in Trypanosoma brucei biology and the parasite life cycle, whether or not dividing slender bloodstream forms must transition to growth-arrested stumpy forms before differentiating to the procyclic form in the Tsetse midgut. The authors provide further evidence that slender bloodstream forms can infect Tsetse flies, and that although their differentiation is considerably delayed, they do not become classical stumpy forms during the process. The study is solid in design and execution, and addresses several criticisms made of the authors' earlier work, although discrepancies with results from other laboratories remain.

eLife Assessment

This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.

eLife Assessment

This manuscript presents openretina, an open-source platform that integrates retinal datasets, model training, benchmarking, and in silico analysis tools within a unified framework. The resource is valuable because it addresses long-standing challenges in reproducibility, accessibility, and cross-study comparison in computational retina research, while providing a foundation for community-driven model development and evaluation. The supporting evidence is solid, with the authors demonstrating a functional and well-documented platform across multiple datasets and species, although a clearer discussion of model interpretability, current performance limitations, and data quality standards would strengthen the resource.

eLife Assessment

This manuscript describes an important development of several variants of optogenetic tools to control endogenous p53 activity. They are based on peptides competing with Mdm2/MdmX for binding to p53, thus releasing p53 from its negative regulators and stabilizing its cellular levels. In principle, the data are convincing but should be complemented by investigations of p53 target genes at endogenous levels (instead of only reporter constructs). The study therefore remains incomplete but will be of interest to scientists working on optogenetics as well as the p53 field.

eLife Assessment

Verma and colleagues interrogate the mechanisms of phagosome maturation arrest during Mycobacterium tuberculosis infection. While cellular events that culminate in this arrest have been largely elucidated, involvement of other organelles, such as mitochondria, has not been highlighted mechanistically. In this valuable study, elements of mitochondrial quality control, such as mitophagy and mitochondrial-derived vesicles involvement, are shown to be paramount in the host-pathogen tussle. The evidence supporting the main conclusions is solid, based on multiple complementary approaches and appropriate controls, although some central mechanistic aspects of the proposed pathway remain only partially resolved.

eLife Assessment

This valuable study provides a cross-species single-cell transcriptomic resource for early female gonadal development in mammals. The data supporting the main conclusion remain incomplete, and experimental validation is needed to strengthen the conclusions. The work will be of interest to reproductive biologists and developmental biologists.

eLife Assessment

The Review Article by Bal and co-workers presents an overview of skeletal muscle physiology, focusing on Sarcoplasmic Reticulum and Mitochondria-Associated Membranes (MAMs) in relation to calcium handling, ROS, and signaling. It provides a foundation based on the current literature but could have gone further by identifying future research directions and potential avenues for therapeutic intervention.

eLife Assessment

This study investigates the cellular mechanisms underlying theta-nested gamma oscillations in the medial entorhinal cortex; the experiments are rigorous, and the analyses and modeling provide potentially useful insights into cell-type-dependent circuit dynamics. However, the evidence supporting several key conclusions remains incomplete. The study is limited by conceptual constraints in the experimental design and a modeling approach that does not fully address underlying physiological mechanisms. Overall, this is a careful study that addresses how distinct neuronal populations in superficial MEC participate in theta-gamma coordination and provides new data linking cell-type-specific activity patterns to oscillatory network structure.

eLife Assessment

This study makes a solid and valuable contribution to elucidating the intricate relationship between mitochondrial calcium and neuronal survival. Well-controlled experiments show that homeostatic mitochondrial calcium correlates with the most resilient neuronal subtypes after optic nerve injury. However, altering mitochondrial calcium levels does not affect neuronal survival as initially predicted by this correlation.

eLife Assessment

This article describes the comprehensive metabolic phenotype of a mouse model of Down Syndrome, together with supporting transcriptomic, metabolomic, and biochemical data. The evidence presented is compelling and highlights several core phenotypes including insulin resistance, dyslipidemia, and tissue signatures indicating inflammatory and cellular stress pathways. Similarities and differences in male and female mice are highlighted. This important study provides essential groundwork for the further genetic dissection of dosage-sensitive genes causing metabolic dysregulation in Down Syndrome.

eLife Assessment

This study presents an important large-scale behavioral and transcriptomic analysis of Drosophila that are heterozygous for putative loss-of-function alleles of homologs of human genes that have been linked to autism spectrum disorders. The authors consider 48 genes as hits from their screen, which show significant behavioral alterations in sleep, basal activity, and/or social behavior, and significant sexual dimorphism. The authors then focus on the domino/SRCAP gene as a candidate regulator of sleep, social behavior, transcriptional programs, and RNA splicing. The work generates a solid dataset and applies quantitative analytical approaches that will be of interest to researchers in the field, yet the evidence presented remains incomplete because issues of genetic background need to be further addressed.

eLife Assessment

In this useful Tools & Resources article, the authors describe a new cryogenic light microscopy design and characterize its temperature and spatial stability. This compelling system avoids the challenges associated with vacuum-based designs, particularly vacuum transfer systems, which are difficult to engineer. A key advantage of the system is that it reduces ice contamination and drift, which are the primary challenges in open cryostat systems.

eLife Assessment

This manuscript describes a valuable study of the mechanism by which acetylation on the histone H3 core domain regulates RNA polymerase II transcription passing through nucleosomes. The authors provide convincing evidence that acetylation influences transcription in a context-specific fashion. Some questions relating to the static nucleosome structures and the polymerase passage remain, but this manuscript will be of considerable interest to researchers in the chromatin and transcription fields.

eLife Assessment

This important study provides a mechanistic view of how antibody affinity maturation can reshape encounter-state landscapes and association pathways, with implications for understanding HIV antibody maturation and vaccine design. The results are solid, supported by a coherent integration of adaptive molecular dynamics, Markov state modeling, SPR kinetics, mutagenesis, and double-mutant cycle analysis, although aspects of the kinetic validation, MSM-state robustness, and causal interpretation would benefit from further support. The work will be of interest to immunologists, structural biologists, and computational biophysicists.

eLife Assessment

Muetter et al. provide an important argument that luminescence is a reliable, high-throughput alternative to colony-forming units (CFU) for super-MIC investigations, particularly when the quantity of interest is biomass. By examining 20 antimicrobials spanning 11 classes, the work shows that discrepancies between CFU and luminescence are often biological (filamentation, Viable But Not Culturable). The work provides a convincing view of how these three common measurements (luminescence, optical density, and CFU) relate to one another across a range of drug treatments, although testing on clinical isolates could be of further benefit.

eLife Assessment

This valuable study introduces MULTI i², a robust and high-throughput method to measure Plasmodium falciparum viability in the presence of drugs. This new assay offers significant time savings over the traditional Parasite Reduction Rate (PRR) assay and should enable faster screening of drug combinations, which is urgently needed in the field. The assay is well validated, with convincing data showing it can reproduce known drug interactions and identify new interaction patterns.

eLife Assessment

This important study combines anatomical tracing, tissue clearing, and functional manipulations to demonstrate lateralized brainstem control of hepatic glucose metabolism and identify a site of sympathetic nerve crossover supplying the liver. The evidence supporting the anatomical organization of hepatic sympathetic innervation is compelling, and the functional studies provide solid support for a role of asymmetric sympathetic outflow in regulating glucose homeostasis. While some uncertainty remains regarding the contribution of sensory innervation and the extent to which these findings generalize beyond mice, the work provides an invaluable advance in understanding neural regulation of liver metabolism.

eLife Assessment

This valuable study demonstrates that self-motion strongly affects neural responses to visual stimuli, comparing humans moving through a virtual environment to passive viewing. The evidence for visuomotor mismatch responses is solid, although the interpretation in terms of prediction remains somewhat preliminary. This study bridges human and rodent studies on the role of prediction in sensory processing, and is therefore expected to be of interest to a large community of neuroscientists.

eLife Assessment

This study presents a key finding: self-generated mechanical stresses enable collective protocell proliferation without dedicated division machinery, offering insight into primitive life's population growth. While quantitative imaging, membrane tension measurements, and computational modeling support the mechanism, establishing causal links between deformation and division and testing sensitivity assumptions would strengthen the work. Overall, the work reports important findings, and although the evidence in support of the conclusions is largely solid, some incomplete elements need to be addressed.

eLife Assessment

This important study combines experimental evidence with computational modeling to suggest that neurons in the frontal eye field form two overlapping topographical maps, one for visual inputs and the other for eye movement directions. The experiments leverage the smooth cortex of the marmoset to provide solid evidence that two maps exist at different scales. The modelling work provides a potential mechanistic insight into how these patterns may be used for flexible visuomotor transformations.

eLife Assessment

In this valuable study, Bhojappa et al. investigate the function of four septin-associated kinases (Elm1p, Gin4p, Hsl1p and Kcc4p) in controlling septin ring stability, actomyosin ring organization and constriction, and cytokinesis in budding yeast. The evidence supporting the conclusions is convincing. The results are a meaningful addition to previously published work and provide a clearer picture of a complex mechanism involving proteins of partially redundant functions.

eLife Assessment

This useful study provides new insights into the liver-stage antigen LSA3, its export to erythrocytes, and its role in liver-stage development. While the functional importance of LSA3 is well demonstrated, the data underlying the conclusions regarding antibody specificity, liver-stage localization, and phenotype remain incomplete. A key strength of the study is the use of mosquito and humanized mouse models to access life-cycle stages that are rarely studied in most laboratories.

eLife Assessment

This study offers an important set of literature-based parameter ranges for calibrating cardiac electromechanical models. The key scientific claims are largely supported by convincing evidence and carefully-documented methodologies, but a few specific issues remain only partially supported, in particular relating to the locking-free formulation, reporting of adequate details regarding the electrophysiological model (Eikonal approach), and the fact that physiological accuracy is predominantly achieved in a single chamber (the LV).

eLife Assessment

The study presents important findings from a very rich EEG-fMRI dataset including 107 participants, which was collected during nocturnal naps. Using overall solid methods, the authors link activity in memory related brain regions (e.g., hippocampus, thalamus, and medial prefrontal cortex), as well as their functional connectivity, to the occurrence of canonical sleep rhythms (spindles and slow oscillations) during non-rapid eye movement (NREM) sleep. This work will be of broad interest to researchers studying sleep, memory, and related domains.

eLife Assessment

By mining the Logan assemblage of the Sequence Read Archive to reveal substantial papillomavirus diversity, this valuable study establishes a framework for integrating viral discovery with host, geographic, and ecological metadata. The evidence for identifying novel papillomavirus sequences is convincing, supported by large-scale sequence searches, established L1-based typing criteria, phylogenetic analyses, protein annotation, and structural comparisons. The broader host-association and ecological conclusions are more tenuous due to heterogeneous public metadata and uneven sampling, and would benefit from clearer discussion of potential biases, contamination, endogenous viral elements, and alternative explanations. The work should be of interest to a broad range of colleagues in the areas of microbiome research, virology, and viral evolution.

eLife Assessment

This valuable study reports that ALDH-abundant cells exhibit stem cell properties and may play a key role in endometrial epithelial development in mice. The data support the main conclusion and are convincing. This work will be of great interest to reproductive biologists and biomedical researchers working on women's reproductive health.

eLife Assessment

The authors use solid high resolution microscopy techniques to present a model in which SARS-CoV-2 attachment and endocytosis are mediated by heparan sulfate, whereas ACE2 only functions downstream of these early processes. These findings serve as a potentially valuable starting point to examine SARS-CoV-2 entry models that challenge current paradigms. However, examination of the model in a clean heparan sulfate deficient background and in the context of TMPRSS2-dependent plasma membrane fusion are lacking. Thus, the broader impact remains uncertain in the absence of additional controls and orthogonal approaches.

eLife Assessment

This important study investigates the mechanisms by which Mycobacterium tuberculosis suppresses protective Th17 differentiation during infection. Using ESX-1- and PDIM-deficient mutants of M. tuberculosis, which lack functional eccC1 and fadD28 respectively, the authors demonstrate that these virulence factors actively restrict IL-17 responses via a T-bet-dependent pathway, independent of overall bacterial attenuation or infection duration. While the precise molecular interactions by which ESX-1 and PDIM modulate Th17 differentiation warrant further elucidation, the experiments are rigorously designed, the findings are clearly presented, and the evidence is solid for a specific role for these factors in limiting protective IL-17 immunity in M. tuberculosis infection.