9,966 Matching Annotations
  1. Last 7 days
    1. eLife Assessment

      This valuable study investigates whether the activity of an ABC transporter, BmrA, can be modulated by mechanical stimuli. The authors develop a single-molecule experimental system to address this question, although aspects of the methodological framework are incomplete. This work also develops a convincing theoretical model to explain the effect of membrane curvature on the conformational transitions observed during the activity cycle of this membrane protein. This study is of interest to the fields of membrane biophysics and membrane transport.

    1. eLife Assessment

      This valuable work explores how synaptic activity encodes information during memory tasks. All reviewers agree that the work is of very high quality and that the methodological approach is praiseworthy. The experimental data support the possibility that phospholipase diacylglycerol signaling and synaptotagmin 7 (Syt7) dynamically regulate the vesicle pool required for presynaptic release. Overall, this is a convincing study.

    1. eLife Assessment

      This set of experiments provides important knowledge for how the infralimbic cortex is recruited to inhibit behavior after extinction training. The evidence supporting the conclusions is convincing with multiple sophisticated behavioral designs providing converging lines of evidence, though reviewers note possible alternative interpretations and limitations of small group sizes in some cases. This work will be of interest to those interested in cortical function, learning and memory, aversive behavior, and/or related psychiatric factors.

    1. eLife Assessment

      This valuable study introduces CAAMO, a computational framework that combines structure prediction, in silico mutagenesis, molecular simulations, and energy calculations to design RNA aptamers with improved binding affinity. The computational methodology is solid, demonstrating strong theoretical foundations and systematic integration of multiple prediction techniques. However, the experimental validation is incomplete, with methodological weaknesses that limit the strength of support for the computational predictions.

    1. eLife Assessment

      This fundamental study uses the Drosophila mushroom body as a model to understand the molecular machinery that controls the temporal specification of neuronal cell types. With convincing experimental evidence, the authors make the finding that the Pipsqueak domain-containing transcription factor Eip93F plays a central role in specifying a later-born neuronal subtype while repressing gene expression programs for earlier subtypes.

    1. eLife Assessment

      This important study describes a computational model of the rat spinal locomotor circuits and how they could be plastically reconfigured after lateral hemisection or contusion injuries to replicate gaits observed experimentally in vivo. Overall, the simulation results convincingly mirror the gait parameters observed experimentally. The model suggests the emergence of detour circuits after lateral hemisection, whereas after a midline contusion, the model suggests plasticity of left-right and sensory inputs below the injury.

    1. eLife Assessment

      This paper provides important findings towards understanding the role of the lncRNA EPB41L4A-AS1 in a human cell line. The data is generally convincing, supported by extensive and clever integrative analysis. The work provides insights into how this lncRNA regulates gene expression via complex mechanisms; however the biological relevance awaits validation in other models.

    1. eLife Assessment

      In this important work, it is demonstrated that certain high-resolution cryo-EM structures can be obtained by using concentrated cell extracts without purification. The compelling results with the mammalian ribosomes demonstrate the utility of this approach for this molecule and complexes with elongation factor 2. Moreover, this work also demonstrates the utility of 2D template matching for particle picking for structure determination by single-particle averaging pipelines.

    1. eLife Assessment

      The study proposed hemogenic endothelium in adult BM using lineage tracing. Though the study is potentially valuable, the data is incomplete due to the lack of control and insufficient analysis. There is potential for the study to be improved by further revision.

    1. eLife Assessment

      This important work shows that corticotrophin-releasing factor is delivered monosynaptically to dorsal striatal cholinergic interneurons from the central amygdala and bed nucleus of the stria terminalis. CRF increases cholinergic interneuron firing and release of acetylcholine, and this action is attenuated by pre-exposure to ethanol, suggesting a potential role in stress- and alcohol use disorders. This revision addressed prior concerns, presented convincing evidence supporting the conclusions, and set the stage for additional important studies.

    1. eLife Assessment

      This important study provides solid evidence to support the anti-tumor potential of citalopram, originally an anti-depression drug, in hepatocellular carcinoma (HCC). In addition to their previous report on directly targeting tumor cells via glucose transporter 1 (GLUT1), the authors tried to uncover additional working mechanisms of citalopram in HCC treatment in the current study. The data here suggests that citalopram may regulate the phagocytotic function of TAM via C5aR1 or CD8+T cell function to suppress HCC growth in vivo.

    1. eLife Assessment

      This fundamental work significantly advances our understanding of gravity sensing and orientation behavior in the ctenophore, an animal of major importance in understanding the evolution of nervous systems. Through comprehensive reconstruction with volumetric electron microscopy, and time-lapse imaging of cilia motion, the authors provide compelling evidence that the aboral nerve net coordinates the activity of balancer cilia. The resemblance to the ciliomotor circuit in marine annelids provides a fascinating example of how neural circuits may convergently evolve to solve common sensorimotor challenges.

    1. eLife Assessment

      This study presents an important study into the molecular function of AT-HOOK MOTIF NUCLEAR LOCALIZED 15 (AHL15), a member of the AHL protein family, identifying it as a potential regulator of three-dimensional gene-loop organization within transcribed gene bodies. The authors support this claim with compelling genome-wide evidence, integrating AHL15 binding profiles with transcriptional and chromatin accessibility changes, as well as demonstrating overlap with genes known to form loops across transcribed regions. The evidence supporting the claims of the authors is solid. Collectively, these findings will be of broad interest to biologists seeking to understand the core regulatory mechanisms underlying gene expression.

    1. eLife Assessment

      This fundamental study advances our understanding of population-level immune responses to influenza in both children and adults. The strength of the evidence supporting the conclusions is compelling, with high-throughput profiling assays and mathematical modeling. The work will be of interest to immunologists, virologists, vaccine developers, and those working on mathematical modeling of infectious diseases.

    1. eLife Assessment

      This important manuscript evaluates how sample size and demographic balance of reference cohorts affect the reliability of normative models. The evidence supporting the conclusions is convincing. This work will be of interest to clinicians and scientists working with normative models.

    1. eLife Assessment

      This valuable study provides insights into the role of Pten mutations in SHH-medulloblastoma, by using mouse models to resolve the effects of heterozygous vs homozygous mutations on proliferation and cell death throughout tumorigenesis. The experiments presented are convincing, with rigorous quantifications and orthogonal experimentation provided throughout, and the models employing sporadic oncogene induction, rather than EGL-wide genetic modifications, represent an advancement in experimental design. However, additional experimentation focused on a greater characterization of macrophage phenotypes (e.g., microglia vs circulating monocytes) would enhance this study. The work will be of interest to medical biologists studying general cancer mechanisms, as the function of Pten may be similar across tumor types.

    1. eLife Assessment

      This manuscript presents a valuable study of the activity and functional relevance of different circuits in the dentate gyrus of mice performing a pattern separation task. The study is likely to be of interest to those studying the subregional organization and cell type-specific functions of the dentate gyrus. However, the strength of evidence for the study's conclusions is currently incomplete.

    1. eLife Assessment

      This useful study by Palo et al proposes that FRG1 functions as a negative regulator of Nonsense-Mediated mRNA decay (NMD) by associating with the exon junction complex (EJC) and destabilizing UPF1 independently of DUX4. The authors present solid evidence to dissect the relationship between FRG1 and DUX4 in NMD. However, the evidence to support the claim that FRG1 is a component of the EJC or the NMD machinery is incomplete.

    1. eLife Assessment

      This study presents a valuable finding on maternal SETDB1 as a key chromatin repressor that shuts down the 2C gene program and enables normal mouse embryonic development. The evidence supporting the claims of the authors is solid, although the inclusion of a causality test, a mechanistic understanding of SETDB1 targeting, and phenotypic quantification would have greatly strengthened the study. The work will be of broad interest to biologists working on embryonic development, stem cells and gene regulation.

    1. eLife Assessment

      This study presents a method for expressing single-stranded DNA fluorescent aptamers in E. coli using a retron-based strategy. The evidence supporting the successful expression and folding of DNA aptamers is solid, with clear demonstration of fluorescence after extraction, though the aptamers do not function in living cells. The method represents an important technical advance that will likely become standard for DNA aptamer expression in bacterial systems.

    1. eLife Assessment

      This study offers important insights into how entorhinal and hippocampal activity support human thinking in feature spaces. It replicates hexagonal symmetry in entorhinal cortex, reports a novel three-fold symmetry in both behavior and hippocampal signals, and links these findings with a computational model. The task and analyses are sophisticated, and the results appear convincing and of broad interest to neuroscientists.

    1. eLife Assessment

      This valuable study introduces a model to help researchers understand how multivariate processes affect observed relationships in genetic data. The authors provide a tool to estimate model parameters. Overall, the authors provide solid evidence that their tool can obtain median-unbiased estimates of the true parameters when using simulated data under the model.

    1. eLife Assessment

      This important study addresses the question of how organ-specific blood vessels form during different stages of development, and how specific genes may regulate these processes. New genetic tools were developed to label distinct endothelial cell populations and track them over time in different mutant backgrounds. The results are solid; however, additional data quantification, lineage tracing, and cell autonomy experiments would further strengthen the conclusions.

    1. eLife Assessment

      This manuscript provides valuable insight into how genome organization changes as cells progress through the cell cycle after mitotic exit. The conclusions are supported by solid, rigorous data, and the use of sorted unsynchronized cells rather than cells treated with drugs is a particular strength. Two sharp genome remodeling events are identified at G1-S and to a lesser extent, at S-G2 transitions. A discussion on the limitations of Hi-C and a broader interpretation of results in the context of other mechanistic models would strengthen the overall rigor.

    1. eLife Assessment

      This important work demonstrates the role of physically linking the core and CTD kinase modules of TFIIH via separate domains of subunit Tfb3 in confining RNA Polymerase II Serine 5 CTD phosphorylation to promoter regions of transcribed genes in budding yeast. The main findings, resulting from analyses of viable Tfb3 mutants in which the linkage between TFIIH core and kinase modules has been severed, are supported by solid evidence from in vitro and in vivo experiments. There is an intriguing possibility that the Tfb3-mediated connection between core and kinase modules of TFIIH is an evolutionary addition to an ancestral state of physically unconnected enzymes, which could be examined more rigorously with additional evolutionary analyses.

    1. eLife Assessment

      This manuscript uses adaptive-bandit simulations to describe the dynamics of the Pseudomonas-derived chephalosporinase PDC-3 β-lactamase and its mutants to better understand antibiotic resistance. The finding, that clinically observed mutations alter the flexibility of the Ω- and R2-loops, reshaping the cavity of the active site, is valuable to the field. The evidence is considered incomplete, however, with the need for analysis to demonstrate equilibrium weighting of adaptive trajectories and related measures of statistical significance.

    1. eLife Assessment

      This study presented valuable findings regarding the basic molecular pathways leading to the cystogenesis of Autosomal Dominant Polycystic Kidney Disease, suggesting BICC1 functions as both a minor causative gene for PKD and a modifier of PKD severity. Solid data were supplied to demonstrate the functional and structural interactions between BICC-1, PC1 and PC2, respectively. The characterization of such interactions remains to be developed further, which renders the specific relevance of these findings for the etiology of relevant diseases unclear.

    1. eLife Assessment

      This study investigated the dynamics of human cortical network activity with functional magnetic resonance imaging during movie watching and studied the modulation of these dynamics by subcortical areas using an energy landscape mapping method. The authors identified a set of brain states defined at the level of canonical functional networks, quantified how the brain transitions between these states, and related transition probabilities to inter-subject correlations in evoked brain activity. A major emphasis of the work concerns the role of the thalamus, which shows transition-linked activity changes and dynamic connectivity patterns, including differential involvement of parvalbumin- and calbindin-associated thalamic subdivisions. The analytical strategy developed in this study is applicable to other task- and resting-state fMRI data and would be useful for many researchers in the field; however, the evidence supporting the overall conclusions remains incomplete due to limitations associated with fMRI data preprocessing, analysis, and cross-validation.

    1. eLife Assessment

      This study investigates whether heavy metal stress can induce maize-like phenotypic and molecular responses in teosinte and whether these responses overlap with genomic regions implicated in domestication. By combining copper and cadmium treatments with quantitative phenotyping, gene-expression analyses, and expanded assessments of nucleotide diversity across a key chromosome 5 interval, the authors provide an integrated view of how abiotic stress responses intersect with domestication-related traits. The significance of the findings is valuable, as the work offers meaningful insights for the subfield of maize evolution and stress biology by extending heavy-metal response analyses to teosinte and linking them to domestication-associated loci, although the evolutionary implications remain indirect. The strength of evidence is solid, with appropriately designed and quantitatively supported experiments that broadly support the claims, but do not yet establish a causal or historical role for heavy metal stress in domestication.

    1. eLife Assessment

      This is an important work implementing data mining methods on IMC data to discover spatial protein patterns related to the triple-negative breast cancer patients' chemotherapy response. The evidence supporting the claims of the authors is solid, although more detailed methodology clarification and validation are needed. While the accuracy of the methods is not very high, the work shows potential for translational application.

    1. eLife Assessment

      This important study focuses on the molecular mechanisms underlying the generation of neuronal diversity. Taking advantage of a well-defined neuroblast lineage in Drosophila, the authors provide convincing evidence that two transcription factors of the conserved forkhead box (FOX) family offer a mechanistic link between transient spatial cues that specify neuroblast identity and terminal selector genes that define post-mitotic neuron identity. The findings will be of interest to developmental neurobiologists.

    1. eLife Assessment

      This study presents experiments suggesting intriguing mesoscale reorganization of functional connectivity across distributed cortical and subcortical circuits during learning. The approach is technically impressive and the results are potentially of valuable significance. The authors have also made clear effort to address concerns in revision. However, the strength of evidence remains incomplete. Acquisition of data from additional animals in the primary experiment could bolster these findings.

    1. eLife Assessment

      This study provides valuable insight into the role of actin protrusions in mediating early pre-endoyctic steps of human papillomavirus entry at the cell surface. Using state-of-the-art microscopy in an immortalized keratinocyte model, the authors present mostly solid evidence that filopodia actively promote the transfer of heparin sulfate-coated virions from the extracullar matrix to the viral entry factor CD151. Remaining gaps in the mechanistic model could be further supported by including a more expansive analysis of the fixed microscopy samples and live cell imaging to distinguish virion transfer from direct binding.

    1. eLife Assessment

      This valuable work advances our understanding of the relationship between multimodal magnetic resonance imaging (MRI) measures, cognition, and mental health. Compelling use of statistical learning techniques in UK Biobank data shows that 48% of the variance between an 11-task derived g-factor and imaging data can be explained. Overall, this paper contributes to the study of brain-behaviour relations and will be of interest for both its methods and its findings on how much variance in g can be explained.

    1. eLife Assessment

      This study offers a valuable methodological advance by introducing a gene panel selection approach that captures combinatorial specificity to define cell identity. The findings address key limitations of current single-gene marker methods. The evidence is compelling, but would be strengthened by further validation of rare cell states and unexpected marker categories.

    1. eLife Assessment

      This manuscript presents a valuable methodological approach to investigating context-dependent activity of cis-regulatory activity within defined genomic loci. The authors combine a locus-specific massively parallel reporter assay, enabling unbiased and high-coverage profiling of enhancer activity across large genomic regions, with a degenerate reporter assay to identify nucleotides critical for enhancer function. The data supporting the conclusions are solid, highlighted by successful identification and characterization of both previously known and new regulatory elements across multiple developmental stages, cell types, and species. While the approach has inherent limitations in sensitivity, and indirect assignment of regulatory elements to target genes, it provides a flexible platform for nominating candidate cis-regulatory elements across defined loci.

    1. eLife Assessment

      This study provides valuable mechanistic insight into the mutually exclusive distributions of the histone variant H2A.Z and DNA methylation by testing two hypotheses: (i) that DNA methylation destabilizes H2A.Z nucleosomes, thereby preventing H2A.Z retention, and (ii) that DNA methylation suppresses H2A.Z deposition by ATP-dependent chromatin remodelling complexes. Through a series of well-designed and carefully executed experiments, findings are presented in support of both hypotheses. However, the evidence in support of either hypothesis is incomplete, so that the proposed mechanisms underlying the enrichment of H2A.Z on unmethylated DNA remain somewhat speculative.

  2. Jan 2026
    1. eLife Assessment

      This study uses a valuable combination of functional magnetic resonance imaging and electroencephalography (EEG) to study brain activity related to prediction errors in relation to both sensorimotor and more complex cognitive functions. It provides incomplete evidence to suggest that prediction error minimisation drives brain activity across both types of processing and that elevated inter-regional functional coupling along a superior-inferior axis is associated with high prediction error, whereas coupling along a posterior-anterior axis is associated with low prediction error. The manuscript will be of interest to neuroscientists working on predictive coding and decision-making, but would benefit from more precise localisation of EEG sources and more rigorous statistical controls.

    1. eLife Assessment

      This manuscript provides evidence that mouse germline cysts develop an asymmetric Golgi, ER, and microtubule-associated structure that resembles the fusome in Drosophila germline cysts. This fundamental study provides new evidence that fusome-like structures exist in germ cell cysts across species. Overall, the data are convincing and represent a significant advance in our understanding of germ cell biology.

    1. eLife Assessment

      This paper develops a fundamental theory that explains how the brain can hold in working memory not only the identity but also the order of presented stimuli. Previous theories did not explain the ability of people to immediately recall the correct order of the stimulus presentation. The authors present compelling evidence that this can be achieved through synaptic augmentation, an experimentally observed phenomenon with a time scale of tens of seconds.

    1. eLife Assessment

      This valuable study a computational language model, i.e., HM-LSTM, to quantify the neural encoding of hierarchical linguistic information in speech, and addresses how hearing impairment affects neural encoding of speech. Overall the evidence for the findings is solid, although the evidence for different speech processing stages could be strengthened by a more rigorous temporal response function (TRF) analysis. The study is of potential interest to audiologists and researchers who are interested in the neural encoding of speech.

    1. eLife Assessment

      This study investigates low-affinity Ca2+ binding by WT calreticulin and mutant calreticulin associated with type I myeloproliferative neoplasms, as well as the impact on Ca2+ fluxes in suspension cultures of megakaryocyte-like cells in vitro in response to ER Ca2+ ATPase inhibitors that deplete endoplasmic reticulum (ER) Ca2+ store and open plasma membrane Ca2+ channels through STIM1-Orai interactions. The results are important in that they show that Ca2+ binding by calreticulin and store-operated Ca2+ entry are not fundamentally impacted by the type I deletion mutation in calreticulin, which rules out a direct effect of the calreticulin mutation on its own low-affinity Ca2+ binding and any broad impact on ER Ca2+ regulation. The strength of the data and methods used ranges from solid to convincing, although the use of suspension-based flow cytometric assays to investigate ER Ca2+ levels and Ca2+ entry can be challenged. High-affinity Ca2+ binding sites could be further considered, and possible confounding effects of Abl kinase activity in the megakaryocyte-like cell lines could be offset.

    1. eLife Assessment

      This article reports an algorithm for inferring the presence of synaptic connection between neurons based on naturally occurring spiking activity of a neuronal network. One key improvement is to combine self-supervised and synthetic approaches to learn to focus on features that generalize to the conditions of the observed network. This valuable contribution is currently supported by incomplete evidence.

    1. eLife Assessment

      This important study combines a two-person joint hand-reaching paradigm with game-theoretical modeling to examine whether, and how, one's reflexive visuomotor responses are modulated by a partner's control policy and cost structure. The study provides a solid and novel set of behavioral findings suggesting that involuntary visuomotor feedback is indeed modulated in the context of interpersonal coordination. The work will be of interest to cognitive scientists studying the motoric and social aspects of action control.

    1. eLife Assessment

      This important study addresses a classic debate in visual processing, using a strong method applied to a rare clinical population to evaluate hierarchical models of visual object perception. The paper finds only partial support for the hierarchical model: as expected, neural responses in ventral visual cortex show increased representational selectivity for faces along the posterior-anterior axes, but the onsets of the signals do not show a temporal hierarchy, indicating more parallel processing. The iEEG dataset is impressive, but the evidence for lack of temporal hierarchy is incomplete: essential quality checks need to be performed, and statistical analyses adapted to ensure that the data and analyses would be able to reveal temporal hierarchy if it were present in the data.

    1. eLife Assessment

      This valuable study provides a practical computational framework for inferring latent neural states directly from calcium fluorescence recordings, bypassing the traditional need for a separate spike deconvolution step. The evidence supporting the method is solid, featuring rigorous validation across multiple latent variable model families (including HMM, GPFA, and LFADS) using both simulated and experimental data. However, the assessment of the method's generality would be further strengthened by application to a broader range of experimental datasets, such as recordings from different brain regions or using different calcium indicators.

    1. eLife Assessment

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

    1. eLife Assessment

      The authors address a hard question and propose a pipeline for using Large Language Models to reconstruct signalling networks as well as to benchmark future models. The findings are valuable for a defined subfield, as the proposed framework allows for assessing such approaches systematically. The overall support is solid, although the present evaluation remains limited in scope and would benefit from a wider range of networks and performance metrics.

    1. eLife Assessment

      Important findings from this study include clear evidence of the impact of methylphenidate on cognitive control over Pavlovian biasing of actions and decision-making in humans, in a manner dependent on baseline working memory capacity. The design used drug dosing after learning, allowing a compelling test of the influence of catecholamines on decision processes independent of learning. The task is very well designed, using a combination of aversive and appetitive Pavlovian to Instrumental Transfer, and the in-depth behavioural analysis extends the authors' previous work, which will be of interest to those working in cognitive psychopharmacology. The results challenge the view that catecholamines operate by modulating behavioural invigoration alone.

    1. eLife Assessment

      This is a valuable polymer model that provides insight into the origin of macromolecular mixed and demixed states within transcription clusters. The simulations are well performed and clearly presented in the context of existing experimental datasets. This compelling study will be of interest to those studying gene expression in the context of chromatin.

    1. eLife Assessment

      This important study identifies a metal transporter in the plasma membrane of the obligate intracellular pathogen, Toxoplasma gondii. Using an array of different approaches, the authors convincingly demonstrate that this transporter mediates iron and zinc uptake and regulates diverse cellular processes, including parasite metabolism and differentiation. This work will be of broad interest to cell biologists and biochemists studying metal ion transport mechanisms.

    1. eLife Assessment

      This important study provides new insights into how Staphylococcus aureus adapts to disulfide stress through the redox-sensitive regulator Spx, which coordinates nutrient uptake, cysteine import, redox homeostasis, and bacterial growth. While the authors present compelling evidence supporting the central role of Spx in managing disulfide stress, several aspects require further clarification. In particular, the precise mechanisms regulating cysteine uptake and the proposed link between disulfide stress responses and iron limitation would benefit from additional explanation and experimental or conceptual justification.

    1. eLife Assessment

      Optical tweezers have been instrumental to the determination of mechanical parameters of molecular motors. This study by Takamatsu et al. reports key mechanical parameters of kinesin KIF1A using fluorescence microscopy, wherein the motor is tethered to a DNA nanospring, without the use of an optical trapping apparatus, which represents an exciting development. The approach and the findings reported change current thinking about KIF1A‑mediated transport, with potential implications for understanding human disease. The findings are important and the strength of the evidence is compelling.

    1. eLife Assessment

      This study presents a valuable human stem cell-derived organoid model that captures key morphological and cellular features of spinal cord development and provides evidence for a YAP-dependent mechanism of lumen formation relevant to secondary neurulation. Overall, the evidence is convincing, using strong and validated approaches consistent with the current state of the art, including systematic protocol optimisation across multiple cell lines and quantitative analysis of tissue architecture. However, some claims regarding precise anterior-posterior and dorsoventral spinal cord identity, as well as several novelty claims, are at times overstated and would benefit from more direct validation and more careful positioning. The work will be of interest to developmental biologists and researchers studying neural tube defects.

    1. 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.

    1. eLife Assessment

      In this useful paper, the authors present a comprehensive method for the purification of recombinant Snake Venom Metalloproteinases (SVMPs) using the MultiBac expression system, explain the self-activation of the enzymes by Zn2+ incubation, and establish high-throughput screening (HTS) techniques. The authors addressed a key problem: producing a substantial amount of pure and enzymatically active SVMPs required for structural and functional studies. Altogether, this work builds a solid foundation for the large-scale production of active SVMPs for future biochemical and structural characterization as well as for drug discovery, albeit leaving certain caveats about the universal applicability of the described methodology for the production of any recombinant SVMPs.

    1. eLife Assessment

      The authors used genetic mutations in VANGL2 to study cell morphological changes during differentiation of hPSCs and understand the mechanisms underlying neural tube closure defects. The findings are important as they establish a quantitative, reproducible 2D human iPSC-to-neural-progenitor platform for analyzing cell-shape dynamics during differentiation. The convincing evidence provided, combined with the relative simplicity of the model and its tractability as a patient-specific and reverse genetic platform, make it attractive.

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

    1. eLife Assessment

      The authors describe an interesting approach to studying the dynamics and function of membrane proteins in different lipid environments. The fundamental findings have theoretical and practical implications beyond the study of EGFR to all membrane signalling proteins. The evidence supporting the conclusions is compelling, based on the use of a nanodisk system to study membrane proteins in vitro, combined with state-of-the-art single-molecule FRET. The work will be of broad interest to cell biologists and biochemists.

    1. eLife Assessment

      This valuable paper advances understanding of the role of the HGF receptor, MET, in cancer cell invasion by demonstrating HGF-induced coordinated trafficking of MET and metalloprotease MT1-MMP into invadopodia. The results are generally solid, but there are concerns about the cell biology and whether the trafficking mechanism is clinically relevant. It's also unclear whether this is a general mechanism or specific to triple-negative breast cancer cells. The paper will be of interest to cancer cell biologists.

    1. eLife Assessment

      This paper reports new data on the structure of the human CTF18-RFC clamp loader complex bound to the PCNA clamp. The new and convincing data compliment previous reports of CTF-RFC-PCNA structures and as such, represents an important contribution.

    1. eLife Assessment

      This study presents valuable findings by demonstrating that specific GPCR subtypes induce distinct extracellular vesicle miRNA signatures, highlighting a potential novel mechanism for intercellular communication with implications for receptor pharmacology within the field. The evidence is solid, however, more experiments are needed to determine whether the distinct extracellular vesicle miRNA signatures result from GPCR-dependent miRNA expression or GPCR-dependent incorporation of miRNAs into extracellular vesicles.

    1. eLife Assessment

      This valuable study presents a thorough analysis of protein abundance changes caused by amino acid substitutions, using structural context to improve predictive accuracy. By deriving substitution response matrices based on solvent accessibility, the authors demonstrate that simple structural features can predict abundance effects with accuracy comparable to complex methods such as free energy calculations. The strength of the evidence is convincing, supported by robust experimental design and comprehensive analyses.

    1. eLife Assessment

      This study reports insights into how the caspase Dcp-1, best known for cell death, can also promote tissue growth in Drosophila, extending the authors' earlier work by identifying regulatory factors that shape this non-lethal activity. The valuable findings identify new Dcp-1-interacting proteins Sirt1, Fkbp59, Debcl, Buffy, Atg2, and Atg8a, and help broaden understanding of how growth and death pathways intersect. The evidence is solid, but some conclusions would be strengthened by additional studies, particularly regarding the nature of the cell death observed and the involvement of autophagy.

    1. eLife Assessment

      This study presents a valuable advance by enabling functional mapping of Ca²⁺ responses in live human pancreatic tissue slices, providing new opportunities to study islet heterogeneity and diabetes-related dysfunction in an intact tissue context. The evidence supporting the main conclusions is solid, based on reproducible methodology and functional validation across multiple human donor samples. Key revisions needed include clearer quantification of transduction efficiency and tissue viability, and improved clarification of how CaMPARI2 signals should be interpreted.

    1. eLife Assessment

      This paper addresses valuable questions about the evolution of recombination landscape under domestication by examining recombination maps in domesticated chickens and their wild ancestor. However, despite employing a state-of-the-art deep learning method for recombination map inference, the lack of systematic benchmarking and presence of some unexpected patterns raise concerns about the reliability of the inferred maps, thus providing incomplete support for rapid evolution of recombination landscapes. Additionally, due to methodological limitations in testing for intra-genome correlations between evolutionary processes, the current evidence is inadequate to support the associations of recombination with selection and/or introgression in domesticated chickens.

    1. eLife Assessment

      Koch et al. describe a valuable novel methodology, SynSAC, to synchronise cells to analyse meiosis I or meiosis II or mitotic metaphase in budding yeast. The authors present convincing data to validate abscisic acid-induced dimerisation to induce a synthetic spindle assembly checkpoint (SAC) arrest that will be of particular importance to analyse meiosis II. The authors use their approach to determine the composition and phosphorylation of kinetochores from meiotic metaphase I and metaphase II that will be of interest to the broader meiosis research community.

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

    1. eLife Assessment

      This work offers important insights into the protein CHD4's function in chromatin remodeling and gene regulation in embryonic stem cells, supported by extensive biochemical, genomic, and imaging data. The use of an inducible degron system allows precise functional analysis, and the datasets generated represent a key resource for the field. The revised study offers compelling evidence and makes a significant contribution to understanding CHD4's role in epigenetic regulation. This work will be of interest to the epigenetics and stem biology fields.

    1. eLife Assessment

      This valuable study presents Altair-LSFM, a well-documented implementation of a light-sheet fluorescence microscope (LSFM) designed for accessibility and reduced cost. The approach provides compelling evidence of its strengths, including the use of custom-machined baseplates, detailed assembly instructions, and demonstrated live-cell imaging capabilities. This manuscript will be of interest to microscopists and potentially biologists seeking accessible LSFM tools.

    1. eLife Assessment

      In this study, the authors investigate the role of ZMAT3, a p53 target gene, in tumor suppression and RNA splicing regulation. Using quantitative proteomics, the authors uncover that ZMAT3 knockout leads to upregulation of HKDC1, a gene linked to mitochondrial respiration, and that ZMAT3 suppresses HKDC1 expression by inhibiting c-JUN-mediated transcription. This set of convincing evidence reveals a fundamental mechanism by which ZMAT3 contributes to p53-driven tumor suppression by regulating mitochondrial respiration.

    1. eLife Assessment

      This important study provides the first putative evidence that alteration of the Hox code in neck lateral plate mesoderm is sufficient to induce ectopic development of forelimb buds at neck level. The authors use both gain-of-function (GOF) and loss-of-function (LOF) approaches in chick embryos to test the roles of Hox paralogy group (PG) 4-7 genes in limb development. The GOF data provide strong evidence that overexpression of Hox PG6/7 genes are sufficient to induce forelimb buds at neck level. However, the experiments using dominant negative constructs are lacking some key controls that are needed to demonstrate the specificity of the LOF effect rendering the work as a whole incomplete.

    1. eLife Assessment

      This study reports useful information on the mechanisms by which a high-fat diet induces arrhythmias in the model organism Drosophila. Specifically, the authors propose that adipokinetic hormone (Akh) secretion is increased with this diet, and through binding of Akh to its receptor on cardiac neurons, arrhythmia is induced. The authors have revised their manuscript, but in some areas the evidence remains incomplete, which the authors say future studies will be directed to closing the present gaps. Nonetheless, the data presented will be helpful to those who wish to extend the research to a more complex model system, such as the mouse.

    1. eLife Assessment

      This fundamental study is part of an impressive, large-scale effort to assess the reproducibility of published findings in the field of Drosophila immunity. In a companion article, the authors analyze 400 papers published between 1959 and 2011, and assess how many of the claims in these papers have been tested in subsequent publications. In this article, the authors report the results of validation experiments to assess a subset of the claims that, according to the literature, have not been corroborated. While the evidence reported for some of these validation studies is convincing, it remains incomplete for others.

    1. 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 describes how density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template. However, the evidence described for the claim that this technique "significantly" improves the alignment of the reconstruction of small complexes is incomplete. The authors could better evaluate the effects of model bias on the reconstructed densities.

    1. eLife Assessment

      This work identifies a novel, conserved link between glycolysis and sulfur metabolism that governs fungal morphogenesis and virulence. The compelling evidence, integrating multiple approaches, provides an important conceptual advance. A future mechanistic dissection of how sulfur metabolites interface with known pathways is encouraged.

    1. eLife Assessment

      This study presents DeepTX, a valuable methodological tool that integrates mechanistic stochastic models with single-cell RNA sequencing data to infer transcriptional burst kinetics at genome scale. The approach is broadly applicable and of interest to subfields such as systems biology, bioinformatics, and gene regulation. The evidence supporting the findings is solid, with appropriate validation on synthetic data and thoughtful discussion of limitations related to identifiability and model assumptions.

    1. eLife Assessment

      This study provides important insights into mural cell dynamics and vascular pathology using a zebrafish model of cerebral small vessel disease. The authors present convincing evidence that partial loss of foxf2 function results in progressive, cell-autonomous defects in pericytes accompanied by endothelial abnormalities across the lifespan. By leveraging advanced in vivo imaging and genetic approaches, the work establishes zebrafish as a powerful and relevant model for dissecting the cellular mechanisms underlying cerebral small vessel disease.

    1. eLife Assessment

      This valuable study uses fiber photometry, implantable lenses, and optogenetics, to show that a subset of subthalamic nucleus neurons are active during movement, and that active but not passive avoidance depends in part on STN projections to substantia nigra. The strength of the evidence for these claims is solid and this paper may be of interest to basic and applied behavioural neuroscientists working on movement or avoidance.

    1. eLife Assessment

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

    1. eLife Assessment

      This paper represents a valuable contribution to our understanding of how LFP oscillations and beta band coordination between the hippocampus and prefrontal cortex of rats may relate to learning. Enthusiasm for the reported results was moderated by the concern that some key analyses need to be done, and highly relevant details about task, data, and statistics were missing. Consequently, the reviewers considered the evidence to be incomplete in this version of the manuscript.

    1. eLife Assessment

      This important study uncovers a previously unrecognized light-responsive pathway in C. elegans that depends on live food bacteria and is mediated by the bZIP factors ZIP-2/CEBP-2 and the cytochrome P450 enzyme, CYP-14A5. The authors show that this bacteria-linked pathway modulates long-term memory and can be harnessed as a low-cost light-inducible expression system, opening new directions for sensory biology and genetic engineering in worms. The exact means by which live bacteria modulate light signal that activates ZIP-2/CEBP-2 in the worm remains to be elucidated. The evidence supporting the pathway's role uses multiple genetic, transcriptional, and behavioural assays, and is convincing.

    1. eLife Assessment

      This important study presents a methodologically rigorous framework for stability-guided fine-mapping, extending PICS and generalizing to methods such as SuSiE, supported by comprehensive simulations and functional enrichment analyses. The evidence is now convincing, demonstrating improved causal variant recovery and offering a robust alternative for cross-population fine-mapping. The approach will be of particular interest to statistical geneticists, computational biologists, and biomedical researchers who rely on fine-mapping to interpret genetic association signals.

    1. eLife Assessment

      This fundamental work reveals that the accessibility of the unstructured C-terminal tails of α- and β-tubulins differs with the state of the microtubule lattice. Their accessibility increases with the expansion of the lattice induced by GTP and certain MAPs, which can then dictate the subsequent interactions between MAPs and microtubules, and post-translational modifications of tubulin tails. The evidence supporting the conclusion is compelling, although the characterisation of the probes does not answer whether they directly affect the lattice or expose the C-terminal tails of tubulin. The probes can be used as tools in the future to study differences in microtubule lattice assembly under different conditions both in vitro and in vivo. This work will be of great interest to the cytoskeleton field.

    1. eLife Assessment

      This manuscript presents useful insights into the molecular basis underlying the positive cooperativity between the co-transported substrates (galactoside sugar and sodium ion) in the melibiose transporter MelB. Building on years of previous studies, this convincing study improves on the resolution of previously published structures and reports the presence of a water molecule in the sugar binding site that would appear to be key for its recognition, introduces further structures bound to different substrates, and utilizes binding and transport assays, as well as HDX-MS and molecular dynamics simulations to further understand the positive cooperativity between sugar and the co-transported sodium cation. The work will be of interest to biologists and biochemists working on cation-coupled symporters, which mediate the transport of a wide range of solutes across cell membranes.

    1. eLife Assessment

      This important study uses standard single-cell RNA-seq analyses combined with methods from the social sciences to reduce heterogeneity in gene expression in Drosophila imaginal wing disc cells treated with 4000 rads of ionizing radiation. The use of this methodology from social sciences is novel in Drosophila and allows them to identify a subpopulation of cells that is disproportionately responsible for much of the radiation-induced gene expression. Their compelling analyses reveal genes that are expressed regionally after irradiation, including ligands and transcription factors that have been associated with regeneration, as well as others whose roles in response to irradiation are unknown. This paper would be of interest to researchers in the field of DNA damage responses, regeneration, and development.

    1. eLife Assessment

      This important study, which tackles the challenge of analyzing genome integrity and instability in unicellular pathogens by introducing a novel single-cell genomics approach, presents compelling evidence that this new tool outperforms standard whole-genome amplification techniques. While thorough and rigorous, the work's impact would increase by providing scripts and data, as well as a description of the biological relevance that would make this method more appealing to the broad community studying genetic heterogeneity in diverse organisms.

    1. eLife Assessment

      This work reports the characterization of newly identified genetic variants of SLC4A1 in patients with distal renal tubular acidosis. Cell culture studies supplemented with histological analysis of a previously established disease mouse model provide convincing evidence that some of the variants increase intracellular pH, reduce ATP synthesis, and attenuate autophagic degradative flux. The study is valuable in establishing a mechanistic framework for future exploration of the link between intracellular pH and mutations in SLC4A1 in vivo.

    1. eLife Assessment

      This important study reports convincing evidence of associations between 35 polygenic indices (PGIs) for social, behavioural, and psychological traits, as well as other health conditions (e.g., BMI) and all-cause mortality, based on data from Finnish population-based surveys and a twin cohort linked to administrative registers. PGIs for education, depression, alcohol use, smoking, BMI, and self-rated health showed the strongest associations with all-cause mortality, in the order of ~10% increment in risk per PGI standard deviation. Effect sizes from twin-difference analyses tended to be slightly larger than those from population cohorts, a pattern opposite that generally observed when testing PGI associations with their target phenotypes, and supporting the robustness of findings to confounding by population stratification.

    1. eLife Assessment

      This work significantly advances our understanding of chromatin organization within regions of repetitive sequences in the parasitic protozoan Trypanosoma brucei. Using cutting edge interdisciplinary tools, the authors provide compelling evidence for two discrete types of repetitive DNA element-associated proteins- one set involved in essential centromere function; and, the other involved in glycoprotein antigenic variation via homologous recombination. Thus, these fundamental findings have implications for this parasite's biology, and for therapeutic targeting in kinetoplastid diseases. This work will be exciting to those in the centromere/mitosis and parasite immunity fields.

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

    1. eLife Assessment

      This important study examines the role of map3k1, a MAP3K family member that has both kinase and ubiquitin ligase domains, in the differentiation of progenitors in the flatworm Planaria. The convincing analyses demonstrate that map3k1 acts within progenitors to restrict their premature differentiation and to prevent formation of teratomas. This work would be of interest to researchers in the fields of regeneration, developmental biology, and aging.

    1. eLife Assessment

      This important study employs a closed-loop, theta-phase-specific optogenetic manipulation of medial septal parvalbumin-expressing neurons in rats and reports that disrupting theta-timescale coordination impairs performance of challenging aspects of spatial behaviors, while sparing hippocampal replay and spatial coding in hippocampal place cells. The findings are expected to advance theoretical understanding of learning and memory operations and to provide practical implications for the application of similar optogenetic approaches. The experiments were viewed as technically rigorous, but the strength of evidence provided in the current version of the manuscript was viewed as incomplete, mostly due to limited analyses and the descriptions of some of the experimental protocols.

    1. eLife Assessment

      This is a useful study that investigates the role of the long non-coding RNA Dreg1 for the development, differentiation, or maintenance of group 2 ILC (ILC2). The authors generate Dreg1-/- mice and show a reduction of group 2 innate lymphoid cells (ILC2). However, the strength of evidence supporting the impact of Dreg1 on Gata3 expression, a transcription factor required for ILC2 cell fate decisions, and the cell-intrinsic requirement of Dreg1 for ILC2 remain incomplete. This study will be of interest to immunologists.

    1. eLife Assessment

      This study presents a platform to implement closed-loop experiments in mice based on auditory feedback. The authors provide convincing evidence that their platform enables a variety of closed-loop experiments using neural or movement signals, indicating that it will be a valuable resource to the neuroscience community. The paper could be strengthened by the addition of additional tutorials, such as on how to run an experiment.

    1. eLife Assessment

      This is a valuable study that integrates behavioral and molecular approaches to identify neuromodulators influencing blood-feeding behavior in the disease vector Anopheles stephensi. Through gene expression analyses across blood-seeking life stages and RNA interference experiments, the authors present solid evidence that co-knockdown of the neuromodulators short Neuropeptide F and RYamide affects blood-seeking states in A. stephensi. However, evidence demonstrating that these neuropeptides are sufficient to promote host-seeking is lacking.

    1. eLife Assessment

      This paper provides a useful new theory of the hallucinatory effects of 5-HT2A psychedelics. The authors present convincing evidence that a computational model trained with the Wake-Sleep algorithm can reproduce some features of hallucinations by varying the strength of top-down connections in the model, though it is not clear that this model applies to 5-HT2A hallucinogens in particular. The work will be of interest to researchers studying hallucinations or offline activity and plasticity more broadly.

    1. eLife Assessment

      This valuable study highlights the key role of NK cells and PD-L1+ neutrophils in worsening sepsis responses in the context of MASH (metabolic dysfunction-associated steatohepatitis). It focused on the role of neutrophils in mediating this effect, which is based on a choline-deficient high-fat diet model of various knockouts or selective ablation of immune cell types. While the data presented are of great interest, there are concerns around the reliability of the strength of the evidence provided, which is currently considered incomplete. The study may be of interest to researchers in immunopathological disease mechanisms once confirmatory studies have been completed.

      [Editors' note: the authors no longer have access to the original flow cytometry data and plan to compile new datasets for further consideration.]

    1. eLife Assessment

      This work describes the establishment of an image analysis pipeline for signal correction, segmentation and quantitative data analysis of multilayered organoid and tumoroid systems. The revised study is important for the field to address many practical challenges in deep-tissue visualization. The image analysis pipeline is well-designed and compelling.

    1. eLife Assessment

      This important work compares the size of two brain areas, the amygdala and the hippocampus, across 12 species belonging to the Macaca genus. The authors find, using a convincing methodological approach, that amygdala - but not hippocampal - volume varies with social tolerance grade, with high tolerance species showing larger amygdala than low tolerance species of macaques. Interestingly, their findings also suggest an inverted developmental effect, with intolerant species showing an increase in amygdala volume across the lifespan, compared to tolerant species exhibiting the opposite trend. Overall, this paper offers new insights into the neural basis of social and emotional processing.

    1. eLife Assessment

      The current work uses DNA-tethered motor trapping to reduce vertical forces and improve datasets for kinesin-1 motility under load. The evidence is compelling and the significance is important to the kinesin field. Kinesin-1 is more robust and less prone to premature detachment than previously indicated. This represents a significant advancement in the field and is generally applicable to work with optical tweezers.

    1. eLife Assessment

      This paper undertakes an important investigation to determine whether movement slowing in microgravity is due to a strategic conservative approach or rather due to an underestimation of the mass of the arm. The experimental dataset is unique, the coupled experimental and computational analyses comprehensive, and the effect is strong. However, the authors present incomplete results to support the claim that movement slowing is due to mass underestimation. Further analysis is needed to rule out alternative explanations.

    1. eLife Assessment

      In this useful study, the authors conducted an impressive amount of atomistic simulations with a realistic asymmetric lipid bilayer to probe how the HIV-1 envelope glycoprotein (Env) transmembrane domain, cytoplasmic tail, and membrane environment influence ectodomain orientation and antibody epitope exposure. The simulations convincingly show that ectodomain motion is dominated by tilting relative to the membrane and explicitly demonstrate the role of membrane asymmetry in modulating the protein conformation and orientation. However, due to the qualitative nature of the conducted analyses, the evidence for the coupling between membrane-proximal regions and the antigenic surface is considered incomplete. With stronger integration of prior experimental and computational literature, this work has the potential to serve as a reference for how Env behaves in a realistic, glycosylated, membrane-embedded context.

    1. eLife Assessment

      This valuable study uses NAD(P)H fluorescence lifetime imaging (FLIM) to map metabolic states in the Drosophila brain. The authors reveal subtype-specific metabolic profiles in Kenyon cells and report learning-related changes, supported by solid evidence and careful methodology. However, the FLIM shifts observed after memory formation in α/β neurons are small and only weakly significant, so the ability of FLIM to detect subtle physiological changes still requires further validation. Nevertheless, this work provides a strong starting point and demonstrates the promising potential of FLIM for probing neural metabolism in vivo.

    1. eLife Assessment

      This study provides a useful application of computational modelling to examine how people with chronic pain learn under uncertainty, contributing to efforts to link pain with motivational processes. However, the evidence supporting the main claims is incomplete, as the modelling differences are not reflected in observable behaviour or pain measures, and the interpretation extends beyond what the data can substantiate. The conclusions would benefit from a clearer explanation of the behavioural differences that underlie the computational findings.

    1. eLife Assessment

      This manuscript proposes a lateralized, lobe-specific brain-liver sympathetic neurocircuit regulating hepatic glucose metabolism and presents anatomical evidence for sympathetic crossover at the porta hepatis using viral tracing and neuromodulation approaches. While the topic is of important significance and the methodologies are, in principle, state-of-the-art, significant concerns regarding experimental design, incomplete methodological reporting, sparse and ambiguous labeling, and overi-nterpretation of the data substantially weaken support for the study's central conclusions, thereby limiting the study's completeness. The work will be of interest to biologists, clinicians, and physiologists.

    1. eLife Assessment

      The findings are important, as they identify MIRO1 as a central regulator linking mitochondrial positioning and respiratory chain function to VSMC proliferation, neointima formation, and human vasoproliferative disease. Overall, the strength of evidence is convincing, with comprehensive in vivo and in vitro data, including human cells and added bioenergetic analyses, that broadly support the main claims despite some remaining limitations in mechanistic and mitochondrial assays.

    1. eLife Assessment

      This manuscript provides useful insights into how the brain can simultaneously represent events and the times when they occurred. The results include a comparison between two different basis functions for temporal selectivity and how these generate different predictions for the dynamics of neural populations. The conclusions are partly incomplete because of questions such as the impact of the linear separability assumption and whether joint encodings of event type and time can be made without it.

    1. eLife Assessment

      The authors provide a scholarly review of intracranial research into the neural correlates of consciousness (NCCs). To our knowledge, this is the first such review, and it therefore may become a must-read for anyone working in the field of consciousness research. It is not so persuasive that intracranial recordings are better suited to identifying pure NCCs than other methods, which appears a problem instead solved through novel paradigms and better-developed theories - but this no doubt reflects an in-depth, timely, and insightful contribution to the literature.

    1. eLife Assessment

      This important study establishes a workflow based on environmental sampling for the discovery of bacteriophages capable of infecting antibiotic-resistant pathogens. The experimental design, analysis, and results demonstrating the effectiveness of the workflow are convincing, although a broader sampling scheme and more careful framing of the data within the current limitations of viral taxonomy could strengthen the work. This study will interest researchers working on bacterial infections, environmental microbiology, and phage-based alternatives for addressing antimicrobial resistance.

    1. eLife Assessment

      This important work shows that a history of cocaine self-administration disrupts the orbitofrontal cortex's ability to encode similarities between distinct sensory stimuli that possess identical task information - hidden states. The evidence supporting these conclusions is compelling, with methods and analyses spanning self-administration, a novel 'figure 8' sequential odor task, recordings from 3,881 single units, and sophisticated firing analyses revealing complex orbitofrontal representations of task structure. These results will be of broad interest to psychologists, neuroscientists, and clinicians.

    1. eLife Assessment

      This important study provides the first direct neuroimaging evidence for the integration-segregation theory of exogenous attention underlying inhibition of return, using an optimized IOR-Stroop fMRI paradigm to dissociate integration and segregation processes and to demonstrate that attentional orienting modulates semantic- and response-level conflict processing. Although the empirical evidence is compelling, clearer justification of the experimental logic, more cautious framing of behavioral and regional interpretations, and greater transparency in reporting and presentation are needed to strengthen the conclusions. The work will be of broad interest to researchers investigating visual attention, perception, cognitive control, and conflict processing.

    1. eLife Assessment

      This important work contributes a transcriptional dataset that identifies potential genes involved in axon initial growth and axon regrowth, followed by a characterization of axon phenotypes after knockdown of a subset of these genes. Focused experiments on a single gene, Pmvk, highlight the potential role of the mevalonate pathway in axon regrowth. The methods are convincing, though partially incomplete. The data establish a basis for further studies on axonal development and will be of interest to both developmental neurobiologists and those seeking to develop molecular tools to target, monitor, and manipulate axon morphology and function.

    1. eLife Assessment

      This valuable study characterises the activity of motor units from two of the three anatomical subdivisions ("heads") of the triceps muscle while mice walked on a treadmill at various speeds. Altogether, this is the most thorough characterisation of motor unit activity in walking mice to date, providing solid evidence for probabilistic recruitment of motor units that differed between the two heads.

    1. eLife Assessment

      This important model-based study seeks to mimic bat echolocation behavior and flight under conditions of high interference, such as when large numbers of bats leave their roost together. The simulations convincingly suggest that the problem of acoustic jamming in these situations may be less severe than previously thought. This finding will be of broad interest to scientists working in the fields of bat biology and collective behaviour.

    1. eLife Assessment

      This important mouse study shows that wild-type female progeny of Khdc3 mutants have abnormal gene expression relating to hepatic metabolism, which persists over multiple generations and passes through both female and male lineages. A role for small RNAs on this phenomenon is proposed, and evidence supporting the authors' claims is convincing. Further experiments are required to functionally validate the role of small RNAs in transmission of the phenotype. The work will be of interest to researchers in the field of DNA-independent mechanism of inheritance.

    1. eLife Assessment

      The study presents data on the possible connection of respiratory pathologies like pneumonia in a cohort of dolphins with altered composition and concomitant perturbed biophysical properties of pulmonary surfactant complexes. Overall, it is a valuable contribution that could be of interest to scientists in the field. However, the study as it is appears somewhat incomplete and additional clarification and discussions are required in order to explain a few methodological questions that may limit the impact of the work considerably.

    1. eLife Assessment

      This is a potentially important paper attempting to identify neutral correlates of memory engram expression in humans, and how they change during forgetting. The questions posed are clear and novel. The methods employed, namely behavioral analysis, high-resolution functional magnetic resonance imaging, and representational similarity analysis, are advanced, integrative, and appropriate. The experiments are well designed and combine analysis of recollection and familiarity of object/face associations. However, substantial questions remain as to the validity of the incomplete statistical analyses applied to the imaging data, as well as the parsing of and interpretation of the behavioral data.

    1. eLife Assessment

      This valuable study links psychological theories of chunking with a physiological implementation based on short-term synaptic plasticity and synaptic augmentation. The theoretical derivation for increased memory capacity via hierarchical chunking is solid. However, the model robustness and biological grounding of the mechanism - including many aspects that were hard-wired, chunking cues, and parameter ranges - as well as its evaluation in the task settings that motivated the study, are incomplete. Additional simulations to test robustness in more cognitively and biologically realistic settings, a systematic parameter analysis, and stronger links to prior work would substantially strengthen the manuscript and increase its impact across disciplines.

    1. eLife Assessment

      The granularity with which neural activity in the sensorimotor cortex of mice corresponds to voluntary forelimb motion is a key open question. This paper provides compelling evidence for the encoding of low-level features like joint angles and represents an important step forward toward understanding cortical limb control signals.

    1. eLife Assessment

      This important study uses an original method to address the longstanding question of why reaching movements are often biased. The combination of a wide range of experimental conditions and computational modeling is a strength. Convincing evidence is presented in support of the main claim that most of the biases in 2-D movement planning originate in misalignment between visuo-proprioceptive reference frames.

    1. eLife Assessment

      This valuable study assesses through simulations how several features of local cortical circuits - interneuron subtypes, their specific targeting of dendritic compartments, and certain brain rhythms - together affect the integration of synaptic inputs by a pyramidal cell. Employing several carefully considered simulation setups they convincingly demonstrate that beta rhythms are best suited to modulate and control dendritic Ca-spikes while gamma rhythms affect their coupling to somatic spiking, or how basal inputs are directly integrated into somatic spikes. However, the baseline setup may be idealized for the generation of the events in question and it would be beneficial if the similarity to the in-vivo activity regime was demonstrated further. The results will be relevant for neuroscientists studying local circuits or developing more abstract theories at the systems level.

    1. eLife Assessment

      The presented findings are important for the field of cell-cycle control. They provide new insights into the origin of cell size variability in budding yeast. The strength of evidence is solid. However, the conclusions could be more strongly supported by additional analysis.

    1. eLife Assessment

      This important paper presents the discovery of the molecular basis of differential apterous expression during early Drosophila wing disc development. The evidence supporting these conclusions is compelling, ranging from classical genetic approaches to state-of-the-art genetic engineering techniques. By opening new questions, this paper is expected to be of broad interest to developmental biologists and geneticists working on transcriptional regulation.

    1. eLife Assessment

      In this valuable study, Parrotta et al. showed that it is possible to modulate pain perception and heart rate by providing false heart rate (HR) acoustic feedback before administering electrical cutaneous shocks. The evidence supporting the claims of the authors is rather solid, although what they consider an interoceptive signal is not necessarily supported as such by the results. In this regard, including a larger number of trials per participant, increasing the sample size, and adding a measure of actual pain perception after its induction would have strengthened the study. Although mechanisms and some alternative explanations for this effect remain to be addressed, the work will nonetheless be of interest to neuroscientists working on predictions and perception, health psychologists, pain researchers, and placebo researchers.

    1. 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.

    1. eLife Assessment

      This important study examined age-related changes in cerebellar function by testing a large sample of younger and older adults, including 30 over 80 years old, on motor and cognitive tasks linked to the cerebellum and conducting structural imaging. Their findings show that cerebellar-dependent functions are mostly maintained or even enhanced across the lifespan, with cerebellar-mediated motor abilities remaining intact despite degeneration, in contrast to non-cerebellar measures. Overall, the authors provide solid evidence in support of preserved cerebellar function with age. These results highlight the resilience and redundancy of cerebellar circuits and offer key insights into aging and motor behavior.

    1. eLife Assessment

      This important study employs functional magnetic resonance spectroscopy (fMRS) to demonstrate that GABAergic inhibition in the parietal cortex actively suppresses goal-irrelevant distractors, thereby facilitating goal-directed visual tracking. The data and analyses are solid, and the methodology is validated. However, the link between the metabolic changes and the purported functional mechanisms is incomplete due to concerns with experimental design and interpretations. The study will be of interest to researchers studying goal-directed behavior and neurochemical dynamics in cognitive processing.

    1. eLife Assessment

      This important study shows that a controlled pause in gene reading is required for early heart cells to form during development. The authors demonstrate that loss of this pause prevents the proper activation of the heart-producing program across animal and stem cell systems. The evidence is compelling, supported by careful genomic and functional analyses that clearly define the developmental block. Overall, this work will interest developmental biologists and inspire further studies on the origins of early heart defects.

    1. eLife Assessment

      This useful study reports that the exogenous expression of the microRNA miR-195 can partially compensate in early B cell development for the loss of EBF1, one of the key transcription factors in B cells. While this finding will be of interest to those studying lymphocyte development, the evidence, particularly with regard to the molecular mechanisms that underpin the effect of miR-195, is currently incomplete.

    1. eLife Assessment

      In reporting on a valuable "learning proteome" for a C. elegans gustatory associative learning paradigm, this work identifies a new set of genes to be tested for roles in learning and memory, describes molecular pathways involving these genes and relevant for learning and memory in C. elegans, and deliver a new set of tools for prodding worm behavior. The methods and results convincingly support the findings, which will be of interest to neuroscientists and developmental biologists seeking to understand the self-assembly and operation of neural circuits for learning and memory.

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

    1. eLife Assessment

      This valuable work demonstrates that M. tuberculosis protein PPE2 perturbs adipose tissue biology by modulating adipogenesis, lipolysis, and inflammatory remodeling, thereby contributing to fat loss and insulin resistance during TB. Using M. smegmatis overexpression strains, PPE2-deficient Mtb mutants, and mouse models, the study links PPE2 to downregulation of PPAR-γ, C/EBP-α, adiponectin, and broader transcriptional changes in host fatty acid metabolism. These findings convincingly highlight, for the first time, a direct role for a bacterial virulence factor in TB-associated wasting. However, despite strong associative evidence, the mechanistic basis of PPE2-mediated regulation remains unresolved.

    1. eLife Assessment

      Combining connectomics, optogenetics, behavioral analysis and modeling, this study delivers important findings on the role of inhibitory neurons in the generation of leg grooming movements in Drosophila. The results include convincing evidence that the identified neuronal populations are key in the generation of rhythmic leg movements, structured in distinct polysynaptic pathways articulating inhibition and disinhibition of antagonistic sets of motor neurons, as mapped from an electron microscopy volume of the ventral nerve cord, which orchestrate an alternation of flexion and extension. By analyzing limb kinematics upon experimentally silencing specific populations of premotor inhibitory neurons, together with computational modelling, the potential role of these neurons in rhythmic leg movement is shown. This work will be of interest to neuroscientists working in motor control and limbed locomotion.

    1. eLife Assessment

      This manuscript by Kaur et al. identifies differential gene expression in distinct cell populations, specifically myeloid and lymphoid cells, following short-term exposure to e-cigarette aerosols with various flavors. Their findings are useful because they provide a single-cell sequencing data resource for assessing which genes and cellular pathways could be affected by e-cig aerosols and their components. However, the evidence is incomplete due to limited number of biological replicates per condition, as well as due to the lack of in vivo validation.

    1. eLife Assessment

      The IBEX Knowledge-Base is a fundamental tool that will enhance scientific collaboration by providing a centralized, community-driven resource for immunofluorescence imaging and reagent validation. Its detailed use cases, open-source design, and transparent reporting offer exceptional evidence of its broad utility and impact in the life sciences. It is now up to the community to contribute to its growth. Overall, the resource sets a high standard as a blueprint for future community initiatives in reproducibility and standardization.

    1. eLife Assessment

      This important study identifies a new key factor in orchestrating the process of glial wrapping of axons in Drosophila wandering larvae. The evidence supporting the claims of the authors is convincing and the EM studies are of outstanding quality. After the revision, the authors have addressed most of the concerns and the manuscript has been significantly improved. Both reviewers have agreed on the significance of the work. The work will be of interest to neuroscientists working on glial cell biology.

    1. eLife Assessment

      This important study investigates why the 13-lined ground squirrel (13LGS) retina is unusually rich in cone photoreceptors, the cells responsible for color and daylight vision. The authors perform deep transcriptomic and epigenetic comparisons between the mouse and the 13-lined ground squirrel (13LGS) to provide convincing evidence that identifies mechanisms that drive rod vs cone-rich retina development. Overall, this key question is investigated using an impressive collection of new data, cross-species analysis, and subsequent in vivo experiments.

    1. eLife Assessment

      This valuable retrospective analysis identified three independent components of glucose dynamics - "value," "variability," and "autocorrelation" - which may be used in predicting coronary plaque vulnerability. The study is solid and of interest to a wide range of investigators in the medical field who are interested in the role of glycemia on cardiometabolic health. The manuscript has been substantially strengthened by clarifying methods, improving transparency, and validating key findings, resulting in a coherent and persuasive case for autocorrelation as a meaningful third dimension of glucose dynamics despite remaining design-related limitations.

    1. eLife Assessment

      This valuable study identifies a novel regulator of stress-induced gene quiescence in C. elegans: the multi-Zinc-finger protein ZNF-236. The work provides evidence for an active mechanism that maintains the repressed state of inducible genes under basal conditions in the absence of stress. The claims for discovery made in the title and abstract are supported by solid experimental data. However, a deeper investigation into the mechanisms of ZNF-236 action could substantially enhance the manuscript's impact and value.

    1. eLife Assessment

      This study delivers valuable new insights into the neural circuits involved in post-mating responses (PMR) in Drosophila females, supported by convincing evidence that the circuits for mating receptivity and egg-laying are distinct. The new experimental evidence adds to the current understanding the neural circuits and molecular mechanisms underpinning PMR.

  3. Dec 2025
    1. eLife Assessment

      This study investigates the function of Chi3l1 in hepatic macrophages in the context of MASLD, providing useful insights at a time when the distinct roles of Kupffer cells or monocyte-derived macrophages in this disease remain incompletely defined. The data suggests that CHI3L1 in Kupffer cells modulates glucose handling in obesity and mitigates systemic metabolic dysfunction and hepatic steatosis during high-fat, high-fructose feeding. However, the loss-of-function studies employing Kupffer cell restricted versus a pan myeloid Cre lines are not sufficient to support the assertion that CHI3L1 activity is confined to resident Kupffer cells. Additionally, the flow-cytometric analyses reveal a modest depletion of Kupffer cells and no recruitment of TIM4low monocyte-derived macrophages, indicating that the system reflects simple steatosis rather than substantial macrophage turnover or niche remodelling. While the findings are intriguing, further experimentation is required to clarify the cellular specificity and mechanistic basis of the phenotypes observed.

    1. eLife Assessment

      This study describes a genetic screen to identify deubiquitinases (DUBs) that counteract the activity of small molecule degraders (PROTACs). The presented data is valuable, identifying OTUD6A and UCHL5 as DUBs that impact the efficacy and potency of PROTAC-mediated degradation in distinct subcellular compartments. While the conclusions are broadly supported and the methods employed are solid, the validation of OTUD6A and UCHL5 mechanisms requires additional study. Overall, these findings merit further evaluation by the targeted protein degradation community when developing and optimizing PROTACs and efforts to achieve compartment-specific degradation.

    1. 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, although several aspects of the model remain only partially supported due to 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, but the conclusions would be strengthened by greater precision in methodology, terminology, and interpretation.

    1. eLife Assessment

      This study uses a novel 3D imaging method to identify the Periportal Lamellar Complex (PLC), an important new structure. Although the methodological advancement and morphological descriptions are convincing, the evidence for its proposed function is incomplete, relying on transcriptomic correlation rather than direct experimental validation. The work would therefore be strengthened by focusing its claims on the robust methodological advancement and detailed morphological characterization.

    1. eLife Assessment

      In this valuable study, the authors present traces of bone modification on ~1.8 million-year-old proboscidean remains from Tanzania, which they infer to be the earliest evidence for stone-tool-assisted megafaunal consumption by hominins. Challenging published claims, the authors argue that persistent megafaunal exploitation roughly coincided with the earliest Achulean tools. Notwithstanding the rich descriptive and spatial data, the behavioral inferences about hominin agency rely on traces (such as bone fracture patterns and spatial overlap) that are not unequivocal; the evidence presented to support the inferences thus remains incomplete. Given the implications of the timing and extent of hominin consumption of nutritious and energy-dense food resources, as well as of bone toolmaking, the findings of this study will be of interest to paleoanthropologists and other evolutionary biologists.

    1. eLife Assessment

      This manuscript presents a fundamental advance in our understanding of nuclear receptor pharmacology by expanding on previous work demonstrating dual ligand occupancy in the peroxisome proliferator-activated receptor-gamma (PPARγ). Using a compelling combination of biophysical, biochemical, and cellular approaches, the authors show that covalent inverse agonists with enhanced efficacy shift the receptor conformation toward a transcriptionally repressive state that limits orthosteric ligand co-binding more effectively. This revised manuscript further strengthens support for a proximal, bidirectional allosteric model of dual ligand occupancy by sharpening the distinction between prior and new findings, adding clear conceptual figures, and strengthening statistical rigor.

    1. eLife Assessment

      This study addresses an important problem in gene regulation, namely, which features of chromatin regulate potential RNA Polymerase 2 activity at a locus. The authors provided evidence that specific post-translational modifications of histones within the gene body are correlated with Pol II transcription, that these modifications are dynamic, and that they can be regulated by Pol II activity. The manuscript contributes to the concept of "fragile nucleosomes" as a unifying framework for key epigenetic drivers of transcription; however, the quality of the evidence provided is inadequate in support of the claims made, and further evidence teasing out the mechanistic aspects of the work would strengthen its impact. This work will be of interest to the fields of transcriptional regulation, chromatin structure, and epigenetics.

    1. eLife Assessment

      This is an important study on the sensory roles of Cerebrospinal fluid-contacting neurons (CBF-cn) in mammals. The authors identify PKD2L1 as the predominant pH-sensing channel CBF-cn and show how the apical extension is used as an amplifier of chemical changes in the content of the Cerebrospinal fluid. The evidence is solid in experimental design but limited in mechanistic interpretation, as the electrophysiological analyses require re-evaluation.

    1. eLife Assessment

      This study presents important findings on how cardiac regenerative capacity diverges across species by examining heart repair in two species of livebearers, platyfish and swordtails. In contrast to zebrafish, the livebearer species show persistent scarring after cryo-injury, and the work highlights how lineage-specific anatomical and immunological traits may constrain regenerative competence. The study is compelling, the data are convincing, and the results contribute to our understanding of the mechanisms underlying heart regeneration across vertebrates.

    1. eLife Assessment

      In this work, the authors intend to assess the existence of a redox potential across germline stem cells and neighbouring somatic stem cells in the Drosophila testis. Some aspects of the manuscript are convincing, like the clear effect of SOD KD on cyst cell differentiation state. Other conclusions of the work, such as the non-autonomous effect of this KD on germ cells are not sufficiently supported by the data. This remains true even with the revised version of the paper, as the effect of redox state of the soma on the germline is a major point of the paper, and this remains a critical flaw. The work could be potentially useful if the critiques of the reviewers were fully addressed; the strength of the evidence of the manuscript as it stands is still inadequate. Readers should use their own judgment about the validity and meaningfulness of different findings.

    1. eLife Assessment

      This important work advances our understanding of the development of the visual system. The data presented is compelling and provides a detailed single-cell atlas of post-natal anterior chamber development in mice, highlighting the trabecular meshwork and Schlemm's canal.

    1. eLife Assessment

      This important study introduces a new biology-informed strategy for deep learning models aiming to predict mutational effects in antibody sequences. It provides solid evidence that separating selection from the nucleotide-level mutation process improves performance over the objectives of protein language models inspired by natural language processing. This paper should be of interest to computational immunologists, but also to the broader community interested in deep learning for biological sequence data and evolution.

    1. eLife Assessment

      This potentially valuable manuscript focuses on the phosphorylation of residue T495 as a mechanism to inactivate HSP70 and disrupt cell cycle progression in response to DNA damage. The evidence supporting this model is incomplete and would be strengthened by additional studies defining the extent of T495 phosphorylation induced by DNA damage, identifying the kinase responsible for phosphorylating T495 of HSP70, and further elucidation of the functional implications of T495 phosphorylation in human cells. This work will be of interest to scientists focused on topics including chaperone biology, proteostasis, cell cycle progression, and DNA damage.

    1. eLife Assessment

      Rickert and colleagues demonstrate that the host peptidoglycan-binding protein PGLYRP1 has both beneficial and detrimental effects on Bordetella pertussis infection in mice. Using a solid array of techniques, the study provides useful insights into how peptidoglycan species may alter host immune responses. The data on the bactericidal effects on B. pertussis are incomplete, and further experiments are needed to draw conclusions on this question.

    1. eLife Assessment

      This fundamental work substantially advances our understanding of a major research question: whether collagen can be directly imaged with MRI. The evidence supporting the conclusion is compelling, with methods, data, and analyses that are more rigorous than those currently considered state-of-the-art. The work will be of high interest to MR physicists and clinicians, as collagen is the most abundant protein in the human body and plays an essential role in health.

    1. eLife Assessment

      This study presents a valuable analysis of a large dataset of [NiFe]-CODHs, integrating genomic context, operon organization, and clade-specific gene neighborhoods to discern patterns of functional diversification and adaptation. Carefully looking at the CODH genomic context, e.g., CODH-HCP co-occurrence, the authors gain insight into enzymatic activity, biotechnological potential, and differential functional roles. The approach aligns with current standards in genomic enzymology to characterize newly identified enzymes. With solid support, this work provides a broadly informative contribution to the field.

    1. eLife Assessment<br /> <br /> This study examines an important question regarding the developmental trajectory of neural mechanisms supporting facial expression processing. Leveraging a rare intracranial EEG (iEEG) dataset including both children and adults, the authors reported that facial expression recognition mainly engaged the posterior superior temporal cortex (pSTC) among children, while both pSTC and the prefrontal cortex were engaged among adults. In terms of strength of evidence, the solid methods, data and analyses broadly support the claims with minor weaknesses.

    1. eLife Assessment

      This important contribution to enzyme annotation offers a deep learning framework for catalytic site prediction. Integrating biochemical knowledge with large language models, the authors demonstrate how to extract meaningful information from sequence alone. They introduce Squidly, a freely available new ML modeling framework, that outperforms existing tools on standard benchmarks, including the CataloDB dataset. The evidence is convincing, with an extensively and carefully addressed narrative upon revision.

    1. eLife Assessment

      This important study presents a well-constructed multiscale simulation framework to investigate ATP-driven DNA translocation by prokaryotic SMC complexes, supporting a segment-capture mechanism. The strength of evidence is convincing, highlighting the necessity of a precise balance between electrostatic interactions and hydrogen bonding, as well as the critical role of kleisin asymmetry in ensuring unidirectional movement.

    1. eLife Assessment

      This important study reports three experiments examining how the subjective experience of task regularities influences perceptual decision-making. Although the evidence linking subjective ratings to behavioral measures is solid, the study would be strengthened if potential reverse influences of response times on subjective ratings were ruled out and if more comprehensive model comparisons supporting the main claims were performed. The findings will appeal to a wide range of researchers in decision-making and perception.

    1. eLife Assessment

      This paper uses a new computational method that integrates bulk sequencing and single-cell sequencing data to provide refined gene expression datasets for 52 neuron classes in C. elegans. The paper's findings are convincing, presenting an approach that alleviates a key shortcoming of single-cell RNA sequencing. While the datasets have some limitations that the authors acknowledge, the new methodology and refined datasets will be important resources for those interested in understanding how gene expression shapes neuronal morphology and physiology.

    1. eLife Assessment

      This valuable study describes an interesting infection phenotype that differs between adult male and female zebrafish. The authors present data indicating that male-biased expression of Cyp17a2 appears to mediate viral infection through STING and USP8 activity regulation. Through experimentation on male fish, the authors present solid evidence linking this factor to direct and indirect antiviral outcomes through ubiquitination pathways. These findings raise interesting questions about immune mechanisms that underlie sex-dimorphism and the selective pressures that might shape it.

    1. eLife Assessment

      This study makes an important contribution by revealing how saccades selectively disrupt spatial working memory while sparing other object features, and by demonstrating how this mechanism is altered in aging and neurodegeneration. The findings are supported by convincing evidence derived from well-controlled eye-tracking experiments and systematic generative model comparisons. Together, the work provides a computationally grounded framework that is of importance for understanding trans-saccadic memory and its clinical relevance.

    1. eLife Assessment

      This important study presents the rational redesign and engineering of interleukin-7. The data from the integrated approach of using computational, biophysical, and cellular experiments are convincing. This paper is broadly relevant to those studying immunomodulation using biologics.

    1. eLife Assessment

      This study addresses a key question in developmental cognitive neuroscience by identifying early neural correlates of variability in language learning and showing how syllable tracking and word segmentation develop from birth to two years in infants with differing likelihoods of autism. The evidence is generally strong, with rigorous longitudinal EEG acquisition, careful preprocessing, and validated statistical approaches, though several methodological clarifications would further strengthen confidence in the inferences. Overall, the findings offer important insights with clear theoretical implications for understanding early mechanisms of speech perception and statistical learning, supported by convincing evidence.

    1. eLife Assessment

      This is an important study showing that movement vigor is not solely an individual property but emerges through interaction when two people are physically linked. The evidence is convincing, supported by a well-controlled experimental design and modeling that closely match the observed behavior. While the authors provided a helpful comparison of several candidate models of human-human interaction dynamics, the statistical power and the statistical analyses could be further improved.

    1. eLife Assessment

      This important study combines optogenetic manipulations and wide-field imaging to show that the retrosplenial cortex controls behavioral responses to whisker deflection in a context-dependent manner. The evidence is convincing, but the study would benefit from additional analyses to disentangle the contributions of movement initiation to the recorded neural signals. The paper should be of strong interest to neuroscientists studying cortical mechanisms of sensorimotor processing.

    1. eLife Assessment

      This study presents SynaptoGen, a differentiable extension of connectome models that links gene expression, protein-protein interaction probabilities, synaptic multiplicity, and synaptic weights, and demonstrates its use in reinforcement learning agents and a C. elegans-inspired case study. The work is a valuable contribution to computational connectomics and neuro-inspired machine learning, with solid mathematical and computational evidence supporting the proposed optimization framework. However, the broader biological and synthetic-biology claims - particularly genomic control of synaptogenesis and drug-discovery applications - are currently overstated and would benefit from a more tempered framing and clearer articulation of biological limitations.

    1. eLife Assessment

      This is an important contribution that largely confirms prior evidence that word recognition - a cornerstone of development - improves across early childhood and is related to vocabulary growth. This study is distinguished by its use of a large, multi-study dataset that is uncommon in prior research on cognitive development. It provides solid evidence that speed, accuracy, and consistency of word learning improve with age, and will therefore prove of interest to those studying language, and more broadly, perception and development.

    1. eLife Assessment

      This important work investigates cooperative behaviors in adolescents using a repeated Prisoner's Dilemma game. The computational modeling approach used in the study is solid and rigorous. The work could be further strengthened with the consideration of modeling higher-order social inferences and non-linear relationships between age and observed behavior. Findings from this study will be of interest to developmental psychologists, economists, and social psychologists.

    1. eLife Assessment

      This study offers important insights into how entorhinal and hippocampal activity support human thinking in feature spaces. It replicates hexagonal symmetry in entorhinal cortex, reports a novel three-fold symmetry in both behavior and hippocampal signals, and links these findings with a computational model. The task and analyses are sophisticated, and the results appear solid and of broad interest to neuroscientists.

    1. eLife Assessment

      TrASPr is an important contribution that leverages transformer models focused on regulatory regions to enhance predictions of tissue-specific splicing events. The revisions strengthen the manuscript by clarifying methodology and expanding analyses across exon and intron sizes, and the evidence supporting TrASPr's predictive performance is compelling. This work will be of interest to researchers in computational genomics and RNA biology, offering an improved model for splicing prediction and a promising approach to RNA sequence design.

    1. eLife Assessment

      This important work advances our understanding of the role of kisspeptin neurons in regulating the luteinizing hormone (LH) surge in females. The evidence demonstrating increased neuronal activity in anterior hypothalamic kisspeptin neurons just before the LH surge is compelling, though additional neuroanatomical evidence showing the specificity of the methods would strengthen the study. It also confirms that high circulating levels of estradiol, but also other unidentified factors, are required for the full daily activation. This research will be of interest to reproductive biologists and neuroscientists studying the female ovarian cycle.

    1. eLife Assessment

      This study aims to identify the proteins that make up the electrical synapse, which are much less understood than those of the chemical synapse. These findings represent an important step toward understanding the molecular function of chemical synapses and will have broad utility for the wider neuroscience field. The experimental evidence is convincing.

    1. eLife Assessment

      This study presents a valuable finding on how the locus coeruleus modulates the involvement of medial prefrontal cortex in set shifting using calcium imaging. The evidence supporting the claims was viewed as incomplete in comparisons of extra- (EDS) and intradimensional shifts (IDS). The work is of broad interest to those studying flexible cognition.

    1. eLife Assessment

      This study introduces a novel method for estimating spatial spectra from irregularly sampled intracranial EEG data, revealing cortical activity across all spatial frequencies, which supports the global and integrated nature of cortical dynamics. It showcases important technical innovations and rigorous analyses, including tests to rule out potential confounds. However, further direct evaluation of the model, for example by using simulated cortical activity with a known spatial spectrum (e.g., an iEEG volume-conductor model that describes the mapping from cortical current source density to iEEG signals, and that incorporates the reference electrodes and the particular montage used), would even further strengthen the incomplete evidence.

    1. eLife Assessment

      This study offers important insight into the pathogenic basis of intragenic frameshift deletions in the carboxy-terminal domain of MECP2, which account for some Rett syndrome cases, yet similar variants also appear in unaffected individuals. Using base editing and mouse models, the authors present convincing evidence supporting the pathogenicity of select deletion variants, with potential implications for therapeutic development. However, comments regarding the analysis of publicly available genetic databases should be addressed to strengthen the conclusions and provide greater clarity to the field.

    1. eLife Assessment

      This study provides an important assessment of how body size influences the occurrence of macro-organisms in urban areas across the globe. Size in most plants, but only some animal families, was positively associated with urban tolerance. The data set is impressive, but the evidence for broad-scale conclusions is incomplete due to methodological issues that need to be resolved.

    1. eLife Assessment

      The goal of this useful study is to examine learning-related changes in neural representations of global and local spatial reference frames in a spatial navigation task. Although the study addresses an interesting question, the evidence for neural representations in the hippocampus and retrosplenial cortex remains incomplete because of confounds in the experimental design and partial data analysis. There are further concerns about the framing of the study in the context of the relevant literature as well as the discussion.

    1. eLife Assessment

      This study presents a valuable approach for revealing large-scale brain attractor dynamics during resting states, task processing, and disease conditions using insights from Hopfield neural networks. The evidence supporting the findings is convincing across the many datasets analysed. The work will be of broad interest to neuroscientists using neuroimaging data with interest in computational modelling of brain activity.

    1. eLife Assessment

      O'Brien and co-authors provide important data demonstrating that tissue-resident macrophages can exert physiological functions and influence endocrine systems.Their model in which AMs negatively regulate aldosterone production via effects exerted in the lung is solid. The work will be of broad interest to cell biologists and immunologists.

    1. eLife Assessment

      This is an important account of replay as recency-weighted context-guided memory reactivation that explains a number of empirical findings across human and rodent memory literatures. The evidence is compelling and the work is likely to inspire further adaptions to incorporate additional biological and cognitive features.

    1. eLife Assessment

      This study combines genetic, cell biological, and interaction data to propose a model of meiotic double-strand break regulation in C. elegans. Solid evidence supports the main conclusions, while by nature of a screening-type study, more may be needed to solidify speculations in future studies. Yet, comprehensive cataloging of the physical and genetic interactions of factors required for meiotic double-strand break is useful information for the field.

    1. eLife Assessment

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

    1. eLife Assessment

      This useful manuscript reports findings indicating that cell cycle progression and cytokinesis both contribute to the transition from early to late neural stem cell fates. Although orthogonal approaches would help confirm the findings, which are based on loss-of-function, the experimental evidence is convincing. Lastly, an investigation of the underlying mechanisms linking the cell cycle to temporal factor expression is still needed.

    1. eLife Assessment

      The authors investigate arrestin2-mediated CCR5 endocytosis in the context of clathrin and AP2 contributions. Using an extensive set of NMR experiments, and supported by microscopy and other biophysical assays, the authors provide compelling data on the roles of AP2 and clathrin in CCR5 endocytosis. This important work will appeal to an audience beyond those studying chemokine receptors, including those studying GPCR regulation and trafficking. The distinct role of AP2 and not clathrin will be of particular interest to those studying GPCR internalization mechanisms.

    1. eLife Assessment

      This fundamental work by Yamamoto and colleagues advances our understanding of how positional information is coordinated between axes during limb outgrowth and patterning. They provide convincing evidence that the dorsal-ventral axis feeds into anterior-posterior signaling, and identify the responsible molecules by combining transplantations with molecular manipulations. This work will be of broad interest to regeneration, tissue engineering, and evolutionary biologists.

    1. eLife Assessment

      This revised paper provides a valuable and novel neural network-based framework for parameterizing individual differences and predicting individual decision-making across task conditions. The methods and analyses are solid yet could benefit from further validation of the superiority of the proposed framework against other baseline models. With these concerns addressed, this study would offer a proof-of-concept neural network approach to scientists working on the generalization of cognitive skills across contexts.

    1. eLife Assessment

      This study presents compelling new data that combine two FTD-tau mutations, P301L/S320F (PL-SF), that reliably induce spontaneous full-length tau aggregation across multiple cellular systems. The findings are important for the field of neurodegenerative disease. The strength of evidence is solid; however, several conclusions would benefit from more validation.

    1. eLife Assessment

      This study investigates the role of developmental oligodendrocytes in synchronising spontaneous activity in neuronal circuits and influencing cerebellar-dependent behaviour. The authors use advanced viral targeting techniques to deplete oligodendrocytes in a cell-specific manner, paired with in vivo calcium imaging of Purkinje cells, to establish a relationship between oligodendrocyte-mediated neuronal synchrony and complex brain function. The authors present compelling evidence of oligodendrocyte-regulated neuronal synchrony. Overall, this manuscript holds promise as an important contribution to neurodevelopment research.

    1. eLife Assessment

      By investigating spine nanostructure and dynamics across multiple genetic mouse models for neurodevelopmental disorders, this important study has the potential to uncover convergent or divergent synaptic phenotypes that may be specifically associated with autism versus schizophrenia risk. While the imaging and breadth are impressive, there are potential methodological concerns, especially around statistical analyses, which render the evidence incomplete and should be addressed. The purely in vitro nature of the study also slightly limits the generalisability of the findings.

    1. eLife Assessment

      This useful study provides a systematic and solid comparison of sex-biased enteroendocrine peptide expression, including AstC and Tk, to show that these peptides contribute to female-biased fat storage. The major research question of this study is based on the authors' previous papers, and therefore, the presented results are incremental. This study serves as a foundation for future investigation of regulatory mechanisms for the sex-biased fat content by AstC and Tk.

    1. eLife Assessment

      This important study introduces an advance in multi-animal tracking by reframing identity assignment as a self-supervised contrastive representation learning problem. It eliminates the need for segments of video where all animals are simultaneously visible and individually identifiable, and significantly improves tracking speed, accuracy, and robustness with respect to occlusion. This innovation has implications beyond animal tracking, potentially connecting with advances in behavioral analysis and computer vision. The strength of support for these advances is compelling overall, although there were some remaining minor methodological concerns.

    1. 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 have solid support: that most transcriptional targets are generally stable, with notable exceptions in the dentate gyrus and with regard to circadian changes. There are some weaknesses and it would improve the manuscript to address them.

    1. eLife Assessment

      This valuable study uses fiber photometry, implantable lenses, and optogenetics, to show that a subset of subthalamic nucleus neurons are active during movement, and that active but not passive avoidance depends in part on STN projections to substantia nigra. The strength of the evidence for these claims is solid, whereas evidence supporting the claims that STN is involved in cautious responding is unclear as presented. This paper may be of interest to basic and applied behavioural neuroscientists working on movement or avoidance.

    1. eLife Assessment

      This valuable study provides a 3D standardised anatomical atlas of the brain of an orb-weaving spider. The authors describe the brain's shape and its inner compartments-the neuropils-and add information on the distribution of a number of neuroactive substances such as neurotransmitters and neuropeptides. Through the use of histological and microscopy methods the authors provide a more complete view of an arachnid brain than previous studies and also presents convincing evidence about the organisation and homology of brain regions. The work will serve as a reference for future studies on spider brains and will enables comparisons of brain regions with insects so that the evolution of these structures can be inferred across arthropods.

    1. eLife Assessment

      This valuable study addresses T cell receptor activation during autoreactive T cell development and how the strength of T cell receptor engagement in naïve cells can predispose T cells to develop into effector/memory T cells. The authors lead with solid results that are largely consistent with data in the field suggesting that, in comparison to their counterparts with relatively lower basal self-reactivity, naive CD5hi CD8 T cells in non-obese diabetic (NOD) mice are poised for activation. They propose that diabetogenic T cells are preferentially found among the naive CD5hi CD8 T cell population. While the evidence does not fully support all the authors' conclusions, the data provide a foundation that sets up future studies.

    1. eLife Assessment

      This important study demonstrates that in Drosophila melanogaster, tachykinin (Tk) expression is regulated by the microbiota. The authors present convincing evidence that axenic flies raised with no microbiota are longer-lived than conventionally reared animals, and that Tk expression and Tk receptors in the nervous system are required for this effect. They further test individual bacterial strains for their role in these effects and connect the effect to loss of lipid stores and suggest that FOXO may be involved in the phenotype, results that are of interest to the fields of environmental perception, host microbiome interactions, and geroscience.

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

    1. eLife Assessment

      In this important manuscript, the authors establish a vertebrate model for studying the development of circuits that control heart rate. This contribution uses a combination of experimental techniques to provide compelling information for scientists looking to understand how heart rate regulation emerges during development.

    1. eLife Assessment

      This paper presents an important advance in genetically encoded voltage imaging of the developing zebrafish spinal cord in vivo, capturing voltage dynamics in neuronal populations, single cells, and subcellular compartments inaccessible to patch clamp, and diverse spike waveforms and subthreshold voltage dynamics inaccessible to calcium imaging. The work identifies a developmental progression from irregular voltage fluctuations to coordinated contralateral and ipsilateral activity, providing insight into how electrical dynamics and cellular morphology evolve during circuit formation. The strength of evidence is solid, with imaging data supporting the main conclusions, although the manuscript would be strengthened by more complete methodological documentation and clearer context relative to earlier calcium imaging studies. Overall, this study provides a resource that is of importance for researchers investigating neural development and circuit assembly, illustrating the value of voltage imaging as a general tool for probing bioelectric mechanisms in morphogenesis and circuit development.

    1. eLife Assessment

      This study presents a valuable and practical approach for one-photon imaging through GRIN lenses. By scanning a low numerical aperture (NA) beam and collecting fluorescence with a high NA, the method expands the usable field of view and yields clearer cellular signals. The evidence is solid overall, with strong qualitative demonstrations, but some claims would benefit from additional quantitative tests. The work will interest researchers who need simple, scalable tools for large‑area cellular imaging in the brain.

    1. eLife Assessment

      This study provides a valuable advance in understanding how decision boundaries may change over time during simple choices by introducing a method that uses information about non-decision components to improve parameter estimates. The evidence supporting the main claims is convincing, with clear demonstrations on simulated and real data, although additional model comparison work would further strengthen confidence. The findings will be of interest to researchers studying human decision processes and the methods used to analyse them.

    1. eLife Assessment

      This study provides important evidence that myristate, a fatty acid commonly present in soil environments, is taken up by arbuscular mycorrhizal fungi during symbiosis with a plant host. The evidence presented is solid, with multiple experimental approaches including stable isotope tracing, transcriptional analysis, and physiological measurements across different plant species and phosphorus conditions. However, the main claims are only partially supported.