eLife Assessment

This important study introduces a pulsed laser phase plate that generates stable phase contrast in electron microscopy, offering a practical alternative to continuous-wave designs that suffer from optical instabilities and diffraction artifacts. The experimental results demonstrate a controllable and stable electron phase shift, and the evidence supporting the feasibility of this approach for phase-contrast electron microscopy is convincing. Clarifying the agreement between experiment and theory and further elaborating on possible applications would strengthen the manuscript.

eLife Assessment

This valuable study identifies a novel role for Hes5+ astrocytes in modulating the activity of descending pain-inhibitory noradrenergic neurons from the locus coeruleus during stress-induced pain facilitation. The role of glia in modulating neurological circuits including pain is poorly understood, and in that light, the role of Hes5+ astrocytes in this circuit is a key finding with broader potential impacts. This work is supported by convincing evidence, albeit somewhat limited by the indirect nature of the evidence linking adenosine to nearby neuronal modulation, and possible questions on the population specificity of the transgenic approach.

eLife Assessment

This important study reports an endometrial organoid culture system mimicking the window of implantation. The evidence supporting the conclusion drawn is convincing. The data will be of interest to embryologists and investigators working on reproductive biology and medicine.

eLife Assessment

The authors developed a fundamental computational method, which is intended to automatically process bioluminescence imaging-derived tumour images across anatomical regions and over time. This allows quantitative analysis of such data, and the authors applied it to describe the spatiotemporal distribution of tumour cells in response to CD19-targeted CAR-T cells that contained either CD28 or 4-1BB costimulatory domains. Some operational limitations were identified, which relate to the pipeline's reliance on predefined regions of interest instead of aligning signal sites with anatomical information, scaling, and limitations in taking animal pose into account. Overall, the authors provide compelling evidence for the functionality of their computational approach towards automated analysis of bioluminescence imaging data, while applying it to a current topic of wide interest in cell therapy research.

eLife Assessment

This valuable study presents a technically sophisticated intravital two-photon calcium imaging approach to characterize Ca²⁺ dynamics in distinct populations of meningeal macrophages in awake, freely behaving mice. These data are solid and suggest that meningeal macrophage calcium activity is tightly linked to anatomical sub-compartments, with potential implications for migraine and neuroinflammatory processes. Despite these strengths and broad relevance to neuroimmunology, several technical and interpretational issues limit the study, which could be addressed to strengthen this manuscript.

eLife Assessment

This study provides valuable evidence that hepatic DHHC7-dependent palmitoylation is a physiologically relevant regulator of systemic metabolism, and that loss of DHHC7 disrupts Gαi palmitoylation, activates cAMP-PKA-CREB signaling, and increases hepatic transcription and secretion of Prg4. The identification of Prg4 as a hepatokine that is elevated in vivo, together with some in vitro evidence for its interaction with GPR146, represents a conceptually novel contribution to the field. However, the evidence linking these mechanisms to systemic lipolysis, liver-adipose tissue crosstalk, and whole-body metabolic physiology remains incomplete, as the phenotypic analyses rely on a limited set of experiments and do not yet fully support claims regarding adipose tissue dysfunction or altered lipid flux.

eLife assessment

The manuscript presents important findings with theoretical or practical implications beyond a single subfield. The work is overall solid, and the methods, data, and analyses broadly support the claims. Although the novelty of this study and the work put into it are appreciated, there are also clearly some weaknesses that should be addressed.

eLife Assessment

This modelling study tests several hypotheses describing how seasonality and migration drive the epidemiology of Rift Valley Fever Virus among transhumant cattle in The Gambia. The work is methodologically solid, and the findings offer valuable insights into how the movement of cattle in and out of the Gambia River and Sahel ecoregions could lead to source-sink transmission dynamics among cattle subpopulations, sustaining endemic transmission.

eLife Assessment

This useful study examines whether the sugar trehalose, coordinates energy supply with the gene programs that build muscle in the cotton bollworm (Helicoverpa armigera). The evidence for this currently is incomplete. The central claim - that trehalose specifically regulates an E2F/Dp-driven myogenic program - is not supported by the specificity of the data: perturbations and sequencing are systemic, alternative explanations such as general energy or amino-acid scarcity remain plausible, and mechanistic anchors are also limited. The work will interest researchers in insect metabolism and development; focused, tissue-resolved measurements together with stronger mechanistic controls would substantially strengthen the conclusions.

eLife Assessment

This study offers important methodological advances for CRISPR-based mutagenesis in mice, highlighting the potential of founder animals for early phenotypic characterization. The authors present convincing evidence, supported by rigorous experimental design, that "crispant" (F0) analysis in mice, despite prior concerns about genetic mosaicism, can be utilized to assess protein function.

eLife Assessment

This study presents valuable data suggesting that ATP-induced modulation of alveolar macrophage (AM) functions is associated with NLRP3 inflammasome activation and enhanced phagocytic capacity. While the in vivo and in vitro data reveal an interesting phenotype, the evidence provided is incomplete and does not fully support the paper's conclusions. Additional investigations would be of value in complementing the data and strengthening the interpretation of the results. This study should be of interest to immunologists and the mucosal immunity community.

eLife Assessment

This fundamental study provides the first genome-wide characterization of H3K115 acetylation and identifies a striking and previously unappreciated association of this globular-domain histone modification with fragile nucleosomes at CpG island promoters, active enhancers, and CTCF binding sites. While the work is largely descriptive and correlative in nature the evidence is compelling. The authors present multiple, orthogonal genomic and biochemical analyses that consistently support their central conclusions.

eLife Assessment

This fundamental work substantially advances our understanding of OXT (oxytocin) neurons and OXTR (oxytocin receptor) expressions in mammalian brains using an advanced RNAscope at the single transcript level. The evidence supporting the conclusions is compelling using chromogenic assays and state-of-the-art microscopy. The work will be of broad interest to neuroscientists and endocrinologists.

eLife Assessment

This potentially important study explores the specificity of olfactory perceptual learning. In keeping with previous work, the authors found that learning to discriminate between two enantiomers does not generalize across the nostrils or to unrelated enantiomers, whereas learning to discriminate odor mixtures does generalize across the nostrils and to other odor mixtures, with this learning effect persisting over at least two weeks. While the evidence presented to support these findings is convincing, it remains unclear why the results differ for enantiomers and why training on odor mixtures generalizes to other odor mixtures.

eLife Assessment

This important study provides evidence, albeit still incomplete, that high-elevation species lose water at slower rates than low-elevation species. The findings imply that egg physiology may be a factor limiting the distributional range of bird species. While this work reinforces the need for all life stages to be considered when evaluating physiological adjustment to climate change, the analyses as presented by the authors do not clearly highlight the specific impact of species differences in influencing these adjustments.

eLife Assessment

In this manuscript, Jong et al. provide and validate a very useful resource for performing CRISPR screenings to study neutrophil differentiation and function by generating Hoxb8 cells that constitutively express Cas9. This library-screening approach has the potential to improve on the established lentiviral CRISPR-Cas9 editing of Hoxb8 cells. However, the technical advances provided are only incremental and the results presented in this study do not significantly further our understanding of these cells, but rather provide a good validation of their Cas9+ modified version.

eLife Assessment

This study reports an mRNA-based strategy for restoring sperm motility in a mouse model of monogenic male infertility. The work is technically innovative and potentially valuable, as it demonstrates feasibility of in vivo testicular mRNA delivery without genomic integration of foreign DNA. However, although partial recovery of sperm motility is supported, the evidence for meaningful restoration of fertility remains incomplete, with weak IVF outcomes and difficult-to-interpret ICSI results. In addition, mechanistic questions regarding the persistence of mRNA and the specificity of germ-cell targeting remain insufficiently resolved, limiting the strength of the authors' conclusions.

eLife Assessment

In their study, Scherer and colleagues aim to use analyses of single-cell clones of murine granulocyte monocyte progenitors that are conditionally immortalized, and analyses of neutrophils derived from those clones to characterize an experimental system for studying neutrophil heterogeneity. The multi-omic and functional analyses reported are valuable but the strength of the evidence presented in support of them is incomplete because the study lacks a rigorous demonstration that the neutrophil-like cells that they derive are fully mature neutrophils.

eLife Assessment

This important study tackles an interesting aspect of fungal physiology: how a mitochondria-associated gene influences production of the secondary metabolite DON and fungicide sensitivity. The authors have improved the manuscript and the supporting evidence is convincing, although some uncertainties remain around descriptions of the methods.

eLife Assessment

This study proposes a potentially useful improvement on a popular fMRI method for quantifying representational similarity in brain measurements by focusing on representational strength at the single trial level and adding linear mixed effects modeling for group-level inference. The manuscript provides solid evidence of increased sensitivity with no loss of precision compared to more classic versions of the method. However, several assumptions are insufficiently motivated, and it is unclear to what extent the approach would generalize to other paradigms.

eLife Assessment

This is an important study that provides compelling data from a diverse set of approaches from single cell transcriptome data and network analysis from genetically diverse mouse cells to identify novel driver genes underlying human GWAS associations. The authors present evidence that network analysis of scRNA-seq data from genetically diverse mouse bone-marrow derived stromal cells can be informative for identifying human BMD GWAS driver genes. Their approach should be broadly used and applicable to other GWAS studies.

eLife Assessment

This study presents a valuable finding on the neural representation of time from two distinct egocentric and allocentric reference frames. The evidence is solid and largely supports the hypothesis, with one caveat that the task differences could impact the observed effects. The work will be of interest to cognitive neuroscientists working on the perception and memory of time.

eLife Assessment

This manuscript describes a useful integrated proteogenomics pipeline to enable the discovery of novel peptides in cancer cell lines. The method combines long-read RNA sequencing with a multi-protease digestion and proteomics approach. The method is a further development of the authors' previous approaches to identify cancer-specific peptides; however, the current study focuses on a single cell line, and the characterization remains incomplete and lacks validation for candidate alterations. The manuscript will be of interest to scientists focusing on identifying unique alterations in cancer cells.

eLife Assessment

This study provides an important contribution by showing that whiteflies and planthoppers use salivary effectors to suppress plant immunity through the receptor-like protein RLP4, suggesting convergent evolution in these insect lineages. The topic is of clear interest for understanding plant-insect interactions and offers ideas that could stimulate further research in the field. The authors provide mostly solid evidence for the functional roles of the salivary effectors; however, the interpretation of the physiological function of RLP4 in plant defense requires clarification.

eLife Assessment

This study demonstrates that endothelial toll-like receptor 4 is a central regulator of leptomeningeal inflammation in the context of neonatal E. coli meningitis. The data are derived from cell type-specific gene knockout in mice as well as from cultured endothelial cells, and are generally solid, with only minor weaknesses in analysis and interpretation. This work is important as it advances our understanding of host cellular processes and molecular pathways underlying meningitis pathogenesis.

eLife Assessment

This fundamental study advances our understanding of how dietary patterns shape cancer immunity by identifying a link between a Mediterranean-mimicking diet, gut bacteria, and a metabolite that enhances anti-tumor immune responses. The evidence supporting the main conclusions is solid, based on carefully controlled diet experiments, measurements of gut-derived molecules, and functional immune analyses across multiple models, together with supportive observations in human data. The work will be of broad interest to biologists working on microbiota and cancer. However, there are several issues that the authors should address to improve the manuscript.

eLife Assessment

This study presents a valuable finding that depletion of the rRNA methyltransferase METTL5 enhances anti-tumor immunity through a novel mechanism involving neoantigen generation from non-canonical translation. The evidence supporting the central conclusions is solid, with comprehensive multi-omics data including ribosome profiling, immunopeptidomics, TCR sequencing, and multiple in vivo tumor models demonstrating synergy with immune checkpoint blockade.

eLife Assessment

The importance of uterine natural killer (NK) cells in reproductive success has been demonstrated in mice and humans; however, it is still unclear how uterine NK cells are developed. In this valuable manuscript, the authors provide convincing evidence that TGF-b signaling in NK cells supports normal pregnancy in mice by the conversion of conventional NK cells into uterine tissue-resident NK cells. There are some concerns about the paper, particularly around Figures 1A, 1C, and 2E.

eLife Assessment

This important study reports that the human posterior inferotemporal cortex (hPIT) functions as an attentional priority map, integrating both top-down and bottom-up attentional signals rather than serving solely as an object-processing region. The experiments and analyses are well conducted and provide compelling evidence that hPIT bridges dorsal and ventral attention networks and is robustly modulated by attention across diverse visual tasks. The study will be relevant for researchers investigating visual attention, high-level visual cortex, and the neural mechanisms that integrate endogenous and exogenous attentional control.

eLife Assessment

This is an important study that advances our understanding of the transition from quadrupedal to bipedal gait in a neuromechanical model of the Japanese macaque. The method and results are solid; the neuromusculoskeletal model successfully reproduces experimental data, and the stability analysis based on an inverted pendulum model effectively explains the effects of different transition strategies. However, the study would benefit from a more comprehensive sensitivity analysis. The findings are highly relevant for researchers in motor control, comparative physiology/biomechanics, and robotics.

eLife Assessment

Hoverflies are known for their sexually dimorphic visual systems and exquisite flight behaviors. This valuable study reports how two types of visual descending neurons differ between males and females in their motion- and speed-dependent responses, yet surprisingly, the behavior they control lacks any sexual dimorphism. The results convincingly support these findings, which will be of interest for studies of visuomotor transformations and network-level brain organization.

eLife Assessment

This valuable study reports results showing how different neurons in the dysgranular retrosplenial cortex code spatial orientation. Specifically, the paper reports that some neurons maintain tuning for a single head direction across multi-compartmental environments, while other neurons are tuned to different head directions that reflect the geometry within each compartment. The study was viewed as likely to expand the field's understanding of directional tuning of neurons, but incomplete evidence was provided to support the conclusions.

eLife Assessment

This important study substantially advances the imaging toolbox available to neuroscientists by presenting a tunable Bessel (tBessel-TPFM) platform that enables high-speed volumetric two-photon imaging. The evidence supporting the novel methodology is convincing, with rigorous benchmarking and demonstrations of a wide range of neuroimaging applications covering vascular dynamics, neurovascular coupling, optogenetic perturbation, and microglial responses. The work will be of broad interest to neuroscientists and imaging system tool developers.

eLife Assessment

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

eLife Assessment

This study makes a valuable contribution to understanding how negative affect shapes food-choice decision making in bulimia nervosa by leveraging a mechanistic drift diffusion model to quantify the weighting of tastiness and healthiness attributes. The evidence is solid, supported by a randomized crossover design and generally appropriate statistical analyses. However, the interpretability of the findings is limited by ambiguities in the affect manipulation, particularly regarding whether neutral and negative inductions yielded reliably distinct affective states at the time of task performance in the bulimia nervosa group. Consequently, session-related differences in model parameters cannot be unequivocally attributed to negative affect rather than to uncontrolled state or contextual factors, and clearer separation of affective conditions alongside analyses aligned with the paired data structure would strengthen the conclusions.

eLife Assessment

This useful study raises interesting questions but provides inadequate evidence of an association between atovaquone-proguanil use (as well as toxoplasmosis seropositivity) and reduced Alzheimer's dementia risk. The findings are intriguing but they are correlative and hypothesis-generating with the strong possibility of residual confounding.

[Note: The final version has been published in Brain, Behavior, and Immunity: https://doi.org/10.1016/j.bbi.2026.106473]

eLife Assessment

This important work establishes a connection between PRMT1 and SFPQ by identifying common phenotypes downstream of their inactivation. In the resubmission, authors now include NMD as a contributor to aberrant gene expression underpinning craniofacial development. The complementary experiments help strengthen some solid conclusions. This paper describes an interesting mechanism for the regulation of RNA levels, which is of interest to the readers of eLife.

eLife Assessment

This important study provides one mechanism that can explain the rapid diversification of poison-antidote pairs in fission yeast: recombination between existing pairs. The evidence is largely solid, but the study needs to tune down its claims (as it is not shown that the novel poison-antidote can serve as a meiotic driver), and to address small experimental requests. The work is of interest to scientists studying genetic incompatibilities.

eLife Assessment

This valuable study uses tools of population and functional genomics to examine long non-coding RNAs (lncRNAs) in the context of human evolution. Analyses of computationally predicted human-specific lncRNAs and their genomic targets lead to the development of hypotheses regarding the potential roles of these genetic elements in human biology. Compared to previous versions, the conclusions regarding evolutionary acceleration and adaptation have become more solid by more fully taking data and literature on human/chimpanzee genetics and functional genomics into account.

eLife Assessment

This important study provides evidence supporting the hypothesis that postnatal visual experience shapes the patterns of functional connectivity between extrastriate visual cortex and frontal regions, by comparing neonates, blind and sighted adults using resting-state fMRI. The evidence supporting the main claim is convincing, and the authors' interpretations are appropriately calibrated in the discussion. Nevertheless, the study design and methodology are inherently limited to resolve the underlying mechanisms driving connectivity changes during neurodevelopment (experience-related plasticity vs post-natal experience-independent maturation). This study will be of broad interest to neuroscientists and neuroimaging researchers studying vision, plasticity and brain development.

eLife Assessment

This important work describes wing mechanosensory neurons in detail, extending our understanding of sensorimotor processing in the fruit fly. The evidence presented convincingly supports the authors' identification of these neurons and leverages state-of-the-art methods to generate a near-complete map of wing mechanosensory circuitry. Overall, this study provides new hypotheses and invaluable tools for investigating proprioceptive motor control of the wing in Drosophila.

eLife Assessment

This important work examines the effects of side-wall confinement on chemotaxis of swimming bacteria in a shallow microfluidic channel. The authors present convincing experimental evidence, combined with geometric analysis and numerical simulations of simplified models, showing that chemotaxis is enhanced when the distance between the side walls is comparable to the intrinsic radius of chiral circular swimming near open surfaces. This study should be of interest to scientists specializing in bacteria-surface interactions.

eLife Assessment

This fundamental work reveals that the accessibility of the unstructured C-terminal tail of α-tubulin differs with the state of the microtubule lattice. 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 tail of α-tubulin. The probes can be used as tools in the future to study differences in microtubule lattice regulation under different conditions both in vitro and in vivo. This work will be of great interest to the cytoskeleton field.

eLife Assessment

In this important study, the authors conducted extensive sets of computational and investigations of the mechanism of cholesterol transport in the smoothened (SMO) protein. The computational component integrated multiple state-of-the-art approaches such as adaptive sampling, free energy simulations, and Markov state modeling, providing compelling support for the proposed mechanistic model, which is further validated with solid experimental mutagenesis data.

eLife Assessment

This study addresses a key, long-standing question about how visual feature selectivity is organized in mid-level visual cortex, using an ambitious combination of large-scale neural recordings and image synthesis. It provides important insights into the complexity of single-neuron selectivity and suggests a structured organization across cortical depth. While the evidence is generally solid and technically impressive, several key claims would be strengthened by additional controls, particularly regarding the sources of similarity across neurons and the dependence of the results on modeling choices.

eLife Assessment

This valuable study introduces miRTarDS, a novel computational framework that predicts microRNA-target interactions based on a publicly available pretrained Sentence-BERT language model and downstream classification analysis. The strength of the evidence is incomplete, as the evaluation framework relies on unreliable ground-truth and false sets. Furthermore, the analysis fails to compare miRTarDS against existing state-of-the-art biomedical language models.

eLife Assessment

There is a perennial question in the field of birdsong: the contribution of the cerebellum to singing and processing song-related information. This study provides a valuable first step into this discussion, using electrophysiology of cerebellar neurons during a battery of assays, including singing and song playback. While the electrophysiological dataset here is novel and could shed light on key aspects of the neural control of vocal behavior, the evidence provided for the conclusions reached by the authors is currently incomplete.

eLife Assessment

This study makes a valuable contribution to our understanding of how the lipase regulator ABHD5 may control lipase activity through interactions with lipid droplets and cellular membranes. By combining multiscale molecular dynamics simulations with experimental approaches, the authors provide novel molecular insights into this membrane-protein interaction and present evidence suggesting that the regulatory mechanism depends on protein conformational changes and local membrane remodeling. While much of the evidence supporting the main conclusions is convincing, several aspects of the analysis, interpretation, and discussion remain incomplete. Overall, this work will be of interest to structural and molecular biologists working on lipid metabolism and membrane biophysics.

eLife Assessment

This important study introduces NoSeMaze, a semi-naturalistic platform for continuous, high-dimensional tracking of social and cognitive behaviors in group-housed mice, and uses it to show that individual social rank is stable across changing social contexts. By integrating automated dominance measures, proactive social behaviors, and reinforcement-learning-based profiles, the authors demonstrate a novel framework for examining how stable individual differences shape social structure. The strength of evidence is solid, advancing our understanding that social hierarchy can be viewed as a trait-like dimension of individuality. Yet, the interpretation of dominance in this paradigm and its broader ecological meaning remains somewhat ambiguous. This work will be of broad relevance for behavioral neuroscience and social behavior research.

eLife Assessment

This valuable study highlights the challenge of identifying the role of immune imprinting in influenza immunity. The manuscript provides solid evidence that statistical support for imprinting depends heavily on model choice and can be found in the absence of imprinting due to age-related processes. However, the results are incomplete in that the impact of incorrectly modeling imprinting is not clear. The work will be of interest to researchers who study adaptive immunity in any system where imprinting may be observed.

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.

eLife Assessment

Studying the biological roles of polyphosphates in metazoans has been a longstanding challenge to the field given that the polyP synthase has yet to be discovered in metazoans. This important study capitalizes on the sophisticated genetics available in the Drosophila system and uses a combination of methodologies to start to tease apart how polyphosphate participates in Drosophila development and in the clotting of Drosophila hemolymph. The data validating one of these tools (cyto-FLYX ) are solid and well-documented and they will open up a field of research into the functional roles of polyP in a metazoan model. The other tools for tissue specific knockdown of polyP (Mito-FLYX, ER-FLYX, and Nuc-FLYX) have not yet been validated but will be invaluable to the field when they are.

eLife Assessment

This study presents a valuable advance in reconstructing naturalistic speech from intracranial ECoG data using a dual-pathway model. The evidence supporting the claims of the authors is solid. This work will be of interest to cognitive neuroscientists and computer scientists/engineers working on speech reconstruction from neural data.

eLife Assessment

In this important study, the authors engineered and characterised novel genetically encoded calcium indicators (GECIs) and an analytical tool (CaFire) capable of reporting and quantifying various sub-synaptic events, including miniature synaptic events, with a speed and sensitivity approaching that of intracellular electrophysiological recordings. They present compelling data validating this toolset, which will be of interest to neurobiologists studying synaptic calcium dynamics in various model systems.

eLife Assessment

This important study combines real-time key point tracking with transdermal activation of sensory neurons as a general technique to explore how somatosensory stimulation impacts behavior in freely moving mice. After addressing concerns about classification of the behavioral responses to nociceptor stimulation, the authors now convincingly demonstrate a state-dependence in the behavioral response following nociceptor activation, highlighting how their real-time optogenetic stimulation capabilities can yield new insights into complex sensory processing. This work is a technological advancement that will be of interest to a broad readership, in particular labs studying somatosensation, enabling rigorous investigation of behaviors that were previously difficult or impossible to study.

eLife Assessment

This compelling work describes how the cell cycle-regulating phosphatase subunit, RepoMan, is regulated by the oxygen-dependent, metabolite-sensing hydroxylase PHD1. The characterisation of how proline hydroxylation alters signalling at the molecular and cellular level provides important evidence to enhance our understanding of how 2-oxoglutarate-dependent dioxygenases influence the cell cycle and mitosis.

eLife Assessment

This important study explores how the phase of neural oscillations in the alpha band affects visual perception, indicating that perceptual performance varies due to changes in sensory precision rather than decision bias. The evidence is solid in its experimental design and analytical approach, although the limited sample size restricts the generalizability of the findings. This work should interest cognitive neuroscientists who study perception and decision-making.

eLife Assessment

IL21R, being a key cytokine receptor for shaping the T follicular helper and B cell functions, utilizes two STAT family members, STAT1 and STAT3. The authors utilize the IL21R ENU-induced mutant, together with relevant in vitro and in vivo experiments, to dissect the function of STAT1 and STAT3. The approach by itself sounds reasonable, but the main conclusions are incompletely supported by the data presented in this manuscript.

eLife Assessment

This is a useful study presenting solid data indicating that the bacterial GTPases EngA and ObgE enable single-step reconstitution of functional 50S ribosomal subunits under near-physiological conditions. The study elegantly bridges the gap between the non-physiological aspects of the previous two-step reconstitution method and the extract-dependent iSAT system to enable ribosome assembly under translation-compatible conditions; however, it is limited by reliance on rRNA and proteins extracted from native ribosomes and does not achieve a true bottom-up reconstruction from all synthetic components. The evidence is incomplete in not characterizing the spectrum of reporter polypeptides produced and not comparing their rate and yield of synthesis from reconstituted ribosomes to that obtained with pure native ribosomes; and the impact of the study is limited by not including reporters to examine the fidelity of initiation, elongation or termination achieved with the reconstituted ribosomes.

eLife Assessment

This important study reports characterisation of hepatocyte molecular pathways affected by a glycyrrhizin derivative in both in vivo and in vitro mouse models of alcohol-associated liver disease. The authors show convincing evidence indicating that IPP delta isomerase 1 (Idi1) is an intermediate in these pharmacological effects, via the binding of the glycyrrhizin derivative to an upstream regulator of Idi1, HSD11B1, although some more quantitative analyses and better organisation of data would strengthen the study. The findings would be of interest to immunologists and pharmacologists interested in liver inflammation and its amelioration.

eLife Assessment

This important study examines how mismatched light and temperature cycles shape Drosophila locomotor timing and temperature-dependent timeless splicing, and leverages long-term early/late selection lines to probe evolutionary plasticity. The strength of evidence is incomplete at present, mainly because startle/masking under step cues could confound the behavioural readouts, and tim's involvement remains correlative. The authors should address masking in the behaviour analyses and provide causal support for tim's role.

eLife Assessment

The study presents a valuable resource of proline hydroxylation proteins for molecular biology studies in oxygen-sensing and cell signaling with the characterization of Repo-man proline hydroxylation site. The evidence supporting the claim of the authors is solid, although further clarification of the overall efficiency of the HILIC analysis, the specificity/sensitivity of immonium ion analysis, as well as quantification of proline hydroxylation identifications will be helpful. The work will be of interest to researchers studying post-translational modification, oxygen sensing, and cell signaling.

eLife Assessment

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

eLife Assessment

This work provides an important resource identifying 72 proteins as novel candidates for plasma membrane and/or cell wall damage repair in budding yeast, and describes the temporal coordination of exocytosis and endocytosis during the repair process. The data are convincing; however, additional experimental validation will better support the claim that repair proteins shuttle between the bud tip and the damage site.

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.

eLife Assessment

This important study demonstrates that paternal diet influences not only testicular morphology but also placental and fetal development, supporting a role for paternal contributions to offspring health. The authors combine transcriptomic and histological analyses across multiple tissues, and the evidence supporting the central conclusions is convincing. While aspects of the paternal gut phenotype remain largely descriptive, and the paternal and fetoplacental findings are discussed separately, clearer integration of these elements and additional methodological clarification would strengthen interpretation.

eLife Assessment

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

eLife Assessment

This important study reveals intriguing connections between chromosome breakage and DNA elimination during programmed genome rearrangement in the ciliate Tetrahymena thermophila. By developing a novel FISH approach that distinguishes germline and somatic telomeres, the authors provide compelling evidence that chromosome breakage removes germline telomeres along with hundreds of kilobases of germline-limited sequences. By disrupting a single chromosome breakage site, they further showed that DNA elimination was globally affected, which opens up a new direction for mechanistic studies. Thus, this work reveals additional similarity between the programmed DNA elimination in ciliates and nematodes that underlies the transition from germline to somatic telomeres.

eLife Assessment

This important study presents new insights into the post-transcriptional mechanisms that govern cortical development. Through state-of-the-art methodology to track neuronal birth order, the data provide compelling evidence that Imp1 (Igf2bp1/Zbp1) orchestrates radial glia fate transitions and cortical neurogenesis. The findings establish a new framework for understanding how post-transcriptional mechanisms integrate with transcriptional and epigenetic regulatory layers to control cortical temporal patterning.

eLife Assessment

This is a well-executed intrathecal MRI tracer study that provides valuable early in vivo evidence for CSF drainage into human skull bone marrow and explores clinically relevant associations using robust imaging methodology and regional analyses. However, the evidence supporting the interpretation of early (4 h) tracer signal as impaired clearance is incomplete, and appears difficult to reconcile with established CSF tracer kinetics. They also note that the reported links to sleep and cognitive performance are weakened by reliance on subjective, retrospective questionnaires rather than objective physiological measurements.

eLife Assessment

This valuable work describes a computational and experimental workflow that turns a moderately stable α-helical bundle into a very stable fold. The authors advance our understanding of α-helix stabilization and provide a convenient framework with implications for the protein design field. The main claims are supported by convincing evidence through sound and well-validated methods, yet further characterization would strengthen specific conclusions for the design of mechanically, thermally, and chemically stable α-helical bundles.

eLife Assessment

This study provides valuable findings on how the activity of the E3 ubiquitin ligase Highwire (Hiw/Phr1) is regulated and its impact on synaptic growth. The authors propose that impaired endocytosis leads to condensation of Hiw, resulting in increased synaptic growth. They also integrate such a mechanism within the known JNK (c-JUN N-terminal Kinase) and BMP (Bone Morphogenetic Protein) signalling pathways involved in synapse regulation. While the work raises an interesting mechanistic framework, several aspects of the experimental design and methodology are incomplete, and key conclusions, particularly those regarding the liquid-liquid phase separation of the E3 ubiquitin ligase, are not fully supported by the presented data.

eLife Assessment

The authors use sequencing of nascent DNA (DNA linked to an RNA primer, “SNS-Seq”) to localise DNA replication origins in Trypanosoma brucei, so this work will be of interest to those studying either Kinetoplastids or DNA replication. The paper presents the SNS-seq results for only part of the genome, and there are significant discrepancies between the SNS-Seq results and those from other, previously-published results obtained using other origin mapping methods. The reasons for the differences are unknown and from the data available, it is not possible to assess which origin-mapping method is most suitable for origin mapping in T. brucei. Thus at present, the evidence that origins are distributed as the authors claim - and not where previously mapped - is inadequate.

eLife Assessment

This study offers valuable insights into how humans detect and adapt to regime shifts, highlighting dissociable contributions of the frontoparietal network and ventromedial prefrontal cortex to sensitivity to signal diagnosticity and transition probabilities. The combination of an innovative instructed-probability task, Bayesian behavioural modeling, and model-based fMRI analyses provides a solid foundation for the main claims; however, major interpretational limitations remain, particularly a potential confound between posterior switch probability and time in the neuroimaging results. At the behavioural level, reliance on explicitly instructed conditional probabilities leaves open alternative explanations that complicate attribution to a single computational mechanism, such that clearer disambiguation between competing accounts and stronger control of temporal and representational confounds would further strengthen the evidence.

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.

eLife Assessment

This useful paper describes a software tool, "DrosoMating", which allows automated, high-throughput quantification of 6 common metrics of courtship and mating behaviors in Drosophila melanogaster. The validity of the tool is quite convincingly demonstrated by comparing expert human assessments with those made by DrosoMating. The work, however, does not address how DrosoMating compares with or advances on other existing tools for exactly the same purpose, whether it can be used for studies of other Drosophila species, and/or whether finer aspects of courtship response timing - which depend on proximal female signals to the male - could be extracted with more detailed analyses. Some additional statistical analyses would also help further strengthen the authors' current conclusions.

eLife Assessment

This valuable study provides convincing evidence that MgdE, a conserved mycobacterial nucleomodulin, downregulates inflammatory gene transcription by interacting with the histone methyltransferase COMPASS complex and altering histone H3 lysine methylation. This work will interest microbiologists as well as cell and cancer biologists.

eLife Assessment

This work describes a useful computational tool for automated morphometry of dynamic organelles from microscope images. However, the supporting evidence and novelty of the manuscript as presented are incomplete and could be improved. The work will be of interest to microscopists and bioimage analysts who are non-experts but wish to improve quantitative analysis of cellular structures.

eLife Assessment

This important study by Bartas and colleagues examined how patterns of monosynaptic input to specific cell types in the ventral tegmental area are altered by drugs of abuse. The authors applied a dimensionality reduction approach (principal component analysis) and showed that various drugs of abuse, and somewhat surprisingly the anesthesia alone (ketamine/xylasin), caused changes in the distribution of inputs labeled by the transsynaptic rabies virus. The evidence supporting the conclusions is overall convincing and provides foundational information, as well as a cautionary note on the interpretation of rabies virus-based tracing experiments.

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 studies.

eLife Assessment

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

eLife Assessment

This valuable study tests whether prediction error or prediction uncertainty controls how the brain segments continuous experience into events. The paper uses validated models that predict human behavior to analyze multivariate neural pattern changes during naturalistic movie watching. The authors provide solid evidence that there are overlapping but partially distinct brain dynamics for each signal.

eLife Assessment

This study presents valuable analyses of single neuron activity in the subthalamic nucleus (STN) of monkeys performing a decision-making task that manipulates both perceptual evidence and reward. In particular, the study shows convincing evidence of multiple decision variables being represented in the STN. However, the evidence for sub-populations in STN with distinct involvements in decision-making is incomplete at this stage and requires either further efforts to provide stronger support or refinement of that conclusion.

eLife Assessment

This work represents a valuable finding of how single-trial functional connectivity may be used to infer different cognitive states involved in speech perception and production. Although the data and analyses are overall convincing, the theoretical advance and novelty of the finding are less clear. With a clearer idea of the functional significance of the connectivity data, the paper would be of interest to those interested in brain networks and communication.

eLife Assessment

This important study is of relevance for the fields of predictive processing, perception and learning, with a well-designed paradigm allowing the authors to avoid several common confounds in investigating predictions, such as adaptation. Using a state-of-the-art multivariate EEG approach, the authors test the opposing process theory and find evidence in support of it. Overall, the empirical evidence is solid, however, some conclusions rest on limited evidence and need further work to reconcile the present results with previous studies.

eLife Assessment

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

eLife Assessment

This valuable study examined how sensory adaptation supports visual perception in the presence of noise. The authors used a combination of human psychophysics, electroencephalography (EEG), and deep neural networks to show that adaptation to noise can improve perception. The results are solid but are, at present, weakened by a number of concerns, including some related to the experimental design and some regarding the interpretation of the results in terms of particular mechanisms. With these concerns adequately addressed, the study and conclusions would be likely to be of broad interest to the neuroscience community.

eLife Assessment

This study presents a valuable and well-documented computational pipeline for the scalable analysis and spike sorting of large extracellular electrophysiology datasets, with particular relevance for high-density recordings such as Neuropixels. The authors demonstrate the pipeline's utility for benchmarking spike sorter performance and evaluating the effects of data compression, supported by thorough testing, clear figures, and openly available code. The workflow is reproducible, portable, and practical, providing concrete guidance on computational cost and runtime. Overall, the evidence supporting the pipeline's performance and output quality is compelling, and this work will be of broad interest to the systems neuroscience community.

eLife Assessment

This manuscript presents a novel investigation of organizational principles governing brain activity at both global and local scales during naturalistic viewing paradigms, an important advance for theoretical neuroscience, functional neuroimaging, and neurology. The authors demonstrate that brain activity during naturalistic viewing is dominated by two anti-correlated states that toggle between each other with a third transitional state mediating between them. The evidence supporting this finding is compelling, with the successful replication across three independent datasets (StudyForrest, NarrattenTion, and CamCAN) a particular strength.

eLife Assessment

This valuable study uses a computer vision pipeline to infer the motor control of cephalopod skin, revealing that individual chromatophores exhibit anisotropic deformations and can be associated with multiple putative motor units. The evidence supporting these claims is solid, although the study's conclusions are limited to stationary or sedated animals, and the analyses of motor unit characteristics and electrophysiological validation remain incomplete. This work will be of significant interest to biologists studying cephalopod behavior and motor control.

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.

eLife Assessment

This important work investigates cooperative behaviors in adolescents using a repeated Prisoner's Dilemma game. The approach used in the study is solid. The impact of this work could be further enhanced with more rigorous modelling procedures and more modeling selection/comparison details, as well as by framing the findings in terms of the specific game-theoretic context, rather than general cooperation. Findings from this study will be of interest to developmental psychologists, economists, and social psychologists.

eLife Assessment

This important and compelling study establishes a robust computational and experimental framework for the large-scale identification of metallophore biosynthetic clusters. The work advances beyond current standards, providing theoretical and practical value across microbiology, bioinformatics, and evolutionary biology.

eLife Assessment

This manuscript describes a series of studies using four different Go/No Go task variants in combination with fast-scan cyclic voltammetry to determine the role of dopamine release in the ventromedial striatum in action selection, controllability of reward pursuit, effort, and reward approach. The authors conclude that dopamine signals in the ventromedial striatum integrate the invigoration of action initiation with continuous estimation of spatial, but not temporal, proximity to rewards. There are, however, a number of concerns regarding methodology that could affect the interpretation of the results. Thus, while the findings are useful, they are considered incomplete, with the primary claims only partially supported.

eLife Assessment

This important study by Zeng et al characterizes a novel Legionella pneumophila effector, Llfat1 (Lpg1387), which binds actin through a newly identified actin-binding domain. Data is convincing; structural analysis of the Llfat1 ABD-F-actin complex enabled the development of this domain as a probe for F-actin. Additionally, the authors show that Llfat1 functions as a lysine fatty acyltransferase targeting small GTPases, highlighting its importance in both bacterial pathogenesis and cytoskeletal biology.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.