eLife Assessment

This Review Article provides a compendium of advice for MD-PhD students to consider when deciding which, if any, clinical field they will select for residency training. It is grounded in published data and effectively considers factors including the potential for clinical disciplines to sustain research integration, provide mentorship, meet lifestyle expectations, and foster a long-term career as a research-focused physician-scientist.

eLife Assessment

This valuable study presents a tool that uses brain anatomy to predict the layout and size of early visual maps, and it is strengthened by the use of a large and diverse collection of scans to examine differences across people and groups. The evidence is solid for the general usefulness of the approach, but incomplete for some of the broader claims about prediction accuracy and use across data sets, particularly for estimates of map size and for showing that the model improves on repeated functional measurements. This paper is likely to be of significant interest to visual perception researchers, especially those who use fMRI.

eLife Assessment

This is an important and rigorous study that addresses the question of what determines the spatial organization of endocytic zones at synapses. The authors use compelling approaches, in both Drosophila and rodent model systems, to define the role of activity and active zone structure on the organization of the peri-active zone. While the findings are primarily negative, they are carefully executed and contribute to the field by refining existing models of presynaptic organization.

eLife Assessment

This potentially useful manuscript addresses the 3D chromatin architecture in monocytes from a few patients with alcohol-associated hepatitis and its relationship to enhanced transcription of innate immune genes. While the concept and methodological approach are interesting in principle, the evidence is incomplete as a result of insufficient sample sizes as well as other substantive analytical concerns.

eLife Assessment

This manuscript presents a valuable antiviral approach using an engineered ACE2-Fc fusion protein that demonstrates broad-spectrum neutralization capacity against SARS-CoV-2 variants and achieves significant prophylactic protection in animal models through a novel Fc-mediated phagocytosis mechanism. The study provides convincing evidence for protective efficacy through rigorous in vivo validation in mice, mechanistic characterization via transcriptomic analysis and biodistribution studies, and demonstration of antibody-dependent cellular phagocytosis as the primary clearance mechanism mediated by the decoy. The work will be of interest to researchers working in vaccine development and associated immune responses.

eLife Assessment

This study integrates large-scale behavioral, genetic, and molecular analyses in animal models to investigate morphine response. Utilizing high-quality, time-series Quantitative Trait Loci (QTL) mapping, the work provides compelling evidential support for novel, time-dependent genetic interactions (epistasis). A fundamental result of this rigorous analysis is the discovery of a novel Oprm1-Fgf12-MAPK signaling pathway, which offers new insights into the mechanisms of opioid sensitivity.

eLife Assessment

This important study investigates how the nervous system adapts to changes in the mechanics of the body, which are altered through a tendon transfer surgery affecting finger extensor and flexor muscles. By measuring task performance, joint kinematics, and muscle activity for several weeks post surgery, the authors provide convincing evidence that monkeys undergo a two-phase adaptation process. First, they adopt a maladaptive strategy to overcome the functional challenges imposed by the surgery, and then revert to a strategy that uses the same patterns of muscle coactivation observed pre-tendon transfer.

eLife Assessment

This useful study uses a chemoinformatics pipeline to identify a list of candidate mosquito repellants that may be pleasant to smell and safe for humans. The strength of evidence and in particular the computational methodology are incomplete because it is insufficiently benchmarked against other leading models. At the high concentrations tested, there may also be off-target effects of the repellents on the mosquitoes that are not considered.

eLife Assessment

This manuscript proposes a valuable idea on how cortical networks may learn a helpful representation of sensory stimuli. The model implementing this idea is tested in multiple experimental paradigms. However, the evidence remains incomplete as to whether the method supports both invariance and equivariance and whether it can estimate the dynamics of the moving object.

eLife Assessment

This short report is an important study that visual acuity declines nonlinearly with cone dropout, while eye motion partially compensates by improving sampling from remaining cones. The method for experimentally simulating cone dropout is compelling, leveraging state-of-the-art imaging and testing in human subjects. Inclusion of additional analysis on absolute cone density and eye motion would further strengthen the study.

eLife Assessment

Fujita et al. examine the effects of AM-2099, a Nav1.7 inhibitor, on the excitability of human dorsal root ganglion neurons and compare these results to their prior study of Nav1.8 inhibition by suzetrigine. They show that the Nav1.7 inhibitor primarily alters action potential threshold and initiation, but not repetitive firing, whereas Nav1.8 inhibition elicits much stronger inhibition on repetitive firing. These complementary roles of Nav1.7 and Nav1.8 provide a plausible cellular explanation for the limited clinical success of Nav1.7 inhibitors compared to Nav1.8 inhibitors for chronic pain. While the conclusions are important and solid, there are some key shortcomings that should be addressed to strengthen the study.

eLife Assessment

This valuable study analyses correlations between traits of Chinese frog species and their Red List status, finding differences between adults and larvae and thus pointing to the importance of considering different life-cycle stages in this and possibly other animal groups when assessing species extinction risks. The current study is, however, incomplete because of unclear threat categories for tadpoles, the omission of other key species traits, and insufficient statistical analysis.

eLife Assessment

This work provides a fundamental advance through a detailed and integrative analysis of how the tsetse fly feeds on blood, demonstrating that successful penetration depends on subtle structural adaptations rather than extreme forces or unusual anatomy. By combining high-resolution imaging, innovative biomechanical measurements, and experiments on artificial skin, the study offers complementary and compelling evidence, with clear data supporting a robust mechanistic interpretation. These findings have broad significance as they clarify the biomechanics of vector feeding with implications for the transmission of diseases such as African trypanosomiasis across diverse hosts.

eLife Assessment

This useful work addresses a longstanding question of how the extant genetic code came to be selected and conserved almost universally across life. Using a mutational approach and a small set of reporters, the authors demonstrate that the mutational impact was similar for non-standard genetic codes. Considering the limitations of the approach, the data are incomplete in supporting the claim of having provided 'experimental verification of the error minimization theory'.

eLife Assessment

This important study fills a major geographic and temporal gap in understanding Paleocene mammal evolution in Asia and proposes an intriguing "brawn before bite" hypothesis grounded in diverse analytical approaches. The work rests on a solid methodological base. Some limitations remain, including uncertainty introduced by pooling different tooth positions, limited dietary interpretation, and the predominantly herbivorous taxonomic focus, which narrows the ecological scope of the conclusions. However, the manuscript provides a substantially strengthened and well-supported contribution, while appropriately inviting further work to clarify dietary trends, broader ecological context, and links between dental trait evolution and environmental change.

eLife Assessment

This important study links allelic expression imbalance with replication timing, suggesting a stochastic model for haploinsufficiency in dosage-sensitive disease. The integration of allele-specific RNA-seq and replication timing in clonal systems provides solid evidence for an association between asynchronous replication and allelic imbalance, although the scope and generality should be addressed in future work. This study will interest epigeneticists and genome regulation researchers studying replication timing and monoallelic expression, as well as developmental biologists and human geneticists concerned with clonal heterogeneity, haploinsufficiency, and variable disease penetrance.

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

eLife Assessment

This important study highlights how cell size influences various cellular responses, with a particular focus on ferroptosis. The evidence presented is convincing, employing multiple model systems and experimental approaches to support the conclusions. This work will be of significant interest to the fields of cell size, ferroptosis, and cancer biology.

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

eLife Assessment

This study thoroughly assesses tactile acuity on women's breasts, for which no dependable data currently exists. The study provides two important contributions, by convincingly showing that tactile acuity on the breast is poor in comparison to other body parts, and that acuity is worst in larger breasts, indicating that the number of tactile sensors is fixed. This study will be of interest to the broader community of touch, as well as those interested in breast reconstruction and sexual function.

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. The new findings raise the 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.

eLife Assessment

This manuscript reports a high-quality genome assembly of the European cuttlefish, Sepia officinalis, a representative species of the Cephalopod lineage. This solid work relies on current best practices in genome sequencing and assembly, combining PacBio HiFi long reads and Hi-C chromatin conformation capture, and on state-of-the-art comparative genomic analyses, including chromosome number evolution and analyses of expanded gene families. The resulting genome will be a valuable resource for researchers interested in cuttlefish biology and comparative genomics in general.

eLife Assessment

This study presents valuable evidence of sex differences in oxycodone relapse-related behavior alongside novel characterization of synaptic adaptations in the paraventricular thalamus - nucleus accumbens shell circuit. The authors show that females exhibit heightened cue-induced seeking after 14 days, but not 1 day, of abstinence, while both sexes display similar time-dependent strengthening of paraventricular thalamus - nucleus accumbens shell glutamatergic transmission. The revised manuscript strengthens the work through improved statistical analyses, clearer interpretation, and expanded integration with prior literature. The strength of evidence is solid. However, association among experiments is incomplete, as the sex-specific behavioral effect is not reflected in circuit-level plasticity, and no causal manipulations test pathway involvement in relapse. Future work could link these circuit adaptations to sex-specific relapse vulnerability.

eLife Assessment

This study investigates the role of the Z-disc protein Zasp52 in Drosophila flight muscles and provides evidence that an intrinsically disordered region (IDR) helps to stabilize and promote the localization of the protein to the Z-disc. Overall, this represents an important study that provides insights into Z-disc function and maintenance. The data are convincing, supported by strong genetic evidence and behavioral tests, well-controlled experiments, and detailed statistical analyses. Additional functional analyses designed to tease out specialized regions within the newly described isoform of Zasp52 would further strengthen models regarding the function of the protein.

eLife Assessment

This important study identified Mex3a protein with dual RNA-binding protein/ubiquitin ligase function as a pivotal regulator of olfactory sensory neurons (OSN) differentiation and lineage fidelity. The authors employed a combination of systems biology approaches (e.g., single-cell RNA sequencing, proteomics) and newly developed animal models (e.g., HyperTRIBE) to provide solid evidence that abrogation of Mex3a disrupts cilia structure and polarity of OSNs. Notwithstanding that this article is of a broad potential interest across different biomedical disciplines ranging from RNA to developmental biology, additional mechanistic data connecting identified Mex3a mRNA targets and ensuing OSN phenotypes would further strengthen this study.

eLife Assessment

This important study probes the long-standing failure to resolve evolutionary relationships between the classical "spiralian" taxa-i.e., annelids, molluscs, brachiopods, platyhelminths and nemerteans-and provides convincing evidence that the branches leading to them are so short as to be unreliable guides to their relationships. This, in turn, has wide-ranging implications for our understanding of animal body plan evolution and the interpretation of early animal fossils.

eLife Assessment

This is an important study uncovering a new role of the SETD6-PPARγ axis in the regulation of hepatic lipid metabolism. The data convincingly demonstrate that methylation of PPARγ by SETD6 plays a key role in this process, linking lysine methylation to transcriptional control of lipid storage genes.

eLife Assessment

In this useful manuscript, Yang et al attempt to show that platelet recruitment to the liver via macrophages contributes to APAP-induced liver injury, but there were many areas where the data supporting the conclusions were incomplete. For example, the idea that platelets only affected KC glycolysis, but not the metabolism of other cells, to mediate the phenotype after injury is not adequately supported by the evidence. It is recommended to perform additional experiments to strengthen the conclusions.

eLife Assessment

This Review Article nicely synthesizes the development, applications, and recent technical advances of the nitroreductase/prodrug system, highlighting how it enables precise spatiotemporal cell ablation and experimental platforms for studying regenerative mechanisms and screening for pro-regenerative or protective compounds. Together, the article provides a conceptual and practical overview that will help researchers adopt and further develop this versatile approach in regenerative biology. It will be of interest to researchers studying regeneration, disease modelling, and targeted cell ablation, particularly those working with zebrafish and other genetic model systems.

eLife Assessment

This study provides valuable contributions to establish canonical Dhh signaling as a primary mediator in the differentiation of Leydig cells and their steroidogenic capacity. Together, the experimental design using their established stem Leydig cell line alongside relevant genetically mutated models, both derived using the relevant Nile tilapia animal system, provided largely convincing evidence to support their conclusions. The work will be of broad interest to developmental biologists interested in differentiation of steroidogenic or hormone producing cells.

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

eLife Assessment

This important study provides a comprehensive multi-omics characterization of Leishmania donovani stage differentiation, offering insights into the molecular basis of parasite adaptation across host environments. The authors present convincing evidence that stage transitions are not driven by genomic variation but instead rely on coordinated post-transcriptional regulation, including mRNA turnover, translation, and protein degradation. Although experimental validation of these findings and conclusions remains to be completed, the integration of diverse, high-quality datasets establishes a robust resource that will be of broad utility to researchers investigating Leishmania biology and life-cycle progression.

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

eLife Assessment

This study provides valuable insights into mitochondrial cristae organization in Plasmodium falciparum, particularly in the context of its divergent MICOS composition. The authors present convincing evidence, supported by phenotypic and morphological analyses, that cristae junction maintenance can be uncoupled from de novo cristae formation, reinforcing an emerging model of mitochondrial inner membrane organization. Notably, the absence of Mic10 alongside an enlarged and divergent MICOS complex highlights an intriguing evolutionary adaptation, although further characterization of the complex would strengthen the study's overall significance.

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

eLife Assessment

This valuable study used genetic and pharmacological manipulations of insulin/IGF signaling to address the role of insulin/IGF axis in the function of renal glomerular podocyte. Solid data are presented to demonstrate that co-inhibition of insulin/IGF signaling in podocytes led to aberrant splicing of mRNAs, which could contribute to the loss of podocytes in vitro and in vivo in mice. In light of the fact that IR/IGF-1R signaling are critically required for normal development and growth in multiple cells and organs, the lack of the assessment of developmental phenotype of podocytes in the mouse model limits the interpretation of the data.

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

eLife Assessment

This study presents a valuable finding relating to how the state of arousal is represented within the superior colliculus (SC), a principal visuo-oculomotor structure. The main conclusion that the SC's neural representation of arousal is segregated from motor related output appears to have solid support by the data. The work will be of interest to sensory, motor and cognitive neuroscientists.

eLife Assessment

This study explores how exogenous attention operates at the finest spatial scale of vision, within the foveola - a topic that has not been previously explored but is of interest to visual neuroscientists. The question is important for understanding how attention shapes perception, and how it differs between the periphery and the central regions of highest visual acuity. The evidence indicating that attention near the fovea preferentially enhances low spatial frequencies is compelling, as shown by carefully designed experiments with state-of-the-art eye tracking to monitor attended locations just a few tens of minutes of arc away from the fixation target.

eLife Assessment

This is a valuable report describing tracheal terminal cells (TTCs) in Drosophila as an immune privileged organ. The authors demonstrated that TTCs lack expression of the membrane-associated peptidoglycan recognition receptor PGRP-LC, which protects these cells from immune pathway activation and JNK-mediated cell death to maintain TTC homeostasis. While the genetic experiments using RNAi and overexpression are convincing and solid, the broader biological significance of this phenomenon requires further investigation. This work will be of interest to researchers in innate immunity across various model systems.

eLife Assessment

By screening an FDA-approved small-molecule library against a leucine-dependent M. tuberculosis strain, this study identifies semapimod as an inhibitor of Mtb growth that functions by impairing leucine import. The work is useful in linking leucine uptake to cell wall lipid biology in Mtb. However, the mechanistic understanding remains incomplete. Additional experimental evidence is required to clarify how PDIM contributes to or regulates leucine uptake.

eLife Assessment

This study presents valuable findings on the differential effects of RNA on the phase separation, aggregation dynamics, and bioactivity of PSMα3 and LL-37. The authors provide solid evidence from complementary biophysical and cell-based experiments that RNA influences peptide assembly and associated in vitro activities. The study is of interest for understanding interactions between amyloidogenic peptides and nucleic acids, although the physiological significance and some aspects of the mechanistic interpretation would benefit from further clarification.

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.

eLife Assessment

This study provides a useful demonstration that, at least for the systems examined, aspects of the entropic contribution to protein-ligand binding can be inferred directly from crystallographic data. In doing so, it strengthens a view of crystal structures as heterogeneous ensembles that are amenable to statistical-mechanical analysis rather than purely static models. The analytical approaches are carefully developed and transparently discussed, with thoughtful consideration of both successful and less effective methods, lending solid support to the central conclusions. However, because the analysis is based on a relatively small and narrowly sampled set of protein-ligand complexes, the generality of these findings remains speculative and will require broader validation.

eLife Assessment

This study provides valuable insights into how cells maintain sphingolipid homeostasis through transcriptional control and regulated protein degradation in response to changes in sphingolipid levels. The evidence supporting the conclusions is convincing overall, with solid genetic and biochemical approaches, while some mechanistic aspects remain to be clarified. This work will be of interest to researchers studying lipid metabolism and membrane biology.

eLife Assessment

This study presents important findings on the molecular mechanisms governing how the natural killer cell receptor KIR2DL4 interacts with HLA-G and undergoes internalization. The authors provide solid evidence for an allosteric disulfide-bond switch that regulates receptor activity, using a multifaceted approach that includes mutagenesis, mass spectrometry, and imaging. The work would be further strengthened by validating these mechanisms in primary immune cells and providing direct structural evidence for the proposed ligand-binding interface.

eLife Assessment

This study shows that Znhit1, a regulator of chromatin and of the histone variant H2A.Z, is required for progression through meiotic prophase. It is an important observation that describes the role of epigenetics and gene expression during meiosis. The analysis is based on complementary approaches at the cytological, single-cell, and genomic levels that provide solid evidence for the role of Znhit1 in the control of gene expression and in the loading of H2A.Z in mouse spermatocytes.

eLife Assessment

This valuable study provides quantitative data and analysis to reveal that variations in Dorsal (Dl ) nuclear dynamics along the Dorso-ventral axis in the early Drosophila embryo are governed by Dl-Cactus nuclear interactions. The solid evidence partially supports a mechanism where nuclear localized Cactus contributes to the fraction of Dl that binds to DNA, but additional work will be necessary to confirm the claims and the biological significance of these findings.

eLife Assessment

This study provides important insights regarding the temporal dynamics of dopamine across sleep/wake transitions in several brain areas. Using multi-site fiber photometry combined with EEG/EMG recordings, the study revealed heterogenous dynamics across both cortical and several subcortical areas. Although the evidence for these observations is solid, evidence for the proposed mechanisms driving DA dynamics is incomplete. Overall, the study may have a substantial impact on several fields working on the neurobiology of DA signaling.

eLife Assessment

The study presents important findings revealing previously unresolved conformational dynamics of the heterodimeric type IV ABC transporter TmrAB using single-molecule FRET. The evidence presented is solid, integrating careful experimental design with computational approaches to uncover states that are typically masked and difficult to detect. The work will be of interest to scientists studying the molecular mechanisms of primary active transport processes.

eLife Assessment

This study provides direct and compelling evidence that lamellipodial protrusions dynamically adjust Arp2/3 complex incorporation in response to mechanical counterforces, while also modulating cellular responsiveness to upstream signals like Rac GTPase. By combining endogenous labeling, live-cell imaging, and optogenetic signaling activation, the work demonstrates how adhesion state and physicochemical perturbations reproducibly alter branched actin organization, offering a fundamental advance over previous works. The findings deliver significant insights that will resonate broadly with cell biologists and biochemists studying actin dynamics and mechanotransduction.

eLife Assessment

In this study, Yuan and colleagues perform transcriptomic and epigenomic experiments to study open chromatin regions and transcripts that change upon larval settlement in the sponge Amphimedon. The authors present compelling evidence to show that sponge larvae prepare for receiving an environmental cue (sunset) by extensively modifying their chromatin accessibility in the vicinity of genes that are going to be regulated during metamorphosis. The study represents a fundamental advance in understanding the fine genetic control of larval settlement and has significance beyond the immediate field of sponge larval biology.

eLife Assessment

This large-scale comparative study of odorant receptor (OR) genes across more than 100 insect species, combining sequence- and structure-based approaches, aims to explore the evolution of this large gene family involved in the detection of odorant signals by olfactory neurons. This useful work uncovers a structural feature unique to the odorant receptor co-receptor Orco that reduces ligand binding affinity. However, the strength of evidence is incomplete: the pipeline for in silico identification of odorant receptor genes lacks validation through comparison with known odorant receptor repertoires from previously studied species, and claims regarding odor response spectra, evolutionary, and ecological interpretations are not fully supported by the analyses.

eLife Assessment

The study presents useful findings on the behavioral effects of nicotine exposure, suggesting the Drosophila larva as a potential model organism for studying underlying neural circuits. However, the evidence supporting the claims of the authors is incomplete and would benefit from more rigorous analysis and explanations. The study falls short of identifying the neural mechanisms and is therefore of interest to those with an interest in pharmacology and behavior.

eLife Assessment

This work provides an important modeling-based framework for understanding the processes of temporal integration in the claustrum. These mechanisms could support a broader range of integrative brain function. The manuscript presents solid evidence for how claustrum may integrate temporal disparate signals via a novel computational phenomenon with neural dynamics evolving along neural trajectories as opposed to settling into fixed-point attractor states.

eLife Assessment

This important advancement in the field of neurotransmission delivers a novel toolkit for in vivo visualization of vesicular transporters for ACh, GABA, glutamate and monoamines in C. elegans. With the application of newly developed neuron-specific knockout methods for these vesicular transporters, the results convincingly demonstrate that over 10% of the neurons studied show transporter co-expression that may be correlated with co-transmission. These findings and toolkit will be of interest towards the study of neural circuit function.

eLife Assessment

In this important study, the authors used a zebrafish model and scRNAseq analysis to show that a subset of keratinocytes within melanoma microenvironment highly up-regulate Twist and undergo Epithelial-Mesenchymal Transition (EMT). Surprisingly, when overexpressing Twist in keratinocytes, the resulting alteration in keratinocytes is inhibitory for melanoma invasion in both zebrafish and human cell culture models. The results are supported by convincing experimental data that provide new insights into the interactions between melanoma cells and their environment.

eLife Assessment

This important work advances our understanding of the single neuron coding types in the mouse gustatory cortex and the functional roles of these neurons for perceptual decision-making. The conclusions are based on compelling evidence from rigorous behavioral experiments, high-density electrophysiology, sophisticated data analysis, and neural network modeling with in silico perturbations of functionally-identified units. This work will be of broad interest to systems neuroscientists.

eLife Assessment

This study presents valuable findings on the physiological and computational underpinnings of the accumulation of intermittent glimpses of sensory evidence. The evidence supporting the claims of the authors is solid, although a more exhaustive characterisation of how the different signals interact would have strengthened the study. The work will be of interest to cognitive and systems neuroscientists working on decision-making.

eLife Assessment

This valuable cross-sectional longitudinal study leverages high-definition transcranial direct current stimulation to the left dorsolateral prefrontal cortex to examine its effect on procrastination behavior over an extended time span. The cross-sectional longitudinal study provided evidence for how stimulating DLPFC impacts reveal-world procrastination behavior. Support for the conclusions is incomplete owing to missing information about the analyses, and results, as well as some potential alternative interpretations.

eLife Assessment

This study provides valuable insights with convincing evidence detailing altered tactile perception in a mouse model of ASD (Fmr1 mice), paralleling sensory abnormalities in Fragile X and autism. Its main strength lies in the use of a novel and quantitative tactile categorization task and the careful dissection of behavioral performance across training and difficulty levels, suggesting that deficits may stem from an interaction between sensory and cognitive processes. The behavioral experiments are well executed and set the stage for subsequent mechanistic, causal, and computational approaches. The work is relevant to those interested in autism, cognition, and/or sensory processing.

eLife Assessment

Du et al. present a valuable study examining neural activation in medial prefrontal cortex (mPFC) subpopulations projecting to the basolateral amygdala (BLA) and nucleus accumbens (NAc) during behavioral tasks assessing anxiety, social preference, and social dominance. The strength of the evidence linking in vivo neural physiology to behavioral outcomes was considered solid; however, the slice electrophysiology data and their interpretation were less well received. Overall, the reviewers felt that the revised work provides insight into how distinct mPFC→BLA and mPFC→NAc pathways influence anxiety, exploration, and social behaviors.

eLife Assessment

This manuscript examines the evolution of molluscan shells using single-cell analyses of the adult mantle of Crassostrea gigas and compares these data with previous datasets from embryonic and larval stages of this species and other spiralians. The authors provide important support for a scenario in which secretory cells are broadly conserved across spiralians, and the incorporation of lineage-restricted genes contributes to the evolution of molluscan shells. While some of the conclusions of the authors are convincing, many aspects of the manuscript remain incomplete and could be improved, especially aspects of cell-type classification and validation.

eLife Assessment

This study presents a valuable perspective on platelet-mediated fibrin compaction, proposing that fibrin fibers undergo "winding" or coiling, an intriguing framework with potential implications for thrombosis and clot mechanics. However, the evidence supporting an active platelet-driven winding mechanism remains incomplete, relying largely on correlative observations without direct or quantitative validation of the proposed dynamics. Overall, the work is thought-provoking and of clear interest to the field, but stronger mechanistic evidence will be required to substantiate the central claims.

eLife Assessment

This study introduces the "Training Village," a valuable system for which solid evidence shows that it enables group-housed rodents to autonomously learn complex tasks while preserving natural social interactions. The platform is flexible, allowing animals to learn multiple tasks sequentially and supporting applications in continual learning. This approach is likely to be of broad interest to behavioral researchers using rodent models in systems and cognitive neuroscience.

eLife Assessment

This study provides a valuable contribution to our understanding of the neural basis of perceptual decision-making by jointly modeling behavioral outcomes and EEG signals in a contrast comparison task. The methods and analyses are solid, systematically comparing standard models assuming continuous evidence accumulation with models that track evidence without temporal integration (extrema detection). The authors show that behavior and neural signals are equally consistent with both alternatives, highlighting limitations in current modeling approaches and questioning the generality of evidence accumulation mechanisms.

eLife Assessment

This fundamental work significantly advances our understanding of the circuit-level implementation of predictive processing by elucidating the functional influence between putative prediction error neurons in layer 2/3 and putative internal representation neurons in layer 5. The evidence demonstrating that neither the hierarchical nor the non-hierarchical variant of predictive processing fully accounts for the presented data is convincing. Moving forward, this line of work would benefit from explicitly comparing different theories, thereby clearly articulating the points raised in this paper.

eLife Assessment

This study presents a valuable finding on the mutational landscape and expression profile of ZNF molecules in 23 Kenyan women with breast cancer. The evidence supporting the claims of the authors is solid, although inclusion of a larger number of patient samples, more statistical details and sufficient comparison with existing large-scale datasets would have strengthened the study. The work will be of interest to medical biologists working in the field of breast cancer.

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 convincing evidence for probabilistic recruitment of motor units that differed between the two heads.

eLife Assessment

The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. These potentially important results suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, even though the estrogen responsive enhancer does not loop with the TFF3 promoter. To explain these results, the authors invoke a transcriptional condensate model. The claim of a temporal delay and effects of the target gene transcription on the non-target gene expression are supported by solid evidence but there is no direct evidence of the role of a condensate in mediating this effect. The reviewers appreciate that the authors have done a lot of work to strengthen the study. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

eLife Assessment

This important study provides a detailed characterization of individual sarcomeres' contractility and of their synchrony in spontaneously beating cardiomyocytes derived from human induced pluripotent stem cells. The combination of high-resolution tracking, statistical analysis and mesoscopic modeling leads to compelling evidence that sarcomeres operate as dynamically unstable units, leading to stochastic heterogeneities in their contraction-elongation cycles depending on substrate stiffness. The work will be relevant to scientists interested in muscle biophysics, nonlinear dynamics and synchronization phenomena in biological systems.

eLife Assessment

This is a theoretical analysis that gives compelling evidence that length control of bundles of actin filaments undergoing assembly and disassembly emerges even in the absence of a length control mechanism at the individual filament level. Furthermore, the length distribution should exhibit a variance that grows quadratically with the average bundle length. The experimental data are compatible with these fundamental theoretical findings, but further investigations are necessary to make the work conclusive concerning the validity of the inferences for filamentous actin structures in cells.

eLife Assessment

This valuable study explores changes in the Drosophila microbiome in response to environmental temperature over more than ten years. The evidence showing that temperature leads to diversification of bacterial clades is solid, but additional information would help clarify how subspecies competition impacts microbiome composition and the host. The work will interest researchers working with microbiomes, microbial ecology, and evolutionary biology.

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. The new findings raise the 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.

eLife Assessment

This manuscript addresses an important question in clinical neuroscience: the use of the theta/beta ratio as a biomarker of attention deficit hyperactivity disorder (ADHD). The study takes an exceptional "multiverse" analysis approach to show that aperiodic activity differences between healthy controls and people with ADHD are driving the apparent theta/beta ratio differences. From a neuroscientific perspective, this is a critical finding because it has a major impact on guiding research on the diagnosis and treatment of ADHD.

eLife Assessment

This valuable study presents a comprehensive comparison of human and macaque monkey behavior across a range of visual perceptual phenomena. The use of a unified oddball visual search paradigm enables direct cross-species comparison while minimizing task-related confounds. It provides solid evidence that visual perception is largely similar between these two species, with some interesting exceptions. These insights into qualitative and quantitative differences between species are relevant for evaluating macaques as a model organism for understanding human vision.

eLife Assessment

This valuable study examined the geometry of visual object representations across hierarchically organized stages of the mouse visual cortex. The use of large-scale training and recording techniques provides solid evidence for changes along the hierarchy that may contribute to invariant object recognition. These findings, particularly if they could be supported by further analyses and clarifications to rule out alternative explanations, including influences of low-level features on behavior and neural activity, help establish the potential usefulness of the mouse to understand the neural basis of object recognition.

eLife Assessment

This important study investigates the impact of BRCA1/2 mutations on immunotherapy in lung adenocarcinoma using multi-omics approaches. The detailed genetic analysis of two cancer genes (BRCA1 and BRCA2) demonstrated their new roles in causing the tumor microenvironment in lung cancer. The solid findings of this study provide an essential foundation for further developing drugs targeting BRCA1/2 in lung cancer therapy.

eLife Assessment

This study examines the role of the fungal pathogen Candida albicans in the progression of colorectal cancer, a relevant and urgent topic given the global incidence of colon cancer. While the findings are useful and provide solid experimental work and insight into how Candida may contribute to tumor progression, the small patient sample size, reliance on in vitro models, and absence of in vivo validation may limit its impact. This work will interest scientists studying cancer progression and the role played by pathogens.

eLife Assessment

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

eLife Assessment

This useful study addresses the interesting question of how immune cells recognise infected erythrocytes in malaria. It proposes the parasite protein PfGBP-130 as an interaction partner of the human cell surface protein LFA 1, which could help explain how NK cells recognize infected erythrocytes. The conclusions are partially supported by pull-down and cell-based activation data. However, the overall evidence of direct interaction at the cell-cell interface and downstream effects is incomplete; stronger evidence is required to demonstrate surface exposure of PfGBP-130, as well as a direct role of this antigen in killing.

eLife Assessment

This manuscript investigates inter-hemispheric interactions in the olfactory system of Xenopus tadpoles. Using a combination of electrophysiology, pharmacology, imaging, and uncaging, the transection of the contralateral nerve is shown to lead to larger odor responses in the un-manipulated hemisphere, and implicates dopamine signaling, likely originating from the lateral pallium, in this process. The study convincingly uses a rich and sophisticated array of tools to investigate olfactory coding, and uncovers valuable mechanisms of signaling likely to be conserved across vertebrates.

eLife Assessment

This important study addresses the unresolved and long-debated question of whether atypical protein kinase C is required for the maintenance of synaptic potentiation and long-term memory. The convincing results confirm previous findings that persistent activity of PKMζ is required for lasting potentiation of hippocampal synapses and spatial memory. The study also adds new genetic evidence to support the earlier suggestion that enhanced expression of PKC iota/lambda compensates for the genetic reduction of PKM zeta to support synaptic potentiation and memory.

eLife Assessment

This valuable study reports that the ALDH-abundant cells display stem cell properties and may play a key role in the endometrial epithelial development in the mouse. The data supporting the main conclusion are solid, although further improvements are needed to strengthen the conclusions. This work will be of great interest to reproductive biologists and biomedical researchers working on women's reproductive health.

eLife Assessment

This important study examines the evolution of virulence and antibiotic resistance in Staphylococcus aureus under multiple selection pressures, specifically host immune function and antibiotic exposure. The evidence presented is convincing, supported by rigorous phenotypic and genomic data from within-host evolution experiments. The manuscript now provides a nuanced and robust interpretation of how pathogens adapt to complex selective landscapes.

eLife Assessment

This important study shows that action potentials undergo frequency-dependent failure along the axons of fast-spiking interneurons during sustained high-frequency firing, offering a mechanistic explanation for why inhibition may fail to restrain seizures. The evidence is solid, though additional analyses could further strengthen the mechanistic interpretation. The work will be of broad interest to neuroscientists studying axonal physiology, cortical inhibition, and epilepsy.

eLife Assessment

This valuable study contributes to the field of neuro-glial biology by establishing a direct causal link between astrocytic metabolism (glycolysis) and the structural wiring of neural circuits. Connecting the metabolic-synaptic mechanism to locomotor reorientation in the dopaminergic circuit offers new insights into how energy metabolism shapes circuit assembly and function. The evidence offers a solid foundation, moving logically from molecular mechanisms to circuit-level anatomy and finally to behavior; however, several central conclusions currently exceed the direct evidence presented. With appropriate calibration of claims and interpretations and/or additional clarifying experiments, the manuscript has the potential to make a significant contribution to our understanding of glial regulation of circuit assembly.

eLife Assessment

This important study by Kong et al. systematically and rigorously dissects the gene regulatory network underlying melanoma and breast cancer risk at the multi-cancer 2q33 locus. The authors provide compelling evidence that rs3769823 is a key functional variant that acts through allele-preferential binding of the transcription factors E4F1 and IRF2 to regulate CASP8 and FLACC1 in a cell-type-specific manner. The work makes a significant contribution to understanding the mechanisms operating at multi-cancer risk loci.

eLife Assessment

This important study introduces an innovative synthetic nanobody approach to probe the function of the bacterial SMC complex. The work is a compelling example of the potential of this approach. The authors generate protein chimeras to provide convincing evidence that their identified nanobodies target the coiled-coil region of the SMC subunit, demonstrating that this region is critical for SMC function in vivo. Overall, the work is significant for the fields of genome organisation, SMC protein biology, synthetic biology, and bacterial cell biology.

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

eLife Assessment

This valuable study focuses on a unique morphogenetic module, the junction-based lamellipodia (JBL). It provides a biomechanical understanding of how JBLs control endothelial cell-cell junctional remodelling to generate lumenised, multicellular blood vessels. The manuscript represents a robust, thoughtfully executed, and convincing study that uses high-resolution time-lapse imaging combined with pharmacological treatments to advance our understanding of lumen formation in vascular development.

eLife Assessment

This important study presents a technically rigorous and carefully controlled analysis of the signalling potential of cancer-associated gain-of-function Notch alleles. The work is clearly presented, and the experiments are robust, comprehensive, and well-controlled. While some data primarily establish the system or report negative findings, the comparative approach in a well-characterized model provides convincing mechanistic evidence for how these Notch variants function. This study will be of interest to researchers in both developmental and cancer biology.

eLife Assessment

This manuscript offers valuable structural and mechanistic insights into the assembly of the Type II internal ribosome entry site (IRES) from encephalomyocarditis virus (EMCV) and the translation initiation complex, revealing a direct interaction between the IRES and the 40S ribosomal subunit. A solid experimental strategy, combining cryo-EM analysis, complementary biochemistry, and detailed structural comparisons, provides mechanistic insights into IRES-based translation initiation systems. This paper will attract researchers in cap-independent translation, host-pathogen interactions, and virology.

eLife Assessment

This is a valuable study on single-cell transcriptomic analyses, focused on morphogenesis of the zebrafish inner ear in wildtype and lmx1bb mutants. The supporting evidence is mostly convincing, but incomplete in parts.

eLife Assessment

This study analyzes the temporal dynamics of gene expression following TNF stimulation in macrophages. The work brings valuable data and new methodological approaches to implicate the splicing rate of certain introns as a mechanism regulating mature mRNA expression. This will be of interest to audiences in RNA biology and innate immune response regulation. The experimental design is solid for the core findings, although in places the data limit the conclusions.

eLife Assessment

In this important manuscript, Matsuda and colleagues present a model describing the regulation of tracheal tubulogenesis in Drosophila melanogaster embryos. The authors support this model using convincing approaches that combine novel experimental results with previously published work from their group. While some conclusions are consistent with earlier studies, the present manuscript introduces distinct molecular markers not previously reported, which reinforce the authors' prior findings. In addition, the manuscript analyses, using experimental strategies, the requirement of the Dpp and EGFR signalling pathways for the maintenance of trachealess (trh), one of the key transcription factors governing tracheal development.

eLife Assessment

This important work advances our understanding of intraflagellar transport, ciliogenesis, and ciliary-based signaling, by identifying the interactions of IFT172 with IFT-A components, ubiquitin-binding, and ubiquitination, mediated by IFT172 C-terminus and its role in ciliogenesis and ciliary signaling. The evidence supporting the findings is convincing. This paper will be of interest to cell biologists and biochemists, especially those working on cilia and signaling.

eLife Assessment

This valuable study reports the architectural reorganization of the uterine luminal epithelium during the implantation period. The data presented are solid, although improvements are needed. This work is of interest to reproductive biologists and physicians practicing reproductive medicine.

eLife Assessment

This manuscript provides valuable high-resolution structural insights into the interaction between vaccine-elicited antibodies and SARS‑CoV‑2 evolution. The evidence is solid; however, the conclusions could be strengthened with further experimentation and analysis.

eLife Assessment

This valuable study compares orthogonal approaches for detecting RNA chemical modifications and provides a helpful framework for improving the reliability of direct RNA sequencing-based identification of RNA modifications. The evidence supporting the technical benchmarking claims is solid. However, support for the broader biological conclusions is not as strong, and the quantitative interpretation of the results, as well as the limitations of the underlying models, would benefit from further clarification.

eLife Assessment

This well-designed study offers important insights into the development of infants' responses to music based on the exploration of EEG neural auditory responses and video-based movement analysis. The compelling results revealed that evoked responses emerge between 3 and 12 months of age, but no age group demonstrated evidence of coordinated movements to music. This study will be of significant interest to developmental psychologists and neuroscientists, as well as researchers interested in music processing and in the translation of perception into action.

eLife Assessment

This study provides important insights into how tumorous germline stem cells (GSCs) in the Drosophila melanogaster ovary can mimic niche function and suppress the differentiation of neighboring cells. The findings that GSC tumors can incorporate non-mutant cells and inhibit their differentiation are compelling and extend current understanding of stem cell-niche interactions. However, the evidence supporting the conclusion that GSC tumors produce BMP ligands to mediate this effect remains incomplete, due to concerns regarding the quality and interpretation of the HCR-FISH data.

eLife Assessment

This study presents a valuable theoretical exploration on the electrophysiological mechanisms of ionic currents via gap junctions in hippocampal CA1 pyramidal-cell models, and their potentially unique contribution to local field potentials (LFPs). The biophysical foundations of transmembrane electric dipoles, and the associated argument points, are generally compelling. Experimental constraints on gap junctions and strictly quantitative matching between chemical vs. junctional inputs have been hard to achieve. This computational investigation thus offers a specific way to enhance conceptual understanding and provides interesting testable predictions, which would be of great interest to experimental neurophysiologists who interpret relevant recordings.

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.

eLife Assessment

This study provides valuable data on the role of Hsd17b7, a gene involved in cholesterol biosynthesis, as a potential regulator of mechanosensory hair cell function. The authors used both zebrafish and the HEI cell line to examine the effects of deletion of Hsd17b7 on hair cell function and survival. While the study presents convincing evidence, the effect sizes observed across several experiments, including functional readouts such as the acoustic startle response, are modest, which raises questions about the biological significance of the proposed mechanism.

eLife Assessment

This important study describes computationally designed proteins that bind to the chemokine CCL25. The authors present evidence that some binders simply prevent chemokine binding to the CCR9 receptor, while one binder changes the downstream signaling triggered by chemokine binding. The evidence is solid overall, but some uncertainty remains with respect to functional selectivity due to sensitivity differences between functional assays and the degree of binder selectivity between the large family of chemokine ligands.

eLife Assessment

This study presents a valuable theoretical exploration on the electrophysiological mechanisms of ionic currents via gap junctions in hippocampal CA1 pyramidal-cell models, and their potential contribution to local field potentials (LFPs) that is different from the contribution of chemical synapses. The biophysical argument regarding electric dipoles appears solid, but the evidence would be stronger if their predictions are tested against experiments. A shortage of model validation and strictly comparable parameters used in the comparisons between chemical vs. junctional inputs makes the modeling approach incomplete; once strengthened, the finding can be of broad interest to electrophysiologists, who often make recordings from regions of neurons interconnected with gap junctions.

eLife Assessment

This study resolves a cryo-EM structure of the GPCR, human GPR30, which responds to bicarbonate and regulates cellular responses to pH and ion homeostasis. Understanding the ligand and the mechanism of activation is important to the field of receptor signaling and potentially facilitates drug development targeting this receptor. Structures and functional assays provide solid evidence for a potential bicarbonate binding site.

eLife Assessment

This is an important study on the role of the neurokinin-2 receptor (NK2R) as a regulatory node connecting intestinal lipid metabolism, mucosal immunity, and the gut microbiome, bidirectionally regulating enterocyte lipid uptake, lipid droplet storage, chylomicron output, and systemic metabolic parameters in DIO mice. The authors present solid evidence linking Tacr2 deletion to reprogrammed epithelial lineage allocation, dampened immune gene expression, and male-biased protection from DSS colitis, despite dysbiotic microbiota. However, the causal evidence for some mechanistic and pro-inflammatory NK2R claims remains incomplete and potentially confounding, requiring additional cell-type-specific and functional experiments.

eLife Assessment

This useful study identified XAP5 as an ancient transcriptional regulator critical for primary ciliogenesis. The evidence supporting the conceptual framework linking evolutionary conservation to functional specialization in primary ciliogenesis remains incomplete. This work will be of interest to developmental biologists and to those studying diseases caused by ciliopathies.

eLife Assessment

These findings are important because they suggest that more selective JAK inhibition, particularly targeting JAK1 or JAK2, can effectively reduce organ pathology and pathogenic IFN-γ-producing immune cells in AIRE deficiency, refining therapeutic strategies beyond broad JAK inhibition. The work highlights JAK2 inhibition as a promising and potentially more targeted clinical approach for treating autoimmunity in this setting. The evidence is solid and moderately strong, building on the prior efficacy of ruxolitinib and supported by comparative studies in Aire-deficient models, though further validation in human systems would strengthen translational confidence.

eLife Assessment

This is a valuable 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 solid evidence for a reduction of group 2 innate lymphoid cells (ILC2). However, the strength of evidence supporting and analysing the impact of Dreg1 on Gata3 expression, a transcription factor required for ILC2 cell fate decisions, remains incomplete. This study will be of interest to immunologists.

eLife Assessment

This valuable study reports a spatiotemporal atlas of mouse placental development and explores the role of glycogen trophoblast cells in fetal viability. Solid data are presented to support the main conclusion. This work will be of great interest to developmental DNA reproductive biologists.

eLife Assessment

This important study introduces LUNA, a new autofocusing method that achieves nanoscale precision and robustly corrects focus drift during time-lapse microscopy, improving imaging under temperature shifts. The authors exploit this technical advance to investigate the bacterial cold shock response, providing convincing evidence that individual cells continue to grow and divide in a highly coordinated process that cannot be observed in population-level measurements. This work offers a technical and conceptual framework for reconciling discrepancies between bulk and single-cell growth measurements, with broad relevance for cell biology and microbiology.

eLife Assessment

The authors proposed two hypotheses: first, that methamphetamine induces neuroinflammation, and second, that it alters neuronal stem cell differentiation. These are valuable hypotheses, and the authors provided in vivo observations of the methamphetamine response in mice. However, concerns about data interpretation, and the current evidence is incomplete, requiring further experimental validation.

eLife Assessment

This important cross-species study tests whether the corpus callosum contains parallel, segregated pathways for ipsilateral and contralateral visual-field information, rather than mixed inputs from the two hemispheres. A major strength is its use of a combination of high-field functional magnetic resonance inaging and Bayesian population receptive field (pRF) modelling in humans with viral tracing in mice to offer complementary evidence for pathway segregation. At present, the evidence supporting the authors' claims is incomplete and would benefit from ruling out potential confounds that could mimic tract segregation in the human white-matter pRF data and the mouse anatomical tracing results, and from sharpening claims about laminar specificity.

eLife Assessment

This study presents valuable findings regarding cardiac and autonomic effects of seizures and epilepsy, with relevance to sudden unexpected death in epilepsy (SUDEP). They present solid evidence that genetic deletion of the potassium-chloride co-transporter in hypothalamic corticotropin-releasing hormone (CRH) neurons exacerbates bradycardia and enhances autonomic disturbances in a mouse model of temporal lobe epilepsy. However, the evidence that this deletion produces chronic hyperexcitability of the hypothalamic-pituitary-adrenal axis was incomplete, leaving a mechanistic gap. This work will be of interest to neuroscientists working on epilepsy, the HPA axis, and autonomic control.

eLife Assessment

This is a useful study, bolstering our understanding of spatial reference frames of visual perception. The high-resolution data and sophisticated analyses confirm and enhance earlier findings that visual representations operate in a predominantly retinotopic reference frame throughout the visual hierarchy in the human cortex. However, these analyses are currently incomplete, leaving open the possibility that eye-position gain and or spatiotopic representations may also be present.

eLife Assessment

This fundamental study reports convincing evidence for early verbal episodic memory formation. The findings demonstrate that speaker identity is a crucial feature, enabling episodic-like memories from birth, and will be of interest to cognitive neuroscientists working on brain development, memory, language learning and social cognition.

eLife Assessment

This valuable study presents a framework for a shareable data analysis pipeline aimed at improving reproducibility in neuroscience. The evidence for robustness and inter-laboratory operability is convincing. Overall, this work will be of interest to neuroscientists engaged in the analysis of large-scale neuronal recordings.

eLife Assessment

This study provides fundamental insight by identifying C. elegans SET-19 as a key enzyme that deposits H3K23me to somatic chromatin. The evidence is compelling, using a broad and modern toolkit of biochemical, genetic, and genome-wide analyses that consistently support the main claims. The significance of the study is further strengthened by the fact that H3K23me is an understudied histone modification, which is also conserved in mammals.

eLife Assessment

This valuable study examines the subcellular dynamics of the mammalian circadian clock proteins PER2, CRY1, and CK1, providing solid evidence that CK1 modulates the PER2-CRY1 interaction and drives the cytoplasmic localization of PER2 complexes. This could play a key role in modulating transcriptional repression by PER2, CRY1, and CK that contributes to the molecular circadian clock. There are minor concerns regarding the overexpression of the clock proteins in this study.

[Editors' note: this paper was previously reviewed by another journal.]

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. Convincing evidence is presented to support the paper's central conclusions. The study is likely to be of interest to those studying the subregional organization and cell type-specific functions of the dentate gyrus.