eLife Assessment

This study provides valuable insights into the cellular dynamics underlying accelerated tooth regeneration in a vertebrate model. Using single-nucleus RNA sequencing across multiple time points, the authors present a well-structured analysis of cell populations, trajectories, and intercellular signaling events associated with this process. The strength of evidence is solid but incomplete, as the conclusions are primarily supported by computational inference, without experimental validation of key findings.

eLife Assessment

This valuable study suggests that capsaicin nanoparticle administration in rats activates the transcription factor Nrf2 by directly binding to its repressor, KEAP1, leading to the induction of cytoprotective genes and preventing alcohol-induced gastric damage, offering a potential avenue for treating alcoholism-related gastric disorders. The authors provide solid evidence through a wealth of biochemical experiments in vitro, in cultured cells as well as in a rat model. The work will be of great interest to researchers studying oxidative damage in a variety of different diseases and the exploitation of molecules for therapeutic approaches.

eLife Assessment

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

eLife Assessment

This important work provides a new method to extract cfDNA from residual plasma from heparin separators for molecular testing. The evidence supporting the authors' claims is convincing, although some further metrics should also be evaluated. This finding will be interesting to people working in epigenomics and infectious disease diagnostics.

eLife Assessment

This study provides a valuable contribution to understanding the functional and molecular organization of the medial nucleus accumbens shell in feeding behavior. Through a multimodal approach that integrates in vivo imaging, optogenetic manipulation, and genetic strategies, the authors present convincing evidence for rostro-caudal differences in D1-SPN activity, advancing and refining earlier pharmacological frameworks. The discovery of Stard5 and Peg10 as regionally informative markers, together with the introduction of a Stard5-Flp driver line, establishes a foundation for more targeted circuit dissection. While an expanded characterization of other Stard5-positive cell populations (e.g., D2-SPNs, interneurons) would strengthen the work, the experimental rigor and internal consistency of the findings are clear. Overall, this is a technically strong and conceptually meaningful study with broad relevance for those investigating neural mechanisms of reward, affect, and feeding.

eLife Assessment

This fundamental work advances our understanding of the role of kisspeptin neurons in regulating the luteinizing hormone (LH) surge in females. The study uses cutting-edge techniques to provide compelling and rigorous data supporting a critical role of RP3V kisspeptin neurons in the neuroendocrine LH surge process. This research will be of interest to reproductive biologists and neuroscientists studying the female ovarian cycle. Continuing to examine the complexities of the LH surge and the neuronal populations involved, as done in this study, is critical for developing therapeutic treatments for women's reproductive disorders.

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.

eLife Assessment

This important study provides convincing data suggesting that subcellular localization of the spatial regulator of cell division, MinD, is an intrinsic feature of the protein's ability to associate with the membrane as both a dimer and a monomer. These findings distinguish the behavior of MinD in B. subtilis from its counterpart in E. coli and suggest that there is not a need to invoke additional localization factors. The reviewers felt that the revisions, particularly the additional experiments and changes to the text to make the experimental design and conclusions clearer, improve the quality of the manuscript and will increase its impact.

eLife Assessment

This study provides important insights into how immune cells in the brain's protective layers behave under normal and disease-like conditions, revealing location-specific activity patterns that may shape inflammation and disorders such as migraine. The evidence is compelling and supported by advanced imaging approaches and rigorous analyses, although some conceptual and interpretational limitations temper the mechanistic depth. Overall, the work will be of broad interest and represents an invaluable contribution to the growing field linking immune and nervous system function.

eLife Assessment

This valuable study shows that locomotion-related modulations in the mouse visual cortex are not uniform but primarily affect neurons in muscarinic receptor-negative patches, which receive projections from specific cortical areas. While the evidence is mostly solid, some uncertainties remain regarding the link between anatomical data and functional measurements. The study should be of interest to neuroscientists interested in state modulation of cortical function.

eLife Assessment

The authors investigate mechanisms of acquired resistance (AR) to KRAS-G12C inhibitors (sotorasib) in non-small cell lung cancer, proposing that resistance arises from signaling rewiring rather than additional mutations. While the study addresses a valuable clinical question, it is limited by several weaknesses in experimental rigor, data interpretation, and presentation, meaning the strength of evidence is incomplete.

eLife assessment

This study provides an important and biologically plausible account of how human perceptual judgments of heading direction are influenced by a specific pattern of motion in optic flow fields known as retinal curl. By combining psychophysical experiments and neural modeling, the authors demonstrate that what was previously considered an incidental "nuisance" signal actually serves as a functional control signal for estimating heading and steering toward a fixated target. While the evidence for the role of curl signals is convincing and advances our understanding of vision-based navigation, the work's impact would be strengthened by situating these findings among other cues that contribute to heading estimation, and by clarifying both the time course of these computations and their generalizability across different navigational contexts.

eLife Assessment

This paper provides a valuable observation that imiquimod, a compound often used to induce a psoriasis-like skin inflammation in mice, has a TLR7-independent effect acting through the unfolded protein response and binding to Gelsolin. However, the mechanism connecting Gelsolin to skin inflammation presented in this paper is incomplete and requires further investigation. These findings are of interest to the field of skin immunology.

eLife Assessment

This valuable study investigates how multisensory signals influence detection decisions and confidence judgments in presence and absence tasks using pre-registered psychophysical experiments and computational modeling. Across two online samples, the authors argue that audiovisual stimuli improve detection performance but do not enhance metacognitive efficiency, and that confidence is higher for absence than presence judgments. The evidence is broadly solid, although aspects of the computational interpretation and model comparisons would benefit from additional clarification and testing against simpler alternatives.

eLife Assessment

This important study advances a new computational approach to measure and visualize gene expression specificity across different tissues and cell types. The framework is potentially helpful for improving the way gene expression specificity is defined across biological datasets, especially among single-cell datasets. The evidence supporting the method is generally solid, although further evaluation of the method's robustness and comparison to other approaches would strengthen the conclusions.

eLife Assessment

This valuable study introduces an innovative experimental design to address a crucial and timely issue in microbial ecology: the potential bias in soil microbial community analyses caused by extracellular DNA degradation. While the evidence showing variable degradation rates of extracellular DNA is convincing, additional conceptual, methodological, and statistical clarifications could reinforce the claims and the study's contribution to the field. This research will appeal to microbial ecologists and researchers interested in using molecular techniques to evaluate microbial community structure.

eLife Assessment

In this study, the authors use microCT to image an intact hatchling octopus and segment major organ systems, including the vascular, respiratory, digestive, and nervous systems. The resulting dataset is of good quality, and its release through a public web interface is a valuable resource for the community to explore cephalopod mesoscale anatomy. However, the authors claim to have elucidated previously uncharacterized chemotactile pathways from the suckers to the brain, for which there is incomplete evidence, as microCT does not reveal structural connectivity. In addition, the language is often overly complex, obscuring the main points and making it difficult to assess the strength of individual claims. This article would benefit from more cautious framing of the anatomical findings and complementary neuronal tracing experiments to support the proposed pathways.

eLife Assessment

This valuable study investigates the interaction of two integral membrane proteins (Cdhr1a and Pcdh15b) and their roles in cone-rod dystrophy. Convincing evidence using loss-of-function mutants demonstrates clearly that both proteins are required for cone maintenance and survival. Although some evidence (Western blots and cell aggregation assays) demonstrates Cdhr1a and Pcdh15b can physically interact, there is insufficient evidence to support the subcellular localization and the proposed heterodimeric interaction of the two proteins from distinct subcellular compartments in cone photoreceptors.

eLife Assessment

This study provides important insights into how species-specific variation in oxytocin receptor regulatory architecture contributes to diversity in brain expression patterns and social behaviors. By generating multiple BAC transgenic mouse lines carrying the prairie vole oxytocin receptor locus and combining anatomical, molecular, behavioral, and chromatin-structure analyses, the authors present convincing evidence that distal regulatory elements constrain peripheral expression while permitting brain expression aligned with behavior. This study provides an experimental framework and a resource that are of value for dissecting how regulatory variation in neuromodulatory systems contributes to species differences in social behavior. This work will be of interest to those interested in social behavior, oxytocin, neuromodulation, and related conditions.

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

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

eLife Assessment

This important study highlights the role of MIRO1 in regulating mitochondrial oxidative phosphorylation in smooth muscle cells, a process that appears necessary to sustain their proliferation. Overall, the work provides convincing evidence that mitochondrial positioning and function influence vascular disease, although several bioenergetic and mechanistic aspects would benefit from deeper investigation.

eLife Assessment

This study provides valuable insights into how HIV-1 Env modulates the nanoscale organization and dynamics of the CXCR4 co-receptor on T cells, using quantitative imaging and functional approaches, the authors present convincing evidence that gp120 engagement promotes CD4-dependent clustering and altered mobility of CXCR4, distinct from the effects of the natural ligand CXCL12. Some concerns were raised regarding the interpretation of the single-particle tracking analyses, and additional clarification or analysis may help strengthen the conclusions. The physiological relevance of the findings could be further enhanced by validation with infectious virus and by more clearly integrating the CXCR4R334X mutant observations into the central mechanistic narrative. The work will be of interest to researchers studying HIV entry and membrane receptor organization.

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

eLife Assessment

This study presents important findings for the understanding of central brain circuits that underlie nociception-induced escape. Using a laser-based nociception assay, chronic neuronal silencing, trans-Tango anatomical tracing, and reference to connectomic data, the authors propose that nociceptive signals (from painless- and trpA1-expressing neurons) converge on a subset of dopaminergic neurons (subsets of PPL1 and PAM), which in turn engage mushroom body output neurons (MBONs) to shape escape latency. However, methods and controls fall short of fully supporting the findings, rendering the evidence incomplete. This study will be of interest to scientists studying nociception and learning and memory circuits.

eLife Assessment

This work presents a valuable new open-source tool for wirelessly controlling optogenetic stimulation in neuroscience experiments in behaving rodents. Evidence for its potential usefulness in different types of optogenetic experiments is solid, although some details and concerns were viewed as lacking or overlooked (e.g., system latency, battery weight). The work is expected to interest neuroscientists working with optogenetics and neuroengineers developing small-sized integrated devices for rodent experiments.

eLife Assessment

The manuscript by Mancl et al. provides important mechanistic insights into the conformational dynamics of Insulin Degrading Enzyme (IDE), a zinc metalloprotease involved in the clearance of amyloid peptides. Supported by a compelling combination of time-resolved cryo-EM, SEC-SAXS, enzymatic assays, and both all-atom and coarse-grained simulations, the study reveals an insulin-induced allosteric transition and transient β-sheet interactions underlying IDE's unfoldase activity, thereby refining our understanding of IDE's functional cycle and offering a structural framework for developing substrate-selective modulators of M16 metalloproteases. The latest round of revisions further improves clarity and presentation by updating structural statistics, correcting minor textual inconsistencies, and refining supplemental materials, fully addressing the remaining reviewer comments.

eLife Assessment

This study provides valuable insights into addressing the question of whether the prevalence of autoimmune disease could be driven by sex differences in the T cell receptor (TCR) repertoire, correlating with higher rates of autoimmune disease in females. The authors compared male and female TCR repertoires using bulk RNA sequencing, from sorted thymocyte subpopulations in pediatric and adult human thymuses; however, the analyses provided do not provide sufficient discrimination, as paired TCR chains are not examined, and incompletely support the central claims regarding sex differences in the TCR repertoire and potential autoimmune bias.

eLife Assessment

Combining state-of-art in-situ cell-surface proteomics, functional genetic screening, and single-nucleus RNA sequencing, this fundamental work substantially advances our understanding of glial contributions to organismal lifespan. The evidence supporting the conclusions is compelling. The work will be of broad interest to researchers studying aging biology, glia-neuron communication and in vivo proteomic profiling.

eLife Assessment

This study presents a valuable finding on how the locus coeruleus modulates the involvement of medial prefrontal cortex in set shifting using calcium imaging in mice. The evidence supporting the claims was viewed as solid in revealing the dynamics and potential mechanisms supporting extradimensional shifts. The work is of broad interest to those studying flexible cognition.

eLife Assessment

The new development of Neuroplex, a pipeline that links projection-defined neuronal identity to in vivo calcium activity within the same animal, is an important contribution to the field of neuroscience and beyond. The strength of evidence is convincing.

eLife Assessment

This valuable study addresses a critical question regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, despite the inclusion of interesting behavioral and imaging data, significant limitations remain, even after revision, in the design of the motor learning task and the associated data analyses. As a result, the presented data are incomplete to support the central conclusions.

eLife Assessment

This important study provides insights into the role of the cerebellum in fear conditioning, addressing a key gap in the literature. The evidence presented in support of the conclusions is solid. This work will be of interest to both the extinction learning and cerebellar research communities.

eLife Assessment

This valuable work identifies a subpopulation of neurons in the larval zebrafish pallium that responds differentially to varying threat levels, potentially mediating the categorization of negative valence. The evidence supporting these claims is solid; however, the study would be strengthened by more sophisticated analyses of functional imaging results, behavioral confirmation of stimulus valence, and further evidence linking the functionally distinct clusters to their molecular identity. This work will be of interest to systems neuroscientists investigating the circuit-level encoding of emotion and defensive behavior.

eLife Assessment

This valuable study presents a plastic recurrent spiking network model that spontaneously generates repeating neuronal sequences under unstructured inputs. The authors provide solid evidence that, while the global weight distribution stabilizes, individual synaptic connections undergo constant turnover with strength-dependent timescales, supporting sequence generation. However, the study is purely simulation-based and phenomenological, lacking both a mechanistic explanation for sequence emergence and explicit experimental predictions, and robustness to alternative, more biologically realistic plasticity rules remains to be demonstrated. The work will be of interest to theoretical and experimental neuroscientists working on synaptic plasticity and neural sequence generation.

eLife Assessment

In light of the diverse functions associated with the Dorsal Raphe Nucleus across vertebrate species, this important study presents findings on the role of serotonin in promoting behavioral quiescence through the regulation of neuromotor populations. Combining optogenetics with brain-wide activity analyses, the study provides convincing evidence of interest to researchers in neuromodulation and translational medicine fields.

eLife Assessment

This manuscript presents important findings that challenge traditional models of speech processing by demonstrating that theta-gamma phase-amplitude coupling in the auditory cortex is primarily a stimulus-driven alignment to external acoustic structures rather than an intrinsic neural oscillatory mechanism. The evidence supporting these claims is convincing, grounded in a robust cross-linguistic acoustic analysis and high-fidelity, time-resolved intracranial recordings.

eLife Assessment

This is a potentially important study comparing infants (8 months) and adults with respect to rhythmic EEG response properties during periodic and aperiodic visual stimulation. The results provide solid evidence for a ~4 Hz EEG response in infants that emerges independently of stimulation frequency. At this stage, additional work will be required to conclusively establish that this theta-band effect reflects genuine neural resonance rather than oculomotor processes.

eLife Assessment

Shin et al present important new observations regarding novel REM-specific cortical high-frequency oscillations. The evidence demonstrating the presence of a novel rhythm is convincing. However, the data presented is incomplete to demonstrate claims of a) brain-state-specific effects of these events, b) clear structured reactivation, and c) the specific degree of linkage to memory consolidation.

eLife Assessment

This study is useful and unique, since hagfish brains are of phylogenetic importance and can reveal features ancestral to all vertebrates. The manuscript is, however, incomplete and would benefit from contextualization with the current literature; comparisons with the recent amphioxus study are suggested, plus an increased focus on the specific, unique features of the hagfish brain. One significant concern is the apparent absence of Datx2 expression, given that the riboprobe was synthesized from cDNA derived from whole-brain RNA extracts. Ideally, the authors should identify a tissue in which Datx2 is known to be strongly expressed and then apply the probe as a positive control.

eLife Assessment

This important work outlines why commonly applied performance metrics in predictive modelling do not accurately reflect translational potential using the example of psychiatric care; it provides a web-based tool to contextualize effect sizes in psychiatry with respect to reliability and base rates, and to calculate the real-world utility of prediction models under different scenarios. The evidence supporting the conclusions is convincing, incorporating established psychometric principles that will be of use for multiple fields, along with transparent quantitative logic and example applications. The manuscript would benefit from further details about how the tool can be optimally applied and how the resulting outputs should be interpreted. The work will be of broad interest to both clinical experts and scientists in biomedicine and the life sciences.

eLife Assessment

The authors present useful findings demonstrating that the RNA modification enzyme Mettl5 regulates sleep in Drosophila. Through transcriptome- and proteome-wide analyses, the authors identified downstream targets affected in heterozygous mutants and proposed that Mettl5 regulates the translation and degradation of clock genes to maintain normal sleep function. Through additional analyses, the authors provided solid evidence supporting this model.

eLife Assessment

This study provides valuable insights into the role of MATR3 in oocyte maturation and folliculogenesis, using conditional knockout mice and in vitro follicle culture systems to show that MATR3 is required for oocyte growth and gene transcription, with downstream effects on follicle development. The strength of the evidence is incomplete, as key findings lack independent validation, methodological details are insufficient, and inconsistencies in data presentation reduce confidence in the conclusions. The work will be of interest to researchers in reproductive biology and fertility.

eLife Assessment

This important study combines cryo-EM, biochemical, and cell-based assays to examine how Gβγ interacts with and potentiates PLCβ3. The authors present evidence for multiple Gβγ interaction surfaces and argue that Gβγ primarily enhances PLCβ3 activity after membrane recruitment rather than serving mainly as a membrane-recruitment factor. The evidence is solid overall, although uncertainty remains about the physiological relevance and precise arrangement of the proposed interfaces because the structural model relies on engineered crosslinking.

eLife Assessment

Kim et al. provide important findings explaining how T3SS assembly is regulated by a conserved genetic context. The evidence supporting the conclusions is compelling, with numerous experiments demonstrating the validity of the findings. The work will be of interest to molecular biologists, biochemists, and microbiologists working on secretion systems or similar complexes. Further studies revealing similar mechanisms in other systems would enhance the impact of the current study.

eLife Assessment

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

eLife Assessment

This important study shows that orientation tuning of V1 neurons is suppressed during a continuous flash suppression paradigm, especially in neurons with binocular receptive fields. These findings, made using cutting-edge imaging techniques, convincingly implicate early visual processing in continuous flash suppression, in agreement with previous studies suggesting reduced effective contrast of such stimuli in V1.

eLife Assessment

The authors adapt sequencing of nascent DNA (DNA linked to an RNA primer, "SNS-Seq") to map DNA replication origins in Trypanosoma brucei. The main impact of this work is reporting a new set of putative origins, which do not overlap with previously reported origins, but which appear to overlap with previously mapped DNA-RNA hybrid (R-loops). Thus, these valuable findings open up new avenues for further investigation into the mechanistic basis for firing of replication forks in this organism. However, the supporting evidence remains incomplete and would benefit from orthogonal validation. This work will be of interest to those studying DNA replication and epigenetic regulation of fork origins.

eLife Assessment

This important work provides a new method to extract cfDNA from residual plasma from heparin separators for molecular testing. The evidence supporting the authors' claims is convincing, although some further metrics should also be evaluated. This finding will be interesting to people working in epigenomics and infectious disease diagnostics.

eLife Assessment

Ge et al here report a structural study of the native tripartite multidrug efflux pump complexes from Escherichia coli that identifies a novel accessory subunit, YbjP, the structure of the native TolC-YbjP-AcrABZ complex, as well as structures of the AcrB protein in L, T, and O conformations. The strength of the structural data is compelling, and the importance of the findings is potentially fundamental. In the revised manuscript, the authors have included additional analysis and made comparisons with pre-existing data which has helped place the data and its impact in the proper context.

eLife Assessment

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

eLife Assessment

This valuable article provides a convincing and very detailed model of the process regulating the assembly of the spore coat in the model spore-forming bacterium Bacillus subtilis. It focuses on SafA, a morphogenetic coat protein involved in the assembly of the spore coat inner layer, deciphering the contributions of disulfide bond formation and crosslinking reactions catalyzed by a transglutaminase. The process had been studied with a combination of genetics and microscopy, but this is the first complete assessment incorporating detailed biochemical approaches.

eLife Assessment

This valuable study aims to determine mechanisms underlying breast cancer initiation and tumour progression. The manuscript includes a solid set of transcriptomic and proteomic datasets from tumour samples and examines mitochondrial function within the tumours. While the underlying mechanisms linking expression changes to functional effects remain speculative. This paper provides a resource for researchers working on breast cancer and/or HER2-driven bioenergetics changes.

eLife Assessment

This important study addresses the contribution of pericytes to the organization and permeability control of the zebrafish blood-brain barrier (BBB). By analyzing pdgfrb mutant zebrafish that lack brain pericytes, the authors reveal that the resulting cerebrovascular network is abnormally patterned. Remarkably, however, the barrier retains its restrictive permeability during larval and juvenile stages. More pronounced vascular defects become evident in adults, where localized BBB leakage coincides with hemorrhages and aneurysm formation. Based on convincing and beautifully documented imaging data, the authors argue that, unlike what has been reported in rodent systems, pdgfrb-dependent pericytes are not essential for maintaining BBB integrity in the zebrafish brain.

eLife Assessment

The authors aim to understand why Kupffer cells (KCs) die in metabolic-associated steatotic liver disease (MASLD). This is a valuable study using in vitro studies and an in vivo genetic mouse model, suggesting that increased glycolysis contributes to KC death in MASLD. The data presented are now convincing and adequately revised. This work will be of interest to researchers in the immunology and metabolism fields.

eLife Assessment

The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels. The authors suggest that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

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 study introduces a valuable toolkit for zebrafish transgenesis, significantly enhancing the flexibility and efficiency of transgene generation for immunological applications. The authors provide convincing evidence through well-designed experiments, demonstrating the toolkit's utility in generating diverse and functional transgenic lines.

eLife Assessment

This study maps the genotype-phenotype landscapes of three E. coli transcription factors and the topographical features of these landscapes. It shows that ruggedness and epistasis do not hinder the evolution of strong transcription factor binding sites. These convincing findings contribute important insights into fitness landscape theories and highlight the role of chance, contingency, and evolutionary biases in gene regulation. The authors then study the topographical features of these landscapes, especially the number and distribution of local maxima, as well as the statistical properties of evolutionary paths on these landscapes.

eLife Assessment

Findings from this study are considered fundamental because they identify amino acid uptake, cholesterol synthesis, and protein prenylation as key metabolic regulators of B cell activation, proliferation, and survival, advancing understanding of T-independent immune responses. The study links metabolic reprogramming directly to B cell function, highlighting how cellular metabolism supports immune fitness. The evidence is compelling, combining unbiased proteomic profiling with genetic and pharmacological validation to demonstrate causal roles for these pathways.

eLife Assessment

This study represents a useful finding on the social modulation of the complex repertoire of vocalizations made across a variety of strains of lab mice. The evidence supporting the claims is, at present, incomplete, as numerous concerns regarding the appropriate categorization of vocalizations, the averaging of data points with disparate levels of occurrence, the interpretation of the function of noisy calls, and a general lack of adequate analyses of experimental data were raised. With these issues addressed, the work will be of importance to scientists studying rodent vocal communication.

eLife Assessment

This important paper substantially advances our understanding of how Molidustat may work, beyond its canonical role, by identifying its therapeutic targets in cancer. This study presents a compelling and well-structured investigation into the therapeutic vulnerabilities of APC-mutant colorectal cancer. This work will be of broad interest to the cancer community in studying small molecules and their therapeutic targets.

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 modelling, and model-based fMRI analyses provides solid support for the main claims. The addition of new model-comparison figures in revision effectively addresses the previously noted potential confound between posterior switch probability and time in the neuroimaging results. At the behavioural level, while the computational model captures the pattern of "system neglect" well, qualitatively distinct mechanisms, such as hyper-prior attraction toward experiment-wise mean parameters, reporting biases, or probability-outlier underweighting, could produce similar behavioural signatures and cannot be fully disambiguated with the current design alone; however, converging evidence from the authors' prior work partially mitigates this concern.

eLife Assessment

This study represents an important advance in our understanding of how certain inhibitors affect the behavior of voltage gated potassium channels. Robust molecular dynamics simulation and analysis methods lead to a new proposed inhibition mechanism with convincing strength of support. This study has considerable significance for the fields of ion channel physiology and pharmacology and could aid in development of selective inhibitors for protein targets.

eLife Assessment

In this manuscript, based on electron microscopy observations of C. elegans embryos, the authors make the bold claim that the plasma membrane ruptures during cell division and that closure of this opening by membrane extension contributes to cytokinesis. Although the findings are potentially valuable, the evidence in support of the authors' claims is inadequate.

eLife Assessment

This manuscript uncovers the importance of Vinculin in the maintenance of junctional integrity during neural tube closure in regions of increased mechanical stress, by using sophisticated methods such as laser ablation and live imaging. The manuscript also reports a novel application of an established embryonic stem cell protocol to efficiently generate mutant and transgenic embryos for analysis. The findings are fundamental in nature, significantly improve our understanding of a major research question, and are backed by compelling evidence. Whilst there is much to appreciate in this work, exactly how Vinculin mediates neural fold elevation remains unclear, and addressing this lacuna will significantly improve the strength of the manuscript; in addition, some rewriting for better clarity (including technical/methodological details) and inclusion of possible consequences of the increased number of tight junction gaps in the vinculin mutant would be pertinent.

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 convincing in its experimental design and analytical approach. This work should interest cognitive neuroscientists who study perception and decision-making.

eLife Assessment

This is an important study that addresses the role of fever as a conserved response to viral infection. It demonstrates that the heat-shock factor, HSF1, is activated by increased temperature during fever to enhance the anti-viral immune response. The data provides compelling evidence for the conclusions and the work will be of interest to virologists, immunologists, and cell biologists.

eLife Assessment

This article presents valuable findings on how the timing of cooling affects autumn bud set in European beech saplings. The study leverages extensive experimental data and provides an interesting conceptual framework for the various ways in which warming can affect bud set timing. The statistical analysis is very well considered, while indicating some factors that may temper the authors' claims. The factorial experiments offer solid support.

eLife Assessment

This important study combined careful computational modeling, a large patient sample, and replication in an independent general population sample to provide convincing evidence in support of a computational account of a difference in risk-taking between people who have attempted suicide and those who have not. It is proposed that this difference reflects a general change in the approach to risky (high-reward) options and a lower emotional response to certain rewards. While the findings advance our understanding of cognitive mechanisms at the group level, the observation that computational phenotype is predictive of suicidal behavior only in the clinical sample and not in the online sample limits its applicability for individual prediction, early detection and prevention of suicidality.

eLife Assessment

Using single-cell transcriptomic data from mouse inner ear hair cells, the authors compare for the first time gene expression across the four recognized hair cell types in adults, generating information fundamental to understanding hair cell relationships between the ancient vestibular compartment and the more recent cochlea. Among observed differences, compelling evidence is provided for the expression in vestibular hair cells but not cochlear hair cells of certain ciliary motility-related genes, suggesting that the kinocilium of vestibular hair cells may function as an active force generator to increase sensitivity.

eLife Assessment

This important work delineates layered glucose-responsive neuropeptidergic mechanisms that regulate sugar intake. Using a combination of genetic, physiological, and behavioral experiments, the authors convincingly show that Hugin- and Allatostatin A-releasing neurons suppress sugar feeding by reducing the sensitivity of Gr5a-expressing gustatory neurons. They further demonstrate that Neuromedin U neurons share key physiological properties with fly Hugin neurons, highlighting conserved peptide functions across animal phyla.

eLife Assessment

This important study developed a new sensor for TDP-43 activity that is sensitive and robust that should strongly impact the field's ability to monitor whether TDP-43 is functional or not. The evidence, though limited to cell culture, is compelling and is the first demonstration that a GFP on/off system can be used to assess genetic TDP-43 mutants as well as loss of soluble TDP-43.

eLife Assessment

This valuable study addresses mechanisms of feedback inhibition between planar cell polarity protein complexes during convergent extension movements in Xenopus embryos. The authors propose a conceptually new model, in which non-canonical Wnt ligand stimulates transition of Dishevelled from its complex with Vangl to Frizzled, with essential roles of Prickle and Ror in this process. The main observations supporting molecular interactions rely on modest but significant changes in protein association in response to Wnt11. While the study is limited due to insufficient phenotypic analysis at the cellular level and the use of exogenously supplied proteins, this work is convincing and will be of broad interest to cell and developmental biologists.

eLife Assessment

In this important study, a new multi-scale imaging workflow promises to accelerate and democratize comparative connectomics, with projectome-level data informing synapse-level connectivity. While the pipeline and time savings are convincing, the evidence for the segmentation methodology as a reusable community resource is incomplete, with key metrics like error rates, annotation times, and proof-reading times not reported. Furthermore, the evidence on the utility of projectome-level information for analysing brains appears misleading. By clarifying the findings and ensuring that the complete software pipeline is available in online open source repositories alongside precise documentation, the authors would deliver on their vision to enable any laboratory to map and analyse brain connectomes.

eLife Assessment

This manuscript demonstrates the feasibility and potential value of using functional MRI in awake, behaving mice, enabling assessment of distributed brain activity during ongoing behavior in a manner analogous to human fMRI. The valuable findings suggest that the periaqueductal gray (PAG), a midbrain structure classically linked to threat processing and aversive learning, also contributes to reversal learning. If supported, this result would carry theoretical and practical implications for our subfield by expanding the computational roles attributed to the PAG and motivating cross-species circuit-level investigations. However, the strength of evidence is, at present, incomplete, and several key claims are only partially supported by the current analyses.

eLife Assessment

This multi-omics study provides a comprehensive characterization of the context-dependent roles of the JAK-STAT pathway (JSP) across different cellular compartments within the breast cancer microenvironment. The authors present convincing evidence that high JSP activity paradoxically drives anti-tumor cytotoxicity in T cells but promotes malignancy and immunosuppression in tumor epithelial cells, leading to the fundamental discovery that broad JAK-STAT inhibition could be therapeutically counterproductive. Ultimately, the identification of the immune-related JSP score and the STAT4 axis as predictive biomarkers for anti-PD-1 immunotherapy response, particularly in triple-negative breast cancer, offers critical insights for precise patient stratification and targeted therapeutic interventions.

eLife Assessment

It remains unclear how human antibody-secreting cells (ASCs) differentiate. In this study, the authors discovered a CD30⁺ intermediate subset that appears during the transition from B cells to ASCs, providing a potential ontogeny for extra-germinal center B cell differentiation. This study is useful because it identifies novel intermediate markers that enable tracking of human ASC ontogeny, offering new insights into ASC development. However, the evidence is incomplete, and we see three major limitations: (1) the data are largely representative, requiring additional reproducibility; (2) the bioinformatics analysis is limited; and (3) step-wise phenotypic validation would require lineage-tracing experiments on sorted populations.

eLife Assessment

This important study offers insights into the anatomical and physiological features of cold-selective lamina I spinal projection neurons. The evidence supporting the authors' claims is convincing, although including a larger sample size and more quantification would have strengthened the study, and the claims of monosynaptic connectivity would benefit from further experimental evidence. The work will interest those in the field of somatosensory biology, especially researchers studying spinal cord dorsal horn circuits and projection neuron cell types.

eLife Assessment

This study offers valuable insights into the anatomical and physiological features of cold-selective lamina I spinal projection neurons. The evidence supporting the authors' claims is convincing, although including a larger sample size and more quantification would have strengthened the study further, and the claims of monosynaptic connectivity would benefit from being stated more cautiously. The work will interest those in the field of somatosensory biology, especially researchers studying spinal cord dorsal horn circuits and projection neuron cell types.

eLife Assessment

This study presents data suggesting that excitatory cholecystokinin (CCK)-expressing neurons in hippocampal area CA3 influence hippocampal-dependent memory using multiple methods to manipulate excitatory CCK-expressing CA3 neurons. The study is valuable, particularly considering that most past studies of CCK-expressing neurons have focused on those neurons that co-express CCK and GABA. Currently, the strength of evidence is incomplete, but it would improve if evidence of specificity was provided and other concerns were addressed. If this is not possible, the conclusions, particularly those requiring evidence of specific targeting of excitatory neurons, should be modified accordingly.

eLife Assessment

Using isolated frog brainstem preparations, pharmacological manipulation of excitability, systematic extracellular unit mapping, and focal microinjections, this study provides important findings on whether the buccal rhythm generator is a discrete anatomical nucleus or a distributed, state-dependent network. The question is conceptually significant and of interest to researchers working within respiratory neurobiology and rhythmogenicity in general, and the preparation and experimental strategy are generally appropriate. However, the evidence for the strongest architectural claims is incomplete, with pseudoreplication in pooled unit-mapping analyses, inconsistent statistical reporting, and limited controls in necessity/sufficiency experiments. Overall, although data are largely convincing, substantial revision and more nuanced interpretation of the results are required before claims of state-dependent architectural reorganization can be considered well-supported.

eLife Assessment

This valuable study addresses a timely question regarding the contribution of transposable elements to splice isoform diversity in the Drosophila brain, directly engaging with recent conflicting findings in the field. The work provides convincing evidence that TE-gene chimeric transcripts are detectable and that prior discrepancies largely arise from methodological differences in computational pipelines and experimental design. The combination of reanalysis, methodological clarification, and targeted validation represents a technical contribution that will be of interest to researchers studying transcriptome complexity and transposable elements. However, the strength of evidence would be further enhanced by increased methodological transparency, more rigorous experimental controls, and a more cautious interpretation of functional implications.

eLife Assessment

This study presents an important methodological advance-Liver-CUBIC combined with multicolor metallic nanoparticle perfusion-that enables high-resolution 3D visualization of the liver's complex multi-ductal architecture. The identification of the Periportal Lamellar Complex (PLC) as a novel perivascular structure with distinct cellular composition and low-permeability characteristics is convincing, supported by rigorous imaging data. The observed scaffolding role during fibrosis offers intriguing biological insights, though the functional claims would benefit from direct experimental validation.

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. Solid 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.

eLife Assessment

This paper describes Unbend - a new method for measuring and correcting motions in cryo-EM images, with a particular emphasis on more challenging in situ samples such as lamellae and whole cells. The method, which fits a B-spline model using cross-correlation-based local patch alignment of micrograph frames, represents an important tool for the cryo-EM community. The authors elegantly use 2D template matching to provide convincing evidence that Unbend outperforms the previously reported method of Unblur by the same authors. Comparison to alternative programs for motion correction shows smaller gains, but with interesting differences between data sets.

eLife Assessment

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

eLife Assessment

This study presents valuable findings and employs modern analytical approaches on how transient absence of visual input (darkness) affects tactile encoding in the rat somatosensory cortex (S1). The evidence supporting the authors' claims is solid, as population-level neural activity recorded in S1 and decoded by a CNN carries more discriminable texture information in darkness. The underlying basis of this effect remains only partly resolved, however, because it is still unclear which neural features from the CNN drive the decoding and if visual interference is appropriately accounted for, which might confound true neural representational change.

eLife Assessment

The authors test the hypothesis that gonadal steroid signaling influences the transcriptional development of specific neurons in the mPOA during adolescence, and that such adolescent development of the mPOA is necessary for mating behaviors. The valuable findings are supported by convincing evidence. This work contributes new insight into hormone-sensitive transcriptional profiles within genetically defined neuron clusters in the mPOA during adolescence and will be of interest to systems and molecular neuroscientists and those interested in development, sex differences, and/or hormonal regulation.

eLife Assessment

Using the clownfish model, this study examines how growth, feeding, and agonistic behavior result in socially dominant or subordinate states in size- and age-matched individuals of the clownfish, Amphiprion percula. The authors complement this work with whole-body transcriptomics and find significant variation in genes and gene co-expression modules related to growth and satiety-related pathways, as well as ossification-related genes. They provide solid evidence that emerging dominants grow more, eat more, and behave more aggressively than subordinate or solitary individuals; these phenotypic differences are accompanied by distinct gene expression profiles, including variation in growth- and satiety-related pathways. The work is valuable in advancing our understanding of how the social environment regulates phenotypic change; however, claims regarding the mechanistic role of gene expression are only partially supported by the current analyses.

eLife Assessment

In this important study, Bready et al. investigate how a highly conserved long-range enhancer mediates neural-specific SOX2 regulation during neural differentiation using human neural stem cells. This study has broad appeal to developmental neuroscience; however, the data remain incomplete given the need for homozygous enhancer knockouts and biological replicates in the scRNAseq assays.

eLife Assessment

This fundamental work substantially advances our understanding of short-term plasticity mechanisms by providing evidence for release-independent low-frequency synaptic depression that reflects a redistribution of vesicles within the readily releasable pool, via a reduction in docking site occupancy due to vesicle undocking. The evidence supporting this model is convincing, with rigorous electrophysiological and computational analysis. The work will be of broad interest to cellular neuroscientists and synaptic physiologists.

eLife Assessment

Mechanical transduction channels of sensory hair cells possess lipid scramblase activity. Membrane lipid disruption resulting from mechanical transduction is thought to be restored by flippase activities. This fundamental study provides compelling evidence that ATP8B1, a P4-ATP flippase and its subunit TMEM30B, are key in mediating this restorative function in outer hair cells of the mammalian cochlea.

eLife Assessment

This important study examines the stability and compensatory plasticity in the retinotopic mapping in patients with congenital achromatopsia. It provides convincing evidence for a stable mapping of the visual field in V1, alongside changes of the readout from V1 into V3, which shows revised receptive field location and size. This paper would be of interest to scientists studying the visual system, brain plasticity, and development.

eLife Assessment

This valuable study presents a hierarchical computational model that integrates locomotion, navigation, and learning in Drosophila larvae. The evidence supporting the model is convincing, as it qualitatively replicates empirical behavioral data. While some simplifications in neuromechanical representation and sensory-motor integration are limiting factors, the reported modular framework will be of interest for computational modeling of biological movement and adaptive behavior.

eLife Assessment

This important study combines behavioural psychophysics with image-computable modelling to test whether face recognition relies on view-selective or view-tolerant mechanisms. Although the diagnostic orientation content of faces varies with viewpoint (more horizontal for frontal views, more vertical for profiles), human recognition remains predominantly tuned to horizontal information, consistent with the predictions of a view-tolerant model. The evidence for view-tolerant tuning to horizontal orientations is compelling, although questions remain about the plausibility of the computations implemented in the view-tolerant model and how they map onto mechanisms of everyday face recognition.

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 paper provides convincing evidence that humans can navigate better through maps whose local transitions were learned in an intermixed order than maps whose local transitions were learned in neighboring groups. The authors put forward a potential mechanism in which the grouped learning resulted in mental fragmentation, though evidence for this mechanism is incomplete. The work will be of interest to researchers studying cognitive maps and curriculum learning.

eLife Assessment

The authors combined human assembloids, fetal brain tissue, bulk and single cell RNA sequencing, and live imaging to understand the molecular mechanisms affected by hypoxia during cortical development. The findings are very important to the neurodevelopmental field, They reveal new insights into how migration of cortical interneurons can be affected in hypoxic conditions, and provide exciting models to probe broad neurodevelopmental processes in health and disease. The evidence is compelling. The data and analyses are very rigorous and go beyond the state-of-the-art.

eLife Assessment

This valuable study proposes a novel rapid-entry mechanism for Staphylococcus aureus, involving the rapid release of calcium from lysosomes. The paper's strength lies in its very interesting hypothesis. The methods used are solid and adequately support the conclusions.

eLife Assessment

This important study shows that the Nora virus, a natural Drosophila pathogen that also persistently infects many laboratory fly stocks, infects intestinal stem cells (ISCs), leading to a shorter life span and increased sensitivity to intestinal infection with the bacterium Pseudomonas. The authors provide convincing data to support their conclusions. The paper provides new insights into virus-host interactions in the Drosophila gut and serves as a warning for scientists who use the fruit fly as a model to study gut physiology.

eLife Assessment

This valuable study identifies and characterizes probe binding errors in a widely used commercial platform for spatial transcriptomics, discovering that at least 21 out of 280 genes in a human breast cancer panel are not accurately detected. The authors provide convincing evidence for their findings through validation against multiple independent sequencing technologies and reference datasets, and they introduce a computational tool to help predict potential off-target probe binding. Given the broad adoption of this platform in biomedical research, this work provides an essential quality control resource that will improve data interpretation across numerous studies.

eLife Assessment

This important study developed a novel paradigm combined with EEG recordings to examine the neural mechanisms underlying temporal integration in perception and its modulation by prior history (i.e., the serial dependence effect). The results provide solid evidence that two key EEG features, namely the individual alpha frequency and the aperiodic slope, jointly and independently shape perceptual integration and its reliance on prior information. While additional control analyses would further strengthen the main conclusions, the findings will be of broad interest to researchers studying perception, decision-making, inter-individual differences, and brain rhythms.

eLife Assessment

This important study presents convincing evidence that uncovers a novel signaling axis impacting the post-mating response in females of the brown planthopper. The findings open several avenues for testing the molecular and neurobiological mechanisms of mating behavior in insects, and in the revised version the authors provide further evidence supporting their conclusions.

eLife Assessment

This study addresses an important question about how large-scale brain networks interact, and specifically how the default mode network exchanges information with the sensory cortex. The analyses are sophisticated, but at present provide incomplete evidence for the claims made in the paper.

eLife Assessment

This important study addresses a discrepancy between population-level growth laws and single-cell correlations. It shows, for flagellar and synthetic genes in E. coli, that while gene expression of certain genes reduces population-average growth, expression levels positively correlate with growth at the single-cell level. The measurements are mostly convincing, and the proposed mechanism-inheritance of growth factors such as ribosomes during asymmetric division- explains this observation. The theoretical analysis would benefit from clearer explanations and robustness checks.

eLife Assessment

This important study measures single-unit activity in the middle temporal area (MT) of awake-behaving monkeys to test the idea that sensory adaptation contributes to flexible evidence accumulation during decision-making. Solid evidence is provided, showing that adaptation to different temporal contexts shapes both perceptual judgements and neural responses, but analyses aimed at establishing a direct link between them are less persuasive. This work has the potential to be of interest to a broad range of researchers working on visual perception, plasticity, and decision making.

eLife Assessment

The valuable study aims to differentiate between foveal and peripheral attentional mechanisms in visual and frontal brain regions in monkeys engaged in a free-gaze visual search task. The authors interpret differences in responses between target and nontarget conditions as feature-based attention; however, this may not be the correct interpretation. The authors do not provide enough information on how they distinguish foveal and peripheral RFs. Consequently, the study provides only incomplete evidence that does not support the authors' conclusions, and the significance of the findings is not strong.

eLife Assessment

This valuable study introduces a new framework for improving the automated sorting of extracellular action potentials. However, the evidence is incomplete; the biophysical model used for simulation is based on one simulation that does not necessarily reflect real experimental data, the test datasets are insufficiently diverse, and essential algorithmic details are currently missing. This work will be of interest to neuroscientists using high-density multichannel electrophysiology.

eLife Assessment

This valuable study presents a real-time system for identifying multiple unrestrained marmosets in a home cage setting using a combination of face detection and color-coded beads. However, there is incomplete evidence regarding the generalizability and robustness of the system to unconstrained multi-animal environments.

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 article presents valuable findings on how the timing of cooling affects the timing of autumn bud set in European beech saplings. The study leverages extensive experimental data and provides an interesting conceptual framework for the various ways in which warming can affect but set timing. The statistical analysis is compelling, but indicates some factors that may temper the authors' claims, while the designs of experiments offer incomplete support for the current claims as they rely on one population under extreme conditions for only one year each while a confounding effect (time in a chamber) sometimes lacks a control.

eLife Assessment

The authors previously identified SLAP as a key suppressor of the Src tyrosine kinase and a tumor suppressor. In this important study, the authors show SLAP functions in a cell-autonomous fashion in colon stem cells and propose solid evidence that SLAP reduces tumorigenesis by inhibiting an EphB2-SRC axis.

eLife Assessment

This study presents an important study of the relationship between morphogen signaling and cell fate choices in the forming zebrafish neural tube, addressing a topical question in developmental biology. The authors provide a solid characterization of the precision limit for gene regulatory networks interpreting Shh, with single-cell resolution and state-of-the-art in vivo approaches. While the depth of analysis is restricted, particularly by the number of cell traces, the study will be of interest to developmental biologists interested in cellular decision-making.

eLife Assessment

In this important study, DNA and RNA are co-imaged in single cells to show that the proximity of topologically associated domain (TAD) boundaries is uncoupled from the transcriptional activity of nearby genes. The evidence supporting these conclusions is convincing for the regions examined, with high-throughput imaging providing robust statistics. This work will be of interest to researchers studying genome architecture and its relationship to gene regulation.

eLife Assessment

The manuscript presents important findings on how C. elegans can utilize distinct molecular mechanisms and circuit engagements to regulate tactile-dependent locomotory behaviours through the AFD thermosensory neuron. The authors use multiple techniques including microfluidics, genetic manipulations and single-copy rescue experiments, to provide compelling evidence for the role of AFD/AIB electrical synaptic connections in this behaviour. The reviewers are satisfied with the comprehensive revisions made by the authors.

eLife Assessment

This important study deepens our understanding of how populations of a given species may diverge in their molecular and physiological patterns as a result of adaptation to different thermal regimes. By approaching this question from multiple directions, the authors provide solid evidence for adaptive changes in three strains of the diamondback moth after only three years of experimental evolution, and support the causal involvement of the PxSODC gene in thermal adaptation to both cold and hot temperatures. This work would benefit from more sophisticated phylogenetic analyses, better statistical support, and a more detailed discussion of the differences in the three strains at the pathway level.