eLife Assessment

This valuable study uses technically challenging long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The study provides solid evidence that ORNs have a circadian pattern of spontaneous firing that is Orco-dependent although Orco transcript abundance does not itself show circadian rhythmicity, and that cAMP can modulate Orco-dependent activity. Together with the computational work, the study proposes the provocative hypothesis that an Orco-centered post-translational feedback loop generates the circadian rhythm of spontaneous firing. Nevertheless, this mechanistic interpretation will require direct testing in future work.

eLife Assessment

This important study combines a five-year field experiment with a meta-analysis to quantify effects of grazing on ecosystem CO₂ fluxes as modified by wetness. The evidence supporting the conclusions is convincing, but several aspects of the methods and discussion would benefit from clarification to improve reproducibility and interpretability.

eLife Assessment

This important study provides convincing evidence supporting the existence of transposable element (TE)-gene chimeric transcripts in the Drosophila brain and helps reconcile previously conflicting findings. The authors demonstrate that differences in computational approaches, experimental design, and Drosophila lines can substantially influence the detection of these transcripts. The work highlights the importance of standardized approaches for studying TE-derived transcripts, although their broader biological significance remains to be established.

eLife Assessment

This valuable study demonstrates that a multi-step differentiation program in bacteria combining a bistable switch with two quorum-sensing systems is capable of generating autonomous and self-organized spatial patterns. The evidence for the core engineering system using fluorescent reporters support patterning across several conditions is convincing and has significant implications on the process of cell differentiation.

eLife Assessment

This important study employs a closed-loop, theta-phase-specific optogenetic manipulation of medial septal parvalbumin-expressing neurons in rats and reports that disrupting theta-timescale coordination impairs performance of challenging aspects of spatial behaviors, while sparing hippocampal replay and spatial coding in hippocampal place cells. Technically rigorous experiments were performed, and solid evidence is provided to support the claims. The findings are expected to advance theoretical understanding of learning and memory operations and to provide practical implications for the application of similar optogenetic approaches.

eLife Assessment

This important study uses biochemical and single-molecule approaches to characterize how yeast Cdc13 assembles on single-stranded telomeric DNA and contributes to telomere protection. The evidence supporting the proposed model for Cdc13 assembly and its role at telomeres is solid. The findings provide insight into how Cdc13 contributes to the maintenance and protection of chromosome ends. This work will be of interest to researchers in telomere biology, DNA replication, biochemistry, and single-molecule biophysics.

eLife Assessment

This valuable proof-of-concept study tests and validates a novel magnetic resonance-based method - proton-observed proton-edited MRS - for tracking glucose metabolism in the brain beyond simple substrate uptake, without the need for specialist hardware typically restricted to research settings. The approach offers a promising way to assess excitation/inhibition balance by detecting labelled glucose metabolites. The pre-clinical data in mouse models provide convincing support for the authors' hypothesis. The evidence in the human brain is incomplete: the results would require further optimisation of the experimental set-up and validation in a larger group of volunteers. This work will be of broad interest to researchers studying psychiatric, neurodevelopmental, and related brain disorders.

eLife Assessment

There is a significant need for improved understanding of the neural circuit mechanisms for learning and memory dysfunction in Alzheimers disease. In this valuable study, Zheng and colleagues compare neural coding between wild-type and App knock-in rats experiencing different contexts. Solid evidence of a difference emerges when "spatial" and "temporal" neural coding dynamics are considered separately. However, the lack of a link between neural coding and behaviorally measured learning, and minor issues with the analyses, are limiting factors of the evidence and the significance of the work.

eLife Assessment

This study provides valuable findings on computational measures of learning in human subjects with current depression, individuals remitted from depression, individuals at familial risk, and healthy controls using reinforcement learning and risky decision-making tasks. The evidence is solid but could benefit from clear interpretation of model parameters and psychiatric symptoms. The paper will be of interest to scientists interested in learning, reward processing, value-based decision-making, and psychopathology.

eLife Assessment

This important study provides evidence that Clock and fat body proteasome subunits contribute to dietary restriction-mediated lifespan extension in Drosophila. The evidence supporting these conclusions is solid, yet whether dietary restriction-induced daily rhythmicity of proteasomal genes is CLK-dependent remains incompletely demonstrated, and alternative explanations involving feeding differences and non-circadian functions of CLK cannot be, with the current dataset, excluded. The work will definitely be of interest to researchers studying biological rhythms, nutrition, and aging.

eLife Assessment

This valuable study provides a detailed three-dimensional characterization of primary cilia organization in the postnatal mouse growth plate, revealing reproducible spatial patterns in ciliation, ciliary length, and orientation. The evidence supporting these descriptive findings is solid, based on high-quality quantitative imaging and complementary genetic, mechanical, and transcriptomic approaches. However, evidence for the broader mechanistic conclusions is incomplete, particularly regarding whether ciliary orientation is uncoupled from basal-body and cell orientation and whether its stability under altered mechanical loading reflects a cell-intrinsic program. The study provides a helpful foundation for understanding primary cilia organization and mechanobiology in the growing skeleton, while the mechanisms underlying these observations remain to be established.

eLife Assessment

This Review Article addresses a significant and timely topic that concerns the role of cryo-EM in transforming RNA structural biology from static, individual conformations toward the reconstruction of dynamic conformational ensembles and energy landscapes. The authors describe eight case studies spanning different RNA classes and argue that conformational heterogeneity is a source of mechanistic information, rather than a limitation.

eLife Assessment

This is an important study of critical period plasticity, focused on temperature manipulations, and how different parts of the Drosophila larval motor circuit adapt or maladapt. The work convincingly demonstrates that components of the motor network respond in distinct ways to heat shocks, and the combination of functional, structural, and electrophysiological approaches makes the study of significant interest. The work points to central interneurons as primary drivers of maladaptive changes, while motoneurons and neuromuscular junctions show compensatory or homeostatic adjustments. The authors have thoughtfully and substantially addressed the concerns raised in the original reviews through new temporal-window experiments, additional receptor and behavioral analyses, clearer discussion of the study's limitations, and an integrative model.

eLife Assessment

This paper represents a valuable contribution to our understanding of how local field potential (LFP) oscillations and beta band coordination between the hippocampus and prefrontal cortex of rats may relate to learning. Through a set of appropriate analyses, including oscillation-oscillation coupling, oscillation-spike modulation, and behavioral dependant measurements, the study presents convincing evidence for uncoupled beta activity between the two regions. This work will be of interest to researchers working on interaction of brain regions during spatial learning in rodents.

eLife Assessment

This study provides convincing evidence that the genetics of local adaptation in Arabidopsis is shaped by fluctuations in the environment and interactions with genotype and location. This is an important dataset contributing to the developing understanding of non-linear selection in plants and beyond.

eLife Assessment

This important study demonstrates that pyroglutamylation of peptide ligands alters G protein-coupled receptor (GPCR) activation in a subtype-specific manner and proposes a novel mechanism whereby the posttranslational modification steers the distal conformation of the peptide within the orthosteric binding site. The strength of the evidence supporting receptor-specific functional effects is convincing, but the strength of the evidence supporting the proposed structural mechanism is incomplete. This study will be of interest to pharmacologists and cell biologists interested in posttranslational modifications (PTMs) and activation mechanisms of GPCRs.

eLife Assessment

This important paper studies how adiposity affects brain development in the ABCD study. Major findings include: (1) central adiposity indices (BRI, WHtR) show stronger cross-sectional associations with cognition than BMI, partially mediated by frontotemporal cortical morphology; (2) the rate of adiposity accrual, rather than static adiposity at either timepoint, predicts follow-up cognition and altered (attenuated) cortical thinning; and (3) among overweight/obese adolescents, central fat reduction is accompanied by accelerated cortical thinning and catch-up in inhibitory control. The strength of evidence is solid, with the main limitation related to only looking at the cerebral cortex rather than examining the whole brain. The subgroup observation that fat reduction may be accompanied by normalization of both cortical trajectories and inhibitory control is potentially clinically meaningful, suggesting reversibility rather than fixed deficit, and would be of broad interest if it withstands more rigorous analysis.

eLife Assessment

This valuable study investigates the action of a floral homeotic transcription factor in different cell types. The results provide solid evidence that PhDEF shows more extensive binding and regulatory effects in the epidermis than in the mesophyll, supporting the conclusion that cell-layer context influences homeotic gene function. While there are some limitations, they do not undermine the principal observation of layer-dependent PhDEF activity, but the interpretation of the data is complicated by uncertainties in cell-type assignment and composition in the scRNA-seq data, the cell-type-enriched rather than strictly cell-type-specific nature of the ChIP-seq data, and differences in developmental stage between the single-cell and ChIP-seq experiments. The work will be of interest to developmental biologists studying transcriptional regulation and cell identity.

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

eLife Assessment

This important study uses the Cntnap2 mouse model of autism to investigate how reduced activity in the dorsal CA1 region of the hippocampus contributes to impaired temporal binding and memory flexibility. The authors combined trace conditioning and radial maze assays with fibre photometry, optogenetic rescue, and brain-wide c-Fos mapping to provide convincing evidence that dorsal CA1 hypoactivity limits the retention of temporally separated associations and biases learning towards less flexible strategies. The work advances understanding of hippocampal contributions to cognitive alterations associated with autism and will be of broad interest to researchers studying memory, hippocampal function, and neurodevelopmental disorders.

eLife Assessment

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

eLife Assessment

The paper presents a valuable finding that the human brain and models that incorporate sentence structures can capture sentence-level semantics beyond word meaning, while large language models behave differently. The evidence supporting the authors' claims is solid, though the stimuli are highly controlled and some analyses could be more thorough. This work will be of interest to researchers in language neuroscience and those developing language models.

eLife Assessment

This is a potentially valuable study in the area of connectomics, comparing across species to obtain a uniform synaptic density of ~1 synapse per micron. While the methods add to the field, the datasets are limited and filtered, and the role of cell-type on spacing is passed over. Additionally, some of the analyses could be tightened; hence, overall, the findings remain incomplete.

eLife Assessment

This in vitro study provides important evidence that the mitochondrial intermembrane space protein HAX1 functions as a direct activating cofactor of the AAA+ chaperone CLPB, resolving a longstanding question arising from the strong genetic, proteomic, and disease associations between these proteins. The convincing work advances our understanding of mitochondrial proteostasis by demonstrating that HAX1 promotes CLPB oligomerization and will potentially even enable the generation of small molecules that mimic the function of HAX1 in CLPB activation. The study will be of general interest to biochemists working on chaperones and/or mitochondrial biology.

eLife Assessment

This valuable large-scale comparative study of odorant receptor (OR) genes across more than 100 insect species, combining sequence- and structure-based approaches, is a significant step in the exploration of the evolution of this large gene family involved in the detection of odorant signals by olfactory neurons. This 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 relative to the authors' claims about the inferred number of OR genes per species, the odor response spectra and the evolutionary and ecological interpretations.

eLife Assessment

This fundamental study presents experimental evidence on how geomagnetic and visual cues are integrated in a nocturnally migrating insect. The evidence supporting the conclusions is compelling. The work will be of broad interest to researchers studying animal migration and navigation.

eLife Assessment

Davis and colleagues present fundamental findings on pressure mechanosensation in lymphatic vessels, with broad relevance to mechanosensory physiology. Using an impressive array of knockout mouse models and rigorous pressure myography, they provide compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs drives lymphatic vessel contractility via an IP3-IP3R1-ANO1 Ca²⁺ release and depolarization pathway. While the study falls short of pinpointing the specific GPCR(s) mediating pressure-induced chronotropy - having ruled out candidates such as AT1R and G12/13-coupled receptors - their single-cell RNA sequencing profiling establishes a benchmark candidate list (including adhesion and frizzled GPCRs) that provides a foundation for future target identification.

eLife Assessment

This study presents important findings on the structure and functional potential of microbial communities along a vertical sediment profile of a salt marsh. The authors examine hypotheses about the burial microbial assembly process and functional complementarity at depth and provide solid evidence to support their claims. Overall, this work will be broadly of interest to microbial ecologists.

eLife Assessment

This important submission from Ambler and colleagues brings new insights into how torpor conditions may confer resilience in cases of cardioprotection. The study is backed by solid evidence and represents a unique interoceptive mechanism of interest.

eLife Assessment

This work by Pyne and Pandey et al. addresses DNase X (DNase1L1) activity at the macrophage phagocytic cup, using an innovative imaging approach that couples visualization of cup formation to spatially resolve DNA degradation. The methodology is technically sound, and the central finding that DNA digestion begins prior to phagolysosomal maturation is well supported. Overall, the study is solid and provides a valuable framework for investigating early events at the phagocytic cup that may shape responses to pathogens and inflammatory disease.

eLife Assessment

This valuable study provides a very large data set of motor unit recordings in people with multiple sclerosis and, as such, could impact both foundational and clinical studies of the neuromuscular system. The study reports increased variability in firing rate profiles across participants and suggests that this observation reflects differences in the excitatory, inhibitory, and neuromodulatory drive reaching motor neurons. The descriptive finding is solid, but the link to specific neural mechanisms is incomplete as it depends heavily on assumptions related to its model-based framework.

eLife Assessment

This study presents a useful finding on the interplay of CCL5 and miR-324-5p during ischemic stroke injury. The authors have addressed some of the concerns in the revision. The methodological information has been updated, and additional experiments, such as FISH, have been included. After the revision, the evidence supporting the claims of the authors is solid. The work will be of interest to neuroscientists working on brain injury such as stroke.

eLife Assessment

This study presents a valuable finding on the condition dependence of autophagy-mediated lifespan regulation in C. elegans. The evidence is solid, as the data broadly support the main claims, although variability between biological replicates in several of the performed experiments and mechanistic exploration with only a limited set of experimental techniques leave some conclusions less firmly established. The work will be of interest to researchers studying autophagy, ageing, and intracellular trafficking.

eLife Assessment

This is an important study utilizing innovative CRISPR based approaches demonstrating the role of the KLF family of transcription factors in the post-natal maturation of cortical projection neurons. The strength of evidence overall is compelling, and the study is well executed. The screen data presented provides a number of interesting candidates for future analyses into the mechanism of action of KLF family members in neuronal maturation.

eLife Assessment

This study shows that partial cone photoreceptor loss induces pathway-specific circuit remodeling in the mouse retina, with alpha OFF-sustained and OFF-transient retinal ganglion cells adapting differently through changes in their pre- and postsynaptic circuits. The results are valuable because they provide a key understanding of the diversity of circuit remodeling in retinal degeneration. The data are convincing, although clearer reporting of the numbers of independent animals and retinas, a more rigorous distinction between compensation and circuit change, and discussion of the functional consequences would strengthen the mechanistic insights.

eLife Assessment

This Tools & Resources manuscript presents important findings that can help the implementation of research assessment reform in research-performing institutions. The authors employ a three-part Delphi method involving researchers, funders, journal editors, and academic leaders, ultimately reaching consensus on six standards. The manuscript's accompanying appendix provides helpful, modular guidance for research-performing organizations seeking to adopt these six parameters. Overall, the evidence presented is solid, and the manuscript makes a practical contribution that will add value. However, a significant limitation is the lack of evidence demonstrating whether and how implementation of the proposed guidance improves research evaluation in practice.

eLife Assessment

This study establishes the fast-developing tuxedo sea urchin, Mespilia globulus, as a genome-enabled experimental model. With the tools and methods described here, the authors provide a valuable platform with particular potential for developmental biology and physiology as well as comparative studies. The evidence supporting the principal claims of experimental tractability and quality of genomic resources is solid, although fuller documentation, e.g., of husbandry, aquarium-stock provenance and genetic diversity as well as gene-editing efficiency and imaging set up, would strengthen the work. This work will be of particular interest to developmental and evolutionary biologists.

eLife Assessment

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

eLife Assessment

The study presents a fundamental structure interaction model describing how polymyxin interacts with hHepT2 the human oligopeptide transporter's 2 Aspartic acid residues to mediate nephrotoxicity via the D215 mutagenesis. These findings guided the rational design of potent polymyxin B analogues with reduced toxicity. The conclusions are supported by compelling evidence from computational and experimental data. The work will be of use to biochemists and medicinal chemists in developing the next generation of antibiotics for clinically relevant multidrug resistant bacteria.

eLife Assessment

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

eLife Assessment

Davies et al. present a valuable study proposing that the Drosophila homologue of MACF1, Shot, can act as a molecular linker between microtubules and actin during dendrite pruning, suggesting an intriguing role in non-centrosomal microtubule organization. The study provides robust evidence that Shot helps control microtubule organization and dendrite pruning, but the evidence that Shot coordinates these processes through its interaction with actin remains incomplete, particularly because the actin-disrupting experiment does not affect the distal dendrites where the authors propose Shot acts. Overall, the study contains several interesting findings, but additional experimental support is needed to establish how Shot, actin, and microtubules work together to control dendrite pruning.

eLife Assessment

The study presents a valuable conceptual framework by classifying pattern-forming gene subnetworks into three established categories. By meticulously enumerating and simulating various network topologies, the authors provide a systematic catalog of these patterning motifs. However, the supporting evidence remains incomplete, as the mathematical generalizations rely on simplified assumptions that may not hold in more complex or realistic scenarios.

eLife Assessment

The study presents a valuable dataset and analysis on two sympatric Mediterranean clingfishes which will be of interest to the fields of evolutionary genomics, population genetics and comparative phylogeography, and especially to marine biologists working on population connectivity. The comparative design provides solid evidence that contemporary connectivity is more predictable across species than deeper phylogeographic and demographic history. The analysis of the genomic data, which is still incomplete, would benefit from further work and clarification, particularly regarding the evidence for parallel genomic divergence.

eLife Assessment

This paper uses rigorous experimental methods to investigate the role of covert attention in decision-making. The authors identify aspects of the decision problem that shape the allocation of covert attention and show that covert attention attenuates the impact of overt gazes on choice. These findings are solid and methodologically and theoretically valuable for researchers working at the intersection of attention and decision-making.

eLife Assessment

This study presents a useful approach to analyzing brain responses to transcranial focused ultrasound (tFUS), and potentially to neuromodulation-evoked activity more generally. By applying ideas from physics, it reveals changes in brain activity that measures of signal strength alone do not capture. The authors report a surprising non-monotonic relationship between irreversibility and stimulation dose, and a relationship between baseline irreversibility and susceptibility during stimulation. The evidence for the central interpretation remains incomplete, however: it is not yet clear that these changes reflect genuine reorganization of brain activity rather than artifacts of the calcium-recording method or an unaccounted-for side effect of the stimulation itself.

eLife Assessment

This valuable study identifies the IL1R1-IRAK4 axis as a mediator of inflammation-associated ovarian cancer implantation. The evidence is convincing, supported by complementary genetic and pharmacological approaches across multiple in vivo models. These findings advance our understanding of how inflammatory signaling shapes metastatic niche formation and highlight IRAK4 as a potential therapeutic target.

eLife Assessment

This work makes an important contribution to understanding the role of calreticulin and the Del52 variant in calcium homeostasis in cells based on convincing evidence. There was some question as to whether the work in vitro fully recapitulated the physiological setting in which the homozygous Del52 variant has been reported to have defects in calcium homeostasis. Nonetheless, the studies are well performed using appropriate methods to address these questions and make a significant contribution to the understanding of calreticulin, and the Del52 variant, function in health and disease.

eLife Assessment

In this important study, Abdelnaby and colleagues systematically examine the four native Orai channel isoforms (Orai1α, Orai1β, Orai2, and Orai3) and find that all can couple to NFAT1/4 activation, with NFAT responses largely scaling with the magnitude of Ca2+ influx (Orai1β > Orai1α >> Orai2 > Orai3). The study shows that in primary CD4⁺ T cells, Orai1α and Orai1β are functionally redundant, restoring SOCE, NFAT activation, cytokine production, and highly similar transcriptional programs. Human genetic data further show that selective loss of Orai1α does not cause CRAC channelopathy and instead slightly enhances SOCE and NFAT activation. Overall, the findings are significant, and the strength of the evidence supporting the conclusions is convincing.

eLife Assessment

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

eLife Assessment

This is an important study addressing a debated question in brain repair research by testing whether NeuroD1 can convert brain immune cells into nerve cells using a virus-free genetic approach and live imaging. The compelling evidence presented here supports that, under the conditions tested, NeuroD1-expressing cells do not become nerve cells and instead retain their original identity. This work will be of interest to neuro-immunologists.

eLife Assessment

This study characterises the heterogeneity and developmental origins of macrophages in the thymus and demonstrates a role for Csf1r-expressing myeloid cells in the first step of T cell development. The state-of-the-art experiments provide convincing evidence, and the assessors concerns were addressed in the revised submission. These results provide an important advance that furthers our understanding of thymus biology, especially in view of the contribution of heterogenous thymic macrophage subpopulations.

eLife Assessment

AIRE has been well known to contribute to immune self-tolerance in the thymus by expressing auto-antigens. In this manuscript, the authors describe unexpected findings about the interaction of AIRE with AID in B cells, and its function in the immune system, thereby contributing to a fundamental understanding of the broader functions of AIRE. The strength of this manuscript is that, by employing biochemical and genetic experiments, the authors convincingly show interaction between AIRE and AID and subsequent AIRE's function in the GC responses.

eLife Assessment

The manuscript is important in that it has the potential to advance our understanding of how liver regeneration is orchestrated after injury of pericentral hepatocytes, which are a target of many drugs and toxins. The findings are solid and suggest that midlobular hepatocytes are protected from toxin-induced injury by a genetic program delaying proliferation to prevent cell death. The effects of individual actors in the proposed program are convincingly shown but whether they act in concert and whether cell cycle arrest is indeed the protective mechanism remains to be determined.

eLife Assessment

The work provides a valuable analytical and technical framework for relating spatial microRNA patterns to therapeutic response and features of the tumor immune environment in a BRCA1-associated model of triple-negative breast cancer. The evidence supporting the main conclusions is solid, although additional validation and statistical analyses would strengthen claims regarding biomarker performance and the specific contribution of spatial measurements.

eLife Assessment

This Review Article provides a comprehensive overview of whole-brain activity changes induced by brain stimulation and effectively summarizes the current state of the field. However, the integrative framework spanning spatial and mechanistic scales, which is presented in the discussion, should be introduced earlier to guide the reader. A more cohesive conceptual framework throughout the manuscript would improve the synthesis of the literature and enhance accessibility.

eLife Assessment

This study presents an important finding regarding the role of oxytocin neurons in thermogenesis and behavioral thermoregulation. The use of numerous converging methods, including behavior, fiber photometry, optogenetics, thermal recordings, metabolic analyses, and more, produces a multi-dimensional dataset delivering findings that provide solid support for the conclusions. The conclusions could be further strengthen by more extensive analyses of behavior and determining whether it is the release of oxytocin (rather than co-release of glutamate) from the PVN that is critical for the transition between behavioral states, nevertheless, the manuscript had many strengths, the findings are novel, and this work opens new doors for understanding the role of the PVT in thermoregulation. This work will be of strong interest to the thermoregulation, social behavior, and oxytocin signaling communities.

eLife Assessment

The manuscript presents a primary important finding, namely that microbial riboflavin-derived MR1 ligands are pharmacological activators of human MAIT cells and that MR1 ligand stimulation enhances MAIT-mediated tumor killing across multiple tumor models. While the evidence presented is generally solid, there are some limitations of the in vitro and in vivo models used, as well as some overstatements about the broader applicability of the research, which should be revised.

eLife Assessment

This study presents a useful finding on using diverse experimental systems to understand how neuromodulatory signals shape glial inflammatory signaling; however, the strength of evidence is inadequate. The astrocyte-enrichment method used may permit contamination by microglia, oligodendrocyte-lineage cells, or neurons, complicating attribution of TNF expression specifically to astrocytes. This concern is compounded by the strong microglial response to Gi manipulation and the lack of quantitative validation of chemogenetic cell-type specificity in vivo. These weaknesses have hindered further evaluation of the claims.

eLife Assessment

This important study shows that neural responses to visual input during active vision are more closely aligned with self-generated eye movements than with fixation onset. The evidence for neural responses being more aligned to saccade-related events than fixation-related events is convincing, but the evidence for the more novel finding that neural responses are most closely aligned to peak saccade curvature is currently incomplete. This work will be of interest to visual perception and sensory processing researchers.

eLife Assessment

This is a valuable manuscript that leverages information already being collected in mosquito surveillance, but that is currently discarded, building on ideas developed during the SARS-CoV-2 pandemic. The work is rigorous, involving ample data from real-world surveillance, independent laboratory testing, and simulation modeling to validate the inference method. The evidence is solid for demonstrating feasibility and biological plausibility.

eLife Assessment

This manuscript presents an important and timely contribution by incorporating desolvation barriers into coarse-grained models of biomolecular condensates. The findings are convincing, supported by a clear physical model and systematic simulations showing effects on phase behavior, packing, and dynamics. Some clarification and broader context would improve the manuscript, but it provides a foundation that will be of use for developing more realistic coarse-grained interaction schemes.

eLife Assessment

This study presents a valuable perspective on platelet-mediated fibrin compaction, proposing that fibrin fibers undergo "winding" or coiling, a concept with potential relevance for thrombosis and clot mechanics. While the revised manuscript has improved substantially, with clearer presentation, appropriately softened language, and high-quality experimental data, direct evidence for a causal link between cytoskeletal swirling and fibrin winding/compaction is still incomplete; in particular, the actomyosin dependence and rotational fiber movements are consistent with the proposed model but do not exclude alternative mechanisms. The winding/swirl mechanism should therefore be viewed as a hypothesis supported by the observations rather than a mechanism directly demonstrated by the experiments. With this qualification, the evidence is solid and support the main conclusions.

eLife Assessment

This valuable study examines how the rodent prelimbic cortex represents learned and generalized threat over time and identifies distinct stable and dynamic neuronal populations that contribute to these representations. The evidence is convincing, supported by longitudinal calcium imaging, appropriate control groups, and sophisticated analyses showing that the relevant neural signals cannot be explained simply by freezing behavior. The work provides a conceptual framework for understanding how stable threat-related representations supporting memory generalization and discrimination can be maintained despite ongoing changes in neuronal ensemble composition.

eLife Assessment

This is a valuable study on the electrophysiological and computational underpinnings of the accumulation of intermittent glimpses of sensory evidence for decisions. The authors present convincing EEG and behavioural evidence to support their claims. The work will be of interest to cognitive and systems neuroscientists working on decision-making.

eLife Assessment

This important study measures the development of hearing in the zebra finch and shows that two-day-old hatchlings have no detectable electrophysiological response to 95 dB SPL clicks. Because this stimulus carries energy across a broad range of sound frequencies and is some 60 dB louder than faint, high-pitched parental calls, the findings challenge prior proposals that such calls serve as a channel for heat-dependent prenatal developmental programming. Two reviewers found the evidence on the absence of auditory responses convincing, supported by auditory brainstem recordings using validated methods with appropriate controls and by a separate laser vibrometry experiment ruling out detection through egg vibration. A third reviewer disputed these findings and questioned whether absent physiological markers of hearing definitively establish deafness. On the evidence presented, embryonic hearing is unlikely to mediate the developmental effects reported for heat whistle playback. Whether those effects reflect some other pathway or require re-interrogation of the behavioral phenomenon is now the open question, alongside a need for auditory measurements more sensitive than the auditory brainstem response.

eLife Assessment

This manuscript presents important work on macrostructure formation in a freshwater filamentous cyanobacterium, focusing on its ability to aggregate and buckle. The authors employ a wide range of experiments and approaches, including time-lapse imaging and 3D theoretical modelling, to establish the physical dynamics of filaments, such as gliding motility and buckling. They demonstrate that, in addition to gliding motility, filament length and flexibility are essential for the ability of cyanobacteria to capture particles and form aggregates. Overall, the study provides convincing evidence and advances our understanding of the role of microbial motility in the environment. It will be of broad interest to biophysicists and environmental microbiologists.

eLife Assessment

This study presents valuable findings regarding the role of the P2X7 receptor in retinoic acid signaling-mediated retinal remodeling following photoreceptor degeneration. However, the evidence supporting the main conclusions is currently incomplete, as key comparisons are confounded by differences in genetic background, and the cellular source of receptor expression is not sufficiently resolved. While the work offers mechanistic insights of interest to researchers studying retinal degeneration, additional experimental controls are needed to fully support the authors' claims.

eLife Assessment

This important work considerably advances our understanding of the nature of ongoing thought across individuals and across task contexts. Using a combination of fMRI brain data and experience sampling, they find that activation of the MDN leads to greater stability of deliberate task-focused thoughts during task performance. The evidence supporting the claims is convincing and both analytically strong and creative, offering a novel approach to capture thought stability and its relationship to independent brain maps. The findings will be of broad interest to cognitive scientists and neuroimagers.

eLife Assessment

This important study presents compelling evidence for dopamine-based representation learning in the mouse olfactory tubercle. While this work suggests that gradient descent in deep networks serves as a helpful framework for understanding neural representations, the empirical evidence provided remains incomplete. Nonetheless, this work will be of significant interest to systems and computational neuroscientists, cognitive scientists, and machine learning theorists.

eLife Assessment

This revised submission remains a valuable contribution to influenza surveillance. After further addressing a previously highlighted methodological issue, the claims of providing an early warning tool aligns more with the reported study results and is a solid addition to the evidence base.

eLife Assessment

This important study compares how different classes of drugs act on the SARS-CoV-2 main protease, a key antiviral target, and shows that many of them work by controlling whether the enzyme assembles into its active dimeric form. The evidence, based on a range of complementary biophysical methods, is convincing and points to the interface between the two protein protomers, including a newly found binding site, as a promising target for broad-spectrum antiviral drugs. This work will be of interest to biochemists and virologists working on treatments for coronaviruses.

eLife Assessment

This study presents important findings that genome-wide DNA double-strand breaks trigger large-scale genomic amplification (DIGA), which does not require origin re-licensing, but is dependent on some proteins that are involved in break-induced replication (BIR). While the findings and model are compelling, the evidence supporting the claims is largely incomplete, as it depends primarily on a single assay to examine amplification. This work will be of interest to scientists in the DNA repair, replication, and cell cycle fields, as well as cancer biologists.

eLife Assessment

This valuable paper by Dong et al. describes an analysis of mutant phenotypes of the Rab GTPases Rab5, Rab7 and Rab11 in Drosophila second order olfactory neuron development. The revised version presents a convincing characterization and comparison of the different rab mutants on projection neuron development, with clear differences for the three rabs and by inference for the early, late and recycling endosomal functions executed by each.

eLife Assessment

Muenker and colleagues use an optical tweezer setup to apply oscillatory forces to endocytosed/phagocytosed glass beads over a wide frequency range (from ~1 to 1000 Hz) and probe cytoplasmic material properties at multiple time scales in six different cell types. Using statistical methods and principal component analysis, they find that the active and passive mechanical properties of cells can be described by 6 parameters (from power law fits) that allow characterizing the viscous and elastic nature of the cytoplasmic material as well as an effective active energy driven by cellular metabolism. Overall, this is a very well done and important work, using compelling and state-of-the-art methods.

eLife Assessment

This valuable study reports a series of artificial-selection experiments for microbiomes associated with improved drought performance in rice. A major strength is the solid experimental design using multiple starting soil communities, which can guide others in designing related experiments. While interpretation of the results is constrained by inadvertent microbial dispersal between samples, the limited effectiveness of the sterile controls and the absence of healthy well-watered plants, the work nevertheless provides a helpful proof of concept for host-mediated microbiome selection, identifying candidate taxa, functions and simplified communities for downstream study. As a first step towards microbiome engineering in this area, it will be of particular interest to colleagues working in plant-microbiome interactions, microbial community selection and microbiome design.

eLife Assessment

This valuable study combines experiments and theory to investigate the role of spontaneous correlated activity in establishing aligned topographic maps of neural activity in higher-order sensory areas and will be of interest to researchers studying multisensory integration and brain development. The revised work presents solid evidence that spontaneous activity is correlated and spatially organized across the relevant cortical areas and that, in a computational model, an intermediate level of such correlation can refine a coarse initial connectivity scaffold into aligned maps containing neurons responsive to one or both sensory modalities.

eLife Assessment

This study in the Drosophila antennal lobe, which contains multiple non-equivalent sensory channels, provides valuable new insight into how early-life sensory experience can produce lasting, cell-type-specific changes in neural circuit function. The work demonstrates that glial-mediated pruning during a defined developmental window leads to persistent suppression of odor responses in one olfactory neuron type, while sparing another. The evidence is convincing and supported by multiple complementary approaches, although some mechanistic interpretations remain speculative and would benefit from additional functional testing.

eLife Assessment

This is an important study that provides evidence that GATA6-dependent programming of peritoneal macrophages helps to regulate lipid metabolism and influences eosinophil survival. The evidence linking GATA6 deficiency to altered lipid profiles and eosinophil accumulation is solid, although the proposed mechanistic pathway connecting sphingolipid remodelling, LTE4 production and eosinophil survival currently remains incomplete. Strengthening these links and/or appropriately calming the conclusions would help to increase the impact of the study.

eLife Assessment

Avoidance of UV and blue light by the nematode C. elegans is mediated by the unusual transmembrane protein LITE-1, a non-canonical photoreceptor. In this valuable work, the authors report the surprising finding that LITE-1 function is also required for avoidance of very high concentrations of the food-associated odorant diacetyl. Although no molecular evidence is provided, the paper reports convincing studies indicating that LITE-1 can serve as a chemoreceptor for very high concentrations of diacetyl, adding an unexpected layer of complexity to the function of this unusual protein.

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 study, supported by convincing evidence, identifies the specific neuronal components that enable HIF-1 signaling in specific serotonergic neurons to regulate effectors in peripheral tissues. Specifically, stabilizing HIF-1 in ADF and NSM serotonergic neurons is sufficient to extend lifespan and healthspan in C. elegans, and these physiological benefits require several oxygen-sensing neurons, as well as neurotransmitters (GABA and tyramine), and a neuropeptide (NLP-17). The strengths of the study include rigorous experimental design, high quality data, the use of multiple genetic tools, and functional dissection using the well-validated C. elegans model.

eLife Assessment

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

eLife Assessment

This important study links blood-derived dietary content to sustained increases in sleep in the mosquito Aedes aegypti. Using multiple independent approaches, the authors provide convincing evidence for blood-induced changes in sleep. These findings have broad implications for understanding how specialized diets regulate sleep across species and for mosquito vector biology.

eLife Assessment

This important study demonstrates how individual taste preferences change over time, how these changes are reflected in cortical activity, and how sensory experience contributes to reshaping both. The evidence is convincing and broadly supports the main conclusions. The findings should be of interest to neuroscientists studying sensory processing and cortical plasticity.

eLife Assessment

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

eLife Assessment

This study reports a novel function for syntaxin 11, a specialized SNARE protein critical for the immune system whose mutations cause familial hemophagocytic lymphohistiocytosis type 4. The data convincingly show that depletion of STX11 impairs store-operated calcium entry in Jurkat T cells and that this defect is recapitulated in primary cells from a patient suffering from the disease; the authors further show that the syntaxin interacts with the pore subunit of the ORAI1 channel and propose that it primes the channel by promoting the assembly of multimers before activation by its endogenous ligand, the ER Ca2+ sensing protein STIM1. This is a conceptually important claim that challenges the prevailing view that all structural transitions in ORAI1 are STIM-driven. The high-quality data strongly support the interpretations, but the discussion would be strengthened if the authors suggest alternative mechanisms and mention earlier studies reporting ORAI1 regulation by vesicular trafficking.

eLife Assessment

This valuable study provides insights into the role of steroid signaling during tumorigenesis in the adult male drosophila accessory gland (functional equivalent of the prostate gland in mammals), hinting at a possible counterintuitive anti-tumoral role of sex hormones during prostate cancer in certain patients. While the Drosophila model provides an elegant way to study the hypothesis derived from the Cancer Atlas analysis, the analyses of public prostate cancer expression data are incomplete and critical knowledge on patients' treatment modalities and normalization across different datasets is missing. This work would be of interest to prostate cancer researchers as it suggests that the absence of androgen receptor signaling in humans could constitute a mechanism promoting tumor escape.

eLife Assessment

In this solid work, Fukui et al. re-examined the ATP hydrolysis mechanism in GHKL ATPases, revealing a cooperative role for two conserved acidic residues rather than a single one. This valuable study used a range of biochemical and structural techniques on various mutants from different members of the GHKL ATPase family to test and validate their proposed mechanism. An updated and extended mechanistic model of ATP hydrolysis by this class of enzymes is proposed.

eLife Assessment

This work provides important findings that reveal a mechanistic model of how VDAC2 influences BAX activation in mitochondria during BAX-mediated apoptosis. The experimentally supported model is convincing, with several experiments strengthening its validity. Major strengths include the complementary biochemical, biophysical, structural, and computational approaches, as well as the study's broad relevance.

eLife Assessment

This paper provides a useful assessment of the role of macrophages in the development of functional paw withdrawal, which is a feature in the mouse model of vincristine-induced peripheral neuropathy (VIND). The authors suggest a role for E-selectin as a critical molecule promoting VIPN, acting via immune cell recruitment and inflammasome-mediated signalling; however, their data on NLRP3 inflammasome activation in vivo remains somewhat incomplete. This study will be of interest for immunologists.

eLife Assessment

This important study examines the dynamics of late endosomes and lysosomes (LEL) in cultured astrocytes, leading to a model of how synaptic activity might regulate astrocytic specializations surrounding synapses via the lysosomal calcium channel TRPML1, LEL motility, and proteins involved in regulating actin-membrane association. The experimental work is convincing, including appropriate controls and combining different tools (multiple markers, pharmacology, genetic knock-downs) to test each conclusion, although issues with the specificity of some of the drugs or confounding factors arising from genetic knock-downs limit the strength of some conclusions. Dysfunction in glia-neuron crosstalk as well as lysosomal dysfunction are increasingly recognized as highly relevant for neurodegenerative disease development, so this manuscript will be of interest to the wider neuroscience community, as well as scientists interested in the cell biology of astrocytes and lysosomes.

eLife Assessment

This study provides a useful advance in generating mouse oligodendrocytes by direct lineage conversion from cortical astrocytes. The authors demonstrate that Sox10 converts astrocytes to MBP+ oligodendrocytes, whereas Olig2 expression converts astrocytes to PDFRalpha+ oligodendrocyte progenitor cells. The data supporting the conclusions are convincing with comprehensive transcriptomic analysis.

eLife Assessment

This study presents a useful database resource containing protein conformations generated through molecular dynamics simulations, with extensive quality evaluation and benchmarking. While the database is well-constructed and professionally organized, the evidence supporting its claimed representation of protein conformational landscapes is incomplete, as the short simulation times and starting structure bias prevent true Boltzmann sampling of the conformational space.

eLife Assessment

This valuable study investigates communication from the anterior cingulate cortex to the hippocampus during learning. The optogenetic evidence supporting the functional connection including the interneurons likely to be involved, is convincing. However, the evidence linking this pathway to learning and memory and certain aspects of the statistical interpretation remain limited. Overall, the work will be of interest to neuroscientists studying cortical-hippocampal interactions and learning and memory.

eLife Assessment

This valuable study uses EEG and computational modeling to investigate hemispheric oscillatory asymmetries in unilateral spatial neglect. The work benefits from rare patient data and a careful multimethod approach. The study manuscript provides convincing evidence contributing to our understanding of the neural dynamics underlying spatial neglect.

eLife Assessment

This important study uses a combination of experimental and modeling approaches to investigate the role of actomyosin in epithelial invagination during Ciona siphon tube morphogenesis. Several types of convincing quantitative analyses and modeling approaches are presented that support a model in which bidirectional relocation of actomyosin drives invagination. Since epithelial invagination contributes to the morphogenesis of many developing organs, this work has the potential to appeal to both cell biologists and developmental biologists.

eLife Assessment

The main contribution of this potentially useful manuscript is a standardized comparative MRI resource covering multiple avian clades, complemented by histological cross-validation and diffusion-based connectivity analyses. Such a resource could significantly enhance accessibility to internal avian brain anatomy for evolutionary neurobiology. Its central claim that avian brain compartments exhibit modular diversification aligns with the existing literature. However, uncertainties regarding data availability, concerns with the tractography pipeline, and insufficient recognition of prior work lead to the conclusion that the methods, data, and analyses are incomplete.

eLife Assessment

This work has much novelty, supportive data, and the potential for changing thinking about melanoma biology with the discovery of MRGPRX4 as a relatively melanoma-specific G protein-coupled receptor. MRGPRX4 is normally restricted to peripheral sensory neurons, but it is aberrantly expressed in human melanomas; melanomas with neural-crest-like/invasive features were most likely affected. When ectopically expressed in murine melanocytes, MRGPRX4 drives melanoma development with metastasis; the mechanism appears to involve ligand-independent receptor signaling. Overall, the text presents this as a novel model of oncogenesis driven by re-expression of a sensory GPCR - this is an important study with compelling data.

eLife Assessment

This valuable study reveals a role for lactylation in influenza polymerase function and virus replication. The evidence supporting the claims is solid, although the direct involvement of ATAT1 and SIRT1 in this modification and the functional relevance of the identified sites can be further substantiated. These findings will appeal broadly to influenza virologists studying polymerase regulation, as well as researchers investigating the functional roles of lactylation.

eLife Assessment

This important study shows that self-supervised pretraining on related fungal genomes can substantially improve sequence-to-expression prediction in budding yeast. The evidence for the main conclusion is convincing, with careful comparisons to models trained from random initialization and clear gains on held-out expression data. The broader claims about the optimal evolutionary scope and transfer of regulatory grammar are less fully supported.

eLife Assessment

This important study investigates how experimentally introducing two facultative bacterial endosymbionts into the Russian wheat aphid, Diuraphis noxia, affects aphid performance, dispersal, and damage to cereal host plants. The authors provide solid evidence that the two symbionts can generate contrasting phenotypes: Rickettsiella increases plant damage while reducing wing formation and dispersal, whereas Regiella reduces aphid population growth and feeding damage. The successful establishment and stable transmission of these novel symbiont-host associations, combined with experiments spanning individual, whole-plant, population and mesocosm scales, are notable strengths of the work; however, the mechanisms underlying these effects remain unresolved, evidence for horizontal transmission is indirect, and some population-level conclusions rely on relatively small sample sizes or effects that are not consistently detected across time points, and therefore the potential application of these findings to pest management remains promising but speculative. The study will be of broad interest to researchers working on insect symbiosis, plant-insect interactions, and biologically based approaches to pest management.

eLife Assessment

Using a range of complementary approaches, this study examines how type I and type II interferon (IFN) programs exert opposing effects on macrophage responses relevant to tuberculosis. The work addresses a key biological question and provides valuable mechanistic insights. However, the data to support several key conclusions is incomplete and requires further strengthening; in particular, the role of ferritin needs to be established more definitively, the TNF stimulation findings should be validated in the context of M. tuberculosis infection, and in vivo evidence is needed to support the proposed therapeutic strategy. Additionally, aspects of iron metabolism, lipid peroxidation, and the translatability of the findings between mouse and human macrophages would benefit from greater clarity and deeper mechanistic investigation.

eLife Assessment

This valuable study provides a proof of concept for the utility of transcriptomic methods to develop novel diagnostic tests for bovine tuberculosis. A comprehensive analysis using a suite of machine learning models provides convincing evidence for the use of mRNA biomarkers to distinguish between infected and disease-free animals. The analysis also provides major insights into both the levels of individual variation in expression between animals as well as systematic changes with respect to the time from infection.

eLife Assessment

In this fundamental manuscript, Richter et al. present a thorough anatomical characterization of the Drosophila melanogaster larval pharyngeal sensory system, which is involved in taste-guided behaviors.This study fills a major gap in the larval sensory map, providing a detailed neuroanatomical foundation for future investigations into sensory circuits and behavior. The exceptional data will significantly enrich the field of Drosophila neurobiology.

eLife Assessment

This study presents a potentially valuable approach to generate a systems vaccinology framework for enabling the design of optimized poxvirus-based MVA vaccines. The developed Boolean modelling framework provides a novel computational approach to predict immune response dynamics against vaccine candidates, which is validated against previously published data and used to test/predict the response for new genetically modified MVA vaccine candidates. However, the strength of evidence is currently incomplete, as key aspects of model construction, calibration, interpretation, validation, and reproducibility, as well as comparability of the used vaccine candidates, require further clarification and supporting information.

eLife Assessment

This study presents a valuable finding on a potential new regulatory mechanism for cellular proliferation in the mammalian cochlea, taking advantage of the organoid-forming potential of cells from the greater epithelial ridge (GER), or Kolliker's organ, a transient structure in the developing cochlea. The authors highlight three potential regulators - galectin 1, galectin 3, and Myc - providing solid evidence for potential roles in modulating the proliferation of cochlear GER cells using gene expression studies, single-cell profiling, pharmacological inhibition, and genetic overexpression both in vitro and in vivo. However, some of the analyses and interpretations are incomplete, and a better understanding of how the compounds and the gene overexpression studies affect the cells and modulate cell survival/death would aid a fuller interpretation of the data.

eLife Assessment

This is an important study that uses a tripartite transdiagnostic framework to separate depression-specific, anxiety-specific, and shared psychopathology dimensions and relate them to mood variability and mood reactivity to reward prediction errors across several large non-clinical cohorts and a clinical sample. The evidence is compelling: large samples, a well-characterised gambling task, rigorous computational and psychometric analyses (i.e., split-half replication of the factor structure, convergent results with non-orthogonalised factors, an explicitly specified risk-attitude model, diagnostic breakdown and power analyses for the clinical cohort) and replication of the depression-specific blunting of reward prediction error sensitivity in patients. Anxiety-specific associations emerge reliably only when data are pooled and are likely underpowered clinically given co-morbid anxious depression, a constraint the authors now state explicitly. The work advances a mechanistic account of how distinct symptom dimensions shape reward-based mood updating.

eLife Assessment

This important study reports that Sox17 is key to the formation and function of the Sertoli valve, a transition region between the rete testis and seminiferous tubules that remains an understudied domain of testicular biology. The supporting data are convincing. This work will be of interest to developmental and reproductive biologists, as well as andrologists who work on male fertility and men's health.

eLife Assessment

The results of this study are important and the approach to dissect the developmental contribution of RIF1 function is convincing. The finding that replication timing and gene expression may be independently controlled is intriguing and provides a strong foundation for future research. The work will be of interest for researchers both in the transcription and the replication field, especially for scientists investigating the interplay between the two processes.

eLife Assessment

In this manuscript, the authors analyse the nanoscale localisation of α5β1 and αVβ3 integrins in integrin adhesion complexes (IAC) by dual-colour STORM and DNA-Paint and assess the spatial organisation at the nano and mesoscale of their main adaptors (paxillin, talin and vinculin). This is an important work that provides detailed analyses that reveal how elements of these complex structures are really organised at the nanoscale, an essential perspective for a better understanding of how IACs function and regulate mechanotransduction processes. The evidence presented is convincing, using complementary super-resolution imaging techniques and subsequent computational modelling that enabled a quantitative assessment of the resulting data.

eLife Assessment

This important study compares how different classes of drugs act on the SARS-CoV-2 main protease, a key antiviral target, and shows that many of them work by controlling whether the enzyme assembles into its active dimeric form. The evidence, based on a range of complementary biophysical methods, is convincing and points to the interface between the two protein protomers, including a newly found binding site, as a promising target for broad-spectrum antiviral drugs. This work will be of interest to biochemists and virologists working on treatments for coronaviruses.

eLife Assessment

This is a fundamental study on the sensory roles of cerebrospinal-fluid-contacting neurons (CSF-cNs) in mammals, revealing how the apical extension is used as an amplifier of chemical changes in content of the CSF. Specifically, the authors show compelling evidence that PKD2L1 is predominantly a pH-sensing channel in CSF-cNs and link its apical localization to dual phasic and sustained responses underlying CSF chemosensation.

eLife Assessment

This important study reports that neural activity in the auditory cortex (field L) of singing male zebra finches can be modulated by the presence of a female conspecific. These findings extend recent work showing that the activity of dopaminergic neurons in songbirds is also affected by an audience. Solid evidence is presented for the importance of singing context in modulating auditory processing during vocal production, but the study does not yet fully establish that these effects arise specifically from audience-dependent modulation of auditory feedback, as opposed to possible acoustic, temporal, or recording-related confounds. This work should be of interest to researchers studying the context dependence of sensory processing, the role of auditory feedback, and vocal communication during courtship behavior.

eLife Assessment

This important study provides mechanistic evidence for how the tea-adapted Kanzawa spider mite, Tetranychus kanzawai, overcomes the catechin-based defenses of green tea plants. The work identifies the horizontally transferred dioxygenase DOG15 as a key contributor to host adaptation and supports a two-step model involving evolutionary modification of enzyme activity together with strong inducible upregulation upon feeding on tea. The evidence is convincing because comparative behavioral and toxicological assays, transcriptomic and proteomic analyses, RNAi-mediated functional validation, and recombinant enzyme assays converge to link DOG15 activity and expression with improved performance on tea. The revised manuscript appropriately acknowledges that the products of catechin cleavage have not yet been characterized and that additional detoxification pathways may contribute to tea adaptation, providing a balanced interpretation of the otherwise strong mechanistic evidence.

eLife Assessment

This valuable study presents a real-time system for identifying multiple unrestrained marmosets in a home cage setting using a combination of facial features and color-coded beads. While there is solid evidence that the system has a precision comparable to human experimenters in the tested scenarios, there is limited evidence that this would generalize to unconstrained multi-animal environments

eLife Assessment

This important study investigates how distinct honeybee viruses differentially alter flight performance through interactions with octopamine signaling pathways. The combination of behavioral flight assays, pharmacological perturbation, and transcriptomic analyses provides solid evidence that virus-specific effects on flight are associated with octopamine signaling. The data presented also establish a framework for additional analyses that may strengthen the proposed mechanistic model, including quantification of endogenous octopamine levels and receptor specificity studies.

eLife Assessment

This manuscript reports an important study in which the authors apply smFRET imaging to probe HIV-1 Env conformational dynamics in the presence of antibodies. Previous implementations of smFRET imaging of HIV-1 Env, which focus on gp120 conformation, have yielded limited information on antibodies that target gp41. Through the cutting-edge application of smFRET imaging, the study provides convincing insights into the mechanisms of action of relevant antibodies.