eLife Assessment

This study characterizes a potentially targetable mechanism by which phosphate scarcity drives polymyxin B resistance in Enterobacteriaceae. The findings are important. While some aspects of the approach are very strong, particularly the diversity of techniques, it is recommended to include genetic controls and antibiotic resistance experiments in order to strengthen the evidence, which is currently solid. The clarity and presentation of the findings could also be improved.

eLife Assessment

This study used pupillometry to provide an objective assessment of a form of synesthesia in which people see additional color when reading numbers. It provides convincing evidence that subjective color ratings are matched by changes in pupil size that recapitulate brightness-mediated changes when exposed to the real color. The work provides a valuable contribution to the literature on both synesthetic perception and the use of pupillometry to probe perception and related psychological processes.

eLife Assessment

This study presents valuable findings on the high prevalence of pain in women with polycystic ovary syndrome and its association with distinct future health risks across different racial groups. The evidence supporting the conclusions is compelling, utilizing a massive global dataset and rigorous propensity score matching to identify pain as a critical, yet underexplored, clinical marker. The work will be of interest to reproductive endocrinologists, medical biologists, and clinicians involved in the diagnosis and management of polycystic ovary syndrome.

eLife Assessment

Rickert and colleagues demonstrate that the host peptidoglycan-binding protein PGLYRP1 has both beneficial and detrimental effects on Bordetella pertussis infection in mice. Using a solid array of techniques, the study provides useful insights into how the peptidoglycan fragment tracheal cytotoxin alters host immune responses, dampening inflammatory responses later in B. pertussis infection. These studies indicate that release of peptidoglycan fragments with particular structures can be used by bacteria to modulate NOD1 versus NOD2 responses to their advantage.

eLife Assessment

This study provides a fundamental finding regarding the context-dependent roles of the JAK-STAT pathway (JSP) across different cellular compartments within the breast cancer microenvironment, supported by convincing evidence. The comments of the reviewers were sufficiently addressed.

eLife Assessment

This study presents a valuable framework for the rational design of bacterial probiotics to protect against respiratory infections. The evidence supporting the central claim - that metabolic niche overlap predicts probiotic efficacy - is solid, combining innovative in vitro modeling with in vivo validation, though the model appears less effective for probiotics that rely on antimicrobial metabolite production.

eLife Assessment

This study identifies apoptotic retinal ganglion cells as a potential source of ATP-mediated activation of PANX1 channels that initiate developmental retinal Ca²⁺ waves and coordinate microglial activation and vascular outgrowth with postnatal maturation. The work is important because it proposed an integrative framework linking programmed cell death, spontaneous neural activity, immune responses, and angiogenesis into a self-regulating developmental loop. The multimodal data are solid, but the mechanistic conclusions would be strengthened by complementary genetic approaches, such as PANX1 or BAX knockout models, to establish direct causality.

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 convincing evidence for adaptive changes in three strains of the diamondback moth after only three years of experimental evolution. This work will be of interest to anyone working on the response of pest species to environmental change and to workers on adaptive evolution in general.

eLife Assessment

This fundamental work demonstrates that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner. The evidence in this study is compelling. This study will be of interest to readers in the field of synaptic transmission.

eLife Assessment

This is an important study that establishes a zebrafish model of PIK3CA-related overgrowth syndrome. The imaging characterization of the mesodermal, particularly vascular, lesions of the model is compelling. The scRNA-Seq analysis is convincing, revealing key perturbations in the PIK3CA-mutation model, although deeper investigation of the exact mechanism leading to the lesions, as well as validation at different time points, could further strengthen the findings. This work will be of interest to medical biologists working on PROS, and potentially to a broader audience interested in non-cell-autonomous signaling of PIK3CA and its implications in other diseases.

eLife Assessment

This work presents important findings on quantifying gene coexpression from spatial omics. These quantification methods have been applied to gastruloid to describe how genes are spatialised. The description of the quantifying tools might be incomplete, which also weakens the biological message. Clearer formalization and justification of quantification will improve the study.

eLife Assessment

This important study by Bi and colleagues employed a clever genetics screen to uncover the role of the GidB rRNA methylase in translation fidelity, under certain conditions, in Mycobacterium smegmatis. The findings are solid, supporting the findings that the loss of GidB results in mistranslation. The work contributes to a more in-depth understanding of mycobacterial translation fidelity and will be of interest to microbiologists.

eLife Assessment

This valuable work addresses a longstanding question of how the extant genetic code came to be selected and conserved almost universally across life. Using a mutational approach and a small set of reporters, the authors demonstrate that the mutational impact was similar for non-standard genetic codes. The data provide solid support for the claim of having provided experimental verification of the error minimization theory.

eLife Assessment

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

eLife Assessment

This valuable study advances our understanding of best practices for analyzing population-level data using advanced functional alignment methods. It provides convincing evidence that demographic-specific functional templates improve functional neuroimaging studies that use hyperalignment. This study will be of interest to cognitive neuroscientists, neuroimaging methodologists, and computational researchers with an interest in the human brain.

eLife Assessment

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

eLife Assessment

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

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

eLife Assessment

This valuable study uses technically compelling long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The authors further propose the provocative model that post-translational mechanisms, rather than the transcriptional-translational processes, may contribute to circadian regulation of neuronal excitability. However, the evidence for circadian firing in these neurons, and for post-translational modification of Orco as the underlying mechanism, remains incomplete. In contrast, the study does provide strong evidence that the application of cyclic nucleotides can modulate Orco-dependent activity at a single time point, and reports that the temporal pattern of Orco transcript abundance is not circadian.

eLife Assessment

This well-designed, valuable study uses isotope tracing to analyse how iron limitation alters TCA cycle metabolism in Mycobacterium tuberculosis, revealing potential antibiotic targets for non-replicating bacteria in the host. The evidence is solid, providing insights into metabolic remodelling under iron-limited conditions.

eLife Assessment

This paper provides a novel and valuable method improve the accuracy of predictions of the impact of insecticide-treated net (ITN)-based strategies for malaria control and elimination by using sub-national estimates of the duration of ITN access and use over time from cross-sectional survey data and annual country ITNs received. The authors propose a sophisticated methodological framework that accounts for many sources of uncertainty, providing compelling evidence.

eLife Assessment

In this manuscript, the authors investigate programmed DNA elimination (PDE) across nematodes using a large-scale cytological approach. This work is potentially significant because it expands PDE beyond a few known nematodes to a much broader set of Rhabditidae species, providing an important resource for investigating PDE's evolutionary origins and functions. The strength of evidence, however, is incomplete; the technique used to evaluate PDE is insufficient to provide unambiguous support for the phenomenon, so additional methods, such as genomic sequencing from a few species spanning the range of elimination levels, would be required to confirm these findings. This research would be of interest to geneticists, evolutionary biologists, and those working on the regulation of genome integrity.

eLife Assessment

This is a fundamental study of individual variation and the contribution of learning to behavioural individuality. The experimental design of massively parallel behavioural phenotypes is outstanding and the conclusions are supported by a compelling and rigorous analysis across a large number of experiments in thousands of individuals across genotypes and conditions. The dataset further represents an advance in studying visual associative learning thanks to the ability to make longitudinal measurements of many behavioural decisions within the same animals. These results are a major contribution to the understanding of the sources of behavioural individuality.

eLife Assessment

This paper presents a valuable methodology for genetic manipulation of Blastocystis. Although some imaging data are compelling, higher-quality figures together with more rigorous biochemical assays would strengthen support for the authors' claims. With the experimental evidence and graphics improved, the study would be of interest both to researchers investigating mitochondrial evolution under anaerobic conditions and to medical biologists studying human pathogens.

eLife Assessment

This manuscript presents a useful computational framework for systematically characterising how heterogeneity in initial conditions or biophysical parameters shapes the dynamic behaviour of protein signalling networks, with potential relevance to understanding adaptive drug resistance. While the approach represents a significant methodological contribution, the extent to which its conclusions are biologically informative remains debated, as the model is only qualitatively compared with experimental data and lacks quantitative validation. As a result, the strength of evidence supporting the mechanistic claims is viewed as incomplete.

eLife Assessment

This study represents an important contribution to the study of decision-making under risk, bringing an interdisciplinary approach spanning economic theory, behavioral neuroscience, and computational modeling to test how choice preference is influenced by rare and extreme events. The authors aim to test whether rats are indeed sensitive to these rare and extreme events despite their infrequent occurrence, and to isolate behavioral evidence for avoidance of "Black Swans" - rare and extreme losses. The evidence for specific sensitivity to rare and extreme events however remains incomplete, owing in part to the difficulty of isolating the effect of these events beyond that arising from risk preferences more generally in both task design and in the computational modeling of the choice behavior. Despite this, and given the approach here brings a relatively novel and highly interdisciplinary perspective, this paper will be of broad interest to those seeking to understand animal behavior through the lens of economic choice and decision theory.

eLife Assessment

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

eLife Assessment

This fundamental manuscript presents a novel application of the SANDI (Soma and Neurite Density Imaging) model to study microstructural alterations in the basal ganglia of individuals with Huntington's disease (HD). The compelling methods are, to our understanding, the first application of SANDI to neurodegenerative diseases, provide strong evidence for HD-related neurodegeneration in the striatum, account significantly for striatal atrophy, and correlate with motor impairments. The integration of novel diffusion acquisition and modelling methods with multimodal behavioural data are both of high value in their own right, and create a framework for future studies.

eLife Assessment

Using fMRI-based pRF mapping, this important study presents a novel method for estimating visual field (VF) loss and potential restoration by analyzing contrast-sensitivity patterns in early visual cortex. The evidence supporting the main claims is convincing. This work will be of broad interest to researchers in vision and clinical vision, neuroscience, and brain imaging.

eLife Assessment

This important study utilizes behavioral data and computational modeling to show that spatial properties of visual attention affect human planning. The methodology and statistical analyses are convincing, though the way attention is conceptualized and modeled could be refined. The findings of this study will interest cognitive scientists studying attention, perception, and decision-making.

eLife Assessment

This study offers a valuable analysis of how moment-to-moment fluctuations in arousal are associated with structured, non-uniform patterns of brain-wide functional connectivity during wakefulness. Using data-driven analyses of resting-state and naturalistic fMRI with eye tracking, the authors present convincing evidence that arousal is a dynamic, continuous process that shapes brain activity in a structured way beyond a simple global effect. This paper sheds light on the link between brain activity and ongoing fluctuations in arousal and will be of interest to researchers studying large-scale brain functional organization and links between the brain and body.

eLife Assessment

The importance of uterine natural killer (NK) cells in reproductive success has been demonstrated in mice and humans; however, it is still unclear how uterine NK cells are developed. In this important manuscript, the authors provide convincing evidence that TGF-b signaling in NK cells supports normal pregnancy in mice by the conversion of conventional NK cells into uterine tissue-resident NK cells. Previous concerns have been addressed in this revised version.

eLife Assessment

This manuscript provides important insights into how U2AF2-dependent intron retention regulates the localization and function of long noncoding RNAs, with evidence supported by multiple complementary approaches. The work is notable for linking intron retention to nuclear speckle localization and cellular phenotypes, including proliferation and migration, although the mechanistic basis remains incompletely resolved. Overall, the study presents a compelling dataset with clear biological implications but would benefit from additional analyses to strengthen mechanistic interpretation and generality.

eLife Assessment

This important study establishes the first vertebrate models of DeSanto-Shinawi Syndrome, revealing conserved craniofacial and social and behavioral phenotypes across mouse and zebrafish that mirror key clinical features. The convincing evidence is supported by behavioral, anatomical, and molecular analyses of Wac animal mutants. This study sets a baseline for future mechanistic studies and reports a platform to test approaches to reverse phenotypes.

eLife Assessment

This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This work provides convincing evidence, supported by pharmacological perturbations and numerical simulations using the vertex model, that the principle of "high heterotypic interfacial tension" that appears to drive cell sorting and tissue segregation in embryonic models similarly applies to cancer cell behaviour.

eLife Assessment

Overall, this is a manuscript with solid evidence that delivers an important community resource for those performing experimental research in amyotrophic lateral sclerosis. The authors address the lack of validated tools for the detection and quantification of proteins associated with amyotrophic lateral sclerosis (ALS) through an extensive screening of 303 commercially available antibodies to 33 protein targets. The effort invested in generating the knockout lines for validation experiments is a clear strength of the study.

eLife Assessment

Non-essential amino acids such as glutamine have been known to be required for T cell general activation through sustaining basic biosynthetic processes, including nucleotide biosynthesis, ATP generation, and protein synthesis. In this important study, the authors found that extracellular asparagine (Asn) is required not only for T cells to generally refuel metabolic reprogramming, but to produce helper T cell lineage-specific cytokine, for instance, IL17. In particular, the importance of Asn in IL17 production was convincingly demonstrated in the mouse experimental autoimmune encephalomyelitei (EAE) model, mimicking human multiple sclerosis disease.

eLife Assessment

This important study demonstrates that nutrient stress engenders metabolic vulnerabilities in pancreatic ductal adenocarcinoma (PDAC). By combining cell line and mouse models, the authors provide compelling evidence showing that arginine depletion from the microenvironment disrupts lipid homeostasis in PDAC resulting in ferroptosis upon exposure of tumors to polyunsaturated fatty acids. This report is likely to be of broad interest to researchers interested in studying cancer biology, metabolic adaptations and stress responses.

eLife Assessment

This important study provides a quantitative comparison of how zebrafish and medaka larvae process visual motion, revealing clear differences in how they integrate information across space and time. The evidence is convincing, combining a broad set of behavioral assays with response decomposition and mechanistic modeling that together support the central conclusions. Some aspects remain incomplete, particularly the link between the spatial and temporal findings, the extent to which the model accounts for the full range of behavioral results, and the framing of broader evolutionary or social interpretations. Overall, the work offers a careful and informative analysis that should be of broad interest to researchers studying visual processing, sensorimotor computation, and comparative neuroscience.

eLife Assessment

This study presents a large-scale characterization of single-neuron responses during reading and listening, enabling examination of both 'low-level' (orthographic/phonological) and 'higher-level' (syntactic) features, as well as links between single-neuron activity and multi-scale field potentials, making it a valuable resource for bridging micro- and macroscale accounts of language processing. The analyses identify modality-specific and putatively modality-independent responses across distributed brain regions, offering an intriguing framework for understanding how sensory-specific and abstract representations may relate. However, the evidence supporting the central claims is currently incomplete, due to limited population-level quantification, insufficient statistical characterization of how many neurons encode the relevant features, ambiguity in the interpretation of encoding model results, and a lack of rigorous tests of cross-modal generalization and alternative accounts, which together weaken the conclusions about amodal representations and hierarchical processing.

eLife assessment

This is a valuable survey of movements and locomotor patterns produced by circuits in the medial reticular formation (MRF) of the brainstem. The authors provide solid evidence that activation of GABAergic MRF neurons slowed down walking, activation of glutamatergic neurons induced a specific "shuffle" limb trajectory, and the activation of serotonergic neurons increased locomotor speed without affecting walking signature. This study adds to the growing body of knowledge about the effects of brainstem circuits on specific aspects of locomotor function.

eLife Assessment

This study provides valuable mechanistic insight into the mutually exclusive distributions of the histone variant H2A.Z and DNA methylation by testing two hypotheses: (i) that DNA methylation suppresses H2A.Z deposition by ATP-dependent chromatin remodelling complexes, and (ii) that DNA methylation destabilizes H2A.Z nucleosomes, thereby preventing H2A.Z retention. Through a series of well-designed and carefully executed experiments, solid support is presented for the first hypothesis. The evidence supporting the second hypothesis is less complete, and the extent to which either mechanism is responsible for H2A.Z exclusion from methylated DNA remains not entirely clear. This work will be of broad interest to researchers in chromatin biology and epigenetics.

eLife Assessment

This study reports on the development and characterization of chickens with genetic deficiencies in type I or type III interferon receptors, which is an important contribution to the field of avian immunology. The data reflecting the development of the new interferon-receptor-deficient chickens is compelling. The initial characterization of IFN biology and infection responses in these knockout chickens provides a solid foundation for future studies on the distinct contributions of type I and type III interferon signaling to antiviral responses.

eLife Assessment

This important study implicates that changes in cell regulation may contribute to the evolution of multicellularity. The evidence supporting the conclusions is convincing, with rigorous methods used to test alternative hypotheses. The work will be of broad interest to cell and evolutionary biologists and those studying the cell cycle and cancer.

eLife Assessment

This important study demonstrates that paternal diet influences not only testicular morphology but also placental and fetal development, supporting a role for paternal contributions to offspring health. The study also considers potential links between the microbiome and male reproductive health. By combining transcriptomic and histological analyses across multiple tissues, the evidence supporting the central conclusions of the study is convincing.

eLife Assessment

The work by van der Pijl presents important findings on the role of titin-associated muscle ankyrin repeat proteins (MARPs) on hypertrophy via mTOR signalling. The study presents rigourous data using in vivo loss-of-function and pharmacological approaches to investigate effects on hypertrophy. While the evidence supporting the role of MARPs on hypertrophy is solid, there are limitations. For example, the use of Rapamycin only inhibits some aspects of mTORC1 signalling and the study is limited to analysis of the diaphragm and thus it is not clear if the mechanisms are conserved across other muscle types.

eLife Assessment

This potentially valuable study investigates the anti-senescence effects of red light exposure, proposing that reduced SIRT4 levels enhance fatty acid metabolism and H3K9ac, thereby attenuating ageing-related phenotypes. The authors use multiple approaches, including cultured cells, animal models, and molecular analyses, to support their conclusions. However, the evidence remains incomplete, as additional controls and stronger mechanistic data are needed to fully support the proposed pathway, particularly how red light exposure reduces SIRT4 levels.

eLife Assessment

The study presents valuable findings regarding the impact of ARHGEF6 deletion, a RhoGTPase regulator linked to X-linked intellectual disability (XLID46), in the development of interneurons. The evidence supporting the observed cellular and developmental phenotypes collected in both mouse and human iPSC models is convincing, although further work would strengthen the mechanistic interpretation and clarify the specificity of the findings. This work offers new insights into ARHGEF6 function and the potential contribution of its dysfunction to neurodevelopmental disorders.

eLife Assessment

This important study examines the effects of diet and exercise on brain structure and behaviour in the 3xTg mouse model of Alzheimer's disease. They show that combined access to a low-fat diet and exercise improves regional brain volume and behaviour in transgenic and wild-type control mice in a sex-specific manner, with analyses linking functional improvements to glucose homeostasis. Although some claims are well supported, the overall strength of the evidence is incomplete and hampered by a lack of clarity regarding the statistical analyses chosen. The work may be of interest to researchers studying neurodegenerative disease, particularly in preclinical contexts.

eLife Assessment

The manuscript by Rotsides et al. reports the design and validation of SMART-MR1, a miniaturized MR1 metabolite-display platform in which the α1/α2 ligand-binding domain is stabilized by a synthetic helical domain in place of the α3 domain and β2-microglobulin. Supported by biochemical, biophysical, and structural approaches, including ITC, NMR, and cryo-EM, the work provides solid evidence that SMART-MR1 retains native-like ligand binding and A-F7 TCR recognition while enabling experimental approaches for ligand screening that are difficult with conventional MR1 constructs. The study is valuable for the MR1 and MAIT-cell fields, particularly as a tool for ligand screening and mechanistic studies of MR1-restricted antigen presentation. There are several suggestions to further strengthen the study's impact, including clearer benchmarking against existing MR1 platforms, broader validation across ligands and TCRs, and functional evidence from MAIT-cell staining or activation assays.

eLife Assessment

The study by Izquierdo and colleagues provides important insights into the field of genomic and transcriptomic prediction of traits across multiple environments. The rationale and analyses conducted to integrate the two types of ~omics datasets across two environments are solid. However, some clarification would be appreciated in the presentation of the results, and adding some statistical control to clarify how the predictors were selected, or assessing their importance using the SHAP framework, would further consolidate the findings.

eLife Assessment

This Review Article provides an overview of circadian findings obtained using the zebrafish model and will be of particular interest to researchers working with zebrafish in chronobiology and behavioural neuroscience. The article would benefit from a broader conceptual framework that more clearly positions zebrafish within the wider landscape of animal models used in circadian biology, including comparisons with other extensively studied systems. In addition, several citation inaccuracies and interpretational issues identified during peer review should be carefully addressed to strengthen the accuracy and impact of the review.

eLife Assessment

This important study demonstrates that a perinuclear actomyosin network, present in some types of human cells, facilitates kinetochore-spindle attachment of chromosomes in unfavorable locations, thereby reducing their missegregation rate. This actomyosin network and its general role have been studied previously, but this study convincingly clarifies the underlying mechanism and expands the investigation to additional cell lines. The results are relevant to understanding chromosome missegregation in cancer cells.

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

eLife Assessment

This potentially useful paper presents an intriguing hypothesis about the evolutionary origins of the SLC25 family of mitochondrial carrier proteins common to all eukaryotic life, proposing that all members originated from the ADP/ATP carrier (AAC) and that AAC itself may have emerged from bacterial homologs such as CysZ and YihY. While the phylogenetic analyses and structural searches are reasonable methodologies to explore ancient evolutionary events, the evidence provided here is deemed to provide incomplete support for the conclusion that the mitochondrial ATP transporter is related to CysZ and Yih.

eLife Assessment

This valuable study uses a computer vision pipeline to infer the motor control of cephalopod skin, revealing that individual chromatophores exhibit anisotropic deformations and can be associated with multiple putative motor units. The evidence supporting these claims is convincing, and the authors present some limited electrophysiological validation of the findings from their computational analysis. This work will be of significant interest to biologists studying cephalopod behavior and motor control.

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 study addresses an important question in aging biology by combining metabolic, genetic, and functional approaches to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast. The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in shaping distinct aging-associated phenotypes is convincing overall, with the engineered A2A strain providing a particularly elegant demonstration of coordinated metabolic regulation. However, several conclusions would benefit from clarification or moderation, particularly regarding the relationship between late-life fitness and replicative lifespan, the interpretation of "senescence," the proposed existence of distinct aging subpopulations, and the extent to which the data support mechanistic claims about lipid starvation, acetyl-CoA excess, and chromatin-based aging pathways.

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.

eLife Assessment

This important study provides novel information on multi-enzyme complexes, known as metabolons, that form between sequential enzymes in a metabolic pathway. Using an innovative NanoBiT split-luciferase system, the authors present compelling evidence that malate dehydrogenase (MDH1) and citrate synthase (CIT1) dynamically associate under different metabolic conditions in Saccharomyces cerevisiae. The findings suggest the dynamic MDH1-CIT1 interaction facilitates control of TCA pathway flux rate.

eLife Assessment

This important study utilizes behavioral data and computational modeling to show that spatial properties of visual attention affect human planning. The methodology and statistical analyses are solid, though the way attention is conceptualized and modeled could be refined. The findings of this study will interest cognitive scientists studying attention, perception, and decision-making.

eLife Assessment

This manuscript presents a useful mean-field model for a network of Hodgkin-Huxley neurons retaining the equations for ion exchange between the intracellular and extracellular space. The mean-field model derived in this work relies on approximations and heuristic arguments that, on the one hand, allow a closed-form derivation of the mean-field equations, but also raise questions about their justifications and the degree to which the results agree with experiments as well as direct numerical simulations. While the revised manuscript is much improved, reviewers continue to question the methodology for reducing model dimensionality and therefore the evidence for the utility of this approach remains incomplete at present.

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 considered well supported, though some mechanistic claims may benefit from further evidence and more cautious framing. 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 important study combines single-molecule imaging and CUT&TAG to address the molecular mechanism underlying the differentiation process that initiates the formation of red blood cells in the bone marrow. The authors provide evidence that the transcription factor GATA2 transiently associates with a new set of genomic loci early in the differentiation process before it is replaced by GATA1. Together, the experiments across three biological systems are solid, but they could benefit from additional details and controls to strengthen the conclusions.

eLife Assessment

This manuscript presents a valuable 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 framework that uses anticipatory eye movements to track how expectations are formed and revised during implicit probabilistic sequence learning. The evidence supporting a behavioural dissociation between errors arising from environmental noise and errors reflecting an inaccurate internal model is solid, but the oculomotor data describe behaviour rather than explain the underlying computational mechanisms, and the stronger mechanistic claims - that learning is more repetition-based than error-driven - remain incomplete without formal comparison against computational models of error-driven learning. The emerging reaction-time difference between conditions appears driven by slowing to low-probability stimuli rather than facilitation of high-probability ones, an asymmetry that requires decomposition and consideration of alternative explanations. The potential contamination of the anticipatory measure by starting gaze position should be addressed through control analyses, and the "process-pure" framing should be tempered, given that oculomotor behaviour is itself subject to motor learning.

eLife Assessment

This valuable study uses large-scale 7T naturalistic fMRI data and nonlinear pRF modeling to map the tonotopic organization of the human auditory cortex, linking spectral tuning to speech selectivity and cortical hierarchy. The evidence is solid, demonstrating that movie-based stimuli can recover robust population-level auditory maps and offering tools for leveraging existing datasets, although there is room for improvement in relating static tonotopy to dynamic speech processing and in presentation clarity. The study will be of interest to a broad audience working on auditory cortex organization and mapping.

eLife Assessment

This important study identifies two pairs of dopaminergic neurons (DA-WED) in Drosophila that coordinate cardiac deceleration and locomotor responses to a mechanical threat. The evidence is convincing, supported by comprehensive optogenetic, physiological, and behavioral experiments showing that these neurons are required for and sufficient to drive threat-associated cardiac slowing. The proposed role of cardiac deceleration as an interoceptive contributor to locomotion is intriguing, but should be presented more cautiously, as the causal relationship between heartbeat changes and locomotor output remains less directly established. The work will be of broad interest to those interested in neural circuits, neuromodulation, and the integration of physiological and behavioral responses.

eLife Assessment

This study proposes that fitness level influences exercise-induced hypoalgesia in women. However, the evidence to support this claim is incomplete: the conclusions rely on a small interaction that emerges only under specific conditions and are incongruent with the title, the findings are inconsistent across pain modalities and stimulus intensities, the analysis approach does not fully exploit the continuous pain ratings collected, and the absence of a baseline condition limits the interpretability of results as reflecting true hypoalgesia. Additionally, the methods by which fitness level was categorized across cohorts can be questioned, and the results and figures do not clearly illustrate how between-group comparisons were conducted. With a proper revision, it could be useful for sports medicine practitioners to consider how they administer exercise protocols to help those experiencing pain.

eLife Assessment

This study presents important findings on the relationship between nutrient availability and NAD/NADH levels, which in turn regulate biomass production in cancer cells. The authors provide convincing evidence to support their claims, offering insight into why it is difficult to predict which nutrients limit cancer cell growth: both cell type and nutrient availability together determine the oxidative capacity that constrains the synthesis of various metabolic intermediates. The manuscript will be of broad interest to researchers working in cancer and cell metabolism.

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 and are highly convincing.

eLife Assessment

The nematode C. elegans is an ideal model in which to achieve the ambitious goal of a genome-wide atlas of protein expression and localization. In this paper, the authors develop a rational and useful strategy for at-scale tagging of all protein coding genes with fluorescent markers, providing solid evidence that it could be a feasible foundation for a large-scale, community-wide project.

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 used pupillometry to provide an objective assessment of a form of synesthesia in which people see additional color when reading numbers. It provides convincing evidence that subjective color ratings are matched by changes in pupil size that recapitulate brightness-mediated changes when exposed to the real color. The work provides a valuable contribution to the literature on both synesthetic perception and the use of pupillometry to probe perception and related psychological processes.

eLife Assessment

This study presents a large, systematically curated catalog of non-canonical open reading frames (ncORFs) in human and mouse through the reanalysis of nearly 400 Ribo-seq datasets using a standardized pipeline; the resulting atlas consolidates ncORF annotations across tissues and provides a valuable resource for investigating non-canonical translation and ORF emergence. The main conclusions are supported by consistent data processing and multiple computational measures of translation and conservation. While the pipeline is transparent and technically robust, some analytical criteria and dataset limitations could be described more explicitly, and several downstream conclusions would benefit from more cautious interpretation, some evolutionary inferences are primarily correlative; dataset heterogeneity, uneven tissue representation, and limited experimental validation also constrain the strength of a subset of the findings. Overall, the evidence is solid, and the resource is likely to be broadly beneficial to the community.

eLife Assessment

This study offers an important contribution to our understanding of the role of layer 6b cortical neurons in sleep-wake regulation, providing new insight into how this understudied neural population may regulate cortical arousal via orexin signaling. The evidence supporting these findings is solid, although somewhat constrained by limitations in the specificity of the genetic targeting strategy. Nonetheless, the work introduces new avenues for uncovering how the classical wake-promoting peptide, orexin, exerts its effects on the cortex.

eLife Assessment

In this potentially valuable computational study, the authors conducted extensive atomistic and coarse-grained simulations to probe the temperature-dependent phase behaviors of ELF3, a disordered component of the evening complex in plant. The results aim to highlight the role of polyQ tracts in modulating temperature-responsive structural and condensation behavior. Despite considerable improvements in the revised manuscript, the level of evidence is considered incomplete, since several of the supplementary observables introduced to support the revised claim indicate that the variants studied are not statistically distinguishable within the reported replicate uncertainty.

eLife Assessment

This is an important study describing 'SPEx', a broadly accessible method that combines cell expansion, laser microdissection, and mass spectrometry to enable subcellular proteomic profiling. The authors provide convincing evidence that this flexible integration of established techniques provides a robust and practical approach for compartment-resolved spatial proteomics. The authors support their main claims with appropriate validation across multiple subcellular compartments and show that the method can recover known markers while also identifying previously uncharacterized components. Overall, the work is likely to be of broad interest to cell and molecular biologists, particularly those seeking scalable and cost-effective strategies for mapping organelle composition.

eLife Assessment

This valuable study investigates whether high-level physical reasoning is grounded in real-time bodily and vestibular signals using an innovative combination of virtual tool-use tasks and galvanic vestibular stimulation. The evidence is incomplete, as the main claims rely on limited and partially exploratory effects, including uncorrected multiple comparisons and cross-study comparisons that weaken the strength of the conclusions. The work, if it can be supported by clearer statistical support and more cautious interpretation, will be of interest to researchers in embodied cognition and physical reasoning.

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

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

eLife Assessment

By using a combination of patch clamp recordings, calcium imaging and computer modeling, the authors analyze the spatial distribution of voltage gated calcium channels at glutamatergic synapses formed between layer 5 pyramidal neurons (L5PNs) and between layer 2/3 and L5PNs in the prefrontal cortex (PFC) and primary somatosensory cortex (S1); they conclude that the calcium channel-vesicle coupling is looser in the PFC compared to S1, although additional experiments are needed to determine how the distinct functional characteristics of these synapses in different brain regions might affect data interpretation. Overall, these findings are important because they have implications for shaping synaptic plasticity and neural circuit function across brain regions. They are solid because they are based on the use of a multi-pronged approach, although the presentation would benefit from stronger integration of the current findings with the existing literature and a more explicit discussion of potential limitations and confounding factors for data interpretation.

eLife Assessment

The findings of this study are important since they cover the repurposing of small molecules as metalloprotease and phospholipase inhibitors for early intervention in the treatment of bothropic envenoming in the Neotropics, and thus provide a strong rationale for the progression of these inhibitors into future preclinical and clinical evaluation for snakebite indications across various ecological zones, albeit the current evidence casts doubts on the viability of repurposing nafamostat. The strength of the evidence is solid; however, there are some weaknesses, such as a lack of translatability of the in vivo model and insufficient venom characterization. Thus, the strength of the evidence can be enhanced by using a mouse model in future studies. The paper remains of interest to ophiologists, biochemists and medicinal chemists.

eLife Assessment

This study introduces an important method to estimate the probability of malaria importation with a new Bayesian approach that integrates epidemiological, travel reports, and genetic data. The authors provide convincing evidence for the value of this model in identifying the main sources of malaria transmission and risk factors. This work will be of interest to the area of genomic epidemiology and public health strategies aiming to eliminate malaria.

eLife Assessment

This important study presents a theoretically grounded framework for dimensionality reduction in single-cell RNA sequencing data, utilizing the principles of Riemannian manifolds. The proposed method addresses a critical challenge in bioinformatics-extracting highly informative latent dimensions without relying on the heuristic assumptions common in existing workflows. The evidence supporting the method's utility in estimating intrinsic dimensionality and identifying cell types is convincing, though the work would benefit from more rigorous validation against established ground truths and a clearer strategy for addressing prevalent batch effects.

eLife Assessment

This study reports the relative importance of Tie1 and Tie2 signaling for atrial versus ventricular trabeculation. It is an important study and is one of the few works to date that have carefully and simultaneously analyzed these two processes. In line with a previous study in zebrafish, the authors demonstrate key differences between atrial and ventricular trabeculation. While the imaging and quantitative data were conducted with solid and validated methodology throughout the manuscript, the work would benefit from more rigourous approaches where Tie1/2 signaling is disrupted prior to the onset of atrial/ventricular trabeculation, to allow for a more direct comparison.

eLife Assessment

This Review Article provides a scholarly, clear and well-structured review of intracranial research into the neural correlates of consciousness (NCCs). To our knowledge this is the first such review and is therefore likely to become a must-read for anyone working in the field of consciousness research. The authors discuss the difficulties that researchers must face when studying NCCs and how insights may emerge via intracranial recordings in humans. This no doubt reflects an in-depth, timely, and insightful contribution to the literature.

eLife Assessment

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

eLife Assessment

This important study identifies a physiologically relevant interaction between LRRK2 and drebrin, an actin-binding protein crucial for neuronal structure. A solid body of evidence, including multiple cell models, highlights the complexities of how modifiers like BDNF intersect with LRRK2-kinase dependent function, and that many modifiers between AKT and LRRK2 in different cellular pathways are yet to be identified and understood.

eLife Assessment

This important study provides solid evidence that early childhood malaria exposure affects the development of antibody responses to unrelated pathogens and vaccine-derived antigens in Kenyan children. The findings are of major public health importance and limitations of the observational study design are properly acknowledged.

eLife Assessment

This valuable study identifies a brown adipose tissue-specific heat shock factor 1 (HSF1)-alcohol dehydrogenase 5 (ADH5) axis that regulates oxidative stress and cellular senescence during aging. The authors show that ADH5 deficiency drives BAT dysfunction and contributes to organismal health decline in aged mice. The evidence is convincing, and the work will be of broad interest to the adipose tissue and aging research communities.

eLife Assessment

The study by Reed et al. provides fundamental findings defining the topological changes that occur during tumorigenesis. These compelling findings enhance the understanding of stable long-range connections among genes that reprogram cancer-related functions.

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 data are high-quality and broadly consistent with the interpretation, but alternative mechanisms for the defects are not considered; additional work should rule out vesicular trafficking, discuss other mechanisms, and address methodological issues.

eLife Assessment

This valuable study demonstrates that a multi-step differentiation programme 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 supporting patterning across several conditions is convincing, albeit incomplete for the stronger differentiation/maturation claims because the irreversibility of the proposed states is not consistently established, and some modelling and conceptual interpretation details require further clarification.

eLife Assessment

This important study provides detailed insights into the metabolic states of hemocyte populations across developmental stages and in both physiological and pathological contexts, including during immune challenge. The study provides convincing evidence by comparing the relative utilization of glycolysis and oxidative phosphorylation in Drosophila larval immune cells, and can have implications for metabolic programs that shape immune function in health and disease.

eLife Assessment

This manuscript makes a valuable contribution to the concept of fragility of meta-analyses via the so-called 'ellipse of insignificance for meta-analyses' (EOIMETA). The strength of evidence is convincing, supported primarily by an example of the fragility of meta-analyses in the association between Vitamin D supplementation and cancer mortality, but the approach could be applied in other meta-analytic contexts. The significance of the work could be enhanced with a more thorough assessment of the impact of between-study heterogeneity, additional case studies, and improved contextualization of the proposed approach in relation to other methods.

eLife Assessment

This is a valuable study presenting convincing data indicating that the bacterial GTPases EngA and ObgE enable single-step reconstitution of functional 50S ribosomal subunits under near-physiological conditions. The study elegantly bridges the gap between the non-physiological aspects of the previous two-step reconstitution method and the extract-dependent iSAT system to enable assembly of highly functional ribosomes under translation-compatible conditions. The reported findings represent substantial progress towards achieving a bottom-up reconstruction of the translation machinery from synthetic parts.

eLife Assessment

This study investigates how the HIV inhibitor lenacapavir influences capsid mechanics and interactions with the nuclear pore complex. It provides important insights into how drug-induced hyperstabilization of the viral shell can compromise its structural integrity during nuclear entry. The modeling is technically sophisticated, and the analyses provide convincing support for the mechanistic conclusions.

eLife Assessment

This valuable study examines the cleavage of motor neuron nucleoporins by proteases of enterovirus D68, a pathogen associated with acute flaccid myelitis. The evidence supporting the effects of EV-D68 proteases on nuclear import and export is generally solid, as is the independent examination of EV-D68 protease on spinal cord neuron toxicity. The specific conclusions related to RNA export were considered overstated relative to the data presented.

eLife Assessment

This study offers an important advance by extending an intuitive visualization tool that enables assessment of how dendritic and synaptic currents potentially shape neuronal output. The evidence supporting the tool's capabilities is convincing, with well-documented code, algorithmic innovation, and application to hippocampal pyramidal neurons. The work will be of interest to computational and systems neuroscientists seeking accessible methods to examine dendritic computations.

eLife Assessment

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

eLife Assessment

This valuable study advances our understanding of how organisms respond to chronic oxidative stress. Using the nematode C. elegans, the authors identified key neuronal signaling molecules and their receptors that are required for stress signaling and survival. The evidence supporting the conclusions is solid, including rigorous genetics, stress response analysis, and transcriptional profiling. This research will be of broad interest to neuroscientists and researchers working in the field of oxidative stress regulation.

eLife Assessment

In this valuable study, the authors conducted an impressive amount of atomistic simulations with a glycosylated HIV-1 envelope glycoprotein (Env) trimer in a realistic asymmetric lipid bilayer. The aim was to probe how Env transmembrane domain, cytoplasmic tail, and membrane environment influence ectodomain orientation and antibody epitope exposure. The simulations convincingly show that ectodomain motion is dominated by tilting relative to the membrane and explicitly demonstrate the role of membrane asymmetry in modulating the protein conformation and orientation. Additional analyses of the authors' deposited MD trajectories could serve as invaluable extensions of this work to probe, for example, for exposure of cryptic epitopes and potential allosteric coupling.

eLife Assessment

This study provides fundamental insights by demonstrating that the Nanog mRNA coding sequence (CDS) and 3′UTR domains are spatially segregated and functionally distinct in pluripotent stem cells and blastocysts, with 3′UTR-enriched border cells primarily influencing morphogenesis and CDS-enriched inner cells largely regulating transcription and epigenetic programs. The work opens a novel conceptual avenue for understanding how separable mRNA domains can differentially control cell behavior and differentiation. However, the evidence is incomplete, as key aspects of the molecular nature, biogenesis, and precise characterization of the separated 3′UTR and CDS RNA species, as well as causal links between their perturbation and the observed phenotypes (e.g., via rescue and deeper characterization of 3′UTR elements), remain to be fully established.

eLife Assessment

There is a need for better and safer dengue virus live attenuated vaccines. This manuscript describes important findings that could lead to the design of a strongly immunogenic, tetravalent live attenuated vaccine for dengue, without the risk of causing antibody-dependent enhancement. However, the experimental evidence presented is incomplete since only constructions of one serotype were tested to prove the principle.

eLife Assessment

The authors propose a "simplified" model for intrinsically bursting neurons with explicitly controllable parameterization of oscillatory dynamics. The evidence that the modeling approach is generally appropriate and practical for modeling rhythmic bursting neurons and neural circuits is currently incomplete. Based on what the authors present, this model appears to have limited neurobiological relevance and utility but may be useful as a controller for an artificial system, such as in neuro-robotics applications.

eLife Assessment

This study presents potentially important findings linking peripheral inflammation to the remodeling of perinodal adipose tissue and draining lymph nodes, suggesting a mechanism by which local tissue inflammation can reshape LN structure and metabolism. The idea is solid and supported by observations. However, the evidence remains incomplete in parts, as several conclusions rely on correlative weight and cellularity measurements, and macrophage involvement requires further validation.

eLife Assessment

This important study provides a comprehensive map of how touch-sensitive neurons in the fly head connect to downstream circuits, revealing parallel pathways that preserve spatial organization and identifying a developmentally defined circuit linking sensory input to grooming behavior. The evidence is convincing, with detailed anatomical reconstruction and quantitative analysis supporting the main claims, while the link to behaviour remains based on prior functional work. The study will be of interest to neuroscientists studying sensory processing and motor control, and provides an invaluable resource for future functional investigations.

eLife Assessment

This important study combines optogenetic manipulations with wide-field cortical imaging to investigate the neural basis of context-dependent sensory processing. It provides compelling evidence that the retrosplenial cortex modulates behavioral responses to whisker deflection depending on the behavioral context. The paper will be of strong interest to neuroscientists studying cortical mechanisms of sensorimotor processing.

eLife Assessment

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

eLife Assessment

This important study is the first characterization of the phenotype caused by a lack of Eml3 expression in mice. Mutant animals present a disrupted pial basement membrane, leading to focal extrusions from the cerebral cortex, called ectopias. The methodology is convincing and the conclusions are solid, although further investigations on the molecular and cellular mechanisms are required to improve the manuscript. This work would be of interest to neural development biologists and human geneticists working on brain disorders.

eLife Assessment

In this important study, Li et al. identify estrogen receptor 1-expressing neurons (ESR1+) in Barrington's nucleus as key regulators coordinating both bladder contraction and the relaxation of the external urethral sphincter. Using appropriate and validated methodologies aligned with the current state of the art, the data are convincing and of generally high quality.

eLife Assessment

This manuscript applies a theoretical analysis to two published datasets on yeast and bacterial evolution to compare different ways of quantifying fitness. It makes an important advance by clarifying how discrepancies can arise by using different approaches and provides recommendations for best practices. Overall, this is an impressive and highly beneficial study that is based on convincing evidence and has the potential of setting standards in this rapidly growing field.

eLife Assessment

This is a valuable study presenting solid data indicating that the bacterial GTPases EngA and ObgE enable single-step reconstitution of functional 50S ribosomal subunits under near-physiological conditions. The study elegantly bridges the gap between the non-physiological aspects of the previous two-step reconstitution method and the extract-dependent iSAT system to enable assembly of highly functional ribosomes under translation-compatible conditions. The reported findings represent progress towards achieving a bottom-up reconstruction of the translation machinery from synthetic parts.

eLife Assessment

This is an important study that develops multiple human iPSC-based models to study the consequences of DNMT3A mutations in Tatton-Brown-Rahman Syndrome. Convincing evidence shows dysregulation of GABAergic interneuron development and function, and the authors identify some of the key signaling mechanisms underlying these changes. This study will be of interest for understanding the functions of DNMT3A in brain development and the causes of neurological dysfunction in Tatton-Brown-Rahman Syndrome.

eLife Assessment

This is a useful study investigating the role of peristalsis in the elongation of the gut, using the chick ceca as a model. The work employs optogenetics together with embryological approaches to establish links between peristaltic muscle contractions and downstream cell behaviors that lead to tube elongation. However, the work is somewhat incomplete, limited in mechanistic insights that would extend beyond prior work in the literature, which has already suggested a role for smooth muscle contractility in avian gut elongation.

eLife Assessment

This valuable study builds a novel auditory-motor paradigm to investigate how the brain learns associations between movements and their auditory consequences. Solid evidence is provided for early ERPs (50-100 ms latency) reflecting violations of established key-pitch mappings. The writing, however, could be streamlined to better emphasize the paper's key contribution, and some statistical analyses might be improved.

eLife Assessment

This useful study asked whether the behaviour of motor units from a hand muscle changed across the two mechanical actions it performs. The authors used high-density intramuscular electrodes to record the activity of several motor units and reported changes in motor unit recruitment order across tasks that were not dependent on motor unit properties, suggesting differential spinal contributions to the two actions. However, the evidence supporting their main claims is incomplete, and some of the conclusions are based on unsubstantiated assumptions: the authors should correct several key analyses and temper claims that are not directly backed up by their data.

eLife Assessment