eLife Assessment

This study investigates the folding and unfolding behavior of the doubly knotted protein TrmD-Tm1570, providing insight into the molecular mechanisms underlying protein knotting. The findings reveal multiple unfolding pathways and suggest that the formation of double knots may require chaperone assistance, offering valuable insights into topologically complex proteins. The evidence is convincing, supported by consistent agreement between simulation and experiment, though some aspects of the presentation and experimental scope could be clarified or expanded.

eLife Assessment

This important study provides a comprehensive comparison of the mechanisms through which different inhibitors affect the SARS-CoV-2 main protease, a pivotal antiviral drug target, and suggests a potentially broad-spectrum strategy to inhibit this critical viral enzyme by disrupting its dimerization states. However, whereas the biophysical analyses of the dimer stability are convincing, evidence supporting this new mode of mechanism to inhibit the main protease is incomplete and would benefit from a correlation of the biophysical observations with functional activity. With the functional validation part strengthened, this work would be of interest to biochemists and virologists working on anti-coronavirus drug discovery.

eLife Assessment

This work presents a brain-wide atlas of vasopressin (Avp) and vasopressin receptor 1A (Avpr1a) mRNA expression in mouse brains using high-resolution RNAscope in situ hybridization. The single-transcript approach provides precise localization and identifies additional brain regions expressing Avpr1a, creating a valuable resource for the field. The revised manuscript is clearer and more impactful, with improved figures, stronger data organization, and enhanced scholarship through added context and citations. Overall, the evidence is compelling, and the atlas should be broadly of use to researchers studying vasopressin signaling and related neural circuits.

eLife Assessment

Recent studies have shown that mRNA can be acetylated (ac4c), altering mRNA stability and translation efficiency; however, the role of mRNA acetylation in the brain remains unexplored. In this important study, the authors demonstrate that ac4c occurs in synaptically localised mRNAs, mediated by NAT10. Conditional reduction of NAT10 protein levels led to decreases in ac4c of mRNAs and deficits in synaptic plasticity and memory. These solid results suggest that mRNA acetylation may play a role in memory consolidation.

eLife Assessment

This valuable study examines the role of E2 ubiquitin enzyme, Uev1a in tissue resistance to oncogenic RasV12 in Drosophila melanogaster polyploid germline cells and human cancer cell lines. The solid evidence suggests that Uev1a works with the E3 ligase APC/C to degrade Cyclin A. This work would be of interest to researchers in germline biology and cancer.

eLife Assessment

This study presents valuable findings on the role of KLF6 in in vitro endothelial cells exposed to altered (high or low) shear stress with a customized microfluidic device to investigate mechanisms of atherosclerosis. The finding that altered shear stress results in endothelial cell ferroptosis through reduced expression of KLF6 is compelling and adds a new layer of complexity to the pathogenesis of atherosclerotic plaques. However, more detailed characterization of ferroptosis is needed.

eLife Assessment

Using genome databases, the authors performed solid bioinformatic analyses to trace the genomic history of the clinically relevant Staphylococcus aureus tetracycline resistance plasmid pT181 over the last seven decades. They discovered that this element has transitioned from a multicopy plasmid to a chromosomally integrated element, and the work represents a valuable demonstration of the use of publicly available data to investigate plasmid biology and inform clinical epidemiology. This work will appeal to researchers interested in staphylococcal evolution and plasmid biology.

eLife Assessment

This valuable study describes significant differences in prey capture behavior between PSD-95 knock-out and wild-type mice, despite prior work by the same authors showing only modest visual deficits in the former. The data convincingly demonstrated prey capture performance in PSD-95 knock-out mice to improve under monocular viewing conditions. However, this finding alone was inadequate to support the interpretation of results as revealing a deficit in binocular visual integration, especially given the lack of eye and head tracking data or consideration of alternative explanations for the observed behavior.

eLife Assessment

In this valuable study, the authors present traces of bone modification on ~1.8 million-year-old proboscidean remains from Tanzania, which they infer to be the earliest evidence for stone-tool-assisted megafaunal consumption by hominins. Challenging published claims, the authors argue that persistent megafaunal exploitation roughly coincided with the earliest Acheulean tools. Notwithstanding the rich descriptive and spatial data, the behavioral inferences about hominin agency rely on traces (such as bone fracture patterns and spatial overlap) that are not unequivocal; the evidence presented to support the inferences thus remains incomplete. Given the implications of the timing and extent of hominin consumption of nutritious and energy-dense food resources, as well as of bone toolmaking, the findings of this study will be of interest to paleoanthropologists and other evolutionary biologists.

eLife Assessment

This is an important study that identifies the developmental time window during which re-expression of TCF4 mutated in Pitt-Hopkins syndrome, can rescue phenotypic features of brain function in a TCF4 knockout mouse. The study presents compelling data using a viral transgenic intersection approach to show that TCF4 expression is required early in perinatal life. These findings have implications for the timing of possible gene therapy in people with Pitt-Hopkins-associated TCF4 mutations.

eLife Assessment

This study proposes a cross-species transcriptomic framework to predict vaccine reactogenicity, with implications for preclinical vaccine safety assessment. The findings show that mouse muscle transcriptomic signatures capture conserved inflammatory programs and can identify highly reactogenic formulations, with supportive but limited evidence for finer discrimination among licensed human vaccines. Overall, the work establishes a valuable foundation for translational biomarkers of reactogenicity, although the strength of evidence for broad cross-species predictive performance remains incomplete and would benefit from further validation.

eLife Assessment

The study presents a valuable finding on the ubiquitin-dependent regulatory loop in which proapoptotic Bim is targeted to the E3 ubiquitin ligase Cul5-Wsb2-mediated degradation through its sequestration by BCL2 proteins. The conclusions are supported by incomplete evidence and would benefit from additional experiments addressing both the mechanistic understanding and the physiological/cancer-related significance of the study.

eLife Assessment

This important work substantially advances our understanding of the role of synaptotagmin-7 (Syt7) in short-term plasticity at cortical glutamatergic synapses. The evidence supporting the conclusions is convincing, with rigorous and elegant quantal-level iGluSnFR imaging and failure-based analyses at single boutons. The work will be of broad interest to synaptic physiologists and molecular biologists.

eLife Assessment

This study presents useful findings on the molecular mechanisms driving female-to-male sex reversal in the ricefield eel (Monopterus albus) during aging, which would be of interest to biologists studying sex determination. The manuscript describes an interesting mechanism potentially underlying sex differentiation in M. albus. However, the current data are incomplete and would benefit from more rigorous experimental approaches.

eLife Assessment

This manuscript details important findings that DNA polymerase kappa shows age-related changes in subcellular localization within different cell types in the brains of mice, from the nucleus in young cells to the cytoplasm in old cells. The authors' findings suggest that age-related alterations in POLK localization could drive mechanistic and functional changes in the aging brain. The authors provide solid evidence for their study, with data broadly supporting their claims with minor weaknesses.

eLife Assessment

This structural biology study provides insights into the assembly of the GID/CTLH E3 ligase complex. The multi-subunit complex forms unique, ring shaped assemblies and the findings presented here describe a "specificity code" regulates formation of subunit interfaces. The data supporting the conclusions are convincing, both in thoroughness and rigor. This study will be valuable to biochemists, structural biologists, and could lay foundation for novel designed protein assemblies.

eLife Assessment

This important study provides mechanistic evidence that tea-adapted two-spotted spider mite overcomes green tea catechin defenses via the horizontally transferred dioxygenase TkDOG15, supporting a two-step adaptation model, combining enzyme refinement and inducible upregulation. The evidence is convincing because multi-omics signals converge with functional validation (RNAi knockdown and recombinant enzyme assays) and well-controlled behavioral/toxicity assays to link TkDOG15 activity and expression to survival and feeding on tea.

eLife Assessment

This convincing study examines a novel interaction of RAB5 with VPS34 complex II. Structural data are combined with site-directed mutagenesis, sequence analysis, biochemistry, yeast mutant analysis, and prior data on RAB1-VPS34 and RAB5-VPS34 interactions to provide a new perspective on how RAB GTPases recruit related but distinct VPS34 complexes to different organelles. Although minor revisions are recommended, the judgment is that this work represents a fundamental advance in our understanding of VPS34 localization and regulation.

eLife Assessment

Li et al. present an important and innovative study linking developmental changes in sleep to ecological context in Drosophila mojavensis, and propose that sleep at one stage of an animal's life might anticipate needs at a future stage. The results fit well with this model, but are correlative in nature. The work is convincing, scientifically rigorous, and effectively bridges sleep biology and evolutionary ecology, opening promising new directions for the field.

eLife Assessment

This work presents a brain-wide atlas of vasopressin (Avp) and vasopressin receptor 1A (Avpr1a) mRNA expression in mouse brains using high-resolution RNAscope in situ hybridization. The single-transcript approach provides precise localization and identifies additional brain regions expressing Avpr1a, creating a valuable resource for the field. The revised manuscript is clearer and more impactful, with improved figures, stronger data organization, and enhanced scholarship through added context and citations. Overall, the evidence is compelling, and the atlas should be broadly of use to researchers studying vasopressin signaling and related neural circuits.

eLife Assessment

This study provides useful insights regarding the alterations of sleep architecture in a knock-in mouse model of Alzheimer's Disease (AD). These include age-related hyperactivity that is typically associated with increased arousal, a normal homeostatic response to sleep loss, and a stronger AD-like phenotype in females. Although the analyses are robust, evidence for the proposed mechanisms underlying abnormal sleep architecture is incomplete. Overall, the study may have a focused impact on the sleep and AD fields.

eLife Assessment

This important work employed a recent functional muscle network analysis to evaluate rehabilitation outcomes in post-stroke patients. While the research direction is relevant and suggests the need for further investigation, the strength of evidence supporting the claims is incomplete. Muscle interactions can serve as biomarkers, but improvements in function are not directly demonstrated, and the method's robustness is not benchmarked against existing approaches.

eLife Assessment

This important work introduces a splitGFP-based labeling tool with an analysis pipeline for the synaptic scaffold protein bruchpilot, with tests in the adult Drosophila mushroom bodies, a learning center in the Drosophila brain. The evidence supporting the conclusions is convincing.

eLife Assessment

This useful study uses creative scalp EEG decoding methods to attempt to demonstrate that two forms of learned associations in a Stroop task are dissociable, despite sharing similar temporal dynamics. However, the evidence supporting the conclusions is incomplete due to concerns with the experimental design and methodology. This paper would be of interest to researchers studying cognitive control and adaptive behavior, if the concerns raised in the reviews can be addressed satisfactorily.

eLife Assessment

Stearns and Poletti present a technically impressive study that aims to uncover a deeper understanding of microsaccade function: their role in perceptual modulation and the associated temporal dynamics. The question is useful, and advances prior work by adding temporal granularity. However, the strength of the evidence is currently incomplete. Additional analysis is needed to control for the effects of endogenous attention and to demonstrate changes in perceptual performance.

eLife Assessment

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

eLife Assessment

This important study provides evidence for dynamic coupling between translation initiation and elongation that can help maintain low ribosome density and translational homeostasis. The authors combine single-molecule imaging with a new approach to analyze mRNA translation kinetics using Bayesian modeling. This work is overall solid and will be of interest to those studying translational regulation.

eLife Assessment

This manuscript reports important findings indicating that cell cycle progression and cytokinesis both contribute to the transition from early to late neural stem cell fates. Loss-of-function experimental evidence convincingly shows that disrupting the cell cycle or cytokinesis can alter cell fate. This work sets the stage for future investigations into the underlying mechanisms linking the cell cycle to the expression of temporal factors controlling cell fate.

eLife Assessment

This valuable study investigates the computational role of top-down feedback - a property found in biological circuits - in artificial neural network (ANN) models of the neocortex. Using hierarchical recurrent ANNs in an audiovisual integration task, the authors show that an anatomically inspired feedback motif induces a stable visual bias consistent with human perception and yields modest but meaningful benefits for learning dynamics and robustness. The strength of evidence is solid: the modeling, analyses, and controls mostly support the central claim that top-down feedback motifs impose persistent inductive biases that shape functional specialization and behavior. But the evidence for a broad, general framework that predicts behavior remains only partially supported, and the Methods would benefit from a compact, reproducible summary of hyperparameters and architectural details.

eLife Assessment

This study investigates the temporal dynamics of neural activity preceding self-initiated movements and makes a valuable contribution to this field. The authors identify key methodological and analytical limitations in previous work and introduce a novel approach to overcome the shortcomings in assessing how predictive neural activity is of an upcoming event. Applying generally solid methods and analyses, they show that a late-stage neural event, ~100 ms before movement execution, is most predictive of upcoming movements, whereas earlier neural activity is less informative. Although interesting, additional analyses are needed to strengthen confidence in this central claim.

eLife Assessment

This fundamental study reports the effects of the psychedelic drug psilocin on iPSC-derived human cortical neurons, analyzing different aspects of structural and functional neuronal plasticity. The evidence is convincing and supports the value of using iPSC-derived human cortical neurons for testing the potentially translational effects of psilocin and other psychedelic-related compounds.

eLife Assessment

This study provides valuable insight into stress biology by showing that yeast populations can rapidly evolve a trehalose producing resting state that substantially improves survival and rapid regrowth after freeze-thaw. This finding is consistent with the role of trehalose metabolism as a biophysical adaptation that is broadly relevant to the community working on environmental resilience and dormancy. The evidence is convincing: the authors integrate experimental evolution, cell-level biophysical measurements, and modelling in a mutually reinforcing manner.

eLife Assessment

The authors present an important set of data implicating ETFDH as an epigenetically suppressed gene in cancer with tumor suppressive functions. The evidence is convincing, with the authors demonstrating that suppression of ETFDH activity results in accumulation of amino acids that impact metabolism via hyperactive mTORC1.

eLife Assessment

This manuscript investigates the extremely interesting and important claim that the human hippocampus represents interactions with multiple social interaction partners on two relatively abstract social dimensions - and that this ability correlates with the social network size of the participant. This research potentially demonstrates the intricate role of the hippocampus in navigating our social world. While most of the results are solid, the paper requires some further clarification.

eLife Assessment

This study presents a potentially valuable exploration of the role of thalamic nuclei in language processing. The results will be of interest to researchers interested in the neurobiology of language. However, the evidence is incomplete to support robust conclusions at this point.

eLife Assessment

This manuscript reports high-resolution cryo-EM structures of a trimethylamine N-oxide demethylase and advances the intriguing hypothesis that the enzyme is bifunctional, coupling TMAO demethylation to formaldehyde capture at a distal tetrahydrofolate-binding site via an enclosed intramolecular tunnel. Supported by biochemical assays and molecular dynamics simulations, the structural findings are valuable and potentially of broad interest, particularly the unusual oligomeric architecture and the proposed conduit for a reactive intermediate. However, the mechanistic framework is considered incomplete, raising substantial concerns regarding the proposed catalytic mechanism, metal/cofactor requirements, and the interpretation of biochemical data supporting formaldehyde channelling.

eLife Assessment

This study provides a useful contribution to understanding how wearable augmentation devices interact with human proprioception, using a longitudinal design over a single session. Results demonstrate that the perceptual representation of the biological finger and augmentation device changes across different phases of device exposure and use. The evidence supporting a representational change over time is solid, although it is still not clear whether these changes reflect three distinct phases of sensorimotor plasticity, as argued, versus 'washout' or adaptation effects. This work will be of interest to researchers studying body representation, sensorimotor learning, and human-technology interaction.

eLife Assessment

This paper investigates the Achilles' heel of an aggressive pediatric bone cancer known as Ewing sarcoma. The authors aimed to better understand how its previously undruggable drivers mediate oncogenic mechanisms using several omics approaches. Transcriptomic changes aligned with their findings provide convincing evidence for the role of a short alpha helix in the DNA binding domain of FLI1 in modulating binding to GGAA microsatellites and promoting enhancer activity. The study provides valuable new insights into the underlying oncogenic mechanisms in Ewing sarcoma.

eLife Assessment

This fundamental manuscript describes how the posterolateral cortical amygdala (plCoA) generates appetitive or aversive behaviors in response to odors. By combining optogenetic stimulation, single-cell RNA sequencing, and spatial analysis, the authors identify a topographically organized circuit within plCoA that governs these behaviors. The manuscript shows convincingly that multiple features (spatial, genetic, and projection) contribute to overall population encoding of valence. Overall, the authors conduct many challenging experiments, each of which contains the relevant controls, and the results are interpreted within the framework of their experiments.

eLife Assessment

This is an important study with direct implications for the rational selection of antimalarial drug combinations. The authors present data demonstrating antagonism between 4-aminoquinoline antimalarials and peroxide drugs under physiologically relevant conditions, including robust effects at the trophozoite stage and for chloroquine at the ring stage. While the conclusions are based on in vitro assays and further work will be needed to fully resolve the underlying mechanism, the findings are convincing and provide a strong rationale for evaluating drug combinations in relevant preclinical models prior to clinical testing.

eLife Assessment

In this study, the authors identify EOLA1 as a novel mitochondrial protein required for mitochondrial translation and normal cardiac function. The characterization of the molecular role of EOLA1 is still incomplete, and additional controls will be necessary. Nevertheless, the identification of a novel factor critical for mitochondrial gene expression and oxidative phosphorylation will be useful for cell biologists working on mitochondrial dysfunction.

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

This fundamental work reveals that the accessibility of the unstructured C-terminal tail of α-tubulin differs with the state of the microtubule lattice. Accessibility increases with the expansion of the lattice induced by GTP and certain MAPs, which can then dictate the subsequent interactions between MAPs and microtubules, and post-translational modifications of tubulin tails. The evidence supporting the conclusion is compelling, although the characterisation of the probes does not answer whether they directly affect the lattice or expose the C-terminal tail of α-tubulin. The probes can be used as tools in the future to study differences in microtubule lattice regulation under different conditions both in vitro and in vivo. This work will be of great interest to the cytoskeleton field.

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

This study makes an important contribution by revealing how saccades selectively disrupt spatial working memory while sparing other object features, and by demonstrating how this mechanism is altered in aging and neurodegeneration. The findings are supported by convincing evidence derived from well-controlled eye-tracking experiments and systematic generative model comparisons. Together, the work provides a computationally grounded framework that is of importance for understanding trans-saccadic memory and its clinical relevance.

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

The study proposed hemogenic endothelium in adult BM using lineage tracing. Though the study is potentially valuable, the data is incomplete due to the lack of control and insufficient analysis. There is potential for the study to be improved by further revision.

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

This article reports an algorithm for inferring the presence of synaptic connection between neurons based on naturally occurring spiking activity of a neuronal network. One key improvement is to combine self-supervised and synthetic approaches to learn to focus on features that generalize to the conditions of the observed network. This valuable contribution is currently supported by incomplete evidence.

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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

eLife Assessment

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