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 study illustrates a valuable application of BID-seq to bacterial RNA, allowing transcriptome-wide mapping of pseudouridine modifications across various bacterial species. The evidence presented includes a mix of solid and incomplete data and analyses, and would benefit from more rigorous approaches. The work will interest a specialized audience involved in RNA biology.

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 convincing study, which is based on a survey of researchers, finds that women are less likely than men to submit articles to elite journals. It also finds that there is no relation between gender and reported desk rejection. The study is an important contribution to work on gender bias in the scientific literature.

eLife Assessment

This valuable study introduces a modern and accessible PyTorch reimplementation of the widely used SpliceAI model for splice site prediction. The authors provide convincing evidence that their OpenSpliceAI implementation matches the performance of the original while improving usability and enabling flexible retraining across species. These advances are likely to be of broad interest to the computational genomics community.

eLife Assessment

This fundamental work advances our understanding of how SP5 and SP8 promote neuromesodermal competent progenitors in murine embryos. Generally the evidence is compelling, with strong developmental genetics, transcriptomic, and genomic transcription binding surveys contributing to the strength of the data. Some of the language could be softened to avoid overinterpretation of the data, and figures and diagrams could be improved.

eLife Assessment

This work presents important information on rhythmicity of overlapping target and distractor processing and how this affects behaviour. The methods are, in general, clearly laid out and defensible, with several supplementary analyses leading to a solid base of evidence for their claims.

eLife Assessment

This fundamental work significantly advances our understanding of gravity sensing and orientation behavior in the ctenophore, an animal of major importance in understanding the evolution of nervous systems. Through comprehensive reconstruction with volumetric electron microscopy, and time-lapse imaging of cilia motion, the authors provide compelling evidence that the aboral nerve net coordinates the activity of balancer cilia. The resemblance to the ciliomotor circuit in marine annelids provides a fascinating example of how neural circuits may convergently evolve to solve common sensorimotor challenges.

eLife Assessment

This valuable work presents a novel computational framework for modeling macroscopic traveling waves in the mouse cortex by integrating open-source connectomic and transcriptomic data into a spiking network model. This approach allows the computational model to assign excitatory/inhibitory connections based on neurotransmitter profiles and extends simulations to the 3D domain. The authors present results that demonstrate how spatiotemporal dynamics such as slow oscillations (0.5-4 Hz) emerge and self-organize at the whole-brain scale. This study provides convincing initial insights into the structural basis of traveling waves at the whole-brain scale in the mouse.

eLife Assessment

This study presents a valuable and rigorous molecular resource, offering subtype-specific insight into the composition of ribosome-associated protein complexes in the developing cerebral cortex. The evidence is compelling in terms of data quality and is strongly supported by the results, given the rigorous technical execution. However, the findings remain primarily descriptive, as the study lacks functional validation to support mechanistic conclusions.

eLife Assessment

This valuable model-based study seeks to mimic bat echolocation behavior and flight under conditions of high interference, such as when large numbers of bats leave their roost together. Although some of the assumptions made in the model may be questioned, the simulations convincingly suggest that the problem of acoustic jamming in these situations may be less severe than previously thought. This finding will be of broad interest to scientists working in the fields of bat biology and collective behaviour.

eLife Assessment

In this fundamental manuscript, Richter et al. present a thorough anatomical characterization of the Drosophila melanogaster larval pharyngeal sensory system, which is involved in taste-guided behaviors. This study fills a major gap in the larval sensory map, providing a compelling neuroanatomical foundation for future investigations into sensory circuits and behavior. The data presented here are of exceptional quality and will be of interest to the Drosophila neurobiology community.

eLife Assessment

This important work provides convincing evidence of the cognitive and neural mechanisms that give rise to feelings of shame and guilt, as well as their transformation into compensatory behavior. The authors combine well-designed manipulations of responsibility and harm with computational cognitive modeling and neuroimaging to provide a comprehensive account of how emotions are experienced and acted upon.

eLife Assessment

This is a useful analysis of STORM data that characterizes the clustering of active zones in retinogeniculate terminals across ages and in the absence of retinal waves. The design makes it possible to relate fixed time point structural data to a known outcome of activity-dependent remodeling. However, the evidence is incomplete, weakening the claims the authors make regarding how activity influences the clustering of these synapses. This basic criticism has not improved with revisions.

eLife Assessment

This manuscript uses modeling approaches to provide mechanistic insight into the structural and dynamic properties of enhancer-promoter interactions in Drosophila. Given the interest in this field, this is a timely approach, and the results give useful insights by providing predictions about the processivity of cohesin loop extrusion in Drosophila and concluding that the compartmental interaction strength is poised near criticality in the coil-globule phase space. The evidence provided to support some of the conclusions is, however, incomplete and would be strengthened by better considering some of the caveats in the data used to constrain the models, such as the use of "homie" genetic elements in the dynamic data. There is insufficient evidence provided for the dynamics being criticality-driven, and in addition, consideration of alternative models would further strengthen the conclusions of the manuscript.

eLife Assessment

This paper explores the role of extracellular vesicles in providing extracellular matrix signals for migration of vascular smooth muscle cells. The evidence, based on cell culture experiments and supporting imaging of human samples, is mostly convincing. The paper will be valuable for researchers investigating cell migration during vessel repair and atherogenesis.

eLife Assessment

Decron and colleagues combine common psychiatric treatments with a probabilistic reward learning task and trial-by-trial ratings of affect, confidence, and engagement. Using computational cognitive modeling, they show that, while both treatments serve to counter negative biases in affect and confidence, cognitive distancing and antidepressant medication have dissociable effects on subjective evaluations and reward-based choice behavior. This work provides convincing evidence regarding an important line of investigation into the dynamic integration of affect, cognition, and learning.

eLife Assessment

This important study describes the development and validation of an Automated Reproducible Mechano-stimulator (ARM), a tool for standardizing and automating tactile behavior experiments. The data supporting the use of the ARM system are compelling, and demonstrate that by removing experimenter effects on animals, it reduces variability in various parameters of stimulus application. Moreover, the authors demonstrate that any noise emitted from the ARM does not induce an increased stress state. Once commercially available, the ARM system has the potential to increase experimental reproducibility between laboratories in the somatosentation and pain fields.

eLife Assessment

This paper discusses the cognitive implications of potential intentional burial, wall engraving creation, and fire as light source use behaviors by relatively small-brained Homo naledi hominins. The discussion presented in the paper is valuable theoretically in its healthy questioning of prior assumptions concerning the socio-biological constraints of hominin meaning-making behavior. The discussion also contributes practically given that these behaviors have been ascribed to Homo naledi in two associated papers. Still, the strength of evidence in this contribution relies on the validity of the conclusions from the two associated papers, which remain actively questioned. The ultimate assessment of this work will vary among individual readers depending on how they view this debate, but if the conclusions from the associated papers hold up, the conclusions in the current paper can be considered solid.

eLife Assessment

This manuscript introduces a useful protein-stability-based fitness model for simulating protein evolution and unifying non-neutral models of molecular evolution with phylogenetic models. The model is applied to five viral proteins that are of structural and functional importance. While the general modelling approach is solid, and effectively preserves folding stability, the evidence for the model's predictive power remains limited, since it shows little improvement over neutral models in predicting protein evolution. The work should be of interest to researchers developing theoretical models of molecular evolution.

eLife Assessment

This work characterizes the function and localization of SLC4A1 variants associated with distal renal tubular acidosis in human patients. Cell culture and limited animal studies provide partial but incomplete support to the authors' claim that the variants disrupt normal protein degradative flux by alkalinizing the intracellular pH. The study is valuable in providing preliminary evidence for future exploration of the link between intracellular pH regulation by SLC4A1 and kidney cell function in vivo.

eLife Assessment

This study presents the important finding that lysosomal damage triggers inflammatory signaling through ubiquitination and the TAB-TAK1-IKK-NF-kB axis. The data obtained from the unbiased transcriptomic and proteomic analyses are convincing and provide invaluable information to the field. Although further experiments will be required to clarify how TAB2/3 are recruited after various types of lysosome damage, this work will be of interest to researchers in the fields of organelle biology and inflammation.

eLife Assessment

This important work describes the adaptation and evaluation of two red-shifted anion channelrhodopsins (RubyACRs) for optogenetic inhibition in Drosophila. The study provides convincing evidence for the effectiveness of RubyACRs in fly neurons, including electrophysiology, calcium imaging, and behavioral analysis. With minor revisions to address potential toxicity and compatibility with 2-photon imaging, this paper and the publicly available fly lines it describes will be resources that are of value to the neuroscience community.

eLife Assessment

This manuscript is useful as it demonstrates that Rv2577, a Fe³⁺/Zn²⁺-dependent metallophosphatase, is secreted by Mycobacterium bovis BCG and localizes to the nucleus of mammalian cells, altering transcriptional and inflammatory responses. However, the study is incomplete as it lacks activity validation in macrophage cells and with virulent Mycobacterium tuberculosis strains. It is necessary to confirm Rv2577 secretion from a virulent strain and to clarify the direct or indirect role of MmpE in modulating host pathways, together with mechanistic insight into how MmpE influences lysosomal biogenesis and trafficking.

eLife Assessment

This important study applies a novel signal decomposition method to disentangle distinct signals contributing to the decision-making process, and provides convincing evidence for the operation of separate sensory encoding, attentional orienting, and ramping evidence accumulation signals. These findings are consistent with previous work, except for the absence of a motor component, which may relate to limitations of the analysis approach.

eLife Assessment

This important report describes the changing antiviral activity of IFIT1 across mammals and in response to distinct viruses, likely as a result of past arms races. One of the main strengths of the manuscript is the breadth of mammalian IFIT1 orthologs and viruses that were tested, as well as the thoroughness of the positive selection analysis. Overall the evidence is convincing, and the discussion conveys well the limitations due to physical interactions with other IFITs that are not accounted for.

eLife Assessment

In this valuable contribution, the authors present a novel and versatile probabilistic tool for classifying tracking behaviors and understanding parameters for different types of single-particle motion. The software package will be broadly applicable to single-particle tracking studies. The methodology has been convincingly tested by computational comparisons and experimental data, although the mathematical foundation for the hypothesis testing method can be further strengthened.

eLife Assessment

The paper reports valuable findings about the mechanism of regulation of the heat shock response in plants that acts as a brake to prevent hyperactivation of the stress response, which have theoretical or practical implications for a subfield. The study presented by the authors provides solid methods, data, and analysis that broadly support the claims. This report presents helpful information regarding new spliced HSFs forms in Arabidopsis that highlights key information in the understanding of heat stress and plant growth.

eLife Assessment

This manuscript reports the development and characterization of iGABASnFR2, a genetically encoded GABA sensor that demonstrates substantially improved performance compared to its predecessor, iGABASnFR1. The work is comprehensive and methodologically rigorous, combining high-throughput mutagenesis, functional screening, structural analysis, biophysical characterization, and in vivo validation. The significance of the findings is fundamental, and the supporting evidence is compelling. iGABASnFR2 represents a notable advance in GABA sensor engineering, enabling enhanced imaging of GABA transmission both in brain slices and in vivo, and constitutes a timely, technically robust addition to the molecular toolkit for neuroscience research.

eLife Assessment

This paper performs a valuable critical reassessment of anatomical and functional data, proposing a reclassification of the mouse visual cortex in which almost all the higher visual areas are consolidated into a single area V2. However, the evidence supporting this unification is incomplete, as the key experimental observations that the model attempts to reproduce do not accurately reflect the literature. This study will likely be of interest to neuroscientists focused on the mouse visual cortex and the evolution of cortical organization.

eLife Assessment:

This study addresses valuable questions about the neural mechanisms underlying statistical learning of room acoustics, combining robust behavioral measures with non-invasive brain stimulation. The behavioral findings are strong and extend previous work in psychoacoustics, but the TMS results are modest, with methodological limitations and over-interpretation that weaken the mechanistic conclusions. The strength of evidence is therefore incomplete, and a more cautious interpretation of the stimulation findings, alongside strengthened analyses, would improve the manuscript.

eLife Assessment

This important study evaluates a model for multisensory correlation detection, focusing on the detection of correlated transients in visual and auditory stimuli. Overall, the experimental design is sound and the evidence is compelling. The synergy between the experimental and theoretical aspects of the article is strong, and the work will be of interest to both neuroscientists and psychologists working in the domain of sensory processing and perception

eLife Assessment

This study is a fundamental advance in the field of developmental biology and transcriptional regulation that demonstrates the use of hPSC-derived organoids to generate reproducible organoids to study the mechanisms that drive neural tube closure. The work is exceptional in its development of tools to use CRISPR interference to screen for genes that regulate morphogenesis in human PSC organoids. The additional characterization of the role of specific transcription factors in neural tube formation is solid. The work provides both technical advances and new knowledge on human development through embryo models.

eLife Assessment

This useful manuscript reports mechanisms behind the increase in fecundity in response to sub-lethal doses of pesticides in the crop pest, the brown plant hopper. The authors hypothesize that the pesticide works by inducing the JH titer, which through the JH signaling pathway induces egg development, for which the evidence was judged to be solid.

eLife assessment

This is a useful study that applies deep transfer learning to assign patient-level disease attributes to single cells of T2D and non-diabetic patients, including obese patients. This analysis identified a single cluster of T2D-associated β-cells; and two subpopulations of obese- β-cells derived from either non-diabetic or T2D donors. The findings were validated at the protein level using immunohistochemistry on islets derived from non-diabetic and T2D organ donors, contributing solid experimental evidence for the computational analyses.

eLife Assessment

This is an important study that takes a key step towards understanding developmental disorders linked to mutations in the O-GlcNAc transferase enzyme by generating a mouse model harboring the C921Y mutation. The study thoroughly examines behavioral and anatomical differences in these mice and finds behavioral hyperactivity and learning/memory deficits, as well as phenotypic differences in skull and brain formation. However, the experimental evidence is incomplete owing to discrepancy in OGT protein/RNA levels in the C921Y mutant mice in this paper and the previous paper ("Neurodevelopmental defects in a mouse model of O-GlcNAc transferase intellectual disability "). This line of research will benefit from investigation of the differences in associated glycoproteins and mechanistic insights. This study will be of interest to those studying neurodevelopment, learning and behavior, or associated brain mechanisms.

eLife Assessment

This useful study uses fiber photometry, implantable lenses, and optogenetics to show that a subset of subthalamic nucleus neurons is active during movement, and that active but not passive avoidance depends in part on STN projections to substantia nigra. The strength of the evidence for these claims is solid, whereas evidence supporting the claims that STN is involved in cautious responding or the speed of avoidance is incomplete. This paper will be of interest to basic and applied behavioural neuroscientists working on avoidance if suitably streamlined to support the strongest claims.

eLife Assessment

This study demonstrates the potential role of 17α-estradiol in modulating neuronal gene expression in the aged hypothalamus of male rats, identifying key pathways and neuron subtypes affected by the drug. While the findings are useful and provide a foundation for future research, the strength of supporting evidence is incomplete due to the lack of female comparison, a young male control group, unclear link to 17α-estradiol lifespan extension in rats, and insufficient analysis of glial cells and cellular stress in CRH neurons.

eLife Assessment

This manuscript introduces a potentially valuable large-scale fMRI dataset pairing vision and language, and employs rigorous decoding analyses to investigate how the brain represents visual, linguistic, and imagined content. The current manuscript blurs the line between a resource paper and a theoretical contribution, and the evidence for truly modality-agnostic representations remains incomplete at this stage. Clarifying the conceptual aims and strengthening both the dataset technicality and the quantitative analyses would improve the manuscript's significance for the fields of cognitive neuroscience and multimodal AI.

eLife Assessment

This study provides new important insights concerning pathogen variant-specific reproduction parameters from molecular sequencing and case finding. The methods for inferring which variants will likely emerge in subsequent epidemic cycles are solid. This article is of broad interest to infectious disease epidemiology researchers and mathematical modellers of the COVID-19 pandemic.

eLife Assessment

This study provides an important extension of credibility-based learning research with a well-controlled paradigm by showing how feedback reliability can distort reward-learning biases in a disinformation-like bandit task. The strength of evidence is convincing for the core effects reported (greater learning from credible feedback; robust computational accounts, parameter recovery) but incomplete for the specific claims about heightened positivity bias at low credibility, which depend on a single dataset, metric choices (absolute vs relative), and potential perseveration or cueing confounds. Limitations concerning external validity and task-induced cognitive load, and the use of relatively simple Bayesian comparators, suggest that incorporating richer active-inference/HGF benchmarks and designs that dissociate positivity bias from choice history would further strengthen this paper.

eLife Assessment

This valuable study combined careful computational modeling, a large patient sample, and replication in an independent general population sample to provide a computational account of a difference in risk-taking between people who have attempted suicide and those who have not. It is proposed that this difference reflects a general change in the approach to risky (high-reward) options and a lower emotional response to certain rewards. Evidence for the specificity of the effect to suicide, however, is incomplete, which would require additional analyses.

eLife Assessment

This study presents a valuable finding on the molecular mechanisms that govern GABAergic inhibitory synapse function. The authors propose that Endophilin A1 serves as a novel regulator of GABAergic synapses by acting as a component of the inhibitory postsynaptic density. The findings are convincing and likely to interest a broad audience of scientists focusing on inhibitory synaptic transmission, the excitation-inhibition balance, and its disruption in disorders such as epilepsy.

Editors Assessment:

This paper presents present the genome sequencing of the house sparrow (Passer domesticus) carrying out genome assembly and annotation using in silico approaches with tools that could be a valuable resource for understanding passerine evolution, biology, ethnology, geography, and demography. The final genome assembly was generated using short read sequencing and a computational workflow that included Shovill, SPAdes, MaSuRCA, and BUSCO benchmarking. Producing a 922 MB reference genome with 24,152 genes. The first draft was significantly smaller than this but peer review provided suggestions on how to improve the assembly quality. And after a few attempts and assembly with a reasonable size and BUSCO score was achieved. This openly available data potentially serving as a valuable resource for checking adaptation, divergence, and speciation of birds.

This evaluation refers to version 2 of the preprint

eLife Assessment

This paper presents an important theoretical exploration of how a flexible protein domain with multiple DNA binding sites may simultaneously provide stability to the DNA-bound state and enables exploration of the DNA strand. The authors propose a mechanism ("octopusing") for protein doing a random walk while bound to DNA which simultaneously enables exploration of the DNA strand and enhances the stability of the bound state. This study presents compelling evidence that their findings has implications for the way intrinsically disordered regions (IDR) of transcription factors proteins (TF) can enhance their ability to efficiently find their binding site on the DNA from which they exert control over the transcription of their target gene. The paper concludes with a comparison of model predictions with experimental data which gives further support to the proposed model.

eLife Assessment

This is an important study that examines the impact of Streptococcus pneumoniae genetics on its in vitro growth kinetics, aiming to identify potential targets for vaccines and therapeutics. The study identified significant variations in growth characteristics among capsular serotypes and lineages, linked to phylogeny and high heritability, but genome-wide association studies did not reveal specific genomic loci associated with growth features independent of the genetic background. The evidence supporting these findings is convincing.

eLife Assessment

This important study describes newly identified light-gated ion channel homologs (channelrhodopsins, ChRs) in several protist species, with a primary focus on the biophysical characterization of ChRs of ancyromonads. The authors employed a powerful combination of bioinformatics, manual and automated patch-clamp electrophysiology, absorption spectroscopy, and flash photolysis. Additionally, they evaluated the applicability of the newly discovered anion-conducting ChRs in cortical neurons of mouse brain slices and in living C. elegans worms. The evidence supporting most of the claims is compelling, and this work will be of interest to the microbial rhodopsin community and neuro- and cardioscientists utilizing optogenetics in their research.

eLife Assessment:

In this revised version, the authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide compelling evidence that the existence of a dense cage-like pericellular structure containing laminin γ1 and α4 and collagen IV is key to fixing the perisinusoidal localization of MK and preventing their premature intravasation. Adhesion of MK to this ECM cage is dependent on integrin beta1 and beta3 expressed by MK. This strong conclusion is based on the use of state-of-the art techniques such f primary murine bone marrow MK cultures, mice lacking ECM receptors, namely integrin beta1 and beta3 null mice, as well as high-resolution 2D and 3D imaging. The study provides valuable insight into the role of cell-matrix interactions in MK maturation and provides an interesting model with practical implications for the fields of hemostasis and thrombosis.

eLife Assessment

This paper is important in demonstrating a requirement for sulfation in organizing apical extracellular matrix (aECM) during tubulogenesis in Drosophila melanogaster. The authors identify and characterize the organization of some of the first known components of the non-chitinous aECM in the Drosophila salivary gland tube, and these findings are supported by convincing data. This study would be of interest to developmental and cell biologists.

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

eLife Assessment

This valuable study concerns a highly interesting and biologically relevant topic, the regulation of the PIN auxin transporter, which is of broad interest to the plant biology community. The authors propose NPY1 to act downstream of PID in auxin-mediated development by modulating PIN phosphorylation, which, if experimentally solidified, would expand our understanding of PIN regulation. While the genetic evidence is solid, the mechanistic role of NPY1 and the functional relevance of phosphorylated PIN residues are still uncertain. There are also concerns regarding experimental rigor and methodological transparency.

eLife Assessment

This important study investigates how signals from the nervous system can influence the response to different food sources. To demonstrate the role of specific neuronal and intestinal regulators in sensing food quality and modulating digestion, the authors present evidence through a combination of genetic screening, RNA-seq analysis, and functional studies. These findings shed light on an adaptive strategy to integrate food perception with physiological responses, with a mix of solid and convincing evidence supporting the work.

eLife Assessment

In this valuable manuscript, Rao and colleagues investigate the UFD-1/NPL-4 complex, which is involved in extracting misfolded proteins in the plasma membrane and the accumulation of pathogenic bacteria in the intestine. Using convincing methods, the authors find that knockdown of the ufd-1 and npl-4 genes leads to shortened lifespan of the nematode C. elegans and reduced accumulation of the bacterial pathogen P. aeruginosa in the intestine.

eLife Assessment

The identification of RBMX2 as a novel regulator linking mycobacterial infection to Epithelial-Mesenchymal Transition and cancer progression are fundamental findings that advance our understanding of a major research question about the link between infectious and non-infectious diseases, microbiology and oncology. It does so by introducing RBMX2 as a novel host factor, a potential therapeutic target and biomarker for both TB and lung cancer. The evidence provided is convincing because it is appropriate and the validated multi-omics methodologies used are in line with the current state of the art. This study will be of interest to scientists working in the fields of drug discovery, microbiology and oncology.

eLife Assessment

The article presents important findings describing the role of IL27 in maintaining HSCs at steady state, and in emergency haematopoiesis in response to T. goodii by limiting the inflammatory monocyte outcomes. The evidence provided are solid and support that IL27 acts at the level of HSCs and not downstream. This study will be of interest to immunologists and hematologists, as well as infectious disease researchers.

eLife Assessment

This important study describes the effect of beta-glucan innate training of macrophages and its effect on uptake of tumour cells and on the production of inflammatory cytokines. The data are convincing and show decreased phagocytic activity of apoptotic tumour cells accompanied by lower levels of secreted IL-1β, and in vivo findings are also provided in the revision. This finding has potential impact on designing potential macrophage-targeted cancer immuno-therapeutic approaches.

eLife Assessment

The manuscript provides important findings on how striatal projection neurons regulate spontaneous locomotion speed in the context of implicit motivation and distinct contextual valence. The manuscript presented convincing supporting evidence for the findings. This work will be of broad interest to neuroscientists in the fields of basal ganglia, movement control, and cognition.

eLife Assessment

In this manuscript, Park et al. developed a multiplexed CRISPR construct to genetically ablate the GABA transporter GAT3 in the mouse visual cortex, with effects on population-level neuronal activity. This work is important, as it sheds light on how GAT3 controls the processing of visual information. The findings are compelling, leveraging state-of-the-art gene CRISPR/Cas9, in vivo two-photon laser scanning microscopy, and advanced statistical modeling.

eLife Assessment

This important study presents a cross-species and cross-disciplinary analysis of cortical folding. The authors use a combination of physical gel models, computational simulations, and morphometric analysis, extending prior work in human brain development to macaques and ferrets. The findings support the hypothesis that mechanical forces driven by differential growth can account for major aspects of gyrification. The evidence presented, though limited in certain species-specific and parametric details, is overall strong and convincingly supports the central claims; the findings will be of broad interest in developmental neuroscience.

eLife Assessment

This valuable study introduces a novel experimental and modeling framework to quantify passive joint torques in Drosophila, revealing that passive forces are insufficient to support body weight, contrary to prior assumptions based on larger insects. The approach is technically impressive, combining genetic silencing, kinematic tracking, and biomechanical modeling. However, the strength of evidence is incomplete, limited by concerns about the specificity of the genetic tools, simplifications in the mechanical model, and limited functional interpretation.

eLife Assessment

This important study characterises the morphogenesis of cortical folding in the ferret and human cerebral cortex using complementary physical and computational modelling. Notably, these approaches are applied to charting, in the ferret model, known abnormalities of cortical folding in humans. The study finds that variation in cortical thickness and expansion account for deviations in morphology, and supports these findings using cutting-edge approaches from both physical gel models and numerical simulations. The strength of evidence is convincing, and although it could benefit from more quantitative assessment, the study will be of broad interest to the field of developmental neuroscience.

eLife Assessment

This is an important study reporting a new phenotype for a gene cluster that has previously been associated with the responses of the Gram-negative opportunistic pathogen Pseudomonas aeruginosa to flow fluid. Expression of the froABCD gene cluster is induced by HOCl in vitro and by activated immune cells, which produce these types of reactive chlorine species. Overall, the evidence presented by the authors is solid; however, the mechanism of fro-induction by HOCl remains unclear, and the evidence in support of the authors' claims is descriptive, which needs to be improved. This study is of interest to infection biologists interested in mechanisms of bacterial pathogenicity.

eLife Assessment

This study provides valuable insights into the host's variable susceptibility to Mycobacterium tuberculosis, using a novel collection of wild-derived inbred mouse lines from diverse geographic locations, along with immunological and single-cell transcriptomic analyses. While the data are convincing, a deeper mechanistic investigation into neutrophil subset functions would have further enhanced the study. This work will interest microbiologists and immunologists in the tuberculosis field.

eLife Assessment

In this important study, the authors develop a microfluidic "Vessel-on-Chip" model to study Neisseria meningitidis interactions in an in vitro vascular system. Compelling evidence demonstrates that endothelial cell-lined channels can be colonized by N. meningitidis, triggering neutrophil recruitment with advantages over complex surgical xenograft models. This system offers potential for follow-on studies of N. meningitidis pathogenesis, though it lacks the cellular complexity of true vasculature including smooth muscle cells and pericytes.

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

eLife Assessment

Yabaji et al. reports a fundamental study highlighting the mechanistic connection for susceptibility to TB infection via the sst1 locus, this was shown to involve increased IFN and Myc production causing the down-regulation of anti-oxidant defence genes and chronic lipidation. Ultimately, lipid peroxidation may underlie infectivity and macrophage dysfunction. Overall, the data presented are compelling, supported by a well designed multi-omics approach and the findings will be of broad interest to researchers investigating the molecular mechanisms of TB infection.

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

eLife Assessment

This useful study shows that stimuli of a certain size elicit theta oscillations in V1 neurons both in spikes and local field potentials, and monkeys performing a dot detection task on these stimuli show theta rhythmicity in their response times. This replicates previous findings showing rhythmic theta activity in V4 and behaviour when stimuli are presented in the receptive field along with a surrounding flanker stimulus. However, there is incomplete evidence that rhythmicity in neural activity is related to the rhythmicity in behavior, and the mechanisms underlying these oscillations remain unclear.

eLife Assessment

In this useful study, ectopic expression and knockdown strategies were used to assess the effects of increasing and decreasing Cyclic di-AMP on the developmental cycle in Chlamydia. The authors convincingly demonstrate that overexpression of the dacA-ybbR operon results in increased production of c-di-AMP and early expression of the transitionary gene hctA and late gene omcB. Whilst the authors have attempted to revise the submission, the model proposed in the revised manuscript is still not fully supported by the data presented.

eLife Assessment

This valuable study revisits the effects of substitution model selection on phylogenetics by comparing reversible and non-reversible DNA substitution models. The authors provide solid evidence that 1) it can be beneficial to include non-time-reversible models in addition to general time-reversible models when inferring phylogenetic trees out of simulated viral genome sequence data sets, and that 2) non time-reversible models may fit the real data better than the reversible substitution models commonly used in phylogenetics, a finding consistent with previous work.

eLife Assessment

This useful paper presents evidence from several experimental approaches that suggest that changes in membrane potential directly affect ERK signaling to regulate cell division. This result is relevant because it supports an ion channel-independent pathway by which changes in membrane voltage can affect cell growth. The reviewers point out that while some experimental results and interpretations are compelling, the strength of evidence is still incomplete and changes to the manuscript are needed to rule out other possible interpretations of the data.

eLife Assessment

This is a fundamental study providing molecular insight into how cross-talk between histone modifications regulates the histone H3K36 methyltransferase SETD2. The manuscript contains excellent quality data, and the conclusions are convincing and justified. This work will be of interest to many biochemists working in the field of chromatin biology and epigenetics.

eLife Assessment

This study identifies novel approaches to improving transgene expression in the injured mammalian myocardium through a combination of a tissue regeneration enhancer element and engineered AAVs - specifically, a liver-detargeting capsid, AAV.cc84, and an in vivo library screen-selected AAV-IR41. The evidence is convincing, and the AAV vectors are of fundamental value to the field of cardiac gene therapy. Future research exploring how to combine the features of AAV.cc84 and AAV-IR41 could yield an even more promising vector for therapeutic use.

eLife Assessment

This important study provides a conceptual advance in our understanding of how membrane geometry modulates the balance between specific and non-specific molecular interactions, reversing multiphase morphologies in postsynaptic protein assemblies. Using a mesoscale simulation framework grounded in experimental binding affinities, the authors successfully recapitulate key experimental observations in both solution and membrane-associated systems, providing novel mechanistic insight into how spatial constraints regulate postsynaptic condensate organization. The conclusions are supported by solid strength of evidence and the findings are of broad significance for both computational and experimental biologists

eLife Assessment

Kin selection and inclusive fitness have generated significant controversy. This paper reconsiders the general form of Hamilton's rule in which benefits and costs are defined as regression coefficients, with higher-order coefficients being added to accommodate non-linear interactions. The paper is a landmark contribution to the field with compelling, systematic analysis, giving clarity to long-standing debates.

eLife Assessment

The ratio of nuclei to cell volume is a well-controlled parameter in eukaryotic cells. This study now reports important findings that expand our understanding of the regulatory relationship between cell size and number of nuclei. The evidence supporting the conclusions is convincing obtained by applying appropriate and validated methodology in line with current state-of-the-art. The paper will be of broad interest for cell biologists and fungal biotechnologists seeking to understand mechanisms determining cell size and number of nuclei and why this knowledge might also be of importance for the production of enzymes and thus production strains not only of Aspergillus oryzae but also other industrially used fungi.

eLife Assessment

This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This is explained based on the differential interfacial tension hypothesis, and supported by pharmacological perturbations and numerical simulations using the vertex model. The study conveys a key message, but, as it stands, the strength of evidence is incomplete, and a more detailed analysis of the mechanistic origin of the different tensions and better comparison between experiments and simulations would strongly strengthen the message.

eLife Assessment

In this important study, the authors use computational modeling to explore how fast learning can be reconciled with the accumulation of stable memories in the olfactory bulb, where adult neurogenesis is prominent. Their model demonstrates that changes in excitability, plasticity, and susceptibility to apoptosis during the maturation of adult-born granule cells can help resolve the flexibility-stability dilemma. These compelling results provide a coherent picture of a neurogenesis-dependent learning process that is consistent with diverse experimental observations and may serve as a foundation for further experimental and computational studies.

eLife Assessment

This important work sets out to identify the neural substrates of associative fear responses in adult zebrafish. Through a compelling and innovative paradigm and analysis, the authors suggest brain regions associated with individual differences in fear memory. While several findings are well supported, aspects of the interpretation and presentation are partially incomplete, and the manuscript would benefit from adjusting key claims or including additional experiments. Nonetheless, this study showcases the strength of zebrafish for systems-level neuroscience and will be of broad interest to the neuroscience community.

eLife Assessment

This valuable study focuses on defining how the HSP70 chaperone system utilizes J-domain proteins to regulate the heat shock response-associated transcription factor HSF1. Using a combination of orthogonal techniques in yeast, this manuscript provides compelling evidence that the J-domain protein Apj1 facilitates attenuation of HSF1 transcriptional activity through a mechanism involving its dissociation from heat shock gene promoter regions. This work generates new insight into the mechanism of HSF1 transcriptional regulation and is a significant contribution of broad interest to cell biologists interested in proteostasis, chaperone networks, and stress-responsive signaling.

eLife Assessment

This important study provides compelling evidence that fever-like temperatures enhance the export of Plasmodium falciparum transmembrane proteins, including the cytoadherence protein PfEMP1 and the nutrient channel PSAC, to the red blood cell surface, thereby increasing cytoadhesion. Using rigorous and well-controlled experiments, the authors convincingly demonstrate that this effect results from accelerated protein trafficking rather than changes in protein production or parasite development. These findings significantly advance our understanding of parasite virulence mechanisms and offer insights into how febrile episodes may exacerbate malaria severity.

eLife Assessment

This study provides important insights into how the EBH domain of microtubule end-binding protein 1 (EB1) interacts with SxIP peptides derived from the MACF plus-end tracking protein. The revised manuscript includes convincing ITC and NMR experiments that clarify the role of flanking residues and address the influence of dimerization and cooperativity on binding. While some mechanistic aspects remain difficult to resolve experimentally, the data and analysis now more clearly justify the proposed "dock-and-lock" model and its interpretive value. This work will be of interest to structural biologists and biophysicists studying microtubule-associated protein interactions.

eLife Assessment

This useful study develops an individual-based model to investigate the evolution of division of labor in vertebrates, comparing the contributions of group augmentation and kin selection. The model incorporates several biologically relevant features, including age-dependent task switching and separate manipulation of relatedness and group-size benefits. However, the evidence remains inadequate to support the authors' central claim that group augmentation is the primary driver of vertebrate division of labor. Key modelling assumptions-such as floater dominance advantages, the absence of task synergy, and the narrow parameter space explored-restrict the potential for kin selection to produce division of labor, thereby limiting the generality of the conclusions.

eLife Assessment

This study introduces a novel and potentially valuable metric-phenological lag-to quantify the gap between observed and expected phenological shifts under climate warming. While the dataset is extensive and the framework is clearly defined, key assumptions (e.g., base temperature, linear forcing response) are not empirically tested, and the analysis underexplores key spatial and climatic gradients. The strength of evidence is mostly solid but would benefit from further validation and deeper analysis.

eLife Assessment

This paper presents a valuable software package, named "Virtual Brain Inference" (VBI), that enables faster and more efficient inference of parameters in dynamical system models of whole-brain activity, grounded in artificial network networks for Bayesian statistical inference. The authors have provided convincing evidence, across several case studies, for the utility and validity of the methods using simulated data from several commonly used models, but more thorough benchmarking could be used to demonstrate the practical utility of the toolkit. This work will be of interest to computational neuroscientists interested in modelling large-scale brain dynamics.

eLife Assessment

This important study identifies and partially characterises two proteins optimised for coordinated peptidoglycan degradation during two spore morphogenesis programs in the bacterium Myxococcus xanthus. The evidence supporting the conclusions is solid, although the description of the data is somewhat overstated. After some editing, the paper will be of interest to those studying peptidoglycan synthesis and reorganisation, which is a central aspect of microbial cell biology.

eLife Assessment

In this manuscript, Chen et al. used cryo-ET and in vitro reconstituted system to demonstrate that the autoinhibited form of LRRK2 can also assemble into filaments on the microtubule surface, with a new interface involving the N-terminal repeats that were disordered in the previous active-LRRK2 filament structure. The structure obtained in this study is the highest resolution of LRRK2 filaments done by subtomogram averaging, representing a major technical advance compared to the previous paper from the same group. This is an important study, especially considering the pharmacological implications of the effect of inhibitors of the protein. The strengths of the data are convincing, but the study would be considerably strengthened if the authors explored the physiological significance of the new interfaces and the incomplete decoration of microtubules described here.

eLife Assessment

This is an important study that demonstrates that blood pressure variability impairs myogenic tone and diminishes baroreceptor reflex. The study also provides evidence that blood pressure variability blunts functional hyperemia and contributes to cognitive decline. The evidence is compelling whereby the authors use appropriate and validated methodology in line with or more rigorous than the current state-of-the-art.

eLife Assessment

This study offers a valuable 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 valuable study, the authors use a cutting-edge method to perform voltage imaging of CA1 pyramidal cells in head-fixed mice running on a track while local field potentials (LFPs) were recorded in the contralateral hemisphere. The authors provide solid evidence of synchronous ensembles of CA1 pyramidal neurons that are associated with contralaterally recorded theta rhythms but not with contralaterally recorded sharp wave-ripples during exploration of a novel environment. The paper will be of interest to scientists who are interested in hippocampal neuronal coding of novel environments, particularly those with experimental questions that can benefit from this cutting-edge imaging technique.

eLife Assessment

This paper reports a valuable discovery that specific-mode electroacupuncture (EA) transiently opens the blood-brain barrier (BBB) in rats. The evidence is solid but lacks functional validation of BBB permeability changes. The work will be of interest to medical scientists working in the field of electroacupuncture and drug delivery.

eLife Assessment

This study presents valuable computational findings on the neural basis of learning new motor memories without interfering with previously learned behaviours using recurrent neural networks. The evidence supporting the claims of the authors is solid, but it would benefit from stronger and clearer links with experimental findings. This work will be of interest to computational and experimental neuroscientists working in motor learning.

eLife Assessment

This important study introduces the Life Identification Number (LIN) coding system as a powerful and versatile approach for classifying Neisseria gonorrhoeae lineages. The authors show that LIN codes capture both previously defined lineages and their relationships in a way that aligns with the species' phylogenetic structure. The compelling evidence presented, together with its integration into the PubMLST platform, underscores its strong potential to enhance epidemiological surveillance and advance our understanding of gonococcal population biology.

eLife Assessment

This study provides valuable insights into microtubule remodeling during liver-stage Plasmodium berghei development, demonstrating that deletion of the alpha-tubulin C-terminal tail impairs parasite growth in mosquitoes and abolishes infection in HeLa cells. The work is technically ambitious, employing advanced microscopy, genetic mutants, and pharmacological approaches. However, key claims are only partially supported due to incomplete evidence linking tubulin modifications to microtubule dynamics and uncertain antibody-based PTM detection.

eLife Assessment

This important work shows that fine particulate matter exposure to the lungs led to nociceptor-dependent neutrophilic inflammation. Likely macrophage-neuronal crosstalk, via release of artemin from macrophages and activation of Gfra3 on the JNC neuron, potentiated the response. The data convincingly strengthens links between pollutants, immune and neural interactions.

eLife Assessment

CCL2 is a chemokine with immune cell chemoattractant properties, and it appears to play a role in several chronic inflammatory diseases. The RNA-binding protein HuR controls the stability and translation of CCL2 mRNA. This paper presents convincing evidence that a relatively common genetic variant tied to several disease phenotypes affects the interaction between the mRNA of CCL2 and the RNA-binding protein HuR. While the experiments cannot definitively distinguish between effects on RNA transcription and stability, CCL2 is thought to be relevant for leukocyte migration in various conditions, including chronic inflammation and cancer, and the study presents important findings that may be relevant to a broad audience.

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. While the evidence supporting the improvements in the speed and accuracy of these tools is convincing, including additional information about key imaging parameters, the Bar8f experiments, and CaFire would strengthen the study. This work will be of interest to neurobiologists studying synaptic calcium dynamics in various model systems.

eLife Assessment

This important study describes a non-canonical role for IκBα in regulating mouse embryonic stem cell pluripotency and differentiation, independent of the classical NF-κB pathway. The conclusions are convincingly supported through orthogonal approaches and separation of function mutants. The findings add new insight into pluripotency regulation in mouse cells.

eLife Assessment

This valuable work shows that subcortically-generated behaviors, like grooming, can have widespread representations in cortical activity. While the evidence is solid, additional analyses are necessary to strengthen the claims associated with outsized cortical representations of grooming onsets, as well as to address atypical grooming events. This work will be of interest to neuroscientists interested in how subcortically-generated behaviors are represented across the cortex.

eLife Assessment

This valuable study applies transcranial direct current stimulation (tCDS) to the prefrontal cortex of non-human primates during two states: (1) propofol-induced unconsciousness; and (2) wakeful performance of a fixation task. The analysis offers incomplete evidence to indicate that the effect of tDCS on brain dynamics, as recorded with functional magnetic resonance imaging, is contingent on the state of consciousness during which the stimulation is applied. The findings will be of interest to researchers interested in brain stimulation and consciousness.

eLife Assessment

This interesting study presents important information on how human cytomegalovirus (HCMV) infection disrupts the activity of the TEAD1 transcription factor, leading to widespread chromatin alterations. The strength of evidence in revised manuscript is convincing, and includes additional functional data teasing out how TEAD1-driven chromatin changes might influence HCMV replication. This work will be of interest to the virology, chromosome biology and transcriptional co-regulation fields.

eLife Assessment

This paper is important in demonstrating a requirement for sulfation in organizing apical ECM (aECM) during tubulogenesis in Drosophila melanogaster. The authors identify and characterize the organization of some of the first known components of the non-chitinous aECM in the Drosophila salivary gland tube, and these findings are supported by convincing data. This study would be of interest to developmental and cell biologists.

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

eLife Assessment

This valuable study combines anatomical tracing and slice physiology to examine how anterior thalamic and retrosplenial inputs converge in the presubiculum, a key region in the navigation circuit. The authors show that near-simultaneous co-activation of retrosplenial and thalamic inputs drives supra-linear presubiculum responses, revealing a potential cellular mechanism for anchoring the brain's head direction system to external visual landmarks. Their thorough experimental approach and analyses provide convincing evidence for the cellular basis of how the brain's internal compass may be anchored to the external world, laying the groundwork for future experimental testing in vivo.

eLife Assessment

This study presents a useful set of experiments to explore how a salivary protein might facilitate planthopper-transmitted rice stripe virus infection by interfering with callose deposition and if fully validated, these findings would significantly advance our understanding of tripartite virus-vector-plant interactions and could be of broad interest to plant science research. The authors provide additional data supporting protein-protein interactions and clarify the transient presence of LssaCA in plants. However, the mechanistic framework remains incomplete, particularly regarding the temporal dynamics of callose function and the sustained effect of LssaCA after virus inoculation. Evidence for the tripartite interaction's functional relevance is still limited, and several critical phenotypic and biochemical details require further substantiation.

eLife Assessment

This paper presents an analysis of demography and selection from whole-genome sequencing of 40 Faroese, with data that are useful beyond the study region. Much of the analysis is solid, but a more fine-scale analysis of demographic history could have led to more interesting findings. In addition, there are concerns about the selection analyses, given the special nature of the studied population and sampling scheme. Finally, lack of data availability limits the broader value of the paper.

eLife Assessment

This valuable study identifies and characterizes probe binding errors in a widely used commercial platform for visualizing gene activity in tissue samples, discovering that at least 21 out of 280 genes in a human breast cancer panel are not accurately detected. The authors provide convincing evidence for their findings validated against multiple independent sequencing technologies and reference datasets. Given the broad adoption of this spatial gene detection platform in biomedical research, this work provides an essential quality control resource that will improve data interpretation across numerous studies.

eLife Assessment

This valuable study reveals the pro-locomotor effects of activating a deep brain region containing diverse range of neurons in both healthy and Parkinson's disease mouse models. While the findings are solid, mechanistic insights remain limited due to the small sample size. This research is relevant to motor control researchers and offers clinical perspectives.

eLife Assessment

Bonnifet et al. present data on the expression and interacting partners of the transposable element L1 in the mammalian brain. The work includes important findings addressing the potential role of L1 in aging and neurodegenerative disease. The reviewers conclude that several aspects of the study are well done and most evidence is solid, with a noted concern related to the RNA-seq analysis.

eLife Assessment

This useful 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, with 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

This important work by Lesser et al provides a first and comprehensive description of Drosophila wing proprioceptors at an EM resolution. By linking peripheral neurons with information on their morphology and connectivity in the central nervous system, the authors provide new hypotheses and tools to study proprioceptive motor control of the wing in the fruit fly. The evidence and techniques supporting this work are solid, and this resource will contribute to connectome-based modeling of fly behavior.

eLife Assessment

This fundamental study identifies specific neural mechanisms through which HIF-1 signaling in ADF serotonergic neurons extends lifespan in C. elegans, revealing that downstream signaling in multiple types of neurons, as well as other neuromodulators like GABA, tyramine, and NLP-17, is required for this effect. The strength of the evidence is largely convincing, as the authors establish the necessity and causality of key neuronal components using multiple genetic tools and functional dissection in a well-validated model organism.

eLife Assessment

This study presents a valuable application of a video-text alignment deep neural network model to improve neural encoding of naturalistic stimuli in fMRI. The authors found that models based on multimodal and dynamic embedding features of audiovisual movies predicted brain responses better than models based on unimodal or static features. The evidence supporting the claims is generally solid, with clear benchmarking against baseline models. The work will be of interest to researchers in cognitive neuroscience and AI-based brain modeling.

eLife Assessment

This important Research Advance builds on the authors' previous work delineating the roles of the rodent perirhinal cortex and the basolateral amygdala in first- and second-order learning. The convincing results show that serial exposure of non-motivationally relevant stimuli influences how those stimuli are encoded within the perirhinal cortex and basolateral amygdala when paired with a shock. This manuscript will be interesting for researchers in cognitive and behavioral neuroscience.

eLife Assessment

This manuscript describes the identification and characterization of 12 specific phosphomimetic mutations in the recombinant full-length human tau protein that trigger tau to form fibrils. This fundamental study will allow in vitro mechanistic investigations. The presented evidence is convincing. This manuscript will be of interest to all scientists in the amyloid formation field.

eLife Assessment

This important work presents a stochastic branching process model of tumour-immune coevolution, incorporating stochastic antigenic mutation accumulation and escape within the cancer cell population. They then used this model to investigate how tumour-immune interactions influence tumour outcome and the summary statistics of sequencing data of bulk and single-cell sequencing of a tumour. The evidence is compelling and the work will be of interest to cancer-immune biology fields.

eLife Assessment

This important study introduces a new class of spectrally tunable, dye-based calcium sensors optimized for imaging in organelles with high calcium concentrations, such as the endoplasmic reticulum and mitochondria. The experimental evidence supporting the applicability of these sensors is convincing, with thorough validation in cultured cells and neurons. The work will be of high interest to researchers studying calcium signaling dynamics in subcellular compartments.

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 important work advances our understanding of DNA methylation and its consequences for susceptibility to DNA damage. This work presents evidence that DNA methylation can accentuate the genomic damage propagated by DNA damaging agents as well as potentially being an independent source of such damage. The experimental results reported are sound. The evidence presented to support the conclusions drawn is convincing and alternative interpretations are considered. The work will be of broad interest to biochemists, cell and genome biologists.

eLife Assessment

This study presents DeepTX, a valuable methodological tool that integrates mechanistic stochastic models with single-cell RNA sequencing data to infer transcriptional burst kinetics at genome scale. The approach is broadly applicable and of interest to subfields such as systems biology, bioinformatics, and gene regulation. The evidence supporting the findings is solid, with appropriate validation on synthetic data and thoughtful discussion of limitations related to identifiability and model assumptions.