eLife Assessment

This valuable study establishes a novel genetic model for chronic, in vivo visualization of protein engulfment in brain macrophages from the naturally short-lived African turquoise killifish. The solid data presented here show that brain phagocytes exhibit transcriptional features resembling mammalian border associated macrophages and monocyte derived macrophages rather than classical microglia and that their engulfment capacity declines with age, providing a resource for future studies on brain immune cells in teleosts. This research will interest a broad audience across developmental biology, genetics, neuroimmunology, aging research, and evolutionary biology.

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

eLife Assessment

This paper describes a valuable tool for the detection and analysis of dentate spikes, network events in the dentate gyrus that are common yet understudied. This tool could help standardize dentate spike detection and analysis across labs and is therefore likely to be of interest to hippocampal neurophysiologists. However, the strength of evidence for its broad usefulness was viewed as incomplete, due to several identified bugs in the program and insufficient explanations of parameter selection and methods.

eLife Assessment

This valuable descriptive study describes the expression of a developmentally relevant transcription factor in the adult Tribolium brain. The evidence supporting the claims is convincing and based on a very detailed and rigorous analysis of light microscopy data, which, however, lacks single-cell resolution. This neuroanatomical study is of interest to the field of insect neural development and neuroscience.

Editors Assessment:

The paper presents high-quality reference genome assemblies for two closely related widow spider species, the Australian redback (Latrodectus hasselti) and the New Zealand endemic katipō (L. katipo), providing an important genomic resource for studies of venom evolution, adaptation, and conservation biology. Rather than simply reporting assembly statistics, the authors compare the genomic architecture of the two species, showing that both genomes are highly complete (BUSCO scores >94%) and share similar repeat content, while differing in overall genome size, scaffold continuity, and predicted gene numbers. The chromosome-level assembly achieved for L. katipo enables more detailed comparative analyses than previously possible, whereas the more fragmented L. hasselti assembly still captures a highly complete gene repertoire. Ortholog analyses reveal substantial conservation between the species but also indicate lineage-specific differences, with evidence suggesting either gene duplication in L. hasselti or gene loss in L. katipo, providing insight into their divergent evolutionary histories despite their close relationship and contrasting ecological distributions. Beyond generating sequence data, the study establishes foundational genomic resources that will facilitate future investigations into venom gene evolution, population genomics, species divergence, and the conservation of these ecologically and medically significant spiders.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This Data Release presents a multilingual dataset collected from a survey of participants and community members at the 2025 DBCLS BioHackathon, with the goal of understanding how AIis being used in bioinformatics and related scientific fields. The survey, available in English, Japanese, and Thai, gathered responses from 105 participants about AI usage frequency, applications, challenges, institutional support, satisfaction, concerns, and demographic information. The released dataset includes anonymized raw responses, a cleaned English-language version for quantitative analysis, the original questionnaire, a data dictionary, and a translation lookup table to support reproducible research. To protect participant privacy, the authors carefully removed personally identifiable information. This openly available resource provides researchers with valuable data for studying AI adoption, evaluating policy and institutional support, and developing methods for analyzing survey data related to AI use in scientific research. Overall, this work contributes a well-documented, reusable dataset that can help inform future research on the evolving role of artificial intelligence in genomics, bioinformatics, software development, and the broader scientific community.

This evaluation refers to version 1 of the preprint

eLife Assessment

This important study builds on previous work from the same authors to present a conceptually distinct workflow for cryo-EM reconstruction that uses 2D template matching to enable high-resolution structure determination of small (sub-50 kDa) protein targets. The paper provides convincing evidence that the density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template, and it provides an insightful quantification of the level of model bias that remains in the resulting reconstructions. The convenient visualisation of small molecules bound to protein targets of a known structure will be relevant for the pharmaceutical industry.

eLife Assessment

This set of studies provides important knowledge for the role of zona incerta neurons in motivation and food-seeking in mice. The evidence supporting the findings is convincing, with the use of multiple approaches and nice behavioral procedures to provide converging lines of evidence. Additional analyses and data from the current studies would further strengthen the evidence. This work will be of interest to those interested in motivation and its brain substrates.

eLife Assessment

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

eLife Assessment

The authors provide convincing evidence that, during early mouse embryogenesis, distal visceral endoderm cells migrate in a coordinated, intermittent start-and-stop manner along an axis that correlates with the asymmetric morphology of the ectoplacental cone. This fundamental finding is supported by high-quality live imaging and quantitative image analysis, while computational modelling suggests that the observed intermittent behavior may be explained by the movement of a cohesive cell group through a viscoelastic tissue, rather than by fluctuations in DVE migration velocity itself.

eLife Assessment

This valuable study provides fMRI evidence for a hierarchical representation of sequence, arranged along the anterior-posterior axis of the entorhinal cortex, as well as evidence from human single-unit recordings for sequence position coding in the hippocampus and entorhinal cortex. Weaknesses include tenuous links between the single-unit and fMRI datasets, incomplete evidence for some claims, lack of discussion of relevant hippocampal literature, and potential over-interpretation of the findings in relation to rodent grid coding. This work will be of interest to researchers studying memory, sequence representations, and spatial coding in the medial temporal lobe.

eLife Assessment

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

eLife Assessment

This important study provides convincing evidence that envelope-carrying Ty3/gypsy retrotransposons (errantiviruses) are ancient and widespread across nearly all major animal phyla, with distribution in many lineages that are consistent with recent or ongoing genomic expansion. Using comprehensive phylogenetic and AlphaFold2-based structural analyses, together with new host-taxonomy concordance tests, the authors show that these elements independently acquired membrane fusion proteins early in metazoan evolution, likely predating the bilaterian-non-bilaterian split. The work offers significant insights into the deep evolutionary roots of retroelement-envelope associations and the origins of retroviruses.

eLife Assessment

In this important study, the authors have performed a zebrafish drug screen to identify suppressors of atherogenic lipoproteins. They utilize a well-established LipoGlo assay to find molecules that modulate these lipoproteins, identifying 49 potential hits and they perform validation experiments, including studies linking enoxolone to its likely inhibitory effect on a specific transcription factor, HNF4alpha. Overall, the results are convincing and robust, and will open up new areas of exploration for those investigators interested in in vivo lipid biology.

eLife Assessment

This study provides important insights into how researchers can use perceptual metamers to formally explore the limits of visual representations at different processing stages. The framework is compelling and the data support the claims.

eLife Assessment

This is an important study establishing the mechanistic principles how NUP98-KDM5A phase separates together with H3K4me3 chromatin in leukemia. Methods are sound and results are convincing, providing a framework to understand gene expression changes in leukemia patients.

eLife Assessment

In this important study, the authors describe the mechanisms by which CDK4/6 overexpression mediates resistance to Osimertinib in EGFR mutant lung cancer models. Their data show that CD4/6 overexpressing cells had increased replicative stress and genomic instability. The evidence is solid, but inclusion of some additional experiments would make this stronger.

eLife Assessment

This study presents a potentially important structure-interaction model describing recognition of polymyxin antibiotics by the human transporter hPepT2 and applies these insights to guide the rational design of potent polymyxin B analogues with reduced nephrotoxicity. The conclusions are supported by compelling evidence, integrating molecular dynamics simulations, transporter mutagenesis, uptake assays, protein expression analyses, antibacterial testing, and mouse nephrotoxicity studies, although some mechanistic interpretations remain limited by altered transporter expression and the absence of direct structural validation.

possible conclusion

possible evidence for topic/subtopic

possible topic/subtopic

eLife Assessment

This valuable study provides solid evidence that N6 methylation of A74 by METTL3 is required for efficient translation directed by the SARS-CoV-2 5′UTR in uninfected cells, likely by limiting access of protein factors to the 5′UTR that are necessary for efficient translation. These findings advance our understanding of the role of RNA modification in coronavirus replication and m6A-mediated regulation of gene expression more broadly, while further supporting METTL3 as a potential anticoronaviral therapeutic target. However, the evidence that m6A acts by destabilizing the third stem-loop (SL3) of the 5′UTR remains incomplete. The impact of the study would be strengthened by biochemical analyses directly assessing structural changes in the 5′UTR induced by A74 methylation.

Most African Americans were living in the south as slaves in what is the U.S. now, around the late 1700's slaves could not learn to read or write because of harsh laws. Most of the African American literary traditions became oral and not written around that time. Their literature started to get past down to many people, and generations using the oral tradition.

eLife assessment

In this manuscript, Rademacher and colleagues examined the effect of a chemogenetic approach on the integrity of the dopamine system in mice with chronically stimulating dopamine neurons. These findings are important: (1) This approach led to an axon-first degeneration over a time course (2–4 weeks) that is suitable for experimental investigation; (2) The finding that direct excitation of dopaminergic neurons causes differential degeneration sheds light on dopaminergic neuron selective vulnerability mechanisms. Overall, the strength of the evidence is solid, but the behavior experiments that do not include a CNO control provide incomplete support for the findings.

eLife Assessment

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

eLife Assessment

This study identifies apoptotic retinal ganglion cells as a potential source of ATP-mediated activation of PANX1 channels that initiates developmental retinal Ca²⁺ waves and coordinates microglial activation and vascular outgrowth during postnatal maturation. The work is important because it proposes an integrative framework linking programmed cell death, spontaneous neural activity, immune responses, and angiogenesis into a self-regulating developmental loop. Although the mechanistic conclusions would benefit from complementary genetic validation, the study provides a convincing foundation for future investigations into the coordination of neural circuit development and tissue remodeling.

eLife Assessment

This convincing contribution addresses a question of practical importance: when collecting tilt-series data, what is the optimal angular step size between successive tilt images? The work provides valuable practical insights into cryo-ET data acquisition by demonstrating that balancing two competing demands - sufficient dose per individual tilt image and fine angular sampling - is essential to achieve high-quality tomographic reconstructions. They demonstrate that tilt-series acquired with finer increments (1-3 degrees) yield superior alignment accuracy and improved template-matching performance.

eLife Assessment

This is a valuable study on the metabolic adaptations upon succinate dehydrogenase loss in cancer cells. If confirmed, this study will offer some therapeutic vulnerabilities in treating SDH-deficient cancer. However, the evidence supporting the authors' claim is incomplete and would benefit from additional experimental evidence. This study will be of broad interest for cancer biologists focusing on metabolism.

eLife Assessment

This valuable study documents, for the first time, the degree of preference for contralateral versus ipsilateral forelimb movements in the motor cortex of mice, revealing subtly distinct profiles across cortical areas, with the orofacial region showing comparatively little limb selectivity relative to the forelimb motor areas. The experiments and analyses are, in general, solid and well-designed, and the data support the paper's conclusions.

eLife Assessment

This manuscript employs cryo-EM, mutational analysis, and biochemical assays to explore the molecular basis by which glutamine promotes filamentation and regulates the activity of human glutamine synthetase (hGS) by stabilizing interactions between hGS decamers. The combined structural and biochemical data supporting the proposed mechanism are solid, although the evidence for a higher-order filamentous architecture and the precise assignment of the interface density would benefit from additional support. This work will be of particular interest and useful to groups interested in understanding the molecular basis of nutrient sensing, cellular metabolism, and structural regulation of enzyme activity.

eLife Assessment

This work presents important findings on quantifying gene coexpression from spatial omics. These quantification methods have been applied to gastruloid to describe how genes are spatialised. The description of the quantifying tools is characterized by exceptional evidence after a thorough revision.

eLife Assessment

This multimodal neuroimaging study leverages fMRI, PET, and deep learning to predict memory performance. The authors introduce the brain-cognition gap to link these different imaging modalities to cognition and evaluate their results in two independent cohorts. The results are solid and provide an important contribution to the literature and will be of interest to neuroscientists working at the interface of cognition, neuroimaging.

eLife Assessment

This study explores how complement protein C3 and its signalling may modulate immune training in alveolar macrophages. The findings are an important contribution to the field of trained immunity. The findings are convincingly supported by in vivo and ex vivo experiments, encompassing both pharmacological and genetic-based approaches.

eLife Assessment

This valuable study presents an analysis of the gene regulatory networks that contribute to tumour heterogeneity and tumor plasticity in Ewing sarcoma, with key implications for other fusion-driven sarcomas. The authors employed compelling orthogonal approaches, including single-cell sequencing and xenografts, to reveal the existence and plasticity of specific gene regulatory networks (e.g., TGF-beta signaling) within Ewing sarcoma, as well as significant differences that exist between cell lines and patient tumors.

Bias can cause students who speak Black English to be though of as less intelligent, when they aren't

Teachers need to make sure to respect others' cultures and dialects and prepare students for the real world by teaching Standard English.

Getting farther in society means that you have to speak the way that other, "dominant" people do.

We should change the way standard English is being taught in schools so that it focuses more on diversity.

Requiring standardized English makes it harder for some people to get education, jobs, and talk to people in conversations and actively telling students to not use their home language at school.

eLife Assessment

This manuscript reports an important new statistical method for calculating the significance of correlations between two time-series, which provides more accuracy than other methods when the data has few replicates. The proposed method solves a real-life problem that is frequently encountered and is broadly applicable to many realistic datasets in many experimental contexts. The technique is supported with compelling mathematical derivations as well as analysis of both computer-generated and previously published experimental data.

eLife Assessment

This important study by Otgonbaatar and colleagues employs advanced live microscopy, optogenetics, and an endogenous fluorescent timer system to investigate short- and long-term stabilization dynamics of β-catenin/Armadillo (Arm) during Drosophila development. The authors identify an unexpected and functionally relevant enrichment of stabilized junctional Arm in leading-edge cells during dorsal closure, providing evidence for a stabilization mechanism that appears independent of canonical Wingless signaling. These findings are significant because they expand current understanding of β-catenin/Arm beyond its canonical signaling functions and suggest a role in tissue mechanics and force transmission during dorsal closure. The proposed model represents a key advance in the field, but the strength of evidence is currently incomplete: the main conclusions regarding Wingless independence, JNK-mediated regulation, and the mechanical role of stabilized Arm are only partially supported by the available data and would benefit from further experimental testing and corroboration.

eLife Assessment

This study presents a valuable RNA velocity solution which integrates cell differentiation and gene regulation, with a balance between neuralODE and raw gene space. The evidence supporting the claims of the authors is solid, although inclusion of discussion on the challenges in capturing cell cycle transitions would have strengthened the study. The work will be of interest to scientists working in the field of computational biology and gene regulation.

eLife Assessment

This study demonstrates that endothelial toll-like receptor 4 is a central regulator of leptomeningeal inflammation in neonatal E. coli meningitis. The data are derived from cell-type-specific gene knockouts in mice and cultured endothelial cells and are convincing. This work is important as it advances our understanding of host cellular processes and molecular pathways underlying meningitis pathogenesis and specifically expands the knowledge of how breakdown of the blood brain barrier contributes to the pathogenesis.

eLife Assessment

This important study addresses how the molecular identity of a single neuron specifies its hard-wired synaptic connectivity, using repeated single-cell RNA sequencing of identified Drosophila sensory neurons together with functional perturbation of candidate cell-surface molecules. It demonstrates remarkably low transcriptomic variability across animals for the same identified neuron, defines a tractable set of differentially expressed cell-surface molecules that distinguish mechanosensory from chemosensory neurons, and links several of these molecules to axonal targeting and circuit function. The evidence is solid, with the single-neuron transcriptomic datasets and Dscam isoform repertoires offering a lasting resource for the field, though clearer articulation of the experimental logic, additional controls in the RNAi screen, and a more complete characterization of the neuronal re-wiring would further strengthen the central claims.

eLife Assessment

This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury? The authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival after a variety of chemical and surgical liver injury models. The authors provide evidence that some zones mount tailored stress responses, which ultimately promote regeneration and liver healing; however, the "mid-zone" changes with different injury models, making it difficult to conclude that the ATF4-CHOP response is specific to this zone in all injury contexts. In addition, it is possible that Atf4 and Btg2 overexpression could lead to Cyp2e1 suppression, which could reduce the extent of injury after CCl4 or APAP. To some extent, these points make the strength of the evidence incomplete, but do not entirely detract from the significance of the study, which is underscored by the helpful observation that there are zone-specific stress responses that mediate liver regeneration and survival.

eLife Assessment

This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents a valuable addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. However, the experimental evidence supporting the underlying cellular and molecular mechanisms and the integration of foundational background literature to provide the necessary context are incomplete.

eLife assessment

The authors present a valuable open-source tool for three-dimensional analysis of dissected slices of human brains including 3D reconstruction and high-resolution 3D segmentation. Convincing evidence is provided based on experiments on both real and synthetic data. This tool would be of use to researchers in the neuropathology and neuroimaging field.

eLife assessment

The study presents a tool for searching molecular dynamics simulation data, making such data sets accessible for open science. The authors provide convincing evidence that it is possible to identify noteworthy molecular dynamics simulation data sets and their analysis can produce valuable information.

eLife Assessment

This valuable manuscript by Alonso-Caraballo et al is a novel piece of work that examines the impact of oxycodone self-administration on neural plasticity within paraventricular thalamic (PVT) to nucleus accumbens shell (Shell) pathway - two regions shown to play a key role in cue-induced drug seeking on their own - and whether this plasticity varies based on abstinence period and biological sex. Data show that a clinically relevant long-access model of self-administration promotes dependence in both male and female rats and provide compelling data that when compared to current literature indicate that craving-induced relapse for opioids may develop faster and may be more pronounced in females compared to males. In addition to these behavioral findings, the authors provide the first evidence that glutamate signaling within the PVT-to-Shell pathway is selectively strengthened at the output medium spiny neurons by opioids following protracted, but not acute abstinence. These data highlight a potential role for these adaptations in relapse behavior and identify a potential therapeutic target during abstinence to reduce relapse risk in abstaining individuals.

eLife Assessment

This important study addresses the role of sphingolipid metabolism in maintaining endolysosomal membrane integrity and its impact on tau pathology in Caenorhabditis elegans and human cell culture models. The findings are convincing, and the proposed mechanisms are conceivable. The experimental evidence supports the conclusions of the study. The work will be of broad interest to cell biologists and biologists working on Alzheimer's disease and related proteinopathies.

eLife Assessment

This study presents a fundamental finding that the JAK-STAT pathway (JSP) exerts context-dependent roles across distinct cellular compartments within the breast cancer microenvironment. The conclusions are supported by convincing evidence from multi-omics analyses. This study may inspire future studies to explore specific factors that selectively modulate JAK-STAT activity in immune cells to achieve favorable therapeutic outcomes.

eLife Assessment

In this valuable study, the authors performed cell-specific ribosome pulldown to identify gene expression (translatome) differences in the anterior (NT1) vs middle & posterior (NT2-9) cells of the C. elegans intestine, under fed, starved, or refeeding conditions. The data generated will be very helpful to the C. elegans community, and the evidence supporting the conclusions of the study is assessed to be solid. Some methodological caveats remain and are discussed.

eLife Assessment

This study investigated mitochondrial dysfunction and the impairment of the ciliary Sonic Hedgehog signaling in Lowe syndrome (LS), a timely topic given the limited research in this area. The data obtained from patient-derived iPSC neurons and a mouse model are solid. Although the main claims of the study are only partially supported by the current evidence, it provides a useful starting point for future functional studies investigating the link between mitochondrial defects and primary cilia in neural development.

eLife Assessment

This study introduces an artificial-intelligence tool that estimates fat in skull bone marrow from routine brain scans, enabling large studies that were previously impractical. The evidence for the method's repeatability and for identifying genetic links is convincing overall. The authors identify genes, diseases, and other biological characteristics that are linked to skull marrow fat, which represents an important advance. The work will be of most interest to researchers using large imaging biobanks and those studying ageing-related changes across bone, blood, and brain.

eLife Assessment

This work presents valuable new data on the role of D-Serine and how it competes with its stereoisomer L-Serine to influence metabolism. The work presents a variety of convincing experimental data combined with simulated results to investigate the mechanisms focused on one-carbon metabolism, which is relevant for several research fields. However, some claims are only partially supported by data, and critical areas comparing L- vs D-Serine and further mechanistic studies are required. Furthermore, while the work has potential for various fields, the work has only been studied in a limited cell type and context.

eLife Assessment

This useful study investigates how plasticity and homeostatic adaptation can lead to the emergence of synchronization patterns associated with different sleep phases. The ideas are novel and interesting, but the evidence at present remains incomplete. Further work is needed to determine whether the reported states persist for larger system sizes, longer integration times, and how robust the results are to different initial conditions.

eLife Assessment

This important study introduces a non-perturbative pulse-labeling strategy for yeast nuclear pore complexes (NPCs), employing a nanobody-based approach in order to selectively capture Nup84-containing complexes for imaging and biochemical analysis. The data convincingly demonstrate that a short induction period (20 minutes to 1 hour) yields a strong and sustained signal, enabling affinity purification that faithfully recapitulates the endogenous Nup84 interactome. This tool offers a powerful framework for investigating NPC dynamics and associated interactomes through both imaging and biochemical assays.

eLife Assessment

This valuable study presents a comparative analysis of the transcriptomic features underlying C. elegans longevity, providing insights into how different changes in gene expression can promote longevity. The authors present solid evidence with analysis and selected functional validation showing that some long-lived animals share common changes while others appear to use opposing strategies. The datasets and analyses contained within and the user-friendly website developed will be of interest to researchers interested in complicated transcriptomic analyses and/or the biology of aging.

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

eLife Assessment

This valuable study provides insights into the role of MATR3 in oocyte maturation and folliculogenesis, using conditional knockout mice and in vitro follicle culture systems to show that MATR3 is required for oocyte growth and gene transcription, with downstream effects on follicle development. The evidence is solid, but some minor inadequacies in replication of key methods and independent validation reduce confidence in the conclusions. The work will be of interest to researchers in reproductive biology and fertility.

eLife Assessment

This study reports important and invaluable findings that advance understanding of how attention is distributed between what we look at directly and what lies outside the center of gaze during active visual search. The evidence supporting the main claims is solid, with a large and rich dataset spanning multiple brain areas, although some aspects of the interpretation would benefit from additional controls and clearer separation of attention from eye-movement planning. The work will be of particular interest to researchers studying attention, visual perception, and eye movements behavior.

eLife Assessment

One-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this valuable study, the authors employ a solid genetics-based approach to demonstrate that three distinct metabolic pathways are essential for synthesising 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence.

eLife Assessment

This is a detailed and well-designed simulation study of the utility of replication metrics in animal-to-human study translations in bridging the gap between laboratory discoveries and health practice, a critical consideration in turning laboratory scientific research findings into tangible, real-world applications, to directly help human health. The study approaches are convincing, and the findings are important, as they offer insights into clinical research translations to advance health decision-making.

eLife Assessment

This fundamental study uses simultaneous EEG and fMRI recordings to shed light on the relationship between alpha and gamma oscillations and specific cortical layers. The sophisticated methodology provides compelling evidence for correlations between oscillatory power and the strength and contents of fMRI signals in different cortical layers. This paper will be of interest to neuroscientists studying the role and mechanisms of alpha and gamma oscillations.

eLife Assessment

The report by Liu and colleagues provides a valuable analysis of environmental adaptation across diverse lineages of the grass Phragmites australis differing by their level of ploidy. The analysis reports solid evidence that lineages with distinct levels of ploidy occupy different climate niches. The use in tandem of regional survey and common garden experiment represents a convincing approach to suggest a correlation between ploidy and climate adaptation. This manuscript will be of interest to a broad community of ecological genomicists interested in how structural variation in gene dosage potentially affects the pattern of adaptation.

eLife Assessment

This work presents a software and hardware suite for targeted photostimulation that can be used in vivo. The package is a well-designed and documented hardware/software suite with a comprehensive build guide. This tool will likely promote important neuroscience advances through targeted real-time perturbation of the cerebral cortex. Overall, this manuscript makes a compelling case on how to design and make available power tools for the research community.

eLife Assessment

This important study combines peptide engineering, molecular docking, and functional assays to define the molecular basis of ligand recognition and activation of the human Y4 receptor and to identify three novel small-molecule agonists. The evidence supporting the conclusions is convincing, with complementary experimental and computational approaches providing strong support for the proposed receptor-ligand interactions. While concentration-response analyses of the small-molecule agonists and additional structural or mutagenesis studies would further strengthen the work, these are not essential to support the main conclusions. The work will be of interest to researchers studying GPCR pharmacology, structural biology, and ligand discovery.

eLife Assessment

This study presents a valuable metagenomic analysis of the gut microbiome in sickle cell disease (SCD) patients, revealing associations between bacteriophage, host immunity, and SCD pathophysiology. While these data are interesting and helpful for hypothesis generation, they are deemed incomplete; additional experiments would be needed to test causality and to provide mechanistic insight. Despite these limitations, this work will be of broad interest to researchers studying SCD, immunology, phage biology, and the microbiome, adding to the small but growing literature suggesting a microbial component to SCD.

eLife Assessment

This is an important study that applies a new chromatin profiling technique to the study of cellular responses to low oxygen. The authors provide convincing evidence for distinct kinetic phases of the response and identify many new putative regulators of the response. This work will be of broad interest to those studying low oxygen responses and transcriptional regulation.

eLife Assessment

The manuscript concerns a fundamental and controversial question in Trypanosoma brucei biology and the parasite life cycle, whether or not dividing slender bloodstream forms must transition to growth-arrested stumpy forms before differentiating to the procyclic form in the Tsetse midgut. The authors provide further evidence that slender bloodstream forms can infect Tsetse flies, and that although their differentiation is considerably delayed, they do not become classical stumpy forms during the process. The study is solid in design and execution, and addresses several criticisms made of the authors' earlier work, although discrepancies with results from other laboratories remain.

eLife Assessment

This important study reports the development of the first tankyrase degrader and demonstrates its enhanced ability to inhibit β-catenin signaling compared to conventional tankyrase inhibitors. The evidence supporting the conclusions is comprehensive and convincing, based on rigorous biochemical and cellular analyses. The findings will be of broad interest to researchers studying Wnt signaling, protein degradation, and cancer biology.

eLife Assessment

This manuscript presents openretina, an open-source platform that integrates retinal datasets, model training, benchmarking, and in silico analysis tools within a unified framework. The resource is valuable because it addresses long-standing challenges in reproducibility, accessibility, and cross-study comparison in computational retina research, while providing a foundation for community-driven model development and evaluation. The supporting evidence is solid, with the authors demonstrating a functional and well-documented platform across multiple datasets and species, although a clearer discussion of model interpretability, current performance limitations, and data quality standards would strengthen the resource.

eLife Assessment

In this manuscript, the authors describe a cell-specific mechanism by which glutamate transporters regulate the fidelity with which T-stellate cells in the mouse ventral cochlear nucleus relay information from auditory nerve inputs. The study is supported by solid electrophysiological data. It provides valuable insights into how the rapid binding of glutamate to transporters shapes auditory information processing at specific synapses.

eLife Assessment

This manuscript describes an important development of several variants of optogenetic tools to control endogenous p53 activity. They are based on peptides competing with Mdm2/MdmX for binding to p53, thus releasing p53 from its negative regulators and stabilizing its cellular levels. In principle, the data are convincing but should be complemented by investigations of p53 target genes at endogenous levels (instead of only reporter constructs). The study therefore remains incomplete but will be of interest to scientists working on optogenetics as well as the p53 field.

eLife Assessment

Verma and colleagues interrogate the mechanisms of phagosome maturation arrest during Mycobacterium tuberculosis infection. While cellular events that culminate in this arrest have been largely elucidated, involvement of other organelles, such as mitochondria, has not been highlighted mechanistically. In this valuable study, elements of mitochondrial quality control, such as mitophagy and mitochondrial-derived vesicles involvement, are shown to be paramount in the host-pathogen tussle. The evidence supporting the main conclusions is solid, based on multiple complementary approaches and appropriate controls, although some central mechanistic aspects of the proposed pathway remain only partially resolved.

eLife Assessment

This valuable study provides a cross-species single-cell transcriptomic resource for early female gonadal development in mammals. The data supporting the main conclusion remain incomplete, and experimental validation is needed to strengthen the conclusions. The work will be of interest to reproductive biologists and developmental biologists.

eLife Assessment

The Review Article by Bal and co-workers presents an overview of skeletal muscle physiology, focusing on Sarcoplasmic Reticulum and Mitochondria-Associated Membranes (MAMs) in relation to calcium handling, ROS, and signaling. It provides a foundation based on the current literature but could have gone further by identifying future research directions and potential avenues for therapeutic intervention.

eLife Assessment

This study investigates the cellular mechanisms underlying theta-nested gamma oscillations in the medial entorhinal cortex; the experiments are rigorous, and the analyses and modeling provide potentially useful insights into cell-type-dependent circuit dynamics. However, the evidence supporting several key conclusions remains incomplete. The study is limited by conceptual constraints in the experimental design and a modeling approach that does not fully address underlying physiological mechanisms. Overall, this is a careful study that addresses how distinct neuronal populations in superficial MEC participate in theta-gamma coordination and provides new data linking cell-type-specific activity patterns to oscillatory network structure.

eLife Assessment

This study makes a solid and valuable contribution to elucidating the intricate relationship between mitochondrial calcium and neuronal survival. Well-controlled experiments show that homeostatic mitochondrial calcium correlates with the most resilient neuronal subtypes after optic nerve injury. However, altering mitochondrial calcium levels does not affect neuronal survival as initially predicted by this correlation.

eLife Assessment

This article describes the comprehensive metabolic phenotype of a mouse model of Down Syndrome, together with supporting transcriptomic, metabolomic, and biochemical data. The evidence presented is compelling and highlights several core phenotypes including insulin resistance, dyslipidemia, and tissue signatures indicating inflammatory and cellular stress pathways. Similarities and differences in male and female mice are highlighted. This important study provides essential groundwork for the further genetic dissection of dosage-sensitive genes causing metabolic dysregulation in Down Syndrome.

eLife Assessment

This study presents an important large-scale behavioral and transcriptomic analysis of Drosophila that are heterozygous for putative loss-of-function alleles of homologs of human genes that have been linked to autism spectrum disorders. The authors consider 48 genes as hits from their screen, which show significant behavioral alterations in sleep, basal activity, and/or social behavior, and significant sexual dimorphism. The authors then focus on the domino/SRCAP gene as a candidate regulator of sleep, social behavior, transcriptional programs, and RNA splicing. The work generates a solid dataset and applies quantitative analytical approaches that will be of interest to researchers in the field, yet the evidence presented remains incomplete because issues of genetic background need to be further addressed.

eLife Assessment

In this useful Tools & Resources article, the authors describe a new cryogenic light microscopy design and characterize its temperature and spatial stability. This compelling system avoids the challenges associated with vacuum-based designs, particularly vacuum transfer systems, which are difficult to engineer. A key advantage of the system is that it reduces ice contamination and drift, which are the primary challenges in open cryostat systems.

eLife Assessment

This manuscript describes a valuable study of the mechanism by which acetylation on the histone H3 core domain regulates RNA polymerase II transcription passing through nucleosomes. The authors provide convincing evidence that acetylation influences transcription in a context-specific fashion. Some questions relating to the static nucleosome structures and the polymerase passage remain, but this manuscript will be of considerable interest to researchers in the chromatin and transcription fields.

eLife Assessment

This important study provides a mechanistic view of how antibody affinity maturation can reshape encounter-state landscapes and association pathways, with implications for understanding HIV antibody maturation and vaccine design. The results are solid, supported by a coherent integration of adaptive molecular dynamics, Markov state modeling, SPR kinetics, mutagenesis, and double-mutant cycle analysis, although aspects of the kinetic validation, MSM-state robustness, and causal interpretation would benefit from further support. The work will be of interest to immunologists, structural biologists, and computational biophysicists.

eLife Assessment

Muetter et al. provide an important argument that luminescence is a reliable, high-throughput alternative to colony-forming units (CFU) for super-MIC investigations, particularly when the quantity of interest is biomass. By examining 20 antimicrobials spanning 11 classes, the work shows that discrepancies between CFU and luminescence are often biological (filamentation, Viable But Not Culturable). The work provides a convincing view of how these three common measurements (luminescence, optical density, and CFU) relate to one another across a range of drug treatments, although testing on clinical isolates could be of further benefit.

eLife Assessment

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

eLife Assessment

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

eLife Assessment

This valuable study demonstrates that self-motion strongly affects neural responses to visual stimuli, comparing humans moving through a virtual environment to passive viewing. The evidence for visuomotor mismatch responses is solid, although the interpretation in terms of prediction remains somewhat preliminary. This study bridges human and rodent studies on the role of prediction in sensory processing, and is therefore expected to be of interest to a large community of neuroscientists.

eLife Assessment

This study presents a key finding: self-generated mechanical stresses enable collective protocell proliferation without dedicated division machinery, offering insight into primitive life's population growth. While quantitative imaging, membrane tension measurements, and computational modeling support the mechanism, establishing causal links between deformation and division and testing sensitivity assumptions would strengthen the work. Overall, the work reports important findings, and although the evidence in support of the conclusions is largely solid, some incomplete elements need to be addressed.

eLife Assessment

This important study combines experimental evidence with computational modeling to suggest that neurons in the frontal eye field form two overlapping topographical maps, one for visual inputs and the other for eye movement directions. The experiments leverage the smooth cortex of the marmoset to provide solid evidence that two maps exist at different scales. The modelling work provides a potential mechanistic insight into how these patterns may be used for flexible visuomotor transformations.

eLife Assessment

In this valuable study, Bhojappa et al. investigate the function of four septin-associated kinases (Elm1p, Gin4p, Hsl1p and Kcc4p) in controlling septin ring stability, actomyosin ring organization and constriction, and cytokinesis in budding yeast. The evidence supporting the conclusions is convincing. The results are a meaningful addition to previously published work and provide a clearer picture of a complex mechanism involving proteins of partially redundant functions.

eLife Assessment

This useful study provides new insights into the liver-stage antigen LSA3, its export to erythrocytes, and its role in liver-stage development. While the functional importance of LSA3 is well demonstrated, the data underlying the conclusions regarding antibody specificity, liver-stage localization, and phenotype remain incomplete. A key strength of the study is the use of mosquito and humanized mouse models to access life-cycle stages that are rarely studied in most laboratories.

eLife Assessment

This study offers an important set of literature-based parameter ranges for calibrating cardiac electromechanical models. The key scientific claims are largely supported by convincing evidence and carefully-documented methodologies, but a few specific issues remain only partially supported, in particular relating to the locking-free formulation, reporting of adequate details regarding the electrophysiological model (Eikonal approach), and the fact that physiological accuracy is predominantly achieved in a single chamber (the LV).

eLife Assessment

The study presents important findings from a very rich EEG-fMRI dataset including 107 participants, which was collected during nocturnal naps. Using overall solid methods, the authors link activity in memory related brain regions (e.g., hippocampus, thalamus, and medial prefrontal cortex), as well as their functional connectivity, to the occurrence of canonical sleep rhythms (spindles and slow oscillations) during non-rapid eye movement (NREM) sleep. This work will be of broad interest to researchers studying sleep, memory, and related domains.

eLife Assessment

By mining the Logan assemblage of the Sequence Read Archive to reveal substantial papillomavirus diversity, this valuable study establishes a framework for integrating viral discovery with host, geographic, and ecological metadata. The evidence for identifying novel papillomavirus sequences is convincing, supported by large-scale sequence searches, established L1-based typing criteria, phylogenetic analyses, protein annotation, and structural comparisons. The broader host-association and ecological conclusions are more tenuous due to heterogeneous public metadata and uneven sampling, and would benefit from clearer discussion of potential biases, contamination, endogenous viral elements, and alternative explanations. The work should be of interest to a broad range of colleagues in the areas of microbiome research, virology, and viral evolution.

eLife Assessment

This valuable study reports that ALDH-abundant cells exhibit stem cell properties and may play a key role in endometrial epithelial development in mice. The data support the main conclusion and are convincing. This work will be of great interest to reproductive biologists and biomedical researchers working on women's reproductive health.

eLife Assessment

The authors use solid high resolution microscopy techniques to present a model in which SARS-CoV-2 attachment and endocytosis are mediated by heparan sulfate, whereas ACE2 only functions downstream of these early processes. These findings serve as a potentially valuable starting point to examine SARS-CoV-2 entry models that challenge current paradigms. However, examination of the model in a clean heparan sulfate deficient background and in the context of TMPRSS2-dependent plasma membrane fusion are lacking. Thus, the broader impact remains uncertain in the absence of additional controls and orthogonal approaches.

eLife Assessment

This important study investigates the mechanisms by which Mycobacterium tuberculosis suppresses protective Th17 differentiation during infection. Using ESX-1- and PDIM-deficient mutants of M. tuberculosis, which lack functional eccC1 and fadD28 respectively, the authors demonstrate that these virulence factors actively restrict IL-17 responses via a T-bet-dependent pathway, independent of overall bacterial attenuation or infection duration. While the precise molecular interactions by which ESX-1 and PDIM modulate Th17 differentiation warrant further elucidation, the experiments are rigorously designed, the findings are clearly presented, and the evidence is solid for a specific role for these factors in limiting protective IL-17 immunity in M. tuberculosis infection.

eLife Assessment

This useful study reports findings that support the use of the Open Field Test in Drosophila as a model to study "emotion-like states", which are behavioral responses to several stressful or aversive treatments, and resilience upon their subsequent removal. Behavioral data, by employing established stress-causing treatments and genetic manipulations, are solid. The main advance of this work over previous Drosophila work using a similar experimental setup is systematic analysis of various stressors.

eLife Assessment

This important study addresses a timely issue at the intersection of mitochondrial and telomere biology by focusing on the relationship between naturally occurring variants in the mitochondrial genome and telomere length. This work thereby provides a conceptual and experimental framework for investigating communication between mitochondria and telomeres. Using an innovative transmitochondrial cybrid approach, the authors provide evidence that mitochondrial DNA variants influence telomere maintenance through effects on mitochondrial function, reactive oxygen species, and NAD⁺-dependent repair processes. The evidence supporting the central conclusion that mitochondrial genotype influences telomere-associated phenotypes is convincing and is strengthened by the use of complementary functional and rescue experiments. However, some of the mechanistic interpretations and broader conclusions regarding telomere length inheritance in humans would benefit from additional donors and longitudinal analyses following cybrid generation, or more cautious framing.

eLife Assessment

This fundamental manuscript describes a key role for the integrated stress response-regulated transcription factor CHOP in regulating liver biology in response to endoplasmic reticulum stress through both the downregulation of transcription factors involved in regulating hepatic identity and altering the capacity for integrated stress response and unfolded protein response signaling to induce protective signaling. The data supporting this model is convincing, but including some additional discussion on the mechanism and importance of the work in the context of the published literature would be helpful to better define the complex importance of CHOP signaling. This work will be of interest to a wide range of biologists interested in liver biology, stress-responsive signaling, and ER stress.

eLife Assessment

This important study combines behavioural analysis, voltage imaging and electrophysiology to advance our understanding of muscle coordination at the cell-to-cell level, in Caenorhabditis elegans. The evidence supporting the conclusions is convincing; however, the use of correlation in some aspects of data interpretation is a relative weakness. The technically sophisticated optogenetic voltage clamp approach introduced here can be applied to other small, transparent animals, making these findings of broad interest to researchers studying electrical coupling between cells or utilising optical electrophysiology techniques.

eLife Assessment

This important study describes how selective lesions of key cortical and subcortical motor areas affect reaching actions in macaque monkeys. The results will be of interest to both basic and clinical researchers studying the neural control of movement. Kinematic analysis of movement quality is solid but could be improved by considering other metrics, especially those that relate to grasping. Evidence for the general claims related to the role of specific motor areas is incomplete because the lesions did not fully eliminate any single area while simultaneously involving neighbouring areas.

eLife Assessment

The framework of this potentially important study – with the integration of multiple levels of analysis, glymphatic MRI, transcriptomics, functional MRI, and public amyloid maps, in one framework – is clever. The assertion that regional amyloid vulnerability may depend not just on neural activity alone, but on whether clearance is appropriately matched to activity, is an interesting and novel concept. However, the chosen approach to imaging glymphatic clearance relies on indirect inferences from a small subgroup. In its current form, the main conclusions of this study are therefore incompletely supported.

eLife Assessment

The OpenApePose dataset presented in this manuscript represents an important contribution to the field of primate behaviour and computer-vision science with methodological applications that are sure to be applicable for a wide variety of taxa. The analysis supporting the utility of this database is solid and compelling but would benefit from some additional clarity, particularly with regards to the annotation of landmarks, model parameters and division of the dataset for training, validation and testing.

eLife Assessment

This study addresses an important question in aging biology by combining metabolomics, transcriptomics, molecular genetics, and functional analyses to examine how cytosolic acetyl-CoA metabolism influences late-life fitness in replicatively aging yeast. The evidence supporting the roles of AMPK activation, mitochondrial acetyl-CoA utilization, and fatty acid synthesis in preserving fitness during aging is convincing overall, and the engineered A2A strain provides an elegant demonstration that coordinated modulation of distinct acetyl-CoA metabolic branches can increase the proportion of aged cells with a low-senescence phenotype. The study provides significant insight into mechanisms that allow aging cells to maintain fitness without extending replicative lifespan.

eLife Assessment

This study offers important insight into the pathogenic basis of intragenic frameshift deletions in the carboxy-terminal domain of MECP2, which account for some Rett syndrome cases, yet similar variants also appear in unaffected individuals. Using base editing and mouse models, the authors present convincing evidence supporting the pathogenicity of select deletion variants, with potential implications for therapeutic development.

eLife Assessment

This valuable study presents a comprehensive exploration of c-di-GMP-associated protein interaction networks in Pseudomonas fluorescens, with a particular focus on biofilm-related phenotypes. The evidence is convincing, supported by a genome-wide yeast two-hybrid screen, phenotypic analyses, and experimental validation. The work identifies multiple interaction hubs and provides a resource that will be of use to the biofilm and c-di-GMP communities, while additional mechanistic exploration would further enhance its impact by clarifying the biological roles of many of the identified interactions.

eLife Assessment

This important study conducted by Hall and colleagues advances our understanding of host-pathogen co-evolution by providing an elegant multi-omic comparative framework that uncovers a profound, pathogen-directed epigenomic reprogramming of bovine alveolar macrophages uniquely driven by host-adapted Mycobacterium bovis. Convincing evidence supports these findings and draws on robust, multi-layered high-throughput sequencing data integrated with large-scale cattle GWAS metadata to prioritize actionable genetic variants linked to disease susceptibility and to highlight key immune response genes/pathways upregulated in response to infection and pathogen-specific host adaptation mechanisms.

eLife Assessment

This important study investigates how verbal and nonverbal working-memory processing is distributed across large-scale functional networks in the human brain using precision fMRI. By leveraging extensive within-subject data and individualized network mapping, the authors provide solid evidence that hemispheric specialization for verbal versus nonverbal information extends across multiple association networks and is reproducible across independent datasets. The use of state-of-the-art precision neuroimaging approaches reveals fine-grained laterality patterns that are likely obscured in conventional group analyses.

eLife Assessment

Murrell et al. describe a high-throughput method, the Feeding Experimentation Device (FED3), to study food foraging strategies in mice. The authors provide solid evidence about key sex differences in foraging strategies, specifically the finding of greater male win-stay behavior. Further consideration of how sex differences could be uniquely influenced by FED3 testing conditions (e.g., single-housing, hormones) and task demands (e.g., 100-0 vs. 80-20) would be helpful. Given this open source FED3 platform, the authors provide valuable findings that have utility to the field of behavioral neuroscience, specifically to those interested in studying reward-related behavior.

eLife Assessment

This study sets out to show that the directionality of bacterial transport in confined environments is affected by a salt gradient. Using Pseudomonas putida in microfluidics devices, the authors hypothesize that salt-induced diffusiophoresis acts as a steering mechanism to guide microbial movement. However, the evidence to support this hypothesis is incomplete, because the underlying reorientation process is not directly demonstrated, and the necessary controls to rule out alternative hypotheses are not presented.

eLife Assessment

This important manuscript presents a way to understand allostery and allostery-inspired mechanical systems. It presents a mechanochemical model of an ATPase-like molecular machine in which geometric constraints and mechanically coupled linkages generate negative allostery, yielding a large stochastic reaction network that captures productive and futile cycling behavior. The work presents an interesting framework for bridging concepts from molecular motors and allostery. It provides a compelling, intuitive physical mechanism for mechanochemical transduction and reveals nontrivial tradeoffs that emerge from geometry-induced constraints.

eLife Assessment

This study presents a useful application of trans-omic network analyses to existing human brain datasets, generating systems-level insights into metabolic dysregulation in Alzheimer's disease. Overall, the authors' analytical choices are solid, with appropriate use of existing data and methods, and with many of their results confirming previous findings. However, some of the authors' key claims, related to previously unknown details of regulatory relationships, are only partially supported due to limitations in dataset cell-type resolution and network robustness, as well as a lack of functional validation. This work will be of interest to cellular or systems neurobiologists studying Alzheimer's disease and could serve as a helpful starting point for future work.

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

eLife Assessment

The authors propose a pipeline using large language models (LLMs) to benchmark experimentally well validated computational models of signaling networks. The findings are important, with available methods that guide testing future models and find new molecular interactions. Furthermore, the work shows how general-purpose LLMs can generate up to 91% of reactions of a bacterial metabolic network. The support is convincing and offers a number of performance metrics.

eLife Assessment

The study presents important findings revealing previously unresolved conformational dynamics of the heterodimeric type IV ABC transporter TmrAB using single-molecule FRET. The evidence presented is convincing, integrating careful experimental design with computational approaches to uncover states that are typically masked and difficult to detect. The work will be of interest to scientists studying the molecular mechanisms of primary active transport processes.

eLife Assessment

This important study addresses a classic debate in visual processing, using a strong method applied to an impressive dataset obtained from a rare clinical population to evaluate hierarchical models of visual object perception. The paper provides compelling evidence that the hierarchical model is only partly supported: as expected, neural responses in ventral visual cortex show increased representational selectivity for faces along the posterior-anterior axes, but the onsets of the signals do not show a temporal hierarchy, indicating more parallel processing.

eLife Assessment

This important study provides convincing evidence for our understanding of HIV transmission dynamics by age and sex in Zambia during the PopART trial. By combining phylogenetic and individual-based mathematical modelling (IBM), it adds depth to the epidemiological literature and may inform more strategic allocation of HIV prevention resources in sub-Saharan Africa. The authors employ two complementary and well-established methodologies (phylogenetics and IBM), and this dual approach is a notable strength.

eLife Assessment

This valuable study describes PXGS, a poly-transgene expression system that exploits the mutually exclusive splicing of Dscam variable exon 4 to enable conditional, simultaneous expression of up to 12 transgenes in Drosophila, addressing a longstanding limitation in which conditional co-expression has been restricted to a handful of genes. The approach is conceptually elegant and technically accessible, with potential applications spanning neuroscience, synthetic biology, and biomanufacturing across arthropod species. The evidence that Dscam exon 4 splicing is preserved in a UAS vector and that individual alternates can be replaced with functional transgenes is solid, and the in vivo axonal re-wiring application provides a convincing proof of principle. Quantitative characterization of expression levels, a direct demonstration of expression across all twelve positions, and additional imaging controls would further substantiate the system's utility and scope.

eLife Assessment

This study presents a valuable finding on linking the frequency of neural activity to cortical depths of blood flow in a naturalistic setting of participants listening to music. The presentation of evidence in the version of the original submission is incomplete, as further clarifications in methods and results, as well as performing additional analyses, would strengthen the study. The work will be of interest to cognitive neuroscientists working on multimodal recordings, auditory perception and music.

eLife Assessment

This study provides a useful anatomical resource by mapping the expression of four putative chemoreceptors in spinal cerebrospinal fluid-contacting neurons (CSF-cNs) of larval zebrafish. These descriptive findings offer an interesting entry point to explore how the nervous system senses signals within the spinal fluid microenvironment. The evidence supporting the spatial expression patterns of these receptors is convincing, utilizing high-resolution hybridization chain reaction (HCR) to validate previous transcriptomic data. However, the evidence remains incomplete regarding the actual functional roles of these receptors, as the study lacks protein-level validation, evidence of ligand availability in the CSF, or functional assays to demonstrate active chemoreception.