Evaluated articles

eLife Assessment

The authors use a novel patch-leaving task to reveal a reward-reset strategy when mice choose to leave a depleting resource, and find that accumulated step-like activity in the dorsomedial striatum is correlated with the timing of these decisions. These important behavioral and neural findings are supported by substantial and convincing data. Additional control analyses would strengthen the evidence that these signals are specifically related to timing and patch-leaving decisions, rather than alternative task-related processes.

eLife Assessment

In this valuable study, the authors identified a rare population of Nestin-expressing cells within the external granule layer of the early postnatal mouse cerebellum. They demonstrated that these cells are distinct from Sox2+ progenitors and can give rise to medulloblastoma. Collectively, the findings provide convincing evidence that this unique Nestin+ population is susceptible to oncogenic transformation and may underlie the preferential emergence of Sonic hedgehog-driven medulloblastomas.

eLife Assessment

This study offers a large-scale resource that maps the transcriptional landscape following combinatorial transcription factor overexpression. The authors propose a modular framework for understanding gene regulatory networks and identify transcription factor cocktails for cellular reprogramming. While the dataset and proposed principles are valuable, the strength of the evidence is incomplete, in part due to the complexity of the computational analyses and limited orthogonal experimental validation. The study will be of interest to the fields of gene regulation and developmental biology.

eLife Assessment

The study presents valuable findings on early behavioral phenotypes that arise in an ADHD-associated adgrl3.1 mutant zebrafish, using a new behavioral approach with a closed-loop OMR assay. The evidence supporting the claims of the authors is solid; however, the validation of the method and analysis is incomplete and would benefit from more rigorous approaches and validation practices. This work will be of broad interest to developmental biologists and behavioral neuroscientists.

eLife Assessment

This study presents a valuable human organoid platform for investigating neuron-immune interactions in Alzheimer's disease and modeling the interplay between innate and adaptive immunity in the context of amyloid pathology. The system has the potential to advance the field by enabling the study of human-specific neuroimmune interactions that is difficult to recapitulate in rodent models. The evidence on the microglia-T cell crosstalk are convincing. The study will interest researchers in neuroimmunology and Alzheimer's disease.

eLife Assessment

This valuable paper reports on a measure of flexible brain state engagement, derived from fMRI, as a predictor of cognitive control. One strength of the study is the use of external datasets for validation and replication. The results are solid, although some may benefit from further explanation.

eLife Assessment

This valuable study aimed to explore whether sensory representations in the cortex reorganize on the same timescale over which behavioral changes first emerge. Convincing evidence is presented to show that reward-dependent plasticity takes place in the mouse barrel cortex within a single recording session as mice learn a whisker detection task. However, the evidence supporting the authors' proposal that this rapid reorganization may involve spontaneous reactivation of neurons that gain stimulus responsiveness during training is incomplete. The work will be of interest to systems neuroscientists studying cortical circuits and learning.

eLife Assessment

This valuable study describes a simple and robust approach for estimating information-limiting noise by splitting neural populations and comparing estimator values. The authors report more accurate and robust results compared to previous methods. The evidence for the robustness of the method is currently incomplete; some concerns regarding bias need to be resolved, and additional tests need to be provided on how the number of trials and neurons affect performance.

eLife Assessment

This work establishes a valuable theoretical finding about how the spike timing dependence of inhibitory plasticity shapes recurrent network connectivity. The combination of theoretical analysis and simulations provides convincing evidence that effective inhibitory connectivity forms a so-called Mexican-hat profile when multiple inhibitory neuron types follow distinct learning rules. These mechanisms are thought to be implicated in the contextual modulation of neuronal responses to stimuli.

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 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.

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 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 important study provides a detailed analysis of the transcriptional landscape of the mouse hippocampus in the context of various physiological states. The main conclusions are convincingly supported: that most transcriptional targets are generally stable, with notable exceptions in the dentate gyrus and with regard to circadian changes. The authors comprehensively addressed the concerns raised in the first round of review.

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 is an important study establishing the mechanistic principles on 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

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

eLife Assessment

This 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.