Evaluated articles

eLife Assessment

This study presents an important examination of the role of cis-acting versus trans-acting genetic variation on DNA methylation divergence between humans and chimpanzees, including its consequences for gene expression. By differentiating fused interspecies tetraploid cell lines into multiple cell types, the study provides compelling evidence for the importance of cis-acting changes, but incomplete evidence that these changes are of importance for adaptive trait evolution in humans. This work will be of interest to biologists and evolutionary anthropologists studying the evolution and genetics of gene regulation, particularly in primates.

eLife Assessment

This valuable study combines previously established mathematical models to investigate why cortical waves in starfish and Xenopus embryos propagate in opposite directions. The modeling results are solid and plausible, but remain experimentally untested. Improving the presentation and discussion of the results could make the study more accessible to a wider audience.

eLife Assessment

This study shows that combining forced cell cycle re-entry with Rbpj deletion enhances Müller glia dedifferentiation and promotes their conversion into retinal neuron-like cells in the uninjured mouse retina. It provides a valuable strategy for improving Müller glia-mediated neurogenesis and advancing regenerative potential in the mammalian retina. Overall, the data are convincing, but the conclusions would be strengthened by functional validation of the newly generated neurons and retinal performance, as well as an assessment of Müller glia long-term function and cell survival.

eLife Assessment

This important study probes the long-standing failure to resolve evolutionary relationships between the classical "spiralian" taxa-i.e., annelids, molluscs, brachiopods, platyhelminths and nemerteans-and provides convincing evidence that the branches leading to them are so short as to be unreliable guides to their relationships. This, in turn, has wide-ranging implications for our understanding of animal body plan evolution and the interpretation of early animal fossils.

eLife Assessment

This manuscript has convincing data that provides a high-resolution structure of the Egl-RNA complex. The findings are important to understand the formation, stability, and interactions of this complex. However, the manuscript could be improved by conducting a rigorous statistical analysis, a deeper understanding of apparent discrepancies in the stoichiometric Egl-to-RNA ratio, and exploring the specificity of this complex using a more diverse set of control RNAs.

eLife Assessment

This important study employed a multi-stage behavioural paradigm of increasing cognitive complexity to investigate the role of inhibitory interneurons in the medial prefrontal cortex (mPFC) in avoidance behaviour in mice. The authors used imaging and optogenetic techniques combined with this behavioural task to show that mPFC interneurons are necessary for encoding but not executing avoidance under threat. The evidence supporting these claims is compelling, and findings will be of interest to researchers in behavioural and systems neurosciences.

eLife Assessment

This important study investigates how the brain categorizes written words from different writing systems (e.g., alphabetic vs. non-alphabetic). The evidence supporting the authors' claims is solid and sheds light on the neural basis of language's social‑categorization function.

eLife Assessment

This important technical study introduces SCOPE, an optics-free spatial reconstruction method based on bidirectional sender and receiver oligonucleotides on barcoded hydrogel beads. By sequencing proximity-encoded chimeric molecules, the authors computationally reconstruct 2D and 3D spatial information at an impressive scale. The technical demonstrations in synthetic bead systems are convincing and establish proof-of-principle that large spatial domains can be reconstructed without microscopy. The methodological advance is clear and the scale is impressive. Direct validation in biological samples would help clarify what additional limitations on applicability may exist. This work will be of interest to those working on spatial mapping.

eLife Assessment

This valuable study addressed a key question in epilepsy research: whether the recordings of very fast oscillations in the brain (>250Hz, fast ripples) reflect underlying pathology or might be a property that emerges from a neuronal network at random. The strengths of the study are the importance of the question, the multiple methods, and the solid evidence. However, there are limitations to the methods that should be addressed.

eLife Assessment

This study provides a valuable contribution to understanding grid-to-place transformations, offering new insights into the structure and reliability of these representations and extending prior work in a meaningful way. The evidence supporting the authors' conclusions is solid, based on careful analyses and well-executed experiments, although clarity and mechanistic interpretation would be strengthened by improving sample size reporting, expanding population-level analyses, and future studies including simultaneous entorhinal-hippocampal recordings. The work will be of interest to neuroscientists studying spatial coding and hippocampal-entorhinal circuit function.

eLife Assessment

This study uses convincing modeling methods and analyses of rich behavioral datasets to investigate the role of attention in value-based decision making; for instance, as when choosing between two snacks. The results are valuable, as they challenge existing theories that assume that paying attention to an available option biases the eventual choice toward that option. The results suggest that the correlation between attention and decision-making is formed largely after and not before the (internal) choice process has terminated, a finding that offers an intuitively appealing rethinking of how attention and decision-making processes interact during value-based choices.

eLife Assessment

This study uses convincing modeling methods and analyses of rich behavioral datasets to investigate the role of attention in value-based decision making; for instance, as when choosing between two snacks. The results are valuable, as they challenge existing theories that assume that paying attention to an available option biases the eventual choice toward that option. The results suggest that the correlation between attention and decision-making is formed largely after and not before the (internal) choice process has terminated, a finding that offers an intuitively appealing rethinking of how attention and decision-making processes interact during value-based choices.

eLife Assessment

This fundamental study provides a major contribution to our understanding of Amyotrophic Lateral Sclerosis (ALS) pathogenesis by utilizing a primate model that overcomes the historical limitations of rodent paradigms. By demonstrating the retrograde and trans-synaptic spread of pathological TDP-43 from the periphery to the spinal cord and motor cortex, the authors propose a new model for the disease spreading. The evidence supporting these findings is compelling, characterized by rigorous post-mortem histological observations. This work will be of profound interest to neuroscientists and translational researchers seeking to decode the mechanisms of systemic disease progression in ALS.

eLife Assessment

This study presents a useful array of analyses of the effects of training and/or instruction to use the method of loci during episodic encoding and retrieval. A major strength of the experiment is the impressive recruitment of memory athletes and the training of novice athletes to use the method of loci, long known to improve the precision of memory recall. That said, the sheer number of results and their organization should be addressed; streamlining the results and placing them, whenever possible, in a theoretical framework. As it stands, the presented work is incomplete with respect to the major conclusions that training itself leads to neural differentiation of prefrontal cortical neural patterns, and the authors need to temper these claims.

eLife Assessment

This important paper provides novel information on the function of the Drosophila ryanodine receptor (RyR) during muscle development. The authors analyze the effects of a rare human mutation that causes myopathy that affects a conserved region of the gene. They present compelling evidence that this variant affects muscle function in flies. These results suggest that Drosophila can be used as a tool for screening additional variants.

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

eLife Assessment

This work provides a map of enhancer-promoter interactions associated with genes controlling the development of a specific neuronal cell population. The study offers a valuable resource and integrates multiple complementary datasets to provide insights into regulatory mechanisms, although the conceptual advances are moderate and the central message could be clearer. The evidence supporting the conclusions is generally solid, but the lack of direct functional testing of key regulatory elements limits the strength of some claims.

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

eLife Assessment

The authors provide valuable findings showing that GM-CSF prevents the loss of ILC3 populations during gut inflammation and inhibits pro-inflammatory cytokine production. They combine a preclinical model of gut inflammation in zebrafish with spatial transcriptomic analysis of samples from Crohn's disease patients. Although the data provided are clear and point to an anti-inflammatory role of GM-CSF, the strength of evidence remains incomplete as no mechanistic insights into GM-CSF regulation of ILCs are provided, and the most significant mechanistic question remains unanswered: what are the signals downstream of GM-CSF that maintain the ILC3 population? This work will be of interest to immunologists.

eLife Assessment

This is a useful study that seeks to elucidate the molecular mechanisms underlying spinal motor circuit assembly. The authors demonstrate that loss of Onecut transcription factors in spinal motor neurons affects the size and spatial distribution of pre-motor interneurons. However, the study in its current form is incomplete: the data and analyses do not fully support the main conclusion that Onecut acts through Neurotrophin-3 to regulate interneuron development in a non-cell autonomous manner. The work will be of broad interest to cell and developmental biologists.

eLife Assessment

This important study examines how chronic pain and opioid exposure interact at the cellular and molecular levels in a reward-related brain region. Using single-nucleus RNA sequencing, the authors map transcriptional changes in the rat ventral tegmental area following chronic inflammatory pain and acute morphine exposure. Notably, their convincing data support that acute morphine, not chronic pain, elicits a stress-related transcriptional response primarily in glial cells rather than neurons, challenging prevailing views of opioid action and supporting growing evidence for glucocorticoid signaling in glial responses. A limitation is the use of a single opioid dose and time point, and further discussion of these constraints would help clarify the broader implications of the findings.

eLife Assessment

The authors developed and validated a gut-on-chip system to mimic the gut environment for studies of Clostridioides difficile infection in vitro. Although the data generated is useful to the field, the evidence provided to support the conclusions is incomplete. Methodology that is not complete, as well as discrepancies regarding the proposed mode of action of lipoxin A4, are significant weaknesses.