Evaluated articles

eLife Assessment

This is an important study that develops multiple human iPSC-based models to study the consequences of DNMT3A mutations in Tatton-Brown-Rahman Syndrome. Convincing evidence shows dysregulation of GABAergic interneuron development and function, and the authors identify some of the key signaling mechanisms underlying these changes. This study will be of interest for understanding the functions of DNMT3A in brain development and the causes of neurological dysfunction in Tatton-Brown-Rahman Syndrome.

eLife Assessment

This valuable study builds a novel auditory-motor paradigm to investigate how the brain learns associations between movements and their auditory consequences. Solid evidence is provided for early ERPs (50-100 ms latency) reflecting violations of established key-pitch mappings. The writing, however, could be streamlined to better emphasize the paper's key contribution, and some statistical analyses might be improved.

eLife Assessment

This useful study asked whether the behaviour of motor units from a hand muscle changed across the two mechanical actions it performs. The authors used high-density intramuscular electrodes to record the activity of several motor units and reported changes in motor unit recruitment order across tasks that were not dependent on motor unit properties, suggesting differential spinal contributions to the two actions. However, the evidence supporting their main claims is incomplete, and some of the conclusions are based on unsubstantiated assumptions: the authors should correct several key analyses and temper claims that are not directly backed up by their data.

eLife Assessment

The authors make the valuable observation that directional memory during epithelial cell migration is enhanced compared to single-cell migration. They attribute this effect to adherens junctions and vinculin dimerization. In the work, central measures should be defined more precisely, and the support for their claims about the roles of adherens junctions and vinculin dimerization in memory enhancement remains incomplete.

[Editors' note: this paper was previously reviewed by another journal.]

eLife Assessment

The study provides valuable findings suggesting that modifying the donor's diet improves the effectiveness of fecal transplant therapies for liver disease. Although the reported results are of value, the evidence supporting the overall conclusions is incomplete. In particular, causal inferences regarding the effects of microbiota composition, as well as caproic acid signaling on the phenotypes studied, need further confirmation.

eLife Assessment

This study addresses the mechanism of action of benzoylurea insecticides and explores the metabolic consequences of inhibiting glycogen breakdown in insects. Both reviewers identify major flaws with the premise of the work. The strength of the provided evidence is inadequate as the data do not, or poorly, support several central claims. The significance of the findings is considered marginal.

eLife Assessment

This manuscript proposes a valuable idea on how cortical networks may learn a helpful representation of sensory stimuli. The model implementing this idea is tested in multiple experimental paradigms. However, the evidence remains incomplete as to whether the method supports both invariance and equivariance and whether it can estimate the dynamics of the moving object.

eLife Assessment

This valuable study examines how the prelimbic cortex represents learned and generalized threat over time and identifies potentially distinct stable and dynamic subnetworks that may support these functions. The work is conceptually interesting and is strengthened by the longitudinal calcium imaging approach and the inclusion of key control groups. However, the evidence supporting the claims is incomplete, particularly because the interpretations regarding inference, time-dependent representational change, and the dissociation of neural activity from freezing behavior extend beyond what is currently established by the data.

eLife Assessment

This valuable study presents a tool that uses brain anatomy to predict the layout and size of early visual maps, and it is strengthened by the use of a large and diverse collection of scans to examine differences across people and groups. The evidence is solid for the general usefulness of the approach, but incomplete for some of the broader claims about prediction accuracy and use across data sets, particularly for estimates of map size and for showing that the model improves on repeated functional measurements. This paper is likely to be of significant interest to visual perception researchers, especially those who use fMRI.

eLife Assessment

Fujita et al. examine the effects of AM-2099, a Nav1.7 inhibitor, on the excitability of human dorsal root ganglion neurons and compare these results to their prior study of Nav1.8 inhibition by suzetrigine. They show that the Nav1.7 inhibitor primarily alters action potential threshold and initiation, but not repetitive firing, whereas Nav1.8 inhibition elicits much stronger inhibition on repetitive firing. These complementary roles of Nav1.7 and Nav1.8 provide a plausible cellular explanation for the limited clinical success of Nav1.7 inhibitors compared to Nav1.8 inhibitors for chronic pain. While the conclusions are important and solid, there are some key shortcomings that should be addressed to strengthen the study.

eLife Assessment

This short report is an important study that visual acuity declines nonlinearly with cone dropout, while eye motion partially compensates by improving sampling from remaining cones. The method for experimentally simulating cone dropout is compelling, leveraging state-of-the-art imaging and testing in human subjects. Inclusion of additional analysis on absolute cone density and eye motion would further strengthen the study.

eLife Assessment

This valuable study analyses correlations between traits of Chinese frog species and their Red List status, finding differences between adults and larvae and thus pointing to the importance of considering different life-cycle stages in this and possibly other animal groups when assessing species extinction risks. The current study is, however, incomplete because of unclear threat categories for tadpoles, the omission of other key species traits, and insufficient statistical analysis.

eLife Assessment

This work provides a fundamental advance through a detailed and integrative analysis of how the tsetse fly feeds on blood, demonstrating that successful penetration depends on subtle structural adaptations rather than extreme forces or unusual anatomy. By combining high-resolution imaging, innovative biomechanical measurements, and experiments on artificial skin, the study offers complementary and compelling evidence, with clear data supporting a robust mechanistic interpretation. These findings have broad significance as they clarify the biomechanics of vector feeding with implications for the transmission of diseases such as African trypanosomiasis across diverse hosts.

eLife Assessment

This useful work addresses a longstanding question of how the extant genetic code came to be selected and conserved almost universally across life. Using a mutational approach and a small set of reporters, the authors demonstrate that the mutational impact was similar for non-standard genetic codes. Considering the limitations of the approach, the data are incomplete in supporting the claim of having provided 'experimental verification of the error minimization theory'.

eLife Assessment

This important study highlights how cell size influences various cellular responses, with a particular focus on ferroptosis. The evidence presented is convincing, employing multiple model systems and experimental approaches to support the conclusions. This work will be of significant interest to the fields of cell size, ferroptosis, and cancer biology.

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

eLife Assessment

This study investigates the role of the Z-disc protein Zasp52 in Drosophila flight muscles and provides evidence that an intrinsically disordered region (IDR) helps to stabilize and promote the localization of the protein to the Z-disc. Overall, this represents an important study that provides insights into Z-disc function and maintenance. The data are convincing, supported by strong genetic evidence and behavioral tests, well-controlled experiments, and detailed statistical analyses. Additional functional analyses designed to tease out specialized regions within the newly described isoform of Zasp52 would further strengthen models regarding the function of the protein.

eLife Assessment

This important study identified Mex3a protein with dual RNA-binding protein/ubiquitin ligase function as a pivotal regulator of olfactory sensory neurons (OSN) differentiation and lineage fidelity. The authors employed a combination of systems biology approaches (e.g., single-cell RNA sequencing, proteomics) and newly developed animal models (e.g., HyperTRIBE) to provide solid evidence that abrogation of Mex3a disrupts cilia structure and polarity of OSNs. Notwithstanding that this article is of a broad potential interest across different biomedical disciplines ranging from RNA to developmental biology, additional mechanistic data connecting identified Mex3a mRNA targets and ensuing OSN phenotypes would further strengthen this study.

eLife Assessment

This is an important study uncovering a new role of the SETD6-PPARγ axis in the regulation of hepatic lipid metabolism. The data convincingly demonstrate that methylation of PPARγ by SETD6 plays a key role in this process, linking lysine methylation to transcriptional control of lipid storage genes.

eLife Assessment

In this useful manuscript, Yang et al attempt to show that platelet recruitment to the liver via macrophages contributes to APAP-induced liver injury, but there were many areas where the data supporting the conclusions were incomplete. For example, the idea that platelets only affected KC glycolysis, but not the metabolism of other cells, to mediate the phenotype after injury is not adequately supported by the evidence. It is recommended to perform additional experiments to strengthen the conclusions.

eLife Assessment

This study presents a useful database resource containing protein conformations generated through molecular dynamics simulations, with extensive quality evaluation and benchmarking. While the database is well-constructed and professionally organized, the evidence supporting its claimed representation of protein conformational landscapes is incomplete, as the short simulation times and starting structure bias prevent true Boltzmann sampling of the conformational space.