Evaluated articles

eLife Assessment

This useful study reports potential loss-of-function variants, pseudogenes and gene presence-absence variation across multiple chicken genomes, with potential implications for understanding genome evolution and domestication. The evidence for the central claims is unfortunately incomplete, as the inferences of gene loss are not sufficiently robust to account for assembly and annotation artifacts, and, in addition, the analyses can not distinguish between positive selection and relaxed constraint. The overall claim of large-scale gene loss being adaptive and thus being a major driver of chicken evolution and domestication is therefore not sufficiently supported. The area of the study is of interest to colleagues in evolutionary and comparative genomics as well as animal domestication.

eLife Assessment

This important study investigates how GDNF treatment restores nerve cells in the bowel of a mouse model of Hirschsprung disease, and proposes that this regeneration occurs through diverse resident precursor cells and a non-canonical signaling pathway. The evidence is solid for the ability of the treatment to induce new bowel nerve cells and for a contribution from multiple precursor populations, supported by extensive cell tracing and imaging experiments. This work will be of interest to researchers in developmental biology and peripheral neurobiology.

eLife Assessment

Dohi et al. asked what role the dorsal hippocampus and medial prefrontal cortex play during different temporal epochs of a memory-guided navigation task, a long-standing question for neuroscientists studying hippocampal-prefrontal contributions to working memory. This useful study used a delayed, cue-guided T-maze task in mice and reported impaired choice accuracy when silencing occurred early in the central-arm run but not during the delay. However, the evidence for the study's claim is incomplete in its current form: the silencing windows are not duration-matched across epochs, key negative findings rest on three to four mice without power analysis or reported effect sizes, no non-mnemonic control task distinguishes disrupted memory-guided behavior from a general action-selection deficit, and no neural recordings accompany the causal manipulations to verify the manipulations' assumed mechanistic effects. The reported perseveration also reflects an increased directional bias rather than repetition of the previous choice, and the language should be revised accordingly.

eLife Assessment

This study presents a valuable tool for comparing immune receptor data across multiple samples while properly accounting for statistical uncertainty and receptor similarity. The evidence supporting the tool is solid overall. However, some key concerns regarding potential sequencing artifacts in one of the validation datasets and an unclear strategy for false discovery rate control in the proposed framework remain to be addressed.

eLife Assessment

This study presents an open-source reinforcement learning framework for the real-time, closed-loop optimization of spatiotemporal electrical stimulation in engineered neuronal networks. Using single-spike-resolution activity as continuous feedback, the authors provide solid evidence that their platform can identify stimulation patterns that drive specific activity motifs within a structurally constrained four-node circuit. While this reproducible system offers a valuable and accessible tool for interacting with biological neural networks in an adaptive manner, further validation is needed to determine how well these stimulation strategies generalize to larger, unstructured, or more conventional network architectures.

eLife Assessment

This valuable study examines the relationship between simultaneous LC single-unit recordings and pupillometry, both within and across baseline and evoked epochs, finding that cross-epoch relationships are unreliable. The evidence is solid and suggests that care should be taken when interpreting pupil responses as reflecting LC activity. This manuscript will be interesting to basic and clinical researchers working in cognitive and decision neuroscience as well as computational psychiatry.

eLife Assessment

This study addresses a key question concerning whether neurofeedback can enhance the neural representation of a selected speaker during competing continuous speech and whether such enhancement translates into behavioral benefits. The solid findings provide important insights into the online modulation of auditory attention and the extent to which selective listening can be voluntarily controlled. Although the observed effects were relatively small and did not consistently persist beyond the feedback period, the study advances understanding in an under-explored area and provides a helpful foundation for future research on sustained learning and behavioral transfer.

eLife Assessment

This important study provides convincing evidence that somatosensory relay nuclei remain engaged during attempted hand movements following chronic cervical spinal cord injury, including in individuals with severe motor impairment. The combination of functional and quantitative MRI with physiological controls supports the main findings and may have implications that are of importance in understanding sensorimotor processing after spinal cord injury. However, the interpretation of this activity as specifically reflecting top-down, and particularly corticocuneate, signaling may be overstated. The origin and anatomical route of the observed activity appears to remain less firmly established.

eLife assessment

This study presents a reaction-coupled molecular simulation framework to investigate how enzymatic post-translational modifications regulate biomolecular condensates and where reactions preferentially occur within them. These findings are important, in particular, to the emergence of spatially heterogeneous reaction fluxes and enhanced activity at condensate interfaces. The work is timely and has implications beyond the immediate subfield, especially for understanding condensates as biochemical reaction centers. The strength of evidence is solid overall: the computational framework is well motivated and broadly supports the main conclusions, although some aspects of the model implementation, parameter choices, and controls would benefit from further clarification and validation.

eLife Assessment

This meta-analysis provides a valuable contribution by integrating findings from dozens of macaque electrophysiology studies to reconcile discrepancies in choice probability and identify factors that robustly influence choice signals in the visual cortex. Such systematic synthesis across studies is rare in this field, and the analysis provides solid evidence for several conclusions, including the cross-study consistency of the relationship between choice probability and sensitivity and the distinctiveness of V1.

eLife Assessment

This important study uses biochemical and single-molecule approaches to characterize how yeast Cdc13 assembles on single-stranded telomeric DNA and contributes to telomere protection. The evidence supporting the proposed model for Cdc13 assembly and its role at telomeres is solid. The findings provide insight into how Cdc13 contributes to the maintenance and protection of chromosome ends. This work will be of interest to researchers in telomere biology, DNA replication, biochemistry, and single-molecule biophysics.

eLife Assessment

This valuable proof-of-concept study tests and validates a novel magnetic resonance-based method - proton-observed proton-edited MRS - for tracking glucose metabolism in the brain beyond simple substrate uptake, without the need for specialist hardware typically restricted to research settings. The approach offers a promising way to assess excitation/inhibition balance by detecting labelled glucose metabolites. The pre-clinical data in mouse models provide convincing support for the authors' hypothesis. The evidence in the human brain is incomplete: the results would require further optimisation of the experimental set-up and validation in a larger group of volunteers. This work will be of broad interest to researchers studying psychiatric, neurodevelopmental, and related brain disorders.

eLife Assessment

There is a significant need for improved understanding of the neural circuit mechanisms for learning and memory dysfunction in Alzheimers disease. In this valuable study, Zheng and colleagues compare neural coding between wild-type and App knock-in rats experiencing different contexts. Solid evidence of a difference emerges when "spatial" and "temporal" neural coding dynamics are considered separately. However, the lack of a link between neural coding and behaviorally measured learning, and minor issues with the analyses, are limiting factors of the evidence and the significance of the work.

eLife Assessment

This important study demonstrates that pyroglutamylation of peptide ligands alters G protein-coupled receptor (GPCR) activation in a subtype-specific manner and proposes a novel mechanism whereby the posttranslational modification steers the distal conformation of the peptide within the orthosteric binding site. The strength of the evidence supporting receptor-specific functional effects is convincing, but the strength of the evidence supporting the proposed structural mechanism is incomplete. This study will be of interest to pharmacologists and cell biologists interested in posttranslational modifications (PTMs) and activation mechanisms of GPCRs.

eLife Assessment

This important paper studies how adiposity affects brain development in the ABCD study. Major findings include: (1) central adiposity indices (BRI, WHtR) show stronger cross-sectional associations with cognition than BMI, partially mediated by frontotemporal cortical morphology; (2) the rate of adiposity accrual, rather than static adiposity at either timepoint, predicts follow-up cognition and altered (attenuated) cortical thinning; and (3) among overweight/obese adolescents, central fat reduction is accompanied by accelerated cortical thinning and catch-up in inhibitory control. The strength of evidence is solid, with the main limitation related to only looking at the cerebral cortex rather than examining the whole brain. The subgroup observation that fat reduction may be accompanied by normalization of both cortical trajectories and inhibitory control is potentially clinically meaningful, suggesting reversibility rather than fixed deficit, and would be of broad interest if it withstands more rigorous analysis.

eLife Assessment

This in vitro study provides important evidence that the mitochondrial intermembrane space protein HAX1 functions as a direct activating cofactor of the AAA+ chaperone CLPB, resolving a longstanding question arising from the strong genetic, proteomic, and disease associations between these proteins. The convincing work advances our understanding of mitochondrial proteostasis by demonstrating that HAX1 promotes CLPB oligomerization and will potentially even enable the generation of small molecules that mimic the function of HAX1 in CLPB activation. The study will be of general interest to biochemists working on chaperones and/or mitochondrial biology.

eLife Assessment

This valuable study provides a detailed three-dimensional characterization of primary cilia organization in the postnatal mouse growth plate, revealing reproducible spatial patterns in ciliation, ciliary length, and orientation. The evidence supporting these descriptive findings is solid, based on high-quality quantitative imaging and complementary genetic, mechanical, and transcriptomic approaches. However, evidence for the broader mechanistic conclusions is incomplete, particularly regarding whether ciliary orientation is uncoupled from basal-body and cell orientation and whether its stability under altered mechanical loading reflects a cell-intrinsic program. The study provides a helpful foundation for understanding primary cilia organization and mechanobiology in the growing skeleton, while the mechanisms underlying these observations remain to be established.

eLife Assessment

This valuable study investigates the action of a floral homeotic transcription factor in different cell types. The results provide solid evidence that PhDEF shows more extensive binding and regulatory effects in the epidermis than in the mesophyll, supporting the conclusion that cell-layer context influences homeotic gene function. While there are some limitations, they do not undermine the principal observation of layer-dependent PhDEF activity, but the interpretation of the data is complicated by uncertainties in cell-type assignment and composition in the scRNA-seq data, the cell-type-enriched rather than strictly cell-type-specific nature of the ChIP-seq data, and differences in developmental stage between the single-cell and ChIP-seq experiments. The work will be of interest to developmental biologists studying transcriptional regulation and cell identity.

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

eLife Assessment

This is a potentially valuable study in the area of connectomics, comparing across species to obtain a uniform synaptic density of ~1 synapse per micron. While the methods add to the field, the datasets are limited and filtered, and the role of cell-type on spacing is passed over. Additionally, some of the analyses could be tightened; hence, overall, the findings remain incomplete.

eLife Assessment

This valuable study provides a very large data set of motor unit recordings in people with multiple sclerosis and, as such, could impact both foundational and clinical studies of the neuromuscular system. The study reports increased variability in firing rate profiles across participants and suggests that this observation reflects differences in the excitatory, inhibitory, and neuromodulatory drive reaching motor neurons. The descriptive finding is solid, but the link to specific neural mechanisms is incomplete as it depends heavily on assumptions related to its model-based framework.