Evaluated articles

eLife Assessment

This manuscript makes a valuable contribution to understanding learning in multidimensional environments with spurious associations, which is critical for understanding learning in the real world. The evidence is based on model simulations and a preregistered human behavioral study, but remains incomplete because of inconclusive empirical results and insufficiencies in the modeling. Moreover, there are open questions about the nature and extent to which the behavioral task induced semantic congruency.

eLife Assessment

This important study uncovers a previously unrecognized light-responsive pathway in C. elegans that depends on live food bacteria and is mediated by the bZIP factors ZIP-2/CEBP-2 and the cytochrome P450 enzyme, CYP-14A5. The authors show that this bacteria-linked pathway modulates long-term memory and can be harnessed as a low-cost light-inducible expression system, opening new directions for sensory biology and genetic engineering in worms. The exact means by which live bacteria modulate light signal that activates ZIP-2/CEBP-2 in the worm remains to be elucidated. The evidence supporting the pathway's role uses multiple genetic, transcriptional, and behavioural assays, and is convincing.

eLife Assessment

This important study describes a deep learning framework that analyzes single-cell RNA data to identify a tumor-agnostic gene signature associated with brain metastases. The identified signature uncovers key molecular mechanisms, highlights potential therapeutic targets, and demonstrates a metastasis-specific transcriptional signal in circulating platelets, suggesting its promise for non-invasive diagnostics through liquid biopsy. The evidence supporting the findings is solid, utilizing interpretable deep learning methodologies and large-scale datasets across multiple cancer types, though some aspects may benefit from additional analysis and validation.

eLife Assessment

This important study provides new insights into the neuronal dynamics of the locus coeruleus in relation to hippocampal sharp-wave ripples. Using high-temporal-resolution, multi-site electrophysiological recordings in rats, the authors present solid evidence supporting their main claims. Nonetheless, some aspects of the evidence remain incomplete, and several points in the data presentation would benefit from clarification. Overall, the work will be of interest to neuroscientists studying large-scale brain coordination and memory processes.

eLife Assessment

This work offers important insights into the protein CHD4's function in chromatin remodeling and gene regulation in embryonic stem cells, supported by extensive biochemical, genomic, and imaging data. The use of an inducible degron system allows precise functional analysis, and the datasets generated represent a key resource for the field. The revised study offers compelling evidence and makes a significant contribution to understanding CHD4's role in epigenetic regulation. This work will be of interest to the epigenetics and stem biology fields.

eLife Assessment

Dong et al. present a valuable analysis of mutant phenotypes of the Rab GTPases Rab5, Rab7, and Rab11 in Drosophila second-order olfactory neuron development. This is a solid characterization and comparison of the different Rab mutants on projection neuron development, with clear differences for the three Rabs, and by inference for the early, late, and recycling endosomal functions executed by each.

eLife Assessment

This manuscript presents a valuable antiviral approach using an engineered ACE2-Fc fusion protein that demonstrates broad-spectrum neutralization capacity against SARS-CoV-2 variants and achieves significant prophylactic protection in animal models through a novel Fc-mediated phagocytosis mechanism. The study provides convincing evidence for protective efficacy through rigorous in vivo validation in mice, mechanistic characterization via biodistribution studies and macrophage depletion assays, and demonstration of antibody-dependent cellular phagocytosis as the primary clearance mechanism. However, there are some gaps that require attention, including the need for comparison with a previously reported ACE2 decamer, inclusion of control molecules, insufficient discussion of potential limitations such as off-target binding and immunogenicity risks, and lack of clarity regarding certain methodological aspects.

eLife Assessment

This valuable study uses mathematical modeling and analysis to address the question of how neural circuits generate distinct low-dimensional, sequential neural dynamics that can change on fast, behaviorally relevant timescales. The authors propose a circuit model in which spatially heterogeneous inhibition constrains network dynamics to sequential activity on distinct neural subspaces and allows top-down sequence selection on fast timescales. The study convincingly demonstrates how this mechanism could operate and makes predictions about connectivity patterns and dynamics.

eLife Assessment

This report provides useful evidence that EABR mRNA is at least as effective as standard S mRNA vaccines for the SARS-CoV-2 booster vaccine. Although the methodology and the experimental approaches are solid, the inconsistent statistical significance throughout the study presents limitations in interpreting the results. Also, the absence of results showing possible mechanisms underlying the lack of benefit with EABR in the pre-immune makes the findings mostly observational.

eLife Assessment

This useful study uses a combination of experimental and modeling approaches to investigate the role of actomyosin in epithelial invagination during Ciona siphon tube morphogenesis. Several types of solid quantitative analyses are presented, yet the evidence supporting the central claim of bidirectional translocation of actomyosin remains incomplete. Since epithelial invagination contributes to the morphogenesis of many developing organs, this work has the potential to appeal to both cell biologists and developmental biologists.

eLife Assessment

This important study presents a technically rigorous and carefully controlled analysis of the signalling potential of cancer-associated gain-of-function Notch alleles. The work is clearly presented, and the experiments are robust, comprehensive, and well-controlled. While some data primarily establish the system or report negative findings, the comparative approach in a well-characterized model provides convincing mechanistic evidence for how these Notch variants function. This study will be of interest to researchers in both developmental and cancer biology.

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 important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

eLife Assessment

This important study provides a theoretical framework for quantifying privacy risk from publicly shared genome-wide association summary statistics. The findings reveal the conditions under which genotype reconstruction may become feasible, challenging long-held assumptions about personal data safety. While the evidence is solid, supported by clear mathematical derivations and simulations, validation on large empirical datasets would further strengthen the claims.

eLife Assessment

The manuscript by Shukla et al. provides important mechanistic insights into kinesin-1 autoinhibition and cargo-mediated activation. Using a convincing combination of protein engineering, computational modeling, biophysical assays, HDX-MS, and electron microscopy, the authors reveal how cargo binding induces an allosteric transition that propagates to the motor domains and enhances MAP7 binding. Despite limitations arising from conformational heterogeneity and structural resolution, the study presents a unified mechanism for kinesin-1 activation that will be of broad interest to the motor protein, structural biology, and cell biology communities.

eLife Assessment

Mitochondrial DNA (mtDNA) exhibits a degree of resistance to mutagenesis under genotoxic stress, and this study on the mitochondrial Transcription Factor A (TFAM) presents valuable data concerning the possible mechanisms involved. The presented data are solid, technically rigorous, and consistent with established literature findings. The experiments are well-executed, providing reliable evidence on the change of TFAM-DNA interactions following UVC irradiation. However, the evidence is inadequate to support the primary claims.

eLife Assessment

This important study describes a new link between nutrient signaling and chromosome regulation, providing compelling evidence that reduced activity in the central nutrient-sensing pathway governed by TORC1 improves chromosome stability and alters gene expression in S. pombe through effects on cohesin. While the biological importance of this newly described circuit is not yet fully known, and some data would benefit from further clarification, the overall body of evidence supports the main conclusions.

eLife Assessment

This study investigates the folding and unfolding behavior of the doubly knotted protein TrmD-Tm1570, providing insight into the molecular mechanisms underlying protein knotting. The findings reveal multiple unfolding pathways and suggest that the formation of double knots may require chaperone assistance, offering valuable insights into topologically complex proteins. The evidence is solid, supported by consistent agreement between simulation and experiment, though some aspects of the presentation and experimental scope could be clarified or expanded.

eLife Assessment

This valuable work provides new insights into the role of lysine acetylation of alpha-synuclein, the protein involved in Parkinson's Disease. The evidence is mostly solid, but the claims around the potential disease relevance based on seeding assays and structural work need to be toned down, or else supported by additional experimental evidence. Overall, the work will be of interest to researchers in the fields of protein biophysics and post-translational modifications, as well as Parkinson's Disease.

eLife Assessment

Davis and colleagues describe findings that are fundamental to the understanding of pressure mechanosensation in lymphatic vessels and are of significant importance to other areas of mechanosensory physiology. Based on many different knockout mouse models and rigorous state-of-the-art pressure myography recordings, they present compelling evidence that mechano-activation of GNAQ/GNA11-coupled GPCRs generates IP3, which induces Ca2+ release from internal stores through IP3R1 and drives depolarization through the activation of ANO1 Cl- channels to induce lymphatic vessel contractility. Nevertheless, some aspects of the manuscript are incomplete. The specific identity of the GPCR(s) involved remains to be uncovered, as evidence of frequency-pressure impairment is only demonstrated with abolition of GNAQ/GNA11action, not the receptors per se.