Evaluated articles

eLife Assessment

Recent studies have shown that mRNA can be acetylated (ac4c), altering mRNA stability and translation efficiency; however, the role of mRNA acetylation in the brain remains unexplored. In this important study, the authors demonstrate that ac4c occurs in synaptically localised mRNAs, mediated by NAT10. Conditional reduction of NAT10 protein levels led to decreases in ac4c of mRNAs and deficits in synaptic plasticity and memory. These solid results suggest that mRNA acetylation may play a role in memory consolidation.

eLife Assessment

This manuscript presents a valuable investigation of the peptidoglycan (PG) recycling pathway in Caulobacter crescentus. The authors showed that PG recycling in C. crescentus is essential not only for β-lactam (ampicillin) resistance but also for cell morphology, efficient division, and overall fitness. The study is comprehensive and compelling.

eLife Assessment

This study presents a large, systematically curated catalog of non-canonical open reading frames (ncORFs) in human and mouse through the reanalysis of nearly 400 Ribo-seq datasets using a standardized pipeline; the resulting atlas consolidates ncORF annotations across tissues and provides a valuable resource for investigating non-canonical translation and ORF emergence. The main conclusions are supported by consistent data processing and multiple computational measures of translation and conservation. While the pipeline is transparent and technically robust, some analytical criteria and dataset limitations could be described more explicitly, and several downstream conclusions would benefit from more cautious interpretation, some evolutionary inferences are primarily correlative; dataset heterogeneity, uneven tissue representation, and limited experimental validation also constrain the strength of a subset of the findings. Overall, the evidence is solid, and the resource is likely to be broadly beneficial to the community.

eLife Assessment

This study provides a useful investigation of human-AI interaction and decision-making, using both behavioral and electrophysiological measures. However, the theoretical framework and experimental design are incomplete, with an unclear task structure and feedback implementation limiting interpretability. With these issues addressed, the work could make a significant contribution to understanding human-AI collaboration.

eLife Assessment

This important study provides convincing evidence that envelope-carrying Ty3/gypsy retrotransposons (errantiviruses) are ancient, widespread, and actively expanding across nearly all major animal phyla. Using comprehensive phylogenetic and AlphaFold2-based structural analyses, the authors show that these elements independently acquired membrane fusion proteins early in metazoan evolution, likely predating the bilaterian-non-bilaterian split. While some aspects could be more clearly contextualized and explained better, the work offers insights into the deep evolutionary roots of retroelement-envelope associations and the origins of retroviruses.

eLife Assessment

The authors identify the Bearded-type small protein E(spl)m4 as a physical and genetic interactor of TRAF4 in the Drosophila wing disc. These valuable findings with potential biomedical relevance are, however, supported by incomplete evidence based largely on overexpression studies that lack quantification, limited molecular support for their model, and issues with Bearded family protein specificity. The work could be of interest to researchers in the fields of cell signaling and developmental biology.

eLife Assessment

This manuscript makes a valuable contribution to the concept of fragility of meta-analyses via the so-called 'ellipse of insignificance for meta-analyses' (EOIMETA). The strength of evidence is convincing, supported primarily by an example of the fragility of meta-analyses in the association between Vitamin D supplementation and cancer mortality, but the approach could be applied in other meta-analytic contexts. The significance of the work could be enhanced with a more thorough assessment of the impact of between-study heterogeneity, additional case studies, and improved contextualization of the proposed approach in relation to other methods.

eLife Assessment

This study presents a useful overview of the taxonomic composition of the microbiome associated with Dactylorhiza traunsteineri, a widely distributed orchid species in Central Europe. The evidence supporting the claims of the authors is incomplete, especially when it comes to the (secondary) metabolic pathways found in the metagenome assembled genomes, and requires more substantial analysis to be able to claim that these pathways play a key role in microbiome-orchid symbiosis.

eLife Assessment

The authors aim to understand why Kupffer cells (KCs) die in metabolic-associated steatotic liver disease (MASLD). This is a valuable study using in vitro studies and an in vivo genetic mouse model, suggesting that increased glycolysis contributes to KC death in MASLD. The data presented are now convincing and adequately revised. This work will be of interest to researchers in the immunology and metabolism fields.

eLife Assessment

This is a useful study that examines the relationship between neuropeptide signaling and the precision of vocal motor output using the songbird as a model system. The study presents evidence based on differential expression patterns and genetic or pharmacological inhibition of various neuropeptide genes for a causal role in song performance; however, this evidence is incomplete.

eLife Assessment

This study examines the role of the fungal pathogen Candida albicans in the progression of colorectal cancer, a relevant and urgent topic given the global incidence of colon cancer. While the findings are useful and provide solid experimental work and insight into how Candida may contribute to tumor progression, the small patient sample size, reliance on in vitro models, and absence of in vivo validation may limit its impact. This work will interest scientists studying cancer progression and the role played by pathogens.

eLife Assessment

The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels. The authors suggest that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

eLife Assessment

The study curated a set of Liver X receptor ligands that may guide the design of future drugs that activate the Liver X receptor as potential therapeutics for cardiovascular disease, Alzheimer's and type 2 diabetes, without inducing mechanisms that promote fat/lipid production. The authors also present improved multiplexed precision CRT (coregulator TR-FRET) and cellular assays which allows measurement of ligand potencies to displace corepressors in the presence of coactivators, which cannot be achieved in a regular CRT assay. This makes the evidence presented compelling as it stretches beyond the current state-of-the-art, and these important findings are expected to have practical implications in many sub-fields and remain of interest to scientists working in cell and molecular biology, drug discovery, medicinal chemistry and pharmacology.

eLife Assessment

The one-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this study, the authors employ a genetics-based approach to demonstrate that three different metabolic pathways are essential for synthesizing 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence. Although the work presented is valuable, the experimental evidence remains incomplete without direct quantification of folate intermediates.

eLife Assessment

This important study presents convincing evidence that uncovers a novel signaling axis impacting the post-mating response in females of the brown planthopper. The findings open several avenues for testing the molecular and neurobiological mechanisms of mating behavior in insects, and in the revised version the authors provide further evidence supporting their conclusions.

eLife Assessment

This important study reports on the relationships between cerebral haemodynamics and a number of factors that relate to genetics, lifestyle, and medical history using data from a large cohort. Compelling evidence suggests that brief arterial spin labelling MRI acquisition can lead to both expected observations about brain health, as manifested in cerebral blood flow, and biomarkers for use in diagnosis and treatment monitoring. The results can be used as a starting point for hypothesis generation and further evaluation of conditions expected to affect haemodynamics in the brain.

eLife Assessment

This manuscript describes a valuable screening approach to identifying nanobodies with the potential to modulate gene expression via epigenetic regulators. While the concept is of interest and the screening strategy is well designed, the current evidence supporting mechanistic specificity remains incomplete.

eLife Assessment

This valuable study addresses a critical question regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, despite the inclusion of interesting behavioral and imaging data, significant limitations remain, even after revision, in the design of the motor learning task and the associated data analyses. As a result, the presented data are incomplete to support the central conclusions.

eLife Assessment

This valuable study shows that regions of the human auditory cortex that respond strongly to voices are also sensitive to vocalizations from closely related primate species. The study is methodologically solid, though additional analyses - particularly those isolating the acoustic features that differentiate chimpanzee from bonobo calls - would further strengthen the conclusions. With additional analyses and discussions, the work has the potential to offer key insights into the evolutionary continuity of voice processing and would be of interest to researchers studying auditory processing and evolutionary neuroscience in general.

eLife Assessment

This study presents a valuable RNA velocity method which predicts the transcription rate linearly based on the expression of RNA levels of transcription factors with addition of comprehensive analyses. The evidence supporting the claims of the authors is solid, although inclusion of a full simulation would have strengthened the study. The work will be of interest to scientists working in the field of RNA biology and precision medicine.