Evaluated articles

eLife Assessment

This study offers important insights into how outer membrane vesicles (OMVs) secreted by Serratia marcescens, which carry various virulence factors, contribute to pathogenicity. The experiments provide solid preliminary support for OMV-mediated pathogenic effects, with a critical role for the metalloprotease virulence factor PrtA. However, the evidence remains incomplete, and the current level of validation limits confidence in the strength of the conclusions.

eLife Assessment

This valuable study presents an analysis of the gene regulatory networks that contribute to tumour heterogeneity and tumor plasticity in Ewing sarcoma, with key implications for other fusion-driven sarcomas. The authors employed compelling orthogonal approaches, including single-cell sequencing and xenografts, to reveal the existence and plasticity of specific gene regulatory networks (e.g., TGF-beta signaling) within Ewing sarcoma, as well as significant differences that exist between cell lines and patient tumors.

eLife Assessment

This useful study examines whether microsaccade direction primarily indexes shifts rather than the maintenance of covert spatial attention, offering a potentially informative account of inconsistencies in the prior literature. However, the evidence remains incomplete because the key effects are based on relatively sparse microsaccadic events, while concerns about event detection, fixation control, subject-level robustness, and the interpretation of gaze-density analyses remain unresolved. The correlational design and absence of a neutral condition or independent measure of attentional shifting further limit the central claim. The work will be of interest to researchers studying attention, eye movements, and visuomotor mechanisms.

eLife Assessment

This potentially important study examines the consequences of manipulating the expression of thyroxine-binding and amyloidogenic hepatocyte secretory protein transthyretin (TTR). Solid in vivo evidence from two dietary models supports that TTR production exacerbates liver injury, whereas the evidence for a link between TTR production, uptake, and calcium dysregulation is incomplete. If the findings are confirmed, they would provide evidence for a novel cell biological pathway of liver injury.

eLife Assessment

This fundamental work advances our understanding of the role of human hippocampal theta oscillations in memory encoding and retrieval. The evidence supporting the conclusions is convincing, using both scopolamine administration and intracranial EEG recordings. This work will be of broad interest to neuroscientists and has translational implications.

eLife Assessment

The authors adapt sequencing of nascent DNA (DNA linked to an RNA primer, "SNS-Seq") to map DNA replication origins in Trypanosoma brucei. The main impact of this work is reporting a new set of putative origins, which do not overlap with previously reported origins, but which appear to overlap with previously mapped DNA-RNA hybrid (R-loops). Thus, these valuable findings open up new avenues for further investigation into the mechanistic basis for firing of replication forks in this organism. However, the supporting evidence remains incomplete and would benefit from orthogonal validation. This work will be of interest to those studying DNA replication and epigenetic regulation of fork origins.

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 valuable study provides a systematically curated atlas of non-canonical open reading frames translated across normal human and mouse tissues by uniformly integrating nearly 400 ribosome-profiling datasets with independent mass-spectrometry evidence for ncORF-encoded peptides. The convincing analyses connect ncORF evolutionary age and coding constraint with translation level, tissue distribution, and co-translation with canonical coding sequences, offering a broad comparative view of how non-canonical translation changes over mammalian evolution. Although the functions of most ncORF-encoded peptides remain unknown, the scale of their detection across tissues, together with their proteomic and evolutionary signatures, suggests that a substantial subset may have biological functions.

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 and widespread across nearly all major animal phyla, with distribution in many lineages that are consistent with recent or ongoing genomic expansion. Using comprehensive phylogenetic and AlphaFold2-based structural analyses, together with new host-taxonomy concordance tests, the authors show that these elements independently acquired membrane fusion proteins early in metazoan evolution, likely predating the bilaterian-non-bilaterian split. The work offers significant 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

One-carbon tetrahydrofolate metabolism plays a crucial role in producing essential metabolic intermediates. In this valuable study, the authors employ a solid genetics-based approach to demonstrate that three distinct metabolic pathways are essential for synthesising 1C-tetrahydrofolates (1C-THF). Disrupting any of these pathways impairs both growth and virulence.