Evaluated articles

eLife Assessment

This fundamental work significantly advances our understanding of how contact-dependent antagonism enables keystone bacteria to establish and maintain their niche over time. The evidence obtained is convincing, supporting most of the conclusions drawn. This work will be of significant interest to the microbiome research community.

eLife Assessment

This study reports an important and novel finding that TENT5A, an enzyme involved in fine-tuning poly(A) tail length on selected mRNAs, is required for proper enamel mineralization in mice. The evidence supporting the authors' conclusion that reduced expression of enamel matrix proteins (EMPs) in TENT5A-deficient mice results from shortened poly(A) tails remains incomplete, as TENT5A may possess additional functions independent of post-transcriptional regulation that are not addressed in the current study.

eLife Assessment

This important study characterizes a cascade of neural processes triggered by memory-based prediction errors. The study uses an impressive collection of approaches and methods to characterize and measure cognitive control, arousal, and memory changes as a function of memory-based violations. The analyses are technically sophisticated and rigorous and, taken together, provide solid evidence that there are multiple processes accompanying prediction errors, and that they differentially relate to successful encoding. The manuscript would be much improved by the addition of a discussion or visual schematic that integrates the numerous findings together into a more coherent model.

eLife Assessment

This computational study constitutes an extension to prior work on biophysical calcium-based synaptic plasticity rules with metaplasticity, investigating how single neurons can learn to perform non-linear pattern classification. This important work presents a significantly simpler solution to the studied problem with potentially broad applicability, there is however incomplete evidence to support the core conclusions.

eLife Assessment

This valuable study describes significant differences in prey capture behavior between PSD-95 knock-out and wild-type mice, despite prior work by the same authors showing only modest visual deficits in the former. The data convincingly demonstrated prey capture performance in PSD-95 knock-out mice to improve under monocular viewing conditions. However, this finding alone was inadequate to support the interpretation of results as revealing a deficit in binocular visual integration, especially given the lack of eye and head tracking data or consideration of alternative explanations for the observed behavior.

eLife Assessment

Using genome databases, the authors performed solid bioinformatic analyses to trace the genomic history of the clinically relevant Staphylococcus aureus tetracycline resistance plasmid pT181 over the last seven decades. They discovered that this element has transitioned from a multicopy plasmid to a chromosomally integrated element, and the work represents a valuable demonstration of the use of publicly available data to investigate plasmid biology and inform clinical epidemiology. This work will appeal to researchers interested in staphylococcal evolution and plasmid biology.

eLife Assessment

This study is a valuable contribution that comprehensively identifies and characterizes LC3B-binding peptides through a bacterial cell-surface display screen covering approximately 500,000 human peptides. The data presented are solid, although this approach has limitations (e.g., it cannot assess the effects of post-translational modifications, which are often relevant to LIR-mediated interactions). Validation of the newly identified binding peptides by demonstrating their interactions with full-length proteins in cells would further strengthen this manuscript.

eLife Assessment

This is an important study that identifies the developmental time window during which re-expression of TCF4 mutated in Pitt-Hopkins syndrome, can rescue phenotypic features of brain function in a TCF4 knockout mouse. The study presents compelling data using a viral transgenic intersection approach to show that TCF4 expression is required early in perinatal life. These findings have implications for the timing of possible gene therapy in people with Pitt-Hopkins-associated TCF4 mutations.

eLife Assessment

This important work substantially advances our understanding of the role of synaptotagmin-7 (Syt7) in short-term plasticity at cortical glutamatergic synapses. The evidence supporting the conclusions is convincing, with rigorous and elegant quantal-level iGluSnFR imaging and failure-based analyses at single boutons. The work will be of broad interest to synaptic physiologists and molecular biologists.

eLife Assessment

This study proposes a cross-species transcriptomic framework to predict vaccine reactogenicity, with implications for preclinical vaccine safety assessment. The findings show that mouse muscle transcriptomic signatures capture conserved inflammatory programs and can identify highly reactogenic formulations, with supportive but limited evidence for finer discrimination among licensed human vaccines. Overall, the work establishes a valuable foundation for translational biomarkers of reactogenicity, although the strength of evidence for broad cross-species predictive performance remains incomplete and would benefit from further validation.

eLife Assessment

The study presents a valuable finding on the ubiquitin-dependent regulatory loop in which proapoptotic Bim is targeted to the E3 ubiquitin ligase Cul5-Wsb2-mediated degradation through its sequestration by BCL2 proteins. The conclusions are supported by incomplete evidence and would benefit from additional experiments addressing both the mechanistic understanding and the physiological/cancer-related significance of the study.

eLife Assessment

This important study provides mechanistic evidence that tea-adapted two-spotted spider mite overcomes green tea catechin defenses via the horizontally transferred dioxygenase TkDOG15, supporting a two-step adaptation model, combining enzyme refinement and inducible upregulation. The evidence is convincing because multi-omics signals converge with functional validation (RNAi knockdown and recombinant enzyme assays) and well-controlled behavioral/toxicity assays to link TkDOG15 activity and expression to survival and feeding on tea.

eLife Assessment

This structural biology study provides insights into the assembly of the GID/CTLH E3 ligase complex. The multi-subunit complex forms unique, ring-shaped assemblies and the findings presented here describe a "specificity code" that regulates formation of subunit interfaces. The data supporting the conclusions are convincing, both in thoroughness and rigor. This study will be valuable to biochemists, structural biologists, and could lay foundation for novel designed protein assemblies.

eLife Assessment

This convincing study examines a novel interaction of RAB5 with VPS34 complex II. Structural data are combined with site-directed mutagenesis, sequence analysis, biochemistry, yeast mutant analysis, and prior data on RAB1-VPS34 and RAB5-VPS34 interactions to provide a new perspective on how RAB GTPases recruit related but distinct VPS34 complexes to different organelles. The judgment is that this work represents a fundamental advance in our understanding of VPS34 localization and regulation.

eLife Assessment

This important study presents a convincing methodological approach to probe the structural features of the full-length human Hv1 channel as a purified protein. The method is supported by rigorous biochemical assays and spectral FRET analysis, which will interest biophysicists and physiologists studying Hv1 and other ion channels and membrane proteins. Overall, the work introduces an interesting labeling strategy and provides a methodology that is of value in investigating hHV1 in particular and can be extended to other ion channels. The authors also provide preliminary observations regarding conformational changes induced by zinc.

eLife Assessment

Li et al. present an important and innovative study linking developmental changes in sleep to ecological context in Drosophila mojavensis, and propose that sleep at one stage of an animal's life might anticipate needs at a future stage. The results fit well with this model, but are correlative in nature. The work is convincing, scientifically rigorous, and effectively bridges sleep biology and evolutionary ecology, opening promising new directions for the field.

eLife Assessment

This study provides useful insights regarding the alterations of sleep architecture in a knock-in mouse model of Alzheimer's Disease (AD). These include age-related hyperactivity that is typically associated with increased arousal, a normal homeostatic response to sleep loss, and a stronger AD-like phenotype in females. Although the analyses are robust, evidence for the proposed mechanisms underlying abnormal sleep architecture is incomplete. Overall, the study may have a focused impact for the sleep and AD fields.

eLife Assessment

This manuscript describing the phenotypes associated with loss and gain of RVCL-S documents important findings that have practical implications. Although the data and methods are solid and support many claims, there remain some concerns about mechanisms.

eLife Assessment

This manuscript reports high-resolution cryo-EM structures of a trimethylamine N-oxide demethylase and advances the hypothesis that the enzyme is bifunctional, coupling TMAO demethylation to formaldehyde capture via an enclosed intramolecular tunnel. The structural findings remain valuable, particularly the unusual oligomeric architecture and proposed conduit for a reactive intermediate. While the revision improves clarity and addresses several technical concerns, the central mechanistic framework remains incomplete, with persistent concerns regarding the proposed catalytic mechanism and metal dependence.

eLife Assessment

This important study provides a comprehensive comparison of the mechanisms through which different inhibitors affect the SARS-CoV-2 main protease, a pivotal antiviral drug target, and suggests a potentially broad-spectrum strategy to inhibit this critical viral enzyme by disrupting its dimerization states. However, whereas the biophysical analyses of the dimer stability are convincing, evidence supporting this new mode of mechanism to inhibit the main protease is incomplete and would benefit from a correlation of the biophysical observations with functional activity. With the functional validation part strengthened, this work would be of interest to biochemists and virologists working on anti-coronavirus drug discovery.