Evaluated articles

eLife Assessment

This study presents an important large-scale behavioral and transcriptomic analysis of Drosophila that are heterozygous for putative loss-of-function alleles of homologs of human genes that have been linked to autism spectrum disorders. The authors consider 48 genes as hits from their screen, which show significant behavioral alterations in sleep, basal activity, and/or social behavior, and significant sexual dimorphism. The authors then focus on the domino/SRCAP gene as a candidate regulator of sleep, social behavior, transcriptional programs, and RNA splicing. The work generates a solid dataset and applies quantitative analytical approaches that will be of interest to researchers in the field, yet the evidence presented remains incomplete because issues of genetic background need to be further addressed.

eLife Assessment

This manuscript describes a valuable study of the mechanism by which acetylation on the histone H3 core domain regulates RNA polymerase II transcription passing through nucleosomes. The authors provide convincing evidence that acetylation influences transcription in a context-specific fashion. Some questions relating to the static nucleosome structures and the polymerase passage remain, but this manuscript will be of considerable interest to researchers in the chromatin and transcription fields.

eLife Assessment

This important study provides a mechanistic view of how antibody affinity maturation can reshape encounter-state landscapes and association pathways, with implications for understanding HIV antibody maturation and vaccine design. The results are solid, supported by a coherent integration of adaptive molecular dynamics, Markov state modeling, SPR kinetics, mutagenesis, and double-mutant cycle analysis, although aspects of the kinetic validation, MSM-state robustness, and causal interpretation would benefit from further support. The work will be of interest to immunologists, structural biologists, and computational biophysicists.

eLife Assessment

This valuable study introduces MULTI i², a robust and high-throughput method to measure Plasmodium falciparum viability in the presence of drugs. This new assay offers significant time savings over the traditional Parasite Reduction Rate (PRR) assay and should enable faster screening of drug combinations, which is urgently needed in the field. The assay is well validated, with convincing data showing it can reproduce known drug interactions and identify new interaction patterns.

eLife Assessment

This study makes a solid and valuable contribution to elucidating the intricate relationship between mitochondrial calcium and neuronal survival. Well-controlled experiments show that homeostatic mitochondrial calcium correlates with the most resilient neuronal subtypes after optic nerve injury. However, altering mitochondrial calcium levels does not affect neuronal survival as initially predicted by this correlation.

eLife Assessment

This study presents a key finding: self-generated mechanical stresses enable collective protocell proliferation without dedicated division machinery, offering insight into primitive life's population growth. While quantitative imaging, membrane tension measurements, and computational modeling support the mechanism, establishing causal links between deformation and division and testing sensitivity assumptions would strengthen the work. Overall, the work reports important findings, and although the evidence in support of the conclusions is largely solid, some incomplete elements need to be addressed.

eLife Assessment

This important study combines experimental evidence with computational modeling to suggest that neurons in the frontal eye field form two overlapping topographical maps, one for visual inputs and the other for eye movement directions. The experiments leverage the smooth cortex of the marmoset to provide solid evidence that two maps exist at different scales. The modelling work provides a potential mechanistic insight into how these patterns may be used for flexible visuomotor transformations.

eLife Assessment

By mining the Logan assemblage of the Sequence Read Archive to reveal substantial papillomavirus diversity, this valuable study establishes a framework for integrating viral discovery with host, geographic, and ecological metadata. The evidence for identifying novel papillomavirus sequences is convincing, supported by large-scale sequence searches, established L1-based typing criteria, phylogenetic analyses, protein annotation, and structural comparisons. The broader host-association and ecological conclusions are more tenuous due to heterogeneous public metadata and uneven sampling, and would benefit from clearer discussion of potential biases, contamination, endogenous viral elements, and alternative explanations. The work should be of interest to a broad range of colleagues in the areas of microbiome research, virology, and viral evolution.

eLife Assessment

This important study addresses a timely issue at the intersection of mitochondrial and telomere biology by focusing on the relationship between naturally occurring variants in the mitochondrial genome and telomere length. This work thereby provides a conceptual and experimental framework for investigating communication between mitochondria and telomeres. Using an innovative transmitochondrial cybrid approach, the authors provide evidence that mitochondrial DNA variants influence telomere maintenance through effects on mitochondrial function, reactive oxygen species, and NAD⁺-dependent repair processes. The evidence supporting the central conclusion that mitochondrial genotype influences telomere-associated phenotypes is convincing and is strengthened by the use of complementary functional and rescue experiments. However, some of the mechanistic interpretations and broader conclusions regarding telomere length inheritance in humans would benefit from additional donors and longitudinal analyses following cybrid generation, or more cautious framing.

eLife Assessment

This important study combines behavioural analysis, voltage imaging and electrophysiology to advance our understanding of muscle coordination at the cell-to-cell level, in Caenorhabditis elegans. The evidence supporting the conclusions is convincing; however, the use of correlation in some aspects of data interpretation is a relative weakness. The technically sophisticated optogenetic voltage clamp approach introduced here can be applied to other small, transparent animals, making these findings of broad interest to researchers studying electrical coupling between cells or utilising optical electrophysiology techniques.

eLife Assessment

This important study describes how selective lesions of key cortical and subcortical motor areas affect reaching actions in macaque monkeys. The results will be of interest to both basic and clinical researchers studying the neural control of movement. Kinematic analysis of movement quality is solid but could be improved by considering other metrics, especially those that relate to grasping. Evidence for the general claims related to the role of specific motor areas is incomplete because the lesions did not fully eliminate any single area while simultaneously involving neighbouring areas.

eLife Assessment

This valuable study presents a comprehensive exploration of c-di-GMP-associated protein interaction networks in Pseudomonas fluorescens, with a particular focus on biofilm-related phenotypes. The evidence is convincing, supported by a genome-wide yeast two-hybrid screen, phenotypic analyses, and experimental validation. The work identifies multiple interaction hubs and provides a resource that will be of use to the biofilm and c-di-GMP communities, while additional mechanistic exploration would further enhance its impact by clarifying the biological roles of many of the identified interactions.

eLife Assessment

Murrell et al. describe a high-throughput method, the Feeding Experimentation Device (FED3), to study food foraging strategies in mice. The authors provide solid evidence about key sex differences in foraging strategies, specifically the finding of greater male win-stay behavior. Further consideration of how sex differences could be uniquely influenced by FED3 testing conditions (e.g., single-housing, hormones) and task demands (e.g., 100-0 vs. 80-20) would be helpful. Given this open source FED3 platform, the authors provide valuable findings that have utility to the field of behavioral neuroscience, specifically to those interested in studying reward-related behavior.

eLife Assessment

This important study conducted by Hall and colleagues advances our understanding of host-pathogen co-evolution by providing an elegant multi-omic comparative framework that uncovers a profound, pathogen-directed epigenomic reprogramming of bovine alveolar macrophages uniquely driven by host-adapted Mycobacterium bovis. Convincing evidence supports these findings and draws on robust, multi-layered high-throughput sequencing data integrated with large-scale cattle GWAS metadata to prioritize actionable genetic variants linked to disease susceptibility and to highlight key immune response genes/pathways upregulated in response to infection and pathogen-specific host adaptation mechanisms.

eLife Assessment

This important study investigates how verbal and nonverbal working-memory processing is distributed across large-scale functional networks in the human brain using precision fMRI. By leveraging extensive within-subject data and individualized network mapping, the authors provide solid evidence that hemispheric specialization for verbal versus nonverbal information extends across multiple association networks and is reproducible across independent datasets. The use of state-of-the-art precision neuroimaging approaches reveals fine-grained laterality patterns that are likely obscured in conventional group analyses.

eLife Assessment

This study presents a useful application of trans-omic network analyses to existing human brain datasets, generating systems-level insights into metabolic dysregulation in Alzheimer's disease. Overall, the authors' analytical choices are solid, with appropriate use of existing data and methods, and with many of their results confirming previous findings. However, some of the authors' key claims, related to previously unknown details of regulatory relationships, are only partially supported due to limitations in dataset cell-type resolution and network robustness, as well as a lack of functional validation. This work will be of interest to cellular or systems neurobiologists studying Alzheimer's disease and could serve as a helpful starting point for future work.

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

eLife Assessment

This valuable study describes PXGS, a poly-transgene expression system that exploits the mutually exclusive splicing of Dscam variable exon 4 to enable conditional, simultaneous expression of up to 12 transgenes in Drosophila, addressing a longstanding limitation in which conditional co-expression has been restricted to a handful of genes. The approach is conceptually elegant and technically accessible, with potential applications spanning neuroscience, synthetic biology, and biomanufacturing across arthropod species. The evidence that Dscam exon 4 splicing is preserved in a UAS vector and that individual alternates can be replaced with functional transgenes is solid, and the in vivo axonal re-wiring application provides a convincing proof of principle. Quantitative characterization of expression levels, a direct demonstration of expression across all twelve positions, and additional imaging controls would further substantiate the system's utility and scope.

eLife Assessment

This study presents a valuable finding on linking the frequency of neural activity to cortical depths of blood flow in a naturalistic setting of participants listening to music. The presentation of evidence in the version of the original submission is incomplete, as further clarifications in methods and results, as well as performing additional analyses, would strengthen the study. The work will be of interest to cognitive neuroscientists working on multimodal recordings, auditory perception and music.

eLife Assessment

This study provides a useful anatomical resource by mapping the expression of four putative chemoreceptors in spinal cerebrospinal fluid-contacting neurons (CSF-cNs) of larval zebrafish. These descriptive findings offer an interesting entry point to explore how the nervous system senses signals within the spinal fluid microenvironment. The evidence supporting the spatial expression patterns of these receptors is convincing, utilizing high-resolution hybridization chain reaction (HCR) to validate previous transcriptomic data. However, the evidence remains incomplete regarding the actual functional roles of these receptors, as the study lacks protein-level validation, evidence of ligand availability in the CSF, or functional assays to demonstrate active chemoreception.

eLife Assessment

This work provides a reassessment of VBIT-4, a compound previously proposed to inhibit oligomerization of the crucial protein known as the mitochondrial voltage-dependent anion channel. Combining complementary experimental approaches with molecular dynamics simulations, the authors provide compelling evidence that VBIT-4 primarily disrupts lipid membranes and induces channel-independent cytotoxicity. The study has important implications for interpreting previous work using VBIT-4 as a probe of channel function and highlights the need to consider membrane-disruptive effects when evaluating drug mechanisms.