Evaluated articles

eLife Assessment

In this study, the authors describe the degradation of HDACs in late HSV-1 infection and attempt to link this phenomenon to HDAC export to the cytoplasm and to DNA damage response. However, the evidence is incomplete, as many of the experiments are lacking in rigor. As a result, mechanistic links to the proposed model are weak.

eLife Assessment

This study addresses an important gap in drug discovery by delivering a rigorous, large-scale evaluation of widely used co-folding methods for predicting ligand-bound protein complexes and virtual screening. A key strength is the comprehensive benchmarking framework, which leverages structures and chemical compounds that were absent from the AI models training set, thereby providing particularly compelling and unbiased evidence of co-folding performance. The findings clearly delineate the complementary roles of deep learning-based co-folding and physics-based docking, offering practical guidance for their rational integration into drug discovery workflows. Although the conclusions are convincing, improvements in the test cases, presentation, and usability can further strengthen the overall impact.

eLife Assessment

This important study explores whether complex structures that are lost during evolution can re-evolve, which is a long-standing debate in evolutionary and developmental biology. The authors demonstrate that re-evolution can occur if the gene regulatory network that underlies the development of complex traits is maintained. The evidence supporting its conclusions is solid and the work will be of interest to those studying the evolution and development of complex traits.

eLife Assessment

This valuable computational study presents a conceptually simple and biologically plausible reinforcement-learning framework for motor learning based on policy-gradient methods. The evidence supporting the conclusions is convincing, including rigorous mathematical derivations of learning rules for the mean and variance of motor commands and simulation results for three sets of experimental data, based on three different motor learning tasks from the literature. However, there is a lack of a clear description of the specific conditions under which this framework yields unique mechanistic insights or predictive values, hence falling short of qualifying as a "general theory of motor learning". The work will be of interest to researchers in computational motor learning and motor neuroscience.

eLife Assessment

This useful study examines patterns of clonal reproduction and somatic mutations in 'Pando', a massive, quaking aspen clone consisting of ~47000 stems. Because the study relies on relatively low-coverage, reduced-representation genomic resequencing data for the detection of somatic mutations, the evidence provided for several of the primary conclusions about clone age and the relationship between mutation accumulation and geographic distance is incomplete.

eLife Assessment

This valuable study uses a large cohort of clinical malaria cases collected over 18 years to address a critical knowledge gap regarding the role of PfEMP1 variants across distinct severe malaria syndromes. The conclusions are potentially of importance and interest to those who study malaria severity, but the evidence is incomplete, largely due to a lack of clarity on data inclusion and the correct use of statistical tests. More up-to-date data analysis methods would further strengthen the conclusions.

eLife Assessment

This important study presents a novel immunotherapy strategy for cancer. The authors develop a whole-tumor cell vaccine comprised of senescent tumor cells and a COX2 inhibitor in a hydrogel matrix. They present convincing evidence of the efficacy of this approach in preclinical models, demonstrating that prostaglandin E2 (PGE2) modulates the senescence-associated secretory phenotype (SASP) toward an immunostimulatory state, although more mechanistic/functional work would strengthen their conclusions. This work is timely and will be of interest to immunologists and others interested in the development of novel cancer therapies.

eLife Assessment

This fundamental work uncovers an unexpected lysosomal function for NINJ2 and links it to ferroptosis and cancer biology. The evidence supporting the conclusions appears to be convincing. Additional mechanistic clarification, particularly around the NINJ2-LAMP1 interaction and ferroptosis specificity, will further strengthen the manuscript. This work will be of general interest to the community of ferroptosis and cancer biology.

eLife Assessment

This manuscript explores the dynamic behaviors of Pol II and Pol III puncta that encompass the SL1 and 5S genes, following up on the authors' prior studies on ATTF-6. The authors show that ATTF-6 is required for RNA Pol II but not RNA Pol III foci, demonstrating that within the gene cluster, the regulation of RNA Pol II and RNA Pol III remain distinct from each other. The study is useful for analyzing understudied gene families, but it is incomplete and needs additional edits and experiments.

eLife Assessment

This valuable work extends a previously published regression framework for trial-aligned photometry data incorporating functional variables. However, the evidence is generally incomplete, due to the way that within-trial changes in variables have been incorporated into an inherently cross-trial analysis framework, which will limit general adoption. The ideas in this work will be of interest to researchers analyzing photometry signals.

eLife Assessment

This study presents a valuable finding on the condition dependence of autophagy-mediated lifespan regulation in C. elegans. The evidence is solid, as the data broadly support the main claims, although variability between biological replicates and limited mechanistic exploration leave some conclusions less firmly established. The work will be of interest to researchers studying autophagy, ageing, and intracellular trafficking.

eLife Assessment

This important study addresses the long-debated hypothesis that humans preferentially choose partners with dissimilar immune genes, using data from a small-scale society that allows comparison between arranged and self-chosen partnerships. Across multiple analyses controlling for genome-wide relatedness and examining functional immune diversity, the authors find no evidence of HLA/MHC-based (dis)assortative mating, suggesting that immune gene variation has limited influence on mate choice in this relatively homogeneous population and that the observed patterns instead reflect selection acting directly on immune loci. While the strength of the evidence is compelling for this population, several conclusions rely on indirect reconstruction methods and imputed data for a very complex region of the genome, which may limit how firmly some claims can be supported.

eLife Assessment

This valuable study is an approach to integrating and comparing single-cell genomics data across species. The evidence supporting the conclusions of this work is solid, and ANTIPODE presents an updated methodological approach to determining how gene expression at the cell-type level has evolved. Thus, ANTIPODE should provide broad utility to studies of comparative neurogenomics and be of use to neuroscientists and evolutionary biologists.

eLife assessment

This manuscript provides an important contribution to the field of platelet biogenesis, and the convincing evidence will advance our understanding of signal transduction driving the development of late megakaryopoiesis and platelet reactivity that results in bleeding diathesis. The paper is noteworthy for analyzing two related, either singly or in combination, tyrosine phosphatases in this conditional, stage development gene knockout. Because SHP1 is a negative regulator and SHP2 is an activator, the synergistic effects found in the double knockout were surprising.

eLife Assessment

This study provides valuable findings in the study of enhancer biology by identifying and dissecting a minimal enhancer regulating dlx2b expression during zebrafish tooth development, supported by promoter dissection, reporter assays, and genome-editing approaches. The work offers a resource and extends previous findings but has limited broader impact, with several conclusions about general cis-regulatory principles and functional consequences remaining only partially supported. Accordingly, the strength of evidence is at present incomplete, as additional functional validation would be needed to fully substantiate some of the claims.

eLife Assessment

This work of fundamental significance introduces a novel statistical model of spiking activity that incorporates continuous-time gain modulation. The authors provide exceptional evidence that the model outperforms earlier approaches and alternative candidates in capturing spiking responses across multiple visual areas in the macaque. Beyond its methodological contribution, the study offers new insights into how stimulus-driven variability and internally generated gain fluctuations evolve over time and between brain areas. The framework is likely to find broad application beyond the datasets examined here.

eLife Assessment

This study presents valuable insights into cellular sites of monoamine production and presence in Pristionchus pacificus, providing a comparative reference for the detailed knowledge of C. elegans, as well as using this information to compare serotonergic anatomy in 22 nematode species. Functional assays support evolved differences in monoaminergic control over certain, but not all, tested behaviors. The evidence is convincing, combining careful genetic experiments and comparative analysis that are well aligned with the conclusions. The results will serve as a basis for (comparative) structural-functional studies of nematode behavior.

eLife Assessment

This valuable study demonstrates how individual taste preferences shift over time, how these changes relate to cortical activity, and how experience reshapes both. The evidence is largely solid, although additional analyses are needed to strengthen some of the conclusions. The results should be of interest to neuroscientists studying sensory physiology.

eLife Assessment

This useful study presents a new method to identify the activity of single motor units from intramuscular EMG recordings. Validation against state-of-the-art techniques is limited to a small sample of simulated motor units; consequently, the evidence supporting the method's accuracy remains incomplete. The manuscript would be significantly strengthened by using more unbiased simulations for validation, validating the method with experimental datasets, comparing it against more recent techniques, and investigating how muscle physiology impacts accuracy.

eLife Assessment

In this fundamental work Horne et al present compelling evidence that YbjP is a novel binding partner of the TolC channel protein. The YbjP is characterized using cryo-EM, and its role probed using pull-down experiments, in vivo crosslinking, functional assays along with phylogenetic analysis which are all properly performed and presented and support the main conclusions. While the study does not identify a clear role for this protein, the revised manuscript offers improved clarity and contributes invaluable insight into membrane transport and antimicrobial resistance.