Evaluated articles

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.

eLife Assessment

This study presents valuable findings on how retrieval practice protects memory inferences from stress via covert memory reactivation. Via two EEG experiments manipulating stress and retrieval practice, the authors provide solid evidence supporting the conclusion. This work will be of interest to cognitive and affective neuroscientists working on the intersection between memory and stress.

eLife Assessment

This modeling study proposes important new insights into the circuit mechanisms underlying navigational control in insects. High-speed video recordings of ants are compared to detailed predictions from a new computational model, whose description is incomplete. If the model is sound, the similarities between the model and behavioral data suggest how complex behavioral motifs can emerge from a simple neural circuit. These results will be of interest to scientists studying the neural circuit basis of behavior, particularly in insects.

eLife Assessment

This important study investigates how infestation by the small brown planthopper (Laodelphax striatellus) reshapes rice carbohydrate allocation and demonstrates that host-derived glucose enhances insect fecundity and imidacloprid tolerance, through the activation of conserved nutrient-sensing and endocrine pathways. Across extensive and complementary approaches, including plant manipulations, glucose supplementation, RNAi, pharmacological inhibition, rescue experiments, and biochemical assays, the authors provide convincing evidence that glucose activates the TOR-juvenile hormone-vitellogenin axis to promote reproduction and co-regulates GST-mediated detoxification via both TOR-JH signaling and GCL-GSH metabolism. The mechanistic framework is coherent and well supported by hierarchical validation and functional assays. Some limitations remain regarding the generality of the findings across other pest species and insecticides, and aspects of the evolutionary framing would benefit from more cautious interpretation; nonetheless, the work substantially advances our understanding of how plant-derived nutrients interface with conserved insect signaling pathways to shape fitness-related traits, and will be of broad interest to researchers studying plant-insect interactions, insect physiology, and pest management.

eLife Assessment

This valuable study identifies a novel neurodevelopmental syndrome caused by variants in ARID5B, supported by solid human genetic evidence from a well-characterized cohort. While the clinical data establish a clear genotype-phenotype correlation, the functional evidence regarding the proposed molecular mechanisms remains incomplete. Addressing the gaps in the functional characterization and refining the clinical assertions would significantly strengthen the conclusions.

eLife Assessment

This important study advances our understanding of developmental timing mechanisms by studying the cleavage, nuclear translocation, and oscillation of the transcription factor MYRF-1 (vertebrate MYRF) during C. elegans larval development. The evidence supporting the conclusions is solid, with elegant genome engineering experiments and state-of-the-art microscopy. The work will be of broad interest to cell and developmental biologists.

eLife Assessment

This study presents important findings by identifying small molecules that can stabilize and refold missense-mutated VHL tumor suppressor protein, offering a potential therapeutic approach for clear cell renal cell carcinoma. The computational design approach is well-executed, but the evidence is incomplete due to insufficient demonstration that HIF2 downregulation occurs through on-target VHL rescue rather than off-target effects. Additional experiments with appropriate controls are needed to establish the specificity of the mechanism.

eLife Assessment

This important study analyzed the impact of amino acid homorepeats on protein expression and solubility in yeast and E. coli. The authors provided convincing evidence that hydrophobic and positively charged amino acids are toxic and that counterselection during evolution reduced the occurrence of such proteotoxic protein sequences. This study will be of interest to cell biologists and biochemists, particularly those working on proteostasis.