Evaluated articles

eLife Assessment

This valuable study examined the roles of the posterior parietal cortex in rats performing an auditory change-detection decision task. It provided solid evidence for two subpopulations with opposing modulation patterns during decision formation and for a correspondence between neural and behavioral measures of the short timescale used for evidence evaluation.

eLife Assessment

This important study uses a combination of behavioral and molecular techniques to identify neuromodulators that influence blood-feeding behavior in the disease vector, Anopheles stephensi. Through a combination of gene expression analysis and RNA knockdown, the authors identify neuropeptides RYamide and sNPF as candidate regulators for blood-feeding, demonstrate behavioral changes upon co-knockdown, and anatomically characterize their expression patterns. While the evidence for behavioral characterization and expression mapping is solid, the evidence supporting a direct causal role for these neuropeptides in promoting host-seeking remains unproven.

eLife Assessment

This manuscript investigates inter-hemispheric interactions in the olfactory system of Xenopus tadpoles. Using a combination of electrophysiology, pharmacology, imaging, and uncaging, the transection of the contralateral nerve is shown to lead to larger odor responses in the unmanipulated hemisphere, and implicates dopamine signaling in this process. The study uses a rich and sophisticated array of tools to investigate olfactory coding and uncovers valuable mechanisms of signaling. However, the data is incomplete, with a few of the conclusions not being well-supported by the data; the interpretation should be adjusted with some caveats, or additional experiments should be done to support these conclusions.

eLife Assessment

This valuable developmental study provides intriguing but incomplete evidence suggesting that, relative to adults, the enhancement of instrumental learning by Pavlovian bias is most pronounced in adolescence, while reward-induced memory enhancements are strongest in childhood. Although the authors tackle a key aspect of learning and motivation with rigorous experimental methods and sophisticated modeling techniques, there are substantial concerns about the absence of relevant analyses, the lack of accord between model-based and exploratory analyses, and the lack of an explanation for how the results cohere with inconsistent findings in the literature.

eLife Assessment

This study provides a valuable contribution to understanding the functional and molecular organization of the medial nucleus accumbens shell in feeding. Using in vivo imaging, optogenetics, and genetic engineering, the authors present solid evidence for a rostro-caudal gradient in D1-SPN activity that refines earlier pharmacological models. The identification of Stard5 and Peg10 as molecular markers and the creation of a Stard5-Flp line represent meaningful advances for future circuit-specific studies. While stronger integration of molecular and functional results and additional analyses of other Stard5-expressing cell types (e.g., D2-SPNs, interneurons) would enhance completeness, the overall methodological rigor and convergence of findings make this a well-executed and informative study. This will be of interest to those interested in brain circuits, reward, emotion, and feeding behavior.

eLife Assessment

This study presents a valuable in-depth comparison of statistical methods for the analysis of ecological time series data, and shows that different analyses can generate different conclusions, emphasizing the importance of carefully choosing methods and of reporting methodological details. The evidence supporting the claims, based on simulated data for a two-species ecosystem, is solid, although testing on more complex datasets could be of further benefit. This paper should be of broad interest to researchers in ecology.

eLife Assessment

This is an important study of critical period plasticity, focused on temperature manipulations, and how different parts of the Drosophila larval motor circuit adapt or maladapt. The work convincingly demonstrates that components of the motor network respond in distinct ways to the heat shock, and the combination of functional, structural, and electrophysiological approaches makes the study of significant interest. The work points to central interneurons as primary drivers of maladaptive changes, while motoneurons and neuromuscular junctions show compensatory or homeostatic adjustments. The study is methodologically rigorous, contributing significant insights into critical period biology using a tractable invertebrate model.

eLife Assessment

This important work combines theoretical analysis with precise experimental perturbation to demonstrate that the Wnt signaling pathway is characterized by anti-resonance, or a suppression of pathway output at intermediate activation frequencies. The authors identify an anti-resonance behavior, with compelling evidence from optogenetic stimulation in multiple cell types, alongside modeling results that corroborate the phenomenon. While the demonstration of this phenomenon has yet to be extended to fully physiological situations, its clear existence within optogenetically stimulated systems shows that it is likely a significant factor that contributes to the behavior of this central signaling pathway.

eLife Assessment

This important work employed a recent, functional muscle network analysis for evaluating rehabilitation outcomes in post-stroke patients. While the research direction is relevant and suggests the need for further investigation, the strength of evidence supporting the claims is incomplete. Muscle interactions can serve as biomarkers, but improvements in function are not directly demonstrated, and the method's robustness is not benchmarked against existing approaches.

eLife Assessment

This valuable study is a comprehensive investigation into the regulatory mechanisms and regional distribution of enteroendocrine cell subtypes in the Drosophila midgut, significantly advancing the understanding of how WNT and BMP gradients contribute to EE diversity. The methodological foundation and robust genetic evidence are solid in supporting the key roles of compartment boundary signals, particularly WNT and BMP, in specifying EE subtypes and division modes. However, there is a lack of full mechanistic insight regarding Notch pathway involvement, incomplete quantification of phenotype data, and insufficient global pattern analysis, which detracts from fully supporting some proposed models. Overall, the study provides a platform for future work but would benefit from stronger data integration and expanded mechanistic exploration.

eLife Assessment

This valuable study addresses the effects of selection on aggression on fitness and life-history trade-offs in Drosophila melanogaster. However, the evidence presented is incomplete and does not support the claims proposed in the study of increased survival of highly aggressive males at the expense of reproductive success and shorter mating duration. The main limitation of the study is the choice to use males from only one aggressive Drosophila line in combination with CantonS females, that do not allow disambiguation between nonaggression-related factors, such as hybrid vigor and aggression-related factors influencing mating and lifespan.

eLife Assessment

This valuable study examines how mammals descend effectively and securely along vertical substrates. The conclusions from comparative analyses based on behavioral data and morphological measurements collected from 21 species across a wide range of taxa are convincing, making the work of interest to all biologists studying animal locomotion.

eLife Assessment

This important study provides a systematic investigation of parent-of-origin (POE) effects on gene expression using large trio-based data from the Framingham Heart Study, uncovering thousands of potentially novel associations. While the findings are potentially significant, the statistical support for classifying POE eQTLs and some downstream analyses is incomplete, and more stringent re-analysis is needed. With such revisions, the work would serve as a foundation for advancing understanding of POEs and their role in gene regulation.

eLife Assessment

This important work provides a new method to extract cfDNA from residual plasma from heparin separators for molecular testing. The evidence supporting the authors' claims is convincing, although some further metrics should also be evaluated. This finding will be interesting to people working in epigenomics and infectious disease diagnostics.

eLife Assessment

The characterization of a dissociable Mediator subunit implicated in cellular pathways, particularly lung alveolar function and HIV latency, would be conceptually interesting. The authors have preliminary evidence for a stable Med16 subcomplex that may regulate specific genes. This work is useful in that it points to interactions between Med16 and UBP1, but the evidence is preliminary and incomplete.

eLife Assessment

This important study systematically investigates repeat expansion in the plant Arabidopsis thaliana using a new k-mer-based method, expanding on smaller studies to more comprehensively identify cis- and trans-acting loci associated with repeat dynamics. The approach is methodologically sound and broadly applicable to large-scale short-read datasets for assessing copy number variation and genomic repeat content. While convincing in its scope and novelty, the findings would be further strengthened with exploratory analyses of datasets from other species with more or fewer repeats in their genomes.

eLife Assessment

This work introduces FunC-ESMs, a proteome-scale framework to classify loss-of-function missense variants into distinct mechanistic groups by combining two complementary state-of-the-art machine learning models. The strength of evidence is convincing, supported by solid benchmarking, integration with experimental datasets, and careful methodological design. The significance of the findings is valuable, providing a resource of clear interest to researchers and diagnostic laboratories working on variant interpretation.

eLife Assessment

This study offers a valuable methodological advance by introducing a gene panel selection approach that captures combinatorial specificity to define cell identity. The findings address key limitations of current single-gene marker methods. The evidence is compelling, but would be strengthened by further validation of rare cell states and unexpected marker categories.

eLife Assessment

This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury; using spatial transcriptomics, mechanistic perturbations, and functional assays, the authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival during APAP-induced hepatotoxicity. The idea that distinct intrahepatic zones mount tailored stress responses is conceptually significant and has implications for regeneration and toxicology. The dataset is rich and the methodology modern, but several conclusions rely on assumptions about zonation under injury, limited injury models, and incomplete functional validation of the Atf4-Chop-Btg2 axis. With targeted revisions and additional experiments, the work has the potential to provide strong mechanistic insights into liver zonation and injury responses.

eLife Assessment

This study presents an important finding by identifying OPG as a novel stromal checkpoint influencing T-cell anti-tumor responses, thereby shedding new light on the complex interplay between the tumor microenvironment and immune regulation. The data are robust and the experimental approaches are sound, providing solid support for the study's conclusions; however, there are a number of additional questions raised by the data. Of particular note are the questions raised on the mechanistic effects of TRAIL versus RANKL. In addition, it would broaden the interest in this study to include more translational human data to complement the work presented.