eLife Assessment

This important study resolves the structure of one missing piece of the eukaryotic DNA replication fork, the leading strand clamp loader. Overall, the data are convincing, with electron microscopy data providing a strong basis for analyzing differences and similarities with other RFC complexes. A minor point is that the evidence supporting the proposed role of the β-hairpin is incomplete.

eLife Assessment

This valuable study uses single-molecule imaging to characterize factors controlling the localization, mobility, and function of RNase E in E. coli, a key bacterial ribonuclease central to mRNA catabolism. The supporting evidence for the differential roles of RNAse E's membrane targeting sequence (MTS) and the C-terminal domain (CTD) to RNAse E's diffusion and membrane association is convincing. It provides insight into how RNAse E shapes the spatiotemporal organization of RNA processing in bacterial cells. This interdisciplinary work will be of interest to cell biologists, microbiologists, biochemists, and biophysicists.

eLife Assessment

In their study, Neiswender et al. provide important insights into how BicD2 variants linked to spinal muscular atrophy alter dynein activity and cargo specificity. The authors present convincing evidence that disease-associated mutations lead to interactome changes, supported by additional validation of the BicD2/HOPS complex and discussion of their functional implications. This well-executed study offers invaluable datasets and a strong foundation for future exploration of disease mechanisms.

eLife Assessment

This study presents a fundamental discovery of how cerebellar climbing fibers modulate plastic changes in the somatosensory cortex by identifying both the responsible cortical circuit and the anatomical pathways. The evidence supporting the conclusions is convincing and well supported by modern neuroscience methodologies. Overall, this work represents a significant contribution that will be of broad interest to neuroscientists, especially those studying the long-distance cerebellar influence on non-motor brain functions.

eLife Assessment

This valuable manuscript presents findings supported by solid data to identify a surprising glia-exclusive function for betapix in vascular integrity and angiogenesis. The manuscript also describes the optimisation of a modified CRISPR-based Zwitch approach to generate conditional knockouts in zebrafish

eLife Assessment

This paper addresses the significant question of quantifying epistasis patterns, which affect the predictability of evolution, by reanalyzing a recently published combinatorial deep mutational scan experiment. The findings are that epistasis is fluid, i.e. strongly background dependent, but that fitness effects of mutations are predictable based on the wild-type phenotype. However, these potentially interesting claims are inadequately supported by the analysis, because measurement noise is not accounted for, arbitrary cutoffs are used, and global nonlinearities are not sufficiently considered. If the results continue to hold after these major improvements in the analysis, they should be of interest to all biologists working in the field of fitness landscapes.

eLife Assessment

This valuable study introduces the peptidisc-TPP approach as a promising solution to challenges in membrane proteomics, enabling thermal proteome profiling in a detergent-free system. The concept is innovative and holds significant potential, and the demonstration of its utility and validation is solid. The method presents a strong foundation for broader applications in identifying physiologically and pharmacologically relevant membrane protein-ligand interactions.

eLife Assessment

This valuable study reports the physiological function of a putative transmembrane UDP-N-acetylglucosamine transporter called SLC35G3 in spermatogenesis. The conclusion that SLC35G3 is a new and essential factor for male fertility in mice and probably in humans is supported by convincing data. This study will be of interest to reproductive biologists and physicians working on male infertility.

eLife Assessment

This study reports important negative results, showing that genetically removing the RNA-binding protein PTBP1 in astrocytes is insufficient to convert them into neurons, thereby challenging previous claims in the field. It also offers a compelling analysis of PTBP1's role in regulating astrocyte-specific splicing. The evidence is strong, as the experiments are technically sound, carefully controlled, and supported by both imaging and transcriptomic analyses.

eLife Assessment

This computational study examines how neurons in the songbird premotor nucleus HVC might generate the precise, sparse burst sequences that drive adult song. The findings would be useful for understanding how intrinsic conductances and HVC microcircuitry may produce neural sequences, but the work is incomplete because of arbitrary network assumptions, insufficient consideration of biological details such as how silent gaps in song sequences are represented, and failure to incorporate interactions with auditory and brainstem inputs. As a result, the study offers limited advance and only a modest conceptual advance over prior models.

eLife Assessment

This is a valuable analysis of STORM data that characterizes the clustering of active zones in retinogeniculate terminals across ages and in the absence of retinal waves. The design makes it possible to relate fixed time point structural data to a known outcome of activity-dependent remodeling. The latest revision has tempered the causal claims made in previous versions. The result provides solid structural support for the hypotheses regarding how activity influences the clustering of these synapses.

eLife Assessment

This important work advances our understanding of NMDAR diversity in the brain by providing evidence into the subunit arrangement, architecture, and activation mechanism of GluN1-N2-N3A tri-NMDAR. However, the evidence supporting the conclusions provides incomplete proof for the presence and functional properties of this NMDA receptor subtype. The work will be of broad interest to neuroscientists and biophysicists.

eLife Assessment

This important study sought to investigate the role that early childhood malaria exposure plays in the development of antibody responses to unrelated pathogens and vaccine-derived antigens in Kenyan children. In this natural experiment, the authors compare antibody levels among children who have been exposed to different levels of malaria transmission by using protein microarray technology. Although the findings are of importance, the evidence remains incomplete, and the analysis would benefit from a more in-depth evaluation of potential confounders. With the appropriate analysis, the findings will be of great interest for global health, immunology, and vaccine development.

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 fundamental study presents a new method for longitudinally tracking cells in two-photon imaging data that addresses the specific challenges of imaging neurons in the developing cortex. It provides compelling evidence demonstrating reliable longitudinal identification of neurons across the second postnatal week in mice. The study should be of interest to development neuroscientists engaged in population-level recordings using two-photon imaging.

eLife Assessment

This is a valuable study that explores the role of the conserved transcription factor POU4-2 in the maintenance, regeneration, and function of planarian mechanosensory neurons. The authors present convincing evidence provided by gene expression and functional studies to demonstrate that POU4-2 is required for the maintenance and regeneration of mechanosensory neurons and mechanosensory function in planarians. Furthermore, the authors identify conserved genes associated with human auditory and rheosensory neurons as potential targets of this transcription factor.

eLife Assessment

This valuable manuscript presents an open-source and low-cost acoustic system for quantifying biting and chewing in mice. The approach is carefully validated against human observers, demonstrating strong methodological reliability and enabling high-resolution analysis of feeding microstructure. The tool has broad relevance for studies of appetite circuits and pharmacological interventions. A significant contribution is the identification of previously unrecognized "meal-related" neurons in the lateral hypothalamus, providing novel biological insight into food consumption. While the support for the methodological advances is compelling and robust, some circuit-level conclusions are preliminary or incomplete, relying on small pilot samples and manual classification, and should be interpreted with caution. This paper will be of interest to those interested in ingestive behavior and/or hypothalamus.

eLife Assessment

This paper is an important overview of the currently published literature on low-intensity focused ultrasound stimulation (TUS) in humans, providing a meta-analysis of this literature that explores which stimulation parameters might predict the directionality of the physiological stimulation effects. The overall synthesis is convincing. The database proposed by the paper has the potential to become a key community resource if carefully curated and developed.

eLife Assessment

This important study addresses a topic that is frequently discussed in the literature but is under-assessed, namely correlations among genome size, repeat content, and pathogenicity in fungi. Contrary to previous assertions, the authors found that repeat content is not associated with pathogenicity. Rather, pathogenic lifestyle was found to be better explained by the number of protein-coding genes, with other genomic features associated with insect association status. The results are considered solid, although there remain concerns about potential biases stemming from the underlying data quality of the analyzed genomes.

eLife Assessment

This valuable study uses a sophisticated array of techniques to investigate the mechanisms through which the chordotonal receptors in the locust ear (Müller's organ) sense auditory signals. Ultrastructural reconstruction of the sensory organ provides convincing evidence of the organization of the scolopidial structure that wraps the sensory neuron cilium. However, the recordings of sound-evoked motion and electrophysiological activity from the chordotonal sensory neurons provide incomplete evidence for the proposed axial stretch model of mechanotransduction.

eLife Assessment

This study provides new and interesting findings that SCoR2 acts as a denitrosylase to control cardioprotective metabolic reprogramming and prevent injury following ischemia/reperfusion. The compelling evidence is supported by a novel multi-omics approach, but questions remain regarding the stability and human relevance of BDH1 as well as the sufficiency of SCoR2. Overall, the work will be of interest to cardiovascular researchers and provides valuable information to the field, though some mechanistic aspects require further clarification.

eLife Assessment

Using high-throughput small-molecule screening, this study discloses novel modulators of the mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial function. Reviewers viewed the targeting of TFAM as innovative and the study's conclusions as potentially important (especially the effects on inflammation). However, the lack of evidence for a direct effect of the compounds on TFAM activity weakens the paper's key conclusion and renders the study incomplete.

eLife Assessment

This study presents a useful inventory of genes that are up- and down-regulated in the mouse small intestine (duodenum and ileum) during the first postnatal month; the data were collected and analyzed using solid and validated methodology and can be used as a starting point for additional validation of specific markers and for follow-up functional studies. Some aspects of the study were incomplete, with claims being only partially supported by the data, and it is suggested that additional validation be performed. The authors attempted to correlate gene expression changes with periods of high and low NEC susceptibility, but these correlations are speculative and not supported by functional follow-up studies. Discussion of gene expression changes with NEC susceptibility would be more appropriate to include in the Discussion section and to be tempered in the results section.

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 study presents valuable findings regardingg a rare mode of reproduction called hybridogenesis in a species pair of frogs. While parts of the study provide solid support for the claim of hybridogenesis, other parts are incomplete with certain claims being only partially supported, as alternative modes of reproduction cannot be fully ruled out.

eLife Assessment

This study provides valuable insights into the influence of sex on bile acid metabolism and the risk of hepatocellular carcinoma (HCC). The data to support that there are inter-relationships between sex, bile acids, and HCC in mice are convincing, although this is a largely descriptive study. Future studies are needed to understand the interaction of sex hormones, bile acids, and chronic liver diseases and cancer at a mechanistic level. Also, there is not enough evidence to determine the clinical significance of the findings given the differences in bile acid composition between mice and men.

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 study provides novel and convincing evidence that both dopamine D1 and D2 expressing neurons in the nucleus accumbens shell are crucial for the expression of cue-guided action selection, a fundamental component of decision-making. The research is systematic and rigorous in using optogenetic inhibition of either D1- or D2-expressing medium spiny neurons in the NAc shell to reveal attenuation of sensory-specific Pavlovian-Instrumental transfer, while largely sparing value-based decision on an instrumental task. The findings in this report build on prior research and resolve some conflicts in the literature regarding decision-making.

eLife Assessment

This study provides important evidence that negative affect is associated with slower cognitive processing in daily life, with findings replicated across three independent samples and supported by rigorous statistical analyses. The strength of evidence is convincing, though reliance on a proxy measure of processing speed limits the completeness of the conclusions.

eLife Assessment

This important work develops the C. elegans as a model organism for studying effort-based discounting by asking the worms to choose between patches of easy and hard to digest bacteria. The authors provide convincing evidence that the nematodes are effort discounting. They also provide solid evidence of involvement of dopamine in the food preference and that the finding is not restricted to lab-acclimated strains.

eLife Assessment

This important study combines behavioural psychophysics with image-computable models to contrast a view-selective model of face recognition with a view-tolerant process. Although diagnostic orientations vary with viewpoint (horizontal for frontal, vertical for profile), human recognition remains consistently tuned to horizontal information, aligning with the view-tolerant model's predictions. The evidence for view-invariant recognition is solid, though testing more plausible model variants and considering generalisability to more naturalistic face stimuli would strengthen the conclusions.

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 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

The authors collected time-course RNA-seq data from four tree species in natural environments and analyzed seasonal patterns of gene expression. This fundamental study substantially advances our understanding of how seasonal environments shape gene expression. The evolutionary effects of seasonal environments on gene expression are rarely studied at this scale and the dataset is extensive. The evidence supporting the conclusions is compelling, with caveats and limitations clearly described. The work will be of broad interest to colleagues studying evolution and gene expression.

eLife Assessment

The authors used comprehensive approaches to identify Gyc76C as an ITPa receptor in Drosophila. They revealed that ITPa acts via Gyc76C in the renal tubules and fat body to modulate osmotic and metabolic homeostasis. The designed experiments, data, and analyses convincingly support the main claims. The findings are important to help us better understand how ITP signals contributes to systemic homeostasis regulation.

eLife Assessment

This study provides convincing evidence that homologous recombination can occur in telophase-arrested cells, independently of cohesin subunits Smc 1-3. These findings are valuable as they point to investigate the role of cohesins re-association with chromatin in the allelic inter-sister repair by homologous recombination.

eLife Assessment

This important study by Zheng et al characterizes a novel Legionella pneumophila effector, Llfat1 (Lpg1387), which binds actin through a newly identified actin-binding domain. Data is convincing; structural analysis of the Llfat1 ABD-F-actin complex enabled the development of this domain as a probe for F-actin. Additionally, the authors show that Llfat1 functions as a lysine fatty acyltransferase targeting small GTPases, highlighting its importance in both bacterial pathogenesis and cytoskeletal biology.

eLife Assessment

This study provides important insights into bacterial genome evolution by analyzing single-cell genome sequences of cyanobacteria from Yellowstone hot springs. Using compelling evidence, the authors demonstrate that both homologous recombination within species and frequent hybridization across species are major drivers of genome diversification. Despite the challenges that are inherent to sparse and fragmented single-cell data, the analyses are thorough, carefully controlled, and supported by multiple complementary approaches, making the conclusions highly robust. This work represents a significant advance in our understanding of microbial evolution in natural environments.

eLife Assessment

This valuable study uses tools of population and functional genomics to examine long non-coding RNAs (lncRNAs) in the context of human evolution. Analyses of computationally predicted human-specific lncRNAs and their genomic targets lead to the development of hypotheses regarding the potential roles of these genetic elements in human biology. The conclusions regarding evolutionary acceleration and adaptation, however, only incompletely take data and literature on human/chimpanzee genetics and functional genomics into account.

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 study shows that retinal bipolar cell subtype-specific differences in the size of synaptic ribbon-associated vesicle pools contribute to the transient versus sustained kinetics of the responses of retinal ganglion cells. The data are extensive and compelling. This work will be of broad interest to researchers working on synaptic transmission, retinal signal processing, and sensory neurobiology.

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 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 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 work reveals metabolic pathways and molecular events mechanistically linked to B cell activation. Using an unbiased, comprehensive proteome profiling method and various functional validation approaches, this study generated convincing evidence suggesting a role for amino acid uptake, cholesterol accumulation, and protein prenylation in the proliferation, survival, and biogenesis of B cells stimulated with LPS and other activating stimuli. The significance of the findings is considered to be fundamental, in that they will advance our understanding of cell metabolism during B cell activation.

eLife Assessment

This important study advances our understanding of how cellular quality control machinery influences cystic fibrosis (CF) drug responsiveness by systematically analyzing the effects of the chaperone calnexin on more than two hundreds of CFTR (cystic fibrosis transmembrane regulator) variants. The evidence supporting the conclusions is convincing, with a comprehensive deep mutational scanning methodology and rigorous quantitative analysis. The findings reveal that calnexin is critical for both CFTR protein expression and corrector drug efficacy in a variant-specific manner, providing invaluable insights that could guide the development of personalized CF therapies. This work will be of significant interest to researchers in protein folding, CF drug development, and genetic disease therapeutics.

eLife Assessment

This important study uses data from OpenAlex on more than 50 million journal articles in over 50,000 research journals to examine the dynamics of interdisciplinarity and international collaboration in research journals. The data analytics used to quantify disciplinary and national diversity are convincing, and support the claims that journals have become more diverse in both aspects. The revisions made by the authors have addressed the small number of concerns the reviewers had about the original version.

eLife Assessment

The authors investigated the potential role of IgG N-glycosylation in Haemorrhagic Fever with Renal Syndrome (HFRS), which may offer significant insights for understanding molecular mechanisms and for the development of therapeutic strategies for this infectious disease. The findings are thought to be valuable to the field and the strength of evidence to support the findings is solid.

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.

eLife Assessment

This useful study attempts to place an ancient maize sample from Bolivia, dated to the end of the Incan empire, in genetic and geographical context. The analyses show that this sample is most closely related to ancient Peruvian maize, but the data remain inadequate to determine the direction of dispersal and the extent of Inca influence over the genetic make up of the analyzed sample. There are additional deficiencies in the statistical analyses and selection inferences. The topic of the study would appeal to researchers studying maize dispersal and adaptation.

eLife Assessment

This study presents a meta-analysis of two independent genome-wide association studies (GWAS) that investigate the role of plasma proteins as potential biomarkers for enhancing the early detection of prostate cancer (PCa). The results provide useful confirmatory data that support existing evidence currently published. The evidence is incomplete: the study does not provide a comprehensive synthesis of all currently published work, does not explore other clinical outcomes related to prostatic disease, and its findings have not been validated through an external cohort study. These shortcomings notwithstanding, the work may be of interest to researchers studying correlates and predictors of prostate cancer risk.

eLife Assessment

This global study compares environmental niche model outputs of avian influenza pathogen niche constructed for two distinct periods, and uses differences between those outputs to suggest that the changed case numbers and distribution relate to intensification of chicken and duck farming, and extensive cultivation. While a useful update to existing niche models of highly pathogenic avian influenza, the justification for the use of environmental niche models to explore correlative relationships between land cover change and changed case epidemiology is incomplete. Key assumptions have not been adequately clarified for the readers benefit, and in consequence the communication of the likely limitations of the work are not sufficiently clear.

eLife Assessment

This study presents valuable findings regarding the basic molecular pathways leading to the cystogenesis of Autosomal Dominant Polycystic Kidney Disease, suggesting BICC1 functions as both a minor causative gene for PKD and a modifier of PKD severity. Solid data were supplied to show the functional and structural interactions between BICC-1 and PKD2 and their relevance to the pathogenesis of ADPKD, although the characterization of such interactions remains to be developed further and the clinical relevance is currently unclear.

eLife Assessment

This study provides new single-cell multi-omics datasets that may be useful in the study of early cardiac lineages. However, the authors' conclusions regarding the mutual regulation of key regulators for cardiac specification and new cardiac lineage trajectories are inadequately supported by persuasive analysis and do not align with prior published studies. If revised to address the serious caveats adequately, the findings may be of interest to researchers in the field of cardiac development and congenital heart disease.

eLife Assessment

This study provides valuable information on the impact of Lamin A/C knockdown on gene expression using RNA-Seq analysis, as well as on telomere dynamics through live cell imaging. However, the conclusions remain inadequately supported by the current data, and several of the major technical concerns raised in the first round have not yet been fully resolved.

eLife Assessment

This important work represents an advance in our understanding of resident myeloid cells in the zebrafish brain, particularly as it provides a molecular definition of dendritic cell subtypes associated with their localization. Combined evidence from single cell transcriptomics and histology is compelling. The associated atlas will be used as a resource by the zebrafish community and beyond.

eLife Assessment

This work provides high-precision single-cell data on the relationship between DnaA activity and cell size, offering important insights for the field of cell cycle control. These findings motivate a novel and intriguing hypothesis for DNA replication initiation -the "extrusion model"- in which DNA-binding proteins modulate free DnaA availability in response to biomass-DNA imbalance. While the current indirect evidence does not fully establish the model, an experimental perturbation involving H-NS offers convincing support for its plausibility, laying the groundwork for future investigation.

eLife Assessment

This manuscript provides an improved version of an important cancer risk estimation tool and refines and expands upon resources that are currently available to the cancer genetics community. The new program is validated in a set of clinical pedigrees demonstrating its practical accuracy and relevance to the field. Collectively, the data are compelling and support the major conclusions of this manuscript.

eLife Assessment

This study developed a novel continuous dot-motion decision-making task, in which participants can see another player's responses as well as their own, to measure perceptual performance and confidence judgments in a social context. The study is a useful contribution to social decision-making primarily by introducing a new task and offering convincing evidence on how participants are impacted by others' decisions during continuous perceptual choices. The manuscript delivers clear evidence that participants judgements are driven by metacognitive confidence over simpler primary uncertainty.

eLife Assessment

This paper presents a valuable software package, named "Virtual Brain Inference" (VBI), that enables faster and more efficient inference of parameters in dynamical system models of whole-brain activity, grounded in artificial network networks for Bayesian statistical inference. The authors have provided convincing evidence, across several case studies, for the utility and validity of the methods using simulated data from several commonly used models, but more thorough benchmarking could be used to demonstrate the practical utility of the toolkit. This work will be of interest to computational neuroscientists interested in modelling large-scale brain dynamics.

eLife Assessment

This is a valuable study that presents convincing evidence on the genesis of the CPSF6 condensates that form upon HIV-1 infection and the specific molecular determinants involved in their formation, as well as their interactions with SRRM. The study could be strengthened by assessing the relevance of their findings to infection, and in particular, with reverse transcription and gene expression

eLife Assessment

The results by Zhu et al provide valuable insights into the representation of border ownership in area V1. They used neuropixel recording to demonstrate the clustering of border ownership, and compared cross-correlation functions between neurons in different layers to demonstrate that they depend on the type of stimulus. The strength of the evidence is solid but can be improved by performing additional analyses and addressing some concerns (as raised in the previous and current review), and accounting for the differences in classical and non-classical receptive field stimulation conditions.

eLife Assessment

This study presents SegPore, a valuable new method for processing direct RNA nanopore sequencing data, which improves the segmentation of raw signals into individual bases and boosts the accuracy of modified base detection. The evidence presented to benchmark SegPore is solid, and the authors provide a fully documented implementation of the method. SegPore will be of particular interest to researchers studying RNA modifications.

eLife assessment

This is a valuable study that combines a wide range of approaches to provide a biophysical and evolutionary mechanism that could explain why some particular mutations in the SARS-CoV-2 protein N arose during the COVID-19 pandemic. The evidence is solid and relies on multiple experimental approaches. However, some of the results were dependent on extremely high protein concentrations, which may affect certain conclusions.

eLife Assessment

The study reports a potential pathway for isoleucine biosynthesis mediated by the underground activity of AHASII, which converts glyoxylate and pyruvate to 2-ketobutyrate. While the findings are valuable in revealing a possible alternative route for isoleucine production, the evidence presented remains incomplete. More comprehensive biochemical experiments are required to substantiate the physiological feasibility of this pathway.

eLife Assessment

This valuable biomechanical analysis of kangaroo kinematics and kinetics across a range of hopping speeds and masses is a step towards understanding a long-standing problem in locomotion biomechanics: the mechanism for how kangaroos, unlike other mammals, can increase hopping speed without a concomitant increase in metabolic cost. The authors convincingly demonstrate that changes in kangaroo posture with speed increase tendon stress/strain and hence elastic energy storage/return. This greater tendon elastic energy storage/return may counteract the increased cost of generating muscular force at faster speeds and thus allows for the invariance in metabolic cost. This methodologically impressive study sets the stage for further work to investigate the relation of hopping speed to metabolic cost more definitively.

eLife Assessment

This important paper employs multiple experimental approaches and presents evidence that changes in membrane voltage directly affect ERK signaling to regulate cell division. This result is relevant because it supports an ion channel-independent pathway by which changes in membrane voltage can affect cell growth. The evidence now presented is solid and the data support the conclusions. This paper should be of interest to a broad readershp in the areas of cell and developemental biology and electrophysiology.

eLife Assessment

This high-N, multi-task study offers a comprehensive examination of rhythmicity in behavioral performance during listening. It presents a valuable set of findings that reveal task- and ear-specific effects, challenging the notion of a universal rhythmicity in auditory perception. The evidence is solid and the work is likely to be of significant interest to behavioral and cognitive scientists focused on perception and neural oscillations.

eLife Assessment

The reviewers have found that this manuscript is a valuable contribution, and the evidence in support of its conclusions is mostly solid. It provides novel insights and raises interesting possibilities about the functions of an understudied histone modification within the nucleosome core; however, the data are mostly descriptive and correlative, and although this has value, it is not totally persuasive. Short of additional non-genomic experiments, a more detailed analysis of the genomic data and perhaps additional data would strengthen the conclusions. The manuscript crucially needs further antibody validation to raise confidence in the data.

eLife Assessment

This important study establishes bathy phytochromes, a unique class of bacterial photoreceptors that respond to near-infrared light (NIR), as versatile tools for bacterial optogenetics. NIR light is a key control signal in optogenetics due to its deep tissue penetration and the ability to combine with existing red- and blue-light sensitive systems, but thus far, NIR-activated proteins have been poorly characterized. The strength of evidence is convincing, with comprehensive in vitro characterization, modular design strategies, and validation across different hosts, supporting the versatility and potential for these tools in biotechnological applications. This study should advance the fields of optogenetics and photobiology and inspire future work.

eLife Assessment

This important manuscript presents a thorough analysis of the evolution of Major Histocompatibility Complex gene families across Primates. A key strength of this analysis is the use of state-of-the-art phylogenetic methods to estimate rates of gene gain and loss, accounting for the notorious difficulty to properly assemble MHC genomic regions. Overall the evidence for the authors' conclusions -- that there is considerable diversity in how MHC diversity is deployed across species -- are compelling.

eLife Assessment

This study provides important insights into how researchers can use perceptual metamers to formally explore the limits of visual representations at different processing stages. The framework is compelling and the data largely support the claims, subject to minor caveats.

eLife Assessment

This study presents a valuable finding relating to how the state of arousal is represented within the superior colliculus, a principal visuo-oculomotor structure. The main conclusion that the representation of arousal is segregated, and thus influences visual activity but not motor output, is incompletely supported by the evidence, but could be stronger if a specific concern relating to an alternative explanation for the dichotomy was addressed. The work will be of interest to sensory, motor, and cognitive neuroscientists.

eLife Assessment

This important study presents a novel approach to enhance the therapeutic potential of mesenchymal stromal cells (MSCs) by genetically modifying their glycogen synthesis pathway, resulting in increased glycogen accumulation and improved cell survival under starvation conditions, particularly in the context of experimental pulmonary fibrosis. The methods and findings are generally solid and could be strengthened in the future by investigating the kinetics of persistence, the immunomodulatory effects, and the underlying improved mechanism of action of MSCs in this pulmonary fibrosis model. If confirmed, this approach could suggest potential methods to improve the therapeutic functionality of MSCs in cell therapy strategies.

eLife Assessment

This important manuscript evaluates how sample size and demographic balance of reference cohorts affect the reliability of normative models. The evidence supporting the conclusions is convincing, although some additional analysis and clarifications could improve the generalisability of the conclusions. This work will be of interest to clinicians and scientists working with normative models.

eLife Assessment

This important paper reports the development of proteins and small molecules that induce degradation of a clinically-relevant oncogenic transcription factor, LMO2. The findings provide a proof of concept that PROTAC-type chemicals can be developed against intrinsically disordered proteins. The methods provide a blueprint for rational design of PROTACs starting from intracellular antibody paratopes. Overall, the paper is supported by solid evidence and will be of interest to chemical biologists and cancer pharmacologists.

eLife Assessment

This valuable study concerns a model for transgenerational epigenetic inheritance, the learned avoidance by C. elegans of the PA14 pathogenic strain of Pseudomonas aeruginosa. A recent study questioned whether transgenerational inheritance in this paradigm lacks robustness. The authors of this study have worked independently of the group that reported the original phenomenon and also independently of the group that challenged the original report. With solid data, this study independently validates findings previously reported by the Murphy group, confirming that the paradigm is reproducible elsewhere. The reviewers also appreciated the information on reagent sources used by different groups. The present study is therefore of broad interest to anyone studying genetics, epigenetics, or learned behavior.

eLife Assessment

This paper presents a valuable theory and analysis of the role of neurogenesis and inhibitory plasticity in the drift of neural representations in the olfactory system. For one of the findings, regarding the impact of neurogenesis on the drift, the evidence remains incomplete. The reason lies in the differences in variability/drift of the mitral/tufted cell responses observed in the model compared to experimental observations, where these responses remain stable over extended time scales.

eLife Assessment

This valuable study compares auditory cortex responses to sounds and cochlear implant stimulation measured with surface electrode grids in rats. Beyond the reduced frequency resolution of cochlear implants observed previously, this study suggests key discrepancies between neuronal representations of cochlear stimulations and natural sounds. However, the evidence for this potentially interesting result is incomplete because there is a lack of evidence for the effectiveness of the comparison method. This study is of interest to researchers in the auditory neuroscience field and clinicians implementing treatments with cochlear implants.

eLife Assessment

This important study uses simultaneous EEG and fMRI recordings to shed light on the relationship between alpha and gamma oscillations and specific cortical layers. The sophisticated methodology provides solid evidence for correlations between oscillatory power and the strength and contents of fMRI signals in different cortical layers, though some caveats remain. This paper will be of interest to neuroscientists studying the role and mechanisms of alpha and gamma oscillations.

eLife Assessment

This important study shows that visual search for upright and rotated objects is affected by rotating participants in a VR and gravitational reference frame. However, the evidence supporting this conclusion is incomplete, given the authors' use of normalized response time and the assumption that object recognition across rotations requires mental rotation.

eLife Assessment

This study provides important results with regard to the ongoing debate of the relationship between internalizing psychopathology and learning under uncertainty. The methods and analyses are solid, and the results are backed by a large sample size, yet the study could still benefit from a more detailed discussion about the difference in experimental design and analysis compared to previous studies. If these concerns are addressed, this study would be of interest to researchers in clinical and computational psychiatry for the behavioral markers of psychopathological symptoms.

eLife Assessment

This valuable study describes MerQuaCo, a computational and automatic quality control tool for spatial transcriptomics datasets. The authors have collected a remarkable number of tissues to construct the main algorithm. The compelling strength of the evidence is demonstrated through a combination of empirical observations, automated computational approaches, and validation against existing software packages. MerQuaCo will interest researchers who routinely perform spatial transcriptomic imaging (especially MERSCOPE), as it provides an imperfection detector and quality control measures for reliable and reproducible downstream analysis.

eLife Assessment

This study provides a valuable contribution to spatial transcriptomics by introducing MerQuaCo, a computational tool for standardizing quality control in image-based spatial transcriptomics datasets. The tool addresses the lack of consensus in the field and provides robust metrics to identify and quantify common imperfections in datasets. The work is supported by an impressive dataset and compelling analyses, and will be of significant interest to researchers focused on data reproducibility and downstream analysis reliability in spatial transcriptomics.

eLife Assessment

This important study shows how the relative importance of inter-species interactions in microbiomes can be inferred from empirical species abundance data. The methods based on statistical physics of disordered systems are compelling and rigorous, and allow for distinguishing healthy and non-healthy human gut microbiomes via differences in their inter-species interaction patterns. This work should be of broad interest to researchers in microbial ecology and theoretical biophysics.

for - paper - title - Memory, Sleep, Dreams, and Consciousness: A Perspective Based on the Memory Theory of Consciousness - author - Andrew E. Budson, Ken A Paller - adjacency - memories - sleep - dreams - Memory Theory of Consciousness - MToC

summary - The authors present a theory of dreaming and sleep that I resonate with, that sleep is a time in which the brain performs unconscious processing of memories, consolidating them by taking advantage of consciousnesss down time to perform massive parallel processing to connect memories together. - dreams are seen as a small conscious byproduct of the massive parallel processing task, and their meaning may have value depending on how we interpret them.

eLife Assessment

This manuscript characterizes a mutated clone of RNA polymerase I in yeast, referred to as SuperPol, to understand the mechanisms of RNA polymerase I elongation and termination. The authors present convincing evidence that demonstrates the existence of premature termination in Pol I transcription. Overall, the characterization of this RNA pol I offers important insights into the regulation of ribosomal RNA transcription and its potential application in cancer pharmacology.

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

eLife Assessment

In this study, the authors offer a theoretical explanation for the emergence of nematic bundles in the actin cortex, carrying implications for the assembly of actomyosin stress fibers. As such, the study is a valuable contribution to the field actomyosin organisation in the actin cortex. The theoretical work is solid and provides a rigorous theoretical framework to study active self-organisation in actomyosin systems, including qualitative comparison with experimental observations.

eLife Assessment

The study is useful for advancing spatial transcriptomics through its novel regression-based linear model (glmSMA) that integrates single-cell RNA-seq with spatial reference atlases, and its methodological framework is convincing. The approach demonstrates notable utility by enabling higher-resolution cell mapping across multiple biological systems and spatial platforms compared to existing tools.

eLife Assessment

This study provides a fundamental advancement in our understanding of trabecular meshwork cell diversity and its role in eye pressure regulation and glaucoma using multimodal single-cell analysis, spatial validation, and functional testing that go beyond the current state-of-the-art. The study demonstrates that mitochondrial dysfunction, specifically in one of three distinct cell subtypes (TM3), contributes to elevated IOP in a genetic mouse model of glaucoma carrying a mutation in the transcription factor Lmx1b. While the identification of TM3 cells as metabolically specialized is compelling, there is somewhat limited evidence linking mitochondrial dysfunction to the Lmx1b mutation in TM3 cells.

eLife Assessment

This useful study investigates how intrinsically disordered domains can interact to dictate the sub-cellular localization of a major innate immune sensor termed cGAS. The data from various cellular and biochemical assays are mostly solid, but the main conclusions from these experiments need to be validated further. This paper is relevant to immunologists, especially those interested in cytosolic DNA-sensing pathways.

eLife Assessment

Ruppert et al. investigated how activation of thermogenesis by cold exposure (CE) and methionine restriction (MetR) impacts health and leads to weight loss in mice. The authors provided valuable datasets showing that the responses to MR and CE are tissue-specific, while MR and CE affect beige adipose similarly. Although the study is descriptive, the data analyses are solid, with well-supported conclusions drawn from the findings.

eLife Assessment

This interesting study adapts machine learning tools to analyze movements of a chromatin locus in living cells in response to serum starvation. The machine learning approach developed is useful, the experiments are well controlled, and the data are solid. The study would be greatly strengthened by testing key predictions made using perturbation experiments. This work will be of interest to those studying chromosome biology and gene expression patterns.

eLife Assessment

This study characterises motor and somatosensory cortex neural activity during naturalistic eating and drinking tongue movement in nonhuman primates. The data, which include electrophysiology, three-dimensional tracking of tongue movements, and nerve block manipulations, are valuable to neuroscientists and neural engineers interested in tongue use. Although the current analyses provide a solid description of single neuron activity in these areas, both the population level analyses and the characterisation of activity changes following nerve block could be improved.

eLife Assessment

The authors describe an interesting approach to studying the dynamics and function of membrane proteins in different lipid environments. The important findings have theoretical and practical implications beyond the study of EGFR to all membrane signalling proteins. The evidence supporting the conclusions is convincing, based on the use of a nanodisk system to study membrane proteins in vitro, combined with state-of-the-art single-molecule FRET. The work will be of broad interest to cell biologists and biochemists.

eLife Assessment

In this valuable study, through carefully executed and rigorously controlled experiments, the authors challenged a previously reported role of the Death Receptor 6 (DR6/Tnfrsf21) in Wallerian degeneration (WD). Using two DR6 knockout mouse lines and multiple WD assays, both in vitro and in vivo, the authors provided convincing evidence that loss of DR6 in mice does not protect peripheral axons from WD after injury. Questions remain about whether this conclusion is generalizable to CNS axonal degeneration in disease models such as ALS, AD, and prion diseases. In addition, the authors need to provide information about the sex, age, and genetic background of their animal studies to allow readers to better assess the basis for inconsistencies from previous reports on the protective effects of DR6.

eLife Assessment

In their study, Brown et. al. provide an important advance in understanding the architecture of the mycobacterial outer membrane. Using all-atom simulations of model mycomembranes, the work reports compelling structural insights into how α-mycolic acids and outer leaflet lipids (PDIM and PAT) shape membrane organisation. The work revealed membrane heterogeneity with ordered inner leaflets and disordered outer leaflets that provide a molecular explanation for the resilience of the mycobacterial envelope.

eLife Assessment

This important study uses innovative microfluidics-based single-cell imaging to monitor replicative lifespan, protein localization, and intracellular iron levels in aging yeast cells. The evidence for the proposed role of Ssd1 and reduced nutrients for lifespan through limiting iron uptake is convincing, even though some mechanistic details remain unclear. This work will be of interest to cell biologists working on aging and iron metabolism.

eLife Assessment

With the goal of investigating the assembly and fragmentation of cellular aggregates, this manuscript investigates cyanobacterial aggregates in a laboratory setting. This investigation of the conditions and mechanisms behind aggregation is an important contribution as it yields basic understanding of natural processes and offers potential strategies for control. The combination of computational and experimental investigations in this manuscript provides solid support for the role of shear on aggregation and fragmentation. However, the role of extracellular matrix, with possibly a strong effect on aggregation, is not adequately studied.

eLife Assessment

This important and creative study finds that the uplift of the Qinghai-Tibet Plateau - via its resultant monsoon system rather than solely its high elevation - has shifted avian migratory directions from a latitudinal to a longitudinal orientation. The authors have expanded and clarified their lines of evidence (including an enlarged tracking set and explicit caveats on species-level eBird inference), such that the central claims are now solid. The conclusions - that monsoon dynamics, rather than elevation per se, are most consistent with observed longitudinal reorientation - illustrates how large, community-sourced and climate-model datasets can inform continent-scale shifts in migratory behavior over time that complement traditional approaches.

eLife Assessment

This important work has the potential to expand the repertoire of transgenic animals for systems neuroscience investigations across multiple fields. The generation of new reagents has the potential to open new directions in experimental design, and the Cas9-based approach for generating mice may provide additional benefits compared to existing BAC transgenic mouse lines. However, whereas some of the imaging data are compelling, quantitative analysis of transgene fidelity is incomplete, as it relies on a qualitative description of reporter XFP expression at low magnification, with some electrophysiological characterization.

eLife Assessment

This important study reports on the redundant roles of the decapping activators Edc3 and Scd6 in orchestrating post-transcriptional programs to modulate metabolic responses to nutrients in yeast. The authors employed mutagenesis studies in conjunction with a battery of transcriptome-wide analyses to provide convincing evidence supporting their conclusions. Considering the broad implications of post-transcriptional regulation of gene expression, this study will be of interest across a variety of biomedical disciplines ranging from biochemistry and molecular and cellular biology to those specializing in studying various pathologies.

eLife Assessment

This manuscript revisits the well-studied KdpFABC potassium transport system from bacteria with a convincing set of new higher resolution structures, a protein expression strategy that permits purification of the active wildtype protein, and solid insight obtained from mutagenesis and activity assays. The thorough and thoughtful mechanistic analyses makes this a valuable contribution to the membrane transport field.

eLife Assessment

This is a methodologically rich manuscript that is important for revealing the center-surround inhibition profile of expectation in orientation space. The analyses are compelling in validating the critical role of predictive coding feedback. The findings provide novel insights into how expectation optimizes perception via enhancement and suppression.

eLife Assessment

This important study reports the results of efforts to replicate two phenomena of significant interest to early-career scientists and scientific policymakers: the Matthew effect and the early-career setback effect. Several previous studies of these effects have focused on early-career researchers with grant proposals that fell just below or just above a funding threshold. Those just above the threshold were more likely to be successful when they applied for funding later in the career (an example of the well-known Matthew effect), while those just below were more likely to go on to have stronger publication records (the early-career setback effect). In this study the Matthew effect was found to be robust across funders, and to generalize from those close to the funding threshold to the whole population. The early-career setback effect was not robust across funders and did not generalize to the whole population. The evidence reported is convincing.

eLife Assessment

This important research addresses the effects of subjective control and task difficulty on experienced stress using a novel behavioral task administered on the same day in two large online samples. Convincing evidence is provided, establishing the internal and external task validity of the task, as well as a relationship between the sense of control and task difficulty, with individual differences in relevant mental health constructs. Evidence for the specificity of the link between control and stress would be more substantial if the design had not conflated control and reward rate. This work will be of interest to psychologists and clinicians studying the concepts of controllability, stress, and psychopathology.