eLife Assessment

This study provided useful information regarding the role of a subpopulation of cortical interneurons (Chrna2-expressing Martinotti cells) in motor learning and cortical dynamics. However, while some behavior and imaging data are compelling, limitations in the motor-learning task design and data analysis make it difficult to support the central conclusions.

eLife Assessment

This paper presents a collection of analyses relating structure and function in the whole-brain Drosophila EM connectome and whole-brain calcium imaging data. The linkage of detailed anatomical structure with population activity is of broad interest in circuit neuroscience in light of increasingly detailed brain maps, but the methods used made the evidence incomplete due to indirect consideration of biological detail such as neurotransmitter identity and assumptions about the relationship between structural correlations and functional correlations. The conclusions are useful for specific network observations, but a more thorough analysis of the anatomical and functional data is needed to support the overall claims.

eLife Assessment

This valuable study compares orthogonal approaches for detecting RNA chemical modifications and provides a helpful framework for improving the reliability of RNA modification identification by direct RNA sequencing. The evidence supporting the technical benchmarking claims is solid, with multiple complementary controls, including in vitro-transcribed RNA, chemical inhibition of METTL3, and orthogonal m6A mapping. However, claims regarding relative method accuracy and cell-type- and isoform-specific biological differences remain less well supported due to limited biological replication and validation.

eLife Assessment

This study reports the relative importance of Tie1 and Tie2 signaling for atrial versus ventricular trabeculation. It is an important study and is one of the few works to date that have carefully and simultaneously analyzed these two processes. In line with a previous study in zebrafish, the authors demonstrate key differences between atrial and ventricular trabeculation. While the imaging and quantitative analyses are conducted using solid and validated methodologies throughout the manuscript, future studies using additional experimental approaches will be invaluable to further establish the underlying mechanisms.

eLife Assessment

This valuable study relating brain anatomy to reading ability in children studied longitudinally finds that a difference in sulcal anatomy is more predictive of reading ability than cognitive measures. The evidence that this anatomical difference is predictive and confers some benefit in the connectivity between brain areas is based on careful analyses and is solid. The findings would be of interest to researchers studying brain and cognitive development.

eLife Assessment

This study shows that the compound Yoda potentiates the function of the PIEZO2 channel, challenging the assumption that they selectively activate PIEZO1. This is an important finding and the evidence supporting this claim is solid. The authors have addressed the methodological and conceptual issues raised during review. Overall, this work will be of broad interest to researchers working with PIEZO channels across various biological scales.

eLife Assessment

The study investigates, from multiple angles, the still-debated function of insect rhodopsin-7 (Rh7). The authors present compelling results for its ancient phylogenetic origin across pan-arthropods, a non-visual role based on expression analyses in the fly brain, an unusual G-protein signalling pathway, and - using behavioural genetics - that Rh7 affects how Drosophila melanogaster interprets and responds to light-dark transitions. Through this, the work provides fundamental new insights into the evolution and function of non-visual opsins.

eLife Assessment

This study provides important information on the role of ErbB4 expression in parvalbumin-positive cells in relation to olfactory behaviour and circuit dynamics in the olfactory bulb. The central question is both timely and novel, and the findings could shed light on the critical role that ErbB4 may play in modulating olfactory bulb cell function and olfactory perception. The authors conducted a comprehensive set of experiments which provide solid evidence in support of their conclusions. However, some concerns remain regarding the technical approaches used, such as spike sorting and control/baseline comparisons.

Editors Assessment:

This Technical Release (software) presents a serverless cloud workflow for the computationally intensive alignment step of single-cell RNA-seq processing, extending the authors’ earlier serverless approach for bulk RNA-seq. Hung et al. built on the Piscem-Alevin-Fry pipeline and implemented it with AWS Lambda functions, working around their memory, storage and runtime limits by splitting large FASTQ files into four-million-read shards, streaming inputs from S3 straight into the aligner, and merging shard outputs as they complete. Because every stage overlaps, alignment adds only seconds beyond the cost of splitting and uploading. Compared with an optimized 32-thread on-server run on identical EC2 hardware, the serverless workflow was faster for all three datasets tested (two 10x Genomics PBMC datasets and a 450 GB, 13-sample MorPhiC pancreatic differentiation knockout dataset). The speedup grew with dataset size, from 1.27× to 1.93× to 7.01× for the largest, cutting about 2.4 hours of alignment to under 21 minutes, with outputs validated as identical to the conventional pipeline. The authors are transparent that this speed comes at a cost: the serverless runs were more expensive at list prices, though the premium shrank to about 13% for the largest dataset, and gains for small datasets are limited by driver-side preprocessing. With open-source code under an MIT license, an automated orchestration script, and deposited reference index and count matrices, this is a useful and reproducible template for processing large single-cell datasets, and for applying serverless computing to other bioinformatics workflows.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This Technical Release (software/workflow paper) presents Poly Pipeline, an open-source spatial transcriptomics workflow designed to handle the data sparsity, fragmented proprietary formats and duplicated-gene complexity that make polyploid plant genomes difficult to analyze. Carvalho et al. combine a converter that turns h5ad and GEM files into the GEF format used by Stereopy, quality filtering, Louvain, Leiden and Spatial Leiden clustering, a user-defined “anchoring” step for assigning regions, and highly variable and marker gene detection. Optional hdWGCNA co-expression networks are built on KNN-derived metacells, intended to retain low-expressed duplicated genes that would otherwise be discarded as dropouts. The pipeline was developed on a hexaploid wheat seed Stereo-seq dataset and benchmarked on rice, Arabidopsis and mouse data in different formats. Spatial Leiden gave more cohesive tissue domains than standard Leiden (15 versus 26 clusters in wheat), and the largest dataset (40,248 cells, 70,766 genes) ran in about 23.5 minutes using a peak of 31.8 GB of RAM. The benchmarking mainly shows that the workflow runs reliably and produces spatially coherent domains across organisms and formats. It does not directly test the claim that hdWGCNA better preserves duplicated-gene signatures, so that remains largely supported by argument rather than comparison with other methods. Nonetheless, with the code available on GitHub under an MIT license (with Zenodo, WorkflowHub, RRID and bio.tools entries), this provides a reproducible, HPC-ready framework that should help plant researchers working with complex genomes and multi-platform spatial datasets.

This evaluation refers to version 1 of the preprint

Editors Assessment:

This Data Release presents shotgun metagenomic sequencing data from the oral microbiome of patients with oral squamous cell carcinoma (OSCC), a setting where most previous studies have used 16S rRNA amplicon sequencing with limited species-level resolution. The authors sequenced dental plaque, saliva and tumor tissue from 10 OSCC patients, alongside plaque and saliva from 10 healthy controls, on the Illumina MiSeq platform. After three control saliva samples failed quality control, 46 samples remained, with roughly 75,000-100,000 reads per sample after filtering. Reads were classified with Kraken2 and Bracken, and the sequencing data are deposited in NCBI, with supporting data in GigaDB and a Conda-based pipeline on GitHub. The authors report that dental plaque had the highest diversity, that saliva was more homogeneous, and that tumor tissue had a distinct profile dominated by taxa such as Sellimonas catena, Escherichia coli and Lacrimispora sp. HJ-01. The plaque of OSCC patients was enriched in Pyramidobacter piscolens and Parvimonas parva, compared with Streptococcus koreensis in controls. The authors are open about the limitations of this small, convenience-sampled exploratory cohort: oral hygiene differs markedly between patients and controls, 90% of participants are female, and no negative extraction controls or mock communities were included. The taxonomic differences should therefore be read as hypothesis-generating rather than disease-specific. Even so, the matched multi-niche sampling, open data and reproducible workflow make this a useful resource for integration with other metagenomic datasets and for follow-up functional studies of the oral microbiome in OSCC.

This evaluation refers to version 1 of the preprint

eLife Assessment

This work presents valuable new data on the role of D-Serine and how it competes with its stereoisomer L-Serine to influence metabolism. The work presents a variety of convincing experimental data combined with simulated results to investigate the mechanisms focused on one-carbon metabolism, which is relevant for several research fields. However, some claims are only partially supported by data, and critical areas comparing L- vs D-Serine and further mechanistic studies are required. Furthermore, while the work has potential for various fields, the work has only been studied in a neural context.

eLife Assessment

This important study identifies two pairs of dopaminergic neurons (DA-WED) in Drosophila that coordinate cardiac deceleration and locomotor responses to a mechanical threat. The conclusions are supported by convincing evidence from a combination of optogenetic, physiological, and behavioral experiments. The work provides invaluable insights into the neural coordination of behavioral and cardiac responses to threat and will be broad interest to neuroscientists, physiologists, and researchers studying brain-body interactions.

eLife Assessment

This study utilizes a two-choice assay to examine how groups of Drosophila melanogaster respond to temperature changes. The findings are useful, offering focused importance for the collective decision-making community. However, the strength of the evidence is incomplete, as the current data only partially support the primary claims and the work lacks the necessary integration into the existing literature to contextualize the findings.

eLife Assessment

This fundamental paper describes the role of the Pre-rRNA in meiotic sex chromosome inactivation in mouse spermatocytes. The cytological and genome-wide analyses on components of the nucleolus and chemical inhibition of RNA polymerase I for rDNA transcription provided solid evidence to support the authors' conclusion. The results shown in the paper are of interest to researchers in meiotic chromosome structure and the nucleolus.

eLife Assessment

This study presents an important examination of the role of cis-acting versus trans-acting genetic variation in DNA methylation divergence between humans and chimpanzees and its relationship to gene expression. By differentiating fused interspecies tetraploid cell lines into multiple cell types, the study provides compelling evidence that cis-acting changes predominate in DNA methylation divergence. The evidence linking directional methylation divergence to lineage-specific selection and, particularly, to adaptive human phenotypes is less clear. This work will be of interest to biologists and evolutionary anthropologists studying the evolution and genetics of gene regulation, particularly in primates.

eLife Assessment

The authors established a novel three-dimensional culture system for stratified epithelia that allows epithelial cells to undergo epithelial-to-mesenchymal transition (EMT) and subsequent mesenchymal-to-epithelial transition (MET) while migrating through a membrane with 3.0-µm micropores, and, thus, provides a highly valuable tool to study EMT and possibly wound regeneration or metastasis. Furthermore, a set of experiments provides compelling data suggesting that TGF beta signaling and actin polymerization promote movement of epithelial cells into the pores, while Piezo1 and Keratin 6 prevent keratinocyte migration and EMT.

eLife Assessment

This important study describes computationally designed proteins that bind to the chemokine CCL25. The authors present evidence that some binders simply prevent chemokine binding to the CCR9 receptor, while one binder changes the downstream signaling triggered by chemokine binding. The evidence is convincing, showing a degree of selectivity between chemokine ligands that could be further improved. The study will be of interest to pharmacologists, cell biologists studying chemokine function, and protein engineers.

eLife Assessment

This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents an important addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. The experimental evidence supporting the core ideas is solid and provides mechanistic insight into how ITK deficiency promotes a tissue-protective Treg phenotype, although additional studies will be needed to further define the molecular pathways involved.

eLife Assessment

This manuscript seeks to understand the hierarchical temporal representation of social actions in the lateral visual pathway in the human brain. It introduces a potentially valuable methodological approach for characterizing the spatiotemporal dynamics of social-interaction representations, with the data supporting the hypothesis that the anterior portion of the superior temporal sulcus responds to communicative actions, and providing a temporal estimate of when it begins responding. However, the failure to recover several previously reported effects regarding mid-level representations in this and other visual brain regions, combined with unresolved concerns about the correspondence between EEG, fMRI, and stimulus-feature measures, limits confidence in the method's sensitivity and validity, rendering the current empirical evidence against a hierarchical feedforward architecture incomplete.

eLife Assessment

This valuable study identifies Gcn5 as a regulator of blood cell development in the Drosophila lymph gland, with links to autophagy and nutrient-sensing mTORC1 signalling. While the mechanistic ordering between Gcn5, mTORC1 and TFEB/autophagy remains less fully resolved, the evidence is solid that perturbing Gcn5, autophagy genes and mTORC1 activity affects blood cell homeostasis. The work will be of interest to researchers studying developmental haematopoiesis, metabolic regulation and autophagy.

eLife Assessment

This important study extends a model of cortical normalization (ORGaNICs) to interacting cortical areas and shows that communication through coherence and communication subspaces can arise from a single set of dynamics. The evidence is convincing, showing analytically that contrast-dependent gamma dynamics and a low-dimensional inter-areal communication subspace arise from one parameter set. The work will interest neuroscientists and theorists concerned with inter-areal communication, cortical oscillations, and divisive normalization.

eLife Assessment

Using their unique Fish-On-Chips optofluidics platform, the authors make three important findings: the presence of precise coupling between saccades and tail flips can be used to discriminate between turning or gliding behaviours; aversive and appetitive chemosensory cues differentially modulate these behaviours; transformation from cue valence to behaviour is encoded by the pallium. The evidence supporting these findings is solid. The work advances our understanding of the ancient interplay between chemosensation and motor output through the modulation of eye-body coordination.

eLife Assessment

This study presents a valuable contribution to comparative cognitive neuroscience by directly mapping functional homologues of the human multiple-demand network in macaques using a matched spatial maze task. It provides solid evidence for functional correspondence between human and macaque cognitive control networks in dorsomedial frontal cortex and insula. However, given only two animals and no cross-animal convergence in parietal or ventrolateral prefrontal regions, claims that these regions form part of a macaque MD network should be read as provisional. The work will be of interest to researchers studying the evolution of cognitive control and cross-species neuroimaging.

eLife Assessment

This work has much novelty, supportive data, and the potential for changing thinking about melanoma biology with the discovery of MRGPRX4 as a relatively melanoma-specific G protein-coupled receptor. MRGPRX4 is normally restricted to peripheral sensory neurons, but it is aberrantly expressed in human melanomas; melanomas with neural-crest-like/invasive features were most likely affected. When ectopically expressed in murine melanocytes, MRGPRX4 drives melanoma development with metastasis; the mechanism appears to involve ligand-independent receptor signaling. Overall, the text presents this as a novel model of oncogenesis driven by re-expression of a sensory GPCR - this is an important study with compelling data.

eLife Assessment

This important study presents a cell-based screen for small-molecule activators of GCN2, an eIF2α kinase that regulates the Integrated Stress Response under diverse stress conditions. The authors identify a compound as a potent GCN2 activator with GCN1-independent activity under the tested conditions, providing a new pharmacological tool for probing GCN2 regulation. The revised manuscript provides compelling support for the central conclusions through a clearer description of the screening workflow, extended kinetic analyses, and demonstration that the identified compound causes a GCN2-dependent reduction in protein synthesis.

eLife Assessment

This valuable study investigates the cleavage-independent functions of Gasdermins in keratinocytes. The data collected using advanced microscopy methods and Western blotting are solid, but the main conclusions from these experiments remain partially supported. This paper is relevant to those studying cell-type specific inflammatory responses and client/cargo specificities of Gasdermins.

eLife Assessment

This study provides valuable insights into the role of thalamic nuclei in associative threat and extinction learning, underpinned by a large dataset and rigorous, multipronged analyses. The evidence provided is solid, supporting the main conclusions. The manuscript will be of broad interest to researchers in learning and memory, fear, thalamic circuitry, and related mental health conditions.

eLife Assessment

This valuable study uses single-cell profiling, lineage barcoding, and functional assays to examine drug-tolerant persisters in a BRAF-inhibited melanoma cell line. The data provide solid evidence that persisters arise from many lineages and have altered calcium handling and increased sensitivity to ferroptosis, although the lineage result is difficult to interpret without knowing how many cells survived treatment. The broader claim that these cells represent substates within a single persister state is less well supported, as it rests largely on transcriptomic projections, lacks time-resolved data, and has been examined in only one cell line.

eLife Assessment

This important study provides convincing novel evidence for a role of ripples in the hippocampus in visual short-term memory. The work is strong in employing state-of-the-art intracranial electrophysiology in epilepsy patients with multivariate pattern classifiers in the context of an elegant experiment, though some reviewers had concerns about interpretation of the ripple activity. The work will be of interest to researchers studying working memory and hippocampal ripples.

eLife Assessment

This is a very helpful study that presents an easy to use and reliable alternative to conventional and UV-based tetramers for the identification of antigen-specific CD8 T cells. The authors demonstrate that tetramers for a number of HLA alleles can be subjected to specific temperatures that facilitate peptide exchange whilst maintaining structural integrity, thereby generating detection reagents. They provide convincing evidence for this method, and the approach is likely to provide a useful alternative to generating reagents for examining T cell specificities.

eLife Assessment

This valuable study compares orthogonal approaches for detecting RNA chemical modifications and provides a helpful framework for improving the reliability of RNA modification identification by direct RNA sequencing. The evidence supporting the technical benchmarking claims is solid, with multiple complementary controls, including in vitro-transcribed RNA, chemical inhibition of METTL3, and orthogonal m6A mapping. However, claims regarding relative method accuracy and cell-type- and isoform-specific biological differences remain less well supported due to limited biological replication and validation.

eLife Assessment

In this important study, the authors demonstrate that generative AI techniques (restricted Boltzmann machine) can be used effectively to design and characterize mutational pathways of WW domains with different binding specificities. The computational studies are complemented by experimental validations, and the results provide convincing evidence supporting the idea that sequence landscape holds significance in understanding protein evolution from a transition path perspective. The minor weakness of the study has been largely addressed in the revision. The work will likely have a major impact on research aimed at understanding how evolution navigates fitness landscapes as well as reconstructing ancestral sequences.

eLife Assessment

In this manuscript the authors established a novel three-dimensional culture system for stratified epithelia that allows epithelial cells to undergo epithelial-to-mesenchymal transition (EMT) and subsequent mesenchymal-to-epithelial transition (MET) while migrating through a membrane with 3.0-µm micropores, and, thus, provides a highly valuable tool to study EMT and possibly wound regeneration or metastasis. Furthermore, a set of experiments provides compelling data suggesting that TGF beta signaling and actin polymerization promote movement of epithelial cells into the pores, while Piezo1 and Keratin 6 prevent keratinocyte migration and EMT.

eLife Assessment

This important study presents convincing findings on creating an exhaustive library of new enhancer-AAVs targeting astrocytes and oligodendrocytes with high potential for both basic and translational work, which will be of value to a large and growing community. The revisions appropriately addressed some of the previous concerns by updating description of glial biology in the Introduction and modifying text on experimental results and approaches. Overall, these amendments have strengthened the claims. The work will be of interest to neuroscientists working on glial cell biology.

eLife Assessment

The study provides an important empirical assessment of a non-adaptive hypothesis on transposable element evolution grounded in population genetics principles. The results suggest that the impact of genetic drift on transposable element amplification is not global, but depends on the phylogenetic scale being considered and can be overwhelmed by lineage-specific dynamics. The analyses are mostly appropriate, but currently incomplete in some aspects. Former conclusions will require additional crosschecks.

eLife Assessment

This important study tackles the challenge of analyzing genome integrity and instability in unicellular pathogens by introducing a novel single-cell genomics approach. It presents compelling evidence that this new tool outperforms standard whole-genome amplification techniques and describes a method that shows promise for probing questions regarding the biology of Leishmania and other microbial eukaryotes.

eLife Assessment

This study investigates the role of Interleukin-2-inducible T cell kinase (ITK) deficiency in autoimmune lung injury using a pristane-induced pulmonary hemorrhage (PH) model, suggesting that ITK-deficient regulatory T cells (Tregs) restrict severe tissue pathology. The work represents an important addition to the fields of autoimmunity, inflammation, and T-cell biology in the lung. The experimental evidence supporting the core ideas is solid, but there is additional work needed to define the underlying mechanisms.

eLife Assessment

This important study presents evidence that the human brain encodes perceptual absence and numerical absence through distinct neural codes, while confirming that symbolic and non-symbolic forms of zero share a common representation. The evidence supporting this dissociation is convincing, although the tasks differ substantially, and it remains unclear whether the result reflects a divide between numerical and non-numerical absence or between perception and abstract concepts. The work will be of interest to neuroscientists and psychologists studying numerical cognition and the boundary between perception and higher-level cognition.

eLife Assessment

The authors provide valuable findings showing that GM-CSF prevents the loss of ILC3 populations during gut inflammation and inhibits pro-inflammatory cytokine production. They combine a preclinical model of gut inflammation in zebrafish with spatial transcriptomic analysis of samples from Crohn's disease patients. Although the data provided are clear and point to an anti-inflammatory role of GM-CSF, the strength of evidence remains incomplete especially on the nature of the cells involved. This work will be of interest to immunologists.

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, along with a comparison to the human intestine and organoids; 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.

eLife Assessment

This is an important study that establishes a novel and enabling 3D super-resolution imaging approach for visualizing the nanoscale organization of AMPA receptors in thick mouse brain tissue. The biological findings are of importance and interest to the neuroscience field, with potential implications for neurodegenerative disease research. However, the evidence remains incomplete and some of the biological conclusions would benefit from strengthened quantitative analysis and revisions to the manuscript to ensure that the interpretations are appropriately aligned with what is supported by the analysis.

eLife Assessment

This important study shows that induced expression of transglutaminase 2 (TG2) fused to an antigenic peptide in mouse intestinal epithelial cells can trigger an anti-TG2 autoantibody response similar to that seen in celiac disease. The conclusions are supported by convincing evidence from a well-designed mouse model, although some additional experiments would strengthen the study. The work will be of interest to researchers studying celiac disease, other autoimmune conditions, and mucosal immunologists.

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 in several of the performed experiments and mechanistic exploration with only a limited set of experimental techniques leave some conclusions less firmly established. The work will be of interest to researchers studying autophagy, ageing, and intracellular trafficking.

eLife Assessment

This study provides useful data on oscillatory coupling during speech planning, particularly suggesting that theta-band phase coupling may differentiate networks involved in object recognition and semantic-lexical retrieval. However, the strength of the evidence is incomplete because the absence of a linguistic manipulation and key confounds between the naming and control conditions limit the ability to attribute the reported effects specifically to word production, leaving the main mechanistic conclusions only partially supported.

eLife Assessment

This valuable study reports the architectural reorganization of the uterine luminal epithelium during the implantation period. Solid data are presented to support the main conclusion. This work is of interest to reproductive biologists and physicians practicing reproductive medicine.

eLife Assessment

This work presents valuable findings that identify ergosterol binding by the human ABC transporter ABCG5/G8 and show that ergosterol stimulates its ATPase activity more strongly than cholesterol, advancing understanding of sterol recognition and transport. The evidence from single-particle cryo-EM, molecular dynamics simulations, and biochemical assays is convincing, although additional structures and mutational studies would strengthen the proposed mechanism. These results provide key insight into the molecular basis of sterol recognition and regulation of ABCG5/G8 and will be of interest to researchers studying sterol transport and ABC transporter function.

eLife Assessment

This study presents an open-source reinforcement learning framework for the real-time, closed-loop optimization of spatiotemporal electrical stimulation in engineered neuronal networks. Using single-spike-resolution activity as continuous feedback, the authors provide solid evidence that their platform can identify stimulation patterns that drive specific activity motifs within a structurally constrained four-node circuit. While this reproducible system offers a valuable and accessible tool for interacting with biological neural networks in an adaptive manner, further validation is needed to determine how well these stimulation strategies generalize to larger, unstructured, or more conventional network architectures.

eLife Assessment

In this valuable study, the authors build on previous work demonstrating that the microtubule-associated protein CKAP2 functions at the mitotic spindle to regulate microtubule dynamics for proper chromosome segregation. Here, the authors show that CKAP2 and its paralog CKAP2L also function at the cilium to regulate cilium formation and Hedgehog signaling. The writing is clear, the experiments and data are generally convincing, and the proper data analysis is carried out; however, the evidence supporting the proposal that CKAP2 and CKAP2L compensate for each other is incomplete. Overall, the findings advance the field in our knowledge of microtubule-associated proteins with roles in both the mitotic spindle and the cilium.

eLife Assessment

This valuable study shows first that yeast strains potentially associated with the [MRPL10+] prion state strongly influence Drosophila cold tolerance and locomotor behavior, and it goes on to exploit natural variation to identify host pathways contributing to these responses. The evidence for host physiology and genetics is solid, but the evidence for MRPL10 prion causality is incomplete because the prion state has not been directly validated in the yeast strains used. The study would be substantially strengthened either by establishing the presence of the MRPL10 prion state, or by tempering the prion-specific causal claims and framing involvement of MPRL10 or other prions in the yeast strains as a plausible but unproven mechanism. The work will be of interest to many fields, including quantitative genetics, insect physiology and microbe-host interactions.

eLife Assessment

This valuable study presents a comparative framework for quantifying adaptation in SARS-CoV-2 and influenza H3N2 from changes in clade frequencies, enabling comparison of rates of adaptation across the two viruses on a common per-generation scale and showing that a simple count of mutations performs as well as much more sophisticated protein language models in predicting variant fitness. The evidence supporting the quantitative estimates of fitness flux is currently incomplete because the analysis assumes a single, time-independent fitness for each clade; for antigenically evolving viruses, clade fitness changes with population immunity, and it remains unclear how this assumption affects the estimated fitness flux. The interpretation of cumulative fitness flux in relation to changes in absolute fitness over time also requires clarification.

eLife Assessment

This important study investigates how retinoic acid signaling and retinal support cells called Müller glia might contribute to regional differences in the morphology and function of cone photoreceptors - light-sensitive neurons in the zebrafish retina - and may have broader implications for understanding how non-neuronal cells such as glia shape neuronal cell specialization in other regions of the nervous system. Despite well-executed imaging and pharmacological experiments, the evidence remains incomplete because the proposed mechanism is not established as specific to Müller glia, and broader effects on retinal development, cell growth, maturation, and/or differentiation could explain the observed shortening of light-sensitive structures. The work will interest researchers studying vision, nervous system development, and interactions between neurons and their supporting cells.

eLife Assessment

This valuable study examines excitation/inhibition (E/I) balance in the CA3-CA1 circuit of the hippocampus, yielding results that suggest a way in which CA1 neurons can perform mismatch detection. A combination of experimental and computational modeling results are presented and supported by solid evidence. The results are likely to be of interest to researchers who study computations in the hippocampal circuit.

eLife Assessment

This valuable study employs an innovative chemoproteomic and multi-modal experimental approach to support VDAC2 as a key functional mediator of STX effects on mitochondrial bioenergetics. The authors assimilated convincing evidence for targeting VDAC2 within POMC neurons to demonstrate neuroprotective therapies against Alzheimer's disease and menopause-associated neurodegeneration, with the potential to minimize adverse off-target side effects.

eLife Assessment

This important study investigates whether high-level physical reasoning is grounded in real-time bodily and vestibular signals using an innovative combination of virtual tool-use tasks and galvanic vestibular stimulation. The evidence is solid for the specific conclusion that ongoing vestibular information can influence selected aspects of physical reasoning in a context-dependent manner, while is incomplete for the broader mechanistic interpretations.

eLife Assessment

This important study shows that long-range somatostatin-expressing neurons in the ventrolateral periaqueductal grey that project to the rostral ventromedial medulla selectively suppress pain responses during conditioned fear. The evidence supporting these conclusions is exceptional, with methods spanning a novel cued fear-conditioned analgesia paradigm, cell-type-specific optogenetic activation and inhibition, anatomical circuit tracing, and in vivo spinal cord electrophysiology. These results will be of broad interest to systems and behavioral neuroscientists studying fear, pain, and descending pain-control circuitry.

eLife Assessment

This valuable study builds a novel auditory-motor paradigm to investigate how the brain learns associations between movements and their auditory consequences. Solid evidence is provided for early ERPs (50-100 ms latency) reflecting violations of established key-pitch mappings. The study is of potential interest to researchers studying audition, sensorimotor integration, or predictive coding, but some statistical analyses, however, could still be improved.

eLife Assessment

This fundamental study examines the benefits of spatial cognition in a wild population of mountain chickadees. Using robust genetic analyses and experimental design, the authors show with compelling evidence that females seeking out extra-pair copulations prefer males with strong spatial cognition, and that these males have a reproductive advantage over other males. This work will be of broad interest to evolutionary and behavioural biologists.

eLife Assessment

This important study examines how temporal and spatial discrepancies between an action and its visual feedback are combined in judgments related to the sense of agency. Using a virtual-reality reaching task and computational modeling, the authors show that both discrepancies influence self-attribution and that a multiplicative model outperforms the prespecified alternatives, a result reproduced in a preregistered replication. The evidence is convincing for the conclusion that temporal and spatial information is integrated. Other models - beyond multiplication - may in principle account equally well for the observed data; sharpening these claims and situating the findings more clearly within Bayesian accounts of cue integration would further strengthen this key contribution.

eLife Assessment

This valuable study evaluates how different learning curricula in a complex planning task impact performance. The authors provide convincing evidence across eight behavioral studies that practicing increasingly difficult examples of a concept before moving to the next concept benefits immediate performance, despite participants having a preference for the reverse - learning new concepts before practicing. However, there is incomplete evidence for claims about relevance to real-world learning settings, as the curriculum effects did not persist across a delay or support transfer to new problem types. The paper will be of interest to researchers studying learning curricula, problem solving, planning, and education.

eLife Assessment

The primary aim of this study is to measure the different dimensions of executive function in non-human primates and the classification of animals into distinct cognitive phenotypes. To achieve this, it uses a multi-task touchscreen battery for six rhesus macaques with repeated measurements to examine how performance across inhibitory control, shifting/learning, working memory, and updating covaries within and across individuals. Overall, this is an important finding with relevance for anyone interested in behavioural assessment of cognitive functions in non-human primates or dimensionality of executive functions. The strength of evidence is overall convincing, with some minor methodological weaknesses that should be addressable in future versions.

eLife Assessment

This valuable study uses chemogenetic inactivation techniques in behaving macaque monkeys to ask whether the locus coeruleus (LC), an area that is involved in the control of arousal, is also involved in regulating access to mental resources for a task that requires working memory. The data show that moderate locus coeruleus inhibition impairs foraging efficiency without affecting response times, total rewards accrued, or overall motivation. However, the evidence supporting the more specific claim that the locus coeruleus regulates cognitive and/or working memory function is currently incomplete, as the experimental design is confounded by elapsed time, lacks formal statistical interaction tests, and relies on behavioral measures that cannot cleanly separate effort allocation from working memory capacity or strategy shifts. These limitations may be ameliorated with further analyses.

eLife Assessment

This study suggests that caspases strengthen the antiviral response by cleaving Drp1, which otherwise restrains mitochondria-mediated type I interferon signaling. The authors report an important finding supported by solid evidence. However, further mechanistic work is needed to firmly establish whether apoptotic caspases are indeed required for Drp1 depletion in virus-infected cells.

eLife Assessment

This manuscript addresses an important and conceptually ambitious question by using a synthetic biology strategy to perturb ATP homeostasis in yeast and examine its relationship with replicative lifespan. While the lifespan phenotype is robust and the experimental approach is generally solid, the current evidence is limited to establish intracellular ATP abundance as the causal determinant of lifespan, particularly given the apparent uncoupling from NTT1-dependent ATP import and single-cell ATP levels, as well as the possibility of extracellular ATP-induced stress responses. Further clarification of the mechanistic interpretation, including more cautious treatment of Snf1/AMPK signaling and NTT1 transport directionality, will be needed before the biological significance of the findings can be fully assessed.

eLife Assessment

This important large-scale comparative study of odorant receptor (OR) genes across more than 100 insect species, combining sequence- and structure-based approaches, represents a significant contribution in the exploration of the evolution of this large gene family involved in the detection of odorant signals by olfactory neurons. Most notably, the authors uncover a structural feature unique to the odorant receptor co-receptor Orco that reduces ligand binding affinity. From this solid data emerges a general integrative framework to apprehend the diversity and evolution of odorant receptor genes in insects.

eLife Assessment

This paper presents important findings on how the shapes of leaves might be biased towards simpler shapes due to biases in how variation is generated by developmental processes rather than selection. The authors present convincing evidence that combines image analysis of a herbarium dataset and computational analysis of a model of leaf development. The paper should be of interest to diverse researchers, ranging from plant development to the evolution of complexity more broadly.

eLife Assessment

This important study demonstrates how individual taste preferences change over time, how these changes are reflected in cortical activity, and how sensory experience contributes to reshaping both. The evidence is convincing and broadly supports the main conclusions. The findings should be of interest to neuroscientists studying sensory processing and cortical plasticity.

eLife Assessment

This study proposes that fitness level, but not sex, influences exercise-induced hypoalgesia in women. However, the evidence to support this claim is incomplete: the conclusions rely on a small-effect interaction that emerges only under specific conditions, the findings are inconsistent across pain modalities and stimulus intensities, and the absence of a baseline condition limits the interpretability of results as reflecting true hypoalgesia. Additionally, the methods by which fitness level was categorized across cohorts can be questioned. The results of this study could be useful to improve future experimental designs exploring these factors in more depth.

eLife Assessment

This study presents important findings linking peripheral inflammation to the remodeling of perinodal adipose tissue and draining lymph nodes, suggesting a mechanism by which local tissue inflammation can reshape LN structure and metabolism. The evidence is solid and supported by observations, future studies will address any outstanding questions.

eLife Assessment

This is a useful and clearly presented study showing how simple feedback between cell crowding and cell growth can maintain tissue balance and lead to the spontaneous formation of stem-cell clusters. The evidence supporting the behavior of the model is solid, but the significance of the clustering result would be strengthened by relating the emphasizing the differences to prior studies, and potentially relating the clustering mechanism to properties of critical birth-death processes in two dimensions.

eLife Assessment

This valuable study investigates the role of dinucleoside polyphosphates in regulating the cGAS-STING-TBK1 axis of innate immunity. The data collected using multiple biochemical and cellular assays, plus X-ray crystallography, are solid, but testing additional polyphosphates and using NUDT2KO cells will further strengthen the main conclusion. This paper will be broadly relevant to those studying various innate immune pathways.

eLife Assessment

This valuable study tests to what extent dopamine neuron stimulation produces striatal serotonin release, and vice versa - a topic of interest to neuroscientists studying the basal ganglia, neuromodulation, and reward learning. Employing a combination of modern optical and genetic methods, it provides solid evidence that the mesolimbic dopamine and serotonin systems operate primarily in parallel, with little crosstalk observed when each of the pathways are activated individually. The results are generally convincing, although the reviewers were still concerned about the absence of control experiments examining light artifacts.

eLife Assessment

This study demonstrates a critical role of the glycolipid membrane protein insertase (MPIase) in the twin-arginine translocation (TAT) pathway, a protein translocation system that is conserved across all domains of life. The successful reconstitution of the bacterial TAT system in both bacteria-derived and artificial liposomes provides solid experimental evidence that MPIase has a broader role in membrane protein translocation than previously recognized. By revealing the essential function of a nonproteinaceous membrane component in catalyzing a core cellular process, this work offers fundamental insights into the molecular mechanisms of protein translocation.

eLife Assessment

This study is a valuable contribution that comprehensively identifies and characterizes LC3B-binding peptides through a bacterial cell-surface display screen covering approximately 500,000 human peptides. The data presented are solid, although this approach has some limitations. For example, it cannot assess the effects of post-translational modifications, which are often relevant for LIR-mediated interactions. Validation of the newly identified binding peptides by demonstrating their interactions with full-length proteins in cells would further strengthen this work.

eLife Assessment

This valuable study substantially improves the phylogenetic framework for Kinetoplastea through greatly expanded sampling of free-living neobodonids; the phylogenomic analyses provide convincing evidence that neobodonids are paraphyletic and establish a substantially revised framework for deep relationships within Metakinetoplastina. The work forms the foundation for future comparative studies of kinetoplastid evolution and systematics, although its implications for the origins of parasitism should not be overstated. An 18S rRNA phylogeny documenting the placement of the newly sampled strains within previously recognized neobodonid lineages and/or confirmation of the principal topology using a well-documented phylogenomic set of marker genes would further strengthen the study. The work will be of particular interest to researchers studying protist evolution and the evolutionary context of trypanosomatids.

eLife Assessment

This valuable study applies a hidden Markov model to freezing, ultrasonic vocalizations, and lever pressing in male rats to ask whether fear extinction restores normal behavior or only suppresses defensive responding. The evidence is incomplete because the model states are not related back to raw behavior or group manipulations, and the states are not tested as predictors of relapse. The work will be of interest to researchers studying fear extinction and computational approaches to behavior.

eLife Assessment

This useful study presents Penumbria, a method for segmenting cells in three-dimensional microscopy images, released with publicly available code and documentation. The implementation is technically sound, and the reported performance gains would be a welcome contribution; the advance is incremental, since regression on distances to boundaries is already widespread in the field. The evidence is incomplete: the main text does not state which setting it used for the main competing method, and the setting used is the one that handles data of this kind poorly, so the central claim of better accuracy is unsettled; current leading methods are missing from the comparison; and five architectural and training choices are combined without attributing the gains to any of them. Every evaluation dataset labels nuclei, so the work should present itself as nuclei segmentation; describing and completing the comparisons, and attributing the gains, would raise the strength of evidence.

eLife Assessment

This important study uses coarse-grained molecular simulations to investigate how phosphorylation and small-molecule ligands reshape the interactions underlying condensation and multidomain assembly of HDAC6. The findings provide mechanistic insights into how modifications of intrinsically disordered regions and ligand binding may regulate protein condensation. The evidence is solid: although the simulations broadly agree with previous experimental observations, concerns about model robustness and sampling in full-length assemblies limit support for the proposed mechanism and its pharmacological implications.

eLife Assessment

The work presented represents important new evidence linking the cascade of neural processes triggered by memory-based prediction errors. The study uses an impressive collection of approaches and methods to characterize and measure cognitive control, arousal, and memory changes as a function of memory-based violations. The analyses are technically sophisticated and rigorous and, taken together, provide solid evidence that there are multiple processes accompanying prediction errors, and that they differentially relate to successful encoding.

eLife Assessment

This study provides valuable new insights into the functional differentiation of human amygdala subnuclei during the observation of negative images and emotional reappraisal. The evidence is convincing, particularly regarding differences in the time course of evoked responses and their partial correspondence with broad anatomical subdivisions. The work will be of interest to researchers studying the amygdala, emotional processing, and emotion regulation.

eLife Assessment

This study provides important novel insight into how Wnt/beta-catenin signaling may regulate the responsiveness of blood vessels in the brain and retina to vascular endothelial growth factor, with potential relevance to Wnt surrogate therapies aimed at restoring vascular barriers. Solid evidence that Wnt/beta-catenin signaling changes the protein abundance and relative balance of two vascular endothelial growth factor receptors in brain blood vessels is provided by informative genetic mosaic experiments; in the retina, however, regulation of VEGFR2 was difficult to establish because expression by neighboring cells obscured its detection in blood vessels. Physiological implications are discussed, but evidence remains incomplete because the observed changes in receptor abundance were not directly linked to altered signaling or vascular function in living animals. A second mechanism, in which Wnt/beta-catenin signaling suppresses signaling through VEGFR2 with little or no change in receptor abundance, was inferred from reporter experiments in cell-based systems.

eLife assessment

This study provides a useful inventory of genes that are up- or down-regulated during the early metamorphic development of male and female larvae and proposes that the microRNA cluster miR-277/34 is involved in the development of sexual differences during early metamorphosis of Drosophila melanogaster, although its precise role remains unclear. The strength of evidence, based on a combination of diverse methods including mRNA and small RNA sequencing, in silico analyses, in vitro assays, and loss-of-function experiments, is incomplete as it lacks a general model and an examination of the potential effects of the miR-277/34 mutations on phenotypes such as morphology or developmental time. This work will be of interest to developmental biologists interested in sexual dimorphism and in the interplay between hormones and microRNAs during development.

eLife Assessment

This important study used several genome-wide approaches to compare dormancy in S. pombe spores and killifish diapause embryos. The findings include a trade-off between longevity and heat resistance in yeast spores and, in both these systems, a relatively higher expression of ribosomal-protein mRNAs but not proteins. While the evidence for the findings is overall solid, some interpretations should still be tempered. The large-scale datasets provide an excellent resource for future research in the dormancy field.

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

eLife Assessment

The results of this study are important and the approach to dissect the developmental contribution of RIF1 function is convincing. The results that suggest a possibly separate control of replication timing and gene expression are intriguing and represent a strong foundation for future research. The work will be of interest for researchers both in the transcription and the replication field, especially for scientists investigating the interplay between the two processes.

eLife Assessment

This important study explores the function of SIRT2 in inhibiting Japanese encephalitis virus infection and disease progression in rodent models. The findings presented are novel as sirtuins are known for their roles in aging, metabolism, and cell survival, but have not been studied in the context of viral infections until recently. The evidence supporting the claims is solid and reveals a mechanism for SIRT2 in modulating acetylated NF-kB transcription factor levels and additional inflammatory response mediators. The work will be of interest to biologists studying viruses, sirtuins, and inflammation.

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 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 somewhat preliminary and incomplete.

eLife Assessment

This is a useful study that seeks to elucidate the molecular mechanisms underlying spinal circuit assembly. The authors demonstrate that loss of Onecut transcription factors in spinal motor neurons affects the size and spatial distribution of pre-motor interneurons. The main conclusion that Onecut acts through Neurotrophin-3 to regulate interneuron development in a non-cell autonomous manner is partially supported by the data, rendering the study incomplete. The work will be of broad interest to cell and developmental biologists.

eLife Assessment

This valuable study is a rigorous and comprehensive anatomical description of populations of spinal-projecting neurons in the brain of the larval zebrafish. The compelling data reveal a far more complete and robust visualization of these populations than past work. The scholarship is also notable, featuring thoughtful contextualization of the findings with respect to both non-mammalian and mammalian literature.

eLife Assessment

This is an important study with implications for signal transduction, breast cancer, and metastasis research. The study uses cell lines from the innovative HER2BOW model mouse to compare and contrast properties of mouse mammary tumors induced by wt-HER2, dex16-HER2, and p95-HER2. The study involves mechanistic approaches that are convincing for distinguishing signaling from dex16-HER2 and p95-HER2; this will be of interest to the cancer field.

eLife Assessment

This is a valuable study that aims to resolve the mechanistic details of the final steps of bacterial lipoprotein trafficking. The evidence supporting the conclusions is mostly solid but support for other claims is incomplete. This work will be of interest to biochemists and microbiologists studying the bacterial cell envelope and those aiming to develop novel antibacterial molecules.

eLife Assessment

This valuable study carefully assesses the anatomical organization of the adult zebrafish olfactory bulb using a densely reconstructed electron microscopy dataset. The data were generated using a previously acquired state-of-the-art serial block-face scanning electron microscopy dataset, followed by manual classification of cells into distinct anatomical groups. The analysis is a convincing application of careful expert neuroanatomical understanding that reveals key details of the cell class and connectivity in the olfactory bulb, with helpful detailed descriptions of why each cell class was distinguished.

eLife Assessment

This fundamental study delivers a population reference panel for long-read sequencing-based structural variants and demonstrates its utility for disease association analyses in the UK Biobank, expanding genetic discovery beyond conventional SNV-based approaches. The authors provide convincing evidence through extensive benchmarking and systematic analyses that the panel improves structural variant detection and can support fine-mapping of trait associations.

eLife Assessment

This important paper introduces a generalisable tissue-clearing method to study human anatomy and the organisation of complex tissues and organs. The evidence for its broad applicability is compelling, based on results from 15 diverse human tissues, including highly heterogeneous specimens, with successful labelling using five antibodies and five fluorescent dyes. The method has broad potential applications across multiple disciplines.

eLife Assessment

This valuable study introduces an innovative task and framework for examining whether movement vigor and reward-seeking behavior are governed by common or separate processes. The behavioral findings provide solid evidence that these behaviors can be differentially influenced by effort and delay, but support for the proposed model and its mechanistic claims remains incomplete, requiring more rigorous validation and analyses to address potential confounds. The work will be of interest to researchers studying motor control, decision-making, and effort-based behavior.

eLife Assessment

This study presents an important study into the molecular function of AT-HOOK MOTIF NUCLEAR LOCALIZED 15 (AHL15), a member of the AHL protein family, identifying it as a potential regulator of three-dimensional gene-loop organization within transcribed gene bodies. The authors support this claim with strong genome-wide evidence, integrating AHL15 binding profiles with transcriptional and chromatin accessibility changes, as well as demonstrating overlap with genes known to form loops across transcribed regions. The evidence supporting the claims of the authors is convincing. Collectively, these findings will be of broad interest to biologists seeking to understand the regulatory mechanisms underlying gene expression.

eLife Assessment

This study provides important findings on the composition of glutamate receptor (GluR) subunits across diverse Drosophila neuromuscular junctions, spanning larval and adult stages and multiple muscle types. Most previous work has focused on larval body wall muscles, and this study demonstrates that this model does not capture the full diversity of GluR composition across development and tissues. The revised manuscript provides a convincing account of this diversity and will be of broad interest to researchers across neuroscience.

eLife Assessment

Overall, this is an important manuscript that delivers an invaluable community resource. The execution is relatively simple, but the evidence of this resource is solid. The effort invested in generating the knockout lines that for validation experiments is a clear strength of the study, but it doesn't substitute for a careful evaluation of the same reagents in the end-users' specific protocols before making any biological statement.

eLife Assessment

This study used several approaches (computational modeling, neuronal cultures, rodent epilepsy model, and human intracranial recordings) to address a significant question in epilepsy research, with additional relevance to EEG studies more broadly: Are high frequency oscillations (or "fast ripples", defined as >200 Hz by the authors) distinct from randomly occurring clustering of spikes? The results suggest fast ripples can occur by chance and how this may occur. The significance was considered important and the strength of evidence convincing, with minor revisions suggested to temper conclusions related to stochastic vs. oscillatory fast ripples.

eLife Assessment

This landmark study is part of an impressive large-scale effort to assess the consistency of published findings in the field of Drosophila immunity. In this article, the authors report an analysis of claims made in approximately 400 research papers from the Drosophila immunity literature. The authors perform validation experiments to test a subset of the claims that are most inconsistent with current understanding in the field. These experiments do not necessarily aim to reproduce the original experiments, but instead to test the repeatability of the result using updated tools and methods. In some cases, the original claim is validated and in others it is not. The conclusions on the consistency of the claims, as presented in this paper, are based on mostly convincing evidence.

eLife Assessment

This important study presents an impressive large-scale effort to assess the reproducibility of published findings in the field of Drosophila immunity. The authors analyse 400 papers published between 1959 and 2011 and assess how many of the claims in these papers have been tested in subsequent publications. In a companion article they report the results of experiments to test a subset of the claims that, according to the literature, have not been tested. The evidence presented is convincing, and the limitations inherent to evaluating reproducibility primarily on the basis of the published literature - as opposed to repeating experiments - are acknowledged. The authors also explore if various factors related to authors, institutions and journals influence reproducibility in this field: in general, most correlations between these factors and reproducibility are weak, and some are dependent on analysis choices.

eLife Assessment

This useful study shows that neural activity before a conversational response contains information about the duration and timing of the subsequent turn. The evidence that this information originates from speech-production planning is incomplete. Because the analyzed EEG is recorded during processing of the partner's speech, and because that speech causally determines the subsequent response, production planning and comprehension/context are confounded in the current analyses. It would strengthen the production interpretation considerably if the authors could show that the relationship with forthcoming duration survives richer controls for the preceding turn, or ideally after accounting for EEG variance driven by the incoming speech.

eLife Assessment

This important study provides theoretical and experimental evidence that aliphatic-to-threonine substitutions in transmembrane domains improve the translocation properties of mitochondrial proteins from the cytosol to mitochondria. The authors provide convincing evidence that substitutions within hydrophobic transmembrane regions of mitochondrial proteins may have contributed to their evolutionary adaptation following the transfer of their genes from the mitochondria to the nucleus. This study will be of interest to biologists and biochemists working on mitochondrial protein import and mitochondrial evolution.

eLife Assessment

This study investigates the temporal dynamics of neural activity preceding self-initiated movements and makes a valuable contribution to this field. To overcome methodological and analytical limitations in previous work the authors introduce a matched control condition in which no response is required to assess when neural activity is predictive of self-initiated movement (using electro- and magnetoencephalography). Applying solid methods and machine-learning analyses, the authors show that a late-stage neural event is most predictive of upcoming movements (~100 ms before the response), whereas earlier neural activity is less informative. This finding contradicts previous work that suggested that earlier build-up of neural activity (e.g., starting 500 ms before the response) reflects the planning and preparation of movement.

eLife Assessment

This study introduces a valuable simulation-based inference (SBI) framework to identify degenerate compensatory mechanisms that stabilize network activity despite neuronal hyperexcitability, a feature common to many brain disorders. By estimating posterior distributions of network parameters, the authors highlight factors such as threshold potential and interneuron-to-principal cell connectivity as key compensators for increased intrinsic excitability and interneuron loss. The approach is promising and can become a convincing tool for probing network degeneracy.

eLife Assessment

This is a very helpful study that presents an easy to use and reliable alternative to conventional and UV-based tetramers for the identification of antigen-specific CD8 T cells. The authors demonstrate that tetramers for a number of HLA alleles can be subjected to specific temperatures that facilitate peptide exchange whilst maintaining structural integrity, thereby generating detection reagents. They provide convincing evidence for this method, and the approach is likely to provide a useful alternative to generating reagents for examining T cell specificities.

eLife Assessment

This important study reports a novel phenomenon of maternal growth during pregnancy that is independent of growth hormone (GH), adding a new dimension to maternal biology of reproduction. The evidence is convincing and supported by state-of-the-art methodologies conducted in mice and persuasive, interesting and unique observations in humans with hereditary isolated GH deficiency.

eLife Assessment

By integrating RelB proximity labeling with targeted CRISPR screening, the authors identify several potential regulators of HIV latency and provide evidence implicating RelB, KAT7, and p300 in AZD5582-mediated HIV reactivation. While the study is important, the current work is incomplete, as it needs to establish physiological relevance. The findings require validation in primary latency models, and the unusually high basal RelB expression in the experimental system raises concerns about whether the observed effects accurately reflect endogenous mechanisms regulating HIV latency.

eLife Assessment

This manuscript presents valuable experimental results describing the localisation and regulation of casein kinase CK1δ during the cell cycle. During the G2 phase of the cell cycle, the autophosphorylation of the C-terminal tail stabilises and inhibits the kinase which might protect CK1δ in the subsequent G1 phase. The results may be of interest to researchers working on casein kinase function and regulation but due to lack of some controls remain incomplete.

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

eLife Assessment

This study provides an important insight into how the medial and lateral entorhinal cortices interact through distinct excitatory and inhibitory pathways. Using anatomical tracing, optogenetics, and electrophysiology, the authors show that glutamatergic medial entorhinal neurons provide broad excitatory input to lateral entorhinal, while long-range SST+ interneurons deliver selective inhibition to layer I. These findings reveal a novel layer- and cell-type-specific organization of medial to lateral entorhinal connectivity with implications for spatial and episodic memory. The evidence for the paper's overall conclusions is convincing.

eLife Assessment

This important study introduces Hetlearn, a novel learning algorithm that demonstrates that an ensemble of simple sub-learners with varying learning rates can effectively manage inference in complex, unstable environments. While the theoretical framework and its proposed application to parallel memory traces in the insect mushroom body are intriguing, the evidence supporting the core claims is currently incomplete. To fully validate the authors' conclusions, further exploration is needed to rigorously define the boundaries of the model's hyperparameter space, along with a deeper justification and clarification of its biological plausibility.

eLife Assessment

In this useful study, Millard et al. assessed the effects of nicotine on pain sensitivity and peak alpha frequency (PAF). They propose a solid experimental framework to test the modulatory effects of nicotine on PAF and pain sensitivity, but the evidence is incomplete to support the claims that the chosen experimental intervention may actually play a significant mechanistic role in pain sensitivity given the modest effect sizes observed. The work can be incorporated into the literature investigating the relationship between nicotine and pain and could be of broad interest to pain researchers.

eLife Assessment

The identification of a pleiotropic EPAS1 enhancer that influences adipocyte responses to hypoxia and thermogenic stimulation provides a valuable contribution to our understanding of high-altitude adaptation in Tibetans. The data are solid, although additional experiments would strengthen the link between ENH5 activity and the mechanisms underlying high-altitude adaptation.

eLife Assessment

This study provides important insights into the regulation of neuroblast lifespan and proliferation in the Drosophila mushroom body, identifying Krüppel (Kr) as a key transcription factor promoting timely termination of these neuroblasts by regulating Imp/Syp transition and E93 expression. This study proposes that Kr acts antagonistic to Krüppel homolog 1 (Kr-h1), whose overexpression leads to prolonged mushroom body neuroblast proliferation and tumor-like expansion. The findings are impactful for researchers interested in temporal patterning and neural development. The methods and data analysis are solid.

eLife Assessment

This paper provides a valuable observation that imiquimod, a compound often used to induce a psoriasis-like skin inflammation in mice, has a TLR7-independent effect acting through the unfolded protein response and binding to Gelsolin. These solid findings expand our understanding of imiquimod-mediated inflammation and are of interest to the field of skin immunology.

eLife Assessment

This important study addresses a discrepancy between population-level growth laws and single-cell correlations. It shows, for flagellar and synthetic genes in E. coli, that while gene expression of certain genes reduces population-average growth, expression levels positively correlate with growth at the single-cell level. The measurements are convincing, and the proposed mechanism - inheritance of growth factors such as ribosomes during asymmetric division - can explain this observation.

eLife Assessment

This valuable study examines how the rodent prelimbic cortex represents learned and generalized threat over time and identifies distinct stable and dynamic neuronal populations that contribute to these representations. The evidence is convincing, supported by longitudinal calcium imaging, appropriate control groups, and sophisticated analyses showing that the relevant neural signals cannot be explained simply by freezing behavior. The work provides a conceptual framework for understanding how stable threat-related representations supporting memory generalization and discrimination can be maintained despite ongoing changes in neuronal ensemble composition.