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 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.

eLife Assessment

This study presents a valuable human organoid platform for investigating neuron-immune interactions in Alzheimer's disease and modeling the interplay between innate and adaptive immunity in the context of amyloid pathology. The system has the potential to advance the field by enabling the study of human-specific neuroimmune interactions that is difficult to recapitulate in rodent models. The evidence on the microglia-T cell crosstalk are convincing. The study will interest researchers in neuroimmunology and Alzheimer's disease.

eLife Assessment

This study presents an important examination of the role of cis-acting versus trans-acting genetic variation on DNA methylation divergence between humans and chimpanzees, including its consequences for gene expression. By differentiating fused interspecies tetraploid cell lines into multiple cell types, the study provides compelling evidence for the importance of cis-acting changes and solid evidence for the relevance of these changes to adaptive evolution in humans. This work will be of interest to biologists and evolutionary anthropologists studying the evolution and genetics of gene regulation, particularly in primates.

eLife Assessment

This computational study constitutes an extension to prior work on biophysical calcium-based synaptic plasticity rules, investigating how the regulation thresholds for strengthening and weakening connection help solve learning tasks. This important work presents a significantly simpler solution to the studied problem with potentially broad applicability, the evidence to support the core conclusions is solid.

eLife Assessment

This valuable study provides a practical computational framework for inferring latent neural states directly from calcium fluorescence recordings, bypassing the traditional need for a separate spike deconvolution step. The evidence supporting the method is convincing, featuring rigorous validation across multiple latent variable model families (including HMM, GPFA, and LFADS) using both simulated and experimental data. To further strengthen method's generality, it would require further application to a broader range of experimental datasets, such as recordings from different brain regions or using different calcium indicators.

eLife Assessment

This important study identifies underappreciated experimental factors that influence α-synuclein amyloid polymorphism, with practical implications for the reproducibility of in vitro fibril preparations. Extensive cryo-EM analyses provide convincing evidence that protein purity, monomer preparation, and agitation conditions influence polymorph selection, including substantial effects from small amounts of an N-terminally truncated variant. The study provides a substantial resource for researchers studying amyloid assembly and synucleinopathies, although the proposed nucleation mechanisms need stronger kinetic support and reliable protocols for producing specific polymorphs require further development.

eLife Assessment

This useful study reports potential loss-of-function variants, pseudogenes and gene presence-absence variation across multiple chicken genomes, with potential implications for understanding genome evolution and domestication. The evidence for the central claims is unfortunately incomplete, as the inferences of gene loss are not sufficiently robust to account for assembly and annotation artifacts, and, in addition, the analyses can not distinguish between positive selection and relaxed constraint. The overall claim of large-scale gene loss being adaptive and thus being a major driver of chicken evolution and domestication is therefore not sufficiently supported. The area of the study is of interest to colleagues in evolutionary and comparative genomics as well as animal domestication.

eLife Assessment

This study provides a valuable and comprehensive in vivo map of proteins in proximity to three vesicle-tethering complexes. The evidence supporting the overall proximity mapping is convincing. However, some aspects of the functional characterization of selected candidates remain incomplete.

eLife Assessment

This important study investigates how GDNF treatment restores nerve cells in the bowel of a mouse model of Hirschsprung disease, and proposes that this regeneration occurs through diverse resident precursor cells and a non-canonical signaling pathway. The evidence is solid for the ability of the treatment to induce new bowel nerve cells and for a contribution from multiple precursor populations, supported by extensive cell tracing and imaging experiments. This work will be of interest to researchers in developmental biology and peripheral neurobiology.

eLife Assessment

This work demonstrates an objective way to select parameter values for a quadratic integrate-and-fire model so that its bifurcation diagram matches a specific target diagram, generated from the Wang-Buzsaki model. The method is useful for the field and is presented with convincing evidence. The method is currently limited in its ability to be applied to data, but improves our mathematical tools to treat a rarely studied type of bifurcation.

eLife Assessment

This important study investigates how experimentally introducing two facultative bacterial endosymbionts into the Russian wheat aphid, Diuraphis noxia, affects aphid performance, dispersal, and damage to cereal host plants and the authors provide solid evidence for contrasting symbiont-associated phenotypes under controlled conditions: Rickettsiella increases plant damage while reducing wing production and dispersal, whereas Regiella reduces feeding damage and, at some time points, aphid population growth. The stable establishment of these novel symbiont-host associations and complementary experiments spanning individual aphids, whole plants, populations, and mesocosms are notable strengths and the revised manuscript better clarifies the experimental approaches and the context dependence of symbiont effects; however, the underlying mechanisms remain unresolved, horizontal transmission is inferred rather than directly demonstrated, and limited replication and temporal variability constrain some population-level conclusions. Potential applications to pest management therefore require further validation under field conditions. The study will interest researchers working on insect symbiosis, plant-insect interactions, and biologically based pest management.

eLife Assessment

This valuable study provides a systematically curated atlas of non-canonical open reading frames translated across normal human and mouse tissues by uniformly integrating nearly 400 ribosome-profiling datasets with independent mass-spectrometry evidence for ncORF-encoded peptides. The convincing analyses connect ncORF evolutionary age and coding constraint with translation level, tissue distribution, and co-translation with canonical coding sequences, offering a broad comparative view of how non-canonical translation changes over mammalian evolution. Although the functions of most ncORF-encoded peptides remain unknown, the scale of their detection across tissues, together with their proteomic and evolutionary signatures, suggests that a substantial subset may have biological functions.

eLife Assessment

This study presents valuable findings regarding cardiac and autonomic effects of seizures and epilepsy, with relevance to sudden unexpected death in epilepsy (SUDEP). They present solid evidence that genetic deletion of the potassium-chloride co-transporter in hypothalamic corticotropin-releasing hormone (CRH) neurons exacerbates bradycardia and enhances autonomic disturbances in a mouse model of temporal lobe epilepsy. This work will be of interest to neuroscientists working on epilepsy, the HPA axis, and autonomic control.

eLife Assessment

This important study provides new insights into the patterns of organelle inheritance in the protozoan parasite Toxoplasma gondii. The authors introduce an innovative dual-labeling approach to distinguish maternally inherited from de novo synthesized organelles, representing convincing evidence that different organelles follow distinct inheritance fates during parasite replication. Future studies will be needed to determine whether the residual body functions as a central recycling hub, as the current data are also consistent with alternative models.

eLife Assessment

This important study shows that nutrient resorption efficiency in the widespread wetland grass Phragmites australis varies with population origin and remains largely stable under experimentally imposed salt stress, supporting limited short-term plasticity and a role for genetic differentiation. The findings suggest that predictions of wetland nutrient cycling under increasing salinization should account for intraspecific variation and phylogeographic composition, the evidence is compelling, based on a common-garden experiment involving 110 genotypes, paired control and salinity treatments, and convergent metabolomic, ionomic, and whole-plant evidence confirming substantial physiological stress. The revised manuscript clarifies the partial overlap between ecotype and phylogeographic lineage and appropriately qualifies the modest explanatory contribution of latitude, conclusions remain restricted to one species, one growing season, and a single moderate salinity treatment; an ecotype-specific nitrogen resorption response also indicates that plasticity is not entirely absent and the physiological mechanisms and responses to chronic, stronger, or multigenerational salinity exposure remain unresolved. The study will interest researchers working on plant functional ecology, nutrient cycling, and wetland responses to global change.

eLife Assessment

Dohi et al. asked what role the dorsal hippocampus and medial prefrontal cortex play during different temporal epochs of a memory-guided navigation task, a long-standing question for neuroscientists studying hippocampal-prefrontal contributions to working memory. This useful study used a delayed, cue-guided T-maze task in mice and reported impaired choice accuracy when silencing occurred early in the central-arm run but not during the delay. However, the evidence for the study's claim is incomplete in its current form: the silencing windows are not duration-matched across epochs, key negative findings rest on three to four mice without power analysis or reported effect sizes, no non-mnemonic control task distinguishes disrupted memory-guided behavior from a general action-selection deficit, and no neural recordings accompany the causal manipulations to verify the manipulations' assumed mechanistic effects. The reported perseveration also reflects an increased directional bias rather than repetition of the previous choice, and the language should be revised accordingly.

eLife Assessment

Using sci-L3-Strand-seq, this study shows genome-wide, single-cell evidence that DSBs triggered by CRSIPR/Cas9 are frequently resolved through sister chromatid exchange (SCE), which is undetectable with conventional whole genome sequencing approaches. This important work provides helpful metrics quantifying the occurrence of SCE events at targeted and repetitive genomic loci that are of particular interest to those working in gene editing, DNA repair, genome instability, or repetitive genomic loci. The analysis of reciprocal daughter-cell pairs provides compelling evidence for SCE events, providing evidence consistent with CDK1-TTF2-TRAIP mediated cell-cycle regulated CMG helicase disassembly and fork cleavage at unreplicated regions.

eLife Assessment

This study presents a valuable tool for comparing immune receptor data across multiple samples while properly accounting for statistical uncertainty and receptor similarity. The evidence supporting the tool is solid overall. However, some key concerns regarding potential sequencing artifacts in one of the validation datasets and an unclear strategy for false discovery rate control in the proposed framework remain to be addressed.

eLife Assessment

This meta-analysis provides a valuable contribution by integrating findings from dozens of macaque electrophysiology studies to reconcile discrepancies in choice probability and identify factors that robustly influence choice signals in the visual cortex. Such systematic synthesis across studies is rare in this field, and the analysis provides solid evidence for several conclusions, including the cross-study consistency of the relationship between choice probability and sensitivity and the distinctiveness of V1.

eLife Assessment

This important study provides convincing evidence that somatosensory relay nuclei remain engaged during attempted hand movements following chronic cervical spinal cord injury, including in individuals with severe motor impairment. The combination of functional and quantitative MRI with physiological controls supports the main findings and may have implications that are of importance in understanding sensorimotor processing after spinal cord injury. However, the interpretation of this activity as specifically reflecting top-down, and particularly corticocuneate, signaling may be overstated. The origin and anatomical route of the observed activity appears to remain less firmly established.

eLife Assessment

This valuable study examines the relationship between simultaneous LC single-unit recordings and pupillometry, both within and across baseline and evoked epochs, finding that cross-epoch relationships are unreliable. The evidence is solid and suggests that care should be taken when interpreting pupil responses as reflecting LC activity. This manuscript will be interesting to basic and clinical researchers working in cognitive and decision neuroscience as well as computational psychiatry.

eLife Assessment

This study addresses a key question concerning whether neurofeedback can enhance the neural representation of a selected speaker during competing continuous speech and whether such enhancement translates into behavioral benefits. The solid findings provide important insights into the online modulation of auditory attention and the extent to which selective listening can be voluntarily controlled. Although the observed effects were relatively small and did not consistently persist beyond the feedback period, the study advances understanding in an under-explored area and provides a helpful foundation for future research on sustained learning and behavioral transfer.

eLife Assessment

This study presents a fundamental molecular resource, offering subtype-specific insight into the composition of ribosome-associated protein complexes in the developing cerebral cortex. The evidence is compelling in terms of data quality and is strongly supported by the results, given the rigorous technical execution. While primarily descriptive in nature, this resource will be of great use to the field.

eLife Assessment

This important study addresses how listeners learn the statistical properties of acoustic spaces, combining well-designed psychophysics in virtual rooms with non-invasive brain stimulation. The evidence is solid: the behavioral results are strong and show that speech understanding is best in rooms with everyday levels of reverberation, and the stimulation data are consistent with a contribution of dorsolateral prefrontal cortex, though the effects are modest and the spatial precision of TMS is inherently limited. The work will be of interest to researchers in auditory neuroscience and psychoacoustics, helping to understand how the brain copes with reverberant environments.

eLife Assessment

This important study reveals the roles of two lytic transglycosylases in the progression of spore formation in the research model species Myxococcus xanthus. Solid evidence is provided for the roles of these two enzymes in spore formation and for interplay between their functions and peptidoglycan synthetic systems. These findings may have broader implications for studies of peptidoglycan metabolism across a range of species.

eLife Assessment

This valuable study provides convincing evidence for deficits in aversive taste learning and taste coding in a mouse model of autism spectrum disorders. Specifically, the authors found that Shank3 knockout mice exhibit behavioral deficits in learning and extinction of conditioned taste aversion, and calcium imaging of the gustatory cortex identified impaired neuronal responses to taste stimuli. This paper will likely be of interest to researchers studying how learning and sensory processes are affected by genetic causes of autism spectrum disorders.

eLife Assessment

This important study uses diffusion magnetic resonance imaging to non-invasively map the white matter fibres connecting the zona incerta and cortex in humans. The authors present compelling evidence to indicate that these connections are organized along a rostro-caudal axis. The findings will be of interest to researchers interested in neuroanatomy and cortico-subcortical connectivity.

eLife Assessment

This work presents a software and hardware suite for targeted photostimulation that can be used in vivo. The package is a well-designed and documented hardware/software suite with a comprehensive build guide. This tool will likely promote important neuroscience advances through targeted real-time perturbation of the cerebral cortex. Overall, this manuscript makes a compelling case on how to design and make available power tools for the research community.

eLife Assessment

In this study, Yuan and colleagues carry out transcriptomic and epigenomic experiments to study open chromatin regions and transcripts that change upon larval settlement in the sponge Amphimedon. The authors present compelling evidence to show that sponge larvae prepare for receiving an environmental cue (sunset) by extensively modifying their chromatin accessibility. The study represents a fundamental advance in understanding the fine genetic control of larval settlement and has significance beyond the immediate field of sponge larval biology.

eLife assessment

This study presents a reaction-coupled molecular simulation framework to investigate how enzymatic post-translational modifications regulate biomolecular condensates and where reactions preferentially occur within them. These findings are important, in particular, to the emergence of spatially heterogeneous reaction fluxes and enhanced activity at condensate interfaces. The work is timely and has implications beyond the immediate subfield, especially for understanding condensates as biochemical reaction centers. The strength of evidence is solid overall: the computational framework is well motivated and broadly supports the main conclusions, although some aspects of the model implementation, parameter choices, and controls would benefit from further clarification and validation.

eLife Assessment

This study addresses a recent discovery by others that electroconvulsive therapy (ECT) generates seizure activity and spreading depolarization (SD), reflected in large increases in calcium, which can be observed through imaging fluctuations in neuronal calcium. Revisions addressed some concerns of reviewers but not the main issues. Therefore, the consensus was that the work is useful but the evidence showing that SD, rather than seizures, confers the neuroplastic and other therapeutic effects of ECT is incomplete.

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. However, the evidence is incomplete due to methodological asymmetries in the task design that appear to affect the results in ways that are not fully analyzed and discussed. The work will be of interest to researchers studying the evolution of cognitive control and cross-species neuroimaging.

eLife Assessment

This valuable descriptive study describes the expression of a developmentally relevant transcription factor in the adult Tribolium brain. The evidence supporting the claims is convincing and based on a very detailed and rigorous analysis of light microscopy data, which, however, lacks single-cell resolution. This neuroanatomical study is of interest to the field of insect neural development and neuroscience.

eLife Assessment

This valuable study uses technically challenging long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The study provides solid evidence that ORNs have a circadian pattern of spontaneous firing that is Orco-dependent although Orco transcript abundance does not itself show circadian rhythmicity, and that cAMP can modulate Orco-dependent activity. Together with the computational work, the study proposes the provocative hypothesis that an Orco-centered post-translational feedback loop generates the circadian rhythm of spontaneous firing. Nevertheless, this mechanistic interpretation will require direct testing in future work.

eLife Assessment

This important study combines a five-year field experiment with a meta-analysis to quantify effects of grazing on ecosystem CO₂ fluxes as modified by wetness. The evidence supporting the conclusions is convincing, but several aspects of the methods and discussion would benefit from clarification to improve reproducibility and interpretability.

eLife Assessment

This important study provides convincing evidence supporting the existence of transposable element (TE)-gene chimeric transcripts in the Drosophila brain and helps reconcile previously conflicting findings. The authors demonstrate that differences in computational approaches, experimental design, and Drosophila lines can substantially influence the detection of these transcripts. The work highlights the importance of standardized approaches for studying TE-derived transcripts, although their broader biological significance remains to be established.

eLife Assessment

This valuable study demonstrates that a multi-step differentiation program in bacteria combining a bistable switch with two quorum-sensing systems is capable of generating autonomous and self-organized spatial patterns. The evidence for the core engineering system using fluorescent reporters support patterning across several conditions is convincing and has significant implications on the process of cell differentiation.

eLife Assessment

This important study employs a closed-loop, theta-phase-specific optogenetic manipulation of medial septal parvalbumin-expressing neurons in rats and reports that disrupting theta-timescale coordination impairs performance of challenging aspects of spatial behaviors, while sparing hippocampal replay and spatial coding in hippocampal place cells. Technically rigorous experiments were performed, and solid evidence is provided to support the claims. The findings are expected to advance theoretical understanding of learning and memory operations and to provide practical implications for the application of similar optogenetic approaches.

eLife Assessment

This important study uses biochemical and single-molecule approaches to characterize how yeast Cdc13 assembles on single-stranded telomeric DNA and contributes to telomere protection. The evidence supporting the proposed model for Cdc13 assembly and its role at telomeres is solid. The findings provide insight into how Cdc13 contributes to the maintenance and protection of chromosome ends. This work will be of interest to researchers in telomere biology, DNA replication, biochemistry, and single-molecule biophysics.

eLife Assessment

This valuable proof-of-concept study tests and validates a novel magnetic resonance-based method - proton-observed proton-edited MRS - for tracking glucose metabolism in the brain beyond simple substrate uptake, without the need for specialist hardware typically restricted to research settings. The approach offers a promising way to assess excitation/inhibition balance by detecting labelled glucose metabolites. The pre-clinical data in mouse models provide convincing support for the authors' hypothesis. The evidence in the human brain is incomplete: the results would require further optimisation of the experimental set-up and validation in a larger group of volunteers. This work will be of broad interest to researchers studying psychiatric, neurodevelopmental, and related brain disorders.

eLife Assessment

There is a significant need for improved understanding of the neural circuit mechanisms for learning and memory dysfunction in Alzheimers disease. In this valuable study, Zheng and colleagues compare neural coding between wild-type and App knock-in rats experiencing different contexts. Solid evidence of a difference emerges when "spatial" and "temporal" neural coding dynamics are considered separately. However, the lack of a link between neural coding and behaviorally measured learning, and minor issues with the analyses, are limiting factors of the evidence and the significance of the work.

eLife Assessment

This study provides valuable findings on computational measures of learning in human subjects with current depression, individuals remitted from depression, individuals at familial risk, and healthy controls using reinforcement learning and risky decision-making tasks. The evidence is solid but could benefit from clear interpretation of model parameters and psychiatric symptoms. The paper will be of interest to scientists interested in learning, reward processing, value-based decision-making, and psychopathology.

eLife Assessment

This important study provides evidence that Clock and fat body proteasome subunits contribute to dietary restriction-mediated lifespan extension in Drosophila. The evidence supporting these conclusions is solid, yet whether dietary restriction-induced daily rhythmicity of proteasomal genes is CLK-dependent remains incompletely demonstrated, and alternative explanations involving feeding differences and non-circadian functions of CLK cannot be, with the current dataset, excluded. The work will definitely be of interest to researchers studying biological rhythms, nutrition, and aging.

eLife Assessment

This valuable study provides a detailed three-dimensional characterization of primary cilia organization in the postnatal mouse growth plate, revealing reproducible spatial patterns in ciliation, ciliary length, and orientation. The evidence supporting these descriptive findings is solid, based on high-quality quantitative imaging and complementary genetic, mechanical, and transcriptomic approaches. However, evidence for the broader mechanistic conclusions is incomplete, particularly regarding whether ciliary orientation is uncoupled from basal-body and cell orientation and whether its stability under altered mechanical loading reflects a cell-intrinsic program. The study provides a helpful foundation for understanding primary cilia organization and mechanobiology in the growing skeleton, while the mechanisms underlying these observations remain to be established.

eLife Assessment

This Review Article addresses a significant and timely topic that concerns the role of cryo-EM in transforming RNA structural biology from static, individual conformations toward the reconstruction of dynamic conformational ensembles and energy landscapes. The authors describe eight case studies spanning different RNA classes and argue that conformational heterogeneity is a source of mechanistic information, rather than a limitation.