eLife Assessment

This study of BDNF signaling in heterogeneous spinal cord cultures provides a fundamental conceptual advance by demonstrating that cell identity and maturation state, rather than receptor stoichiometry alone, ultimately determine how a trophic message is interpreted, in a framework the authors call "prepared competence." The evidence is compelling, with the discrete subpopulation behavior, the maturation-dependent acquisition of signaling competence, and the dissociation between receptor abundance and signaling output emerging clearly from the high-dimensional dataset. This study will be of interest to neurobiologists as well as cell biologists who study the molecular basis of cell signaling.

eLife Assessment

This Review Article provides a scholarly, clear and well-structured review of intracranial research into the neural correlates of consciousness (NCCs). To our knowledge this is the first such review and is therefore likely to become a must-read for anyone working in the field of consciousness research. The authors discuss the difficulties that researchers must face when studying NCCs and how insights may emerge via intracranial recordings in humans. This no doubt reflects an in-depth, timely, and insightful contribution to the literature.

eLife Assessment

This useful study examines excitation/inhibition (E/I) balance in the CA3-CA1 circuit of the hippocampus. Experimental and computational modeling results are presented. The computational modeling results were viewed as a novel advance supported by solid evidence, but incomplete evidence was provided to support the paper's main experimental claims due to deficiencies in the experimental methodology and concerns about the neurobiological relevance of the experimental observations.

eLife Assessment

This study makes a valuable contribution to understanding how negative affect shapes food-choice decision making in bulimia nervosa by using a mechanistic drift diffusion model to quantify the weighting and temporal integration of tastiness and healthiness attributes. The approach is solid and has clear potential to advance understanding of the decision processes underlying pathological food choices. The evidence is strengthened by the randomised crossover design and appropriate statistical analyses. The results are consistent across different analytic approaches, increasing confidence in the robustness of the findings.

eLife Assessment

This important study investigates frequency-dependent effects of transcutaneous tibial nerve stimulation (TTNS) on bladder function in healthy humans and, through a computational model, shows that low-frequency stimulation accelerates, and high-frequency delays, the urge to void. The integration of experimental and modeling approaches provides a solid proof-of concept foundation for clinical trials targeting urinary retention. However, concerns were raised about over-interpretation of modest effects and the limited physiological validity of the computational model, and the need for replication in clinical populations. Some conclusions, particularly in the abstract, could be further tempered to better align with the strength of the available evidence.

eLife Assessment

This study reports important findings by showing that two classes of kinase inhibitors, which stabilise the LRRK2 enzyme in either an active (Type I) or inactive state (Type II), have distinct effects on the formation of LRRK2 filaments and their association with cellular structures. Using correlative light microscopy, cryo-electron tomography and sub-tomogram averaging, the authors provide convincing evidence that a Type I inhibitor leads to the extensive decoration of microtubules with LRRK2 in a closed-kinase conformation, and that such decoration is not seen for a type-II inhibitor. The conclusions are consistent with previous work, although the physiological relevance of the work remains somewhat limited due to reliance on overexpression and the use of a rare mutation in a single cell type.

eLife Assessment

This important study identifies inhibitory cerebellar nuclei neurons as drivers of dystonic crisis and shows that their modulation can both induce and alleviate severe motor symptoms, proposing a cerebello-thalamic circuit mechanism with clear therapeutic relevance. The evidence is convincing, supported by rigorous bidirectional optogenetic manipulations, iCNN-to-CL thalamic monosynaptic tracing, and deep brain stimulation experiments, although the specificity of the genetic strategy remains to be fully resolved. The study will be of broad interest to neuroscientists and clinicians working on movement disorders and circuit-based therapies.

eLife Assessment

This important study provides new insights into the neuronal dynamics of the locus coeruleus in relation to hippocampal sharp-wave ripples. Using high-temporal-resolution, multi-site electrophysiological recordings in rats, the authors present convincing evidence that ripples and locus coeruleus activity are inversely correlated to levels of arousal and noradrenaline tone is modulated by hippocampo-cortical coupling. Overall, the work will be of interest to neuroscientists studying large-scale brain coordination and memory processes.

eLife Assessment

This valuable study shows that macaque monkeys preferentially fixate regions in natural scenes that are classified as "meaningful" by a computational model - an earlier model that was developed to identify locations that are semantically informative to humans - suggesting that overt attention to structured visual content is shared across primates. However, support is incomplete for the stronger claim that macaques are guided by semantic meaning, which is confounded by lower-level visual features that co-vary with it and by methodological limitations that complicate interpretation. If the semantic interpretation were more reliably established, the significance of the findings would increase, as they would connect the human cognitive process of scene understanding to neural circuit mechanisms accessible in non-human primates.

eLife Assessment

This valuable study rigorously examines how motor learning is influenced by the feedback response to a previous movement error. Using a series of well-conducted experiments, the authors provide solid evidence that the learning response following a cursor jump does not depend on the timing of the perturbation and is influenced by the tonic component of the feedback responses. Further work is needed to determine whether this generalizes to other perturbation paradigms and to more fully understand the relationship between learning and the tonic and phasic components of the feedback response.

eLife Assessment

This valuable study analyses correlations between traits of Chinese frog species and their Red List status and finds differences between adults and larvae. Of broad relevance, this solid study makes the statement to consider different life-cycle stages when assessing species extinction risks, although many conclusions are based on limited data and thus offer hypotheses rather than direct conservation advice.

eLife Assessment

This study leverages publicly available datasets to confirm, validate and extend the knowledge of the transcriptional profile of beta cells that resist destruction in Type 1 diabetes. The significance of the findings is considered valuable as they could be used for engineering stem cell-derived islets and for identifying therapeutic targets to preserve beta cell survival. The strength of the evidence is solid, in that the findings are supported by a sophisticated bioinformatic analysis pipeline and are largely consistent with and extend the existing literature.

eLife Assessment

This study provides an important assessment of how body size influences the occurrence of macro-organisms in urban areas across the globe. Size in most plants, but only some animal families, was positively associated with urban affinity. The data set is impressive and the strength of evidence solid.

eLife Assessment

This important study investigates how the brain categorizes written words from different writing systems (e.g., alphabetic vs. non-alphabetic). The evidence supporting the authors' claims is solid and sheds light on the neural basis of language's social‑categorization function.

eLife Assessment

This valuable study compares auditory cortex responses to sounds and cochlear implant stimulation measured with surface electrode grids in rats. Beyond the reduced frequency resolution of cochlear implants observed previously, this study suggests key discrepancies between neuronal representations of cochlear stimulations and natural sounds. The evidence for this result is solid but could be strengthened with a clarification of the methodology and an adaptation of the claim to the actual precision of the measurements. This study is of interest to researchers in the auditory neuroscience field and clinicians implementing treatments with cochlear implants.

eLife Assessment

This valuable study explores the role of Pink1 in regulating mitochondria-organelle contacts and glial function, advancing our understanding of the mechanisms underlying neurodegenerative diseases. The findings highlight key genes and cellular processes that are critical in maintaining neuronal health, with implications for glial biology and Parkinson's disease research. The methodology and data are solid. This work will be of significant interest to researchers in neuroscience, cell biology, and neurodegenerative diseases.

eLife Assessment

This important study reveals intriguing connections between chromosome breakage and DNA elimination during programmed genome rearrangement in the ciliate Tetrahymena thermophila. By developing a novel FISH approach that distinguishes germline and somatic telomeres, the authors provide compelling evidence that chromosome breakage removes germline telomeres along with hundreds of kilobases of germline-limited sequences. By disrupting a single chromosome breakage site, they further showed that DNA elimination was globally affected, which opens up a new direction for mechanistic studies. Thus, this work reveals additional similarity between the programmed DNA elimination in ciliates and nematodes that underlies the transition from germline to somatic telomeres.

eLife Assessment

This valuable study presents convincing data demonstrating that alpha herpesvirus triggers nuclear export of HDACs, which are then degraded in an MDM2-dependent manner. This virus-driven process leads to histone hyperacetylation and activation of the DNA damage response, which promotes viral replication.

eLife Assessment

This important study establishes an environmental sampling workflow for the discovery of bacteriophages capable of infecting antibiotic-resistant pathogens. The authors convincingly demonstrate the effectiveness of the approach, even with the limited sampling scheme and the current challenges in viral taxonomy. This study will interest researchers working on bacterial infections, environmental microbiology, and phage-based alternatives for addressing antimicrobial resistance.

eLife Assessment

This important study uses a feedback-driven recurrent neural network framework to explore the dynamics underlying learning of BCI decoder perturbations. With convincing evidence, the authors demonstrate that behavioral learning trajectories that match those of primates learning within-manifold and outside-manifold perturbations are likely tied to the dynamical controllability of the network and input-driven learning. This work is likely to motivate a new generation of BCI and learning experiments combining large-scale neural recordings with latent dynamical systems analyses.

eLife Assessment

This important study employed a multi-stage behavioural paradigm of increasing cognitive complexity to investigate the role of inhibitory interneurons in the medial prefrontal cortex (mPFC) in avoidance behaviour in mice. The authors used imaging and optogenetic techniques combined with this behavioural task to show that mPFC interneurons are necessary for encoding but not executing avoidance under threat. The evidence supporting these claims is compelling, and findings will be of interest to researchers in behavioural and systems neurosciences.

eLife Assessment

This important study demonstrates that paternal diet influences not only testicular morphology but also placental and fetal development, supporting a role for paternal contributions to offspring health. The study also considers potential links between the microbiome and male reproductive health. By combining transcriptomic and histological analyses across multiple tissues, the evidence supporting the central conclusions of the study is convincing.

eLife Assessment

This study presents a valuable finding on the direct cytotoxic effects of DuoHexaBody-CD37 in diffuse large B-cell lymphoma through antibody clustering, independent of complement. The central findings are supported by solid evidence, although some mechanistic details, including the specific Fc receptor requirements for crosslinking-mediated cytotoxicity, remain unresolved. As the findings are based primarily on in vitro models, further validation would be required to support broader translational conclusions. The previous review comments were addressed by the authors and have improved the work.

eLife Assessment

This valuable study re-evaluates a published simulation model on the role of heterozygote advantage in shaping MHC diversity. By modifying key modeling assumptions, the author argues that the original conclusions depend on a narrow and potentially unrealistic parameter range. While the work is in principle solid, the robustness of this claim is viewed differently by the reviewers. The manuscript further proposes an alternative modeling framework in which expansion of the MHC gene family allows homozygotes to outperform heterozygotes, thereby challenging the idea that heterozygote advantage alone can account for high allelic diversity at MHC loci. The topic is highly relevant for eco-immunology and evolutionary genetics, although it is not clear yet how well the model generalizes to other genes with different patterns of haplotype diversity in the population and different degrees of heterozygous advantage.

eLife Assessment

This study reports important findings by showing that two classes of kinase inhibitors, which stabilise the LRRK2 enzyme in either an active (Type I) or inactive state (Type II), have distinct effects on the formation of LRRK2 filaments and their association with cellular structures. Using correlative light microscopy, cryo-electron tomography and sub-tomogram averaging, the authors provide convincing evidence that a Type I inhibitor leads to the extensive decoration of microtubules with LRRK2 in a closed-kinase conformation, and that such decoration is not seen for a type-II inhibitor. The conclusions are consistent with previous work, although the physiological relevance of the work remains somewhat limited due to reliance on overexpression and the use of a rare mutation in a single cell type.

eLife Assessment

This solid paper reports on the use of artificial intelligence to assess bone marrow adipose tissue in the skull. The method employing MRI is novel and that approach allows for the identification of genetic loci that regulate this trait as well as others using data from the UK biobank. Overall this is an important contribution although the authors should consider several points: 1-validation of the T1-weighted MRI signal intensity; 2-further discussion of the sex differences; and 3-cross-trait linkage disequilibrium score regression (LDSC) for osteoporosis, Parkinson's disease, and cognitive function.

eLife Assessment

This study provides conditionally useful evidence that amino acid starvation and other stresses induce RNF25-dependent ubiquitination of RPS27A/eS31, extending this pathway beyond A-site-trapping conditions and implicating GCN1. However, incomplete and largely indirect evidence was provided to support key mechanistic claims-notably competition between RNF25 and GCN2 for GCN1 and a role in resolving ribosome collisions. Additional direct and orthogonal evidence is required to substantiate these conclusions.

eLife Assessment

Using a genetic screen in C. elegans, Benbow et al., identify mutations in alpha-tubulin genes that suppress Tau-induced neurodegenerative phenotypes. The results provide solid support the authors' claim that the tubulin mutants protect against neurodegeneration without altering tau aggregation and hyperphosphorylation. While precise mechanisms of protection by tubulin mutants remain to be established, the results are valuable for understanding the underlying cellular mechanisms of Tauopathies and for the development of therapeutic interventions.

eLife Assessment

This potentially valuable study describes the development of protein binders targeting DELE1, a protein involved in activating the integrated stress response when mitochondria are perturbed (the mitoISR pathway. The strategy appears to be successful, as several designed proteins were shown to bind DELE1, disrupt DELE1 oligomerization, and attenuate ISR activation. However, the demonstration of the utility of these inhibitory binders is incomplete, particularly given the limited biological outcomes examined in the current study, thus limiting the significance of the paper in its current form.

eLife Assessment

This study presents a valuable finding that coordinated changes in epigenetic modifications and three-dimensional chromatin architecture may drive primary trastuzumab resistance in HER2+ breast cancer. Moreover, this manuscript identifies SGK1 as a potential therapeutic target. The evidence supporting the claims of the authors is solid, although the inclusion of a more direct validation of the key findings using tumor samples from patients with clinical trastuzumab resistance would have strengthened the study. The work will be of interest to scientists or clinicians working in the field of BCs.

eLife Assessment

This manuscript provides a timely and important statistical re-evaluation of a paper by Epp et al., on the discordance of BOLD and CMRO2 measures. The authors present a convincing case based on rigorous re-analysis of the data that these previous results arise predominantly from uncertainty in measurement, rather than physiological features. These findings have implications that are of importance to all studies of brain function using BOLD FMRI.

eLife Assessment

This useful study employs longitudinal widefield cortical imaging to investigate how bilateral vision loss reshapes spontaneous activity across the mouse cortex over time, revealing a state-dependent alteration in the locomotion-related modulation of visual cortical activity. The work provides solid support for its main findings and offers a thorough characterization of the large-scale reorganization of cortical dynamics following adult vision loss. However, the mechanistic interpretation remains limited, as the conclusions are based on a single abrupt and irreversible manipulation without sham controls and on a recording approach that cannot resolve the cell-type-specific mechanisms invoked in the discussion.

eLife Assessment

This is a valuable paper that compares various deep learning models, trained with different objective functions, on their ability to predict fMRI data collected during naturalistic video gameplay. The data and analysis provide solid within-distribution evidence that models trained with PPO and imitation learning outperform untrained models and standard convolutional networks. However, the evidence for brittleness in out-of-distribution encoding remains incomplete, as the claim that this stems from the networks' training rather than from alternative causes-like overfitting of ridge regression parameters-is not yet fully supported.

eLife Assessment

This study adds important data on the transcriptional identity of the motor neurons innervating eye muscles in larval zebrafish, and shows how disruption to a specific gene, sim1a, impairs the movements of the eye. The evidence supporting the claims is convincing, with bulk and single-cell RNA sequencing as well as functional testing of the vestibulo-ocular reflex. This work will be of interest to developmental biologists and eye movement specialists.

eLife Assessment

This paper presents a valuable theoretical model of cell breakout from spheroids, a situation relevant to tissue invasion and metastasis; a helpful feature of the model is to include the extracellular matrix as a network of springs. The paper explains the interesting observation that fluid-like spheroids made of soft cells appear experimentally more able to remodel the extracellular matrix (ECM) while they generically display smaller mechanical stress, by invoking feedback loops between shape, strain, stress, and adhesion. While the theoretical evidence is solid, the model suffers from topological limitations inherent to the vertex model and leaves open questions regarding the means by which cells achieve cell-level stress amplification. The connection between the model's assumptions and known molecular mechanisms could be developed further.

eLife Assessment

The authors combine experiments and mathematical modeling to determine how the infectivity of human cytomegalovirus scales with the viral concentration in the inoculum, i.e., considering the multiplicity of infection (MOI). They propose and test different model assumptions to explain a mechanism termed "apparent cooperativity" of virions based on an observed super-linear increase of the number of infected cells with increasing inocula. The authors present a solid study showing valuable findings for virologists and quantitative scientists working on the analysis and interpretation of viral infection dynamics for which quantitative knowledge of MOI is needed.

eLife Assessment

This is a valuable study of changes in host genome histone methylation and transcription changes associated with Chlamydia infection. The data presented are solid but further analysis would strengthen the authors overall conclusions.

eLife Assessment

This valuable study advances our understanding of confidence in reinforcement learning by considering value confidence and decision confidence within a common Bayesian computational framework. The evidence is solid, supported by converging analyses across multiple datasets, though the direct interaction between the two forms of confidence and the model identifiability requires further clarification. The work will be of primary interest to researchers in reinforcement learning, decision-making, and metacognition.

eLife Assessment

This important study identifies a non-canonical essential role for acyl carrier protein in maintaining apicoplast metabolism and blood-stage survival in Plasmodium falciparum. The main conclusions are largely supported by strong genetic and biochemical evidence, although some claims regarding the dispensability of fatty acid synthesis pathways remain incomplete. The work provides novel mechanistic insight into ACP-mediated stabilization of pyruvate kinase II and will be of broad interest to the malaria and apicoplast biology communities.

eLife Assessment

This important work uses a sophisticated combination of neuromodulator imaging, optogenetics, and two-photon calcium imaging to examine how locus coeruleus-mediated norepinephrine signaling influences distinct hippocampal cell types. The evidence is solid and provides novel insights into cell type-specific responses to norepinephrine release. However, the conclusions would be strengthened by a more thorough analysis of the differences between locomotion-associated activity and optogenetic stimulation of the locus coeruleus.

eLife Assessment

This important technical development for neural circuit tracing in larval zebrafish consists in an enhanced rabies virus for improved retrograde transneuronal tracing, supporting a new method for combined structural and functional brain mapping which is demonstrated with compelling evidence. The work will interest zebrafish neurobiologists for the identification of neuronal connectivity patterns while simultaneously monitoring circuit activity.

eLife Assessment

In this valuable study, de Vries and colleagues aim to determine how the perception of biological motion is organized at the neural level, specifically testing whether this process rests on hierarchical predictive processing by extending a methodological framework that the authors previously published. The evidence is solid for the empirical claim that neural representations of body motion systematically lead the stimulus in time, with simulations validating the regression approach and consistent effects on both peak magnitude and peak latency. Support for the stronger theoretical interpretation that these signatures specifically reflect active hierarchical predictive inference requires further substantiation, since the design and analysis do not distinguish such inference from cached associative retrieval or from nonlinear temporal integration of slowly varying features.

eLife Assessment

This study presents a fundamental methodological advance that enables measurements of single-channel gating behavior of CRAC channels whose unitary currents are too small to be resolved electrically. By combining a channel-tethered calcium-sensitive dye (JF646-BAPTA) with voltage-clamp TIRF imaging, the authors discovered new kinetic behaviors of CRAC channels and further identified a dye-blinking artifact with implications that are of importance for optical single-channel studies. Although the work is convincing and the findings have biological relevance, some quantitative aspects of the study can be strengthened by additional analysis.

eLife Assessment

This study presents a valuable finding that perception of a material's properties and hardness during brief touches can be altered using only vibrotactile feedback. The user studies show that vibration energy can influence judgements of material hardness, but the evidence is incomplete to support the broader claim made by the authors that spectral energy is the dominant feature governing hardness perception.

eLife Assessment

This important study developed a novel theory to account for various aspects of dopamine signals, particularly dopamine ramps. The authors propose that dopamine reward prediction error (RPE) signals are generated by a dual-process learning system in which values inferred by a model-based system enter the RPE asymmetrically into the update target but not the prediction. The results are well-presented and convincing, and make a contribution that is of importance to the field. This work will be of interest to those studying dopamine specifically or brain learning computations and systems more broadly.

eLife Assessment

This important study advances methods for improved analyses of wide-field optical imaging of mice expressing the genetically encoded calcium indicator GCaMP6f in different neocortical layers through registering to layer-specific cortical atlases and deconvolution to account for depth-dependent light scattering. However, the key underlying assumption of the work, that widefield signals originate in somata, and not in their superficial axonal and dendritic compartments, remains untested. Similarly, other signal sources like intrinsic optical signals and hemodynamic occlusion are incompletely considered. This study is likely to be of interest to neuroscientists carrying out wide-field optical imaging of the mouse neocortex.

eLife Assessment

This study characterizes the heterogeneity and developmental origins of macrophages in the thymus and offers tantalizing evidence of their potential involvement in the first step of T cell selection. The macrophage characterisation is interesting, although the evidence for the specific involvement of macrophages in beta-selection is incomplete, as alternative explanations have not been ruled out. These results provide an important advance that further our understanding of thymus biology, especially in view of the contribution of heterogenous thymic macrophage subpopulations.

eLife Assessment

On the basis of convincing computational, biophysical, and cell-based evidence, this study reports the important finding that the dynamin inhibitor Dyngo-4a broadly affects lipid packing and plasma membrane dynamics, independently of its action on dynamin. The evidence, obtained by a wide range of methods including a newly developed assay visualizing internalized caveolae, provides solid support for the authors' main claim on the role of lipid packing in caveolae internalization. This work will be of significant interest to cell biologists, biophysicists, and chemists interested in membrane remodeling and drug-membrane interactions.

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

eLife Assessment

This study presents analyses of single neuron activity in the subthalamic nucleus (STN) of monkeys performing a decision-making task that manipulates both perceptual evidence and reward. The study shows convincing evidence of distinct subpopulations of neurons in STN that differ in their representations of key quantities related to decision formation. These findings reveal important functional heterogeneity within the STN that helps provide new insights into its contributions to decision processing.

eLife Assessment

This study presents a valuable RNA velocity method which predicts the transcription rate linearly based on the expression of RNA levels of transcription factors with addition of comprehensive analyses. The evidence supporting the claims of the authors is solid, although inclusion of a full simulation would have strengthened the study. The work will be of interest to scientists working in the field of RNA biology and precision medicine.

eLife Assessment

The authors present a solid study in the unique conditions of weightlessness providing evidence that movements carried out in 0g are underactuated. They further provide a thorough discussion based on computational modelling to address the question as to whether the CNS underestimates mass when programming movements in weightlessness. In all cases, the persistence of the observed effects in weightlessness has important implications for theories of motor adaptation.

eLife Assessment

This study combines mathematical models and experimental data to analyse the emergence of heterogeneity within clonal NK cell responses during antigen-specific cell expansion. It comprises different experimental data and extensively explores various mathematical models, to study NK cell turnover during acute immune responses and homeostatic turnover within murine cytomegalovirus infection (MCMV). This solid study presents valuable findings and provides relevant insights on heterogeneous NK cell development.

eLife Assessment

By investigating spine nanostructure and dynamics across multiple genetic mouse models for neurodevelopmental disorders, this important study has the potential to uncover convergent or divergent synaptic phenotypes that may be specifically associated with autism versus schizophrenia risk. The imaging and overall breadth of the methods are convincing. The purely in vitro nature of the study slightly limits the generalisability of the findings.

eLife Assessment

This study by Roseby and colleagues shows that region-specific mechanosensation - especially anterior-dorsal inputs - controls larval self-righting, and links this to Hox gene function in sensory neurons. The work is important for understanding how body plan cues shape sensorimotor behaviour, and the experimental toolkit will be of use to others. The strength of evidence is compelling with respect to the assays developed and the involvement of the anterior region, the evidence is more limited with respect to the dorso-ventral organization of sensory inputs in that region and the mechanism by which Hox genes contribute to the process. These findings will be of broad interest to researchers studying neural circuits, developmental genetics, and the evolution of behaviour.

eLife Assessment

This study presents a valuable finding on the mutational and expression profile of ZNF217, ZNF750, ZNF703 Zinc finger genes in Kenya women with BCs. The evidence supporting the claims of the authors is solid. The work will be of interest to scientists or clinicians working in the field of diagnosis and detection for breast cancer.

eLife Assessment

In this important theoretical contribution, the authors study the evolution of large microbial populations competing for resources in the challenging and relevant regime of overlapping ecological and evolutionary timescales. The modeling approach is overall convincing, anlthough its presentation would benefit from clarifications, e.g. on assumptions and approximations. The results will be of broad interest to researchers in evolutionary biology, ecology and microbiology.

eLife Assessment

This valuable study demonstrates that the inner membrane protease YME1 contributes to the formation of mitochondrial-derived compartments in yeast through the modulation of both the lipid transporter UPS2 and the MICOS complex. The evidence supporting this model is solid, although this manuscript could be improved by providing additional evidence supporting the independent roles for UPS2 and MICOS regulation in this process. This work will be of interest to cell biologists, biochemists, and geneticists interested in understanding the molecular basis of mitochondrial regulation and function.

eLife Assessment

This important study investigates the peptide-binding principles of promiscuous chicken MHC molecules. The data from crystallography, mass spectrometry, and modeling are convincing. However, the presentation would benefit from streamlining and clear links between data and conclusions. This paper will be of broad interest to immunologists and those interested in vaccine development.

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 task design and preprocessing parameters that warrant careful consideration. The work will be of interest to researchers studying the evolution of cognitive control and cross-species neuroimaging.

eLife Assessment

This valuable study provides the first broad cross-species evolutionary analysis of the pir multigene family in malaria parasites, showing that the family evolved through rapid duplication and loss while retaining a small number of conserved orthologs with essential functions. The authors identify pirC1 as a key determinant of parasite growth across multiple Plasmodium species. However, the work remains incomplete because the mechanistic role of PIRCl and its precise subcellular localization are not directly resolved.

Editors Assessment:

This is a Data Release paper describing a mouse embryoid body single-cell RNA-seq dataset generated to study how oxygen availability shapes early cell differentiation. Acosta-Iborra et al. differentiated R1 mouse embryonic stem cells into embryoid bodies for 8 or 10 days, exposing them to hypoxia or normoxia for the final 16 or 48 hours of differentiation, then profiled thousands of cells per condition using droplet-based scRNA-seq from 10X. This yielding eight raw/filtered HDF5 count matrices across the four conditions. This was validated with flow cytometry, immunofluorescence, and EdU assays, confirming that hypoxia increased endothelial marker expression and vascular network complexity while inducing cell cycle arrest. This pattern mirrored transcriptionally, with hypoxic samples showing markedly higher proportions of cells in G0/G1 phase and elevated hypoxia gene-signature scores. QC analysis (and peer review in GigaByte) confirmed high data quality across samples, and conservative low-resolution clustering revealed a largely homogeneous progenitor population with a smaller, more differentiated subset. While there are limitations (mature endothelial cells were too sparse to robustly test the original hypothesis) the authors present this as an open, well-validated resource for comparative studies of hypoxia responses, benchmarking single-cell computational tools, and investigating early lineage specification and oxygen signaling more broadly.

This evaluation refers to version 1 of the preprint

eLife Assessment

This important manuscript presents the Crunchometer, an open-source and low-cost acoustic system for high-resolution quantification of biting and chewing in mice. The work addresses a need for reliable measures of food consumption and feeding microstructure, and the tool has broad relevance for studies of ingestive behavior, appetite circuits, hypothalamic function, and pharmacological interventions. The evidence supporting the methodological advance is convincing, and the Crunchometer outputs were carefully validated against human observer scoring, reliably distinguished biting and chewing events, and captured changes in feeding behavior across different foods, physiological states, and semaglutide treatment. The study also demonstrates that the system can reveal biologically meaningful features of feeding, including meal structure, bite and chew dynamics, and altered consumption patterns after pharmacological manipulation. A significant additional contribution is the identification of previously unrecognized meal-related neurons in the lateral hypothalamus, providing novel circuit-level insight into solid food consumption and naturalistic feeding behavior. Although some neuroscience conclusions remain more preliminary than the methodological validation, the study provides strong evidence for the utility of the Crunchometer and will be of interest to researchers studying ingestive behavior, hypothalamic circuits, and metabolic regulation.

eLife Assessment

This important study examines the role of TNF in modulating energy metabolism during parasite infection. The authors perform an elegant set of studies combining genetics, small molecule perturbation, and phenotypic experiments to highlight a role for glycolysis and glucose transport in control of parasitemia. This solid work integrates an interesting set of observations that will be of interest to the Plasmodium and pathogenesis communities with an expanded set of experiments.

eLife Assessment

This valuable study characterizes the emergence of the membrane-associated periodic cytoskeleton (MPS) in the axons of human motor neurons derived from induced pluripotent stem cells. Super-resolution imaging of beta-II spectrin provides convincing evidence for the patterned assembly of spectrin-poor gaps and spectrin-rich MPS in the medial region of the axons and its enhancement by the kinase inhibitor staurosporine. The data advocates against gap formation by axonal degeneration or cytoskeleton disassembly in a continuous MPS. Instead, a continuous MPS may result from nascent MPS patches and their maturation, a model that would benefit from live imaging for validation.

eLife Assessment

This manuscript describes convincing and very interesting findings that substantially advance our understanding of a major research question on the role of Cx32 hemichannels in the Schwann cell paranode. It provides an interdisciplinary integration of imaging, in silico approaches, and functional data. This important study proposes a new mechanism with profound physiological relevance and provides new insights into glial modulation of electrical conduction in sensory/motor myelinated nerves.

eLife Assessment

This study presents a useful methodological advance that better enables the simultaneous measurement of gene expression and chromatin accessibility in individual cells. The evidence supporting the improved detection of gene expression is solid. The method has the potential to be more broadly impactful if it were expanded to include orthogonal validation strategies. This method will be of interest to those studying transcription and gene regulation.

eLife Assessment

This important study provides new insights into the neuronal dynamics of the locus coeruleus in relation to hippocampal sharp-wave ripples. Using high-temporal-resolution, multi-site electrophysiological recordings in rats, the authors present convincing evidence that ripples and locus coeruleus activity are inversely correlated to levels of arousal and noradrenaline tone is modulated by hippocampo-cortical coupling. Overall, the work will be of interest to neuroscientists studying large-scale brain coordination and memory processes.

eLife Assessment

This work presents fundamental findings on the probability of use and access of inseticide-treated nets and evaluates the effectiveness of different distribution strategies in six African countries. The authors propose a sophisticated methodological framework that accounts for many sources of uncertainty, providing compelling strength of evidence.

eLife Assessment

This convincing contribution addresses a question of practical importance: when collecting tilt-series data, what is the optimal angular step size between successive tilt images? The work provides valuable practical insights into cryo-ET data acquisition by demonstrating that balancing two competing demands - sufficient dose per individual tilt image and fine angular sampling - is essential to achieve high-quality tomographic reconstructions. They demonstrate that tilt-series acquired with finer increments (1-3 degrees) yield superior alignment accuracy and improved template-matching performance,

eLife Assessment

This important work employed a recent functional muscle network analysis to evaluate rehabilitation outcomes in post-stroke patients. The research direction is relevant and supported by solid evidence from gross motor function assessment. The framework is a step toward standardized assessment of motor recovery in the rehabilitation process, but future studies would focus on linking functional recovery to muscle interaction biomarkers to provide more physiologically grounded interpretations.

eLife Assessment

This valuable study reports evidence that items maintained in working memory can bias attention in an oscillatory manner, with the attentional capture effect fluctuating at theta frequency. The study provides solid evidence that this dynamic attentional bias is associated with oscillatory neural mechanisms, particularly in the alpha and theta bands, as measured by EEG. The study will be relevant for researchers studying attention, working memory, and neural oscillations, particularly those interested in how memory and perception interact over time.

eLife Assessment

This important study identifies the cribriform plate as a key neuroimmune interface that shapes myeloid cell responses during neuroinflammation. Using imaging, flow cytometry, and single-cell approaches in a mouse model of EAE, the authors provide convincing evidence that dendritic cells and macrophages accumulate in PDPN-rich niches and have transcriptional features consistent with tolerogenic or immunosuppressive states. The work is technically strong and novel, and future studies will be needed to define the functional consequences of these myeloid cell states in autoimmunity.

eLife Assessment

This important study investigates how distinct honey bee viruses differentially alter flight performance through interactions with octopamine signaling pathways. The combination of behavioral flight assays, pharmacological perturbation, and transcriptomic analyses provides solid evidence that virus-specific effects on flight are associated with octopamine signaling. However, some of the stronger mechanistic conclusions regarding direct regulation of octopamine signaling remain incomplete without more specific validation of receptor-level effects and direct quantification of octopamine levels or signaling activity.

eLife Assessment

In this study, the authors propose a role for the Huntingtin protein in the organization of the Golgi apparatus and examine the effect of polyQ aggregates at the Golgi. The observations are interesting and potentially important for the field; however, the key claim that polyQ HTT functionally disrupts the Golgi (Golgipathy) is incompletely supported by the data.

eLife Assessment

This important study builds on previous work from the same authors to present a conceptually distinct workflow for cryo-EM reconstruction that uses 2D template matching to enable high-resolution structure determination of small (sub-50 kDa) protein targets. The paper describes how density for small-molecule ligands bound to such targets can be reconstructed without these ligands being present in the template. However, the evidence described for the claim that this technique improves the alignment of the reconstruction of small complexes compared to standard techniques is incomplete. The authors could better evaluate the effects of model bias on the reconstructed densities, as suggested by reviewer #1.

eLife Assessment

This is an important study that applies a new chromatin profiling technique to the study of cellular responses to low oxygen. The authors provide convincing evidence for distinct kinetic phases of the response and identify many new putative regulators of the response. This work will be of broad interest to those studying low oxygen responses and transcriptional regulation.

eLife Assessment

This paper addresses a key question regarding the molecular mechanisms underlying GABA and glutamate release from co-releasing neurons projecting from the entopeduncular nucleus (EPN) to the lateral habenula (LHb) in mice. The authors conclude that the two neurotransmitters are released from separate vesicle pools and rely on distinct molecular machinery; these conclusions contrast with previous functional studies at the same synapse, suggesting that GABA and glutamate are co-packaged within the same vesicles. The study employs useful electrophysiological and imaging approaches, however, a key limitation is the use of Cre lines that also label a purely glutamatergic EPN population projecting to the LHb. This inadequate methodology complicates the interpretation of the data and weakens the central conclusions regarding neurotransmitter co-release mechanisms.

eLife Assessment

The authors have presented a study which addresses a recognised gap in the literature, the emergence of the neural correlates of cognitive and affective empathy in children; they introduce a task for measuring both positive and negative empathy in a relatively large group of children aged 3-5. The task was combined with functional near-infrared spectroscopy to examine brain regions involved in the task. The findings are interpreted as providing evidence for the earlier emergence of cognitive than affective empathy. The study represents a valuable contribution to understanding the development of cognitive function, but in its current form, the strength of support for the conclusion is incomplete due to limited support for the comparison to the adult literature and a need to more clearly justify the pre-selected brain regions, their links to empathy and the justification of the hypotheses.

eLife Assessment

This study presents a valuable finding that the Par polarity complex, but not Crumbs or Scrib, regulates morphological remodeling during the naive-to-primed transition of pluripotent stem cells, with later effects on differentiation and neural tube organoid lumen formation. The evidence is incomplete, as the developmental significance of the PAR KO phenotype requires clearer framing and deeper characterization, and the proposed signaling pathway is currently presented more strongly than the data support. The work will be of interest to developmental and stem cell biologists studying polarity, pluripotent-state transitions, epithelialization, and lumen formation.

eLife Assessment

In light of the diverse functions associated with the Dorsal Raphe Nucleus across vertebrate species, this important study presents findings on the role of serotonin in promoting behavioral quiescence through the regulation of neuromotor populations. Combining optogenetics with brain-wide activity analyses, the study provides convincing evidence of interest to researchers in neuromodulation and translational medicine fields.

eLife Assessment

This important study reports characterisation of hepatocyte molecular pathways affected by a glycyrrhizin derivative in both in vivo and in vitro mouse models of alcohol-associated liver disease. The authors show convincing evidence indicating that IPP delta isomerase 1 (Idi1) is an intermediate in these pharmacological effects, via the binding of the glycyrrhizin derivative to an upstream regulator of Idi1, HSD11B1. The findings would be of interest to immunologists and pharmacologists interested in liver inflammation and its amelioration.

eLife Assessment

Tropical single-island endemic bird populations are particularly vulnerable to climate change. This study investigates genetic evidence of how such species dealt with climate change in the past as a possible predictor of how they will respond in the future, which could provide an important example for the fields of conservation genetics and island biogeography. The authors' integration of genomics and habitat modeling is commendable, but we find that the support for their conclusions is currently inadequate: some model parameter choices do not seem to reflect the biology of the studied species or to be well founded, which can cause misalignment of modeled dynamics with glaciation windows crucial for interpreting the study's results against its claims.

eLife Assessment

This useful study provides a systematic comparison of sex-biased enteroendocrine hormone expression in Drosophila and suggests that gut-derived peptides may contribute to female-biased triglyceride levels. The revised manuscript includes helpful textual clarifications and an integrative model, but the evidence remains incomplete, because the proposed role of Tk is still over-interpreted relative to authors' stated criterion for statistical significance against both parental controls. The work will be of interest to researchers studying sex differences in metabolism, but the central mechanistic claims require either stronger experimental support or more careful qualification.

eLife Assessment

The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. Their results, which are supported by solid evidence and will be important for the field, suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, through an indirect mechanism as the estrogen responsive enhancer does not loop with the TFF3 promoter. The mechanism of activation may involve condensate formation, however, more future work is needed to fully support a condensate based model. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

eLife Assessment

This important study investigates how infestation by the small brown planthopper (Laodelphax striatellus) reshapes rice carbohydrate allocation and demonstrates that host-derived glucose enhances insect fecundity and imidacloprid tolerance, through the activation of conserved nutrient-sensing and endocrine pathways. Across extensive and complementary approaches, including plant manipulations, glucose supplementation, RNAi, pharmacological inhibition, rescue experiments, and biochemical assays, the authors provide strong evidence that glucose activates the TOR-juvenile hormone-vitellogenin axis to promote reproduction and co-regulates GST-mediated detoxification via both TOR-JH signaling and GCL-GSH metabolism. The mechanistic framework is coherent and well supported by hierarchical validation and functional assays. While minor weaknesses exist regarding the generalizability of the findings and the identification of upstream initiating signals, the work provides a compelling framework linking nutrient sensing to pest adaptation.

eLife Assessment

This valuable study demonstrates that alpha herpes viruses trigger nuclear export of HDACs, which are then degraded in an MDM2-dependent manner. This virus-driven process leads to histone hyperacetylation and activation of the DNA damage response, which promotes viral replication. The presented evidence is mostly solid, but the mechanistic conclusions could be further strengthened with additional controls.

eLife Assessment

This manuscript reports on the application of ribosome profiling (EZRA-seq and eRF1-seq) and massively parallel reporter assays (MPRA) to identify and characterize sequence elements that regulate translation termination. The authors conclude that a GA-rich element upstream of stop codons is associated with ribosome pausing during translation termination; in contrast, C-rich sequences upstream of stop codons abolish termination pausing. While the overall findings of this study are useful and the identification of GA-rich elements upstream of stop codons is compelling, support for several other claims remains incomplete. Specifically, the evidence that the MPRA results mirror the ribosome profiling, that a C-rich sequence preceding the stop codon promotes termination slippage in cellular mRNAs, and that Rps26 interferes with mRNA interactions to regulate translation termination would benefit from further support.

eLife Assessment

Plasmodesmata are channels that allow cell-cell communication in plants; based on the functional similarities between facilitated transport at plasmodesmata and into the nucleus, the authors present the bold and potentially transformational hypothesis that nuclear pore complex proteins (NUPs) might be involved in plasmodesmata function. Here, the authors localize a subset of NUPs to plasmodesmata using proteomics and fluorescent imaging. They acknowledge many limitations to their work, including potential artifacts and the lack of functional validation of multiple NUPs, which may complicate the interpretation of their mostly solid results. Further experiments will be necessary to fully test this fundamental hypothesis about the function of NUPs at plasmodesmata.

eLife Assessment

This study presents fundamental results on the presence of the Entner-Doudoroff pathway in cyanobacteria. In contrast to an earlier study, compelling evidence is given that Synechocystis PCC 6803 lacks both an Entner-Doudoroff pathway and a related bypass but contains a promiscuous aldolase. This study successfully reconciles data from different studies and lessons learned from a previous misconception.

eLife Assessment

This study provides valuable evidence regarding our expectations about task difficulty and how this might influence proactive attention. The findings suggest that anticipated demands enhance the strength of attentional selection at cued locations. The evidence is solid but not definitive, as the conclusions rely on the absence of changes in spatial breadth. Nevertheless, the manuscript puts forth an informative experiment with a well written and thoughtful discussion of the results.

eLife Assessment

This useful study raises interesting questions but provides inadequate evidence of an association between atovaquone-proguanil use (as well as toxoplasmosis seropositivity) and reduced Alzheimer's dementia risk. The findings are intriguing but they are correlative and hypothesis-generating with the strong possibility of residual confounding.

[Note: The final version has been published in Brain, Behavior, and Immunity: https://doi.org/10.1016/j.bbi.2026.106473]

eLife Assessment

CellDetective is an important software package for segmentation, tracking, and analysis of time-lapse microscopy datasets, specifically designed to be accessible to researchers without coding expertise. The authors provide convincing evidence of its capabilities through comprehensive validations and well-executed comparisons across immunological assays, and the latest version adds support for defining and visualizing multiple cell subsets. The current implementation remains limited to 2D widefield imaging, though the authors provide a sound rationale for this scope, and one interface issue (a fixed main-window size on some systems) still affects usability. Overall, this work will be of significant interest to the bioimaging community, especially those in immunology and cell biology, and has applicability extending well beyond immune profiling.

eLife Assessment

This useful study uses a combination of experimental and modeling approaches to investigate the role of actomyosin in epithelial invagination during Ciona siphon tube morphogenesis. Several types of solid quantitative analyses and modeling approaches are presented that support a model in which bidirectional relocation of actomyosin drives invagination. Since epithelial invagination contributes to the morphogenesis of many developing organs, this work has the potential to appeal to both cell biologists and developmental biologists.

eLife Assessment

This valuable study introduces CAAMO, a computational framework that combines structure prediction, in silico mutagenesis, molecular simulations, and energy calculations to design RNA aptamers with improved binding affinity. The computational methodology is solid, demonstrating strong theoretical foundations and systematic integration of multiple prediction techniques. Many of the previously identified methodological weaknesses that limit the strength of support for the computational predictions have been addressed.

eLife Assessment

Based on several lines of interesting data, the authors conclude that neuronal FMRP, which is associated with stalled ribosomes and mRNP granules, does not determine position on the mRNAs at which ribosomes stall. They instead propose a role in subsequent translational activation of arrested mRNAs. Supported by generally solid experimental data, the paper represents a valuable contribution to the field. The generality of these conclusions, particularly for neurons of different development stages and for different subtypes of mRNP granules, should become clear with future studies that replicate and extend this work.

eLife Assessment

This important study identifies a new toxin/antidote (T/A) system in the model nematode C. elegans. These results suggest there are alternative mechanisms to neutralize selfish genetic elements. The authors present solid data that robustly support their central conclusion. This work will be of broad interest to investigators in evolutionary biology and reproductive biology.

eLife Assessment

In this valuable study, the authors conducted an impressive amount of atomistic simulations with a glycosylated HIV-1 envelope glycoprotein (Env) trimer in a realistic asymmetric lipid bilayer. The aim was to probe how Env transmembrane domain, cytoplasmic tail, and membrane environment influence ectodomain orientation and antibody epitope exposure. The simulations convincingly show that ectodomain motion is dominated by tilting relative to the membrane and explicitly demonstrate the role of membrane asymmetry in modulating the protein conformation and orientation, and the results are contextualized well in the revised version. Additional analyses of the authors' deposited MD trajectories could serve as invaluable extensions of this work to probe, for example, for exposure of cryptic epitopes and potential allosteric coupling.

eLife Assessment

This important study clarifies the mechanism by which the kinesin-10 motor protein, chromosome-associated kinesin, Kid (KIF22), enables chromosome movement during mitosis, demonstrating that human and Xenopus Kid proteins function as processive, homodimeric kinesins capable of processive microtubule plus-end motility. The convincing work highlights that Kid can recruit and transport duplex DNA along microtubules via its conserved C-terminal DNA binding domain, revising our understanding of chromokinesins' role in chromosome motility during mitosis. It will be of interest to those in the molecule motor community working at the molecular, cellular, and organismal levels.

eLife Assessment

This important work introduces an integrated open-source platform for behavioral acquisition and pose estimation that substantially improves the accessibility and speed of real-time animal tracking workflows. The evidence supporting the utility and usability of SqueakPose Studio is compelling, particularly the substantial inference speed gains, intuitive graphical interface, flexible pose configuration, and successful testing on independent datasets, although the evidence supporting broader benchmarking claims and the hardware ecosystem surrounding MouseHouse and SqueakView remains somewhat incomplete. The study will be of broad interest to neuroscientists and behavioural researchers seeking scalable and user-friendly approaches for real-time behavioral analysis, and the work would be further strengthened by more rigorous benchmarking, expanded installation and hardware documentation, formal software release practices, and clearer delineation between demonstrated capabilities and future applications.

eLife Assessment

This valuable study used genetic and pharmacological manipulations of insulin/IGF signaling to address the role of insulin/IGF axis in the function of renal glomerular podocyte. Solid data are presented to demonstrate that co-inhibition of insulin/IGF signaling in podocytes led to aberrant splicing of mRNAs, which could contribute to the loss of podocytes in vitro and in vivo in mice. In light of the fact that IR/IGF-1R signaling are critically required for normal development and growth in multiple cells and organs, the lack of the assessment of developmental phenotype of podocytes in the mouse model limits the interpretation of the data.

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

eLife Assessment

This important study combines behavioural psychophysics with image-based observer modelling to investigate which visual information can support view-tolerant face identity recognition. It offers convincing evidence that although diagnostic orientation content about identity varies with viewpoint - more horizontal for frontal views and more vertical for profiles - human recognition remains mainly tuned to horizontal information, identified by a view-tolerant model as carrying the most stable identity cues across viewpoints. Questions remain about how this generalises to ecological scenes and is biologically implemented.

eLife Assessment

This manuscript addresses an important question in clinical neuroscience: the use of the theta/beta ratio as a biomarker of attention deficit hyperactivity disorder (ADHD). The study takes an exceptional "multiverse" analysis approach to show that aperiodic activity differences between healthy controls and people with ADHD are driving the apparent theta/beta ratio differences. From a neuroscientific perspective, this is a critical finding because it has a major impact on guiding research on the diagnosis and treatment of ADHD.

eLife Assessment

GPR52 is an orphan receptor implicated in neuropsychiatric disorders, and this study addresses the lack of real-time monitoring tools by developing GPR52-1.0, a genetically encoded fluorescent sensor built on the GRAB platform. The design of the sensor is elegant and the validation is thorough. The authors also utilized the sensor to discover that striatal neuron excitation may activate the sensor, providing exciting new biological insights into GPR52 functional mechanisms. The work could be useful to the field if presented in the correct context, but as it stands, the work remains incomplete as it overlooks GPR52's well-documented high constitutive activity (PMID: 32076264, PMID: 26384023), which raises major questions about the sensor's physiological relevance.

eLife Assessment

This study provides useful insights regarding the alterations of sleep architecture in a knock-in mouse model of Alzheimer's Disease (AD). These include age-related hyperactivity that is typically associated with increased arousal, a normal homeostatic response to sleep loss, and a stronger AD-like phenotype in females. Although the analyses are robust, evidence for the proposed mechanisms underlying abnormal sleep architecture is incomplete. Overall, the study may have a focused impact for the sleep and AD fields.

eLife Assessment

This modeling study proposes important new insights into the circuit mechanisms underlying navigational control in insects. High-speed video recordings of ants are compared to detailed predictions from a new computational model that captures scanning dynamics. The similarities between the model and behavioral data suggest how complex behavioral motifs can emerge from dynamical interactions between modular components of a neural circuit. These solid results will be of interest to scientists studying the neural circuit basis of behavior, particularly in insects.

eLife Assessment

This is a fundamental study that clarifies the cellular mechanism of sound localization in the horizontal plane. The analysis of medial superior olivary neurons provides experimental and computational evidence for a new mechanism in which a range of asymmetric dendritic delays permits individual MSO neurons to represent the full range of biologically relevant ITDs. Using elegant 2-photon guided simultaneous recordings from distal dendrites and soma, along with compartmental modeling on anatomically reconstructed neurons, the authors provide compelling evidence that this mechanism contributes to microsecond-level tuning.

eLife Assessment

This study provides valuable insights into the protein composition of the C2a projection in mouse motile cilia, building upon prior work in Chlamydomonas. The evidence supporting the claims of the authors is solid. The work will be of interest to biologists and clinicians studying cilia and ciliopathies.

eLife Assessment

This study presents valuable findings on phase-separated condensate formation by the MUT-16 protein, which plays a key role in small RNA biogenesis. A detailed analysis of the interactions governing condensate formation was carried out using coarse-grained and all-atom molecular dynamics simulations, complemented by in vitro phase separation experiments. While many of the results appear solid, a number of technical details are lacking, the computational part appears incomplete and would benefit from additional analyses and clarifications, and the novelty of the study should also be clarified, particularly in comparison with the authors' previous work on MUT-16. Overall, the work will be of interest to biophysicists and molecular biologists studying phase separation and biomolecular condensates.

eLife Assessment

This study presents a valuable examination of two measurements of physical activity (self-report and objective) in relation to widely studied structural MRI measures of the brain (hippocampal volume and BrainAGE) and cognitive function (Trail Making Test). Cross-sectional and longitudinal data were analyzed using established and validated methodology. The results convincingly suggest that brain health is more likely a cause of physical activity than an outcome of it, although limitations to the data could mask evidence of benefits to brain health but these are discussed by the authors. This work will be of interest to neurologists and epidemiologists studying the etiology of cognitive decline, to clinicians interested in advising patients on strategies for preserving brain health in aging, and to members of the lay public.

eLife Assessment

This manuscript represents a valuable contribution to understanding motion processing in the visual cortex. Based on a heterogeneous collection of previous empirical findings, the authors show that the diversity of tuning curves in the middle temporal (MT) area, in response to moving center-surround images, can be explained by Bayesian inference combined with neural sampling. The model rests on strong and solid assumptions about the prior and likelihood; independent evidence that neither of these factors is misspecified would strengthen the work.

eLife Assessment

This manuscript provides a valuable perspective on microbial community diversity and how this is shaped by the presence of cheaters. The evidence provided is solid, and the methods used to assess the research question are convincing. However, a major weakness is the general framing (or lack of embedding in recent literature), reducing the usefulness of the paper for a broad audience.

eLife Assessment

This valuable study presents evidence that DNA Polymerase β strand displacement synthesis within linker DNA is stimulated by the presence of an adjacent nucleosome core particle. The biochemical analyses of the strand displacement synthesis by the DNA polymerase on a reconstituted nucleosome substrate with a linker DNA provided incomplete evidence to support the authors' conclusion. The results in the paper are of interest to researchers in DNA repair and nucleosome biology.

eLife Assessment

This valuable study combines multiscale molecular simulations with supporting biophysical experiments to investigate how the myristoylated VP4 peptide of non-enveloped viruses interacts with host membranes during viral entry. The authors show that myristoylation facilitates VP4 membrane anchoring, condensate formation, and membrane remodeling events linked to early stages of membrane breaching. The work provides a convincing biophysical framework for understanding myristoylation-dependence in membrane-penetrating proteins.

eLife Assessment

This paper demonstrates that a genetic code expansion to tag two amyotrophic lateral sclerosis (ALS) proteins associated with stress granules is useful in an experimental context. The data are solid and demonstrate the feasibility of using ANAP-fluorescence for live cell imaging.

eLife Assessment

This important study investigates how the hippocampus distinguishes between reactive escape and anticipatory withdrawal during approach-avoidance conflict in rats performing a naturalistic decision-making task. Solid evidence supports the main finding that hippocampal neuronal representations differ during different types of defensive behaviors, although the evidence for some of the claims in the paper could be strengthened. The study will be of interest to researchers studying memory, navigation, and decision-making in the presence of competing rewards and threats.

eLife Assessment

The authors describe the important finding that the Legionella-containing vacuole is surrounded by a dense ubiquitin "cloud" that is highly resistant to detergent extraction. The study provides compelling evidence that this structure is generated through a combination of canonical ubiquitination mediated by the SidC Legionella ligase and phosphoribosyl-ubiquitination mediated by the SidE family of Legionella ligases. These findings provide insight into how Legionella remodels the host vacuolar environment through complex ubiquitin modifications.