Editors Assessment:

This data paper is a genome note presenting the assembly of Porites harrisoni, a stony coral species endemic to the thermally extreme southern Persian Gulf. Using ONT PromethION long nanopore reads the final genome size encompassed 626.7 Mb across 1,883 contigs, achieving a BUSCO completeness of 86.3%. This revealed significant repeat content, comprising 59.23% of the nuclear genome and highlighting a diploid structure with predominant homozygosity. A total of 27,823 protein-coding genes were annotated from this assembly, facilitating discussions on thermal resilience under climate change. The research underscores the genomic framework supporting adaptive capacities in corals, with implications for evolutionary biology and conservation science, especially in context to ongoing ocean warming.

This evaluation refers to version 1 of the preprint

eLife Assessment

This study presents a valuable theoretical exploration on the electrophysiological mechanisms of ionic currents via gap junctions in hippocampal CA1 pyramidal-cell models, and their potentially unique contribution to local field potentials (LFPs). The biophysical foundations of transmembrane electric dipoles, and the associated argument points, are generally compelling. Experimental constraints on gap junctions and strictly quantitative matching between chemical vs. junctional inputs have been hard to achieve. This computational investigation thus offers a specific way to enhance conceptual understanding and provides interesting testable predictions, which would be of great interest to experimental neurophysiologists who interpret relevant recordings.

eLife Assessment

This timely and fundamental study presents an innovative iPSC based co-culture system to model Kupffer cell-hepatocyte interactions and hepatotoxicity, demonstrating reciprocal acquisition of tissue identity and enhanced hepatocyte maturation. The work is convincing, supported by well-executed methodology and functional validation, including physiologically relevant, concentration-dependent hepatotoxic responses. The research approach is promising and of broad interest, further clarification of experimental design and interpretation may strengthen its impact.

eLife Assessment

The analysis of neural morphology across Heliconiini butterfly species revealed brain area-specific changes associated with new foraging behaviours. While the volume of the centre for learning and memory, the mushroom bodies, was known to vary widely across species, these new, valuable results show conservation of the volume of a center for navigation, the central complex, but with specific changes in neuropeptide expression in the noduli and in the numbers of ellipsoid body ring neurons. The presented evidence is convincing for both volumetric conservation in the central complex and fine neuroanatomical differences associated with pollen feeding, delivered by experimental approaches that are applicable to other insect species. This work will be of interest to evolutionary biologists, entomologists, and neuroscientists.

eLife Assessment

This valuable study introduces miRTarDS, a novel computational framework that predicts microRNA-target interactions based on a publicly available pretrained Sentence-BERT language model and downstream classification analysis. The strength of the evidence is incomplete, as the evaluation framework relies on unreliable ground-truth and false sets. Furthermore, the analysis fails to compare miRTarDS against existing state-of-the-art biomedical language models.

eLife Assessment

This is an important paper that reports in vivo physiological abnormalities in the hippocampus of a rat model of traumatic brain injury (TBI). In this study, authors focused on changes in theta-gamma phase coupling and action potential entrainment to theta, phenomena hypothesized to be critical for cognition. The authors provide convincing evidence of deficits in both features post-TBI and contributes new understanding to how disruptions in oscillatory coordination and spike timing may relate to cognitive impairment.

eLife Assessment

This important study details changes in the brain functional connectivity in a longitudinal cohort of Gambian children assessed outside a lab setup with functional near-infrared spectroscopy (fNIRS) from age 5 to 24 months, in relation to early physical growth and cognitive flexibility capacities at preschool age. Evidence supporting conclusions on the evolution of brain connectivity is convincing and highlights a different trajectory compared with populations from high-income countries. However, analyses linking connectivity trajectories with early adverse conditions such as undernutrition and later cognitive development are only partially supported due to insufficient longitudinal data and statistical power. This study will be of significant interest to neuroscientists, psychologists and neuroimaging researchers working on infant development in relation to environmental factors.

eLife Assessment

Hoverflies are known for their sexually dimorphic visual systems and exquisite flight behaviors. This valuable study reports how two types of visual descending neurons differ between males and females in their motion- and speed-dependent responses, yet surprisingly, the behavior they control lacks any sexual dimorphism. The results convincingly support these findings, which will be of interest for studies of visuomotor transformations and network-level brain organization.

eLife Assessment

This study provides valuable insight into the role of actin protrusions in mediating early pre-endoyctic steps of human papillomavirus entry at the cell surface. Using state-of-the-art microscopy in an immortalized keratinocyte model, the authors present convincing evidence that filopodia actively promote the transfer of heparin sulfate-coated virions from the extracullar matrix to the viral entry factor CD151. These findings provide a strong framework for future studies aimed at further resolving the dynamics of virion transfer and receptor engagement.

eLife Assessment

This valuable study reports a substantial single-cell RNAseq and bulk RNAseq dataset from multiple high-grade serous ovarian cancers, including a single-cell atlas of human fallopian tube epithelium. The bioinformatic analysis investigating the lineage and location of epithelial progenitor cells is convincing, although this will require experimental validation. The work also provides a resource to examine additional features of normal fallopian tubes and ovarian cancers, and for developing methods for early detection and tumour stratification.

eLife Assessment

This important study has demonstrated that MORC2 undergoes phase separation in cells and established multiple interactions responsible for the phase separation. Upon revision, the data generally provide solid support to the claim that MORC2 condensates are functionally relevant in gene regulation and begins to demonstrate the importance of the physical properties of biological condensates. Nevertheless, there remains some weakness in the connection between condensates and function.

eLife Assessment

This study addresses an important question in gustatory neuroscience by developing a machine-learning classifier to identify distinct ingestive orofacial movement subtypes from electromyographic recordings and relating their dynamics to population-level activity in the gustatory cortex. The evidence that transitions in cortical ensemble firing are temporally associated with reorganization of ingestive movement patterns is convincing, though some aspects of the behavioral classification and neural analyses require further validation and clarification. The work provides a technically innovative framework for linking neural state dynamics to the motor expression of taste-guided decisions.

eLife Assessment

This fundamental study provides a major contribution to our understanding of Amyotrophic Lateral Sclerosis (ALS) pathogenesis by utilizing a primate model that overcomes the historical limitations of rodent paradigms. By demonstrating the retrograde and trans-synaptic spread of pathological TDP-43 from the periphery to the spinal cord and motor cortex, the authors propose a new model for the disease spreading. The evidence supporting these findings is compelling, characterized by rigorous post-mortem histological observations. This work will be of profound interest to neuroscientists and translational researchers seeking to decode the mechanisms of systemic disease progression in ALS.

eLife Assessment

This study presents a useful array of analyses of the effects of training and/or instruction to use the method of loci during episodic encoding and retrieval. A major strength of the experiment is the impressive recruitment of memory athletes and the training of novice athletes to use the method of loci, long known to improve the precision of memory recall. That said, the sheer number of results and their organization should be addressed; streamlining the results and placing them, whenever possible, in a theoretical framework. As it stands, the presented work is incomplete with respect to the major conclusions that training itself leads to neural differentiation of prefrontal cortical neural patterns, and the authors need to temper these claims.

eLife Assessment

This study provides an insight into the role of a Chi3l1 in liver macrophages during metabolic disease. The evidence is solid with the authors now addressing most concerns, although one key conclusion is not fully supported by the data presented. Overall, the work offers a useful contribution to the field.

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, but incomplete evidence that these changes are of importance for adaptive trait 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 study investigates the role of developmental oligodendrocytes in synchronising spontaneous activity in neuronal circuits and influencing cerebellar-dependent behaviour. The authors use advanced viral targeting techniques to deplete oligodendrocytes in a cell-specific manner, paired with in vivo calcium imaging of Purkinje cells, to establish a relationship between oligodendrocyte-mediated neuronal synchrony and complex brain function. The authors present compelling evidence of oligodendrocyte-regulated neuronal synchrony. Overall, this manuscript holds promise as an important contribution to neurodevelopment research.

eLife Assessment

In this important work, it is demonstrated that certain high-resolution cryo-EM structures can be obtained by using concentrated cell extracts without purification. The compelling results with the mammalian ribosomes demonstrate the utility of this approach for this molecule and complexes with elongation factor 2. Moreover, this work also demonstrates the utility of 2D template matching for particle picking for structure determination by single-particle averaging pipelines.

eLife Assessment

This important study convincingly shows that Vibrio bacteria act as predators of ecologically significant algae that contribute to harmful blooms in the lab and in their natural habitat, and that predation is induced by starvation. The authors suggest a working model that can be the basis for future work on this system. The study will be very impactful to those interested in the diversity of microbial predator-prey interactions and controlling toxic algal bloom.

eLife Assessment

This valuable study combines previously established mathematical models to investigate why cortical waves in starfish and Xenopus embryos propagate in opposite directions. The modeling results are solid and plausible, but remain experimentally untested. Improving the presentation and discussion of the results could make the study more accessible to a wider audience.

eLife Assessment

This study shows that combining forced cell cycle re-entry with Rbpj deletion enhances Müller glia dedifferentiation and promotes their conversion into retinal neuron-like cells in the uninjured mouse retina. It provides a valuable strategy for improving Müller glia-mediated neurogenesis and advancing regenerative potential in the mammalian retina. Overall, the data are convincing, but the conclusions would be strengthened by functional validation of the newly generated neurons and retinal performance, as well as an assessment of Müller glia long-term function and cell survival.

eLife Assessment

This important study probes the long-standing failure to resolve evolutionary relationships between the classical "spiralian" taxa - i.e., annelids, molluscs, brachiopods, platyhelminths and nemerteans - and provides convincing evidence that the branches leading to them are so short as to be unreliable guides to their relationships. This, in turn, has wide-ranging implications for our understanding of animal body plan evolution and the interpretation of early animal fossils.

eLife Assessment

The authors provide valuable findings showing that GM-CSF prevents the loss of ILC3 populations during gut inflammation and inhibits pro-inflammatory cytokine production. They combine a preclinical model of gut inflammation in zebrafish with spatial transcriptomic analysis of samples from Crohn's disease patients. Although the data provided are clear and point to an anti-inflammatory role of GM-CSF, the strength of evidence remains incomplete as no mechanistic insights into GM-CSF regulation of ILCs are provided, and the most significant mechanistic question remains unanswered: what are the signals downstream of GM-CSF that maintain the ILC3 population? This work will be of interest to immunologists.

eLife Assessment

This manuscript has convincing data that provides a high-resolution structure of the Egl-RNA complex. The findings are important to understand the formation, stability, and interactions of this complex. However, the manuscript could be improved by conducting a rigorous statistical analysis, a deeper understanding of apparent discrepancies in the stoichiometric Egl-to-RNA ratio, and exploring the specificity of this complex using a more diverse set of control RNAs.

eLife Assessment

This valuable study provides evidence that the integration of the nuclear envelope into the endoplasmic reticulum provides a mechanism for mechanical integration across this continuous membrane system. This work opens up new avenues for studying organelle membrane tension homeostasis. The evidence was found to be convincing and carefully quantified, with minor limitations that we expect to be further explored in future work.

eLife Assessment

This valuable manuscript describes ATP5I, a subunit of F1Fo-ATP synthase, as a key target of medicinal biguanides. The knockout of ATP5I in pancreatic cancer cells mimics biguanide treatment, inducing a metabolic switch from OXPHOS to glycolysis due to a compromised expression of the Complex I protein NDUFB8. This results in a markedly decreased NAD/NADH ratio and decreased cell proliferation. These solid findings point out ATP5I as a promising mitochondrial target for cancer therapies and contribute to our understanding of metformin's mechanism of action since many of its molecular mechanisms remain poorly understood.

eLife Assessment

This important study introduces an experimental approach for studying Drosophila oviposition rhythms and identifies the subset of circadian clock neurons that mediate the circadian control of oviposition. The authors resolve an inherently noisy rhythm to provide convincing evidence by using statistical averaging techniques, which help reduce this noise but at the cost of variation across individual rhythms. This paper will be of interest to anyone interested in insect ovarian physiology, circadian biology, and reproductive fitness.

eLife Assessment

This study presents valuable computational findings on the neural basis of learning new motor memories and the savings using recurrent neural networks. The evidence supporting the claims of the authors is solid, but it would benefit from more detailed discussion on the specific conditions under which savings emerges from purely implicit mechanisms. This work will be of interest to computational and experimental neuroscientists working in motor learning.

eLife Assessment

This study provides compelling evidence that action potential (AP) broadening is not a universal feature of homeostatic plasticity in response to chronic activity deprivation. By leveraging state-of-the-art methods across multiple brain regions and laboratories, the authors demonstrate that AP half-width remains largely stable, challenging previous assumptions in the field. These important findings help resolve longstanding inconsistencies in the literature and significantly advance our understanding of neuronal network homeostasis. The authors have clarified methodological differences with prior work and expanded the discussion of potential mechanisms, strengthening the interpretation of the findings without altering the central conclusions.

eLife Assessment

This valuable study demonstrates that the E3 ligase ITCH regulates several steps of the SARS-CoV-2 replication cycle by enhancing ubiquitination of viral envelope and membrane proteins. The phenotypic data are based on solid evidence showing a role for ITCH in distinct phases of viral replication and host processes. The findings lay the ground work for future studies to decipher detailed molecular mechanisms that explain how ITCH regulates SARS-CoV-2.

eLife Assessment

This study presents an important finding regarding how partner preference formation and pair bonding behavior are related to the oxytocin receptor gene expression in the NAc and paraventricular nucleus of the hypothalamus in prairie voles. The evidence supporting this claim is solid but could benefit from increased sample size and more thorough behavioral phenotyping. This study will be of interest to social scientists and neuroscientists who work on pair bonding and oxytocin.

eLife Assessment

This important study shows that an odorant that is typically thought of as a repellant actually activates both attractant and repellant olfactory neurons in C. elegans. Convincing evidence is provided that nematode worms can integrate signals in different sensory pathways to drive different behavioral responses to the same cue. These findings will be of interest to scientists interested in combinatorial coding in sensory systems.

eLife Assessment

The findings in this paper provide solid support for a hypothesis that has valuable implications at the intersection of value-based and social decision-making. The findings suggest that the brain processes rewards received for effort differently when they are earned for themselves versus someone else.

eLife Assessment

This landmark study investigates how patterned human gastruloids can provide insights into neural tube closure. Using a screen, they identified positive and negative regulators and defines the epistasis among them using optimization of micro-pattern based gastruloid protocol and CRISPRi. This technical tour de force is exceptional and one of the first studies to reveal new knowledge on human development through embryo models.

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 for 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 technical study introduces SCOPE, an optics-free spatial reconstruction method based on bidirectional sender and receiver oligonucleotides on barcoded hydrogel beads. By sequencing proximity-encoded chimeric molecules, the authors computationally reconstruct 2D and 3D spatial information at an impressive scale. The technical demonstrations in synthetic bead systems are convincing and establish proof-of-principle that large spatial domains can be reconstructed without microscopy. The methodological advance is clear and the scale is impressive. Direct validation in biological samples would help clarify what additional limitations on applicability may exist. This work will be of interest to those working on spatial mapping.

eLife Assessment

This important study investigates how the brain categorizes written words from different writing systems (e.g., alphabetic vs. non-alphabetic), shedding potential light on the neural basis of language's social‑categorization function. Overall, the evidence supporting the authors' claims is solid, though some analyses and key interpretations would benefit from fuller justification.

eLife Assessment

This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This is explained by hypothesising the existence of a heterotypic tension at the boundary between different cell types, and supported by pharmacological perturbations and numerical simulations using the vertex model. The solid study conveys a key message, although some uncertainty remains regarding the origin of the heterotypic tension in relation to acto-myosin organisation in the boundary cells.

eLife Assessment

This fundamental work substantially advances our understanding of a major research question: whether collagen can be directly imaged with MRI. The evidence supporting the conclusion is compelling, with methods, data, and analyses that are more rigorous than those currently considered state-of-the-art. The work will be of high interest to MR physicists and clinicians, as collagen is the most abundant protein in the human body and plays an essential role in health.

eLife Assessment

This is a useful study that seeks to elucidate the molecular mechanisms underlying spinal motor 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. However, the study in its current form is incomplete: the data and analyses do not fully support the main conclusion that Onecut acts through Neurotrophin-3 to regulate interneuron development in a non-cell autonomous manner. The work will be of broad interest to cell and developmental biologists.

eLife Assessment

This important paper provides novel information on the function of the Drosophila ryanodine receptor (RyR) during muscle development. The authors analyze the effects of a rare human mutation that causes myopathy that affects a conserved region of the gene. They present compelling evidence that this variant affects muscle function in flies. These results suggest that Drosophila can be used as a tool for screening additional variants.

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

eLife Assessment

This important study uses a tripartite transdiagnostic computational framework to distinguish depression-specific, anxiety-specific, and shared psychopathology dimensions, in their relationships to mood variability and mood reactivity to reward prediction errors across multiple large non-clinical cohorts and a clinical sample. The evidence is convincing overall because the study combines large samples, a well-characterized gambling task and in-depth computational and psychometric analyses, and it replicates the depression-specific association with blunted reward prediction error-sensitivity in a clinical sample. However, the anxiety-specific effects are less consistently supported across individual datasets, may be underpowered in the clinical cohort because of comorbidity, and some aspects of the factor-analytic, risk-attitude, and mediation analyses would benefit from clearer explanation. These findings advance a mechanistic account of how distinct symptom dimensions differentially shape reward-based mood updating and variability, providing a principled framework for future transdiagnostic modeling.

eLife Assessment

This valuable study addressed a key question in epilepsy research: whether the recordings of very fast oscillations in the brain (>250Hz, fast ripples) reflect underlying pathology or might be a property that emerges from a neuronal network at random. The strengths of the study are the importance of the question, the multiple methods, and the solid evidence. However, there are limitations to the methods that should be addressed.

eLife Assessment

This study uses convincing modeling methods and analyses of rich behavioral datasets to investigate the role of attention in value-based decision making; for instance, as when choosing between two snacks. The results are valuable, as they challenge existing theories that assume that paying attention to an available option biases the eventual choice toward that option. The results suggest that the correlation between attention and decision-making is formed largely after and not before the (internal) choice process has terminated, a finding that offers an intuitively appealing rethinking of how attention and decision-making processes interact during value-based choices.

eLife Assessment

This study uses convincing modeling methods and analyses of rich behavioral datasets to investigate the role of attention in value-based decision making; for instance, as when choosing between two snacks. The results are valuable, as they challenge existing theories that assume that paying attention to an available option biases the eventual choice toward that option. The results suggest that the correlation between attention and decision-making is formed largely after and not before the (internal) choice process has terminated, a finding that offers an intuitively appealing rethinking of how attention and decision-making processes interact during value-based choices.

eLife Assessment

This study provides a valuable contribution to understanding grid-to-place transformations, offering new insights into the structure and reliability of these representations and extending prior work in a meaningful way. The evidence supporting the authors' conclusions is solid, based on careful analyses and well-executed experiments, although clarity and mechanistic interpretation would be strengthened by improving sample size reporting, expanding population-level analyses, and future studies including simultaneous entorhinal-hippocampal recordings. The work will be of interest to neuroscientists studying spatial coding and hippocampal-entorhinal circuit function.

eLife Assessment

This work provides a map of enhancer-promoter interactions associated with genes controlling the development of a specific neuronal cell population. The study offers a valuable resource and integrates multiple complementary datasets to provide insights into regulatory mechanisms, although the conceptual advances are moderate and the central message could be clearer. The evidence supporting the conclusions is generally solid, but the lack of direct functional testing of key regulatory elements limits the strength of some claims.

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

eLife Assessment

This important study concerns the propagation of waves in bacterial biofilms, bridging active matter physics and bacterial biophysics. The experimental observations are solid, and the theoretical interpretation and model validation have been refined with revisions. This work will be of interest to microbiologists, biophysicists, and researchers studying collective behavior in biological systems.

eLife Assessment

This important study combines a two-person joint hand-reaching paradigm with game-theoretical modeling to examine whether, and how, reflexive visuomotor responses are modulated by a partner's control policy and cost structure. The study provides a convincing set of behavioral findings suggesting that involuntary visuomotor feedback is indeed modulated in the context of interpersonal coordination. The work will be of interest to cognitive scientists studying the motor and social aspects of action control.

eLife Assessment

This study addresses an important question and shows how social navigation in homing pigeons can be explained by simple averaging, without requiring any complex cognitive abilities. The evidence, based on a rigorous and systematic comparison of seven models and data on how social routes can be generated from solitary routes, is compelling. The authors should be commended for their willingness to critically re-examine established interpretations.

eLife Assessment

This important manuscript reports a very interesting view of how pesticides can be toxic to beneficial insects like the honeybee. The study uses machine learning for the discovery of new honeybee-repellent odorants. The solid evidence predicts compounds that were validated in the lab and in the field. This work will be of great interest to researchers in ecology, pest control and sensory biology.

eLife Assessment

This meta-analysis provides a fundamental synthesis of evidence demonstrating that transcranial magnetic stimulation targeting the hippocampal-cortical network reliably enhances episodic memory performance across diverse study designs. The evidence is convincing, with rigorous methodology and consistent effects observed despite modest sample sizes and some heterogeneity in stimulation approaches. The work highlights the specificity of memory improvements to hippocampal-dependent memories and identifies key methodological factors-such as individualized targeting-that influence efficacy. Overall, this study offers a timely and integrative framework that will inform both basic memory research and the design of future clinical trials for cognitive enhancement.

eLife Assessment

In this important study, the authors conducted atomistic molecular dynamics simulations to probe the interactions between IRE and unfolded peptides. The results help reconcile contradicting experimental findings in the literature and offer mechanistic insights into the activation of the unfolded protein response. The atomistic molecular dynamics simulations performed are solid, leading to convincing conclusions that are partly supported by experimental validations. The use of unbiased molecular dynamics simulations, while appropriate for the current system due to its complexity, limits the time scale of events that can be observed and therefore the proposed mechanism of recognition merits further confirmation by future studies.

eLife Assessment

This manuscript reports high-resolution cryo-EM structures of a trimethylamine N-oxide demethylase and advances the hypothesis that the enzyme is bifunctional, coupling TMAO demethylation to formaldehyde capture via an enclosed intramolecular tunnel. The structural findings remain valuable, particularly the unusual oligomeric architecture and proposed conduit for a reactive intermediate. While the revision improves clarity and addresses several technical concerns, the central mechanistic framework remains incomplete, with persistent concerns regarding the proposed catalytic mechanism and metal dependence.

eLife Assessment

This manuscript reports a valuable modeling study on sequence generation in the hippocampus in a variety of behavioral contexts. The authors model context-depending decision making, and suggest that psychiatric disorders can be interpreted in terms of over or under representation of context information. The presentation is solid, and the work will interest the broad community of researchers studying cortical-hippocampal interactions and sequences.

eLife Assessment

This important study examines how chronic pain and opioid exposure interact at the cellular and molecular levels in a reward-related brain region. Using single-nucleus RNA sequencing, the authors map transcriptional changes in the rat ventral tegmental area following chronic inflammatory pain and acute morphine exposure. Notably, their convincing data support that acute morphine, not chronic pain, elicits a stress-related transcriptional response primarily in glial cells rather than neurons, challenging prevailing views of opioid action and supporting growing evidence for glucocorticoid signaling in glial responses. A limitation is the use of a single opioid dose and time point, and further discussion of these constraints would help clarify the broader implications of the findings.

eLife Assessment

This manuscript presents a useful computational framework for systematically characterising how heterogeneity in initial conditions or biophysical parameters shapes the dynamic behaviour of protein signalling networks, with potential relevance to understanding adaptive drug resistance. While the approach represents a significant methodological contribution, the extent to which its conclusions are biologically informative remains debated, as the model is only qualitatively compared with experimental data and lacks quantitative validation. As a result, the strength of evidence supporting the mechanistic claims is viewed as incomplete.

eLife Assessment

This important study demonstrates the power of the UniDesign computational framework in prospectively engineering a PAM-relaxed Staphylococcus aureus Cas9 variant with editing performance comparable to evolution-derived counterparts. The authors responded promptly and thoroughly to reviewer concerns and strengthened the manuscript with additional experimental validation, providing compelling evidence through expanded biochemical characterization across multiple human cell types, comprehensive deep-sequencing analyses, and direct comparisons with established variants that illuminate the mechanistic basis of PAM specificity remodeling and Cas9 optimization. By establishing computational design as a rigorous and viable alternative to directed evolution for CRISPR systems, this work will be of broad interest to the protein engineering, genome engineering, synthetic biology, and computational protein design communities.

eLife Assessment

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

eLife Assessment

This manuscript introduces a new low-cost and accessible method for assembling combinatorially complete microbial consortia using basic laboratory equipment, which is a valuable contribution to the field of microbial ecology and biotechnology. The evidence presented is compelling, demonstrating the method's effectiveness through empirical testing on both synthetic colorants and Pseudomonas aeruginosa strains.

eLife Assessment

This study presents valuable findings by reanalyzing previously published MEG and ECoG datasets to challenge the predictive nature of pre-onset neural encoding effects. The evidence supporting the central conclusions remains incomplete, as additional details of the analyses are needed and alternative interpretations, such as the possibility that pre-onset predictive and sensory-evoked responses rely on distinct neural representations, have not been sufficiently addressed. The work may be of interest to researchers in language processing, predictive coding, and related fields.

eLife Assessment

This manuscript presents a valuable antiviral approach using an engineered ACE2-Fc fusion protein that demonstrates broad-spectrum neutralization capacity against SARS-CoV-2 variants and achieves significant prophylactic protection in animal models through a novel Fc-mediated phagocytosis mechanism. The study provides convincing evidence for protective efficacy through rigorous in vivo validation in mice, mechanistic characterization via biodistribution studies and macrophage depletion assays, and demonstration of antibody-dependent cellular phagocytosis as the primary clearance mechanism. The work will be of interest to researchers working in vaccine development and associated immune responses.

eLife Assessment

The authors developed and validated a gut-on-chip system to mimic the gut environment for studies of Clostridioides difficile infection in vitro. Although the data generated is useful to the field, the evidence provided to support the conclusions is incomplete. Methodology that is not complete, as well as discrepancies regarding the proposed mode of action of lipoxin A4, are significant weaknesses.

eLife Assessment

This fundamental study describes long-range serial dependence of performance on a visual texture discrimination training task that manipulated conditions to induce differing degrees of location transfer of learning. The authors re-analyzed previously-published, behavioral data, generating compelling evidence from converging approaches that the serial dependence effects persist over multiple days of training, and may share a common causal mechanism with training-induced location transfer. By informing our understanding of the importance of temporal integration to long-term perceptual learning and its propensity towards specificity or generalizability, these results should interest neuroscientists who seek to uncover underlying neural mechanisms for these processes.

eLife Assessment

This study presents important findings that bovine mammary epithelial cells can be infected with both avian and human influenza A viruses, providing a potential site for viral reassortment. The evidence to support these claims is generally solid; however, the evidence suggesting lower permissiveness of cells from other organs is incomplete. The work will be of interest to virologists and evolutionary biologists working on cross-species transmission of viruses and pandemic preparedness.

eLife Assessment

This potentially important paper questions the evolutionary origin of the tunicate endoderm, using single-cell sequencing on a developmental series of the ascidian Styela clava that covers metamorphosis and gut development. The authors base their conclusions on a comparison with the development of mouse gut endoderm, where they point out similarities in the origin of tissues, perhaps representing a case of "deep homology". This work has the potential to make a significant contribution to the field of chordate evolution, but in its current form, the evidence it presents is incomplete and is limited by a problematic discussion of evolutionary implications and by major issues regarding the clarity and cogency of data presentation.

eLife Assessment

This study presents a valuable finding on the role of intracellular zinc as a regulator of the sperm-specific potassium channel Slo3, demonstrating that zinc export during capacitation contributes to alkalinization-induced membrane hyperpolarization. The electrophysiological evidence supporting zinc-mediated inhibition of Slo3 is solid, though the mechanistic basis of this inhibition is not complete, as the proposed zinc-binding site involving E169 and E205 has not been directly tested through double-mutant analysis. This work will be of interest to reproductive biologists and ion channel biophysicists studying the molecular mechanisms of sperm capacitation.

eLife Assessment

The study presents valuable findings of an optimized E. coli cell-free protein synthesis (eCFPS) system that has been simplified by reducing the number of core components from 35 to 7; furthermore, the findings communicate a simplified 'fast lysate' preparation that eliminates the need for traditional runoff and dialysis steps. It is interesting that the system's robustness is exhibited by its applicability to nanoluc, a protein that expresses readily in many systems, to more challenging proteins like the functional self-assembling vimentin and the active restriction endonuclease Bsal. Despite the study representing an advancement towards simplifying protein expression workflows, the evidence supporting some of the claims remains incomplete: performance or efficiency claims of the new system needs to be supported by comparisons with typical cell free expression systems. Despite this shortcoming, the paper remains of interest to scientists in cell and molecular biology, microbiology, biotechnology and protein synthesis.

eLife Assessment

This is a valuable study that presents human single nuclei RNA-seq and spatial transcriptomics data of the developing outflow tract and adult aortic valves that will facilitate research in this area. Data presented are solid, with bioinformatics analyses showing cell lineage and trajectory relationships, intriguingly suggesting persistence of embryonic signature in adult aortic valve cells. The latter results would be strengthened by experimental validation.

eLife Assessment

This important study examines the potential role of ARHGAP36 transcriptional regulation by FOXC1 in controlling sonic hedgehog signaling in human neuroblastoma. While there are many solid findings that strongly support this signaling pathway, there are some aspects of the study that are underdeveloped, particularly the generalizability in the context of cancer cells.

eLife Assessment

This valuable study utilizes a newly developed approach to culture T gondii bradyzoites in myotubes, and then takes advantage of the antiparasitic compound collection known as the Pathogen Box, to find compounds that target both tachyzoite and bradyzoite forms of the parasite. A set of compounds yielding patterns consistent with targeting the mitochondrial bc1 complex was explored further, with convincing evidence for changes in ATP production in bradyzoites to support the conclusions about the importance of this complex. The paper will be interesting for parasitologists studying drug discovery of apicomplexan parasites.

eLife assessment

This study presents an important finding of dynamic reprogramming of global H3K4me2 during mouse oocyte-to-embryo transition. While the H3K4me2 epigenome data is convincing, the interpretation and the potential mechanistic claims of the authors are incomplete in the current shape with the primary concerns regarding the contribution of Kdm1b or Kdm1a, as well as the specificity of the inhibitor and the antibody. The work will be of interest to researchers interested in epigenetic reprogramming.

eLife Assessment

This study characterizes several novel activities of SARS-CoV-2 helicase nsp13, providing valuable insights into potentially new functions of this essential RNA-processing enzyme in the virus life cycle. However, the experimental evidence to support the authors' claims is incomplete. In addition, the placement of the polyhistidine affinity tag on nsp13 may cause artifacts, raising concerns about the interpretation of the results.

eLife Assessment

This useful study presents an improved protocol for long-term in vitro culture of Schistosoma mansoni that enables progression toward sexually dimorphic stages, representing a meaningful advance for studying parasite development and reducing reliance on animal models. The findings show that host-specific culture conditions support essential developmental and metabolic functions required for parasite maturation, although development remains delayed compared to in vivo conditions. The evidence is solid overall, but limited pairing efficiency and the absence of egg production indicate that the system does not yet fully recapitulate complete reproductive development.

eLife Assessment

In this work, the authors demonstrated that blue light mediated mitochondrial contacts attenuated blue light induced mitochondrial dysfunction, and validated this in human cells and C. elegans. This valuable work has the potential to provide novel perspectives into the field of mitochondrial biology but the supporting data are incomplete.

eLife Assessment

This study provides potentially important insights by establishing a human disease model and exploring therapeutic approaches. The evidence is generally convincing for descriptive and comparative findings. The authors present solid data, but evidence for proposed biological mechanisms and functional outcomes remains limited.

eLife Assessment

This study presents a valuable methodological contribution exploiting the DEER background decay to quantify supramolecular packing in amyloid fibrils. The evidence is incomplete: the observation of D < 1 is inconsistent with the theoretical lower bound of the model, and it remains unclear whether this reflects a genuine systematic limitation or falls within experimental uncertainty.

eLife Assessment

In this valuable study, the authors develop new approaches to investigate mRNA imprinting, a phenomenon in which RNA-protein complexes form in the nucleus to influence the fate of transcripts in the cytoplasm. They propose that the Pol II subunit Rpb4 serves as a key node in this pathway, recruiting proteins involved in cytoplasmic processes. Notably, some of the candidates identified in this study were previously thought to function exclusively in the cytoplasm. However, the evidence remains incomplete, as key controls are lacking and alternative explanations have not been fully addressed; additional validation would help strengthen the authors' conclusions.

eLife Assessment

This valuable study by Zhu et al. offers a high-resolution evolutionary framework for spider silk proteins (spidroins) through long-read transcriptomics across a broad phylogenetic range, with theoretical implications for protein family evolution, biomaterials, and silk biology. By identifying putative ancestral spidroin templates in early-diverging spiders, the authors make a significant contribution to understanding genetic innovations underlying silk diversification. The long-read sequencing approach is well-suited to these highly repetitive genes. However, the support is incomplete: key claims regarding direct ancestry between silk protein families, the independent origin of certain silk types, and the co-option of flagelliform spidroins in non-web-building spiders rely on absence-based inferences and indirect phylogenetic reasoning that the data cannot yet fully substantiate, and some gene family assignments overreach the available molecular evidence.

eLife Assessment

This is a valuable study that investigates the role of the long non-coding RNA Dreg1 for the development, differentiation, or maintenance of group 2 ILC (ILC2). The authors generate Dreg1-/- mice and show a reduction of group 2 innate lymphoid cells (ILC2). However, the strength of evidence supporting the impact of Dreg1 on Gata3 expression, a transcription factor required for ILC2 cell fate decisions, and the cell-intrinsic requirement of Dreg1 for ILC2 remain incomplete. This study will be of interest to immunologists.

eLife Assessment

This important study investigated whether the nuclear receptor Nur77 is regulated by a non-canonical mechanism of ligand-induced disruption of its interaction with RXRg, similar to the family member Nurr1. The overall evidence is compelling. This manuscript will be of interest to scientists focusing on mechanisms of transcriptional regulation.

eLife Assessment

This study investigates trial-by-trial intra- and inter-cortical interactions in the visual cortex of the mouse and the monkey. The authors find that activity in one layer (in mice) or one area (in monkeys) can partially predict neural activity in another layer or area on the single-trial level in different experimental contexts. This valuable finding expands previously known contributions of stimulus-independent downstream activity to neural responses in the visual cortex by demonstrating how these change under varying visual stimuli as well as in the absence of visual stimulation. While the methodology is solid, the juxtaposition of mouse and monkey data from different modalities and at difference scales limits the interpretability of the observations and forces superficial comparisons. More in-depth focus on either data set in isolation may reveal more nuanced understanding of cortical interactions rather than trying to draw parallels between very different datasets.

eLife Assessment

This valuable work identifies a subpopulation of neurons in the larval zebrafish pallium that responds differentially to varying threat levels, potentially mediating the categorization of negative valence. The evidence supporting these claims is solid; however, the study would be strengthened by more sophisticated analyses of functional imaging results, behavioral confirmation of stimulus valence, and further evidence linking the functionally distinct clusters to their molecular identity. This work will be of interest to systems neuroscientists investigating the circuit-level encoding of emotion and defensive behavior.

eLife Assessment

This important study uses an optimized IOR-Stroop fMRI paradigm to dissociate integration and segregation processes and to show that attentional orienting modulates conflict processing at both the semantic and response levels. The evidence is compelling, supporting the integration-segregation theory of exogenous attention in inhibition of return while also deepening our understanding of how attentional orienting shapes downstream cognitive processing. The work will therefore be of broad interest to researchers in attention and cognitive control.

eLife Assessment

This important study offers insights into the anatomical and physiological features of cold-selective lamina I spinal projection neurons. The evidence supporting the authors' claims is convincing, although including a larger sample size and more quantification would have strengthened the study, and the claims of monosynaptic connectivity would benefit from further experimental evidence. The work will interest those in the field of somatosensory biology, especially researchers studying spinal cord dorsal horn circuits and projection neuron cell types

eLife Assessment

This manuscript presents a valuable analysis of how locomotion modulates the activity of different subtypes of cortical neurons in the mouse primary visual cortex, showing that locomotion more strongly increases responses in sensitizing than in depressing excitatory cells. This data is then used to constrain a model of the responses. While the data are very interesting, the analyses remain incomplete, in particular due to concerns surrounding the modelling.

eLife Assessment

This important study demonstrates that ocular organoids can generate both retina and lens through a non-canonical, "inside-out" morphogenetic route. The work is supported by convincing data, with well-designed experiments combining imaging, molecular analysis, and transcriptomics to establish that lens formation in organoids follows conserved molecular programs despite an alternative morphogenesis. These findings expand our understanding of self-organization and developmental plasticity, and will be of broad interest to researchers working on eye development, organoids, and tissue engineering.

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

eLife Assessment

This potentially valuable manuscript focuses on the phosphorylation of residue T495 as a mechanism to inactivate HSP70 and disrupt cell cycle progression in response to DNA damage. The evidence supporting this model is solid, but would be significantly strengthened by additional studies defining the extent of T495 phosphorylation induced by DNA damage, identifying the kinase responsible for phosphorylating T495 of HSP70, and further elucidation of the functional implications of T495 phosphorylation in human cells. This work will be of interest to scientists focused on topics including chaperone biology, proteostasis, cell cycle progression, and DNA damage.

eLife Assessment

Zandvoort and colleagues have used an innovative approach to study respiration-brain coupling in the context of apnoea in human newborns. This fundamental question is supported with convincing data and analyses. Having addressed all the reviewer comments, there was a general consensus that this work will be of great interest, not only to neonatal clinicians and physiologists, but also broadly to anyone interested in brain-body interactions.

eLife Assessment

This important study shows how stochastic and deterministic factors are integrated in Dictyostelium discoideum to reliably drive determination of distinct cell types despite exposure to nearly identical environmental conditions. The authors present convincing evidence that gene expression variability contributes to the robustness of cell fate decisions, which reveals an unexpected role of stochasticity during cell differentiation.

eLife Assessment

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

eLife Assessment

This manuscript reports an important study in which the authors apply smFRET imaging to probe HIV-1 Env conformational dynamics in the presence of antibodies. Previous implementations of smFRET imaging of HIV-1 Env, which focus on gp120 conformation, have yielded limited information on antibodies that target gp41. Through the cutting-edge application of smFRET imaging, the study provides convincing insights into the mechanisms of action of relevant antibodies.

eLife Assessment

This study provides valuable insights into the cellular dynamics underlying accelerated tooth regeneration in a vertebrate model. Using single-nucleus RNA sequencing across multiple time points, the authors present a well-structured analysis of cell populations, trajectories, and intercellular signaling events associated with this process. The strength of evidence is solid but incomplete, as the conclusions are primarily supported by computational inference, without experimental validation of key findings.

eLife Assessment

This valuable study suggests that capsaicin nanoparticle administration in rats activates the transcription factor Nrf2 by directly binding to its repressor, KEAP1, leading to the induction of cytoprotective genes and preventing alcohol-induced gastric damage, offering a potential avenue for treating alcoholism-related gastric disorders. The authors provide solid evidence through a wealth of biochemical experiments in vitro, in cultured cells as well as in a rat model. The work will be of great interest to researchers studying oxidative damage in a variety of different diseases and the exploitation of molecules for therapeutic approaches.

eLife Assessment

This important paper presents the discovery of the molecular basis of differential apterous expression during early Drosophila wing disc development. The evidence supporting these conclusions is compelling, ranging from classical genetic approaches to state-of-the-art genetic engineering techniques. By opening new questions, this paper is expected to be of broad interest to developmental biologists and geneticists working on transcriptional regulation.

eLife Assessment

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

eLife Assessment

This study provides a valuable contribution to understanding the functional and molecular organization of the medial nucleus accumbens shell in feeding behavior. Through a multimodal approach that integrates in vivo imaging, optogenetic manipulation, and genetic strategies, the authors present convincing evidence for rostro-caudal differences in D1-SPN activity, advancing and refining earlier pharmacological frameworks. The discovery of Stard5 and Peg10 as regionally informative markers, together with the introduction of a Stard5-Flp driver line, establishes a foundation for more targeted circuit dissection. While an expanded characterization of other Stard5-positive cell populations (e.g., D2-SPNs, interneurons) would strengthen the work, the experimental rigor and internal consistency of the findings are clear. Overall, this is a technically strong and conceptually meaningful study with broad relevance for those investigating neural mechanisms of reward, affect, and feeding.

eLife Assessment

This fundamental work advances our understanding of the role of kisspeptin neurons in regulating the luteinizing hormone (LH) surge in females. The study uses cutting-edge techniques to provide compelling and rigorous data supporting a critical role of RP3V kisspeptin neurons in the neuroendocrine LH surge process. This research will be of interest to reproductive biologists and neuroscientists studying the female ovarian cycle. Continuing to examine the complexities of the LH surge and the neuronal populations involved, as done in this study, is critical for developing therapeutic treatments for women's reproductive disorders.

eLife Assessment

This important study tackles an interesting aspect of fungal physiology: how a mitochondria-associated gene influences production of the secondary metabolite DON and fungicide sensitivity. The authors have improved the manuscript and the supporting evidence is convincing.

eLife Assessment

This important study provides convincing data suggesting that subcellular localization of the spatial regulator of cell division, MinD, is an intrinsic feature of the protein's ability to associate with the membrane as both a dimer and a monomer. These findings distinguish the behavior of MinD in B. subtilis from its counterpart in E. coli and suggest that there is not a need to invoke additional localization factors. The reviewers felt that the revisions, particularly the additional experiments and changes to the text to make the experimental design and conclusions clearer, improve the quality of the manuscript and will increase its impact.

eLife Assessment

This study provides important insights into how immune cells in the brain's protective layers behave under normal and disease-like conditions, revealing location-specific activity patterns that may shape inflammation and disorders such as migraine. The evidence is compelling and supported by advanced imaging approaches and rigorous analyses, although some conceptual and interpretational limitations temper the mechanistic depth. Overall, the work will be of broad interest and represents an invaluable contribution to the growing field linking immune and nervous system function.

eLife Assessment

This valuable study shows that locomotion-related modulations in the mouse visual cortex are not uniform but primarily affect neurons in muscarinic receptor-negative patches, which receive projections from specific cortical areas. While the evidence is mostly solid, some uncertainties remain regarding the link between anatomical data and functional measurements. The study should be of interest to neuroscientists interested in state modulation of cortical function.

eLife Assessment

The authors investigate mechanisms of acquired resistance (AR) to KRAS-G12C inhibitors (sotorasib) in non-small cell lung cancer, proposing that resistance arises from signaling rewiring rather than additional mutations. While the study addresses a valuable clinical question, it is limited by several weaknesses in experimental rigor, data interpretation, and presentation, meaning the strength of evidence is incomplete.

eLife assessment

This study provides an important and biologically plausible account of how human perceptual judgments of heading direction are influenced by a specific pattern of motion in optic flow fields known as retinal curl. By combining psychophysical experiments and neural modeling, the authors demonstrate that what was previously considered an incidental "nuisance" signal actually serves as a functional control signal for estimating heading and steering toward a fixated target. While the evidence for the role of curl signals is convincing and advances our understanding of vision-based navigation, the work's impact would be strengthened by situating these findings among other cues that contribute to heading estimation, and by clarifying both the time course of these computations and their generalizability across different navigational contexts.

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. However, the mechanism connecting Gelsolin to skin inflammation presented in this paper is incomplete and requires further investigation. These findings are of interest to the field of skin immunology.

eLife Assessment

This valuable study investigates how multisensory signals influence detection decisions and confidence judgments in presence and absence tasks using pre-registered psychophysical experiments and computational modeling. Across two online samples, the authors argue that audiovisual stimuli improve detection performance but do not enhance metacognitive efficiency, and that confidence is higher for absence than presence judgments. The evidence is broadly solid, although aspects of the computational interpretation and model comparisons would benefit from additional clarification and testing against simpler alternatives.

eLife Assessment

This important study advances a new computational approach to measure and visualize gene expression specificity across different tissues and cell types. The framework is potentially helpful for improving the way gene expression specificity is defined across biological datasets, especially among single-cell datasets. The evidence supporting the method is generally solid, although further evaluation of the method's robustness and comparison to other approaches would strengthen the conclusions.

eLife Assessment

This valuable study introduces an innovative experimental design to address a crucial and timely issue in microbial ecology: the potential bias in soil microbial community analyses caused by extracellular DNA degradation. While the evidence showing variable degradation rates of extracellular DNA is convincing, additional conceptual, methodological, and statistical clarifications could reinforce the claims and the study's contribution to the field. This research will appeal to microbial ecologists and researchers interested in using molecular techniques to evaluate microbial community structure.

eLife Assessment

In this study, the authors use microCT to image an intact hatchling octopus and segment major organ systems, including the vascular, respiratory, digestive, and nervous systems. The resulting dataset is of good quality, and its release through a public web interface is a valuable resource for the community to explore cephalopod mesoscale anatomy. However, the authors claim to have elucidated previously uncharacterized chemotactile pathways from the suckers to the brain, for which there is incomplete evidence, as microCT does not reveal structural connectivity. In addition, the language is often overly complex, obscuring the main points and making it difficult to assess the strength of individual claims. This article would benefit from more cautious framing of the anatomical findings and complementary neuronal tracing experiments to support the proposed pathways.

eLife Assessment

This valuable study investigates the interaction of two integral membrane proteins (Cdhr1a and Pcdh15b) and their roles in cone-rod dystrophy. Convincing evidence using loss-of-function mutants demonstrates clearly that both proteins are required for cone maintenance and survival. Although some evidence (Western blots and cell aggregation assays) demonstrates Cdhr1a and Pcdh15b can physically interact, there is insufficient evidence to support the subcellular localization and the proposed heterodimeric interaction of the two proteins from distinct subcellular compartments in cone photoreceptors.

eLife Assessment

This study provides important insights into how species-specific variation in oxytocin receptor regulatory architecture contributes to diversity in brain expression patterns and social behaviors. By generating multiple BAC transgenic mouse lines carrying the prairie vole oxytocin receptor locus and combining anatomical, molecular, behavioral, and chromatin-structure analyses, the authors present convincing evidence that distal regulatory elements constrain peripheral expression while permitting brain expression aligned with behavior. This study provides an experimental framework and a resource that are of value for dissecting how regulatory variation in neuromodulatory systems contributes to species differences in social behavior. This work will be of interest to those interested in social behavior, oxytocin, neuromodulation, and related conditions.

eLife Assessment

This important study provides a comprehensive multi-omics characterization of Leishmania donovani stage differentiation, offering insights into the molecular basis of parasite adaptation across host environments. The authors present convincing evidence that stage transitions are not driven by genomic variation but instead rely on coordinated post-transcriptional regulation, including mRNA turnover, translation, and protein degradation. Although experimental validation of these findings and conclusions remains to be completed, the integration of diverse, high-quality datasets establishes a robust resource that will be of broad utility to researchers investigating Leishmania biology and life-cycle progression.

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

eLife Assessment

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

eLife Assessment

This important study highlights the role of MIRO1 in regulating mitochondrial oxidative phosphorylation in smooth muscle cells, a process that appears necessary to sustain their proliferation. Overall, the work provides convincing evidence that mitochondrial positioning and function influence vascular disease, although several bioenergetic and mechanistic aspects would benefit from deeper investigation.

eLife Assessment

This study provides valuable insights into how HIV-1 Env modulates the nanoscale organization and dynamics of the CXCR4 co-receptor on T cells, using quantitative imaging and functional approaches, the authors present convincing evidence that gp120 engagement promotes CD4-dependent clustering and altered mobility of CXCR4, distinct from the effects of the natural ligand CXCL12. Some concerns were raised regarding the interpretation of the single-particle tracking analyses, and additional clarification or analysis may help strengthen the conclusions. The physiological relevance of the findings could be further enhanced by validation with infectious virus and by more clearly integrating the CXCR4R334X mutant observations into the central mechanistic narrative. The work will be of interest to researchers studying HIV entry and membrane receptor organization.

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

eLife Assessment

This study presents important findings for the understanding of central brain circuits that underlie nociception-induced escape. Using a laser-based nociception assay, chronic neuronal silencing, trans-Tango anatomical tracing, and reference to connectomic data, the authors propose that nociceptive signals (from painless- and trpA1-expressing neurons) converge on a subset of dopaminergic neurons (subsets of PPL1 and PAM), which in turn engage mushroom body output neurons (MBONs) to shape escape latency. However, methods and controls fall short of fully supporting the findings, rendering the evidence incomplete. This study will be of interest to scientists studying nociception and learning and memory circuits.