eLife Assessment

In this important study, the authors develop a microfluidic "Vessel-on-Chip" model to study Neisseria meningitidis interactions in an in vitro vascular system. Compelling evidence demonstrates that endothelial cell-lined channels can be colonized by N. meningitidis, triggering neutrophil recruitment with advantages over complex surgical xenograft models. This system offers potential for follow-on studies of N. meningitidis pathogenesis, though it lacks the cellular complexity of true vasculature including smooth muscle cells and pericytes.

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

eLife Assessment

Yabaji et al. reports a fundamental study highlighting the mechanistic connection for susceptibility to TB infection via the sst1 locus, this was shown to involve increased IFN and Myc production causing the down-regulation of anti-oxidant defence genes and chronic lipidation. Ultimately, lipid peroxidation may underlie infectivity and macrophage dysfunction. Overall, the data presented are compelling, supported by a well designed multi-omics approach and the findings will be of broad interest to researchers investigating the molecular mechanisms of TB infection.

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

eLife Assessment

This useful study shows that stimuli of a certain size elicit theta oscillations in V1 neurons both in spikes and local field potentials, and monkeys performing a dot detection task on these stimuli show theta rhythmicity in their response times. This replicates previous findings showing rhythmic theta activity in V4 and behaviour when stimuli are presented in the receptive field along with a surrounding flanker stimulus. However, there is incomplete evidence that rhythmicity in neural activity is related to the rhythmicity in behavior, and the mechanisms underlying these oscillations remain unclear.

eLife Assessment

In this useful study, ectopic expression and knockdown strategies were used to assess the effects of increasing and decreasing Cyclic di-AMP on the developmental cycle in Chlamydia. The authors convincingly demonstrate that overexpression of the dacA-ybbR operon results in increased production of c-di-AMP and early expression of the transitionary gene hctA and late gene omcB. Whilst the authors have attempted to revise the submission, the model proposed in the revised manuscript is still not fully supported by the data presented.

eLife Assessment

This valuable study revisits the effects of substitution model selection on phylogenetics by comparing reversible and non-reversible DNA substitution models. The authors provide solid evidence that 1) it can be beneficial to include non-time-reversible models in addition to general time-reversible models when inferring phylogenetic trees out of simulated viral genome sequence data sets, and that 2) non time-reversible models may fit the real data better than the reversible substitution models commonly used in phylogenetics, a finding consistent with previous work.

eLife Assessment

This useful paper presents evidence from several experimental approaches that suggest that changes in membrane potential directly affect ERK signaling to regulate cell division. This result is relevant because it supports an ion channel-independent pathway by which changes in membrane voltage can affect cell growth. The reviewers point out that while some experimental results and interpretations are compelling, the strength of evidence is still incomplete and changes to the manuscript are needed to rule out other possible interpretations of the data.

eLife Assessment

This is a fundamental study providing molecular insight into how cross-talk between histone modifications regulates the histone H3K36 methyltransferase SETD2. The manuscript contains excellent quality data, and the conclusions are convincing and justified. This work will be of interest to many biochemists working in the field of chromatin biology and epigenetics.

eLife Assessment

This study identifies novel approaches to improving transgene expression in the injured mammalian myocardium through a combination of a tissue regeneration enhancer element and engineered AAVs - specifically, a liver-detargeting capsid, AAV.cc84, and an in vivo library screen-selected AAV-IR41. The evidence is convincing, and the AAV vectors are of fundamental value to the field of cardiac gene therapy. Future research exploring how to combine the features of AAV.cc84 and AAV-IR41 could yield an even more promising vector for therapeutic use.

eLife Assessment

This important study provides a conceptual advance in our understanding of how membrane geometry modulates the balance between specific and non-specific molecular interactions, reversing multiphase morphologies in postsynaptic protein assemblies. Using a mesoscale simulation framework grounded in experimental binding affinities, the authors successfully recapitulate key experimental observations in both solution and membrane-associated systems, providing novel mechanistic insight into how spatial constraints regulate postsynaptic condensate organization. The conclusions are supported by solid strength of evidence and the findings are of broad significance for both computational and experimental biologists

eLife Assessment

Kin selection and inclusive fitness have generated significant controversy. This paper reconsiders the general form of Hamilton's rule in which benefits and costs are defined as regression coefficients, with higher-order coefficients being added to accommodate non-linear interactions. The paper is a landmark contribution to the field with compelling, systematic analysis, giving clarity to long-standing debates.

eLife Assessment

The ratio of nuclei to cell volume is a well-controlled parameter in eukaryotic cells. This study now reports important findings that expand our understanding of the regulatory relationship between cell size and number of nuclei. The evidence supporting the conclusions is convincing obtained by applying appropriate and validated methodology in line with current state-of-the-art. The paper will be of broad interest for cell biologists and fungal biotechnologists seeking to understand mechanisms determining cell size and number of nuclei and why this knowledge might also be of importance for the production of enzymes and thus production strains not only of Aspergillus oryzae but also other industrially used fungi.

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 based on the differential interfacial tension hypothesis, and supported by pharmacological perturbations and numerical simulations using the vertex model. The study conveys a key message, but, as it stands, the strength of evidence is incomplete, and a more detailed analysis of the mechanistic origin of the different tensions and better comparison between experiments and simulations would strongly strengthen the message.

eLife Assessment

In this important study, the authors use computational modeling to explore how fast learning can be reconciled with the accumulation of stable memories in the olfactory bulb, where adult neurogenesis is prominent. Their model demonstrates that changes in excitability, plasticity, and susceptibility to apoptosis during the maturation of adult-born granule cells can help resolve the flexibility-stability dilemma. These compelling results provide a coherent picture of a neurogenesis-dependent learning process that is consistent with diverse experimental observations and may serve as a foundation for further experimental and computational studies.

eLife Assessment

This important work sets out to identify the neural substrates of associative fear responses in adult zebrafish. Through a compelling and innovative paradigm and analysis, the authors suggest brain regions associated with individual differences in fear memory. While several findings are well supported, aspects of the interpretation and presentation are partially incomplete, and the manuscript would benefit from adjusting key claims or including additional experiments. Nonetheless, this study showcases the strength of zebrafish for systems-level neuroscience and will be of broad interest to the neuroscience community.

eLife Assessment

This valuable study focuses on defining how the HSP70 chaperone system utilizes J-domain proteins to regulate the heat shock response-associated transcription factor HSF1. Using a combination of orthogonal techniques in yeast, this manuscript provides compelling evidence that the J-domain protein Apj1 facilitates attenuation of HSF1 transcriptional activity through a mechanism involving its dissociation from heat shock gene promoter regions. This work generates new insight into the mechanism of HSF1 transcriptional regulation and is a significant contribution of broad interest to cell biologists interested in proteostasis, chaperone networks, and stress-responsive signaling.

eLife Assessment

This important study provides compelling evidence that fever-like temperatures enhance the export of Plasmodium falciparum transmembrane proteins, including the cytoadherence protein PfEMP1 and the nutrient channel PSAC, to the red blood cell surface, thereby increasing cytoadhesion. Using rigorous and well-controlled experiments, the authors convincingly demonstrate that this effect results from accelerated protein trafficking rather than changes in protein production or parasite development. These findings significantly advance our understanding of parasite virulence mechanisms and offer insights into how febrile episodes may exacerbate malaria severity.

eLife Assessment

This study provides important insights into how the EBH domain of microtubule end-binding protein 1 (EB1) interacts with SxIP peptides derived from the MACF plus-end tracking protein. The revised manuscript includes convincing ITC and NMR experiments that clarify the role of flanking residues and address the influence of dimerization and cooperativity on binding. While some mechanistic aspects remain difficult to resolve experimentally, the data and analysis now more clearly justify the proposed "dock-and-lock" model and its interpretive value. This work will be of interest to structural biologists and biophysicists studying microtubule-associated protein interactions.

eLife Assessment

This useful study develops an individual-based model to investigate the evolution of division of labor in vertebrates, comparing the contributions of group augmentation and kin selection. The model incorporates several biologically relevant features, including age-dependent task switching and separate manipulation of relatedness and group-size benefits. However, the evidence remains inadequate to support the authors' central claim that group augmentation is the primary driver of vertebrate division of labor. Key modelling assumptions-such as floater dominance advantages, the absence of task synergy, and the narrow parameter space explored-restrict the potential for kin selection to produce division of labor, thereby limiting the generality of the conclusions.

eLife Assessment

This study introduces a novel and potentially valuable metric-phenological lag-to quantify the gap between observed and expected phenological shifts under climate warming. While the dataset is extensive and the framework is clearly defined, key assumptions (e.g., base temperature, linear forcing response) are not empirically tested, and the analysis underexplores key spatial and climatic gradients. The strength of evidence is mostly solid but would benefit from further validation and deeper analysis.

eLife Assessment

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

eLife Assessment

This important study identifies and partially characterises two proteins optimised for coordinated peptidoglycan degradation during two spore morphogenesis programs in the bacterium Myxococcus xanthus. The evidence supporting the conclusions is solid, although the description of the data is somewhat overstated. After some editing, the paper will be of interest to those studying peptidoglycan synthesis and reorganisation, which is a central aspect of microbial cell biology.

eLife Assessment

In this manuscript, Chen et al. used cryo-ET and in vitro reconstituted system to demonstrate that the autoinhibited form of LRRK2 can also assemble into filaments on the microtubule surface, with a new interface involving the N-terminal repeats that were disordered in the previous active-LRRK2 filament structure. The structure obtained in this study is the highest resolution of LRRK2 filaments done by subtomogram averaging, representing a major technical advance compared to the previous paper from the same group. This is an important study, especially considering the pharmacological implications of the effect of inhibitors of the protein. The strengths of the data are convincing, but the study would be considerably strengthened if the authors explored the physiological significance of the new interfaces and the incomplete decoration of microtubules described here.

eLife Assessment

This is an important study that demonstrates that blood pressure variability impairs myogenic tone and diminishes baroreceptor reflex. The study also provides evidence that blood pressure variability blunts functional hyperemia and contributes to cognitive decline. The evidence is compelling whereby the authors use appropriate and validated methodology in line with or more rigorous than the current state-of-the-art.

eLife Assessment

This study offers a valuable contribution to our understanding of the role of layer 6b cortical neurons in sleep-wake regulation, providing new insight into how this understudied neural population may regulate cortical arousal via orexin signaling. The evidence supporting these findings is solid, although somewhat constrained by limitations in the specificity of the genetic targeting strategy. Nonetheless, the work introduces new avenues for uncovering how the classical wake-promoting peptide, orexin, exerts its effects on the cortex.

eLife Assessment

In this valuable study, the authors use a cutting-edge method to perform voltage imaging of CA1 pyramidal cells in head-fixed mice running on a track while local field potentials (LFPs) were recorded in the contralateral hemisphere. The authors provide solid evidence of synchronous ensembles of CA1 pyramidal neurons that are associated with contralaterally recorded theta rhythms but not with contralaterally recorded sharp wave-ripples during exploration of a novel environment. The paper will be of interest to scientists who are interested in hippocampal neuronal coding of novel environments, particularly those with experimental questions that can benefit from this cutting-edge imaging technique.

eLife Assessment

This paper reports a valuable discovery that specific-mode electroacupuncture (EA) transiently opens the blood-brain barrier (BBB) in rats. The evidence is solid but lacks functional validation of BBB permeability changes. The work will be of interest to medical scientists working in the field of electroacupuncture and drug delivery.

eLife Assessment

This study presents valuable computational findings on the neural basis of learning new motor memories without interfering with previously learned behaviours using recurrent neural networks. The evidence supporting the claims of the authors is solid, but it would benefit from stronger and clearer links with experimental findings. This work will be of interest to computational and experimental neuroscientists working in motor learning.

eLife Assessment

This important study introduces the Life Identification Number (LIN) coding system as a powerful and versatile approach for classifying Neisseria gonorrhoeae lineages. The authors show that LIN codes capture both previously defined lineages and their relationships in a way that aligns with the species' phylogenetic structure. The compelling evidence presented, together with its integration into the PubMLST platform, underscores its strong potential to enhance epidemiological surveillance and advance our understanding of gonococcal population biology.

eLife Assessment

This study provides valuable insights into microtubule remodeling during liver-stage Plasmodium berghei development, demonstrating that deletion of the alpha-tubulin C-terminal tail impairs parasite growth in mosquitoes and abolishes infection in HeLa cells. The work is technically ambitious, employing advanced microscopy, genetic mutants, and pharmacological approaches. However, key claims are only partially supported due to incomplete evidence linking tubulin modifications to microtubule dynamics and uncertain antibody-based PTM detection.

eLife Assessment

This important work shows that fine particulate matter exposure to the lungs led to nociceptor-dependent neutrophilic inflammation. Likely macrophage-neuronal crosstalk, via release of artemin from macrophages and activation of Gfra3 on the JNC neuron, potentiated the response. The data convincingly strengthens links between pollutants, immune and neural interactions.

eLife Assessment

CCL2 is a chemokine with immune cell chemoattractant properties, and it appears to play a role in several chronic inflammatory diseases. The RNA-binding protein HuR controls the stability and translation of CCL2 mRNA. This paper presents convincing evidence that a relatively common genetic variant tied to several disease phenotypes affects the interaction between the mRNA of CCL2 and the RNA-binding protein HuR. While the experiments cannot definitively distinguish between effects on RNA transcription and stability, CCL2 is thought to be relevant for leukocyte migration in various conditions, including chronic inflammation and cancer, and the study presents important findings that may be relevant to a broad audience.

eLife Assessment

In this important study, the authors engineered and characterised novel genetically encoded calcium indicators (GECIs) and an analytical tool (CaFire) capable of reporting and quantifying various sub-synaptic events, including miniature synaptic events, with a speed and sensitivity approaching that of intracellular electrophysiological recordings. While the evidence supporting the improvements in the speed and accuracy of these tools is convincing, including additional information about key imaging parameters, the Bar8f experiments, and CaFire would strengthen the study. This work will be of interest to neurobiologists studying synaptic calcium dynamics in various model systems.

eLife Assessment

This important study describes a non-canonical role for IκBα in regulating mouse embryonic stem cell pluripotency and differentiation, independent of the classical NF-κB pathway. The conclusions are convincingly supported through orthogonal approaches and separation of function mutants. The findings add new insight into pluripotency regulation in mouse cells.

eLife Assessment

This valuable work shows that subcortically-generated behaviors, like grooming, can have widespread representations in cortical activity. While the evidence is solid, additional analyses are necessary to strengthen the claims associated with outsized cortical representations of grooming onsets, as well as to address atypical grooming events. This work will be of interest to neuroscientists interested in how subcortically-generated behaviors are represented across the cortex.

eLife Assessment

This valuable study applies transcranial direct current stimulation (tCDS) to the prefrontal cortex of non-human primates during two states: (1) propofol-induced unconsciousness; and (2) wakeful performance of a fixation task. The analysis offers incomplete evidence to indicate that the effect of tDCS on brain dynamics, as recorded with functional magnetic resonance imaging, is contingent on the state of consciousness during which the stimulation is applied. The findings will be of interest to researchers interested in brain stimulation and consciousness.

eLife Assessment

This interesting study presents important information on how human cytomegalovirus (HCMV) infection disrupts the activity of the TEAD1 transcription factor, leading to widespread chromatin alterations. The strength of evidence in revised manuscript is convincing, and includes additional functional data teasing out how TEAD1-driven chromatin changes might influence HCMV replication. This work will be of interest to the virology, chromosome biology and transcriptional co-regulation fields.

eLife Assessment

This paper is important in demonstrating a requirement for sulfation in organizing apical ECM (aECM) during tubulogenesis in Drosophila melanogaster. The authors identify and characterize the organization of some of the first known components of the non-chitinous aECM in the Drosophila salivary gland tube, and these findings are supported by convincing data. This study would be of interest to developmental and cell biologists.

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

eLife Assessment

This valuable study combines anatomical tracing and slice physiology to examine how anterior thalamic and retrosplenial inputs converge in the presubiculum, a key region in the navigation circuit. The authors show that near-simultaneous co-activation of retrosplenial and thalamic inputs drives supra-linear presubiculum responses, revealing a potential cellular mechanism for anchoring the brain's head direction system to external visual landmarks. Their thorough experimental approach and analyses provide convincing evidence for the cellular basis of how the brain's internal compass may be anchored to the external world, laying the groundwork for future experimental testing in vivo.

eLife Assessment

This study presents a useful set of experiments to explore how a salivary protein might facilitate planthopper-transmitted rice stripe virus infection by interfering with callose deposition and if fully validated, these findings would significantly advance our understanding of tripartite virus-vector-plant interactions and could be of broad interest to plant science research. The authors provide additional data supporting protein-protein interactions and clarify the transient presence of LssaCA in plants. However, the mechanistic framework remains incomplete, particularly regarding the temporal dynamics of callose function and the sustained effect of LssaCA after virus inoculation. Evidence for the tripartite interaction's functional relevance is still limited, and several critical phenotypic and biochemical details require further substantiation.

eLife Assessment

This paper presents an analysis of demography and selection from whole-genome sequencing of 40 Faroese, with data that are useful beyond the study region. Much of the analysis is solid, but a more fine-scale analysis of demographic history could have led to more interesting findings. In addition, there are concerns about the selection analyses, given the special nature of the studied population and sampling scheme. Finally, lack of data availability limits the broader value of the paper.

eLife Assessment

This valuable study identifies and characterizes probe binding errors in a widely used commercial platform for visualizing gene activity in tissue samples, discovering that at least 21 out of 280 genes in a human breast cancer panel are not accurately detected. The authors provide convincing evidence for their findings validated against multiple independent sequencing technologies and reference datasets. Given the broad adoption of this spatial gene detection platform in biomedical research, this work provides an essential quality control resource that will improve data interpretation across numerous studies.

eLife Assessment

This valuable study reveals the pro-locomotor effects of activating a deep brain region containing diverse range of neurons in both healthy and Parkinson's disease mouse models. While the findings are solid, mechanistic insights remain limited due to the small sample size. This research is relevant to motor control researchers and offers clinical perspectives.

eLife Assessment

Bonnifet et al. present data on the expression and interacting partners of the transposable element L1 in the mammalian brain. The work includes important findings addressing the potential role of L1 in aging and neurodegenerative disease. The reviewers conclude that several aspects of the study are well done and most evidence is solid, with a noted concern related to the RNA-seq analysis.

eLife Assessment

This useful study advances our understanding of how organisms respond to chronic oxidative stress. Using the nematode C. elegans, the authors identified key neuronal signaling molecules and their receptors that are required for stress signaling and survival. The evidence supporting the conclusions is solid, with rigorous genetics, stress response analysis, and transcriptional profiling. This research will be of broad interest to neuroscientists and researchers working in the field of oxidative stress regulation.

eLife Assessment

This important work by Lesser et al provides a first and comprehensive description of Drosophila wing proprioceptors at an EM resolution. By linking peripheral neurons with information on their morphology and connectivity in the central nervous system, the authors provide new hypotheses and tools to study proprioceptive motor control of the wing in the fruit fly. The evidence and techniques supporting this work are solid, and this resource will contribute to connectome-based modeling of fly behavior.

eLife Assessment

This fundamental study identifies specific neural mechanisms through which HIF-1 signaling in ADF serotonergic neurons extends lifespan in C. elegans, revealing that downstream signaling in multiple types of neurons, as well as other neuromodulators like GABA, tyramine, and NLP-17, is required for this effect. The strength of the evidence is largely convincing, as the authors establish the necessity and causality of key neuronal components using multiple genetic tools and functional dissection in a well-validated model organism.

eLife Assessment

This study presents a valuable application of a video-text alignment deep neural network model to improve neural encoding of naturalistic stimuli in fMRI. The authors found that models based on multimodal and dynamic embedding features of audiovisual movies predicted brain responses better than models based on unimodal or static features. The evidence supporting the claims is generally solid, with clear benchmarking against baseline models. The work will be of interest to researchers in cognitive neuroscience and AI-based brain modeling.

eLife Assessment

This important Research Advance builds on the authors' previous work delineating the roles of the rodent perirhinal cortex and the basolateral amygdala in first- and second-order learning. The convincing results show that serial exposure of non-motivationally relevant stimuli influences how those stimuli are encoded within the perirhinal cortex and basolateral amygdala when paired with a shock. This manuscript will be interesting for researchers in cognitive and behavioral neuroscience.

eLife Assessment

This manuscript describes the identification and characterization of 12 specific phosphomimetic mutations in the recombinant full-length human tau protein that trigger tau to form fibrils. This fundamental study will allow in vitro mechanistic investigations. The presented evidence is convincing. This manuscript will be of interest to all scientists in the amyloid formation field.

eLife Assessment

This important work presents a stochastic branching process model of tumour-immune coevolution, incorporating stochastic antigenic mutation accumulation and escape within the cancer cell population. They then used this model to investigate how tumour-immune interactions influence tumour outcome and the summary statistics of sequencing data of bulk and single-cell sequencing of a tumour. The evidence is compelling and the work will be of interest to cancer-immune biology fields.

eLife Assessment

This important study introduces a new class of spectrally tunable, dye-based calcium sensors optimized for imaging in organelles with high calcium concentrations, such as the endoplasmic reticulum and mitochondria. The experimental evidence supporting the applicability of these sensors is convincing, with thorough validation in cultured cells and neurons. The work will be of high interest to researchers studying calcium signaling dynamics in subcellular compartments.

eLife Assessment

This study presents useful findings on the molecular mechanisms driving female-to-male sex reversal in the ricefield eel (Monopterus albus) during aging, which would be of interest to biologists studying sex determination. The manuscript describes an interesting mechanism potentially underlying sex differentiation in M. albus. However, the current data are incomplete and would benefit from more rigorous experimental approaches.

eLife Assessment

This important work advances our understanding of DNA methylation and its consequences for susceptibility to DNA damage. This work presents evidence that DNA methylation can accentuate the genomic damage propagated by DNA damaging agents as well as potentially being an independent source of such damage. The experimental results reported are sound. The evidence presented to support the conclusions drawn is convincing and alternative interpretations are considered. The work will be of broad interest to biochemists, cell and genome biologists.

eLife Assessment

This study presents DeepTX, a valuable methodological tool that integrates mechanistic stochastic models with single-cell RNA sequencing data to infer transcriptional burst kinetics at genome scale. The approach is broadly applicable and of interest to subfields such as systems biology, bioinformatics, and gene regulation. The evidence supporting the findings is solid, with appropriate validation on synthetic data and thoughtful discussion of limitations related to identifiability and model assumptions.

eLife Assessment

This study reveals that female moths use ultrasonic sounds emitted by dehydrated plants to guide their oviposition decisions. It highlights sound as an additional sensory modality in host searching, adding an important piece to the puzzle of how insects and plants interact. Through convincing experimental approaches, the authors provide insights that advance our understanding of plant-insect interactions.

eLife Assessment

IL-10 balances protective and deleterious immune functions in mice and humans, but if IL-10 also controls avian intestinal homeostasis remains unclear. Generating genetic knockouts, Meunier et al. established that a complete lack of IL-10 strengthened immunity against enteric bacteria in chickens, while also aggravating infection-inflicted inflammatory tissue damage and dysbiosis upon parasite infection, but unlike mouse models, IL-10 deficiency did not provoke spontaneous colitis in chickens. The findings presented are valuable, and the strength of evidence is convincing. The observation may have implications for the livestock industry and additional studies involving genetic knockouts may further unravel conserved and distinct avian IL-10 controls.

eLife Assessment

The authors present a software (TEKRABber) to analyze how expression of transposable elements (TEs) and TE silencing factors KRAB zinc finger (KRAB-ZNF) genes are correlated in experimentally validated datasets. TEKRABber is used to reconstruct regulatory networks of KRAB-ZNFs and TEs during human brain evolution and in Alzheimer's disease. The direction of the work is important, with potentially significant interest from others looking for a tool for correlative gene expression analysis across individual genomes and species. However, the reviews identified biases and shortcomings in the pipeline that could lead to an unacceptable number of false positive and negative signals and thus impact the conclusions, leaving the work in its current form incomplete.

eLife Assessment

Axon growth is essential to formation of neural connections. This manuscript presents a useful presentation of a new method for assessing the adhesion strength of axons with the use of a laser-induced shock wave. However, the strength of the evidence is incomplete as critical controls for calibration and time course are lacking.

eLife Assessment

In this useful study, the authors conducted a set of computational and experimental investigations of the mechanism of cholesterol transport in the smoothened (SMO) protein. The computational component integrated multiple state-of-the-art approaches such as adaptive sampling, free energy simulations, and Markov state modeling, providing support for the proposed mechanistic model, which is also consistent with the experimental mutagenesis data. However, substantial revisions are needed for the discussion of the computational results and interpretation of the literature to provide a more balanced and accurate perspective on cholesterol-mediated SMO regulation. In the current form, therefore, the strength of evidence of the study is considered incomplete.

eLife Assessment

This study is valuable for understanding how dysfunctional mitochondria contribute to vascular diseases by investigating the influence of Miro1 on smooth muscle cell proliferation and neointima development. The solid findings collectively indicate that Miro1 regulates mitochondrial cristae architecture and the efficiency of the respiratory chain. Nevertheless, the analysis would benefit from a more thorough assessment of the relationship between Miro1-dependent mitochondrial defects and vascular smooth muscle cell proliferation.

eLife Assessment

This study reports a dynamic association/dissociation between malate dehydrogenase (MDH1) and citrate synthase (CIT1) in Saccharomyces cerevisiae under different metabolic conditions that control TCA pathway flux rate. The research question is timely, the use of the NanoBiT split-luciferase system to monitor protein-protein interactions is innovative, and the significance of the findings is valuable. However, the strength of evidence needed to support the conclusions was found to be incomplete based on a lack of critical control and mechanistic experiments.

eLife Assessment

This useful study analyzed 335 Mycobacterium tuberculosis Complex genomes and found that MTBC has a closed pangenome with few accessory genes. The research provides solid evidence for gene presence-absence patterns which support the appending conclusions however, the main criticism regarding the dominance of genome reduction remains.

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 important work substantially advances our understanding of how accessory olfactory bulb neurons respond to social odor cues across the estrous cycle, showing that responses vary with the strain and sex of the odor source but display no consistent differences between estrous and non-estrous states. It employs a unique electrophysiology preparation that activates the vomeronasal organ pump via electric stimulation, enabling precise recordings of accessory olfactory bulb cell responses to different chemosignals in anesthetized mice. Overall, the study presents convincing findings on the stability and variability of accessory olfactory bulb response patterns, indicating that while accessory olfactory bulb detects social signals, it does not appear to interpret them based on reproductive state. This work will be of interest to those studying olfaction, social behavior, reproductive cycles, and systems neuroscience more broadly.

eLife Assessment

The study presents a valuable resource of proline hydroxylation proteins for molecular biology studies in oxygen-sensing and cell signaling with the characterization of Repo-man proline hydroxylation site. The evidence supporting the claim of the authors is solid, although further clarification of the overall efficiency of the HILIC analysis, the specificity/sensitivity of immonium ion analysis, as well as quantification of proline hydroxylation identifications will be helpful. The work will be of interest to researchers studying post-translational modification, oxygen sensing, and cell signaling.

eLife Assessment

This valuable study advances our understanding of how bactofilin cytoskeletal proteins associate with cell membranes by identifying and characterizing a conserved membrane-targeting sequence. The evidence is solid, with a well-integrated combination of mutagenesis, biophysical analysis, molecular simulations, and bioinformatics supporting the mechanistic model. The work will be of particular interest to microbiologists and structural biologists studying bacterial cytoskeletons and membrane-protein interactions.

eLife Assessment

This manuscript offers valuable structural and mechanistic insights into the structure and assembly of the Type II internal ribosome entry site (IRES) from encephalomyocarditis virus (EMCV) and the translation initiation complex, revealing a direct interaction between the IRES and the 40S ribosomal subunit. While a solid cryo-EM method was used, enhancing the overall resolution or adding complementary biochemical data would further improve the clarity and impact of this study. This manuscript will attract researchers in cap-independent translation, host-pathogen interactions, and virology.

eLife Assessment

This valuable investigation provides new and solid evidence for a specific cognitive deficit in cerebellar degeneration patients. The authors use three tasks that modulate complexity and violations of cognitive expectations. They show specific slowing of reaction times in the presence of violations but not with task complexity. While some alternative interpretations of the results are possible and are discussed, the work provides a new, invaluable data point in describing the cognitive contribution of cerebellar processing.

eLife Assessment

This study provides fundamental insights into eukaryotic phosphate homeostasis by demonstrating how yeast vacuoles dynamically regulate cytosolic phosphate levels. The conclusions are convincing, supported by an elegant combination of in vitro assays and in vivo measurements. This study will be of interest to cell biologists, particularly for those who are working in the field of phosphate metabolism.

eLife Assessment

This important study suggests that adolescent mice exhibit less accuracy than adult mice in a sound discrimination task when the sound frequencies are very similar. The evidence supporting this observation is solid and suggests that it arises from cognitive control differences between adolescent and adult mice. The adolescent period is largely understudied, despite its contribution to shaping the adult brain, which makes this study interesting for a broad range of neuroscientists.

eLife Assessment

This study presents a valuable finding on the representational structure of task encoding in the prefrontal cortex. The evidence supporting the claims of the authors is solid, representing an impressive data collection effort and best-practice fMRI analyses. However, at least including visual regions as a control and controlling for behavioral differences in the task in representation analyses would have strengthened the study. The work will be of interest to cognitive neuroscientists interested in the neural basis of cognitive control.

eLife Assessment

The study introduces new tools for measuring the intracellular calcium concentration close to transmitter release sites, which may be relevant for synaptic vesicle fusion and replenishment. This approach yields important new information about the spatial and temporal profile of calcium concentrations near the site of entry at the plasma membrane. This experimental work is complemented by a coherent, open-source, computational model that successfully describes changes in calcium domains. The conclusions are solid and well supported by the data.

eLife Assessment

This useful study presents a hierarchical computational model that integrates locomotion, navigation, and learning in Drosophila larvae. The evidence supporting the model is solid, as it qualitatively replicates empirical behavioral data, but the experimental data is incomplete. While some simplifications in neuromechanical representation and sensory-motor integration are limiting factors, the study could be of use to researchers interested in computational modeling of biological movement and adaptive behavior.

eLife Assessment

NeuroSC is an accessible and interactive tool for streamlined observation of neuronal morphology, membrane contact, and synaptic connectivity across developmental stages in the nematode C. elegans. This important tool relies on solid electron microscopy datasets. This resource will be of high interest to C. elegans researchers interested in nervous system wiring and circuit function.

eLife Assessment

This valuable study reports convincing evidence about associations between 35 polygenic indices (PGIs) for social, behavioral, and psychological traits, along with some non-fatal health conditions (e.g., BMI) and all-cause mortality in data from Finnish population-based surveys and a twin cohort linked with administrative registers. PGIs for education, depression, alcohol use, smoking, BMI, and self-rated health showed the strongest associations with all-cause mortality, on the order of ~10% increment in risk per PGI standard deviation. Effect sizes from twin-difference analyses tended to be slightly larger than the effect sizes from population cohorts, opposite the pattern generally observed when testing PGI associations with their target phenotypes and supporting robustness of findings to confounding by population stratification.

eLife Assessment

In this valuable study, the authors developed long-term imaging tools to simultaneously monitor the temporal and spatial dynamics of excitatory and inhibitory synapses and reported that excitatory and inhibitory synapses need to develop synergistically during synaptogenesis to maintain balance. While the analysis and quantification of the imaging data are incomplete, there is convincing evidence that the developed tools are feasible. If these tools can function stably in vivo, their applications will be much broader.

eLife Assessment

This paper presents valuable findings on the processing of sound mixtures in the auditory cortex of ferrets, a species widely used for studies of auditory processing. Using the convenient and relatively high-resolution method of functional ultrasound imaging, the authors provide convincing evidence that background noise invariance emerges across the auditory cortical processing hierarchy. They also draw informative comparisons with previously published fMRI data obtained in humans. This work will be of interest to researchers studying the auditory cortex and the neural mechanisms underlying auditory scene analysis and hearing in noise.

eLife Assessment

This valuable study characterises receptors for calcitonin-related peptides from a deuterostomian animal, the echinoderm Apostichopus japonicus, by a combination of heterologous expression, pharmacological experiments, and the quantification of gene-expression levels. The authors provide solid evidence for a functional calcitonin-related peptide system in the sea cucumber, but further work will be needed to confirm the proposed phylogenetic relationships and physiological functions of PDF receptor system in this species. This work should be of interest to scientists studying the signaling pathways, functions, and evolution of neuropeptides, and could be of relevance to improving the culture conditions of this economically key species.

eLife Assessment

This fundamental study examines infection of the liver and hepatocytes during tuberculosis infection. The authors convincingly demonstrate that aerosol infection of mice and guinea pigs leads to appreciable infection of the liver as well as the lung. A further strength of the study lies in clinical evaluation of the presence of tuberculosis bacteria in human autopsied liver samples from individuals with miliary tuberculosis and the presence of a clear granuloma-like structure, which will prompt further study.

eLife Assessment

This study presents an important finding on the role of GATA4 in aging- and OA-associated cartilage pathology. The conclusions are well supported by compelling in vitro and in vivo evidence. This work will be of broad interest to both cell biologists and orthopedic clinicians.

eLife Assessment

This important study reports the conservation of sperm-egg envelope binding by demonstrating successful recognition of the micropyle in fish eggs by mouse sperm. The evidence supporting the conclusions drawn is convincing. This study will be of interest to reproductive biologists and clinicians studying the biology of fertilization and fertility.

eLife Assessment

The article presents important findings on the impact of climate change on odonates, integrating phenological and range shifts to broaden our understanding of biodiversity change. The study leverages extensive natural history data, offering a convincing analysis of temporal trends in phenology and range limit and their potential drivers.

eLife Assessment

This study is a valuable contribution to the field of neuronal modeling by way of providing a method for rapidly obtaining neuronal physiology parameters from electrophysiological recordings. The method is solid as the generated models reproduce both ground-truth simulated data and empirical data, and there is now a quantitative comparison with other approaches.

eLife Assessment

This valuable study investigates the implementation of an efference copy mechanism in the visual flight control system of Drosophila, a topic of broad interest to sensorimotor neuroscientists. Although the behavioral data and computational analyses are each individually solid, there is limited quantitative evaluation of how the model predictions compare to the experimental data.

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 incomplete 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 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 controls and from considering the role of explicit strategies and other brain regions. This work will be of interest to computational and experimental neuroscientists working in motor learning.

eLife Assessment

This useful study replicates a previous finding that information about peripherally presented visual stimuli is represented in the foveal visual cortex, and extends it by demonstrating that these representations are similar to those evoked by foveally presented stimuli. The authors' gaze-contingent fMRI design provides solid evidence for these findings. Some of the stronger theoretical claims, such as that the effects are due to predictive pre-saccadic remapping, are not fully supported by the current results.

eLife Assessment

This important study uses a combination of eye-tracking and computational models based on Active Inference to explain behavior in a gaze-contingent cued-reversal paradigm with 6 - 10-month-old infants. The study demonstrates solid evidence that the same rigorous computational modeling standards commonly applied in studies in adults can also be applied in studies of infants' learning, and a cluster analysis reveals that the parameters of the winning model provide better pattern separation between identified subgroups than behavior or questionnaire data alone. However, the evidence for some specific claims is incomplete, due to poor behavioral performance, unclear significance of the pupil data, and complexity of the model fitting; the claims regarding implications for psychiatry were also considered to be too strong and unsupported by evidence. This work will be of interest to developmental psychologists and cognitive neuroscientists.

eLife Assessment

This valuable study shows the impact of the metabolic state of bacteria on phage infection. The experimental results, based on various phages infecting E. coli, are solid and consistent with a two-step adsorption mathematical model, although the detailed evidence supporting this model is currently incomplete. This study should be of interest to the communities working on cell metabolism and on host-pathogen interactions.

eLife Assessment

Zandvoort and colleagues describe respiration-brain coupling in the context of apnoea in human newborns. The authors have addressed an important question and supported their claims with solid data. The rigor of the findings could perhaps be further strengthened with some relatively minor changes to the analysis methodology.

eLife Assessment

This study presents valuable and compelling evidence that β-glucan-induced trained immunity can protect against intestinal inflammation by reprogramming innate immune cells toward a reparative phenotype. The authors employ a convincing combination of functional assays, adoptive transfers, and single-cell transcriptomics to uncover mechanistic insights and demonstrate the therapeutic potential of innate immune memory in IBD. While the work is robust, addressing the underlying epigenetic mechanisms and including additional controls would further reinforce the trained immunity-specific interpretation.

eLife Assessment

The study by Takagi and colleagues is an important contribution to the question of how homologous neuronal circuits might be wired differently to elicit specific behaviours. The authors combine genetic, neuroanatomical, and behavioral data to provide convincing evidence that Dfz2/DWnt4 signaling controls the innervation pattern of wave command neurons in the fly larva, and thereby behavioral locomotion program selection.

eLife Assessment

This valuable paper describes the crystal structure of a complex of the Sld3-Cdc45-binding domain (CBD) with Cdc45, which is essential for the assembly of an active Cdc45-MCM-GINS (CMG) double-hexamer at the replication origin. The structural and biochemical analyses of protein-protein interactions and DNA binding provided solid evidence to support the authors' conclusion. The results shown in the paper are of interest to researchers in DNA replication and genome stability.

eLife Assessment

This important study provides a description of how single-neuron firing rates in the human medial temporal lobe and frontal cortex are modulated by theta-burst stimulation of the basolateral amydala. The results are supported by convincing evidence obtained from a rigorous task design and analysis of an incredibly rare dataset. The results may help guide future studies incorporating amygdala stimulation to improve patient health.

eLife Assessment

This study presents an important discovery regarding the diversity and evolution of gall-forming microbial effectors. Supported by convincing computational structural predictions and analyses, the research provides insights into the unique mechanisms by which gall-forming microbes exert their pathogenicity in plants. This study also offers guidance that is of value for future studies on pathogen effector function and co-evolution with host plants.

eLife Assessment

This valuable study presents computational analyses of over 5,000 predicted extant and ancestral nitrogenase structures. The data analyses are convincing, it offers unique insights into the relationship between structural evolution and environmental and biological phenotypes. The data generated in this study provide a vast resource that can serve as a starting point for studies of reconstructed and extant nitrogenases.

eLife Assessment

This fundamental study characterizes the mechanics and stability of bolalipids from archaeal membranes using a minimalist, physics-based computational model. The authors present a robust mesoscale model of bolalipids-containing membranes, systematically evaluating it across diverse membrane configurations. The results are compelling, demonstrating that the incorporation of bolalipids and regular bilayer lipids in archaeal membranes significantly enhances membrane fluidity and structural stability.

eLife Assessment

This compelling work describes how the cell cycle-regulating phosphatase subunit, RepoMan, is regulated by the oxygen-dependent, metabolite-sensing hydroxylase PHD1. The characterisation of how proline hydroxylation alters signalling at the molecular and cellular level provides important evidence to enhance our understanding of how 2-oxoglutarate-dependent dioxygenases influence the cell cycle and mitosis.

eLife Assessment

This manuscript presents solid experimental data using Fmr1 knockout mice to explore the fundamental role of Fmr1 in sleep regulation. The study supports the hypothesis that scheduled feeding can improve circadian rhythm and behavior in a mouse model of Fragile X syndrome. These findings may offer new insights into neurodevelopmental disorders and their potential treatment strategies.

eLife Assessment

This study presents an important finding on the signaling mechanisms underlying Treg cell homeostasis by identifying the simultaneous requirement of diacylglycerol (DAG) kinases (DGK) alpha and zeta for Foxp3+ Treg cell function and follicular responses, with implications for the pathogenesis of some autoimmune diseases. Whereas data based on the characterization of double knock-out mice (for DGK alpha and zeta) is solid, showing the emergence of autoimmune manifestations, the study has gaps in its experimental approaches since it is not clear what can be attributed to the simultaneous DKGα and ζ deficiency, versus the individual deficiency of either one. Experiments on the pathogenic potential of the DKO Tregs in the absence of other T-cells were not presented and results on the role of CD25 downregulation and CD28-independent activation of Treg cells were not properly discussed. Nonetheless, the reported data would be of interest to immunologists working on T-cell intracellular signaling and autoimmunity.

eLife Assessment

This important study decoded target-associated information in prefrontal and sensory cortex during the preparatory period of a visual search task, suggesting a memory component of human subjects performing such visual attention task. The evidence supporting this claim is compelling, based on multivariate pattern analyses of fMRI data. The results will be of interest to psychologists and cognitive neuroscientists.

eLife Assessment

This manuscript by Li, Lu et al., presents important findings on the role of cDC1 in atherosclerosis and their influence on the adaptive immune system. Using Xcr1Cre-Gfp Rosa26LSL-DTA ApoE-/- mouse models, these data convincingly reveal an unexpected, non-redundant role of the XCL1-XCR1 axis in mediating cDC1 contributions to atherosclerosis.

eLife Assessment

This important study elucidates the molecular function of the SARS-CoV-2 helicase NSP13, which inhibits the transcriptional activity of the YAP/TEAD complex in vitro and in vivo. The evidence supporting the authors' claims is compelling, based on cell biological assays and multi-omic studies. This work contributes to the understanding of the new regulatory mechanism of YAP/TEAD after SARS-CoV-2 infection and will be of interest to researchers investigating COVID-19 infection and the Hippo-YAP signaling pathway.

eLife Assessment

The study presents valuable theoretical insights by attempting to classify pattern-forming gene subnetworks and exploring their potential mechanisms. However, the results are incomplete, as they rely on oversimplified models, limited classifications, and assumptions that may not hold in more complex or realistic scenarios.

eLife Assessment

This study presents a sequence-based method for predicting drug-interacting residues in intrinsically disordered proteins (IDPs), addressing an important challenge in understanding small-molecule:IDP interactions. The findings have solid support in illustrative examples that underscore the role of aromatic interactions. While predicted binding sites remain coarse, validation was done on a total of 10 IDPs, four of which thoroughly and six others less so. The method builds on previous work from the authors, with necessarily ad hoc modifications, and offers a starting point for further exploration in this emerging field.

eLife Assessment

This work presents valuable new information on the microtubule-binding mode of the microtubule kinesin-13, MCAK, the authors use quantitative single-molecule studies to propose that MCAK preferentially binds to a GDP-Pi-tubulin portion of the microtubule end. However, the evidence provided to support this claim remains incomplete and would benefit from more rigorous methodology particularly the diffraction limited experiments do not provide sufficient spatial resolution to support the authors' conclusions. In addition, a more through discussion of the existing literature would further strengthen the manuscript.

eLife Assessment

By taking advantage of noise in gene expression, this important study introduces a new approach for detecting directed causal interactions between two genes without perturbing either. The main theoretical result is supported by a proof. Preliminary simulations and experiments on small circuits are solid, but further investigations are needed to demonstrate the broad applicability and scalability of the method.

eLife Assessment

This important study reports an advancement in the diagnosis of Animal African Trypanosomosis (AAT), which adapts a CRISPR-based diagnostic tool (SHERLOCK4AAT) to detect different trypanosome species responsible for AAT. The evidence supporting the conclusions is convincing and in line with the current state-of-the-art diagnostics. This study will be of interest to the fields of Epidemiology, Public Health, and Veterinary Medicine.

eLife Assessment

This useful study integrates experimental methods from materials science with psychophysical methods to investigate how frictional stabilities influence tactile surface discrimination. The authors argue that force fluctuations arising from transitions between frictional sliding conditions facilitate the discrimination of surfaces with similar friction coefficients. However, the reliance on friction data from an artificial finger, combined with correlational analyses that fall short of establishing a mechanistic link to perception, renders the findings incomplete.

eLife Assessment

This valuable simulation study proposes a new coarse-grained model to explain the effects of CpG methylation on nucleosome wrapping energy and nucleosome positioning. The evidence to support the claims in the paper looks solid and this work will be of interest to the researchers working on gene regulation and mechanisms of DNA methylation.

eLife Assessment

The authors addressed an important biological question, namely the role of glutamine metabolism in humoral responses, and they obtained solid conclusions. The strength of this study is that the authors used state-of-the-art transgenic mouse models together with in vitro analysis, thereby providing significant insights into the question posed. The following would strengthen the manuscript: i) adding more in-depth functionality/physiological relevance in the discussion part, and ii) regarding the experiments, the inclusion of more appropriate controls and a clearer and more accurate description of the methods.

eLife Assessment

The manuscript presents a valuable finding that CCDC32, beyond its reported role in AP2 assembly, follows AP2 to the plasma membrane and regulates clathrin-coated pit assembly and dynamics. The authors further identify an alpha-helical region within CCDC32 that is essential for its interaction with AP2 and its cellular function. While live-cell and ultrastructural imaging data are solid, future biochemical studies will be needed to confirm the proposed CCDC32-AP2 interaction.

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

eLife Assessment

This study presents a valuable comparison of the efficiency and precision of two prime editing methods to introduce single-nucleotide variants and longer exogenous DNA sequences into the zebrafish genome. Solid data support the conclusion that the PE2 prime editor Nickase is more effective at introducing single-nucleotide variants, while the PEn prime editor nuclease is more effective at integrating short sequences from 3 up to 30 base pairs, for both somatic and germline editing. The results will be of interest to the zebrafish community, in particular to model human disease variants in this model organism.

eLife Assessment

This important study demonstrates that disruption of a common protein-folding system renders drug-resistant clinical bacteria susceptible to antibiotics. The work convincingly shows that targeting protein folding can be used to combat multidrug-resistant pathogens, both by potentiating the efficacy of existing drugs and by therapeutic use of small-molecule inhibitors. This study is significant and timely as it informs on a new strategy that is relevant to microbiologists and clinicians interested in combating antimicrobial resistance.

eLife Assessment

This work represents an important contribution to our understanding of how membrane energetics influence protein conformation and function in mechano-sensitive channels. Through extensive molecular dynamics simulations and energetic analysis, the study convincingly demonstrates how the channel structure is shaped by a balance of protein and membrane-induced forces, effectively reconciling experimental data from different membrane environments. This work will appeal broadly to researchers and readers with interests in ion channel structure and function, mechanosensation, and membrane biophysics.

eLife Assessment

In this revised version, the authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide compelling evidence that the existence of a dense cage-like pericellular structure containing laminin γ1 and α4 and collagen IV is key to fixing the perisinusoidal localization of MK and preventing their premature intravasation. Adhesion of MK to this ECM cage is dependent on integrin beta1 and beta3 expressed by MK. This strong conclusion is based on the use of state-of-the art techniques such as the use of primary murine bone marrow MK cultures, mice lacking ECM receptors, namely integrin beta1 and beta3 null mice, as well as high-resolution 2D and 3D imaging. The study provides valuable insight into the role of cell-matrix interactions in MK maturation and provides an interesting model with practical implications for the fields of hemostasis and thrombosis