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 paper reports a valuable finding that gastric fluid DNA content can be used as a potential biomarker for human gastric cancer. The evidence supporting the claims of the authors is solid, although an inclusion of explanations for the methodological limitations, moderate diagnostic performance, and the unexpected survival correlation would have strengthened the study. The work will be of interest to medical biologists working in the field of breast cancer.

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

eLife Assessment

This study presents important findings demonstrating that the internalization and degradation of FZD5 and FZD8, two of the ten Frizzled proteins, are WNT dependent and do not involve DVL. The evidence supporting the claims of the authors is convincing. This research will be of interest to biologists specializing in Wnt signaling, cancer, and regenerative medicine.

eLife Assessment

This valuable study demonstrates that it is possible to decode information about characters and locations from single-unit responses in the human brain to a narrative movie, using a convincing technical approach to capture information in population-level dynamics. The study introduces an exciting dataset of single-unit responses in humans during a naturalistic and dynamic movie stimulus, with recordings from multiple regions within the medial temporal lobe. Using both a traditional firing-rate analysis as well as a population decoding analysis to connect these neural responses to the visual content of the movie, they show that in this dataset, the decoding of semantic scene features (e.g., the person currently on screen), but not scene transitions, is surprisingly driven by classically non-responsive neurons. Based on these findings, the authors argue that dynamic naturalistic semantic information may be processed within the medial temporal lobe at the population level.

eLife Assessment

This study presents valuable findings by demonstrating that specific GPCR subtypes induce distinct extracellular vesicle miRNA signatures, highlighting a potential novel mechanism for intercellular communication with implications for receptor pharmacology within the field. The data is compelling, however, more evidence is needed to determine whether the distinct extracellular vesicle miRNA signatures result from GPCR-dependent miRNA expression or GPCR-dependent incorporation of miRNAs into extracellular vesicles.

eLife Assessment

In this important manuscript, Ryan et al perform a genome-wide CRISPR based screen to identify genes that modulate TDP-43 levels in neurons. They identify a number of genes and pathways and highlight the BORC complex, which is required for anterograde lysosome transport as one such regulator of TDP-43 protein levels. Overall, this is a convincing study, which opens the door for additional future investigations on the regulation of TDP-43.

eLife Assessment

This important study of regulatory elements and gene expression in the craniofacial region of the fat-tailed dunnart shows that, compared to placental mammals, marsupial craniofacial tissue develops in a precocious manner, with enhancer regulatory elements as primary driver of this difference. The compelling data, including a new dunnart genome assembly, provide an invaluable reference for future mammalian evolution studies, especially once additional developmental time point for the fat-tailed dunnart become available.

eLife Assessment

Seon and Chung investigate changes in own risk-taking behavior, when they are being observed by a "risky" or "safe" player. Using computational modeling and model-informed fMRI, the authors present convincing evidence that participants adjust their choice congruent with the other player's type (either risky or safe). The conclusions of the paper are an important contribution to the field of social decision-making as they show a differentiated adjustment of choices and not just a universally riskier choice behavior when being observed as has been claimed in previous studies.

eLife Assessment

This fundamental study demonstrates that lipid binding can regulate the dimerization state of the SARS-CoV2 Orf9b protein. The data from biophysical and cellular experiments along with mathematical modeling are compelling. This paper is broadly relevant to those studying coupled equilibria across all aspects of biology.

eLife Assessment

This important work describes a set of parameters that give a robust description of shape features of cells in tissues. The evidence for the usefulness of these parameters is solid. The work should be of interest for anybody analyzing epithelial dynamics, but more details about the analysis of experimental images are necessary and some streamlining of the text would increase the accessibility of the material for non-specialists.

eLife Assessment

The study provides valuable technical advances to generate and isolate neural rosettes. The technique is robust, as indicated by both reviewers. The evidence is solid, as shown in orthogonal characterization by flow cytometry, morphology, and scRNA-seq. Comparison with the manual-rosette-picking protocol will enhance the validity of the claims.

eLife Assessment

This study seeks to determine how synaptic relationships between principal cell types in the olfactory system vary with glomerulus selectivity and is therefore valuable to the field. The methodology is solid, and with the caveat that here was a technical need to group all local interneurons, centrifugal neurons and multiglomerular projection neurons into one category ("multiglomerular neurons"), this work reveals some very interesting potential differences in circuit architecture associated with glomerular tuning breadth.

eLife Assessment

The authors collected valuable time-course RNA-seq data from four tree species in natural environments and analyzed seasonal patterns of gene expression. The genome assemblies and gene expression data across multiple species and tissues are convincing, but the overarching conclusions are inadequately supported due to weaknesses in the study design, which encompasses three different environments and two distinct time periods. This makes it impossible to disentangle genetic effects - which are critical for evolutionary inferences - from environmental influences on gene expression.

eLife Assessment

This important study introduces an advance in multi-animal tracking by reframing identity assignment as a self-supervised contrastive representation learning problem. It eliminates the need for segments of video where all animals are simultaneously visible and individually identifiable, and significantly improves tracking speed, accuracy, and robustness with respect to occlusion. This innovation has implications beyond animal tracking, potentially connecting with advances in behavioral analysis and computer vision. While the strength of support for these advances is solid overall, the presentation could be greatly improved for clarity and broader accessibility; in addition, incorporating more standard metrics in the multi-animal tracking literature would better benchmark the approach against other methods.

eLife Assessment

This useful study presents interesting observations on the potential importance of extracellular transport of human papillomaviruses along actin protrusions by retrograde flow. The focus on the events of HPV infection between ECM binding and keratinocyte-specific receptor binding is unique and interesting. However, the evidence supporting the conclusions is incomplete, and additional experimental support is needed. Because conclusions drawn regarding HS interactions are largely based on experiments using a single HS mAb, the specificity of this mAb needs to be described in more detail, either based on the literature or further experimentation.

eLife Assessment

This valuable study provides outlines the mechanism by which repeated vaccination broadens the breadth of antibody responses against epitope unmatched virus strains. The authors' mathematical model is solid and incorporates various parameters that regulate B cell activation and antibody response.

eLife Assessment

This important study by Wu et al presents convincing data on bacterial cell organization, demonstrating that the two structures that account for bacterial motility - the chemotaxis complex and the flagella - colocalize to the same pole in Pseudomonas aeruginosa cells, and expose the regulation underlying their spatial organization and functioning. This manuscript will be of interest to cell biologists, primarily those studying bacteria.

eLife Assessment

This important computational study investigates homeostatic plasticity mechanisms that neurons may employ to achieve and maintain stable target activity patterns. The work extends previous analyses of calcium-dependent homeostatic mechanisms based on ion channel density by considering activity-dependent shifts in channel activation and inactivation properties that operate on faster and potentially variable timescales. The model simulations provide solid evidence for the potential functional importance of these mechanisms.

eLife Assessment

This valuable study demonstrates that D1- and D2-striatal neurons receive distinct cortical inputs, offering key insights into corticostriatal function. For instance, in the context of striatal-dependent learning, this distinction is highly informative for interpreting synaptic physiology data, particularly when inputs to one neuron subtype may change independently of the other. The strength of the evidence is solid, with anatomical and electrophysiological findings aligning well with results from optogenetic and behavioral studies.

eLife Assessment

This fundamental work substantially advances our understanding of the molecular basis by which early symmetry breaking events connect to the following cell fate specifications in preimplantation mammalian embryos. The evidence supporting the conclusions is compelling, with advanced image based assays and microinjection based functional tests. The work will be of broad interest to cell and developmental biologists.

eLife Assessment

This manuscript applies state-of-the-art techniques to define the cellular composition of the dorsal vagal complex in two rodent species (mice and rats). The result is a fundamental resource that substantially advances our understanding of the dorsal vagal complex's role in the regulation of feeding and metabolism while also highlighting key differences between species. The analyses of single-cell profiling experiments in the manuscript provide compelling insight into the cellular architecture of the dorsal vagal complex, with potential implications for obesity therapeutics.

Summary: This article examines the manner in which students are becoming more unable to think critically as a result of overreliance on technology, shortcuts, and AI. It warns that we must reclaim profound thinking and introspection.

eLife Assessment

Cryptovaranoides, an end-Triassic animal (just over 200 Ma old), was originally described as a possibly anguimorph squamate, i.e., more closely related to snakes and some extant lizards than to other extant lizards, making Squamata much older than previously thought and providing a new calibration date inside it. Following a rebuttal and a defense, this fourth important contribution to the debate makes a meticulous and solid argument that Cryptovaranoides is not a squamate. However, further comparisons to potentially closely related animals would greatly benefit this study, and parts of the text require clarification.

eLife Assessment

This revised manuscript provides fundamental findings on how the mouse barrel cortex connects to the dorsolateral striatum, uncovering that inputs from discrete whisker cortical columns are convergent and SPN-specific, but topographically organized at the population level. The evidence supporting this claim is compelling, demonstrating that SPNs uniquely integrate sparse input from variable stretches across the barrel cortex. The study would be of interest to basal ganglia and sensory-motor integration researchers.

eLife Assessment

In this manuscript, the authors describe a software package for automatic differentiation of action potentials generated by excitatory and inhibitory neurons, acquired using high-density microelectrode arrays. The work is valuable as it offers a tool with the potential to automatically identify these neuron types in vitro. It is solid, as it provides a tool to identify putative excitatory and inhibitory neurons on high-density electrode arrays, which can be used in conjunction with other existing spike sorting pipelines.

eLife Assessment

This is a valuable computational study of odor responses in the early olfactory system of insects and vertebrates. The study addresses the question of how information about odor concentration is encoded by second-order neurons in the invertebrate and vertebrate olfactory system; it offers insights into the transformation of neural signals from receptors to second-order neurons. While reanalysis of published data presents solid evidence supporting compression of concentration information, incomplete analysis is provided to resolve how this observation could be reconciled with the need to preserve information about changes in stimulus intensity. This work will be of interest to neuroscientists studying sensory processing broadly and olfaction specifically.

eLife Assessment

This study reports important negative results by showing that genetic removal of the RNA-binding protein PTBP1 in astrocytes is not sufficient to induce their conversion into neurons, challenging prior claims in the field. It also provides a systematic and insightful analysis of the role of PTBP1 in regulating astrocyte-specific splicing. The evidence is convincing, as the experiments are technically robust, rigorously controlled, and supported by both imaging and transcriptomic analyses.

eLife Assessment

The authors developed a fundamental computational method, which is intended to automatically process bioluminescence imaging-derived tumour images across anatomical regions and over time. This allows quantitative analysis of such data, and the authors applied it to describe the spatiotemporal distribution of tumour cells in response to CD19-targeted CAR-T cells that contained either CD28 or 4-1BB costimulatory domains. Some operational limitations were identified, which relate to the pipeline's reliance on predefined regions of interest instead of aligning signal sites with anatomical information, scaling, and not taking animal pose into account. Overall, the authors provide compelling evidence for the functionality of their computational approach towards automated analysis of bioluminescence imaging data, while applying it to a current topic of wide interest in cell therapy research.

eLife Assessment

This fundamental work provides solid evidence that advances our understanding of the physical mechanisms underlying bacterial cell division by examining the role of membrane tension and FtsZ condensation in sequential stages of division. The effect of accDA overexpression on membrane tension was carefully characterized. To further enhance rigor, the authors could consider examining orthogonal perturbations to membrane tension, addressing membrane tension vs. fluidity, and addressing the ability of FtsZ to bend membranes in cells.

eLife Assessment

This important study presents the rational redesign and engineering of interleukin-7. The data from the integrated approach of using computational, biophysical, and cellular experiments are convincing, but this study can further benefit from more quantitative analyses and structural data. This paper is broadly relevant to those studying immunomodulation using biologics.

eLife Assessment

This fundamental study explores a novel cellular mechanism underlying the degeneration of locus coeruleus neurons during chronic restraint stress. The evidence supporting the overexpression of LC neurons after chronic stress is compelling. However, to fully support the broad implications for LC degeneration and Alzheimer's disease, the study would benefit from stronger causal integration and validation in age-relevant models.

eLife Assessment

This study examines a valuable question regarding the developmental trajectory of neural mechanisms supporting facial expression processing. Leveraging a rare intracranial EEG (iEEG) dataset including both children and adults, the authors reported that facial expression recognition mainly engaged the posterior superior temporal cortex (pSTC) among children, while both pSTC and the prefrontal cortex were engaged among adults. However, the sample size is relatively small, with analyses appearing incomplete to fully support the primary claims.

eLife Assessment

This work presents a useful investigation of functional and structural brain changes following navigation and verbal memory training. The analyses of whole-brain structural changes are incomplete and would benefit from a more comprehensive approach to support the study's main conclusion regarding the lack of a structural whole-brain plasticity effect. However, some analyses are exhaustive and compelling in demonstrating the presence of longitudinal behavioural effects, the presence of functional activation changes, and the lack of hippocampal volume changes.

eLife Assessment

This important study fills a gap in our knowledge of the evolution of GPCRs in holozoans, as well as the phylogeny of associated signaling pathway components such as G proteins, GRKs, and RIC8 proteins. The evidence supporting the conclusions is compelling, with the analysis of extensive new genomic data from choanoflagellates and other non-animal holozoans. Overall, the study is thorough and well-executed. It will be a resource for researchers interested in both the comparative genomics of multicellularity and GPCR biology more broadly, especially given the importance of GPCRs as highly druggable targets.

eLife Assessment

This valuable study tested the impact of DNA methylation on CTCF binding in two cancer cell lines. Increased CTCF binding sites are enriched in gene bodies, and associate with nuclear speckles, indicating a role in increased transcription. In the revised work, the inferred association with nuclear speckles has been supported with more solid data. These results will be of interest to the epigenetics field.

eLife Assessment

This important study investigates changes in oscillatory activity across cortical and subcortical areas during stroke recovery in a nonhuman primate model. The authors distinguish between global and local oscillatory bursts, providing solid evidence that these two types of bursts correlate with distinct aspects of movement; additionally, they show that the likelihood of these bursts occurring follows opposing trends during recovery. The study could be further improved by accounting for inter-individual differences and by some technical improvements, such as employing more robust burst detection methods and more stringent analyses.

eLife Assessment

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

eLife Assessment

The article presents important findings of a dissociation between phasic and tonic pain functions in adaptive behavior, combining immersive VR, computational modeling, skin conductance, and EEG data. The methodology used is solid. Its ecological design and sophisticated computational modeling are major strengths. The article would benefit from adding details on hypotheses, VR implementation, sample size determination, modeling, analysis, and pain specificity.

eLife Assessment

This valuable study presents a mouse gastruloid system to generate successive waves of hematopoietic progenitors that in vivo would emerge during embryonic development. Although this newly revised manuscript has addressed some of the concerns raised during the first round of review, the study is still considered incomplete, as the claims are only partially supported. In particular, the claim of definitive wave hematopoietic progenitors being produced in the gastruloids, and their engraftment after transplantation, would benefit from further validation.

eLife Assessment

This valuable study presents findings linking prophage carriage to lifestyle regulation in the marine bacterium Shewanella fidelis, with potential implications for niche occupation within a host (Ciona robusta) and mediation of host immune responses. The study leverages a unique animal model system that offers distinct advantages in identifying select phenotypes to present overall solid evidence that supports findings relating to the impact of a prophage on host-microbe interaction. Understanding the role of integrated lysogenic phages in bacterial fitness, both within a host and in the environment, is a significant concept in bacterial eco-physiology, potentially contributing to the success of certain strains.

eLife Assessment

This work provides valuable insights by introducing a post-translational extrusion mechanism that could reshape how we understand the coupling between DnaA activity and DNA-replication initiation. While solid evidence is presented for some of the key results, other claims rest on indirect proxies and could be improved.

eLife Assessment

This paper reports the development of proteins and small molecules that drive bridge LMO2, an oncogenic transcription factor in T-ALL, to E3 ligases (Cereblon and VHL), and demonstrates their effectiveness in degrading FMO2, causing growth arrest and inducing apoptosis in T cell lines in vitro. The findings are valuable because they provide evidence that intrinsically disordered proteins can be targeted for degradation by PROTAC-type chemicals. The paper also provides a route for rational PROTAC design based on intracellular antibody paratopes. Overall, the paper is supported by solid evidence and will be of interest to chemical biologists and cancer pharmacologists.

eLife Assessment

This well-designed, valuable study uses isotope tracing to analyse how iron limitation alters TCA cycle metabolism in Mycobacterium tuberculosis, revealing potential antibiotic targets for non-replicating bacteria in the host. The findings provide insights into metabolic remodelling under iron-limited conditions. Whilst some of the evidence is solid, the data around the GABA shunt is incomplete, requiring genetic validation, as was done for the glyoxylate shunt. Questions remain about the underlying mechanisms and their specific role in M. tuberculosis pathogenesis.

eLife Assessment

This important paper reports the discovery of calcarins, a protein family that seems to be involved in calcification in the calcareous sponge Sycon ciliatum, significantly enhancing our understanding of the molecular and cellular mechanisms underlying spicule formation in sponges and the evolution of carbonate biomineralization. The conclusions are supported by compelling evidence based on an integrated analysis that combines transcriptomics, genomics, proteomics, and precise in situ hybridization. These findings will be of broad interest to cell biologists, biochemists, and evolutionary biologists.

eLife Assessment

This revised study provides fundamental insights into the differences in migratory primordial germ cells based on their anterior or posterior location. Through convincing methodology and analysis of single-cell RNA sequencing of an exceptionally large number of migratory primordial germ cells and surrounding somatic cells, the novel findings and datasets generated from this study provide many hypotheses of interest to germ cell biologists.

eLife Assessment

This valuable study highlights how the diversity of the malaria parasite population diminishes following the initiation of effective control interventions but quickly rebounds as control wanes. It also demonstrates that the asymptomatic reservoir is unevenly distributed across host age groups. The data presented are convincing and the work shows how genetic studies could be used to monitor changes in disease transmission.

eLife Assessment

This study presents fundamental new findings introducing a new approach for the reprogramming of brain glial cells to corticospinal neurons. The data is highly compelling, with multiple lines of evidence demonstrating the success of this new assay. These exciting findings set the stage for future studies of the potential of these reprogrammed cells to form functional connections in vivo and their utility in clinical conditions where corticospinal neurons are compromised.

eLife Assessment

The authors use a range of techniques to examine the role of Aurora Kinase A (AurA) in trained immunity. The study is hypothesis driven, it uses solid experimental approaches, and the data are presented in a logical manner. The findings are valuable to the trained immunity field because they provide an in-depth look at a common inducer of trained immunity, beta-glucan.

eLife Assessment

This manuscript reports a large series of experiments to investigate specific aspects of plant adaptation, leveraging genetic and genomic resources of Arabidopsis thaliana. The study provides convincing evidence for local adaptation in this highly selfing plant. This is an important dataset contributing to the developing understanding of non-linear selection in plants and beyond.

eLife Assessment

This valuable study provides a 3D standardised anatomical atlas of the brain of an orb-weaving spider. The authors describe the brain's shape and its inner compartments - the neuropils - and add information on the distribution of a number of neuroactive substances such as transmitters and neuropeptides. Through the use of histological and microscopy methods, the authors provide a more complete view of an arachnid brain than previous studies and also present convincing evidence about the organisation and homology of brain regions. The work will serve as a reference for future studies on spider brains and will enable comparisons of brain regions with insects so that the evolution of these structures can be inferred across arthropods.

eLife Assessment

This manuscript presents an in-depth analysis of gene expression across multiple brown algal species with differing life histories, providing convincing evidence for the conservation of life cycle-specific gene expression. While largely descriptive, the study is an important step forward in understanding the core cellular processes that differ between life cycle phases, and its findings will be of broad interest to developmental and evolutionary biologists.

eLife Assessment

This study presents useful findings on how the transient absence of visual input (i.e., darkness) affects tactile neural encoding in the somatosensory cortex. The evidence supporting the authors' claims is incomplete, as key conclusions rely on subtle differences in surface roughness discriminability between sensory conditions, whose physiological underpinnings remain unclear. Potential methodological confounds are also not fully addressed. With additional analyses and methodological clarifications, this work could substantially inform neuroscientists studying cross-modal interactions.

eLife Assessment

This important study addresses how wing morphology and kinematics change across hoverflies of different body sizes. The authors provide convincing evidence that there is no significant correlation between body size and wing kinematics across 28 species and instead argue that non-trivial changes in wing size and shape evolved to support flight across the size range. Overall, this paper illustrates the power and beauty of an integrative approach to animal biomechanics and will be of broad interest to biologists, physicists and engineers.

eLife Assessment

This valuable observational study was conducted in Dar es Salaam, Tanzania, to investigate potential associations between genetic variation in Mycobacterium tuberculosis and human host vs. disease severity. The authors conclude that human genetic ancestry did not contribute to tuberculosis severity and the evidence supporting this is generally convincing. The findings have significance for the understanding of the influence of host/bacillary genetics on tuberculosis disease.

eLife Assessment

This important study shows that the activity of hypothalamic hypocretin/orexin neurons (HONs) correlates with body movement over multiple behaviors. Compelling evidence, supported by sophisticated, cutting-edge tools and data analyses, highlights a link that appears to be unique to HONs. This work should be of interest to scientists studying peptidergic neurons, movement, energy regulation, and brain-body coordination.

eLife Assessment

This manuscript describes a novel approach for assessing cognitive function in freely moving mice in their home-cage, without human involvement. The authors provide convincing evidence in support of the tasks they developed to capture a variety of complex behaviors and demonstrate the utility of a machine learning approach to expedite the acquisition of task demands. This work is important given its potential utility for other investigators interested in studying mouse cognition.

eLife Assessment

This important study explores the power of computational methods to predict lifespan-extending small molecules, demonstrating that while these methods significantly increase hit rates, experimental validation remains essential. The study uses all-trans retinoic acid in Caenorhabditis elegans as a model, providing genetic and transcriptomic insights into its longevity effects. The data are compelling in describing a robust, computationally informed screening process for discovering compounds that extend lifespan in this species.

eLife Assessment

The authors of this important study investigate how telomere length regulates hTERT expression via non-telomeric binding of the telomere-associated protein TRF2. They conclusively show that TRF2 binding to long telomeres results in a reduction in its binding to the hTERT promoter, while short telomeres restore TRF2 binding in the hTERT promoter, recruiting repressor complexes like PRC2, and suppressing hTERT expression. There is convincing support for the claims and the findings should be of broad interest for cell biologists and those working in fields where telomeres alter function, such as cancer and aging.

eLife Assessment

This study provides valuable insights into the anti-senescence effects of enalapril, identifying pSmad1/5/9 signaling and associated antioxidant pathways as key mediators of its physiological benefits in aged mice. The authors present solid experimental evidence across both in vitro and in vivo systems, demonstrating improved organ function and reduced senescence markers following treatment. Overall, the work supports the repurposing potential of enalapril in aging research and expands understanding of its molecular targets.

eLife Assessment

This valuable study provides solid evidence that MgdE, a conserved mycobacterial nucleomodulin, downregulates inflammatory gene transcription by interacting with the histone methyltransferase COMPASS complex and altering histone H3 lysine methylation. There are areas where the evidence could be strengthened, for example, GFP immunoblotting and examining MgdE localization during infection. To enhance impact, the authors could consider Mycobacterium tuberculosis infection experiments and/or reworking the manuscript to emphasize general relevance to microbiologists and cell biologists.

eLife Assessment

This study addresses an important question in sensory neuroscience: how the olfactory system distinguishes decreases in stimulus intensity from decreases in neural responses due to adaptation. Based on a combination of electrophysiological and behavioral analyses, solid evidence establishes that neural coding changes differently between intensity reductions and adaptation, with intensity changes altering which neurons are activated while adaptation preserves the active ensemble but reduces response magnitude. Intriguingly, behavioral responses tend to increase as the neural responses decrease, suggesting that core features of the odor response persist through adaptation. While the experimental results are convincing overall, the conclusions will be strengthened by future work recording behavior and neural dynamics in the same animals.

eLife Assessment

The manuscript is an important study which aims to demonstrate the conserved and crucial role of IgM in both systemic and mucosal antiviral immunity in teleost, challenging the established differential roles of IgT and IgM. The strength of the evidence is solid and supported by a combination of in vivo studies, viral infection models, and complementary in vitro assays. In the current version, authors validate the MoAb against IgM

eLife Assessment

This study presents important findings on the insecticidal mechanism of betulin, a plant-derived metabolite, in controlling the aphid Myzus persicae and it provides a demonstration that betulin targets the GABA receptor in aphids, with strong supporting evidence from transcriptomic, biochemical, electrophysiological, and genetic approaches. In particular, the identification of a specific conserved residue (THR228) critical for betulin binding advances our understanding of insect neuropharmacology and offers translational potential for pest management strategies. The evidence supporting the primary claims is solid, with well-integrated methodologies and appropriate controls; however, some interpretative and methodological limitations remain, including the option to further explore off-target effects, as well as the broader evolutionary and ecological context. Addressing these points would strengthen the broader implications of the study.

eLife Assessment

This valuable study provides evidence supporting a critical role of the axonemal protein ANKRD5 in male infertility. The data generally supports the conclusions and is considered solid, although there are concerns about the cryo-ET analysis. This work will be of interest to biomedical researchers studying ciliogenesis and fertility.

eLife Assessment

The formation of the Z-ring at the time of bacterial cell division interests researchers working towards understanding cell division across all domains of life. The manuscript by Jasnin et al reports the cryoET structure of toroid assembly formation of FtsZ filaments driven by ZapD as the cross linker. The findings are important and have the potential to open a new dimension in the field, and the evidence to support these exciting claims is solid.

eLife Assessment

This important study provides evidence for dynamic coupling between translation initiation and elongation that can help maintain low ribosome density and translational homeostasis. The authors combine single-molecule imaging with a new approach to analyze mRNA translation kinetics using Bayesian modeling. This work is overall solid, but certain key aspects and model assumptions could be strengthened.

eLife Assessment

This important work elucidates the biological processes and detailed mechanisms by which testosterone influences seminal plasma metabolites in mice. The evidence supporting the upregulation of metabolic enzymes and the role of ACLY is solid, highlighting the potential contributions of fatty acids to sperm motility.

eLife Assessment

This important study provides new insights into the lesser-known effects of the sodium-potassium pump on how nerve cells process signals, particularly in highly active cells like those of weakly electric fish. The computational methods used to establish the claims in this work are compelling and can be used as a starting point for further studies.

eLife Assessment

This study offers a valuable contribution to the understanding of how inorganic nutrient transporters, particularly SUL1, influence yeast lifespan through signaling pathways rather than transport functions. The findings suggest a novel link between SUL1 deletion and extended replicative lifespan, supported by transcriptomic and stress-response data. However, the strength of the evidence remains incomplete, with key experiments-such as sulfate supplementation tests, functional autophagy validation, and transport assays-either missing or insufficiently described. As a result, while the manuscript presents promising insights, additional work is needed to robustly support its conclusions.

eLife Assessment

This study presents useful findings that explore the prognostic and immunotherapeutic relevance of specific immune-related genes (CALR, IL1R1, IFNB1, and IFNG) in the bladder cancer tumor microenvironment. While the analysis highlights potentially meaningful associations with survival and treatment response, the strength of evidence is incomplete, as some claims lack sufficient experimental or mechanistic validation. Further refinement and validation of the predictive models would enhance the impact and generalizability of the conclusions.

eLife Assessment

This study describes a genetic screen to identify deubiquitinases (DUBs) that counteract the activity of small-molecule degraders (PROTACs). The presented data are valuable, identifying OTUD6A and UCHL5 as DUBs that impact the efficacy and potency of PROTACs. While the conclusions are broadly supported and the methods employed are solid, the mechanistic depth and validation are incomplete. Overall, these findings merit further evaluation by the targeted protein degradation community when developing and optimizing PROTACs.

eLife Assessment

In this important contribution, Yan and colleagues describe a powerful and compelling strategy to generate concatamers of the BK channel and their fusion constructs with the auxiliary gamma subunits, which allows exploring contributions of individual subunits of the tetrameric channel to its gating and the study of heteromeric channel complexes of defined composition. Distinct examples are presented, which illustrate great diversity in the stoichiometric control of BK channel gating, depending on the site and nature of molecular perturbations. The molecular approaches could be extended to other membrane proteins whose N and C termini face opposite sides of the membrane.

eLife Assessment

This manuscript reports a high-quality genome assembly of the European cuttlefish, Sepia officinalis, a representative species of the Cephalopod lineage. The data are based on current best practices for sequencing and genome assembly, including PacBio HiFi long reads and Hi-C chromatin conformation capture; the analysis is currently in parts incomplete, as further analyses are required to confirm the correct chromosome number. This genome will be a useful resource for the community of researchers interested in cuttlefish biology and comparative genomics in general.

eLife Assessment

This important study systematically investigates the effects of calnexin, an endoplasmic reticulum chaperone, on the drug response of approximately 230 disease-causing variants of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Through deep mutational scanning, interactome profiling, and functional assays, the findings provide convincing evidence that calnexin significantly influences both CFTR expression and the efficacy of corrector drugs in a variant-specific manner. These insights advance our understanding of how cellular quality control machinery shapes the pharmacological responsiveness of CFTR variants, which are broadly relevant for researchers in protein folding and genetic disease therapeutics.

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

The macromolecular organization of photosynthetic complexes within the thylakoids of higher plant chloroplasts has been a topic of significant debate. Using in situ cryo-electron tomography, this study reveals the native thylakoid architecture of spinach thylakoid membranes with single-molecule precision. The experimental methods are unique and compelling, providing important information for understanding the structural features that impact photosynthetic regulation in vascular plants and addressing several long-standing questions about the organization and regulation of photosynthesis.

Editors Assessment:

This paper presents Chevreul, a new open-source R Bioconductor (meta-)package for processing and integration of scRNA-seq data from cDNA end-counting, full-length short-read or long-read protocols. Alongside a R Shiny app for easy visualization, formatting, and analysis for exploratory analyses of scRNA-seq data processed in the SingleCellExperiment Bioconductor or Seurat formats. The name of the tool is inspired by the colour theorist Michel-Eugène Chevreul and the optical illusion of the same name. To demonstrate the use of Chevreul, the authors provide a sample analysis, which helps to demonstrate how users can visualize a wide range of parameters, enabling transparent and reproducible scRNA-seq analyses. Peer review also pushing the author to provide extensive guidance materials to assist with use. Being implemented in R, the R package and integrated Shiny application are freely available under an open-source MIT license in Bioconductor and their GitHub page here: https://github.com/cobriniklab/chevreul

This evaluation refers to version 1 of the preprint

eLife Assessment

This manuscript provides valuable evidence comparing the performance of mathematical models and opinions from experts engaged in outbreak response in forecasting the spatial spread of an Ebola epidemic. The evidence supporting the conclusions is convincing. It will be of interest to disease modellers, infectious disease epidemiologists, policy-makers, and those who need to inform policy-makers during an outbreak.

eLife Assessment

This important work substantially advances our understanding of the interaction among gut microbiota, lipid metabolism, and the host in type 2 diabetes. The evidence supporting the claims of the authors is convincing. The work will be of interest to medical biologists working on microbiota and diabetes.

eLife Assessment

This is a valuable study that explores the role of the conserved transcription factor POU4-2 in the maintenance, regeneration, and function of planarian mechanosensory neurons. The authors provide solid evidence provided by gene expression and functional studies to demonstrate that POU4-2 is required for the maintenance and regeneration of functional mechanosensory neurons in planarians. Furthermore, the authors identify conserved genes associated with human auditory and rheosensory neurons as potential targets of this transcription factor.

eLife Assessment

This study offers useful findings demonstrating the cartilage-protective effects of osteoactivin in inflammatory experimental models. The study provides compelling evidence that osteoactivin may serve as a promising therapeutic target for inflammatory joint diseases.

eLife Assessment

This valuable study investigates the role of HIF1a signaling in epicardial activation and neonatal heart regeneration in mice. Through a combination of genetic and pharmacological approaches, the authors show that stabilization of HIF1a enhances epicardial activation and extends the regenerative capacity of the heart beyond the typical neonatal window following myocardial infarction (MI). However, several aspects of the study remain incomplete and would benefit from further clarification and additional experimental support to solidify the conclusions.

eLife Assessment

This study introduces a useful method to estimate the probability that a malaria case is imported and to identify the geographic origin of parasites by using a Bayesian approach that integrates epidemiological, travel, and genetic data. The authors provide convincing evidence that the approach can reliably identify the main sources of malaria imports. This work will be of great interest to the area of genomic epidemiology and public health strategies aiming to eliminate malaria.

eLife Assessment

This study presents an important finding that ant nest structure and digging behavior depend on ant age demographics for a ground-dwelling ant species (Camponotus fellah). By asking whether ants employ age-polyethism in excavation, the authors address a long-standing question about how individuals in collectives determine the overall state of the task they must perform, and their results may prove to be a key consideration for interpreting results from other studies in the field of social insect behavior. The experimental evidence that the age of the ants and the group composition affect the digging of tunnels is solid, although some aspects of the modeling and certain analyses may benefit from further clarification regarding their added value to the core findings.

eLife Assessment

The medicinal leech preparation is an amenable system in which to understand the neural basis of locomotion. Here a previously identified non-spiking neuron was studied in leech and found to alter the mean firing frequency of a crawl-related motoneuron, which fires during the contraction phase of crawling. The findings are valuable and the experiments were diligently done and generally solid; The results lay a foundation for additional studies in this system.

eLife Assessment

The paper presents a new behavioral assay for Drosophila aggression and demonstrates that social experience influences fighting strategies, with group-housed males favoring high-intensity but low-frequency tussling over aggressive lunging observed in isolated males. This paper is important for researchers studying the impact of social isolation on aggression, while the description of tussling behavior and the interpretation of the link between tussling and mating success are incomplete.