6,717 Matching Annotations
  1. Nov 2024
    1. eLife Assessment

      The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. These potentially important results suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, even though the estrogen responsive enhancer does not loop with the TFF3 promoter. To explain these results, the authors invoke a transcriptional condensate model. The reviewers were split on the strength and interpretation of the evidence presented, which is considered incomplete at this stage. We encourage a revision which buttresses the findings with additional control experiments and careful consideration of alternative explanations and mathematical models. Further, the depth of the discussion on existing literature could be improved. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

    1. eLife Assessment

      In this manuscript, the authors sought to elucidate mechanistic intricacies of inflammatory responses, with emphasis on T cell dysfunction, to S. aureus-induced pneumonia in the context of aging process using Terc deficient mice. Conceptually, the study is very interesting with a set of useful findings. Although some experimental approaches are appropriate, the work as shown in the revised manuscript remains significantly underpowered and the absence of rigorous controls make this study incomplete in support of its claims.

    1. eLife Assessment

      In this useful study, the authors present convincing evidence linking the enzyme D-alanine-D-alanine ligase (Ddl), crucial for cell wall fortification, to organic acid exposure in Staphylococcus aureus. While it's established that organic acids impede bacterial growth, the researchers reveal a novel coping mechanism where S. aureus maintains elevated levels of D-alanine, the substrate for Ddl, to counteract this inhibition. This discovery illuminates a bacterial strategy for organic acid tolerance, offering new insights for microbiologists and potentially informing future antimicrobial approaches.

    1. eLife Assessment

      The authors have developed a robust machine learning approach to predict radio sensitivity in patients with NPC based on a defined gene signature. Some key aspects of this signature have been validated in vitro using relevant cell lines which strengthens the conclusions of this important and convincing study. The publication will be of interest to clinicians working on this indication as well as a more broader readership made up of scientists working on radiation biology and those with a bioinformatics/machine learning background.

    1. eLife Assessment

      This study presents an important finding on durotaxis in various amoeboid cells that is independent of focal adhesions. The evidence supporting the authors' claims is compelling. The work will be of interest to cell biologists and biophysicists working on rigidity sensing, the cytoskeleton, and cell migration.

    1. eLife Assessment

      This study represents a potentially useful tool for extracting quantitative data from intravital microscopy directed at in vivo cancer models. In general, this is an area of interest as accessible non-proprietary tools are needed and some evidence of the tool's utility is provided. However, the work in its current form is incomplete as it is heavily reliant on proprietary software to segment, track, and correct the data. In addition, there are significant reservations regarding the methods used to produce statistics in the software, limiting its applicability and the potential advance over other approaches.

    1. eLife Assessment

      This manuscript reports important findings that the methyltransferase METTL3 is involved in the repair of abasic sites and uracil in DNA, mediating resistance to floxuridine-driven cytotoxicity. The presented evidence for the involvement of m6A in DNA is incomplete and requires further validation with orthogonal approaches to conclusively show the presence of 6mA in the DNA and exclude that the source is RNA or bacterial contamination.

    1. eLife Assessment

      The study identifies the adhesion G-protein-coupled receptor A3 (ADGRA3) as a potential target for activating adaptive thermogenesis in white and brown adipose tissue, providing valuable information for scientists in the field of adipose tissue biology and metabolism. Although the authors have addressed some concerns raised by reviewers, the interpretations remain somewhat limited, and the work is deemed incomplete. The evidence supporting ADGRA3's role in thermogenesis is insufficient, necessitating more rigorous experiments to validate the receptor's relevance in adipose tissue. Additionally, the lack of experiments using primary cultures, despite feedback from multiple reviewers, highlights significant shortcomings.

    1. eLife Assessment

      This manuscript reports important data providing evidence that a 42 amino acid region of Rev7 is necessary and sufficient for interaction with the Rad50-Mre11-Xrs2 complex in budding yeast. The authors conclude that Rev7 inhibits the Rad50 ATPase and the Mre11 nuclease with the exception of ssDNA exonuclease activity. The convincing data largely support the conclusions, although the effect of Rev7 on homologous recombination is less well documented and the observed effect on resection is moderate. Specifically, the result that the Rev7 C-terminal truncation lacking the 42 amino acid region still suppresses homologous recombination is unexpected and unexplained.

    1. eLife Assessment

      The authors established a useful syndetome differentiation protocol from human induced pluripotent stem cells, guided by single-cell transcriptomic analysis. Their findings could significantly impact the field, particularly for patients needing tendon cell therapy. However, the evidence presented is currently incomplete, as the authors did not yet test the applicability of their protocol across multiple human induced pluripotent stem cell lines.

    1. eLife Assessment

      The study describes a link between beta-amyloid monomers, regulation of microglial activity and assembly of neocortex during development. It brings valuable findings that have theoretical and practical implications in the field of neuronal migration, neuronal ectopia and type II lissencephaly. Unfortunately, the evidence is incomplete and the manuscript would benefit from additional experiments to clarify the relationship between Ric8a and APP and bolster the findings.

    1. eLife Assessment

      This important study describes the function of Laminin y1-dependent basement membranes in development of the olfactory placode, including morphogenesis of the placode, boundary formation, and olfactory axonal pathfinding. The study uses elegant live imaging approaches and extensive quantitative analyses, combined with detailed mutant analyses to provide a compelling description of the role of Laminin in olfactory placode development. In addition to the contributions this study makes to understanding olfactory placode development, it will also be of broader interest to individuals studying extracellular matrix regulation of tissue morphogenesis, and neural development including neuronal pathfinding.

    1. eLife Assessment

      This important study suggests that the composition of the extracellular matrix in a mouse model of liver fibrosis changes depending on the cause of liver fibrosis. The data could be used as a foundation for future antifibrotic therapies. The strength of evidence is solid with respect to the use of animal models and proteomic analysis. The study provides a helpful inventory of proteins up or down-regulated, but functional analyses are limited and translational data are lacking.

    1. eLife Assessment

      This study provides valuable insights into the evolutionary histories and cellular infection responses of two Salmonella Dublin genotypes. While the evidence is compelling, a more phylogenetically diverse bacterial collection would enhance the findings. This research is relevant to scientists studying Salmonella and gastroenteritis-related pathogens.

    1. eLife Assessment

      Following up on their previous work, the authors investigated whether cell-to-cell transmission of HIV-1 activates the CARD8 inflammasome in macrophages. This is important given that inflammasome activation in myeloid cells triggers proinflammatory cytokine release. The data are solid and support the idea that CARD8 is activated by the viral protease and promotes inflammation. However, time-course analyses in primary T cells and macrophages and further information on the specific inflammasome involved would further increase the significance of the study.

    1. eLife Assessment

      This valuable study investigates prey capture by archer fish, showing that even though the visuomotor behavior unfolds very rapidly (within 40-70 ms), it is not hardwired; it can adapt to different simulated physics and different prey shapes. Although there was agreement that the model system, experimental design, and main hypothesis are certainly interesting, opinions were divided on whether the evidence supporting the central claims is incomplete. A more rigorous definition and assessment of "reflex speed", more detailed evidence of stimulus control, and a more detailed analysis of individual subjects could potentially increase confidence in the main conclusions.

    1. eLife Assessment

      This study provides evidence that cerebellar projections to the thalamus are required for learning and execution of motor skills in the accelerating rotarod task. This important study adds to a growing body of literature on the interactions between the cerebellum, motor cortex, and basal ganglia during motor learning. The data presentation is generally sound, especially the main observations, with some limitations in describing the statistical methods and a lack of support for two segregated cerebello-thalamic pathways, which is incomplete in supporting the overall claim.

    1. eLife Assessment

      This important study advances our understanding of the way neurons in the auditory cortex of mice respond to unpredictable sounds. Through the use of state-of-the-art recording methods, compelling evidence is provided that responses to local and global violations in sound sequences are prediction errors and not simply the consequence of stimulus-specific adaptation. Although the cell-type-specific results are intriguing, further work is needed to establish their reliability.

    1. eLife Assessment

      This important study partially fills the gap in the knowledge of olfaction at the level of the Anterior Olfactory Nucleus (AON) and Piriform Cortex with functional magnetic resonance imaging, electrophysiology, and modeling. The methods used are convincing. Some of the findings confirm ongoing hypotheses, such as the behavioral importance of AON for odor source discrimination. Other results shed light on the dynamics of the connection between the olfactory system and the rest of the brain.

    1. eLife Assessment

      This important collection of over 800 new cell type-specific driver lines will be an invaluable resource for researchers studying associative learning in Drosophila. Thoroughly characterized and well documented, this collection will permit researchers to selectively target neurons that deliver information to, or receive it from, the memory center of the fly brain called the Mushroom Body. Given the wealth of new drivers and the genetic access they provide to over 300 cell types, this compelling work will be of interest not only to researchers studying the mechanisms of associative learning but more generally to those dissecting sensorimotor circuits in the fly nervous system.

    1. eLife Assessment

      This study compiles a wide range of results on the connectivity, stimulus selectivity, and potential role of the claustrum in sensory behavior. While most of the connectivity results confirm earlier studies, this valuable work provides incomplete evidence that the claustrum responds to multimodal stimuli and that local connectivity is reduced across cells that have similar long-range connectivity. The conclusions drawn from the behavioral results are weakened by the animals' poor performance on the designed task. This study has the potential to be of interest to neuroscientists.

    1. eLife Assessment

      This valuable study investigates the relationship between neuronal dynamics in the thalamus and brain state modulation. The claims that a specific channel is a critical player in the regulation of brain-states and ethanol-resistance in mice are supported by convincing evidence. The work will be of interest to systems neuroscientists interested in brain dynamics and behavioural states.

    1. eLife Assessment

      This important study investigates how AD(H)D affects attention using neural and physiological measures in a Virtual Reality (VR) environment. Solid evidence is provided that individuals diagnosed with AD(H)D differ from control participants in both the encoding of the target sound and the encoding of acoustic interference. The VR paradigm here can potentially bridge lab experiments and real-life experiments. However, the reviewers identified a few potential technical issues that will need to be verified and discussed.

    1. eLife Assessment

      This study describes a new analysis strategy to compare active neurons during behavioral tasks across the brain. This is significant because analysing how different brain areas are active during behavior requires better methods. The evidence provided in support of the method is solid. Although useful now, the work may increase its significance following appropriate revisions.

    1. eLife Assessment

      This study presents an important application of high-content image-based morphological profiling to quantitatively and systematically characterize induced pluripotent stem cell-derived mixed neural cultures cell type compositions. Compelling evidence through rigorous experimental and computational validations support new potential applications of this cheap and simple assay.

    1. eLife Assessment

      This study provides a valuable description of subtypes of V1 neurons, including birthdates and connections to motor neurons. V1 neurons are one of the main groups of inhibitory neurons in the spinal cord. The methods of data collection and analysis are convincing. This work will interest developmental biologists and neuroscientists working on spinal circuits.

    1. eLife Assessment

      This important study investigates the contribution of cytosolic S100A/8 to neutrophil migration to inflamed tissues. The authors provide convincing evidence for how the loss of cytosolic S100A/8 specifically affects the ability of neutrophils to crawl and subsequently adhere under shear stress. This study will be of interest in fields where inflammation is implicated, such as autoimmunity or sepsis.

    1. eLife Assessment

      This valuable study reports the existence of specific spike-timing dependent synaptic plasticity processes at two excitatory synapses of the dentate gyrus granule cells. These synapses link the entorhinal cortex and the dentate gyrus but via different circuits. With state-of-the-art patch-clamp electrophysiological analysis, the authors provide convincing information on the molecular mechanisms underlying these 2 forms of synaptic plasticity showing a critical role for astrocytes in both alongside some features distinctive to each pathway. These results will be of interest to neuroscientists as they uncover detailed plasticity mechanisms involving the hippocampus.

    1. eLife Assessment

      This study is deemed to be an important work that carefully deconstructs multi-faceted conditioned fear behavior in mice. The well-controlled experiments provide convincing data that will be of interest to other researchers in the field.

    1. eLife Assessment

      This valuable modeling study explores how biophysical properties of different interneuron subtypes in the basolateral amygdala (BLA) enable production of oscillations that facilitate functions such as spike-timing-dependent plasticity. Simulated networks provide solid evidence that highlights the importance of interactions between interneurons for some forms of spike-timing dependent plasticity. This work will likely be of interest to investigators studying interactions among interneurons, rhythms in the amygdala, and mechanisms of plasticity thought to underlie associative learning.

    1. eLife Assessment

      This important study demonstrated that ablation of astrocytes in the lumbar spinal cord not only reduced neuropathic pain but also caused microglia activation. The findings presented add considerable value to the current understanding of the role of astrocyte elimination in neuropathic pain, offering convincing evidence that supports existing hypotheses and insights into the interactions between astrocytes and microglial cells, likely through IFN-mediated mechanisms

    1. eLife Assessment

      The study is valuable to the field, introducing a new model to test BM-periosteal stem cell function in vivo. The authors' findings suggested that periosteal stem cells are linked to hematopoietic regeneration. More comparisons with the conventional model and direct examination of periosteal stem cell factors in hematopoietic regeneration are missing. The observations are solid, however, the limitations in their experimental model made the overall impact incomplete; there is potential for improvements to be made in this area.

    1. eLife Assessment

      This study presents important advances in the discovery and assessment of microcins that improve our understanding of their prevalence and roles. The bioinformatics analysis, expression, and antimicrobial assays are solid, although the diverging evaluations also indicated the need for additional support regarding the sequence analysis and validation to fully back some of the claims and conclusions. This study will appeal to researchers working on the discovery and analysis of novel peptide natural products.

    1. eLife Assessment

      This important study aimed to identify how chronic heat exposure affects subsequent behavior and brain function. This work positively expands the field of thermoregulation. The data were collected using a myriad of next-generation approaches, including extensive behavior testing, thermal monitoring, electrophysiology, circuit mapping, and manipulations. As a result the strength of evidence is mostly solid, however a few weaknesses drove the some of the conclusions to be incompletely supported. These largely circle around the question of how unique these effects are to thermal stress (as opposed to other forms of stress), a lack of statistical analyses and rigor in some of the experiments and figures, and the specificity of the POA-pPVT pathway compared to other inputs to the PVT in the control of observed effects.

    1. eLife Assessment

      This valuable manuscript reports a large-scale, data-driven, biophysically detailed model of the non-barrel primary somatosensory cortex and generates numerous predictions that can further our understanding of how the multiscale organization of the cortex shapes neural activity. While the approach is solid, many of the findings are obtained using a much smaller portion of the model, which, together with the broad scope of the work, makes the narrative somewhat confusing and the strength of findings not entirely clear.

    1. eLife Assessment

      This study provides abundant valuable scRNA-Seq data that profiles fibroblasts involved in myocardium and coronary vasculature development. However, the evidence supporting the authors' claims is currently incomplete. The inclusion of additional citations, more in-depth discussions, and further analyses or experiments to validate the scRNA-Seq data would have significantly strengthened the study. Nonetheless, the scRNA-Seq expression data will be a resource that is of value to researchers in the field.

    1. eLife Assessment

      This study presents two main findings regarding HIV-1 genomic integration. The first, based on convincing evidence in primary cell models, is that HIV-1 induces R loop formation, though the viral driver of this process remains undefined. The second, based on model cell systems with limited physiological relevance to HIV-1, is that a portion of HIV-1 genomes integrates in the vicinity of where R loops form. This finding has the potential to offer fundamental insight into HIV-1 integration, but the strength of the presented evidence was viewed as incomplete and needing additional validation by more direct experimental methods in order to understand what the mechanistic relationship between the formation of R loops and HIV-1 integration is.

    1. eLife Assessment

      This useful study presents a biologically realistic, large-scale cortical model of the rat's non-barrel somatosensory cortex, investigating synaptic plasticity of excitatory connections under varying patterns of external activations and characterizing relations between network architecture and plasticity outcomes. While the model demonstrates several interesting phenomena, the results are less explanatory of causal relationships and more observational in nature; hence the evidence supporting the main conclusions remains incomplete.

  2. Oct 2024
    1. eLife Assessment

      This important study explores the interplay between gene dosage and gene mutations in the evolution of antibiotic resistance. The authors provide solid evidence to connect proteostasis with gene duplication during experimental evolution in a model system. If the experiments are found to be rigorous and reproducible, then this paper will be of high interest to other researchers studying antibiotic resistance, proteostasis, and bacterial evolution.

    1. eLife Assessment

      This valuable work explores the timely idea that aperiodic activity in human electrophysiology recordings shows changes in response to task events, which may be relevant for performance, and that these changes could be misinterpreted as oscillatory changes. While it is a timely and interesting topic in principle, in the present form, the analytic approach is incomplete. Further, the data offer inadequate support for the conclusions related to theta without demonstrations that the task evokes theta power. Impressions were split, but there was consensus that the Discussion should be tempered and that revisions would improve the manuscript.

    1. eLife Assessment

      This important study showing that sleep deprivation increases functional synapses while depleting silent synapses supports previous findings that excitatory signaling increases during wakefulness. This manuscript focuses in particular on AMPA/NMDA ratios. An interesting, although speculative, aspect of the manuscript is the inclusion of a model for the accumulation of sleep need that is based upon the MEF2C transcription factor but also links to the sleep-regulating SIK3-HDAC4/5 pathway. The authors have clarified some questions raised in the previous review, but the evidence for major claims was still found to be incomplete, requiring additional experimentation.

    1. eLife Assessment

      This useful study sheds light on the species-specific nature of sperm-oocyte interactions by examining sperm binding and penetration of the zona pellucida across various mammalian species. While the evidence remains incomplete, the authors propose that two distinct mechanisms drive mammalian sperm-oocyte recognition and penetration: a specific, zona pellucida (ZP)-mediated mechanism, and a non-specific, oviductal glycoprotein 1 (OVGP1)-mediated mechanism. Upon revision, this study would offer insights to reproductive biologists, potentially improving porcine in vitro fertilization (IVF) - which is particularly susceptible to polyspermy - and enhancing sperm selection processes in human IVF, ultimately leading to better outcomes in assisted reproduction techniques.

    1. eLife Assessment

      This useful study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the methods used are solid, a limitation of the study, as of any other laboratory-based investigation is the challenge of demonstrating how well measures for fitness related to diapause and its recovery correlates with realities encountered during development in the wild.

    1. eLife Assessment

      This study presents a useful investigation of the use of small, de novo-designed protein binding domains (mini-binders) against the Spike protein of SARS-CoV-2 and EGFR, as ligand binding domains on two classes of synthetic receptors, second-generation synNotch (SNIPR) and CAR. The methods and evidence supporting the focused claims are solid. This work will be of interest to synthetic biologists and cell engineers as a starting point to map out the rules for receptor engineering based on mini-binders and ultimately to advance them in biomedical applications.

    1. eLife Assessment

      The authors developed a method to allow a hypothermic agent, neurotensin, to cross the blood-brain barrier so it could potentially protect the brain from seizures and the adverse effects of seizures. The work is important because it is known that cooling the brain can protect it but developing a therapeutic approach based on that knowledge has not been done. The paper is well presented and the data are convincing.

    1. eLife Assessment

      Fallah et al carefully dissect projections from substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) – two key basal ganglia nuclei – to the pedunculopontine nucleus (PPN), a brainstem nucleus that has a central role in motor control. They consider inputs from these two areas onto 3 types of downstream PPN neurons – GABAergic, glutamatergic, and cholinergic neurons – and carefully map connectivity along the rostrocaudal axis of the PPN. Overall, this valuable study provided convincing data on PPN connectivity with two key input structures that will provide a basis for further understanding PPN function.

    1. eLife Assessment

      This useful manuscript reports on a new mouse model for LAMA2-MD, a rare but very severe congenital muscular dystrophy; the knockout mice were generated by removing exon3 in the Lama2 gene, which results in a frameshift in exon4 and a premature stop codon. These animals lack any laminin-alpha2 protein and confirm results from previous Lama2 knockout models. Additionally, this study includes transcriptomics data that might be a good resource for the field. However, the experimental evidence supporting the main claims of the manuscript is incomplete, citations of previous Lama2 null mice studies are lacking, and both data presentation and interpretation need improvement.

    1. eLife Assessment

      This study makes an important contribution by characterizing the role of the exocyst in secretory granule exocytosis in the Drosophila larval salivary gland. The results are solid and lead to the novel interpretation that the exocyst participates not only in exocytosis, but also in earlier steps of secretory granule biogenesis and maturation. However, the authors are urged to provide additional proof that the exocyst subunit knockdowns were effective and to acknowledge the possibility that inactivation of an essential exocytosis component could indirectly affect other parts of the secretory pathway.

    1. eLife Assessment

      In this important study, the authors use zebrafish to examine protein absorption in the gut. Using a combination of imaging and single-cell RNA-seq, they characterize a population of lysosome-rich enterocytes that are essential for protein uptake. They find that the microbiome impacts the ability of these cells to uptake protein. The RNA-seq provides a rich dataset for future functional experiments, which makes a convincing case for the importance of these cells.

    1. eLife Assessment

      This fundamental study substantially advances our understanding of how habitat fragmentation and climate change jointly influence bird community thermophilization in a fragmented island system. The authors provide convincing evidence using appropriate and validated methodologies to examine how island area and isolation affect the colonization of warm-adapted species and the extinction of cold-adapted species. While minor clarifications regarding the definition of fragmentation could further enhance the presentation, the study is of high interest to ecologists and conservation biologists, as it provides insight into how ecosystems and communities respond to climate change.

    1. eLife assessment

      This proof-of-concept study focuses on an A->G DNA base editing strategy that converts CAG repeats to CAA repeats in the human HTT gene, which causes Huntington's disease (HD). These studies are conducted in human HEK293 cells engineered with a 51 CAG canonical repeat and in HD knock-in mice harboring 105+ CAG repeats. The findings of this study are valuable for the HD field, applying state-of-the-art techniques. However, the key experiments have yet to be performed in neuronal systems or brains of these mice: actual disease-rectifying effects relevant to patients have yet to observed, leaving the work incomplete.

    1. eLife assessment

      This study presents a useful examination of the prevalence of interactions between amino acids from different periods of Earth's history and coenzymes. While the premise of this work is well founded, the data lend themselves to alternative interpretations, suggesting that the main conclusions might be incompletely supported by the findings. The work would benefit from the inclusion of additional supplementary data and further analysis. This manuscript would be of interest to evolutionary biologists and biophysicists.

    1. eLife assessment

      This is a valuable study of the mechanisms of microtubule organization in pancreatic islet beta cells that enable optimal insulin secretion. Using a combination of live imaging and photo-kinetic assays in an in vitro culture system, the authors provide solid evidence to demonstrate that kinesin-1-mediated microtubule sliding, which has previously been known from neurons and embryos, is essential for establishing the sub-membranous microtubule band in response to glucose levels in beta cells. The inclusion of an animal model or primary cells, as well as data on the physiological relevance of the finding, would have strengthened the study. The work will be of interest to cell biologists studying cytoskeletal dynamics and organelle trafficking and to translational biologists working on diabetes.

    1. eLife Assessment

      In this valuable paper, the authors created a reporter mouse line in which the Axon Initial Segment (AIS) is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro, ex vivo, and in vivo, the authors convincingly document that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. They further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks.

    1. eLife Assessment

      This in several parts valuable study confirms the roles of Dact1 and Dact2, two factors involved in Wnt signaling, during zebrafish gastrulation and demonstrates their genetic interactions with other Wnt components to modulate craniofacial morphologies. Unfortunately, there are several limitations associated with the study, making it challenging to distinguish the primary and secondary effects of each factor, and their roles in craniofacial morphogenesis. The findings of a new potential target of dact1/2-mediated Wnt signaling are potentially of value; however, experimental evidence supporting their functional significance remains incomplete due to inconsistent results and limitations inherent to the overexpression approach.

    1. eLife Assessment

      This important work presents a consolidated overview of the NeuroML2 open community standard and provides convincing evidence for its central role within a broader software ecosystem for the development of neuronal models that are open, shareable, reproducible, and interoperable. A major strength of the work is the continued development over more than two decades to establish, maintain, and adapt this standard to meet the evolving needs of the field. This work is of broad interest to the sub-cellular, cellular, computational, and systems neuroscience communities undertaking studies involving theory, modeling, and simulation.

    1. eLife Assessment

      This useful study uses an intranasal mouse infection model with Streptococcus suis, a gram-positive bacterial pathogen that causes severe losses in pigs around the world. The manuscript provides insights that the capsular polysaccharide, one of the virulence factors of this pathogen, contributes to tissue dissemination and neurotropism in the host. However, the evidence is currently incomplete, and further experiments and careful interpretation of the current results and methods used are necessary to support the conclusions of the manuscript.

    1. eLife Assessment

      A regression discontinuity analysis finds essentially no effect of 1 additional year of secondary education on brain structure in adulthood. This is a valuable finding that adds to the literature on the impact of education on brain health. The evidence presented is solid, with strengths including methodological novelty as well as principled study design; the impact is, however, limited as the manipulated variable only relates to a single additional year of education (remaining in education to 15 vs 16 years of age). The interpretation is further missing discussion of the healthy volunteer bias of the UK Biobank sample, amplified in the imaging extension.

    1. eLife Assessment

      This is an important study examining the role of conserved PCH-2 protein at different stages of C. elegans meiosis. The authors use elegant molecular genetic approaches to provide convincing evidence to support their claims. The work will be of interest to scientists studying meiosis, DNA recombination, and chromosome segregation.

    1. eLife Assessment

      The manuscript provides important new insights into the mechanisms of statistical learning in early human development, showing that statistical learning in neonates occurs robustly and is not limited to linguistic features but occurs across different domains. The evidence is convincing, although an additional experimental manipulation with conflicting linguistic and non-linguistic information as well as further discussion about the linguistic vs non-linguistic nature of the stimulus materials would have strengthened the manuscript. The findings are highly relevant for researchers working in several domains, including developmental cognitive neuroscience, developmental psychology, linguistics, and speech pathology.

    1. eLife Assessment

      This paper contains valuable ideas for methodology concerned with the identification of genes associated with disease prognosis in a broad range of cancers. However, there are concerns that the statistical properties of MEMORY are incompletely investigated and described. Further, more precise details about the implementation of the method would increase the replicability of the findings by other researchers.

    1. eLife Assessment

      The study is important - not only for its comprehensive transcriptomic analysis of the developmental trajectory of syncytiotrophoblasts (STBs), but also for its comparative evaluation of primary human placental tissues and two human trophoblast organoid models. The study highlights the utility of these organoid models in advancing research on human STB biology. The conclusions of this work are supported by compelling analyses and experimental evidence.

    1. eLife Assessment

      This valuable study uses robust time-dependent microscopy assays to show that during HIV-1 infection, the viral accessory protein Vif causes cell cycle arrest during metaphase and not G2/M as previously thought. The conclusions are convincing in the context of the immortalized cellular models used, and they serve as a starting point to determine whether Vif-dependent regulation of the cell cycle modulates HIV-1 replication and pathogenesis in more physiologically relevant primary cells or in vivo.

    1. eLife Assessment

      This important work investigates the mechanism that underlies the switch between feeding and mating behaviors in the oriental fruit fly, Bactrocera dorsalis. Using a variety of approaches, the authors show that this switch is mediated by the neuropeptide, sulfakinin, acting peripherally through the sulfakinin receptor 1 to regulate the expression of antennal odorant receptors. The evidence is solid in support of the hypothesis that sulfakinin signaling mediates changes in the periphery, although additional experimental details would strengthen these claims.

    1. eLife Assessment

      Shen et al. present a computational account of individual differences in mouse exploration when faced with a novel object in an open field from a previously published study (Akiti et al.) that relates subject-specific intrinsic exploration and caution about potential hazards to the spectrum of behaviors observed in this setting. Overall, this computational study is an important contribution that leverages a very general modeling framework (a Bayes Adaptive Markov Decision Process) to quantify and interrogate distinct drivers of exploratory behavior under potential threat. Given their assumptions, the modeling results are convincing: the authors are able to describe a substantial amount of the behavioral features and idiosyncracies in this dataset, and their model affords a normative interpretation related to inherent risk aversion and predation hazard "flexibility" of individual animals and should be of broad interest to researchers working to understand open-ended exploratory behaviors.

    1. eLife Assessment

      This useful study examines the function of the rnc gene, which encodes the RNase III ribonuclease, as it relates to virulence of Salmonella Enteritidis. The authors demonstrate that the rnc gene is markedly upregulated in strains proposed to exhibit high virulence and that the product of the rnc gene promotes the expression of SodA, which contributes to the survival of Salmonella Enteritidis in the face of oxidative stress. The study also suggests that elevated levels of rnc gene expression assist Salmonella Enteritidis in evading immune responses by diminishing the presence of accumulated double-stranded RNA (dsRNA), although the evidence substantiating this and the above assertions remains incomplete.

    1. eLife Assessment

      The authors propose that positive biodiversity-ecosystem functioning relationships found in experiments have been exaggerated because commonly used statistical analyses are flawed. To remedy this, a new type of analysis based on a concept of "partial density monoculture yield" is proposed. However, the presented concept and analysis methods are not reproducibly described, do not appear to be complete, and are inadequate for hypothesis testing. The reviewers found that the authors misinterpret current research in the field and made limited efforts to understand or address the reviewer comments on a previous version of the study.

    1. eLife Assessment

      The authors present an important theoretical framework that describes the interplay between liquid-liquid phase separation and protein aggregation within a mean-field model. This work will be of high interest to the biophysics and molecular biology communities, as it will help understand and analyse assembly within biomolecular condensates in cells or in-vitro. Major strengths of this convincing work are the consideration of aggregates with various dimensionality and the possibility for protein gelation.

    1. eLife Assessment

      This valuable study provides an experimental paradigm and state-of-the-art analysis method for studying the existence of call types and transition differences among Mongolian gerbil families in a naturalistic environment. The analyses are convincing, with a thorough treatment of the acoustic data and a demonstration of the robustness of the observed effect across days. The work will likely be of interest to the auditory neuroscience and neuroethology communities.

    1. eLife Assessment

      This valuable study investigates evolutionary aspects around a single amino acid polymorphism, known to be under long-term balancing selection, in an immune peptide of Drosophila melanogaster. Using alleles with different substitutions, the investigators demonstrate that while one allele provides better survival after systemic infections by a bacterial pathogen, the alternative allele endows its carriers with a longer lifespan under certain conditions. The authors suggest that these contrasting fitness effects of the two alleles contribute to balancing their long-term evolutionary fate. While the work is very interesting, the strength of the provided evidence is still incomplete, and the study would benefit from more rigorous approaches.

    1. eLife Assessment

      This manuscript addresses infections of the parasite Taenia solium, which causes neurocysticercosis (NCC). NCC is a common parasitic infection that leads to severe neurological problems. It is a major cause of epilepsy, but little is known about how the infection causes epilepsy. The authors used neuronal recordings, imaging of calcium transients in neurons, and glutamate-sensing fluorescent reporters. A strength of the paper is the use of both rodent and human preparations. The results provide convincing evidence that the larvae secrete glutamate and this depolarizes neurons. Although it is still uncertain exactly how epilepsy is triggered, the results suggest that glutamate release contributes. Therefore, the paper is a fundamental step towards understanding how Taenia solium infection leads to epilepsy.

    1. eLife Assessment

      This study presents a valuable new method for probing the DNA and proteins associated with targeted genomic elements in cells. The authors present solid evidence that the method can map DNA-DNA interactions for individual loci and can detect enriched proteins at repetitive DNA loci such as telomeres, but benchmarks of the method's resolution and specificity remain incomplete. The methodological details of this study will be of particular interest and utility to chromatin biologists.

    1. eLife Assessment

      This valuable paper describes the crystal structure of a complex of Sld3-Cdc45-binding domain (CBD) with Cdc45, which is essential for the assembly of an active Cdc45- MCM-GINS (CMG) double hexamers at the replication origin. Although the results shown in the paper are of interest to researchers in DNA replication and genome stability, the biochemical analysis of protein-protein interaction and DNA binding is incomplete, and the paper needs additional data and revised discussion.

    1. eLife Assessment

      The aim of this useful study is to investigate the role of semilunar granule cells on memory engrams in the dentate gyrus. Which cells get recruited during contextual memory processing is a timely and significant question. However, evidence for the study's major conclusions is currently incomplete due to caveats in study design, technical limitations, and missing controls.

    1. eLife Assessment

      This study offers a valuable genomic dataset, analyses, and functional studies on gonadal sex determination and development. The work addresses long-standing questions regarding the role of the Drosophila sex determination hierarchy, sex chromosomes, and the interaction between the sex determination hierarchy and sex chromosome composition in gonad development. Although this convincing work has been conducted rigorously, the authors missed some key opportunities in their analysis.

    1. eLife Assessment

      The study presents important findings that reveal SEPHS2 and VPS37C as new potential drug targets for dasatinib and hydroxychloroquine respectively in addition to confirming known targets of these drugs. The evidence provided is solid, however, some of the claims are not fully supported by the data. To enhance the conclusions and readability, the writing clarity, data analysis and justification of experimental design rationale need to be worked on to enhance the study's interest among chemical biologists, biochemists, and scientists in drug discovery.

    1. eLife Assessment

      This valuable paper shows image correlation spectroscopy (ICS) as a new tool to analyze the clustering of proteins involved in DNA damage response (DDR). The solid evidence presented demonstrates that this method is more sensitive than traditional focus counting, although some of the claims require further contextualization. This new method provides an alternative tool to analyze immuno-stained focus for researchers in the fields of DDR and cell biology.

    1. eLife Assessment

      This important study provides a comprehensive analysis of how substitutions within the catalytic domain of the tyrosine kinase Met affect its sensitivity to inhibition by ATP-competitive, small molecule inhibitors and provides a mechanistic framework for understanding drug resistance. The evidence supporting the authors' claims is convincing, the data sets are comprehensive, and the analyses are rigorous. This work will be of broad interest to biochemists, structural biologists, and medicinal chemists.

    1. eLife Assessment

      This important study leverages an impressive and comprehensive longitudinal 16S microbiome dataset from baboons to provide insights regarding the use of a microbiome-based clock to predict biological age, with solid evidence for age-associated microbiome features and environmental and social variables that impact microbiome aging. This study of microbiomes as markers of host age will be relevant to a broad range of researchers, especially those interested in alternatives to measuring biological aging.

    1. eLife Assessment

      This is a valuable report of tracheal terminal cells (TTCs) in Drosophila being immune privileged. The authors demonstrated that TTCs lack the expression of membrane-associated peptidoglycan recognition receptor PGRP-LC, which protects these cells from activating immune pathway or JNK-mediated cell death to maintain TTC homeostasis. While genetic experiments using RNAi and overexpression are mostly convincing, the data on the expression of PGRP-LCx and cell death phenotypes following immune activation are currently incomplete. The work will be of interest to researchers in innate immunity across various model systems.

    1. eLife Assessment

      Ulcerative colitis (UC) is a chronic gut inflammatory condition affecting the colon in humans. This study uses human samples as well as a mouse model of colitis induced by a chemical, DSS, to investigate the role of an immune marker, CD131, in UC pathogenesis. The study, as presented, is incomplete, as experimental details are lacking, the statistical analyses are deficient, and there is not yet direct evidence for a CD131-mediated mechanism of gut inflammation.

    1. eLife Assessment

      This useful study presents the first detailed and comprehensive description of brain sulcus anatomy of a range of carnivoran species based on a robust manual labeling model allowing species comparisons. Although the database is recognized and the method for reconstructing cortical surfaces is convincing, the evidence supporting the conclusions is incomplete due to the lack of appropriate quantitative measurements and analyses. Considering additional specimens to assess intraspecies variations, as well as exploring the functional correlates of interspecies differences would increase the scope of the study. Setting an instructive foundation for comparative anatomy, this study will be of interest to neuroscientists and neuroimaging researchers interested in that field, as well as in brain morphology and sulcal patterns, their phylogeny, and ontogeny in relation to functional development and behaviour.

    1. eLife Assessment

      This important paper by Lechler and colleagues describes the transcriptomic signature and fate of intermediate cells (ICs), a transient and poorly defined embryonic cell type in the skin. The paper convincingly shows through lineage tracing that ICs are granular and not spinous cell precursors, and through ectopic expression in vivo, that cell contractility, a mechanical feature of ICs, lies upstream of differentiation.

    1. eLife Assessment

      This valuable study shows that eliminating a large portion of the principal neurons in the mammalian olfactory bulb does not affect the initial establishment of the circuit but has an impact on its maintenance. The strength of the paper is that the anatomical changes induced by genetic ablation of neurons are clear-cut. There is solid support for the findings, with a description of the structural and behavioral effects of ablating the majority of M/T neurons.

    1. eLife Assessment

      This study presents a valuable finding on a potential signaling pathway responsible for the direct effects of nicotine on intestinal stem cell growth and tumorigenesis.  The evidence supporting the claims of the authors is solid. This research will be of interest to medical biologists specializing in intestinal tumors.

    1. eLife Assessment

      This study provides an important re-evaluation of modality-specific information processing in the thalamus of trained mice. Using an elegant task design that probes competing tactile and visual stimuli, the authors present compelling evidence that behavioral training reshapes the sensitivity of higher-order thalamic nuclei. Despite the powerful task design and the significance of the main findings, the origin of the cross-modal responses remains an open question and requires future investigation.

    1. eLife Assessment

      This paper addresses an important topic (normative trajectory modelling), seeking to provide a method aiming to accurately reflect the individual deviation of longitudinal/temporal change compared to the normal temporal change characterized based on a pre-trained population normative model. The evidence provided for the new methods is, however, incomplete, with the simulations validating the method needing to be extended.

    1. eLife Assessment

      This article presents valuable 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 combined analysis of temporal trends in phenology and distribution and their potential drivers. The support for the findings is solid, though additional clarification regarding the methods and alternative sensitivity analyses could make the conclusions stronger.

    1. eLife Assessment

      This study poses an important step forward in understanding the brain-network embedding of beta oscillations. The study advances our circuit-level understanding of the pathophysiology associated with dopaminergic alterations in psychiatric or neurological disorders. The study provides compelling evidence that beta oscillations across the neocortex and basal ganglia map onto shared functional and structural networks that show significant positive correlations with dopamine receptors.

    1. eLife Assessment

      This important study substantially advances our understanding of nocturnal animal navigation and the ways that animals use polarized light. The evidence supporting the conclusions is convincing, with elegant behavioural experiments in actively navigating ants. The work will be of interest to biologists working on animal navigation or sensory ecology.

    1. eLife Assessment

      This important study presents a statistical framework for the analysis of photometry signals and provides an open-source implementation. The evidence supporting the benefits of the presented functional mixed-effect modeling analysis as opposed to 1) summary statistics and 2) other pointwise regression models is convincing with a thorough comparison with other methods and datasets. This work will be of great interest to researchers using not only fiber photometry, but other time-series data such as calcium imaging or electrophysiology data, and wanting to implement trial-by-trial temporal analysis, taking also into account variability within the dataset.

    1. eLife Assessment

      This valuable study is a companion to a paper introducing a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs). The evidence that recurrent SNVs or CDNs are common in true cancer driver genes is convincing, with more limited evidence that many more undiscovered cancer driver mutations will have CDNs, and that this approach could identify these undiscovered driver genes with about 100,000 samples.

    1. eLife Assessment

      This important paper introduces a theoretical framework and methodology for identifying Cancer Driving Nucleotides (CDNs), primarily based on single nucleotide variant (SNV) frequencies. A variety of solid approaches indicate that a mutation recurring three or more times is more likely to reflect selection rather than being the consequence of a mutation hotspot. The method is rigorously quantitative, though the requirement for larger datasets to fully identify all CDNs remains a noted limitation. The work will be of broad interest to cancer geneticists and evolutionary biologists.

    1. eLife Assessment

      The authors proposed an important novel deep-learning framework to estimate posterior distributions of tissue microstructure parameters. The method shows superior performance to conventional Bayesian approaches and there is convincing evidence for generalizing the method to use data from different protocol acquisitions and work with models of varying complexity.

    1. eLife Assessment

      The manuscript reports a valuable finding on dopamine receptor-mediated regulation, the firing of striatal cholinergic interneurons in both healthy and dyskinesia states, identifying that Kv1 channels play a key role in the burst-dependent pause. The study presents solid experimental data, and provides additional mechanistic insights into how burst activity in SCINs leads to a subsequent pause, highlighting the involvement of D1/D5 receptors. This work will be of interest to researchers studying the pathological mechanisms of Parkinson's disease.

    1. eLife Assessment

      This study introduces a novel method for estimating spatial spectra from irregularly sampled intracranial EEG data, revealing cortical activity across all spatial frequencies, which supports the global and integrated nature of cortical dynamics. The study showcases important technical innovations and rigorous analyses, including tests to rule out potential confounds; however, the lack of comprehensive theoretical justification and assumptions about phase consistency across time points renders the strength of evidence incomplete. The dominance of low spatial frequencies in cortical phase dynamics continues to be of importance, and further elaboration on the interpretation and justification of the results would strengthen the link between evidence and conclusions.

    1. eLife Assessment

      The authors show MRI relaxation time changes that are claimed to originate from cell membrane potential changes. This would be very important if true because it may provide a mechanism whereby membrane potential changes could be inferred noninvasively. However, the membrane potential manipulations applied here will induce cell swelling, and cell swelling has been previously shown to affect relaxation time. Therefore, the claim that the relaxation time changes observed in this manuscript are due to cell membrane potential changes is inadequately supported.

    1. eLife Assessment

      The authors have provided a valuable addition to the literature on large-scale electrophysiological experiments across many labs. The evidence that the authors provided was incomplete - while some comparisons with analyses outside of the manuscript's approaches were provided, a more complete manuscript would have compared with alternative standardized analyses. In particular, alternative spike sorting metrics and the alternative of GLM-based analysis of data would have made the interpretation of the results clearer.

    1. eLife Assessment

      In this paper, 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 solid 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.

    1. eLife Assessment

      In this useful study, the authors tested a novel approach to eradicating HIV reservoirs by constructing a herpes simplex virus (HSV)-based therapeutic vaccine and evaluating efficacy in experimental infections of chronically SIV-infected, antiretroviral therapy (ART)-treated macaques. While mean viremia at rebound was lower in the HSV vaccine-treated group, the evidence presented appears to be incomplete, as the group size was small and the viral load at rebound was highly variable. This is a revised paper, but the support for the conclusions, particularly the effect of the HSV-vectored therapeutic vaccine on the SIV reservoir in the SIV-infected macaques, remains limited.

    1. eLife Assessment

      This useful study reports on the impact of antibiotic pressure on the genomic stability of the mc2155 strain of Mycobacterium smegmatis, a model for Mycobacterium tuberculosis. The findings of the study indicate that exposure to antibiotics did not lead to the development of new adaptive mutations in controlled laboratory environments, challenging the notion that antibiotic resistance arises from drug-induced microevolution. The genomic analysis provides detailed insights into the stability of M. smegmatis following exposure to standard TB treatment antibiotics, and the evidence suggesting that antibiotic pressure does not contribute to the emergence of new adaptive mutations is solid.

    1. eLife Assessment

      Yamamoto and Matano provide convincing evidence that a G63E CD8+ T-cell escape mutation in the accessory viral protein Nef facilitates the induction of neutralizing antibody (nAb) responses in rhesus macaques infected with SIVmac239. Functional analyses support that this mutation specifically impairs Nef`s ability to stimulate PI3K/Akt/mTORC2 signalling. This important study suggests that the accessory viral Nef protein impairs B cell function and effective humoral immune responses and is of interest for researchers and physicians interested in HIV/AIDS and vaccine development.

    1. eLife Assessment

      This important study presents a significant methodological advance by leveraging previously discarded, unmapped DNA sequence reads to estimate pest infestation loads across plant accessions, and map variation in these apparent pest loads to defense genes. The bioinformatics approach is compelling, and the results should bear broad implications for phenotype-genotype prediction, especially regarding the use of unmapped reads for GWAS.

    1. eLife Assessment

      This important study examines the effects of NFKB2 mutations on pituitary gland development through hypothalamic-pituitary organoids. The evidence supporting the main conclusions is solid, although analysis of additional clones to exclude inter-clone variability would strengthen the conclusions. This is a revised study, but insight into the mechanism of action of NFKB2 during pituitary development is incomplete. This work will be of interest to endocrinologists and biologists working on pituitary gland development and disease.

    1. eLife Assessment

      This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.

    1. eLife Assessment

      This study reports important findings on identifying sequence motifs that predict substrate specificity in a class of lipid synthesis enzymes. It sheds light on a mechanism used by bacteria to modify the lipids in their membrane to develop antibiotic resistance. The evidence is compelling, with a careful application of machine learning methods, validated by mass spectrometry-based lipid analysis experiments. This interdisciplinary study will be of interest to computational biologists and to the community working on lipids and on enzymes involved in lipid synthesis or modification.

    1. eLife Assessment

      This important study provides convincing evidence that developing neurons in the neocortex regulate glial cell development. The data demonstrates that the transcription factor FOXG1 negatively regulates gliogenesis by controlling the expression of a member of the FGF ligand family and by suppressing the receptor for this ligand in developing neurons. This study leads to a new understanding of the cascade of events regulating the timing of glial development in the neocortex.

    1. eLife Assessment

      This manuscript establishes a mathematical model to estimate the key parameters that control the repopulation of planarian stem cells after sublethal irradiation as they undergo fate-switching as part of their differentiation and self-renewal process. The findings are valuable for future investigation of stem cell division in planarians. The methods are solid, integrating modeling with perturbations of key transcription factors known to be critical for cell fate decisions, but the authors have only shown that this is the case for a small number of stem cell types.

    1. eLife Assessment

      This important work attempts to establish a causal link between neurotrophin signaling and experience-induced structural plasticity in dopaminergic circuits in the adult fly brain, a topic of broad interest to the neuroscience community. While the authors provide solid evidence for the role of this signaling in regulating the structure and synapses of dopaminergic circuits, the evidence for a direct link between neurotrophin signaling and experience-induced structural plasticity remains incomplete.

    1. eLife Assessment

      This study presents important findings that will allow for a better understanding of the role of mitochondria in behaviours of C. elegans. There is convincing evidence that mutants in a subunit of the mitochondrial calcium uniporter (MCU-1) show defects in olfactory adaptation and this gene regulates neuropeptide secretion and allows for behavioural modulation in C. elegans. However, the evidence that mitochondrial calcium modulates odour-based behaviour in C. elegans is incomplete. This claim would require support from calcium imaging in conditioned WT and mcu-1 animals. This work would be of interest to labs working on behaviours across phyla.

    1. eLife Assessment

      This manuscript presents a valuable minimal model of habituation which is quantified by information theoretic measures. The results here could be of use in interpreting habituation behavior in a range of biological systems. However, the evidence presented is incomplete and would benefit from more rigorous approaches and a fuller accounting of the hallmarks of habituation.

    1. eLife Assessment

      The paper describes a novel approach for inferring features of synaptic networks from recordings of individual cells within the network. The paper will be a valuable contribution to those studying central pattern generators, including those involved in respiration. However, the theoretical approach to drawing inferences regarding the underlying synaptic currents is incomplete as it relies on unsupported simplifying assumptions.

    1. eLife Assessment

      The study by Power and colleagues is important as elucidating the dynamic immune responses to photoreceptor damage in vivo potentiates future work in the field to better understand the disease process. However the evidence supporting the authors' claims is incomplete. The current manuscript would further benefit from validating their conclusion with additional supporting data from earlier time points (6 to 12 hours), additional markers to characterize neutrophils, more n numbers to strengthen the analysis, and evaluation of immune responses in mice with a stronger laser ablation, as well as further evidence to distinguish resident microglia vs. infiltrating macrophages due to the BRB breakdown. The authors should reorganize the article to make it easier and more straightforward to follow.

    1. eLife Assessment

      This useful study combines multiplexed RNA-FISH with downstream analyses and modelling to describe novel dendritic mRNA distribution and behavioural features. Although the downstream analysis pipeline is novel, the results from this study are as of yet incomplete. Further inclusion of key missing controls, further work to better assess the physiological relevance, or additional modelling to expand their conclusions would make this work of greater interest to RNA biologists.

    1. eLife Assessment

      The study is useful for advancing understanding of spinal cord injuries, but it presents inadequate evidence due to the use of multiple datasets. Data were collected from different models of spinal cord injury, various regions of the spinal cord, and an iPSC model, with the differences between these models making it difficult to draw reliable conclusions.

    1. eLife Assessment

      Barzó et al. assessed the electrophysiological and anatomical properties of a large number of layer 2/3 pyramidal neurons in brain slices of human neocortex across a wide range of ages, from infancy to elderly individuals, using whole-cell patch clamp recordings and anatomical reconstructions. This large data set represents a valuable contribution to our understanding of how these properties change across the human lifespan, and although the results presented are convincing, analyzing the data by absolute age rather than age ranges as well as clarifying the methods used and some of the statistical approaches applied would strengthen the conclusions. The analysis of spine density requires additional biological replicates to support the conclusions stated. These data strengthen our understanding of how these properties change with age and will contribute to building more realistic models of human cortical function.

    1. eLife Assessment

      Oor and colleagues report the potentially independent effects of the spatial and feature-based selection history on visuomotor choices. They outline compelling evidence, tracking the dynamic history effects based on their extremely clever experimental design (urgent version of the search task). Their finding is of fundamental significance, broadening the framework to identify variables contributing to choice behavior and their neural correlates in future studies.

    1. eLife Assessment

      The manuscript explores how bacterial evolution in the presence of lytic phages modulates b-lactams resistance and virulence properties in methicillin-resistant Staphylococcus aureus (MRSA). The work is useful as it identifies underlying mutations that may confer sensitivity to b-lactams and alter virulence properties. While the findings are generally convincing, additional experiments linking how particular mutations regulate phenotypic changes are required to improve the work mechanistically.

    1. eLife Assessment

      This study investigates a dietary intervention that employs a smartphone app to promote meal regularity, which may be useful. Despite no self-reported changes in caloric intake, the authors report significant weight loss for the relatively short duration of only 6 weeks. While the concept is very interesting and deserves to be studied due to its potential clinical relevance, the study's rigor needs to be improved upon and is currently considered incomplete, notably the reliance on self-reported food intake, a highly unreliable way to assess food intake. Additionally, the study theorizes that the intervention resets the circadian clock, but the study needs more reliable methods for assessing circadian rhythms, such as actigraphy. Further, if this restrictive dietary intervention has any more promise in achieving long-term weight loss than the myriad other restrictive diets, it remains to be tested.

    1. eLife Assessment

      This important revised report describes the control of the activity of the RNA-activated protein kinase, PKR, by the Vaccinia virus K3 protein. A strength of the manuscript is the powerful combination of a classic yeast-based assay with high-throughput sequencing and its convincing experimental use to characterize large numbers of PKR variants, now with improved controls for potential biases. A minor current limitation that the authors may address in the future is the scope of the screen in terms of the segments of PKR included.

    1. eLife Assessment

      This study retrospectively analyzed clinical data to develop a risk prediction model for pulmonary hypertension in high-altitude populations. The evidence is solid, and the findings are useful and hold clinical significance as the model can be used for intuitive and individualized prediction of pulmonary hypertension risk in these populations.

    1. eLife Assessment

      The authors analyze a comprehensive cohort of human plasma samples to identify an extracellular vesicles protein signature for early diagnosis of pancreatic cancer. The application of liquid biopsies is valuable, and the work addresses a key clinical problem as pancreas cancer is often diagnosed in late stages. The strength of evidence is solid. Altogether, this work supports the potential use of extracellular vesicles in clinical settings, with promising value to scientists and clinicians.

    1. eLife Assessment

      This fundamental work by Mäkelä et al. presents compelling experimental evidence supported by a theoretical model that the amount of chromosomal DNA can become limiting for the total rate of mRNA transcription and consequently protein production in the model bacterium Escherichia coli. The work is based on a mutant that allows inhibition of DNA replication while following growth at the single-cell level due to cell filamentation. The work significantly advances our understanding of growth and of the central dogma, and will be of considerable interest within both systems biology and microbial physiology.

    1. eLife Assessment

      This valuable study uses dynamic metabolic models to compare perturbation responses in a bacterial system, analyzing whether they return to their steady state or amplify beyond the initial perturbation. The evidence supporting the emergent properties of perturbed metabolic systems to network topology and sensitivity to specific metabolites is solid, although the authors do not explain the origin of some significant inconsistencies between models.

    1. eLife Assessment

      This fundamental study generated a single cell atlas of mouse periosteal cells under both steady-state and fracture healing conditions to address the knowledge gap regarding cellular composition of the periosteum and their responses to injury. Based on convincing transcriptome analyses and experimental validation, the authors identified the injury induced fibrogenic cell (IIFC) as a characteristic cell type appearing in the bone regeneration process and proposed that the IIFC is a progenitor undergoing osteochondrogenic differentiation. This study will provide a significant publicly accessible dataset to reexamine the expression of the reported periosteal stem and progenitor cell markers.

    1. eLife Assessment

      This manuscript describes an important study of a new lipid-mediated regulation mechanism of adenylyl cyclases. The biochemical evidence provided is convincing and will trigger more research in this mechanism. This manuscript will be of interest to all scientists working on lipid regulation and adenylyl cyclases.

    1. eLife Assessment

      The neurotrophic factor Neuritin can moderate T-cell tolerance and immunity through both regulatory T (Treg) and effector T cells, promoting Treg cell expansion and suppression while dampening effector T cells to mediate the inflammatory response. Neuritin expression influences the membrane potential, ion channels, and nutrient transporter expression patterns of CD4+ T cells, contributing to differential metabolic states in Treg and effector T cells. These findings are solid and important for understanding immune regulation involving Treg cells and effector T cells.

    1. eLife Assessment

      In this valuable study, Li and others identified cell membrane receptors for juvenile hormone (JH), a terpenoid hormone in insects that regulates their development and reproduction. While intracellular receptors for JH have been well characterized, membrane receptors for JH remained elusive for many years. Although the authors provide solid evidence to indicate that the receptor tyrosine kinases they identified bind to JH in vitro and induce non-genomic responses in cultured cells, their loss-of-function phenotypes are not consistent with known JH functions, so additional work is required to define physiological roles of these receptors.

    1. eLife Assessment

      This important work presents data showing that all non-proneural phenotypes of the Inhibitor of DNA binding (Id) protein Emc are mediated through inappropriate nonapoptotic caspase activity. Using the developing Drosophila retina as a model the authors show that Emc acts by transcriptionally regulating the Death-Associated Inhibitor of Apoptosis 1 (diap1) gene, which impacts on Notch signaling by caspase-dependent increase of Delta protein. These are compelling findings, interesting for the caspase/apoptosis field as they add more non-apoptotic functions of caspases to the list, as well as for the Id field, which examines how Id proteins inhibit cell differentiation.

    1. eLife Assessment

      This important study, which will be of interest to those studying the evolution and maintenance of antibiotic resistance, addresses the hypothesis that antibiotic resistance arising de novo during treatment will carry a higher fitness cost and will revert to susceptibility more readily than resistance that has been transmitted between hosts. There are, however, concerns that the 'putatively transmitted isolates' in this study do not necessarily represent resistant isolates that have been transmitted between hosts. The support for the central claim of different patterns of reversion between isolates with de novo resistance and putatively transmitted resistant isolates is currently incomplete.

    1. eLife Assessment

      This study presents valuable data on the increase in individual differences in functional connectivity with the auditory cortex in individuals with congenital/early-onset hearing loss compared to individuals with normal hearing. The evidence supporting the study's claims is convincing, although additional work using resting-state functional connectivity and further links to how the results align with the underlying biology could have further strengthened the study. The work will be of interest to neuroscientists working on brain plasticity and may have implications for the design of interventions and compensatory strategies.

    1. eLife Assessment

      So et al. present an optimized protocol for single-nuclei RNA sequencing of adipose tissue in mice, ensuring better RNA quality and nuclei integrity. The authors use this protocol to explore the cellular landscape in both lean and diet-induced obese mice, identifying a dysfunctional hypertrophic adipocyte subpopulation linked to obesity. The data analyses are solid, and the findings are supported by the evidence presented. This study provides valuable information for the field of adipose tissue biology and will be particularly helpful for researchers using single-nuclei transcriptomics in various tissues.

    1. eLife Assessment

      The specific questions taken up for study by the authors-in mice of HDAC and Polycomb function in the context of vascular endothelial cell (EC) gene expression relevant to the blood-brain barrier, (BBB)-are potentially useful in the context of vascular diversification in understanding and remedying situations where BBB function is compromised. The strength of the evidence presented is incomplete, and to elaborate, it is known that the culturing of endothelial cells can have a strong effect on gene expression.

    1. eLife Assessment

      This study investigates the role of the Cadherin Flamingo (Fmi) in cell competition in developing tissues in Drosophila melanogaster. The findings are valuable in that they show that Fmi is required in winning cells in several competitive contexts. The evidence supporting the conclusions is solid, as the authors identify Fmi as a potential new regulator of cell competition, however, they don't delve into a mechanistic understanding of how this occurs.

    1. eLife Assessment

      The authors have reported an important study in which they use a double-blind design to explore pharmacological manipulations in the context of a behavioral task. While the sample size is small, the use of varied methodology, including electrophysiology, behavior, and pharmacology, makes this manuscript particularly notable. Overall, the findings are solid and motivate future explanations into the relationships between acetylcholine and motivation.

    1. eLife Assessment

      The paper reports the important discovery that the mouse dorsal inferior colliculus, an auditory midbrain area, encodes sound location. The evidence supporting the claims is solid, being supported by both optical and electrophysiological recordings. The observations described should be of interest to auditory researchers studying the neural mechanisms of sound localization and the role of noise correlations in population coding.

    1. eLife Assessment

      This useful work reveals differential activity to food and shock outcomes in central amygdala GABAergic neurons. Solid evidence supports claims of unconditioned stimulus activity that changes with learning. However, the evidence regarding claims related to valence or salience signaling in these neurons is inadequate. This work will be of interest to neuroscientists studying sensory processing and learning in the amygdala.

    1. eLife Assessment

      This important study reveals that Excitatory Amino Acid Transporters play a role in chromatic information processing in the retina. The combination of (double) mutants, behavioral assays, immunohistochemistry, and electroretinograms provides solid evidence supporting the appropriately conservative conclusions. The work will be of interest to neurobiologists working on color vision or retinal processing.

    1. eLife Assessment

      This important study explores the neural basis for a well known auditory illusion, often utilized in movie soundtracks, in which a sequence of two complex tones can be perceived as either rising or falling in pitch depending on the context in which they are presented. Convincing single-neuron data and analyses are presented to show that correlates of these pitch-direction changes are found in the ferret primary auditory cortex. While these findings provide an interesting link between cortical activity and perception, the manuscript could be clearer on the wider implications of the failure of traditional decoding models to account for these results.

    1. eLife Assessment

      This revised version of the study is important, showing that age-related gut microbiota modulate uric acid metabolism through the NLRP3 inflammasome pathway and thereby regulate susceptibility to age-related gout. Several experimental approaches (mechanistic insights) and methods (data quality) are still incomplete. If strengthened, this paper would be of broad interest to researchers working on gout and the microbiota.

    1. eLife Assessment

      This article describes a novel mechanism allows Drosophila to combat enteric pathogens while also preserving the beneficial indigenous microbiota. The authors provide compelling evidence that oral infection of Drosophila larvae by pathogenic bacteria activate a valve that traps the intruders in the anterior midgut, allowing them to be killed by antimicrobial peptides. This is an important finding revealing a new mechanism of host defense in the gut of insects.

    1. eLife Assessment

      These authors present findings on the role of the sirtuins SIRT1 and SIRT3 during Salmonella Typhimurium infection. This valuable study increases our understanding of the mechanisms used by this pathogen to interact with its host and may have implications for other intracellular pathogens. The reviewers disagreed on the strength of the evidence to support the claims. Although one reviewer found the strength of the evidence convincing, the other found that it was incomplete, and that the main claims are only partially supported, as can be seen from the public reviews.

    1. eLife Assessment

      This valuable study proposes that protein secreted by colon cancer cells induces cells with Paneth-like properties that favor colon cancer metastasis. The evidence supporting the conclusions is solid but the study would benefit from more direct experiments to test the functional role of Paneth-like cells and to monitor metastasis from colon tumors. The work will be of interest to researchers studying colon cancer metastasis.

    1. eLife Assessment

      This useful study presents a novel microscopy technique called "Expansion Tiling Light Sheet Microscopy" and an accompanying computational pipeline for the faster collection and analysis of 3D volumetric images in animals like planarians. This approach produces beautiful 3D microscropy images and is solid on a technical level. However, due to the use of antibody reagents that visualize many – but not all – neurons and muscle subtypes, the evidence for the biological conclusions in this study remains incomplete. With the claims appropriately contextualized, this paper will be of interest to cell biologists working on imaging and analyzing whole animals.

    1. eLife Assessment

      This study provides a valuable perspective on visual cortex architecture by identifying two cortical gradients that change across the lifespan and have distinct functional and structural features. The first gradient captures well-mapped variations in cortical thickness and myelination markers from early sensory to higher-order cortex, while the second gradient shows divergence in these measures with a more localized structure, notably predicting a previously unknown cluster of visual field maps in the anterior temporal lobe. The large-scale lifespan data are compelling, but the evidence overall is incomplete with key questions around methodical checks and implementation, the standard of evidence for the new visual maps, and how the gradient model relates to sharp tissue boundaries parcellating the cortex.

    1. eLife Assessment

      The authors present three valuable transgenic models carrying three representative exon deletions of the dystrophin gene. The findings are supported by rigorous biochemical assays and state-of-the-art microscopy methods, although the evidence, while overall solid, is only partially developed, and some points could be improved.

    1. eLife Assessment

      This study analyzes a cohort of small intestine neuroendocrine tumors, and the description of tumor-intrinsic programs that govern such rare cancers is felt to be valuable. The methods are for the most part felt to be solid, however, some broad concerns were raised that the possible separation of samples by a program may be impacted by fresh versus frozen sequencing. Similarly, the heterogeneity of the SiNET tumor microenvironment is unclear given a mixing of subtypes and the proliferation of NE and immune cells in SiNET could be influenced by technical factors. Recommendations were made to extend these data with other published datasets of SiNET tumors, expanding technical clarity and details, and validating findings using cell lines/PDX if available.

    1. eLife Assessment

      The study by Chen and Phillips provides evidence for a dynamic switch in the small RNA repertoire of the Argonaute protein NRDE-3 during embryogenesis in C. elegans. The work is supported by solid experimental data, although some conclusions regarding the functional role of specific RNA granules remain uncertain. Nevertheless, this study offers valuable insights into RNA regulation and developmental biology, with broader implications for understanding small RNA pathways in other systems.

    1. eLife Assessment

      This study presents valuable findings on changes in neuronal alpha activity elicited by prolonged pain in healthy human participants. The evidence supporting the claims of the authors, however, is incomplete and would benefit from clarifications of analytical strategies, additional statistical analyses, and shaping of the interpretations. With the methodological and interpretative parts strengthened, the work will be of interest to neuroscientists investigating the brain mechanisms of pain to identify new approaches to pain treatment

    1. eLife Assessment

      The study is a valuable addition to the field, showing how particulate matter may be acting via nociceptor neurons towards neutrophilic asthma exacerbations. The solid evidence for the role of a nociceptive pathway in model systems is relevant to human asthma in its current form but would be further strengthened by mechanistic insights. This would be particularly relevant to further translational research towards blocking the exacerbating effect of air pollution on asthma.

    1. eLife Assessment

      This important study presents the first identification of the odorant receptor for the trail pheromone in termites. The evidence supporting the conclusions is compelling, with state-of-the-art neurophysiological and genetic methods. The work will be of broad interest in multiple disciplines, such as entomology, chemical ecology, and sensory physiology.

    1. eLife Assessment

      This valuable study builds on previous work by the authors by presenting a potentially key method for correcting optical aberrations in GRIN lens-based micro endoscopes used for imaging deep brain regions. By combining simulations and experiments, the authors show that the obtained field of view is significantly increased with corrected, versus uncorrected microendoscopes. The evidence supporting the claims of the authors is solid, although some aspects of the manuscript should be clarified and missing information provided. Because the approach described in this paper does not require any microscope or software modifications, it can be readily adopted by neuroscientists who wish to image neuronal activity deep in the brain.

    1. eLife Assessment

      The study provides valuable insight into the biological significance of SARS-CoV-2 by using a series of computational analyses of viral proteins. While evidence is solid, it is obscured by a lack of clarity about the objectives of the analyses and in the overall writing of the article. The study will be impactful to the researchers in the field but will benefit from improved presentation.

    1. eLife Assessment

      This important paper employs multiple experimental approaches and presents evidence that changes in membrane voltage 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 some experimental results and interpretations are compelling, but the strength of evidence is incomplete and additional experiments are needed to rule out other possible interpretations of the data.

    1. Editors Assessment:

      This paper reports the establishment of the International Cannabis Genomics Research Consortium (ICGRC) web portal leveraging the open source Tripal platform to enhance data accessibility and integration for Cannabis sativa (Cannabis) multi-omics research. With the aim of bringing together the wealth of publicly available genomic, transcriptomic, proteomic, and metabolomic data sets to improve cannabis for food, fiber and medicinal traits. Tripal is a content management system for genomics data, presenting a ready-to-use specialized ‘omics modules for loading, visualization, and analysis, and is GMOD (Generic Model Organism Database) standards-compliant. The paper explaining how this was put together, what data and features are available, and providing a case study for other communities wanting to create their own Tripal platform. Covering their setup and customizations of the Tripal platform, and how they re-engineered modules for multi-omics data integration, and addition of many other custom features that can be reused. Peer review fixed a few minor bugs and added clarifications on how the platform will be updated.

      *This evaluation refers to version 1 of the preprint *

    1. eLife Assessment

      This important work advances our understanding of parabrachial CGRP threat function. The evidence supporting CGRP aversive outcome signaling is solid, while the evidence for cue signaling and fear behavior generation is incomplete. The work will be of interest to neuroscientists studying defensive behaviors.

    1. eLife Assessment

      This study presents a valuable finding on the identification of a complex consisting of NHE1, hERG1, β1/integrin and NaV1.5 on the membrane of breast cancer cells. The evidence supporting the claims of the authors is somewhat incomplete. The inclusion of clarification of some experimental design and the amendment of cropping Western blot data would have strengthened the study. The work will be of interest to scientists working on breast cancer.

    1. eLife Assessment

      SGLT2 inhibitors (SGLT2i) have assumed important roles in reducing cardiovascular risk, particularly in those with diabetes. It has become appreciated that its protective effects are likely beyond their ability to lower blood sugar levels. This research presents a novel approach to studying the SGLT2i mechanism of action which is yet to be fully elucidated.

    1. eLife Assessment

      This study provides a valuable new perspective on how motor learning occurring in one state generalizes to new states (for example, a different limb posture). The proposed model improves upon previous theories in its ability to predict patterns of generalization, but evidence supporting this specific proposed model over possible alternatives is incomplete. The newly proposed theory appears promising but would be more convincing if its conceptual and theoretical basis were clearer and more rigorously derived.

    1. eLife Assessment

      This important work advances our understanding of factors influencing early childhood development. The large sample size and methodology applied make the findings of this study convincing; however, support for some of the claims made by the authors is incomplete. The work will be of interest to researchers in developmental science and early childhood pediatrics.

    1. eLife Assessment

      This important work addresses the role of Marcks/Markcksl during spinal cord development and regeneration. The study is exceptional in combining molecular approaches to understand the mechanisms of tissue regeneration with behavioural assays, which is not commonly employed in the field. The data presented is convincing and comprehensive, using many complementary methodologies.

    1. Editors Assessment:

      PhysiCell is an open source multicellular systems simulator for studying many interacting cells in dynamic tissue microenvironments. As part of the PhysiCell ecosystem of tools and modules this paper presents a PhysiCell addon, PhysiMeSS (MicroEnvironment Structures Simulation) which allows the user to accurately represent the extracellular matrix (ECM) as a network of fibres. This can specify rod-shaped microenvironment elements such as the matrix fibres (e.g. collagen) of the ECM, allowing the PhysiCell user the ability to investigate physical interactions with cells and other fibres. Reviewers asked for additional clarification on a number of features. And the paper now clear future releases will provide full 3D compatibility and include working on fibrogenesis, i.e. the creation of new ECM fibres by cells.

      This evaluation refers to version 1 of the preprint

    1. eLife Assessment

      This important paper demonstrates that different PKA subtypes exhibit distinct subcellular localization at rest in CA1 neurons. The authors provide compelling evidence that when all tested PKA subtypes are activated by norepinephrine, catalytic subunits translocate to dendritic spines but regulatory subunits remain unmoved. Furthermore, PKA-dependent regulation of synaptic plasticity and transmission can be supported only by wildtype, dissociable PKA, but not by inseparable PKA.

    1. eLife Assessment

      In this potentially important study, the authors conducted atomistic simulations to probe the salt-dependent phase separation of the low-complexity domain of hnRN-PA1 (A1-LCD). The authors have identified both direct and indirect mechanisms of salt modulation, provided explanations for four distinct classes of salt dependence, and proposed a model for predicting protein properties from amino acid composition. There is a range of opinions regarding the strength of evidence, with some considering the evidence as incomplete due to the limitations in the length and statistical errors of the computationally intense atomistic MD simulations.

    1. eLife Assessment

      This manuscript presents a valuable new quantitative crosslinking mass spectrometry approach using novel isobaric crosslinkers. The data are solid and the method has potential for a broad application in structural biology if more isobaric crosslinking channels are available and the quantitative information of the approach is exploited in more depth.

    1. eLife Assessment

      This useful study by Nandy and colleagues examined relationships between behavioral state, neural activity in cortical area V4, and trial-by-trial variability in the ability to detect weak visual stimuli. They present solid evidence indicating that certain changes in arousal and eye-position stability, along with patterns of synchrony in the activity of neurons in different layers of V4, can show modest correspondences to changes in the ability to correctly detect a stimulus. These findings are likely to be of interest to those who seek a deeper understanding of circuit mechanisms that underlie perception.

    1. eLife Assessment

      This useful manuscript addresses some key molecular mechanisms on the neuroprotective roles of soluble TREM2 in neurodegenerative diseases. Thw study will advance our understanding of TREM2 mutations, particularly on the damaging effect of known TREM2 mutations, and also explain why soluble TREM2 can antagonize Aβ aggregation. However, the primary experimental method, MD simulations, suffers from limited sampling, rendering the results incomplete for definite conclusions.

    1. eLife Assessment

      The study provides a valuable showcase of a workflow to perform large-scale characterization of drug mechanisms of action using proteomics in which on-target and off-targets of 166 compounds using proteome solubility analysis in living cells and cell lysates were determined. The evidence supporting the claims of the authors is solid, however, the inclusion of more replicate experiments and more statistical rigor would have strengthened the study. This will be of broad interest to medicinal chemists, toxicologists, computational biologists and biochemists.

    1. eLife Assessment

      This landmark study elucidates the intricate structural mechanisms by which both covalent and non-covalent synthetic ligands can co-occupy the binding pocket of the nuclear receptor transcription factor PPARγ. Through a compelling integration of structural, biochemical, and biophysical evidence, the authors challenge the reliability of two commonly used covalent inhibitors. These findings have far-reaching implications for the broader field of nuclear receptor research. This work will be of high interest to structural biologists and biochemists exploring ligand interactions within the nuclear receptor superfamily.

    1. eLife Assessment

      The manuscript presents an important model for the field of endosome maturation, providing perspective on the role of the deubiquitinating enzyme UPS-50/USP8 in the process. The evidence presented in the paper is clear, incorporating well-designed experiments that suggest the dual actions of UPS-50 and USP8 in the conversion of early endosomes into late endosomes. Overall, the work is convincing and centers on an intriguing subject.

    1. eLife Assessment

      This study demonstrates mRNA-specific regulation of translation by subunits of the eukaryotic initiation factor complex 3 (eIF3) using convincing methods, data, and analyses. The investigations have generated important information that will be of interest to biologists studying translation regulation. However, the physiological significance of the gene expression changes that were observed is not clear.

    1. eLife Assessment

      The study is considered important with solid evidence that demonstrates the impact of plasma membrane nano-domains and protein interactions in the plant defence response to viruses. It includes a molecular understanding of the role of a calcium dependent kinase (CPK3) and a remorin protein in the cell-to-cell spread of viruses and cytoskeletal dynamics demonstrating, conclusively, the role of CPK3 with multiple lines of evidence. The work opens avenues to investigate different viruses and other plasma membrane proteins to gain a fuller picture of the involvement of plasmodesmata and other nanodomains in virus spreading.

    1. eLife Assessment

      This valuable work describes results from a set of simulation and empirical studies of a set-up assessing exploratory behavior in a potentially rewarding environment that contains danger. The core idea is that an instrumental agent can be helped to be both effective and safe, thus avoiding excessive danger, during exploratory behavior, if its influence is flexibly gated by an independent Pavlovian fear learning system. The conclusion that safe, but effective exploration can be achieved based on a flexibly weighted combination of a Pavlovian and an instrumental agent is solid.

    1. eLife Assessment

      The authors identify a novel relationship between exosome secretion and filopodia formation that has implications for cancer cell metastasis and neuronal synapse formation. Further, they identify the exosomal cargo, THSD7A, as a regulator of this process. The data presented is convincing, and represents an important advancement in our understanding of how these two biological processes are linked and play roles in regulating cell migration and cell-cell communication.

    1. eLife Assessment

      This valuable study investigates how the size of an LLM may influence its ability to model the human neural response to language recorded by ECoG. Overall, solid evidence is provided that larger language models can better predict the human ECoG response. Further discussion would be beneficial as to how the results can inform us about the brain or LLMs, especially about the new message that can be learned from this ECoG study beyond previous fMRI studies on the same topic. This study will be of interest to both neuroscientists and psychologists who work on language comprehension and computer scientists working on LLMs.

    1. eLife Assessment

      This valuable study significantly enhances our understanding of how various ligands and receptors interact within the Notch signaling pathway. By developing novel cell-based assay systems, the authors systematically analyzed the effects of different ligand-receptor combinations on pathway activation. The convincing data reveal intriguing and unexpected differences and provide a foundation for interpreting Notch signalling in both normal and disease-related contexts.

    1. eLife Assessment

      This important study uses in vitro and in vivo methods to identify HpARI proteins from H. polygyrus as modulators of the host immune system. The data from comprehensive approaches for investigating differential roles of HpARI proteins are convincing. This paper is relevant to those who investigate host-pathogen interactions at the systems and molecular levels.

    1. eLife Assessment

      This is an important study on the damage-induced checkpoint maintenance and termination in budding yeast that provides novel and convincing evidence for a role of the spindle assembly checkpoint and mitotic exit network in halting the cell cycle after prolonged arrest in response to irreparable DNA double strand breaks (DSBs). The study identifies particular components from these checkpoints that are specifically required for the establishment and/or the maintenance of a cell cycle block triggered by such DSBs. The authors propose an interesting model for how these different checkpoints intersect and crosstalk for timely resumption of cell cycling even without repairing DNA damage that has been revised by addressing the bulk of the reviewers' comments to the first version of the manuscript.

    1. eLife Assessment

      This important study examines the role of Microrchidia (MORC) proteins in the human malaria parasite Plasmodium falciparum. Solid experimental results, including genome editing and chromatin profiling methods (ChIP-seq and Hi-C), provide a comprehensive picture of the critical role MORC plays in shaping parasite chromatin. Depletion of MORC results in a lethal collapse of heterochromatin and parasite death, nominating the factor as a new target of antimalarial therapies.

    1. eLife Assessment

      This valuable study focuses on the regulation of Notch signaling during the immune response in Drosophila. The authors provide solid evidence in support of roles for Su(H) and Pkc53E-induced phosphorylation in Drosophila immunity. The work will be of interest to colleagues in immunity and receptor signaling.

    1. eLife Assessment

      This important study provides a new perspective on how human immunity shapes the antigenic evolution of pathogens. By combining theory and simulation the authors make a compelling case for the importance of eco-evolutionary interactions in population-level virus-host dynamics, which arise due to coupling between the dynamics of immune memories and viral variants. Although the work does not propose improved data-driven viral forecasting methods, it makes a conceptual contribution that advances the field's understanding of this problem's intrinsic difficulty.

    1. eLife Assessment

      This study presents a valuable methodological advancement in quantifying thoughts over time. A novel multi-dimensional experience-sampling approach is presented, identifying data-driven patterns that the authors use to interrogate fMRI data collected during naturalistic movie-watching. The experimentation is inventive and the analyses carried out are convincing.

    1. eLife Assessment

      This study presents an important finding on the involvement of a Caspase 3-dependent pathway in the elimination of synapses for retinogeniculate circuit refinement and eye-specific territory segregation. This work fits well with the concept of "synaptosis" which has been proposed in the past but lacked in vivo support. Despite its elegant design and many strengths, the evidence supporting the claims of the authors is incomplete, particularly regarding whether Caspase-3 expression can really be isolated to synapses vs locally dying cells, whether microglia direct or instruct synapse elimination, and whether astrocytes are also involved. The work will be of interest to investigators studying cell death pathways, neurodevelopment, and neurodegenerative disease.

    1. eLife Assessment

      This valuable paper provides an unbiased landscape for the cerebellar cortical outputs to the brainstem nuclei. By conducting anatomical and physiological analyses of the axonal terminals of Purkinje cells, the data provide convincing evidence that Purkinje cells innervate brainstem nuclei directly. The results show that in addition to previously known inputs to vestibular and parabrachial nuclei, Purkinje cells synapse onto the pontine central grey nucleus but have little effect on the locus coeruleus and mesencephalic trigeminal neurons.

    1. eLife Assessment

      This important study reports that the neurohormone, bursicon, and its receptor, play a role in the seasonal polyphenism of the bug Cacopsylla chinensis. Low temperature activates the bursicon signaling pathway during the transition from the summer to the winter form, affecting cuticle pigment and thickness as well as chitin content. The solid experiments reveal how bursicon signaling, which is modulated by the microRNA miR-6012, regulates features of polyphenism related to the exoskeleton, although it is less clear what the upstream regulatory events are.

    1. eLife Assessment

      This study presents valuable findings on what networks of genes were impacted by introgression from Denisovans, to identify the biological functions involved in high-altitude adaptation in Tibet. This study applies solid and previously validated methodology to identify genes with signatures of both introgression and positive selection. This paper would be of interest to population geneticists, anthropologists, and scientists studying the genetic basis underlying high-altitude adaptation.

      1. Humans have a very general ability to solve problems and achieve goals across diverse domains.
      2. AI systems could become much more intelligent than humans.
      3. If we create highly intelligent AI systems, their decisions will shape the future.
      4. Highly intelligent AI systems won’t be beneficial by default.
    1. eLife Assessment

      ProtSSN is a valuable approach that generates protein embeddings by integrating sequence and structural information, demonstrating improved prediction of mutation effects on thermostability compared to competing models. The evidence supporting the authors' claims is solid, with well-executed comparisons. This work will be of particular interest to researchers in bioinformatics and structural biology, especially those focused on protein function and stability.

    1. eLife assessment

      This fundamental work provides creative and thoughtful analysis of rodent foraging behavior and its dependence on body reference frame-based vs world reference frame-based cues. Compelling evidence demonstrates that a robust map, capable of supporting taking novel shortcuts, is learned primarily if not exclusively based on self-motion cues, which has rarely if ever been reported outside of the human literature. The work, which will be of interest to a broad audience of neuroscientists, provides a rich discussion about the role of the hippocampus in supporting the behavior that should guide future neurophysiological investigations.

    1. eLife Assessment

      This fundamental work provides creative and thoughtful analysis of rodent foraging behavior and its dependence on body reference frame-based vs world reference frame-based cues. Compelling evidence demonstrates that a robust map, capable of supporting taking novel shortcuts, can be learned primarily if not exclusively based on self-motion cues, which has rarely if ever been reported outside of the human literature. The work, which will be of interest to a broad audience of neuroscientists, provides a rich discussion about the role of the hippocampus in supporting the behavior that should guide future neurophysiological investigations.

    1. eLife Assessment

      This valuable study addresses potential roles of the master regulator of X chromosome inactivation, the Xist long non-coding RNA, in autosomal gene regulation. Using data from mouse cells, the authors propose that Xist can coat specific autosomal promoters, which in turn leads to the attenuation of their transcriptional activity, complementing recently published results from humans. While the evidence from individual genes is suggestive, shortcomings in the data and statistical analyses leave the evidence currently incomplete. The work would be of interest to anyone studying gene regulation and noncoding RNAA

    1. eLife Assessment

      This study provides important insights into the mechanistic basis of neurological manifestations of RNA polymerase III-related disease by creating a mutant mouse to dissect transcriptional changes. The data provide compelling evidence for disease progression initiated by a global reduction in tRNA levels leading to integrated stress and innate immune responses and neuronal loss. The work will be of interest to those engaged in the study of chromosome biology, developmental biology and neurodegeneration.

    1. eLife Assessment

      This important study advances our understanding of the mechanisms controlling lipid flux and ion permeation in the TMEM16 and OSCA/TMEM63 family channels. The study provides compelling new evidence indicating that side chains along the TM4/6 interface play a key role in gating lipid and ion fluxes in these channels. The authors suggest that the transmembrane channel/scramblase family proteins may have originally functioned as scramblases but lost this capacity over evolution.

    1. eLife Assessment

      This study aims to analyse the effect of polymorphism on meiotic recombination in subspecies of Saccharomyces. The detection of reciprocal and non-reciprocal events is based on sequencing the haploid products of meiosis, and frequencies are compared between strains having introgressed genomic segments and strains lacking such segments. Unfortunately, the method used are inadequate for quantifying the non-reciprocal events.

    1. eLife Assessment

      This study presents a valuable finding in understanding the role of plectin in the development and progression of hepatocellular carcinoma (HCC). The evidence supporting the conclusions is convincing because multiple orthogonal ways were used to demonstrate the requirement of this target in liver cancer models. However, the study is incomplete as the downstream molecular activities of plectin that mediate the cancer phenotypes were not fully evaluated.

    1. eLife Assessment

      This study presents a valuable examination of the prevalence of interactions between amino acids from different periods of Earth's history and coenzymes. While the premise of this work is well founded and the analysis is solid, with more data, the interpretation could change. This manuscript would be of interest to evolutionary biologists and biophysicists.

    1. eLife Assessment

      This revised study provides valuable information on the single nucleus RNA sequencing transcriptome, pathways, and cell types in pig skeletal muscle in response to conjugated linoleic acid (CLA) supplementation. Based on the comprehensive data analyses, the data are considered compelling and provide new insight into the mechanisms underlying intramuscular fat deposition and muscle fiber remodeling. The revised study clarifies major aspects of its methodology and analysis, addresses previous reviewer concerns, and contributes significantly to the understanding of nutritional strategies for fat infiltration in pig muscle.

    1. eLife Assessment

      This important study addresses two questions: (i) how danger signaling is altered for people with childhood adversities, and (ii) how this differs across different operationalizations of adversity. The latter is of particularly broad interest to multiple fields, given that childhood adversity is operationalized very differently across the literature. The study provides compelling evidence using a large sample size and rigorous statistical methods. These data will be of interest to scientists and clinicians interested in early life adversity, statistical approaches for quantifying stress exposure, or aversive learning.

    1. eLife Assessment

      This study explores the mechanistic link between glycosylation at the N162 site of the Fc gamma receptor FcγRIIIa and the modulation of NK cell-mediated antibody-dependent cytotoxicity. Using innovative isotope labeling strategies and advanced NMR spectroscopy techniques, the authors provide compelling evidence of how glycan composition influences receptor stability and immune function. These findings offer fundamental insights that may contribute to the development of more effective therapeutic antibodies. The manuscript will be of significant interest to immunologists and researchers focused on therapeutic antibody design.

    1. eLife Assessment

      This valuable study focuses on gene regulatory mechanisms essential for hindbrain development. Through molecular genetics and biochemistry, the authors propose a new mechanism for the control of Hox genes, which encode highly conserved transcription factors essential for hindbrain development. The strength of evidence is solid, as most claims are supported by the data. This work will be of interest to developmental biologists.