7,069 Matching Annotations
  1. Last 7 days
    1. eLife Assessment

      This valuable study describes how trains of mossy fiber stimulation control cerebellar unipolar brush cell discharges. The dissection of the contributions of relevant glutamate receptors to these transformations is convincing. Overall, the topic is compelling, as it broadens our understanding of temporal processing in the cerebellar cortex.

    1. eLife Assessment

      This useful study provides the first assessment of potentially interactive effects of seasonality and blood source on mosquito fitness, together in one study. During revision, the manuscript has been improved, providing additional solid data to support the robustness of observations. However, the discussion still requires further refinement to present the conclusions in manner that is consistent with the data presented. Overall, this interesting study will advance our current understanding of mosquito biology.

    1. eLife Assessment

      This useful study presents a genetically encoded barcoding system that could advance transcriptomic studies and that has the potential for further applications, such as in high-throughput population-scale behavioral measurements. The evidence supporting the claims of the authors is solid and highlights both the usefulness and the limitations of the approach.

    1. eLife Assessment

      Modulation of BMP signalling affects body size in the nematode Caenorhabditis elegans, and this paper examines the effects on C. elegans body size brought about by the modulation of BMP signalling. Thw study provides valuable analyses of ChIP-seq and RNA-Seq data to understand the function of SMA-3 (Smad) and SMA-9 (Schnurri) in this model. The authors provide compelling evidence that the BMP-dependent body size effect could be due to defects in cuticle collagen secretion, a finding of interest to those studying organismal growth and epidermal function.

    1. eLife Assessment

      This valuable paper describes a comprehensive quantitative phospho-proteomic analysis of Xenopus oocytes during meiosis. Using time-resolved proteomic analyses, the authors provide insights into changes in protein levels and phosphorylation states to an unprecedented depth, quality, and quantitative detail. The key findings are solid and offer a helpful resource for the scientific community.

    1. eLife Assessment

      In this important study, the authors combine innovative experimental approaches, including direct compressibility measurements and traction force analyses, with theoretical modeling to propose that wild-type cells exert compressive forces on softer HRasV12-transformed cells, influencing competition outcomes. The data generally provide solid evidence that transformed epithelial cells exhibit higher compressibility than wild-type cells, a property linked to their compaction during mechanical cell competition. However, the study would benefit from further characterization of how compression affects the behavior of HRasV12 cells and clearer causal links between compressibility and competition outcomes.

    2. eLife Assessment

      In this important study, the authors combine innovative experimental approaches, including direct compressibility measurements and traction force analyses, with theoretical modeling to propose that wild-type cells exert compressive forces on softer HRasV12-transformed cells, influencing competition outcomes. The data generally provide solid evidence that transformed epithelial cells exhibit higher compressibility than wild-type cells, a property linked to their compaction during mechanical cell competition. However, the study would benefit from further characterization of how compression affects the behavior of HRasV12 cells and clearer causal links between compressibility and competition outcomes.

    1. eLife Assessment

      This study reveals the important role of upstream open reading frames (uORFs) in limiting the translational variability of downstream coding sequences. Through a combination of computational simulations, comparative analyses of translation efficiency across different developmental stages in two closely related Drosophila species, and manipulative, experimental validation of translation buffering by an uORF for a gene, the authors provide convincing evidence supporting their conclusions. This work will be of broad interest to molecular biologists and geneticists.

    1. eLife Assessment

      This manuscript presents a valuable study utilizing an in vitro organoid system to recapitulate the developmental process of the olfactory epithelium. The authors provided solid evidence indicating that a combination of niche factors can induce organoid development and give rise to multiple cell types. However, the calcium imaging part of the study could be seen as a limitation.

    1. eLife Assessment

      This manuscript reports on an FLIM-based calcium biosensor, G-CaFLITS. It represents an important contribution to the field of genetically-encoded fluorescent biosensors, and will serve as a practical tool for the FLIM imaging community. The paper provides convincing evidence of G-CaFLITS's photophysical properties and its advantages over previous biosensors such as Tq-Ca-FLITS. Although the benefits of G-Ca-FLITS over Tq-Ca-FLITS are limited by the relatively small wavelength shift, it presents some advantages in terms of compatibility with available instrumentation and brightness consistency.

    1. eLife Assessment

      This paper presents useful findings that misfolded proteins in the nucleus can impair proteasomal degradation and activate p53. The results supporting the findings are largely solid, but incomplete. The manuscript could be strengthened by including more quantitative data analyses and additional experimentation/discussions on the mechanism of p53 activation by misfolded nuclear proteins. The work will be interesting primarily to scientists studying protein homeostasis.

    1. eLife Assessment

      This is a valuable polymer model that provides insight into the origin of macromolecular mixed and demixed states within transcription clusters. The well-performed and clearly presented simulations will be of interest to those studying gene expression in the context of chromatin. While the study is generally solid, it could benefit from a more direct comparison with existing experimental data sets as well as further discussion of the limits of the underlying model assumptions.

    1. eLife Assessment

      The role of ACVR2A is potentially of importance to both the biology of trophoblast cells and to the pathogenesis of preeclampsia. In this manuscript, the authors have taken a useful first step towards better understanding this protein using a loss of function model in trophoblast cell lines and then examining invasion, proliferation, and transcription in these cells. At present, the results of this study are only based on the observation of in vitro phenotypes, and the strength of the invasion data is somewhat weak, given the confounding effect on proliferation. The study is currently incomplete as there is a lack of direct evidence on how target factors participate in the occurrence of placental structural disorders and diseases through potential downstream pathways.

    1. eLife Assessment

      This important study introduces a biologically constrained model of telencephalic area of adult zebrafish to highlight the significance of precisely balanced memory networks in olfactory processing. The authors provide compelling evidence that their model performs better in multiple situations (for e.g. in terms of network stability and shaping the geometry of representations), compared to traditional attractor networks and persistent activity. The work supports recent studies reporting functional E/I subnetworks in several sensory cortexes, and will be of interest to both theoretical and experimental neuroscientists studying network dynamics based on structured excitatory and inhibitory interactions.

    1. eLife Assessment

      This work is important because it elucidates how immune cells migrate across the blood brain barrier. In the revised version of this study, the authors present a convincing framework to visualize, recognize and track the movement of different immune cells across primary human and mouse brain microvascular endothelial cells without the need for fluorescence-based imaging using microfluidic devices. This work will be of broad interest to the cancer biology, immunology and medical therapeutics fields.

    1. eLife Assessment

      This study presents a valuable conceptual approach that cell lineage can be determined using methylation data. However, the evidence supporting the claims of the author remains incomplete after revision. If clarified further as described in the reviews, this approach could be of broad interest to neuroscientists and developmental biologists.

    1. eLife Assessment

      This study presents a valuable finding on the mechanism of self-prioritization by revealing the influence of self-associations on early attentional selection. The evidence supporting the claims of the authors is solid, although inclusion of a discussion about the generalization and limitation would have strengthened the study. The work will be of interest to researchers in psychology, cognitive science, and neuroscience.

    1. eLife Assessment

      This study describes a valuable new model for in vivo manipulation of microglia, exploring how mutations in the Adar1 gene within microglia contribute to Aicardi-Goutières Syndome. The methodology is validated with solid data, supporting the authors' conclusions. The paper underscores both the advantages and limitations of using transplanted cells as a surrogate for microglia, making it a resource that is of value for biologists studying macrophages and microglia.

    1. eLife Assessment

      This provocative manuscript presents important comparisons of the morphologies of Archaean bacterial microfossils to those of microbes transformed under environmental conditions that mimic those present on Earth during the same Eon. The evidence in support of the conclusions is solid. The authors' environmental condition selection for their experiment is justified.

    1. eLife Assessment

      Previous studies in mammals and other vertebrates have shown that a noninvasive measure of cochlear tuning, based on the latency derived from stimulus-frequency otoacoustic emissions, provides a reasonable, and non-invasive, estimate of cochlear tuning. This valuable study confirms that finding in a new species, the budgerigar, and provides convincing support for the utility of otoacoustic estimates of cochlear tuning, a methodology previously explored primarily in mammals. The study's remaining claims of a mismatch between behavioral frequency selectivity and cochlear tuning are based on old behavioral data, and collected in an extreme frequency region at the edge of the limits of hearing. Hearing abilities are hard to measure accurately on the upper frequency edge of the hearing range, and the evidence for these claims is weak.

    1. eLife Assessment

      This is an important study using a combination of optogenetics and calcium imaging to provide insight into the function of the cholinergic input to the prelimbic cortex in probabilistic spatial learning as it relates to threat. These data are timely in contributing to an ongoing discussion in the field about the role of phasic cholinergic signaling to the cortex, about which relatively little is known. The strength of the evidence is incomplete and could be improved by changes in task design and analyses, cross-validation of the conditions in calcium imaging, as well as the incorporation of control experiments to more definitively show it is indeed acetylcholine working in this circuit.

    1. eLife Assessment

      This important study leverages the power of Drosophila genetics and sparsely-labeled neurons to propose a new model for neuronal injury signaling. The authors present convincing evidence to support that the somatic response to axonal injury is suppressed if the injury is not complete, suggesting the presence of an integration of axonal injury-related signaling. While the underlying mechanism of this fascinating observation is unknown, the phenomenon itself will be of broad significance in the field.

    1. eLife Assessment

      This important study describes a neural circuit contributing to two behavioral processes affecting pathogen avoidance in the nematode C. elegans. The method used to identify specific contributing neurons is innovative and the experimental evidence supporting the major claims is solid. This study will be of interest to neuroscientists studying behavior, in particular in C. elegans.

    1. eLife Assessment

      This study presents important analyses of the impacts of microexon deletions and loss-of-function in microexon regulators on zebrafish neurite outgrowth and gene expression, as well as adult and larval behavior. While microexons have been mapped in many genes several years ago, information on their functions - in particular with regard to individual gene isoforms - is limited. The authors provide convincing evidence that individual microexon deletions, only in a few cases, produce subtle cellular and behavioural phenotypes, while transcriptomic analysis reveals gene expression alterations that are suggestive of compensatory mechanisms that buffer against microexon disruption.

    1. eLife Assessment

      This important study provides new insights into the plasticity mechanisms underlying the formation of spatial maps in the hippocampus. Supported by a large and comprehensive dataset, the evidence is solid. However, certain aspects of the statistical analysis and data presentation may seem incomplete and warrant improvement. This study will be of interest to neuroscientists focusing on spatial navigation, learning, and memory.

    1. eLife Assessment

      This cleverly-designed and potentially important work supports our understanding regarding how and whether social behaviours promoting egalitarianism can be learned, even when implementing these norms entails a cost for oneself. However, the evidence supporting the major claims is currently incomplete, with major limitations being the statistical approach, the modelling, and over-interpretation. With a strengthening of the supporting evidence, this work will be of interest to a wide range of fields, including cognitive psychology/neuroscience, neuroeconomics, and social psychology, as well as policy making.

    1. eLife Assessment

      This paper shows convincingly that the human visual system can recalibrate itself to compensate for phase alterations in an image induced by optical blur. This phenomenon is studied using state-of-the-art adaptive optics approaches that allow the manipulation of the eye's optics while making concurrent psychophysical measurements. The findings are broadly important because they highlight a neural mechanism by which flawed information is used to create seemingly accurate perceptions of the visual environment.

    1. eLife Assessment

      The study presents some useful findings on Mendelian randomization-phenome-wide association, with BMI associated with health outcomes, and there is a focus on sex differences. Although there are some solid phenotype and genotype data, some of the data are incomplete and could be better presented, perhaps benefiting from more rigorous approaches. Confirmation and further assessment of the observed sex differences will add further value.

    1. eLife Assessment

      Gating of mechanosensitive channels has been explained by the force-from-lipids model in which mechanical coupling of the channel protein to the plasma membrane transfers force from membrane tension to open the channel. In this important manuscript, the authors provide evidence for this mechanism in two different mechanically gated channels. The experiments were carried out in the same membranes, but the evidence is incomplete without a clear explanation of the relationship between measured mechanical parameters and membrane interfacial tension.

    1. eLife Assessment

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

    1. eLife Assessment

      This study reveals that female moths utilize ultrasonic sounds emitted by dehydrated plants to inform their oviposition decisions, highlighting sound as a potential sensory cue for optimal host plant selection. By investigating this novel acoustic interaction, the research adds an important piece to our understanding of plant-insect interactions. While the authors employed an overall solid experimental approach, weaknesses include the lack of raw data and individual data point visualization, inconsistencies in moth responses to sound cues with and without plants, and the use of a click frequency higher than what plants typically produce, which may limit the ecological applicability and broader generalization of the findings.

    1. eLife Assessment

      This descriptive manuscript builds on prior research showing that the elimination of Origin Recognition Complex (ORC) subunits does not halt DNA replication. The authors use various methods to genetically remove one or two ORC subunits from specific tissues and observe continued replication, though it may be incomplete. The replication appears to be primarily endoreduplication, indicating that ORC-independent replication may promote genome reduplication without mitosis. Despite similar findings in previous studies, the paper provides convincing genetic evidence in mice that liver cells can replicate and undergo endoreduplication even with severely depleted ORC levels. While the mechanism behind this ORC-independent replication remains unclear, the study lays the groundwork for future research to explore how cells compensate for the absence of ORC and to develop functional approaches to investigate this process. The reviewers agree that this valuable paper would be strengthened significantly if the authors could delve a bit deeper into the nature of replication initiation, potentially using an origin mapping experiment. Such an exciting contribution would help explain the nature of the proposed new type of Mcm loading, thereby increasing the impact of this study for the field at large.

    1. eLife Assessment

      In this useful manuscript, the authors performed scRNA-seq on a diverse cohort of 15 early-stage cervical cancer patients. Correlative data is provided to support the possible establishment of an immunosuppressive microenvironment near SCL26A3+ cells, and an association of these cells with upstaging at time of surgery. However without more extensive validation, the evidence supporting the conclusions remains incomplete. Overall, this paper will provide a potentially helpful dataset for researchers studying cervical cancer.

    1. eLife Assessment

      This valuable study shows previously unappreciated binding of the eukaryotic translation initiation factor 3 (eIF3) to the poly(A) tail proximal portion of 3' untranslated regions (UTRs) of mRNAs that are efficiently translated in neuronal progenitors. The authors' conclusions are supported by solid experimental evidence which is based on several orthogonal systems biology approaches. This article is of considerable interest to the broad spectrum of biomedical researchers interested in studying post-transcriptional regulation of gene expression.

    1. eLife Assessment

      Yu and colleagues used two-sample MR to test the effect of PUFA on cerebral aneurysms. They found that genetically predicted omega-3 and DHA decreased the risk for Intracranial Aneurysm and Subarachnoid Haemorrhage. This work is useful and the revised version provides solid evidence to support the claims.

    1. eLife Assessment

      This work provides important findings characterizing potential synaptic mechanisms supporting the role of midline thalamus-hippocampal projections in fear memory extinction in mice. The methods and approaches were considered solid, though some evidence is incomplete as there are some concerns with the analytical approaches used for some aspects of the study. This work will be of interest to those in the field of thalamic regulation and fear memory.

    1. eLife Assessment

      The important study established a large-scale objective and integrated multiple optical microscopy systems to demonstrate their potential for long-term imaging of the developmental process. The convincing imaging data cover a wide range of biological applications, such as organoids, mouse brains, and quail embryos, but enhancing image quality can further enhance the method's effectiveness. This work will appeal to biologists and imaging technologists focused on long-term imaging of large fields.

    1. eLife Assessment

      Wang et al. presented visual (dot) motion and/or the sound of a walking person and found solid evidence that EEG activity tracks the step rhythm, as well as the gait (2-step cycle) rhythm, with some demonstration that the gait rhythm is tracked superadditively (power for A+V condition is higher than the sum of the A-only and V-only condition). The valuable findings will be of wide interest to those examining biological motion perception and oscillatory processes more broadly. Some of the theoretical interpretations concerning entrainment must remain speculative when the authors cannot dissociate evoked responses from entrained oscillatory effects

    1. eLife Assessment

      In this manuscript, Griesius et al analyze the dendritic integration properties of NDNF and OLM interneurons, and suggest that the supralinear NMDA receptor-dependent synaptic integration may be associated with dendritic calcium transients only in NDNF interneurons. These findings are important because they suggest there might be functional heterogeneities in the mechanisms underlying synaptic integration in different classes of interneurons of the mouse neocortex and hippocampus. The revised work remains incomplete due to remaining concerns about experimental methodology, cell health, and lack of dendritic Na-spikes which have been recorded in previous works.

    1. eLife assessment

      This manuscript provides valuable information about the genesis of CPSF6 condensates due to HIV-1 infection. However, the evidence is incomplete as it is missing more functional assays. Furthermore, some data on the fusion between CPSF6 Aggregates and SC35 speckles are not novel.

    1. eLife Assessment

      This important study uses machine learning-based network analysis on transcriptomic data from different tissue cell types to identify a small set of conserved (pan-tissue) genes associated with changes in cell mechanics. The new method, which provides a new type of approach for mechanobiology, is accessible, compelling, and well-validated using in silico and experimental approaches. The study provides motivation for researchers to test hypotheses concerning the identified five-gene network, and the method will be strengthened over time with expanded sets of validations, such as testing genes with hitherto unknown roles and different perturbation techniques.

    1. eLife Assessment

      This fundamental work demonstrates that compartmentalized cellular metabolism is a dominant input into cell size control in a variety of mammalian cell types and in Drosophila. The authors show that increased pyruvate import into the mitochondria in liver-like cells and in primary hepatocytes drives gluconeogenesis but reduces cellular amino acid production, suppressing protein synthesis. The evidence supporting the conclusions is compelling, with a variety of genetic and pharmacologic assays rigorously testing each step of the proposed mechanism. This work will be of interest to cell biologists, physiologists, and researchers interested in cell metabolism, and is significant because stem cells and many cancers exhibit metabolic rewiring of pyruvate metabolism.

    1. eLife Assessment

      This work is of fundamental significance and has a compelling level of evidence for the role of mutant p53 in regulation of tumorigenesis using an in vivo mouse model. The study is well-conducted and will be of interest to a broad audience including those interested in p53, transcription factors and cancer biology.

    1. eLife Assessment

      This manuscript provides potentially important findings examining in 2D and 3D models in MYC liver cancer cells changes in DNA repair genes and programs in response to hypoxia. The authors use convincing methodology in most cases, but there is some concern that the analysis is incomplete.

    1. eLife Assessment

      Overall, this fundamental study identified a novel role of NOLC1 in regulating p53 nuclear transcriptional activity and p53-mediated ferroptosis in gastric cancer. The evidence supporting the conclusions is solid, although some new evidence is needed to make it more robust. The work will be of broad interest to cancer biologists and oncologists.

    1. eLife Assessment

      This important work advances our understanding of how the SARS-CoV-2 Nsp16 protein is regulated by host E3 ligases to promote viral mRNA capping. However, support for the overall claims is incomplete as the authors need to demonstrate Nsp16 ubiquitination and the role of E3 ligases in a more biologically relevant context (ie. infection). This work will be of interest to those working in host-viral interactions and the role of the ubiquitin-proteasome system in viral replication.

    1. eLife Assessment

      In the field of early detection of disease and recurrence and monitoring of treatment efficacy by cfDNA analysis, this study presents a useful finding that HPV cfDNA level monitoring provides advantages over serum levels of squamous cell carcinoma antigen (SCC-Ag), specifically for HPV+ cervical cancer. The data were collected and analysed using solid and validated methodology but the sample number was limited.

    1. eLife Assessment

      This work presents a valuable self-supervised method for the segmentation of 3D cells in microscopy images, alongside an implementation as a Napari plugin and an annotated dataset. While the Napari plugin is readily applicable and promises to eliminate time consuming data labeling to speed up quantitative analysis, there is incomplete evidence to support the claim that the segmentation method generalizes to other light-sheet microscopy image datasets beyond the four specific ones used here.

  2. Dec 2024
    1. eLife Assessment

      This important study uses optogenetics in combination with single cell recordings to selectively activate sensory input channels within the olfactory bulb, providing direct evidence for activity-dependent and distance-independent enhancement of stimulus-evoked gamma oscillations via lateral interactions between input channels, most likely via granule cells. The article presents solid evidence to support the main conclusions.

    1. eLife Assessment

      The findings of this study are potentially valuable, offering insights into the neural representation of reversal probability in decision-making tasks, with potential implications for understanding flexible behavior in changing environments. The evidence presented is incomplete, with interesting comparisons between neural data and models, but the analyses do not yet provide clear evidence against line attractor dynamics for the accumulation of evidence of a reversal in this probabilistic reversal learning task.

    1. eLife Assessment

      This important work examines how microexons contribute to brain activity, structure, and behavior. The authors find that loss of microexon sequences generally has subtle impacts on these metrics in larval zebrafish, with few exceptions. The evidence is still partially incomplete and needs to be strengthened by key experiments or more precise data descriptions. Overall, this work will be of interest to neuroscientists and generate further studies of interest to the field.

    1. eLife Assessment

      This study demonstrates the potential role of 17α-estradiol in modulating neuronal gene expression in the aged hypothalamus of male rats, identifying key pathways and neuron subtypes affected by the drug. While the findings are useful and provide a foundation for future research, the strength of supporting evidence is incomplete due to the lack of female comparison, a young male control group, unclear link to 17α-estradiol lifespan extension in rats, and insufficient analysis of glial cells and cellular stress in CRH neurons.

    1. eLife Assessment

      This valuable study suggests that Naa10, an N-α-acetyltransferase with known mutations that disrupt neurodevelopment, acetylates Btbd3, which has been implicated in neurite outgrowth and obsessive-compulsive disorder, in a manner that regulates F-actin dynamics to facilitate neurite outgrowth. While the study provides promising insights and biochemical, co-immunoprecipitation, and proteomic data that enhance our understanding of protein N-acetylation in neuronal development, the evidence supporting larger claims is incomplete. Nonetheless, the implications of these findings are noteworthy, particularly regarding neurodevelopmental and psychiatric conditions tied to altered expression of Naa10 or Btbd3.

    1. eLife Assessment

      This study uncovers and characterizes a role for Pfdn5 in stabilizing axonal microtubules and synaptic morphology in the Drosophila peripheral nervous system. Although the mechanisms remain unresolved, the phenotypic characterization is an important contribution with solid evidence. The work also aims to address a potential interaction between Pfdn5/6 and Tau-mediated mechanisms of neurodegeneration; here, the evidence is partially incomplete.

    1. eLife Assessment

      This valuable study explores the role of spatial genome organization in oncogenic transformation, addressing an ambitious and significant topic. The authors have assembled comprehensive datasets from various subtypes of localized and lung-metastatic breast cancer cells, as well as from healthy and cancerous lung cells. They identified switching patterns in the 3D genome organization of lung-metastatic breast cancer cells, revealing a reconfiguration of genome architecture that resembles that of lung cells. If validated, this study could be critical for the field; however, at this stage, it is incomplete, as the main claims are only partially substantiated.

    1. eLife Assessment

      This study presents the state-dependent role of serotonin for the protein and sugar intake of Drosophila by expressing a dominant-negative serotonin transporter in subsets of serotoninergic neurons. This paper is valuable for neuroscientists working on neuromodulation and the effects of internal states such as hunger, however the characterization of behavioral and neuroanatomical data is incomplete.

    1. eLife Assessment

      This study reports important findings about the nature of feedback to primary visual cortex (V1) during object recognition. The state-of-the-art functional MRI evidence for the main claims is solid, although currently alternative explanations of the findings cannot be fully ruled out. The findings presented here are relevant to a number of scientific fields such as object recognition, categorisation and predictive coding.

    1. eLife Assessment

      This valuable study relating brain anatomy to reading ability in children studied longitudinally finds that a difference in sulcal anatomy is more predictive of reading ability than cognitive measures. The evidence that this anatomical difference is predictive and confers some benefit in the connectivity between brain areas is based on careful analyses and is solid. The findings would be of interest to researchers studying brain and cognitive development.

    1. eLife Assessment

      This valuable study combines evolution experiments with molecular and genetic techniques to study how a genetic lesion in MreB that causes rod-shape cells to become spherical, with concomitant deleterious fitness effects, can be rescued by natural selection. The results are convincing, although further improvement of the statistical analyses and figure presentation, and further clarification of the concrete contribution of the paper and how it relates to previous literature, would be welcome.

    1. eLife Assessment

      Gil Ávila et al. evaluated the aperiodic component in the medial prefrontal cortex using resting-state EEG recordings from 149 individuals with chronic pain and 115 healthy participants. The authors present compelling evidence that the aperiodic component of the EEG does not differentiate between those with chronic pain and healthy individuals. The study was well-designed and rigorously conducted, and the clear and conclusive results provide important insights that can guide future research in the field of pain neuroscience.

    1. eLife Assessment

      This important study enhances our understanding of the foraging behaviour of aerial insectivorous birds. Using solid methodology, the authors have collected extensive data on bird movements and prey availability, which in turn provide support for the main claim of the study. The work will be of broad interest to behavioural ecologists.

    1. eLife Assessment

      This important study describes two findings: first, that TEAD is subject to turnover by the ubiquitin-proteasome system involving RNF146 and Parylation, and second, the development of a pan-TEAD heterobifunctional degrader that is used to inhibit growth of a YAP-dependent cancer cell line and to characterize TEAD binding sites in the genome. Convincing evidence supports the development and specificity of the degrader. This article will be of relevance to cancer biologists and scientists interested in proteostasis, cellular signaling, and post-translation modification of proteins.

    1. eLife Assessment

      This study presents a useful model of genetic drift by incorporating variance in reproductive success, claiming to address several paradoxes in molecular evolution. However, some of the claimed "paradoxes" seem to be overstatements, as previous literature has pointed out the limitations of the standard model and proposed more advanced models to address those limitations. While the proposed new model presented in this paper yields some intriguing theoretical predictions, the analysis and simulations presented are incomplete to support the authors' strong claims, and it is unclear how much the model helps explain empirical observations.

    1. eLife Assessment

      In this important study, the authors employed three types of theoretical/computational models (coarse-grained molecular dynamics, analytical theory and field-theoretical simulations) to analyze the impact of salt on protein liquid-liquid phase separation. These different models reinforce each other and together provide convincing evidence to explain distinct salt effects on ATP mediated phase separation of different variants of caprin1. The insights and general approach are broadly applicable to the analysis of protein phase separation. Still, modeling at the coarse-grained level misses key effects that have been revealed by all-atom simulations, including salt-backbone coordination and strengthening of pi-type interactions by salt.

    1. eLife Assessment

      This manuscript aims to identify the pacemaker cells in the lymphatic collecting vessels - the cells that initiate the autonomous action potentials and contractions needed to drive lymphatic pumping. Through the exemplary use of existing approaches (genetic deletions and cytosolic calcium detection in multiple cell types), the authors convincingly determine that lymphatic muscle cells are the origin of the action potential that triggers lymphatic contraction. The inclusion of scRNAseq and membrane potential data enhances a tremendous study. This fundamental discovery establishes a new standard for the field of lymphatic physiology.

    1. eLife Assessment

      This valuable study presents new observations on white matter organisation at the micron scale, using a combination of synchrotron imaging and diffusion MRI across two species. Notably, the authors provide solid evidence for the fasciculation of axons within major fibre bundles into laminar structures, though these structures are not consistently observed across modalities or species. The study will be of general interest to neuroanatomists and those interested in white matter imaging.

    1. eLife Assessment

      This valuable study extends the previous interesting work of this group to address the potentially different control of movement and posture. Through experiments in which stroke participants used a robotic manipulandum, the authors provide solid evidence supporting a lack of a relation between the resting force postural bias they measure (closely related to the flexor synergy in stroke) and kinematic deficits during movement. Based on these results, the authors propose a conceptual framework that differentially weights the two main descending pathways (corticospinal tract and reticulospinal tract) for neurologically intact and stroke patients. Discussing the potential impact of differences on muscle/spinal circuit state and their responses between holding a posture and movement, as well as the assumptions of their statistical comparisons, would further improve the paper.

    1. eLife Assessment

      This study provides important insights into the regulation of a retained intron in the mRNA coding for OGT, a process known to be regulated by the O-GlcNAc cycling system, and highlights the functional role of the splicing regulator SFSWAP. The evidence supporting the claims of the authors is convincing: the authors performed an elegant state-of-the-art CRISPR knockout strategy and sophisticated bioinformatic analysis to identify SFSWAP as a negative regulator of alternative splicing. The work will be of interest to researchers in the fields of splicing and glycobiology.

    1. eLife Assessment

      This study provides useful findings about the effects of heterozygosity for Trio variants linked to neurodevelopmental and psychiatric disorders in mice. However, the strength of the evidence is limited and incomplete mainly because the experimental flow is difficult to follow, raising concerns about the conclusions' robustness. Clearer connections between variables, such as sex, age, behavior, brain regions, and synaptic measures, and more methodological detail on breeding strategies, test timelines, electrophysiology, and analysis, are needed to support their claims.

    1. eLife Assessment

      This study investigates the fundamental role of polyunsaturated fatty acids (PUFAs) in membrane biology, using a unique model to perform a thorough genetic screen that highlights that PUFA synthesis defects cannot be compensated for by mutations in other pathways. While the data are solid and generally support the claims, additional experimental validation or more detailed descriptions of their results would strengthen the broader conclusions. This study will appeal to researchers in membrane biology, lipid metabolism, and C. elegans genetics.

    1. eLife Assessment

      This paper provides a valuable contribution to our understanding of how adenosine acts as a signal of nutrient insufficiency and extends this idea to suggest that adenosine is released by metabolically active cells in proportion to the activity of methylation events. Convincing data support this idea. The authors use metabolic tracing approaches to identify the biochemical pathways that contribute to the regulation of adenosine levels and the S-adenosylmethionine cycle in Drosophila larval hemocytes in response to wasp egg infection.

    1. eLife Assessment

      This valuable study investigates the neural basis of causal inference of illness, suggesting that it relies on semantic networks specific to living things in the absence of a generalized representation of causal inference across domains. However, the evidence remains incomplete due to some unjustified design and analysis choices. Moreover, the authors do not fully exploit the potential of multivariate fMRI analyses to rigorously test their main hypothesis.

    1. eLife Assessment

      The authors examine the effect of cell-free chromatin particles (cfChPs) derived from human serum or from dying human cells on mouse cells in culture and propose that these cfChPs can serve as vehicles for cell-to-cell active transfer of foreign genetic elements. The work presented in this paper is intriguing and potentially important, but it is incomplete. At this stage, the claim that horizontal gene transfer can occur via cfChPs would strongly benefit from additional evidence emerging from multiple independent approaches. The evolutionary interpretations associated with the concept of "predatory genome" are premature based on the strength of evidence.

    1. eLife Assessment

      Valencia et al. combine elegant in vitro biochemical experiments with functional assays in cardiomyocytes to determine which properties of the FHOD3 formin are essential for sarcomere assembly. Using separation-of-function mutants, they show that FHOD3's elongation activity, rather than its nucleation, capping, or bundling activities, is key to its sarcomeric function. This is an important finding; most of the data presented in the manuscript are convincing, with the exception of two experiments (presence of FHOD3 at the barbed end of actin filaments in the TIRF elongation assays and characterization of the GS-FH1 mutant phenotype) that would merit few additional controls.

    1. eLife Assessment

      This important study investigates the role of vasopressin in modulating same-sex affiliative relationships in the context of linear dominance hierarchies. It provides convincing evidence that vasopressin signaling is involved in modulating aspects of affiliative behavior, although the evidence that affiliative relationships specifically arise from the triadic interaction study design is incomplete. Nevertheless, its focus on broadening the types of social relationships and species studied in this area makes it of interest to both neuroendocrinologists and colleagues studying the evolution and mechanisms underlying social affiliation.

    1. eLife Assessment

      In their valuable study, Lee et al. explore a role for the Hippo signaling pathway, specifically wts-1/LATS and the downstream regulator yap, in age-dependent neurodegeneration and microtubule dynamics using C. elegans mechanosensory neurons as a model. The authors demonstrate that disruption of wts-1/LATS leads to age-associated morphological and functional neuronal abnormalities, linked to enhanced microtubule stabilization, and shows a genetic connection between yap and microtubule stability. Despite some mechanistic gaps, the study employs robust genetic and molecular approaches to reveal a convincing link between the Hippo pathway, microtubule dynamics, and neurodegeneration.

    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 advancement in antiviral research by applying SHAPE-Map to analyze the secondary structure of the Porcine Epidemic Diarrhoea Virus RNA genome in infected cells, identifying promising therapeutic targets within viral genomic RNA. The authors provide convincing evidence of potential antiviral targetable RNA regions through a wide array of data from different methods, supported by well-documented experimental design and data analysis, demonstrating how RNA structural probing can effectively discover RNA targets and enabling further discoveries in the field. The work will be of interest to researchers focused on RNA therapeutics and viral genome studies.

    1. eLife Assessment

      In this report, the authors present valuable findings identifying a novel worm-specific protein (sdg-1) that is induced upon loss of dsRNA import via SID-1, but is not required to mediate SID-1 RNA regulatory effects. The genetic and genomic approaches are well-executed and the revision contain generally solid support for the central findings of the work. These findings will be of interest to those working in the germline epigenetic inheritance field.

    1. eLife Assessment

      This is a valuable study regarding the role of gasdesmin D in experimental psoriasis. The study contains solid evidence for such a role, involving neutrophils, from murine models of skin inflammation, as well as correlative data of elevated gasdermin D expression in human psoriatic skin. The findings will be of interest to researchers trying to unravel pathways of skin inflammation.

    1. eLife Assessment

      This important work is a versatile new addition to the chemical protein modifications and bioconjugation toolbox in synthetic biology. The technology developed cleverly uses Connectase to irreversibly fuse proteins of interest together so they can be studied in their native context, with convincing data showing the technique works for various protein partners. This work will help multiple fields to explore multi-function constructs in basic synthetic biology. This work will also be of interest to those studying fusion oncoproteins commonly expressed in various human pathologies.

    1. eLife Assessment

      This study investigated mitochondrial dysfunction and the impairment of the ciliary Sonic Hedgehog signaling in Lowe syndrome (LS), a timely topic given the limited research in this area. The data from patient iPSC-derived neurons and a mouse model were collected using solid methods, but the evidence supporting key claims is incomplete, and some technical aspects fall short of expectations. Despite these limitations, the study provides a useful foundation for exploring the relationship between mitochondrial defects and primary cilia in neural development.

    1. eLife Assessment

      This valuable study proposes a theoretical model of clathrin coat formation based on membrane elasticity that seeks to determine whether this process occurs by increasing the area of a protein-coated patch with constant curvature, or by increasing the curvature of a protein-coated patch that forms in an initially flat conformation (so called constant curvature or constant area models). Identifying energetically favorable pathways and comparing the obtained shapes with experiments provides solid support to the constant-area pathway. This work will be of interest for biologists and biophysicists interested in membrane remodelling and endocytosis. It provides an innovative approach to tackle the question of constant curvature vs. constant area coat protein formation, although some of the model's assumption are only partially supported by experimental evidence.

    1. eLife Assessment

      This study provides valuable quantitative data and analysis that reveals variations in 'Dorsal' nuclear dynamics along the dorso-ventral axis in the early Drosophila embryo. The evidence that supports that these variations are due to Dorsal/Cactus interactions in dorsal nuclei is convincing, albeit incomplete to understand the biological implications of these findings for developmental patterning.

    1. eLife Assessment

      With compelling electrophysiological and behavioural evidence, this work establishes that the activity of insulin-producing cells (IPCs) depends on the nutritional state in Drosophila and that, like in mammals, there is also an incretin-like effect with IPCs responding to glucose feeding but not to glucose perfusion. Moreover, the authors demonstrate that DH44 neurons respond to glucose perfusion and, together with IPCs, modulate locomotor activity. This important study on the neuronal regulation of metabolic homeostasis will be of interest to both neuroscience and to medical research in diabetes.

    1. eLife Assessment

      Although others have proposed that OHC electromotility subserves cochlear amplification by acting as a "fluid pump", and evidence for this has been found using electrical stimulation of excised cochleae, this fundamental study substantially advances our understanding of cochlear homeostasis. This is the first report to test the pumping effect in vivo and consider its implications for cochlear homeostasis and drug delivery. The manuscript provides compelling evidence for OHC-based fluid flow within the cochlea.

    1. eLife Assessment

      The manuscript presents valuable findings of bone remodeling under chronic unpredictable mild stress (CUMS). This is an interesting work on mental stress on bone health and osteoporosis, and the authors offer solid evidence of decreased bone mass mediated by miR-335-3p/Fos signaling in osteoclasts that are involved in the induction of bone loss caused by CUMS. This revised version provided new data that improved the quality of the manuscript and addressed the reviewers' concerns.

    1. eLife Assessment

      This study presents an advance in efforts to use histone post-translational modification (PTM) data to model gene expression and predict epigenetic editing activity. Such models are broadly useful to the research community, especially ones that can model epigenetic editing activity, which is novel; additionally, the authors have nicely integrated datasets across cell types into their model. The work is mostly solid, but it would be strengthened by performing rigorous comparisons to existing methods that predict gene expression from PTM data and from additional model validation beyond dCas9-p300 based perturbations.

    1. eLife Assessment

      This is an important study showing that people who are hungry (vs. sated) put more weight on taste (vs. health) in their food choices. The experiment is well-designed and includes choice behavior, eye-tracking, and state-of-the-art computational modeling, resulting in compelling evidence supporting the conclusions. The manuscript could be further improved through appropriate revisions to data analysis and interpretation.

    1. eLife Assessment

      This valuable study presents a meta-analysis of the literature, confirming the relationship between the coupling of slow oscillations and fast spindles in memory formation, although the reported effects are weak and should be more clearly justified. Furthermore, while the evidence is convincing overall, the manuscript provides an incomplete description of the methods, which may challenge comprehension for readers unfamiliar with advanced statistical techniques. This study will be of interest to neuroscientists focusing on sleep and memory.

    1. eLife Assessment

      This manuscript describes a fundamental investigation of the functioning of Cas9 and in particular on how variant xCas9 expands DNA targeting ability by an increase-flexibility mechanism. The authors provide compelling evidence to support their mechanistic models and the relevance of flexibility and entropy in recognition. This work can be of interest to a broad community of structural biophysicists, computational biologists, chemists, and biochemists.

    1. eLife Assessment

      This study reports valuable findings that highlight the importance of data quality and data representation for ligand-based virtual screening experiments. The authors' claims are supported by solid evidence, although the conclusions have been inferred from only two datasets. The work would gain much impact if additional datasets were used. The main findings will be of interest to cheminformaticians and medicinal chemists working in QSAR modeling, and possibly in other areas related to machine learning.

    1. eLife Assessment

      This important study used an automated system to collect eggs laid over the course of multiple days by individual female Drosophila to successfully reveal a robust yet noisy circadian rhythm of egg-laying. Their results show that the neural control of this rhythm is entirely different from the one that controls locomotor activity rhythmicity. Preliminary connectome-based analyses provide evidence for connections between the relevant clock neurons and neurons involved in oviposition. The evidence provided is solid, although using an independent tool for targeted knockdown of clock genes and including the time series of representative individuals for all genotypes tested would help interpret the results.

    1. eLife Assessment

      This important study demonstrates the ability for high-throughput recording and categorization of unconstrained and stimulus-based behaviors across a very large population of marmosets (n = 120 animals across 36 family units). The authors implement an analytical approach to identify "outlier" behavior that could be key in the development of next-generation precision psychiatry. While the strength of evidence appears solid overall, many key methodological details are incomplete.

    1. eLife Assessment

      MGPfactXMBD is a novel computational method for investigating cell evolutionary trajectory for scRNA-seq samples. It is important, with several potential future applications. The authors benchmarked this method using synthetic and real-world samples and showed superior performance for some of the tasks in cell trajectory analysis compared to other methods with compelling evidence.

    1. eLife Assessment

      This useful work identifies a key role for Tachykinin-1 parasubthalamic neurons in avoidance learning. At present, the evidence for the conclusions regarding fiber photometry, viral transfection, reporting of behavioral outcomes, and pathway-specificity is incomplete. This work will be of interest to neuroscientists studying neural mechanisms for avoidance and aversion.

    1. eLife Assessment

      This study uses a large dataset from both recent isolates and genomes in databases to provide an important analysis of the population structure of the pathogen Salmonella gallinarum. The authors present convincing results regarding the regional adaptation and the evolutionary trajectory of the resistome and mobilome, even though some issues regarding the genomic analysis could be improved. This work will interest microbiologists and researchers working on genomics, evolution, and antimicrobial resistance.

    1. eLife Assessment

      This valuable study tackles the well-established overflow metabolism issue by applying a coarse-grained metabolic flux model to predict how individual cells execute various energy strategies, such as respiration versus fermentation. The model's population average is convincing enough to align with experimental observations on overflow metabolism. However, the theoretical framework's reliance on single-cell growth rate variability must be questioned because of insufficient correlation with fluxes and the absence of regulatory mechanisms, highlighting the need for single-cell experimental validation to substantiate the proposed model.

    1. eLife Assessment

      This important study explores the association between mother-child interactions and the development of children's social brain networks, specifically the theory of mind and social pain networks. The findings provide solid evidence for enhanced stimulus-evoked neural synchronization between child-caregiver dyads, while the evidence for the other variables is incomplete and could be strengthened with further analyses. The study effectively bridges brain development with children's behavior and parenting practices and would be of interest to broad research communities in social neuroscience and developmental psychology.

    1. eLife Assessment

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

    1. eLife Assessment

      This important study is of significant relevance to the fields of predictive processing, perception, and learning. The well-designed paradigm allows the authors to avoid several common confounds in investigating predictions, such as stimulus familiarity and adaptation. Using a state-of-the-art multivariate EEG approach, the authors test the opposing process theory and find evidence in support of it, but some elements - especially the interactions across block - have only incomplete support at present. This could be strengthened via further analyses and justification.

    1. eLife Assessment

      The findings are considered valuable and have theoretical implications for the interdisciplinary field of value-based social decision-making. Support for the main claims is incomplete and these should be supported by further analyses.

    1. eLife Assessment

      This study presents important findings on the activity of two compounds, BKC and IBC, isolated from Psoralea corylifolia, which act synergistically to inhibit cancer cell proliferation. Using a spectrum of methods, the authors characterized the mechanisms of action of both drugs, providing convincing evidence that BKC targets DNA polymerases and IBC selectively inhibits CHK2. The study opens the possibility of improving the effectiveness of the combination of BKC and other damaging agents with IBC in cancer treatment.

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

    1. eLife Assessment

      This valuable study uses AlphaFold2 to guide the structural modelling of different states of the human voltage-gated potassium channel KV11.1, a key pharmacological drug target. Follow-up molecular dynamics and drug-docking simulations, combined with experimental comparisons, offer convincing evidence supporting the models, showing that drugs bind more effectively to the inactivated state. The work shows potential for improving drug potency predictions in ion channel pharmacology, though its applicability to other systems remains uncertain.

    1. eLife Assessment

      This is an important technical method paper that details the development and quality assessment of a 3D MERFISH method to enable spatial transcriptomics of thick tissues, representing a major step forward in the technical capacity of the MERFISH. The evidence presented is convincing.

    1. eLife Assessment

      This paper advances an important new concept in psoriasis pathogenesis and implicates Sema4a as a homeostatic regulator that is highly epithelial-specific. The findings are convincing and lend support for the biology described here as a mechanism with therapeutic implications.

    1. eLife Assessment

      This paper presents the important discovery that lipid metabolic imbalance caused by Snail, an EMT-related transcription factor, contributes to the acquisition of chemoresistance in cancer cells. However, the incomplete support for the authors' claims is due to concerns about the causal relationship and lack of sufficient quantitative analysis. With strengthened evidence, this work would be of broad interest to researchers in the fields of cancer biology, lipid metabolism, and cell biology.

    1. eLife Assessment

      The authors use deep mutational scanning to assess the effect of all possible protein-coding variants in MC4R, a G protein-coupled receptor associated with obesity. They develop new, more precise approaches, enabling them to probe molecular phenotypes directly relevant to the development of drugs that target this receptor. In this important work, the authors provide convincing evidence that variants impact signaling through MC4R in different ways, that some defective variants are amenable to a corrector drug and that deep mutational scanning data could guide compound optimization.

    1. eLife Assessment

      This important study demonstrates the therapeutic potential of recombinant human PDGF-AB/BB proteins in reducing the senescent signatures of primary human intervertebral disc cells. The study represents a significant advance in the treatment of intervertebral disc degeneration and can be applied broadly to other degenerative musculoskeletal tissues through the suppression of senescence. Solid evidence, primarily based on transcriptomic analysis and direct protein measurements from relatively homogeneous cell populations, supports the therapeutic potential of PDGF, but more experimental details would be needed to make the evidence stronger.

    1. eLife Assessment

      In this manuscript, Yao et al. present solid evidence to show that MnMYL3 may serve as a receptor for NNV via macropinocytosis. This manuscript is valuable for understanding the molecular mechanisms of NNV cell entry. However, the manuscript will benefit from broader implications of these findings for cell entry of other viruses.

    1. eLife Assessment

      This important work develops a new protocol to experimentally perturb target genes across a quantitative range of expression levels in cell lines. The evidence supporting their new perturbation approach is compelling, and the computational analyses to better understand dosage response relationships between genes are convincing. The study will be of broad interest to scientists in the fields of functional genomics and biotechnology. However, the evidence supporting the conclusions can be further improved.

    1. eLife Assessment

      This study presents valuable data on the identification and function of a protein complex present at the Maurer's cleft organelles of Plasmodium falciparum-infected red blood cells. The evidence supporting the findings is solid, but would benefit from greater rigor in presentation and analysis.

    1. eLife Assessment

      Morphological characteristics and phenotypes of mutations in key developmental genes suggest that head, trunk, and tail development are regulated by discernible modules. Gdf11 signalling plays a crucial role in orchestrating the transition from trunk to tail tissues in vertebrate embryos. This important study presents convincing evidence that Tgfbr1 acts upstream of Isl1 (a pivotal effector of Gdf11 signalling) and regulates blood vessels, the lateral plate mesoderm, and the endoderm associated with the trunk-to-tail transition. Together with the previous studies, this work identifies a key signal that acts as the pivot of the trunk-to-tail transition.

    1. We think of ourselves as this little bubble of obsessions and memories going on in our head that’s detached from everything else. That’s the wound.

      for - summary - polycrisis - requires a shift in stories - from little self - to big self - from - Emergence Magazine - interview - An Ethics of Wild Mind - David Hinton

      summary - polycrisis - requires a shift in stories - from little self - to big self - from - Emergence Magazine - interview - An Ethics of Wild Mind - David Hinton - We think of ourselves as this little bubble of obsessions and memories going on in our head detached from everything else - THAT'S THE WOUND! - That sounds and IS FELT as bleak, isn't it? - The scientific story of the cosmos is that there are countless solar systems in our universe, countless suns and planets over vast time scales - Our planet evolved life billions of years ago - Some of those life forms became multicellular animals, like us - Some of them developed eyes, nose, ears, skin and a brain and central nervous system - When we look out into the world, it is the cosmos distilled in us looking out at itself - Hence, we are intertwingled and woven into the fabric of everything - the cosmos in human form experiencing the cosmos itself - When we think about our extinction, it is also the cosmos thinking about extinction - When we feel ANYTHING, that's the cosmos feeling it - And WHEN WE DIE that is the cosmos in this human form dying to itself

    1. eLife Assessment

      This study provides a methodological report on a modified adaptive sampling approach, multiple walker supervised molecular dynamics (mwSuMD), and its application to G protein-coupled receptors (GPCRs), which are the most abundant membrane proteins and key targets for drugs. The mwSuMD approach assists in sampling complex binding processes, leading to useful findings for GPCR activity, although results may be considered incomplete, given the high RMSD values reported and lack of validation using experimental data. The manuscript also needs corrected descriptions of high-resolution PDB structures and better relation to existing computational literature.

    1. eLife Assessment

      This study describes a novel mechanism for how collagen fibrils are formed. The authors present compelling evidence that collagen-I fibrillogenesis relies on a functional endocytic system for recycling collagen-I, with circadian-regulated VPS33b and integrin-α11 being critical for fibril assembly. This is an important study for the understanding of the pathophysiology of collagen fibrillogenesis.

    1. eLife Assessment

      This valuable study discusses a hot topic in post-endoscopic retrograde cholangiopancreatography pancreatitis. The new score for predicting post-ERCP pancreatitis offers an idea about the risk of pancreatitis before the procedure. Although most scores depend on intraprocedural manoeuvres, such as the number of attempts to cannulate the papilla, this is a solid retrospective single-center study in one country. To be validated in the future, this score will need to be done in many countries and on large numbers of patients.

    1. eLife Assessment

      This important study provides one mechanism that can explain the rapid diversification of poison-antidote pairs in fission yeast: recombination between existing pairs. The evidence is largely solid, but the study can benefit from demonstrating that the novel poison-antidote constructed by the authors can serve as a meiotic driver. The work is of interest to colleagues studying genetic incompatibilities.

    1. eLife Assessment

      This important chronobiological study in mice suggests that light modulated activity of Cdk5 activity on the PKA-CaMK-CREB signaling pathway provides missing molecular mechanistic details to understand light-induced circadian clock phase delays during the early night, but not for phase advances in the morning. The authors provide convincing evidence bridging from behavioral to molecular/cellular experiments to neural activity imaging.

    1. eLife Assessment

      This study examined the role of the dorsal medial prefrontal cortex of mice in anticipating reward-value switch points in a two-armed bandit task. They demonstrate the dorsal medial prefrontal cortex is involved in task performance and use model-based methods to uncover the algorithmic processes affected by prefrontal cortex perturbations. If the claims were supported, this would be a valuable finding. Unfortunately, the reviewers recognised significant issues with the task design and analyses, making the evidence to support the role of the prefrontal cortex in anticipation of switches inadequate.

    1. eLife Assessment

      This valuable study presents a thorough analysis of protein abundance changes caused by amino acid substitutions, using structural context to improve predictive accuracy. By deriving substitution response matrices based on solvent accessibility, the authors demonstrate that simple structural features can predict abundance effects with accuracy comparable to complex methods such as free energy calculations. The strength of the evidence is solid, supported by robust experimental design and comprehensive analyses. This work is expected to be of interest to broad audiences as it offers practical tools for analyzing mutational effects and insights into the structural basis of proteostasis.

    1. eLife Assessment

      This manuscript describes work that is fundamental to our understanding of the mechanism of how stress regulates the noradrenergic system and the CRH system. Using a combination of ex vivo physiology and in vitro methods, the study provides compelling evidence as to the signaling mechanisms of how glucocorticoids impact adrenergic GPCRs in CRH cells via receptor trafficking. While the ex vivo work is specific to the hypothalamus, the mechanisms here could be extrapolated and investigated in other brain regions that may have similar signaling regulation.

    1. eLife assessment

      This study reports analysis of the formation of electrosensory ampullary organs in non-model organisms, the sterlet sturgeon. By using a combination of targeted gene knock-out and inhibition, the study provides overall convincing evidence for differential roles of BMP signaling in lateral-line development, with few aspects that could be improved. The study is particularly valuable for understanding the development of a still-mysterious sensory system, and for its evolutionary implications.

    1. eLife Assessment

      This valuable study investigates the neural noise hypothesis of developmental dyslexia using electroencephalography (EEG) and 7T magnetic resonance spectroscopy (MRS). Solid results were reported that indicate no evidence of an imbalance between excitatory and inhibitory (E/I) brain activity in adolescents and young adults with dyslexia compared to controls, thereby challenging the neural noise hypothesis. This research advances our understanding of the neural mechanisms underlying dyslexia and offers broader insights into the neural processes involved in reading development.

    1. eLife Assessment

      This study reported that cold exposure induced mRNA expression of genes related to lipid metabolism in the paraventricular nucleus of the hypothalamus (PVH). The authors provide useful data highlighting the potential role of lipid metabolism in the brain during cold exposure. In the revised manuscript, the authors made adequate editions, such as new immunostaining and immunoblotting of AGTL and HSL in the PVH, and pharmacological inhibition of lipid peroxidation and lipolysis. The authors also increased the sample size of some experiments and revised the text to limit their data interpretation. However, the reviewers consider that some key issues, such as cell type specificity and the functional role of lipids on PVH, remain incomplete. Thus, the main conclusion is only partially supported by the data presented.

    1. eLife Assessment

      This is a useful analysis of STORM data that characterizes the clustering of active zones in retinogeniculate terminals across ages and in the absence of retinal waves. The design makes it possible to relate fixed time point structural data to a known outcome of activity-dependent remodeling. However, the evidence is incomplete, weakening the claims the authors make regarding how activity influences the clustering of these synapses.

    1. eLife Assessment

      This is a fundamental study that addresses the key question of how the tetraspanin Tspan12 functions biochemically as a co-receptor for Norrin to initiate β-catenin signaling. The strength of the work lies in the rigorous and compelling binding analyses involving various purified receptors, co-receptors, and ligands, as well as molecular modeling by AlphaFold that was subsequently validated by an extensive series of mutagenesis experiments. The study advances the field by providing a novel mechanism of co-receptor function and shedding new light on how signaling specificity is achieved in the complex Wnt/Norrin signaling system.

    1. eLife Assessment

      This important study provides insights and strategies for assessing laminar structure in vivo in the visual cortex of the macaque monkey with high-density linear electrode arrays. The paper provides convincing evidence demonstrating that signals in higher frequency bands, related to the discharge of action potentials, are of substantially better use for achieving well-resolved cortical layer identification than are signals in lower frequency bands typically associated with local field potentials and standard-practice Current Source Density (CSD) analyses. These findings are of interest to a wide range of neuroscientists making comparisons between cortical layers or recording with array electrodes.

    1. eLife Assessment

      This important study provides solid evidence for a non-genomic action of progesterone in Xenopus oocyte activation. The findings demonstrate that two non-genomic progesterone receptors, ABHD2 and mPRb, function as a novel progesterone-stimulated phospholipase A2. The findings will be of broad interest to reproductive endocrinologists and physiologists.

    1. eLife Assessment

      This work is of fundamental significance to the field of nervous system development as it advances our mechanistic understanding of axon guidance. The rigorous biochemical and genetic approaches are compelling, experiments are well-controlled, and the major claims are supported by convincing data. The study should be of general interest to the developmental neurobiology community.

    1. eLife Assessment

      The paper presents a new behavioral assay for Drosophila aggression and demonstrates that social experience influences fighting strategies, with group-housed males favoring high-intensity but low-frequency tussling over aggressive lunging observed in isolated males. This paper is valuable for researchers studying Drosophila social behaviors, while the characterization of behavioral and neuroanatomical data is incomplete.

    1. eLife Assessment

      This paper proposes a new source reconstruction method for electroencephalography (EEG) data and claims that it can provide far superior spatial resolution than existing approaches and even superior spatial resolution to fMRI. This primarily stems from abandoning the established quasi-static approximation to Maxwell's equations. If verified, the potential impact of the proposed method is very high indeed, but it is currently impossible to verify because the clarity of presentation and the evidence for the claims in the current version is inadequate.

    1. eLife Assessment

      This important study reveals that disrupting fatty acid metabolism in macrophages significantly restricts the growth of Mycobacterium tuberculosis, showing that impaired lipid processing triggers various antimicrobial responses. Whilst the approach is robust, utilizing CRISPR-Cas9 knockout of multiple genes involved in lipid metabolism which yielded some convincing data, there are aspects that require improvement such as the autophagy assay and redox measurements. This work highlights how host lipid metabolism affects the ability of tubercle bacilli to thrive intracellularly, pointing to potential new therapeutic targets.

    1. eLife Assessment

      This study uses electrophysiological recordings, causal manipulations of activity, and modeling to investigate how the maintenance of a spatial location in working memory affects the representation of visual information in area V4 of monkeys. The work is important not just for understanding how visual information is encoded, but also for determining precisely how prefrontal inputs to the sensory cortex sculpt the corresponding visual responses during working memory. The data provide solid evidence of direct communication between prefrontal circuits that store spatial information and V4, which, under the current experimental conditions, manifests mainly as changes in temporal activity patterns (beta oscillations and phase coding).

    1. eLife Assessment

      Masroor Ahmad Paddar and colleagues reveal noncanonical roles of ATG5 and membrane ATG8ylation in regulating retromer assembly and function. They identify ATG5's unique non-autophagic role and show that CASM partially contributes to these phenotypes. Although the mechanism by which ATG8ylation regulates the retromer remains unclear, the findings provide important insights with solid supporting evidence.

    1. eLife Assessment

      This important study uses reinforcement learning to study how turbulent odor stimuli should be processed to yield successful navigation. They find that there is an optimal memory length over which an agent should ignore blanks in the odor to discriminate whether the agent is still inside the plume or outside of it, complementing recent studies using RNNs and finite state controllers to identify optimal strategies for navigating a turbulent plume. While the overall strength of evidence is convincing, better justification for using Brownian motion as a recovery strategy and the addition of accompanying code for reproducibility would add to this strength.

    1. eLife Assessment

      This study presents valuable findings on the role of a well-studied signal transduction pathway, the Slit/Robo system, in the context of the assembly of the hematopoietic niche in the Drosophila embryo. The evidence supporting the claims of the authors is solid. The work will interest developmental biologists working on molecular mechanisms of tissue morphogenesis.

    1. eLife Assessment

      This study unveils important data describing cell states of olfactory ensheathing cells, and how these cell states may relate to repair after spinal cord injury. The framework used for characterizing these cells is solid, although the study would be strengthened by additional quantification of immunohistochemical data and by complementing expression data with functional outcomes. This work will be of interest to stem cell biologists and spinal cord injury researchers.

    1. eLife Assessment

      This important paper provides solid evidence for an alternative conceptualization of the functional role of the place and grid cell network in the medial temporal lobe for memory as opposed to spatial processing or navigation. The theory is extensive, tightly integrating data on various spatial cell types. It accounts for many experimental results and generates strong predictions for future studies that will be of interest to researchers in this field. The impact of the work would be strengthened if future experiments reveal that grid cells do indeed encode specific nonspatial features.

    1. eLife Assessment

      The authors studied the development of mesentery borders in the rice coral Montipora, a new experimental system, to complement existing data from the sea anemone Nematostella. They make a solid case that in Montipora, there is a sequence of Hox-Gbx genes whose staggered expression in the unsegmented larva is suggestive of their role in subdividing the gastric cavity into repeated units bordered by mesenteries, as in the sea anemone Nematostella. Pharmacological experiments also point to the involvement of the BMP pathway in this process, but additional experiments validating this are necessary. This is a valuable contribution to the field of cnidarian evolution, suggesting that BMP- and "Hox-Gbx code"-dependent patterning of the directive axis was ancestral for Anthozoa.

    1. eLife Assessment

      This manuscript develops a theoretical model of osmotic pressure adaptation in microbes by osmolyte production and wall synthesis. The prediction of a rapid increase in growth rate on osmotic shock is experimentally validated using fission yeast. By using phenomenological rules rather than detailed molecular mechanisms, the model can potentially apply to a wide range of microbes, providing important insights that would be of interest to the wider community studying the regulation of cell size and mechanics. However, because the core assumptions of the model have not been tested across a range of microbial organisms, the evidence for the universality of the model remains incomplete.

    1. eLife Assessment

      This potentially important study describes the progressive transformation of olfactory information across five different brain regions in the olfactory pathway. While the dataset could be of broad interest to olfactory researchers, the analysis is incomplete and would benefit from a reconsideration of the data sampling window, a more uniform analysis framework, and greater clarity of presentation.

    1. .

      Describes the neural dynamics associated with auditory stream segregation and the verbal transformation effect (examples of auditory multistable perception).

      Importantly, multistable perception occurs across sensory modalities. Auditory and visual multistable perception may involve similar neural mechanisms.

    2. Figure I.

      Visual representation of how auditory stream segregation is triggered and perceived.

    3. (c)

      Bistable perception example: binocular rivalry (highly relevant).

    4. (b)

      Bistable apparent motion perception example: the spinning wheel illusion.

    5. (a)

      Bistable perception example: the Necker cube (most cited).

    6. .

      When sensory information about a perceived stimulus is ambiguous, the visual system forms multiple distinct interpretations of said stimulus. Multistable perception occurs when perception of the stimulus alternates between interpretations over time.

      Multistable perception may arise from interactions between lower-order and higher order brain processes. Lower order brain processes are involved in basic mental functions such as attention and perception, whereas higher order brain processes are involved in complex mental functions such as reasoning and abstract thinking.

      The review discusses how brain processes underlying different levels of visual processing (low-level sensory, intermediate extrastriate, and high level frontoparietal) interact with one another to produce visual multistable phenomena such as binocular rivalry.

    1. eLife Assessment

      In this useful study, the authors use published scRNA-seq data to highlight the importance of mast cells (MCs) in TB granulomas, reporting a comparative assessment of chymase- and tryptase-expressing MCs in the lungs of tuberculosis-infected individuals and non-human primates, with MC-deficient mice showing reduced lung bacterial burden and pathology during infection. Whilst the findings are helpful, the evidence to support conclusions is inconsistent across models and thus incomplete. Specifically, the data supporting a role for MCs in coordinating cytokine responses to modulate pathology, susceptibility to tuberculosis, and dissemination during infection are weak.

    1. eLife Assessment

      This interesting study explores whether tumor cells can manipulate their Hydra hosts, and includes important findings on the consequences for the fitness of the host Hydra. The evidence supporting these findings is convincing. The work will be of broad interest to many fields including development biology, evolutionary biology and tumor biology.

    1. eLife Assessment

      This important study provides proof of principle that C. elegans models can be used to accelerate the discovery of candidate treatments for human Mendelian diseases by detailed high-throughput phenotyping of strains harboring mutations in orthologs of human disease genes. The data are compelling and support an approach that enables the potential rapid repurposing of FDA-approved drugs to treat rare diseases for which there are currently no effective treatments. The work will be of interest to all geneticists.

    1. eLife Assessment

      Saijilafu et al. describe that MLCK and MLCP bidirectionally regulate NMII phosphorylation ultimately impinging on axonal growth during regeneration in the central and peripheral nervous systems. However, the evidence is in most cases incomplete, since some key controls are missing, some major claims are too broad to be supported by data and contrasting data on how MLCK and MLCP regulates NMII activity is not fully addressed or discussed. In sum, this knowledge is potentially useful for the field due to the relevance of identifying mechanisms that regulate axonal regeneration.

    1. eLife Assessment

      This study provides important new insights into the contributions of local DNA features to the complex molecular mechanisms and dynamics of copy number variation (CNV) formation during adaptive evolution. While limited to a single CNV of interest, the study is well-designed and carefully controlled, presenting compelling evidence that supports the conclusions. This work will be of general interest to those studying genome architecture and evolution from yeast biologists to cancer researchers.

    1. eLife Assessment

      This important work by Veneditto and colleagues developed a new modeling approach, called a mixture-of-agent hidden Markov model (MoA-HMM), in which choice behaviors are modeled as transitions between discrete states defined by different weighting of several reinforcement learning and decision strategies. The authors apply this approach to their previous data collected from rats performing the two-step task, and show that this method predicts fluctuations in neural and other behavioral data and provides better fits to the data than previous methods. The revision has greatly improved the manuscript, the evidence supporting the conclusions is convincing, and the method is of general interest to the field.

    1. eLife Assessment

      This is an important study that combines an array of genetic, cell biological, and genomic techniques to elucidate the role of the transcription factor Hamlet in reproductive development. It provides compelling evidence that Hamlet is a master regulator of cell fate and differentiation to reveal transcriptional targets that mediate epithelial tissue fusion. While the genetic and genomic analyses are convincing, the images that report the phenotypes are difficult to interpret for non-experts. This, and other identified issues, should be addressed.

    1. eLife Assessment

      This useful study investigates the role of frontotemporal regions in integrating linguistic and extra-linguistic information during communication, focusing on the inferior frontal gyrus and posterior middle temporal gyrus. It uses brain stimulation and electroencephalography to study speech-gesture integration. While the research question is interesting, the methods are insufficient for studying tightly-coupled brain regions over short timescales, leading to incomplete support for the claims due to conceptual and methodological limitations.

    1. eLife Assessment

      This important study will allow for a better understanding of anthelmintic drug resistance in nematodes, a growing concern for public health. The authors provide a detailed analysis of the role of UBR-1 and its underlying mechanism in ivermectin resistance using convincing behavioural and genetic experiments with C. elegans. What is not yet clear is how much of this study applies to parasitic nematodes, in which resistance has naturally emerged in different populations. The study will be of relevance to colleagues working on the evolution of drug resistance and to parasitologists in general.

    1. eLife Assessment

      This important study describes a first-in-human trial of autologous p63+ stem cells in patients with idiopathic pulmonary fibrosis, a lethal condition for which effective treatments are lacking. The authors provide convincing evidence that P63+ progenitor cell therapy can be safely delivered in patients with ILD. However, given that this is a Phase 1 study, conclusions regarding efficacy should not yet be made.

    1. eLife Assessment

      The paper introduces DeepTX, a valuable deep-learning framework linking stochastic, mechanistic modelling with single-cell RNA sequencing data to investigate transcriptional burst kinetics on a genome-wide scale. This tool has been employed by the authors to evaluate transcriptional changes under DNA-damaging treatments, with observations that are of value to the systems biology and bioinformatics communities. The evidence supporting these findings is solid, though some concerns remain regarding specific technical details. This methodological advancement holds potential for application in diverse contexts, such as linking mechanistic models of signalling pathways to transcriptional data.

    1. eLife Assessment

      This study addresses fundamental questions surrounding otitis media effusion in Down syndrome, identifying DYRK1A as a key gene involved in the condition. The findings are compelling, highlighting DYRK1A as a promising therapeutic target for addressing hearing loss in patients with Down syndrome.

    1. eLife Assessment

      This valuable study presents an interesting analysis of the role of the polyamine precursor putrescine in the pili-dependent surface motility of a laboratory strain of Escherichia coli. The genetic data convincingly shows this role, yet without putrescine measurements, the evidence remains incomplete. This work will be of interest to biomedical scientists studying uropathogenic bacteria, and those studying bacterial polyamine function.

    1. eLife Assessment

      This valuable study combines experiments and modelling to advance our understanding of the nonlinear nature of homeostatic structural plasticity and its interaction with synaptic scaling. The methodology and findings are solid, although additional work is needed to better link models with experiments and support some of the conclusions drawn. This study will be of interest to theoretical and experimental neuroscientists working in homeostatic plasticity.

    1. eLife Assessment

      The study is noteworthy for its effort to achieve a deeper understanding of PTH-1 Receptor signaling. The PTH-1 pathway underpins the control of calcium and phosphate metabolism throughout life in land-dwelling animals and it can be targeted to therapeutic benefit in patients with osteoporosis. We consider the significance of the findings in this paper to be valuable to the community of investigators working on PTH receptor signaling, with convincing evidence.

    1. eLife Assessment

      Aging reduces tissue regeneration capacity, posing challenges for an aging population. In this fundamental study, Reeves et al. show that by combining Wnt-mediated osteoprogenitor expansion (using a special bandage) with intermittent fasting, calvarial bone healing can be restored in aged animals. Intermitted fasting improves osteoprogenitor function by rescuing aging-related mitochondrial dysfunction, which can also be achieved by nicotinamide mononucleotide (NMN) supplementation or by modulating the gut microbiome. By employing rigorous histological, transcriptomic, and imaging analyses in a clinically relevant model, the authors provide compelling evidence supporting the conclusions. The therapeutic approach presented in this study shows promise for rejuvenating tissue repair, not only in bones but potentially across other tissues.

    1. eLife Assessment

      This important study is the first comprehensive analysis of the modulatory effects of nitric oxide (NO) on the response properties of retinal ganglion cells (RGCs) in the mouse retina using two-photon calcium imaging and multi-electrode arrays (MEA). The results provide compelling evidence that a subset of suppressed-by-contrast RGCs are affected. These unexpected findings are likely of broad interest to visual neuroscientists.

    1. neoliberalism and its predecessors of industrial capitalism and even proto capitalism were based on separation from the natural world. And and we can we call it sort of separation or dualism

      for - key insight - neoliberalism and industrial capitalism were based on Descarte and our separation from the natural world - Post Capitalist Philanthropy Webinar 1 - Alnoor Ladha - Lynn Murphy - 2023 - adjacency - materialism, science and neoliberalism - will technology save us? - Post Capitalist Philanthropy Webinar 1 - Alnoor Ladha - Lynn Murphy - 2023 - to - The Three Great Separations

      key insight / summary - neoliberalism and industrial capitalism were based on Descarte and our separation from the natural world - Post Capitalist Philanthropy Webinar 1 - Alnoor Ladha - Lynn Murphy - 2023 - FIrst, Descarte separated the mind from the body. We have the paradox of: - godlike mind housed in - animalistic bodies - (incidentally, this sets us up for the exageration of the existential crisis of the denial of death in modernity - Ernest Becker) - Then we impose separation of external vs internal world - Then, we have separate categories of mind and nature, and we begin othering of: - women - other (indigenous) cultures - What Alnoor and Lynn forgot to mention was that there is another separation that preceded the industrial revolution, the separation of people into distinct classes of: - producer - consumer - Then with the advance of Newtonian physics and the wild success of materialist theory applied to create a plethora of industrial technologies, a wedding occurred between: - dualism and - materialism - Materialism decomposes everything into subatomic particles that a rational mind can understand - To those who think science and technology can save us from the crisis it helped create - the deeper understanding reveals that science and technology are themselves agents of separation.

      to - See the three great separations - https://hyp.is/go?url=https%3A%2F%2Finthesetimes.com%2Farticle%2Findustrial-agricultural-revolution-planet-earth-david-korten&group=world

    2. when we analyzed the the dominant cultural operating system, because there's more than a political economy, it's a it's a, as we've said, a totalizing operating system. And we're going to call it neoliberalism

      for - definition - neoliberalism - as the name of the dominant, totalizing, cultural operating system of modernity - Post Capitalist Philanthropy Webinar 1 - Alnoor Ladha - Lynn Murphy - 2023 - summary - neoliberalism - as the name of the dominant, totalizing, cultural operating system of modernity - Post Capitalist Philanthropy Webinar 1 - Alnoor Ladha - Lynn Murphy - 2023 definition - neoliberalism - as the name of the dominant, totalizing, cultural operating system of modernity - Post Capitalist Philanthropy Webinar 1 - Alnoor Ladha - Lynn Murphy - 2023 - Neoliberalism is a totalizing, cultural operating system for modernity - It is all of these things: - a political philosophy - an economic practice - a cosmology - a wordview - an ontology - a theocracy - a religious worldview based on faith - Most of the dogmas of neoliberalism have been proven to be false, and yet it is still taught in most institutions of higher education summary - Some of the premises of neoliberalism are: - 1. humans are homo economicus - our chief concern is our selves and NOT others - Enlightenment theories - Scientism - Evolutionary theory - All our systems are designed on this false premise - 2. Hierarchy is inevitable and necessary for order. Without it, we would revert to beasts - The system embeds - Patriarchism - White Supremacy - Gender inequality - 3. The individual is the primary unit of power - together with 1) and 2), it creates inherent competition - 4. Material wealth and power is the measure of wellbeing - If you have money, you are considered a success, otherwise, you are considered a moral failure

    1. eLife Assessment

      This useful study reports detailed molecular dynamics simulations of T-cell receptors in complex with a peptide/MHC complex, for a better understanding of the mechanism of T-cell activation. The key observation was that tensile force applied in the direction of separation between TCR/pMHC appears to strengthen the interface, which is consistent with the catch bond scenario, although the effect is less apparent than that studied in the earlier work despite many similarities. The analyses are systematic and thus generally solid, although the level of evidence could be considered incomplete due to limited sampling based on a single trajectory for each load.

    1. Evaluation Statement (14 June 2024)

      The study by He et al. explores the structure and mechanisms of the human mitochondrial RNA splicing 2 (MRS2) protein, predicted to form Mg2+-selective channels in the mitochondrial inner membrane based on homology to the CorA family of prokaryotic Mg2+ channels. The authors use an innovative biochemical strategy to express MRS2 and perform single particle reconstructions in the absence and presence of key divalent cations. High resolution reconstructions of the pentameric channel reveal binding sites for Mg2+ and Ca2+, and electrophysiological investigations suggest that MRS2 is a Ca2+-regulated, cation-selective, Mg2+-permeable channel, in contrast to the Mg2+-regulated, Mg2+-selective CorA channel. This is an important study with interesting structural and functional observations, which will motivate further investigations of a potential role for MRS2 in mitochondrial Ca2+ signaling.

      Biophysics Colab recommends this study to scientists interested in the structure, function and regulation of cation channels as well as those working on mitochondrial transport.

      Biophysics Colab has evaluated this study as one that meets the following criteria:

      -        Rigorous methodology

      -        Transparent reporting

      -        Appropriate interpretation

      (This evaluation refers to the version of record for this work, which is linked to and has been revised from the original preprint following peer review.)

    1. eLife Assessment

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

    1. eLife Assessment

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

    1. eLife Assessment

      The study provides valuable insights into the mechanisms underlying neurovascular coupling; the authors present solid evidence demonstrating that layer II/III pyramidal neurons can induce vasoconstriction under conditions of intense optogenetic stimulation. They identify three distinct signalling pathways responsible for this effect, involving direct action on smooth muscle cells, as well as indirect modulation via interneurons or astrocytes. This work will be of interest to the broader neuroscience community and has potential implications for understanding pathological microcirculation in the brain, particularly in conditions characterized by strong excitatory neuronal activation. There are however questions that should be clarified, especially the conflict between three identified parallel pathways and the observed complete inhibition of the constriction by blockage of the NPY Y1 receptors.

    1. eLife Assessment

      This valuable study combines experiments and theory to investigate the putative role of spontaneous correlated activity in establishing aligned topographic maps of neural activity in higher-order sensory areas, and will be of interest to researchers studying multisensory integration and brain development. However, the evidence presented is incomplete, as there are notable disconnects between the experimental data and the modeling setup, and there are methodological details that are either unclear or missing, limiting the strength of the claims.

    1. eLife Assessment

      Briola and co-authors determined the structure of the human CTF18 clamp loader bound to PCNA to high resolution, analyzed the structure, and tested a new mechanism involving a human-specific Ctf18 beta-hairpin docking onto Rfc5, which represents a valuable contribution. The data are solid and complement data recently published by others.

    1. eLife Assessment

      This manuscript describes an important study of the giant virus Jyvaskylavirus. The characterisation presented is solid, although, in the current form, it is not clear to what extent these findings change our perception of how giant viruses, especially those isolated from a cold environment, function. The work will be of interest to virologists working on giant viruses as well as those working with other members of the PRD1/Adenoviridae lineage.

    1. eLife Assessment

      This important study describes a novel flow-responsive gene and its role in regulating the inflammation-associated transcription factor IRF5. While the in vivo experiments are solid, the in vitro data is inadequate since embryonic fibroblasts are used throughout despite the work aiming to investigate mechanisms of endothelial cell activation in atherosclerosis.

    1. eLife Assessment

      This important study demonstrates that screening by artificial intelligence can identify relevant novel compounds for interacting with KATP channels. The experimental work is compelling. The broader significance of this work relates to the possibility that KATP channel mutations linked to congenital hyperinsulinism may be effectively rescued to the cell surface with a drug, which could normalize insulin secretion or enhance the effectiveness of existing KATP channel activators such as diazoxide.

    1. eLife Assessment

      In this important manuscript, the authors investigate the phospho-regulation of the C. elegans kinesin-2 motor protein OSM-3, revealing that the kinase, NEKL-3, phosphorylates a serine/threonine patch at the hinge region of the motor to mediate autoinhibition until it reaches the ciliary middle segment. The findings are supported by robust genetic data, in vivo imaging, and motility assays with wild-type and mutant motors, although the methods section lacks detailed protocols for NEKL-3 assays and in silico analyses. Overall, the study provides a solid contribution to understanding the regulation of OSM-3 kinesin activity.

    1. eLife Assessment

      This important study provides a framework for applying single-cell transcriptome data and network analysis from genetically diverse mouse cells to identify novel driver genes underlying the role of genetic loci associated with bone mineral density. The evidence supporting the identification of the driver genes and the conclusion of the paper is convincing. Overall, this approach may be broadly applicable and of interest to researchers investigating the genetics of complex diseases.

    1. eLife Assessment

      The present study described GEARBOCS, an adeno-associated virus tool for in vivo gene editing in astrocytes, which is both timely and of importance for glial biologists, who often are troubled by efficient gene targeting in astrocytes. Overall, the finding is valuable, and the strength of the evidence is solid. Presumably, there will be great potential associated with GEARBOCS applications in the future.

    1. eLife Assessment

      This is an important study that describes the development of optical biosensors for various Rab GTPases and explores the contributions of Rab10 and Rab4 to structural and functional plasticity at hippocampal synapses during glutamate uncaging. Most of the evidence supporting the conclusions of the paper is solid, while the evidence supporting the finding that Rab10 activation during structural LTP is sustained is incomplete due to the characterization of the relevant sensor.

    1. eLife Assessment

      This study provides a valuable set of analyses and theoretical derivations to understand the mechanisms used by recurrent neural networks (RNNs) to perform context-dependent accumulation of evidence. The novelty of some of the findings needs clarification, and additional details need to be provided for some of the analyses. However, the results regarding the dimensionality and neural dynamical signatures of RNNs are solid and provide new avenues to study the mechanisms underlying context-dependent computations.

    1. eLife Assessment

      This valuable study introduces a novel method for controlling generalization and interference in neural networks undergoing continual learning. The authors provide solid evidence that their parsimonious method performs better than online gradient descent in several continual learning situations while providing biologically plausible links to three-factor learning rules. However, empirical validation is limited to linear networks, which raises questions about the generality of the results in non-linear networks. While the work is interesting to theoretical and experimental neuroscientists, improving the article presentation by clearly defining terminology before using it and providing more details on the setup of the simulation experiments would be vital to make the article more accessible.

    1. eLife Assessment

      This study presents an important contribution to the understanding of neural speech tracking, demonstrating how minimal background noise can enhance the neural tracking of the amplitude-onset envelope. The evidence supporting the claims of the author is solid, through a well-designed series of EEG experiments. This work will be of interest to auditory scientists, particularly those investigating biological markers of speech processing.

    1. eLife Assessment

      This important study identifies neurotrophin signaling as a molecular mechanism underlying previous findings of structural plasticity in central dopaminergic neurons of the adult fly brain. The authors present solid evidence for neurotrophin signaling in shaping the structure and synapses of certain dopaminergic circuits. The work suggests an intriguing potential link between neurotrophin signaling and experience-induced structural plasticity but further research will be necessary to establish this connection definitively.

    1. eLife Assessment

      This is an important and convincing dataset shedding new light on a role for Malat1 in osteoblast physiology. The work is of value to areas other than the bone field because it supports a role and mechanism for beta-catenin that is novel and unusual. The findings are significant in that they support the presence of another anabolic pathway in bone that can be productively targeted for therapeutic goals. Revisions further improved the paper and addressed the reviewers' concerns.

    1. eLife Assessment

      This auhors 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 study provides valuable new insight into the role of Fgf signalling in SUFU mutation-linked cerebellar tumors and indicates novel therapeutic interventions via inhibition of Fgf signalling. The potential impact of this work is therefore very high and it is supported by solid evidence. However, due to current limitations in the full identification of the cell types secreting FGF5, and issues with robustness of evaluation of genetically engineered animals, the validation of some interpretations awaits future experiments.

    1. eLife Assessment

      This study presents valuable quantitative insights into the prevalence of functionally clustered synaptic inputs on neuronal dendrites. The simple analytical calculations and computer simulations provide solid support for the main arguments. The findings can lead to a more detailed understanding of how dendrites contribute to the computation of neuronal networks.

    1. eLife Assessment

      This study presents valuable quantitative insights into the prevalence of functionally clustered synaptic inputs on neuronal dendrites. The simple analytical calculations and computer simulations provide solid support for the main arguments. The findings can lead to a more detailed understanding of how dendrites contribute to the computation of neuronal networks.

    1. eLife Assessment

      This important study combines compelling experiments with optogenetic actuation and convincing theory to understand how signalling proteins control the switch between cell protrusion and retraction, two essential processes in single cell migration. The authors examine the importance of the basal concentration and recruitment dynamics of a guanine exchange factor (GEF) on the activity of the downstream effectors RhoA and Cdc42, which control retraction and protrusion. The experimental and theoretical evidence provides a model of RhoA's involvment in both protrusion and retraction and shows that these complex processes are highly dependent on the concentration and activity dynamics of the components.

    1. eLife Assessment

      The authors provide a solid set of data supporting the safety of transcutaneous auricular vagal nerve stimulation on cardiovascular parameters in the acute setting of critically ill patients presenting with subarachnoid hemorrhage. This important study also suggests a promising effect on autonomic balance.

    1. eLife Assessment

      Ferredoxins are ubiquitous electron transfer proteins that drive essential metabolic processes across all domains of life. This fundamental contribution to the field provides the first description of how specific amino acids, though a series of hydrogen bonds, control the ability of iron-sulfur clusters in ferrodoxins to accept and donate electrons. The evidence supporting the conclusions is compelling as is the combined use of neutron crystallography with X-ray crystallography and classical spectral/redox studies.

    1. eLife Assessment

      This manuscript presents important finding regarding the regulation of a key stem cell population, namely muscle stem cells (or "satellite cells"). The evidence presented is convincing that Scx, a marker for tendon, is expressed in some myogenic cells and is essential for adult muscle regeneration.

    1. eLife Assessment

      This study presents valuable experimental and numerical results on the motility of a magnetotactic bacterium living in sedimentary environments, particularly in environments of varying magnetic field strengths. The evidence supporting the claims of the authors is compelling and the study will be of specific relevance to biophysicists interested in bacterial motility.

    1. eLife Assessment

      This paper provides fundamental insights into the control of Salmonella within human macrophages, with convincing evidence that Salmonella can replicate in the macrophage cytosol in the absence of inflammasome signaling. This paper, which improves our understanding of how the immune system fights bacterial infections, will be of broad interest to cell biologists, immunologists and microbiologists.

    1. eLife Assessment

      This manuscript applies a theoretical analysis to two published datasets on yeast and bacterial evolution to compare different ways of quantifying fitness. It makes an important advance by clarifying how discrepancies can arise by using different approaches and provides recommendations for best practices. While the evidence is solid, some improvements in the presentation of the data and a greater focus on the causes of the discrepancies between the various fitness estimates would strengthen the paper further.

    1. eLife Assessment

      This study provides valuable insights into the efficacy and safety of pyrotinib as an extended adjuvant therapy following trastuzumab-based treatment in patients with high-risk HER2-positive breast cancer. The strength of evidence is solid, supported by the multicenter phase II trial design, which included a substantial number of patients across 23 centers in China. However, the single-arm study design without a control group limits the ability to draw definitive conclusions about the comparative effectiveness of pyrotinib.

    1. eLife Assessment

      This useful modeling study alters a previous model of the intact cat spinal locomotor network to simulate a lateral hemi-section of the spinal cord. The modeling and experimental work described provide solid evidence that this model is capable of qualitatively predicting alterations to the swing and stance phase durations during locomotion at different speeds on intact or split-belt treadmills, but a revision of the figures to overlay the model predictions with the experimental data would facilitate the assessment of this qualitative agreement. This paper will interest neuroscientists studying vertebrate motor systems, including researchers investigating motor dysfunction after spinal cord injury.