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    1. eLife assessment

      This study provides important information on pre-existing epigenetic modification in T cell plasticity. The evidence supporting the conclusions is compelling, supported by comprehensive transcriptional and epigenetic analyses. The work will be of interest to immunologists and colleagues studying transcriptional regulation.

    1. eLife assessment

      This study employed a comprehensive approach to examining how the MT+ region integrates into a complex cognition system in mediating human visuo-spatial intelligence. While the findings are useful, the experimental evidence is incomplete and the study designs, hypotheses, and data analyses need to be improved. The work will be of interest to researchers in psychology, cognitive science, and neuroscience.

    1. eLife assessment

      This study presents valuable framework and findings to our understanding of the brain as a fractal object by observing the stability of its shape property within 11 primate species and by highlighting an application to the effects of aging on the human brain. The evidence provided is solid but the link between brain shape and the underlying anatomy remains unclear. This study will be of interest to neuroscientists interested in brain morphology, whether from an evolutionary, fundamental or pathological point of view, and to physicists and mathematicians interested in modeling the shapes of complex objects.

    1. eLife assessment

      This study presents a valuable finding on predator threat detection in C. elegans and the role of neuropeptide systems in defensive behavioral strategies. The evidence supporting the conclusions is solid, although additional analyses and control experiments would strengthen the claims of the study. Overall, the work is of interest to the C. elegans community as well as neuroethologists and ecologists studying predator-prey interactions.

    1. eLife assessment

      A combination of molecular dynamics simulation and state-of-the-art statistical post-processing techniques provided valuable insight into GPCR-ligand dynamics. This manuscript provides solid evidence for differences in the binding/unbinding of classical cannabinoid drugs from new psychoactive substances. The results could aid in mitigating the public health threat these drugs pose.

    1. eLife assessment

      This useful study reports on the discovery of an antimicrobial agent that kills Neisseria gonorrhoeae. Sensitivity is attributed to a combination of DedA assisted uptake of oxydifficidin into the cytoplasm and the presence of a oxydifficidin-sensitive RpIl ribosomal protein. Due to the narrow scope, the broader antibacterial spectrum remains unclear and therefore the evidence supporting the conclusions is incomplete with key methods and data lacking. This work will be of interest to microbiologists and synthetic biologists.

    1. eLife assessment

      This study convincingly shows that aquaporins play a key role in blood vessel formation during zebrafish development. In particular, the paper implicates hydrostatic pressure and water flow as mechanisms controlling endothelial cell migration during angiogenic sprouting. This important study significantly advances our understanding of cell migration during morphogenesis. As such, this work will be of great interest to developmental and cell biologists working on organogenesis, angiogenesis, and cell migration.

    1. eLife assessment

      This important study, characterizing the epigenetic and transcriptomic response of a variety of cell types representative of somatic, germline, and pluripotent cells to BPS, reveals the cell type-specific changes in DNA methylation and the relationship with the genome sequence. The findings are convincing and provide a basis for future analyses in vivo. This work should be of interest to biomedical researchers who work on epigenetic reprogramming and epigenetic inheritance.

    1. eLife assessment

      This manuscript provides important results that assessed the contribution of two catecholaminergic projections to the hippocampus during environment-guided reward behavior. The authors use 2-photon imaging in the hippocampus of behaving mice to provide solid evidence that there are dissociable roles of dopamine and norepinephrine in this structure. Although of great interest to the field of learning and memory, the results would be strengthened by additional data collected from dopaminergic projections to the hippocampus.

    1. eLife assessment

      In this study the authors revisited the question of the embryonic origin of telencephalic oligodendrocytes using some new and powerful genetic tools. There is convincing evidence to support previous suggestions of a predominantly cortical origin of oligodendrocytes in the cerebral cortex, however the new studies suggest that LGE/CGE-derived oligodendrocytes make a modest contribution in some areas, while MGE/POA-derived oligodendrocytes make a small but enduring contribution. The findings are valuable and should be of interest to developmental and myelin biologists.

    1. eLife assessment

      This study presents valuable data on sensory integration in a model pre-motor neuron, the Mauthner cell. The authors use both stimulation of the optic tectum (a proxy for vision) and auditory stimulation to study the integration of these modalities in the Mauthner cell using convincing, technically demanding, and well done experiments. There are, however, concerns about the degree to which the two modalities interact; multisensory integration of subthreshold unisensory stimuli appears uncommon, and not significantly above events observed from single modalities. This work will be of interest to both synaptic physiologists and neurophysiologists working on sensory-motor integration.

    1. eLife assessment

      Here, the authors developed a cell-based screening assay for the identification of small molecule inhibitors of nonsense-mediated decay (NMD), and used it to validate KVS0001, a new small molecule SMG1 kinase inhibitor derived from the existing inhibitor SMG1i-11, showing it inhibits NMD in cultured cells leading to expression of neoantigens from NMD-targeted genes and slows tumor growth of cancer cell lines possessing a significant number of out-of-frame indel mutations. The conclusions are supported by convincing evidence, and the significance of this work consists in the development of a new and very promising NMD inhibitor drug that acts as an inhibitor of the SMG1 NMD kinase and is effective in animal tumor studies. This is an important advance for the field, as previous NMD inhibitors were not specific, lacked efficacy, or were very toxic and hence not suitable for animal applications.

    1. eLife assessment

      This important study analyzes in an original way how tension pattern dynamics can reveal the contribution of active versus passive intercalation during tissue elongation. The authors develop a compelling, elegant analytical framework (isogonal tension decomposition) to disentangle the passive (adjacent tissues pulling) and active (local tension anisotropy) contributions to intercalation events. This allows the generation of global maps of tissue mechanics that will be extremely helpful in the field of biomechanics.

    1. eLife assessment

      This useful study describes a single set of label-chase mass spectrometry experiments to confirm the molecular function of YafK as a peptidoglycan hydrolase, and to describe the timing of its attachment to the peptidoglycan. Confirmation of the molecular function of YafK will be helpful in further studies to examine the function and regulation of the outer membrane-peptidoglycan link in bacteria. The evidence supporting the molecular function of YafK and that lpp molecules are shuffled on and off the peptidoglycan is solid, however, data supporting conclusions relating to the locations of lpp-peptidoglycan attachment are incomplete. The work will be of interest to researchers studying lipoproteins in gram negative bacteria.

    1. eLife assessment

      This study offers a useful treatment of how the population of excitatory and inhibitory neurons integrates principles of energy efficiency in their coding strategies. The analysis provides a comprehensive characterisation of the model, highlighting the structured connectivity between excitatory and inhibitory neurons. However, the manuscript provides an incomplete motivation for parameter choices. Furthermore, the work is insufficiently contextualized within the literature, and some of the findings appear overlapping and incremental given previous work.

    1. eLife assessment

      The work introduces a valuable new method for depleting the ribosomal RNA from bacterial single-cell RNA sequencing libraries and shows that this method is applicable to studying the heterogeneity in microbial biofilms. The evidence for a small subpopulation of cells at the bottom of the biofilm which upregulates PdeI expression is solid. However, more investigation into the unresolved functional relationship between PdeI and c-di-GMP levels with the help of other genes co-expressed in the same cluster would have made the conclusions more significant.

    1. eLife assessment

      Rademacher and colleagues examined the effect of a chemogenetic approach on the integrity of the dopamine system in mice with chronically stimulated dopamine neurons. These findings are important: 1) This approach led to an axon-first degeneration over a time course of 2-4 weeks; 2) The finding that direct excitation of dopaminergic neurons causes differential degeneration sheds light on dopaminergic neuron selective vulnerability mechanisms. Overall, the strength of the evidence is solid, but the behavior experiments that do not include a CNO control provide incomplete support for the findings.

    1. eLife assessment

      This useful study uses high-field fMRI to test the hypothesized involvement of subcortical structure, particularly the striatum, in WM updating. It overcomes limitations in prior work by applying high-field imaging with a more precise definition of ROIs. Thus, the empirical observations are of use to specialists interested in working memory gating or the reference back task specifically. However, evidence to support the broader implications, including working memory gating as a construct, is incomplete and limited by the ambiguities in this task and its connection to theory.

    1. eLife assessment

      This important work addresses the relationship between the transdiagnostic compulsivity dimension and confidence as well as confidence-related behaviours like reminder setting. The relationship between confidence and compulsive disorders has recently received a lot of attention and has been considered to be a key cognitive change. The authors paired an elegant experimental design and pre-registration to give convincing evidence of the relationship between compulsivity, reminder setting, and confidence. Future work should clarify the link of their findings with prediction error-related processes to test whether they could be causally related to their results, and further clarify some of the implications for their findings and refine hypotheses about confidence-related cognitive changes with compulsivity and OCD.

    1. eLife assessment

      This study presents useful, yet preliminary findings on the transcriptomic changes in cardiac lymphatic cells after myocardial infarction in mice. The conclusions of the authors remain uncertain as sample sizes for lymphatic endothelial cells are very low. The single-cell transcriptomic data were analyzed using solid advanced methodology and may be used as a starting point for future studies of the impact of lymphatic cells on heart disease.

    1. eLife assessment

      This study provides a valuable contribution to the development of small molecules that inhibit the aggregation of tau, a protein involved in several neurodegenerative diseases. The authors present convincing evidence that analogs of the plant alkaloid tryptanthrin can prevent the formation of larger aggregates by targeting the early stages of tau oligomerization. Nevertheless, further studies are needed to elucidate the precise mechanisms of action and to provide a detailed kinetic analysis. This work will be of interest to biochemists and biophysicists focused on designing small molecules to inhibit fibril formation.

    1. eLife assessment

      This paper presents a valuable pipeline based on state-of-the-art analytical software that was used to study genetic pleiotropy between neuropsychiatric disorders. The presented evidence supporting the claims is convincing and now includes an appropriate comparison to previously published methods as well as a detailed exploration of the findings. The created pipeline can thus be used by researchers from diverse fields to study different combinations of diseases and traits.

    1. eLife assessment

      This fundamental work quantifies the stochastic dynamics of neural population activity in the lateral intraparietal area (LIP) of the macaque monkey brain during single perceptual decisions. These single-trial dynamics have been subject to intense debate in neuroscience, and they have significant implications for modelling decision-making in various fields including neuroscience and psychology. Through a combination of state-of-the-art recordings from many LIP neurons and theory-driven data analyses, the authors provide convincing evidence for the notion that single-trial neural population dynamics in LIP encode the decision variable postulated by the drift-diffusion model of decision-making.

    1. eLife assessment

      This study presents high-quality experiments and data analysis of C. elegans locomotion for spontaneous exploration as well as in the presence of an aversive stimulus. This important work shows that the activation of distinct turn types enhances escape performance as well as exploration. The strength of the evidence is still incomplete, particularly regarding optimal exploration and the identification of the range of the aversive stimulus at the boundary of the arena. The work will be of interest to a broad audience extending from movement ecology, to the biology of Caenorhabditis elegans.

    1. eLife assessment

      This study presents a valuable finding on a new role of Foxp3+ regulatory T cells in sensory perception, which may have an impact on our understanding of somatosensory perception. The authors identified a previously unappreciated action of enkephalins released by immune cells in the resolution of pain and several upstream signals that can regulate the expression of the proenkephalin gene PENK in Foxp3+ Tregs. The generation of transgenic mice with conditional deletion of PENK in Foxp3+ cells and PENK fate-mapping is novel and generates compelling data; they also show a comprehensive analysis of Tregs in control and transgenic mice, longitudinal data on heat sensitivity and co-localization of PENK+ Tregs with thermal sensory neurons in the skin further supporting their hypothesis. The study would be of interest to the biologists working in the field of neuroimmunology and inflammation.

    1. eLife assessment

      The work provides valuable genomic resources to address the endocrine control of a life cycle transition in the Malabar grouper fish. The revised manuscript is more solid and the resources and experimental data help to build up a meaningful biological understanding of thyroid signaling in grouper fish.

    1. eLife assessment

      This important study presents the structure of human heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) in the acetyl-CoA bound state, providing the first description of the architecture of this family of integral membrane enzymes, and revealing the mode of acetyl-CoA binding. The structural work is convincing, with a high resolution and isotropic single-particle cryoEM map and an atomic model that is well-justified by the density map, with strong and convincing density for the acetyl-CoA ligand. However, experimental support for the molecular mechanism of the HS acetylation reaction and the impact of disease-causing mutations is incomplete. This work will be of interest to biochemists and structural biologists studying the structure and function of integral membrane enzymes, as well as those interested in genetic diseases resulting from mutations in this family of enzymes, such as mucopolysaccharidosis IIIC (MPS III-C).

    1. eLife assessment

      This meta-analysis presents valuable findings that reexamine the function of butterfly eyespots in predator avoidance and report for conspicuousness over mimicry. The analysis is robust, but the evidence supporting the importance of conspicuousness is incomplete due to the limitations of the literature, and this debate would benefit from additional experiments that would strengthen these claims. This paper is of interest to evolutionary biologists and ecologists working on the evolution of morphology and predator-prey interactions.

    1. eLife assessment

      In this valuable contribution, the authors present a novel and versatile probabilistic tool for classifying tracking behaviors and understanding important parameters for different types of single-particle motion. The tool will be broadly applicable to single-particle tracking studies. While some reviewers feel that the methodology has been convincingly tested by computational comparisons and experimental data, others feel that the mathematical foundation needs to be strengthened and clearly defined.

    1. eLife assessment

      This important study utilizes humanized mice, in which human immune cells are introduced into immune-deficient mice, to provide solid evidence that two helper CD4 T-cell subsets, T-follicular helper (Tfh) and T-peripheral helper (Tph) cells, are able to drive both autoantibody production and induction of autoimmunity. The work will be of broad interest to medical scientists engaged in deciphering how human immune cells mediate immune responses and contribute to the development of autoimmune diseases.

    1. eLife assessment

      This valuable and well-executed study describes how deletion of the autism spectrum disorder risk gene CNTNAP2 in mice increases dorsolateral striatal projection neuron excitability and promotes repetitive behaviors and cognitive inflexibility. The evidence supporting this claim is solid, although additional experimental evidence would strengthen claims of how corticostriatal activity is altered and linked to behavioral changes. The study provides a potential cellular explanation for the repetitive and inflexible behavior in Cntnap2 knockout mice and CNTNAP2 disorder in humans, which would interest both basic and translational neuroscientists.

    1. eLife assessment

      This study represents an important contribution to the study of decision-making under risk, bringing an interdisciplinary approach spanning economic theory, behavioral neuroscience, and computational modeling to test how choice preference is influenced by rare and extreme events. The authors present evidence that rats are indeed sensitive to these rare and extreme events despite their infrequent occurrence, driven primarily by an almost complete avoidance of "Black Swans" - rare and extreme losses. The evidence for specific sensitivity to rare and extreme events however remains incomplete, owing in part to the difficulty of isolating the effect of these events beyond that arising from risk preferences more generally in both task design and in the computational modeling of the choice behavior. Given the approach here brings a relatively novel perspective, with a more detailed treatment of these confounds this paper will be of broad interest to those seeking to understand animal behavior through the lens of economic choice.

    1. eLife assessment

      Lloyd et al. used an evolutionary comparative approach to study DNA damage repair in response to sleep deprivation in Astyanax mexicanus, highlighting how the cavefish population has evolved a reduced DNA damage response compared to the surface-dwelling population. The cavefish have elevated expression of signals commonly associated with aging but do not show evidence of reduced life span nor increased aged-linked pathology, a potentially valuable finding for the field of aging research. A link to alterations in sleep behaviour is outlined, but the evidence for such a link is incomplete.

    1. eLife assessment

      This valuable study provides insights into how the brain learns to better detect a target by predicting when the target may appear. Overall, solid evidence is provided that the power fluctuations of alpha- and beta-band oscillations can reflect the predicted occurrence time of the target, but some conclusions, especially ones related to the neural-network model and temporal gain control account, need further consideration. The study highlights an advanced EEG analysis approach as well as a close combination of human EEG analysis and computational modeling using recurrent neural networks.

    1. eLife assessment

      This is an important characterization of mouse auditory cortex receptive field organization, using two-photon imaging of specific subpopulations. They demonstrate a degradation of tonotopic organization from the input to output neurons. The strength of the evidence is solid, but some controls are needed to further strengthen the conclusion.

    1. eLife assessment

      This study resolves a cryo-EM structure of the GPCR, human GPR30, which responds to bicarbonate and regulates cellular responses to pH and ion homeostasis. Understanding the ligand and the mechanism of activation is important to the field of receptor signaling and potentially facilitates drug development targeting this receptor. While the overall structures are solid, the identification of the bicarbonate binding site is only partly supported by the structural data and cell-based functional assays, leaving a major aim of the study incomplete.

    1. eLife assessment

      This convincing study advances our understanding of the physiological consequences of the strong overexpression of non-toxic proteins in baker's yeast. The findings suggest that a massive protein burden results in nitrogen starvation and a shift in metabolism likely regulated via the TORC1 pathway, as well as defects in ribosome biogenesis in the nucleolus. The study presents findings and tools that are important for the cell biology and protein homeostasis fields.

    1. eLife assessment

      This paper reports important findings on giant organelle complexes containing endosomes and lysosomes (termed endosomal-lysosomal organelles form assembly structures [ELYSAs]) present in mouse oocytes and 1- to 2-cell embryos. The data showing the localization and dynamics of ELYSAs during oocyte/embryo maturation are convincing. This work will be of interest to general cell biologists and developmental biologists.

    1. eLife assessment

      The study describes a valuable new technology in the field of targeted protein degradation that allows identification of E3-ubiquitin ligases that target a protein of interest. The presented data are convincing, however, it is unclear whether the proposed system can be successfully used in high throughput applications. This technology will serve the community in the initial stages of developing targeted protein degraders.

    1. eLife assessment

      This study combines extensive published and new datasets to provide a useful single-cell multi-omics analysis of early cardiac lineage segregation, highlighting the mutual regulation of key regulators for cardiac specification. While the data presentation is robust, the computational methods for delineating cardiac lineage trajectories and the functional analyses are incomplete and require further clarification and additional experiments. If validated, these findings will be of significant interest to researchers in the fields of cardiac development and congenital heart disease.

    1. eLife assessment

      This study represents a valuable addition to the catalog of mitochondrial proteins. With the use of methodology based on the bi-genomic split-GFP technology, the authors generate convincing data, including dually localized proteins and topological information, under various growth conditions in yeast. The study represents a starting point for further functional and/or mechanistic studies on mitochondrial protein biogenesis.

    1. eLife assessment

      This study provides valuable insights into the complex genetics of dominant optic atrophy. Leveraging a fly model, the investigators provide solid evidence, albeit with small effect sizes, for a dominant negative mechanism of certain pathogenic variants that tend to cause more severe phenotypes, a long held hypothesis in the field. The work is of high interest to those in the optic atrophy and degeneration fields.

    1. eLife assessment

      This important study examines the extent to which distinct developmental pathways that result in alternative morphs correlate with transcriptome differences in a marine annelid, Streblospio benedicti. The strengths of the study include the experimental design and dense temporal sampling, which together provide convincing evidence that the two morphs can be clearly distinguished at the transcriptome level, despite relatively modest overall differences. The work will be of particular interest to students of the evolution of development.

    1. eLife assessment

      This study presents valuable findings on how the endocannabinoid system is involved in endometriosis progression using CNR1 and CNR2 knockout (KO) mouse models. The evidence supporting the authors' claims is incomplete; including bulk RNA-seq, flow cytometry, and imaging mass cytometry would have strengthened the study. This work might be of interest to medical scientists working on endometriosis.

    1. eLife assessment

      This valuable study details an aspect of plant immunity where ATG6 was not previously known to have a role. The results suggest a direct relationship between ATG6 and NPR1, a well-studied salicylic acid receptor protein, which could be of interest to researchers studying the regulation of plant immunity. While the data presented are compelling, there are concerns about the interpretation of results, particularly regarding discrepancies in fluorescence and protein blot data. Addressing these issues would improve the overall impact of the work and consistency with prior studies.

    1. eLife assessment

      This valuable manuscript systematically addresses the role of intracellular lipid transfer proteins on cellular lipid levels. It provides convincing evidence on the role of ORP9 and ORP11 in sphingolipid metabolism at the Golgi complex. This article will be of broad interest to cell biologists interested in lipid metabolism and membrane biology.

    1. eLife assessment

      This work presents fundamental new insights into the conductivity of freshwater cable bacteria. The evidence supporting the conclusions, which was collected using appropriate techniques, is compelling. The work will be of interest to environmental microbiologists and the microbial electrochemistry community.

    1. eLife assessment

      Through cellular, developmental, and physiological analysis, this valuable study identifies a gene that functions to regulate the relative growth of roots and shoots under salt stress. The holistic approach taken provides solid evidence that this gene, a member of a larger tandemly duplicated gene family initially highlighted by association mapping, as well as an upstream regulator contribute to salt tolerance. More robust statistical or biological support for some conclusions could further strengthen this manuscript. The manuscript will be of interest to plant biologists studying mechanisms of abiotic stress tolerance and gene family evolution.

    1. eLife assessment

      This useful study presents a real-time transcriptomics analysis, with the aim of providing rapid access to sequenced data to reduce the costs associated with Oxford Nanopore long-read technology. Although the authors illustrate the compelling utility of this approach with three diverse experimental setups, issues with study design and analysis result in incomplete supporting evidence.

    1. eLife assessment

      This study develops a useful metric for quantifying codon usage adaptation - the Codon Adaptation Index of Species (CAIS). This metric permits direct comparisons of the strength of selection at the molecular level across species. The study is based on solid evidence, and the authors identify relationships between CAIS and the presence of disordered protein domains. Other correlations, such as the one between CAIS and body size, are weak and non-significant. In summary, the study introduces an interesting new approach to quantifying codon usage across species, which may be helpful in attempts to measure selection at the molecular level.

    1. eLife assessment

      This is a valuable study in which the authors provide an expression profile of the human blood fluke, Schistosoma mansoni. A strength of this solid study is in its inclusion of in situ hybridisation to validate the predictions of the transcript analysis.

    1. eLife assessment

      This important work provides evidence that glutamate and GABA are released from different synaptic vesicles at supramammillary axon terminals onto granule cells of the dentate gyrus. The study uses complementary electrophysiological and anatomical experimental approaches. Together, these provide solid evidence that the co-release of glutamate and GABA from different vesicles within the same terminal could modulate granule cell firing in a frequency-dependent manner, although thorough elimination of alternative mechanisms would have strengthened the study. The work will be of interest to neuroscientists investigating co-release of neurotransmitters in various synapses in the brain and those interested in subcortical control of hippocampal function.

    1. eLife assessment

      This study provides a novel and valuable alternative explanation for volatility-induced changes in choice behavior, commonly attributed to learning-rate adaptations. Through rigorous and comprehensive computational modeling of previously published data, the authors provide convincing support for the claim that apparent learning-rate adaptations may instead reflect a mixture of decision strategies. Furthermore, they demonstrate that differential weighting of the optimal decision strategy is predicted by psychopathology common to depression and anxiety. This work should be of interest to a wide range of scientists, including psychologists, neuroscientists, computer scientists, and clinicians.

    1. eLife assessment

      In this useful study, the authors tested the ability of bumblebees to use bird-view and ground-view for homing in cluttered landscapes using modeling and behavioral experiments, claiming that bumblebees rely most on ground-views for homing. However, due to a lack of analysis of the bees' behavior during training and a lack of information as to how the homing behavior of bees develops over time, the evidence supporting their claims is currently incomplete. Moreover, there was concern that the experimental environment was not representative of natural scenes, thus limiting the findings of the study.

    1. eLife assessment

      This is an important study, as PIM1/2 control of protein synthesis in differentiated cells has implications beyond T cells. The evidence is convincing in that it makes extensive use of the mouse knockout model and validation in mouse T cells with inhibitors. A rescue experiment in mouse KO T cells would be even stronger than the inhibitor studies to validate the KO phenotype and the evidence would be truly impressive if the results from the rescue experiment support the working model. Extending the observations to human T cells would also be a step towards translation and would further increase the potential impact of the work.

    1. eLife assessment

      This paper explores the relationships among evolutionary and epidemiological quantities in influenza, and presents fundamental findings that substantially advance our understanding of the drivers of influenza epidemics. The authors use a rich set of data sources to gather and analyze compelling evidence on the roles of genetic distance, other influenza dynamics and epidemiological indicators in predicting influenza epidemics. The central findings highlight the significant influence of genetic distance on A(H3N2) virus epidemiology and emphasize the role of A(H1N1) virus incidence in shaping A(H3N2) epidemics, suggesting subtype interference as a key factor. This paper also makes relevant data available to the research community.

    1. eLife assessment

      Maestri et al report the absence of phylogenetic evidence supporting codiversification of mammalian coronaviruses and their hosts, leading to the important conclusion that the evolutionary history of the virus and its hosts are decoupled through frequent host switches. The evidence for frequent host switching, derived from state-of-the-art probabilistic modeling of co-evolution, is convincing. The study adds a new perspective to the ongoing debate over the timescale of coronavirus evolution.

    1. eLife assessment

      This work by Shin et al. demonstrated that a different form of PTH (R25C PTH) generated a comparable anabolic signal to rhPTH 1-34 using a large animal model. This valuable finding may have therapeutic potential in promoting bone formation or the healing process, and the methods seem solid, although there remains a concern regarding the small sample size and surgical procedure.

    1. eLife assessment

      This important paper on measuring molecular connectivity using combined serotonin PET and resting-state fMRI provides both novel methods for studying the brain as well as insights into the effects of ecstasy administration. The methods are solid, with a few doubts that need to be dispelled surrounding the high anaesthetic dose used.

    1. eLife assessment

      In this manuscript, the authors present valuable findings on the apparent role of a salience-network anterior insula node in directing fronto-parietal and default-mode network activity within a tripartite network during control of memory, drawn from an impressive invasive human neurophysiological dataset. While we commend the use of a large intracranial EEG dataset to approach this question, the study at present is incomplete in its methodologies, analysis, and interpretation to support the authors' central claims. The manuscript could be improved by addressing the concerns described.

    1. eLife assessment

      This valuable paper investigates how fish avoid thermal disturbances that occur on fast timescales. The authors use a creative experimental approach that quickly creates a vertical thermal interface, which they combine with careful behavioral analyses. The evidence supporting their results is solid, but there is a potential confounding factor between temperature and vertical positioning, and characterization of the thermal interface would greatly assist in interpreting the results.

    1. eLife assessment

      This study describes the development and validation of an Automated Reproducible Mechano-stimulator (ARM), a valuable tool for standardizing and automating somatosensory behavior experiments. The data supporting the use of the ARM system are compelling, though the determination of whether that device emits any sounds, including in the ultrasonic range when in operation or when at rest, would add value to the study. Nevertheless, the ARM system is anticipated to be popular amongst somatosensory and pain researchers.

    1. eLife assessment

      This manuscript focuses on understanding if and how the glycosylation of SARS-CoV2 spike protein affects a putative allosteric network of interactions controlled by the binding of a fatty acid. The main conclusion is that glycans do not significantly affect the network of allosteric interactions. This useful information - albeit mainly consisting of negative results - is based on solid evidence. It will be of interest to scientists focusing on SARS CoV2 protein structure and dynamics.

    1. eLife assessment

      This study makes a valuable contribution to understanding antiviral responses in fish by revealing a role for the cell cycle protein kinase CDK2 in type I interferon signaling. The evidence supporting the authors' claims is solid, including both in vivo and in vitro investigative approaches. However, the mechanisms underlying CDK2 activity are not completely established. This work will be of interest to cell biologists, immunologists, and virologists.

    1. eLife assessment

      This study provides a useful advance in generating mouse oligodendrocytes by direct lineage conversion from cortical astrocytes. The authors demonstrate that Sox10 converts astrocytes to MBP+ oligodendrocytes, whereas Olig2 expression converts astrocytes to PDFRalpha+ oligodendrocyte progenitor cells. The data supporting the conclusions are solid, but there are concerns regarding select figures and the experiments being limited to in vitro studies.

    1. eLife assessment

      The manuscript presented by Moyse and colleagues provides valuable insight into the origin, morphology, dynamics, and behavior of several populations of mononuclear phagocytes in the zebrafish heart. The study presents solid evidence through the use of transgenic lines and live imaging, although some limitations related to lineage tracing and molecular profiles should be considered. This work exemplifies the use of zebrafish as a model to study the role of leukocytes in cardiac development and regeneration and potentially draw broader interest to biologists working in immunology fields.

    1. eLife assessment

      This useful study describes an antibody-free method to map G-quadruplexes (G4s) in vertebrate cells. While the method might have potential, the current analysis is primarily descriptive and does not add substantial new insights beyond existing data (e.g., PMID:34792172). While the datasets provided might constitute a good starting point for future functional studies, additional data and analyses would be needed to fully support the major conclusions and, at the same time, clarify the advantage of this method over other methods. Specifically, the strength of the evidence for DHX9 interfering with the ability of mESCs to differentiate by regulating directly the stability of either G4s or R-loops is still incomplete.

    1. eLife assessment

      This valuable paper compares blood gene signature responses between small cohorts of individuals with mild and severe COVID-19. The authors provide solid evidence for distinct transcriptional profiles during early COVID-19 infections that may be predictive of severity, within the limitations of studying human patients displaying heterogeneity in infection timelines and limited cohort size.

    1. eLife assessment

      This study provides valuable insights into the specificity and promiscuity of toxic effector and immunity protein pairs. While the work is improved over a previous version, there are still some questions regarding the methodology used to draw certain conclusions, rendering the study somewhat incomplete. Nevertheless, this work will likely be of interest to microbiologists and biochemists working with toxin-antitoxin systems and effector-immunity proteins.

    1. eLife assessment

      This fundamental paper reports a new biosensor to study G protein-coupled receptor activation by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in cell culture, ex vivo (mouse brain slices), and in vivo (zebrafish, mouse). Convincing data are presented that show the new sensor works with high affinity in vitro, while requiring very high (non-physiological) concentrations of exogenous PACAP when applied to intact tissues. The sensor has not yet been used to detect endogenously released PACAP, raising questions about whether the sensor can be used for its intended purpose. While further work must be pursued to achieve broad in vivo applications under physiological conditions, the new tool will be of interest to cell biologists, especially those studying the large and significant GPCR family.

    1. eLife assessment

      In this fundamental study, the authors use innovative fine-scale motion capture technologies to study visual vigilance with high-acuity vision, to estimate the visual fixation of free-feeding pigeons. The authors present compelling evidence for use of the fovea to inspect predator cues, the behavioral state influencing the latency for fovea use, and the use of the fovea decreasing the latency to escape of both the focal individual and other flock members. The work will be of broad interest to behavioral ecologists.

    1. eLife assessment

      The authors performed extensive coarse-grained molecular dynamics simulations of 140 different prion-like domain variants to interrogate how specific amino acid substitutions determine the driving forces for phase separation. The analyses are solid, and the predictive scaling laws can aid in identifying potential phase-separating regions in uncharacterized proteins. Overall, this is a valuable contribution to the field of biomolecular condensates. It exemplifies how data-driven methodologies can uncover new insights into complex biological phenomena.

    1. eLife assessment

      This valuable study tests the functional role of food-washing behavior in removing tooth-damaging sand and grit in long-tailed macaques and whether dominance rank predicts the level of investment in the behavior. The evidence that food-washing is deliberate is compelling, but the evidence for variable and adaptive investment depending on rank is incomplete given confounding between sex and rank and limited sample size. A more careful and perhaps restrained interpretation of the findings, as well as a connection to the existing literature on optimal foraging theory, would increase the value of the study to its intended audience, i.e. researchers interested in foraging behavior, cognition, and primate evolution.

  2. Jul 2024
    1. eLife assessment

      This manuscript is a valuable contribution to our understanding of foraging behaviors in marine bacteria. The authors present a conceptual model for how a marine bacterial species consumes an abundant polysaccharide. Using experiments in microfluidic devices and through measurements of motility and gene expression, the authors offer convincing evidence that the degradation products of polysaccharide digestion can stimulate motility.

    1. eLife assessment

      The present paper describes an important methodological development that combines light (confocal) microscopy with scanning and transmission EM and EM tomography. The method expands the level of structural detail accessible to large-volume EM studies and thus represents an approach to integrate analyses of cellular and sub-cellular structures in biological samples. The study, which provides a compelling proof-of-principle, will be of particular value to cell biologists interested in the in-depth interpretation of high-resolution ultrastructural information from sparsely distributed targets - at multiple scales and in diverse biological structures.

    1. eLife assessment

      The study presents valuable findings on compensatory mechanisms in response to glycosuria. The evidence supporting the claims is solid, although a causal relationship is somewhat uncertain and the addition of a more clinically relevant model would have strengthened the findings. The work will be of interest to diabetes investigators.

    1. eLife assessment

      This valuable study provides new insight into potential subtle dynamics in effector biology. The data presented generally support the claims, but in some cases, significant controls are missing and so the overall work is currently incomplete. If the limitations can be addressed, this work should be of broad relevance for biologists interested in molecular plant-microbe interactions.

    1. eLife assessment

      This valuable study provides new insights into the neural circuits involved in post-mating responses in Drosophila females. It presents convincing evidence that the circuits for mating receptivity and egg-laying are distinct. A more thorough discussion regarding the integration of the new findings into the current understanding of post-mating behavior as well as clarification of some experimental details would further improve the manuscript.

    1. eLife assessment

      This study highlights an important discovery: a bacterial pathogen's effector influences plant responses that in turn affect how the leafhopper insect vector for the bacteria is attracted to the plants in a sex-dependent manner. The research is backed by convincing physiological and transcriptome analyses. This study unveils a complex interdependence between the pathogen effector, male leafhoppers, and a plant transcription factor in modulating female attraction to the plant, shedding light on previously unexplored aspects of plant-bacteria-insect interactions.

    1. eLife assessment

      This important body of work uses state-of-the-art quantitative methods to characterize and compare behaviors across five different fish species to understand which features are conserved and which ones are differentiated. The results from this study will potentially be of interest to ethologists and also have potential utility in understanding the neural mechanisms leading to these behaviors. While some claims are supported with compelling evidence, there are a few results that need further justification or qualification.

    1. eLife assessment

      This is a valuable paper that identifies a potential challenge for embryos during fertilization: holding sperm contents in the fertilized embryos away from the oocyte meiotic spindle so that they don't get ejected into the polar body during meiotic chromosome segregation. The authors identify proteins involved in cytoplasmic streaming and maintaining the grouping of paternal organelles as being critical for this process. There remain minor weaknesses in the data presented but the paper provides solid evidence for the majority of its claims, and while the findings may pertain to a narrow audience the tools used and basic characterization shown will likely be relied upon by many in the community and therefore is of high value.

    1. eLife assessment

      This fundamental study provides a near-comprehensive anatomical description and annotation of neurons in a male Drosophila ventral nerve cord, based on large-scale circuit reconstruction from electron microscopy. This connectome resource will be of substantial interest to neuroscientists interested in sensorimotor control, neural development, and analysis of brain connectivity. However, although the evidence is extensive and compelling, the presentation of results in this very large manuscript lacks clarity and concision.

    1. eLife assessment

      This study presents a valuable development of endometrial organoid culture methodology that mimics the window of implantation. Functional validation to demonstrate its robustness is lacking; therefore, the study is considered incomplete. The data may be interesting to embryologists and investigators working on reproductive biology and medicine.

    1. eLife assessment

      Therapeutic treatments for congenital and acquired craniofacial (CF) bone abnormalities are not well developed. This study provides convincing evidence for an innovative regenerative treatment for pediatric craniofacial bone loss using Jagged1-PEG-MAL hydrogel with pediatric human bone cells. The report is a valuable advance in this field.

    1. eLife Assessment

      This study provides convincing evidence that the quality of research in female-dominated fields of research is systematically undervalued by the research community. The authors' findings are based on analyses of data from a research assessment exercise in New Zealand and data on funding success rates in Australia, Canada, the European Union and the United Kingdom. This work is an important contribution to the discourse on gender biases in academia, underlining the pervasive influence of gender on whole fields of research, as well as on individual researchers.

    1. eLife assessment

      This useful manuscript describes a proteomic analysis of plasma from subjects before and after an exercise regime consisting of endurance and resistance exercise. The work identifies a putative new exerkine, CD300LG, and finds associations of this protein with aspects of insulin sensitivity and angiogenesis. The characterization remains incomplete at present. Because CD300LG may have a transmembrane domain, one possibility is that exercise causes the release of extracellular vesicles containing this protein. As this study reports associations, additional studies will be needed to establish causality. The paper will hopefully prompt further studies to more fully elucidate the underlying biology.

    1. eLife assessment

      This study provides useful insights into inter- and intra-site B cell receptor repertoire heterogeneity, noting that B cell clones from the tumour interact more with their draining lymph node than with the blood and that there is less mutation/expansion/activation of B cell clones in tumours. Unfortunately, the main claims are incomplete and only partially supported. The work could be of interest to an audience including medical biologists/immunologists and computational biologists across cancer specialities.

    1. eLife assessment

      This paper describes an important advance in a 2D in vitro neural culture system to generate mature, functional, diverse, and geometrically consistent cultures, in a 384-well format with defined dimensions and the absence of the necrotic core, which persists for up to 300 days. The well-based format and conserved geometry make it a promising tool for arrayed screening studies. Some of the evidence is incomplete and could benefit from a more direct head-to-head comparison with more standard culture methods and standardization of cell seeding density as well as further data on reproducibility in each well and for each cell line.

    1. eLife assessment

      This important study reports that a transcription factor that stimulates mRNA synthesis can stabilize its target transcripts, possibly through co-transcriptional assembly and action in the cytoplasm. While the primary observation is solid, whether an association of Sfp1 with specific transcripts in the cytoplasm is the critical step in transcript stabilization is not entirely clear. If confirmed by independent means, the authors would have found a novel mechanistic link between mRNA synthesis and cytoplasmic mRNA stability for specific transcripts. Such a finding would be of broad interest to the field of molecular biology.

    1. eLife assessment

      This useful study reports machine learning models derived from large-scale data to predict the risk of post-stroke epilepsy. The evidence supporting the conclusions is, however, incomplete, as many critical methodological aspects have been omitted or described too briefly, the analysis of the results is not complete, and the dataset and code have not been disclosed, which represents an obstacle to reproducibility. The study may be of some interest in the field of clinical neurology.

    1. eLife assessment

      This important study substantially advances our understanding of energy landscapes and their link to animal ontogeny. The evidence supporting the conclusions is compelling, with high-throughput telemetry data and advanced track segmentation methods used to develop and map energy landscapes. The work will be of broad interest to animal ecologists.

    1. eLife assessment

      This important study combines fMRI and electrophysiology in sedated and awake rats to show that LFPs strongly explain spatial correlations in resting-state fMRI but only weakly explain temporal variability. The authors propose that other, electrophysiology-invisible mechanisms contribute to the fMRI signal. The evidence supporting the separation of spatial and temporal correlations is convincing, and the authors consider alternative potential factors that could account for the differences in spatial and temporal correlation that were observed. This work will be of interest to researchers who study the mechanisms behind resting-state fMRI.

    1. eLife assessment

      This study presents a useful method for the extraction of behaviour-related activity from neural population recordings based on a specific deep learning architecture, a variational autoencoder. Although the authors performed thorough benchmarking of their method in the context of decoding behavioural variables, the evidence supporting claims about encoding is incomplete as the results may stem, in part, from the properties of the method itself.

    1. eLife assessment

      Calcium channels are key regulators of synaptic strength and plasticity. The authors generate new endogenous tags of the Drosophila channel Cac as well as auxiliary subunits to investigate distinct calcium channel functions at the fly NMJ, Is and Ib. They demonstrate functions for voltage-gated calcium channel subunits in promoting synaptic strength, diversity, and plasticity with a series of convincing analyses. The work is important and has broad implications. In addition, the newly developed tools should be quite beneficial for fly biologists.

    1. eLife assessment

      This study presents an important finding on the relationship between brain activity related to sustained attention and substance use in adolescence/early adulthood with a large longitudinal dataset. The evidence supporting the claims of the authors is convincing. The work will be of interest to cognitive neuroscientists, psychologists, and clinicians working on substance use or addiction.

    1. eLife assessment

      This paper provides potentially useful insight into why memory consolidation may differ between children (5-7 years of age) and adults. The work hints at developmental differences in neural engagement during the retrieval of recent and remote memories. However, there are several major issues with the experimental design and analyses that render the evidence supporting the authors' main claims incomplete.

    1. eLife assessment

      The authors show that short bouts of chemical ischemia lead to presynaptic changes in glutamate release and long-term potentiation, whereas longer bouts of chemical ischemia lead to synaptic failure and presumably cell death. This convincing work relies on rigorous electrophysiology/imaging experiments and data analysis. It is important as it provides new mechanistic details on chemical ischemia, which could offer potential insights into ischemic stroke in vivo.

    1. eLife assessment

      This study provides valuable insight into the role of miR-199a/b-5p in cartilage formation. The evidence supporting the significance of the identified miRNA and its target mRNA transcripts is convincing. This paper will likely primarily benefit scientists focused on diseases related to this biological process, such as osteoarthritis. Furthermore, researchers with a broader interest in miRNAs may find the computational model to identify novel RNA-RNA interactions particularly helpful.

    1. eLife assessment

      This important study describes the crystallographic screening of a number of small molecules against a viral enzyme critical for the 5' capping of SARS-CoV-2 RNA and viral replication. While the high-quality crystal structures and complementary biophysical assays in this study provide solid evidence to support the major claims regarding how these small molecule compounds bind to the viral enzyme, the mismatch between the antiviral activity and binding to the viral enzyme of several small molecule compounds could have been more thoroughly investigated or discussed. This paper would be of interest to the fields of coronavirus biology, structural biology, and drug discovery.

    1. eLife assessment

      This useful study shows the representations that emerge in a recurrent neural network trained on a navigation task by requiring path integration and decodability. The network modeling was solid, but interpretation of neural data and mechanisms was incomplete.

    1. eLife assessment

      This fundamental study uncovers the detailed structural mechanisms by which covalent and non-covalent synthetic ligands can simultaneously occupy the binding pocket of the nuclear receptor transcription factor PPARγ. Supported by a compelling set of structural, biochemical, and biophysical data, the findings challenge the reliability of two widely used covalent inhibitors and have broader implications for nuclear receptor research. This study will interest structural biologists and biochemists investigating the binding mechanisms of ligands targeting the nuclear receptor superfamily.

    1. eLife assessment

      The authors' innovative use of single-cell sequencing combined with physiological phenotyping of 5 different Parkinsons models in Drosophila provides compelling support for the important conclusion that these different models have a shared convergent effect on olfactory projection neuron (OPN) dysfunction. The effect on OPN occurs early in disease progression, and likely underlies anosmia observed as an early symptom of PD. Additional experiments and analysis are required to support the authors' suggestions that: (a) the defect in these models is specific to cholinergic OPNs; (b) that OPN degeneration is (causally) connected to dopaminergic neuron (DAN) degeneration; and also (c) that observed motor defects are reasonable measure of DAN dysfunction.

    1. eLife assessment

      This study uses state-of-the-art methods to label endogenous dopamine receptors in a subset of Drosophila mushroom body neuronal types. The authors report that DopR1 and Dop2R receptors, which have opposing effects in intracellular cAMP, are present in axons termini of Kenyon cells, as well as those of two classes of dopaminergic neurons that innervate the mushroom body indicative of autocrine modulation by dopaminergic neurons. Additional experiments showing opposing effects of starvation on DopR1 and DopR2 levels in mushroom body neurons are consistent with a role for dopamine receptor levels increasing the efficiency of learned food-odour associations in starved flies. Supported by solid data, this is a valuable contribution to the field.

    1. eLife assessment

      This important work, leveraging state-of-the-art whole-night sleep EEG-fMRI methods, advances our understanding of the brain states underlying sleep and wakefulness. Despite a small sample size, the authors present convincing evidence for substates within N2 and REM sleep stages, with reliable transition structure, supporting the perspective that there are more than the five canonical sleep/wake states.

    1. eLife assessment

      This study presents a valuable finding that PRMT inhibitors may exert synergistic effects with PARP inhibitors to eliminate ovarian and triple-negative cancer cells in vitro and in vivo using preclinical mouse models. The evidence supporting the claims of the authors is solid, although the inclusion of novelty justification would have strengthened the study. The work will be of interest to scientists working on breast cancer and ovarian cancer.

    1. eLife assessment

      This fundamental study identifies protein kinases in the parasitic protozoan, Toxoplasma gondii that are required for parasite invasion of host cells and differentiation to drug-resistant chronic stages. The use of advanced proteomic and functional approaches provides compelling evidence for the proposed signalling pathway, although additional analyses are needed to fully validate some findings. The work will be of broad interest to cell biologists and parasitologists with an interest in cell signalling and environmental sensing.

    1. eLife assessment

      This study presents the valuable finding that TFIIIC interacts with MYCN to regulate RNA polymerase II dynamics by dissecting its impact on 3D chromatin architecture. Authors provide convincing evidence that MYCN and TFIIIC show long-range chromatin contacts, and that the expression of each protein limits the function of the other. The notion emerges that TFIIIC helps MYCN to maintain output at promoters while decreasing less productive associations at larger more extensively connected chromatin hubs. The paper is of interest to molecular biologists working on MYCN-dependent regulation of gene expression.

    1. eLife assessment

      This important study presents new knowledge of the spermatogonial stem cell (SSC) niche in trans women after gender-affirming hormone therapy (GAHT). The evidence supporting the claims is convincing. The work will be of interest to researchers and clinicians working in the field of reproductive medicine and andrology.

    1. eLife assessment

      This is a valuable manuscript that successfully integrates several datasets to determine genome interactions with several nuclear bodies. The integrative datasets are a major strength of the manuscript. The evidence supporting the central claims is varied in its strength ranging from solid to incomplete. Orthogonal evidence validating the novel methodologies with alternative approaches would better support the central claims. We encourage the authors to consider a revised manuscript which addresses these points.

    1. eLife assessment

      This study provides useful insights into the conformational dynamics of the nucleic acid recognition lobe of GeoCas9, a thermophilic Cas9 from Geobacillus stearothermophilus. The influence of local dynamics and allosteric regulation on guide RNA binding affinity and DNA cleavage specificity is investigated via cutting-edge NMR approaches and mutagenesis. While backed by rigorous biophysical analyses, evidence supporting the proposed mechanistic model is found to be incomplete due to the limited impact of the studied mutations on GeoCas9 cleavage activity. This work will be of interest to biochemists and biophysicists interested in interdomain communication and allosteric mechanisms in Cas9 enzymes.

    1. eLife assessment

      This study offers a useful advance by introducing a cord blood DNA methylation score for maternal smoking effects, with the inclusion of cohorts from diverse backgrounds. However, the overall strength of evidence is deemed incomplete, due to concerns regarding low exposure levels and low statistical power, which hampers the generalisability of their findings. The study provides an interesting basis for future studies, but would benefit from the addition of more cohorts to validate the findings and a focus on more diverse health outcomes.

    1. eLife assessment

      This paper investigates how the EWS::FLI1 fusion protein organizes chromatin topology and regulates gene expression in an aggressive pediatric bone cancer known as Ewing sarcoma. The authors used the most recent genomics methodologies to provide solid-based evidence for the role of a short alpha helix in the DNA binding domain of FLI1 in modulating binding to GGAA microsatellites and promoting enhancer activity. The study provides valuable insight into the underlying oncogenic mechanisms in Ewing sarcoma, despite the inherent limitations of the some of the techniques used.

    1. eLife assessment

      This useful study uses fluorescence lifetime imaging (FLIM) and tmFRET to resolve resting vs. active conformational heterogeneity and free energy differences driven by cGMP and cAMP in a tetrameric arrangement of isolated CNBDs from a prokaryotic CNG channel. The data are compelling and the experimental approach features rigorous new methods and analyses. Limitations include (1) only the cytosolic fragments of the channel were studied; (2) the results are not adequately discussed in the context of the extensive prior literature about conformational dynamics and energetics of CNBD-containing ion channels; (3) ambiguity in the stoichiometry of labeled:unlabeled subunits; and (4) the lack of a discussion of alternative interpretations of the data. The study will be of interest to scientists working on the structural mechanisms of membrane proteins.

    1. eLife assessment

      The study presents a framework viewing gene-by-environment (GxE) effect estimation as a bias-variance tradeoff problem. The authors convincingly show that greater statistical power can be achieved in detecting GxE if an underlying model of polygenic GxE is assumed. This polygenic amplification model is a truly novel view with fundamental promise for the detection of GxE in genomic datasets. That said, at present the polygenic architecture investigation presented in the manuscript is somewhat limited to specific models and may not adequately build over the bias-variance tradeoff part of the manuscript. If the authors can show in their simulations that they can in principle detect more complex scenarios of amplification, then the strength of the paper would be enhanced.

    1. eLife assessment

      This valuable study explores T cell receptor activation during autoreactive T cell development and how the strength of T cell receptor engagement in naïve cells can predispose T cells to develop into effector/memory T cells. Solid evidence confirms published data that naïve T cells with higher CD5 expression were poised for activation and more pathogenic in the mouse model of autoimmune diabetes. However, the evidence regarding the regulation of differentiation of these cells during development is still incomplete.

    1. eLife assessment

      The present study provides valuable information into the regulatory mechanisms through which conjugated linoleic acids influence intramuscular fat deposition and muscle fiber transformation in pigs. The data are analyzed comprehensively using solid and validated single nuclei methodology. Overall, the provided data are convincing and support the conclusion of the study.

    1. eLife assessment

      This valuable article represents a significant body of work that addresses some novel aspects of the biology of lung cancer influence of CHIP and its impacts on responses to therapy. While a high clonal hematopoiesis burden was previously linked with an inflammatory phenotype in other disease settings, the authors demonstrate with solid evidence that this is also true for lung cancer.

    1. eLife assessment

      This important study using Drosophila genetics explores the role of TRPγ in Dh44 neuroendocrine cells for lipid and protein metabolism. Evidence for lipid storage and metabolism measured by triacylglycerol levels, lipid droplet size, and starvation resistance are generally solid to support the conclusion. However, the claim on the TRPγ functions in Dh44R2 is still unclear, as the analysis of the role and expression of Dh44R2 in the gut is incomplete.

    1. eLife assessment

      This study investigates the molecular mechanisms underlying chronic pain-related memory impairment by focusing on S1P/S1PR1 signaling in the dentate gyrus (DG) of the hippocampus. Through behavioral tests (Y-maze and Morris water maze) and RNA-seq analysis, the researchers discovered that S1P/S1PR1 signaling is crucial for determining susceptibility to memory impairment, with decreased S1PR1 expression linked to structural plasticity changes and memory deficits. This work has valuable significance and a convincing level of evidence, thus offering new insights into the mechanisms underlying chronic pain-related memory impairment.

    1. eLife assessment

      This important work uses an innovative approach to understand similarities between haemodynamic and electrophysiological activity of the human brain. The study provides incomplete evidence to indicate that while similar functional brain networks are used in both modalities, there is a tendency for these multi-modal networks to spatially converge at synchronous rather than asynchronous time points. This work will be of interest to neurophysiological and brain imaging researchers.

    1. eLife assessment

      Wang et al. presented visual (dot) motion and/or the sound of a walking person and found that EEG activity tracks the step rhythm, as well as the gait (2-step cycle) rhythm, with tentative 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 findings will be of wide interest to those examining biological motion perception and oscillatory processes more broadly, with the potential to be important. However, at present, due to some analysis concerns - most notably, evidence of double-dipping for one of the core findings - the evidence is incomplete. Furthermore, some of the theoretical interpretations concerning entrainment must remain speculative when the authors cannot dissociate evoked responses from entrained oscillatory effects.

    1. eLife assessment

      The work by Han and collaborators describes valuable findings on the role of Akkermansia muciniphila during ETEC infection. If confirmed, these findings will add to a growing list of beneficial properties of this organism. However, as it stands, the strength of the evidence used to justify the conclusions in the manuscript is incomplete.

    1. eLife assessment

      This valuable work explores death coding data to understand the impact of COVID-19 on cancer mortality. The work provides solid evidence that deaths with cancer as a contributing cause were not above what would be expected during pandemic waves, suggesting that cancer did not strongly increase the risk of dying of COVID-19. These results are an interesting exploration into the coding of causes of death that can be used to make sense of how deaths are coded during a pandemic in the presence of other underlying diseases, such as cancer.

    1. eLife assessment

      This work will be of interest to the motor control community as well as neuroAI researchers interested in how bodies constrain neural circuit function. The authors present "MotorNet", a useful software package to train artificial neural networks to control a biomechanical model of an effector. The manuscript provides solid evidence that MotorNet is easy to use and can reproduce past results in the field, both at the neural and behavioural levels. Validation is limited to planar arm-like plants or point-masses, so future work exploring three-dimensional movements and other types of plants would strengthen the impact of the tool.

    1. eLife assessment

      This important study reveals the role of skin-resident mast cells in amphibians in mediating antimicrobial responses. The data are compelling and highlight species-specific biology that can cross-inform human mast cell biology in a species that does not rely on IgE as a primary mechanism for antimicrobial skin responses.

    1. eLife assessment

      This work provides a valuable characterization of neural activity in the anterior insular cortex during fear. Using behavior, single unit recording, and optogenetic control of neural activity, the paper provides convincing data on the role of anterior insular circuits in bidirectionally controlling fear. The study is a great starting point on the path to testing hypotheses about bidirectional control of behavior via neural activity in anatomically defined output populations.

    1. eLife assessment

      This important study reports that FBXO24 is essential for the normal formation and function of the sperm flagellum, motility, and male fertility in mice. The evidence supporting the direct role of this protein in preventing RNP granule formation in the sperm flagellum is compelling. This work will be of interest to biomedical researchers who work on testicular biology and male fertility.

    1. eLife assessment

      This valuable study demonstrates that there is significant variation in the susceptibility of isoniazid-resistant Mycobacterium tuberculosis clinical isolates to killing by rifampicin, in some cases at the same tolerance levels as bona fide resistant strains. The evidence provided is solid, with no clear genetic marker for increased tolerance, suggesting that there may be multiple routes to achieving this phenotype. The work will be of interest to infectious disease researchers.

    1. eLife assessment

      This study presents valuable findings on the role of the sirtuins SIRT1 and SIRT3 during Salmonella Typhimurium infection. Although the work 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 found that the evidence to support the claims is incomplete. In particular, the discrepancy between results obtained using cultured cell lines and the animal model of infection, as well as potential indirect effects through the microbiome stand out.

    1. eLife assessment

      This valuable study combines prospective cohort, metabolomics, and machine learning to identify a panel of 9 circulating metabolites that improved the ability in risk prediction of progression from prediabetes to diabetes. The findings are solid and the methods, data, and analyses support the claims. However, the interpretation would benefit from a more rigorous description. With revision of these weaknesses, this paper would provide insights into the integration of these metabolites into clinical and public health practice.

    1. eLife assessment

      This study provides important findings regarding the stability over time of the response properties of neurons in the auditory cortex, including their nonlinear sensitivity to sound context. The data obtained from chronic recordings combined with nonlinear stimulus-response estimation provide convincing evidence that auditory cortical representations are stable over a period of days to weeks. While this study should be of widespread interest to sensory neuroscientists, the paper would be strengthened by a more thorough assessment and discussion of the effects of context and of the stability of the responses, as well as by the inclusion of more information about the location and types of neurons that were sampled.

    1. eLife assessment

      This study shows that a peptide called galanin can decrease or increase seizure activity in experimental models of seizures depending on the way seizures are induced (genetic vs. pharmacological). The authors use zebrafish and several methods to address the effects of galanin. The study will be useful to researchers who use zebrafish as experimental animals and who are interested in how the peptides in the brain (neuropeptides) regulate seizures. However, the strength of evidence was considered incomplete at the present time due to several limitations of the results.

    1. eLife assessment

      This descriptive study reports the genetic requirements for growth and fitness of multiple clinical strains of a relatively understudied species of mycobacteria, Mycobacterium intracellulare. The findings are valuable however, the study is incomplete as the primary claims related to hypoxia adaptation need additional experimental support and data presentation requires more clarity. The work will be of interest to microbiologists.

    1. eLife assessment

      This important study shows the effect of gut dysbiosis on the colonization of mycobacteria in the lung. The data with comprehensive analysis of gene expression profiles in the lung with dysbiotic mice is compelling and goes beyond the current state of the art. However, the mechanistic insight and the experiments with Mtb infection are incomplete. With those parts strengthened, this paper would be of interest to researchers working on Mtb infection.

    1. eLife assessment

      The manuscript by Carbo et al. reports a novel role for the MltG homolog AgmT in gliding motility in M. xanthus. The authors provide convincing data to demonstrate that AgmT is a cell wall lytic enzyme (likely a lytic transglycosylase), its lytic activity is required for gliding motility, and that its activity is required for proper binding of a component of the motility apparatus to the cell wall. The findings are valuable as they contribute to our understanding of the molecular mechanisms underlying the interaction between gliding motility and the bacterial cell wall.

    1. eLife assessment

      This important study demonstrates a potential mechanism by which adjuvants influence T-cell responses. The observation that adjuvant impacts the exogenous peptide repertoire presented by MHC II molecules is fascinating and the strength of the evidence is solid, with studies comparing different adjuvants and an H pylori vaccine in murine models and in vitro systems, analysis of MHCII: peptide complexes in antigen-presenting cells and assessment of differential peptide binding affinities. This work will be of broad interest to vaccinologists as well as immunologists.

    1. eLife assessment

      This study provides valuable insights into how IL-1 cytokines may protect cells against SARS-COV-2 infection. By inducing a non-canonical RhoA/ROCK signaling pathway, IL-1beta appears to inhibit the ability of SARS-COV-2 infected cells to fuse with uninfected cells and produce syncytia. The evidence underlying the identification of the key signaling components required for this inhibitory phenotype in vitro is solid and could be further improved by addressing key weaknesses. However, data supporting this specific mechanism of inhibition in IL-1-mediated control of SARS-COV-2 infection in vivo remains incomplete.

    1. eLife assessment

      In this valuable study, the authors propose a model wherein the bacterial redox state plays a crucial role in the differentiation of Chlamydia trachomatis into elementary and reticulate bodies. They provide evidence to argue that a highly oxidising environment favours the formation of elementary bodies while a reducing condition slows down development. Whilst aspects related to the role of AhpC in regulating redox, and implications on differentiation, are solid, more precise measurements of the redox potential are required to convincingly demonstrate the role of redox in developmental progression.

    1. eLife assessment

      This important study examines the role of TNF in modulating energy metabolism during parasite infection. The authors perform an elegant set of studies, however the evidence supporting the major claims of the manuscript is incomplete. This work integrates an interesting set of observations that will be of interest to the Plasmodium and pathogenesis communities with an expanded set of experiments.

    1. eLife assessment

      The work provides a valuable assessment of how antibiotics impact the human gut microbiota in diverse observational cohorts. Although the data presented are solid, some of the assumptions underlying their models may have affected the interpretation of their findings. The study is relevant for researchers and clinicians interested in antimicrobial resistance.

    1. eLife assessment

      This valuable study reports data showing the link between a disruption in testicular mineral (phosphate) homeostasis, FGF23 expression, and Sertoli cell dysfunction. The data supporting the conclusion remains incomplete. This work will be of interest to biomedical researchers working on testis biology and male infertility.

    1. This sets up Aciman’s thematic comparison of Elio and Oliverwith Alcibiades and Socrates, which I will address in the following chapter.

      This was just pre-knowledge for the real argument in Alcibiades and Socrates? Because this did not confound expectations, simply established a kind of perceived imbalance in love?

    2. Through Elio’s espousal of Sappho’s affective language, which is marked as effeminate,his performance of gender subverts our gender expectations

      Highlighting that Elio is effeminate and not manly, subverting gender expectations

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    Annotators

    1. eLife assessment

      This valuable study shows how an intersecting network of regulators acting on genes with differences in their RNA metabolism explains why the loss of some regulators of RNAi in C. elegans can selectively impair the silencing of some target genes. The evidence presented is convincing, as the authors use a combination of computational modeling and RNAi assays to support their conclusions.

    1. eLife assessment

      This provocative manuscript from presents valuable 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, although the evidence in support of the conclusions is currently incomplete. The reasons include that taphonomy is not presently considered, and a greater diversity of experimental environmental conditions is not evaluated – which is significant because we ultimately do not know much about Earth's early environments. The authors may want to reframe their conclusions to reflect this work as a first step towards an interpretation of some microfossils as 'proto-cells,' and less so as providing strong support for this hypothesis.

    1. eLife assessment

      This important study aims to understand how the regulation of oligodendrocyte progenitor cell (OPC) remyelination and function contributes to the treatment of multiple sclerosis. The authors provide convincing evidence for the platelets mediating OPC differentiation and remyelination. This work will be of interest to several disciplines.

    1. eLife assessment

      The authors have improved a method to differentiate human iPSC-derived microglial cells with immune responses and phagocytic abilities; and through transplantation into the adult mouse retina, the authors further demonstrated their integration and occupation of native microglial cell space, and functional response to retinal injuries. The study is important and the data are convincing for potential microglial replacement therapy to treat retinal and CNS diseases.

    1. eLife assessment

      This useful study investigates the evolution of the Mycobacterium tuberculosis Complex (MTBC) pangenome using state-of-the-art bioinformatic tools to analyse 324 complete and 11 new genomes representing all known lineages and sublineages, yielding data indicating that MTBC has a closed pangenome with relatively few accessory genes. The strength of the evidence is solid for gene presence-absence analysis and inadequate for the deletion bias claim. Their conclusions regarding pangenome evolution being driven by deletions in sublineage-specific regions of difference are difficult to interpret due to the description of methods not being complete and data interpretation not being adequate.

    1. eLife assessment

      This valuable study explores a new strategy of lysin-derived antimicrobial peptide-primed screening to find peptidoglycan hydrolases from bacterial proteomes. Using this strategy, the authors identified five peptidoglycan hydrolases from Acinetobacter baumannii, which they tested on various Gram-positive and Gram-negative pathogens for antimicrobial activity. The data presented are solid and will be of interest to microbiologists.

    1. eLife assessment

      This manuscript outlines an interaction between senescence-related 15d-PGJ2 and the proliferation and differentiation of myoblasts, with potential implications for muscle health. This manuscript is useful in understanding the role of lipid metabolite 15d-PGJ2 in myoblast proliferation and differentiation. However, in its current form, the manuscript is incomplete as there are several concerns in the statistical analysis, lack of clarity on the mechanistic details, and concerns about the use of an immortalized C2C12 myoblasts cell line to draw major conclusions related to senescence-associated secreted phenotype.

    1. eLife assessment

      The study answers the important question of whether the conformational dynamics of proteins are slaved by the motion of solvent water or are intrinsic to the polypeptide. The results from neutron scattering experiments, involving isotopic labelling, carried out on a set of four structurally different proteins are convincing, showing that protein motions are not coupled to the solvent. A strength of this work is the study of a set of proteins using spectroscopy covering a range of resolutions. A minor weakness is the limited description of computational methods and analysis of data. The work is of broad interest to researchers in the fields of protein biophysics and biochemistry.

    1. eLife assessment

      This method paper proposes a valuable Oscillation Component Analysis (OCA) approach, in analogy to Independent Component Analysis (ICA), in which source separation is achieved through biophysically inspired generative modeling of neural oscillations. The empirical evidence justifying the approach's advantage is solid. This work will be of interest to researchers in the fields of cognitive neuroscience, neural oscillation, and MEG/EEG.

    1. eLife assessment

      This study provides important new insight into how non-synaptic interactions affect the activity of adjacent gustatory neurons housed within the same sensillum. The conclusions are supported by convincing electrophysiological, behavioral, and genetic data. This work will be of interest to neuroscientists studying chemosensory processing or regulation of neuronal excitability.

    1. eLife assessment

      This important study enhances our understanding of how habitat fragmentation and climate change jointly influence bird community thermophilization in a fragmented island system. The evidence supporting some conclusions is incomplete, as while the overall trends are convincing, some methodological aspects, particularly the isolation metrics and interpretation of colonization/extinction rates, require further clarification. This work will be of broad interest to ecologists and conservation biologists, providing crucial insights into how ecosystems and communities react to climate change.

    1. eLife assessment

      This potentially important study employs advanced imaging techniques to directly visualize molecular dynamics and of the immune receptor kinase FLS2 in specific microenvironments. The evidence supporting the ligand-induced association with remorin and the requirement of a previously reported phosphosite as presented is solid, although support by independent methods would be welcome. The work will be of interest to plant biologists working on cell surface receptors.

    1. eLife assessment

      This important study explores how cells maintain subcellular structures in the face of constant protein turnover, focusing on neurons, whose synapses must be kept stable over long periods of time for memory storage. Using proteins from knock-in mice expressing tagged variants of the synaptic scaffold protein PSD95, nanobodies, and multiple imaging methods, there is compelling evidence that PSD95 proteins form complexes at synapses in which single protein copies are sequentially replaced over time. This happens at different rates in different synapse types and is slowest in areas where PSD95 lifetime is the longest and long-term memories are stored. While of general relevance to cell biology, these findings are of particular interest to neuroscientists because they support the notion put forward by Francis Crick that stable synapses, and hence stable long-term memories, can be maintained in the face of short protein lifetimes by sequential replacement of individual subunits in synaptic protein complexes.

    1. eLife assessment

      This important study explored a molecular comparison of smooth muscle and neighboring fibroblast cells found in lung blood vessels afflicted by a disease called pulmonary arterial hypertension. In doing so, the authors described distinct disease-associated states of each of these cell types with further insights into the cellular communication and crosstalk between them. The strength of evidence was convincing through the use of complementary and sophisticated tools, accompanied by rare isolation of human diseased lung blood vessel cells that were source-matched to the same donor for direct comparison.

    1. eLife assessment

      This important study shows that age-related gut microbiota modulates uric acid metabolism through the NLRP3 inflammasome pathway and thereby regulates susceptibility to age-related gout. Whereas some of the data are compelling, several experimental approaches and methods are currently incomplete, which could be remedied with more rigorous approaches. If strengthened, this paper would be of broad interest to researchers working on gout and microbiota.

    1. eLife assessment

      This fundamental study by Yogesh and Keller provides a set of results describing the response properties of cholinergic input and its functional impacts in the mouse visual cortex. They found that cholinergic inputs are elevated by locomotion in a binary manner regardless of locomotor speeds, and activation of cholinergic input differently modulated the activity of Later 2/3 and Layer 5 visual cortex neurons induced by bottom-up (visual stimuli) and top-down (visuomotor mismatch) inputs. The experiments are cutting-edge and well-executed, and the results are convincing.

    1. eLife assessment

      In this compelling study, the authors examine the interactions between stellate cells and PV+ interneurons in the medial entorhinal cortex, shedding light on the circuit mechanisms that underlie grid cell activity. Huang et al., focus on the spatial distribution of synaptic inputs and report that closely located neuron pairs receive common inputs, suggesting a structured functional organization in the entorhinal cortex. Advanced dual whole-cell patch recordings further reveal patterns of postsynaptic activation, indicating intensive interactions within clusters of these neurons, with weaker interactions between clusters. These important findings offer significant insights into the functional dynamics of the entorhinal cortex.

    1. eLife assessment

      In this fundamental study, authors present compelling evidence for the diversity in cellular and synaptic properties of one class of spinal interneurons and tie it to their differentiated role in locomotor pattern generation. The findings reported here will be of broad interest to neuroscientists in general and to motor systems scientists in particular.

    1. eLife assessment

      The authors provide a valuable analysis of what neural circuit mechanisms enable varying the speed of retrieval of sequences, which is needed in situations such as reproducing motor patterns. Their use of heterogeneous plasticity rules to allow external currents to control speed of sequence recall is a novel alternative to other mechanisms proposed in the literature. They perform a convincing characterization of relevant properties of recall via simulations and theory, though a better mapping to biologically plausible mechanisms is left for future work.

    1. eLife assessment

      This important study extends our understanding of how the medial prefrontal cortex regulates flexible action during adversity. The data provide compelling evidence of a role for prefrontal PV neuron activity in active avoidance. This builds on the general idea that these neurons play a role in flexible behavior and demonstrates this in the context of freezing/avoidance conflict. The overall findings contribute to our understanding of mechanisms that support aversively motivated instrumental learning and may provide insight into both stress vulnerability and resilience processes. This work will be of interest to those interested in learning, aversive motivation, interneuron and/or prefrontal cortex function, or conditions relates to these processes and mechanisms.

    1. eLife assessment

      This valuable manuscript reveals sex differences in bi-conditional Pavlovian learning and conditional behavior. Males learn hierarchical context-cue-outcome associations more quickly, but females show more stable and robust task performance. These sex differences are related to cellular activation in the orbitofrontal cortex. Although the evidence supporting these claims is convincing, some assertions of sex differences in context-dependent discrimination behaviour may be slightly overstated yet have strong potential to guide future research to clarify the nature of these differences. The results will be of interest to many behavioural neuroscientists, particularly those who investigate sex-specific behaviours.

    1. eLife assessment

      This important study investigates neurobiological mechanisms underlying the maintenance of stable, functionally appropriate rhythmic motor patterns during changing environmental conditions - temperature in this study in the crab Cancer borealis stomatogastric central neural pattern generating circuits producing the rhythmic pyloric motor pattern, which is naturally subjected to temperature perturbations over a substantial range. The authors present compelling evidence that the neuronal hyperpolarization-activated inward current (Ih), known to contribute to rhythm control, plays a key role in the ability of these circuits to appropriately adjust the frequency of rhythmic neural activity in a smooth monotonic fashion while maintaining the relative timing of different phases of the activity pattern that determines proper motor coordination transiently and persistently to temperature perturbations. This study will interest neurobiologists studying rhythmic motor circuits and systems and their physiological adaptations.

    1. eLife assessment

      This study presents valuable findings on tumor-reactive T cells in liver metastases of uveal melanoma (UM). The authors conducted single-cell RNA sequencing to identify potential tumor-reactive T cells and used PDX models for functional analysis. The evidence supporting their claims is solid. The work will be of interest to scientists working in the field of uveal melanoma.

    1. eLife assessment

      This study presents valuable findings on core genome mutations that might have driven the emergence of the Staphylococcus aureus lineage USA300, a frequent cause of community-acquired infections. The authors present a solid novel approach that combines genome-wide association studies and RNA-expression analyses, both applied to extensive publicly available datasets. This approach generated an intriguing hypothesis that should be validated experimentally. The work will interest microbiologists working in genomic epidemiology and phenotype-genotype association studies.

    1. eLife assessment

      The authors studied the relationship between structural and functional lateralization in the planum temporale region of the brain, whilst also considering the morphological presentation of a single or duplicated Heschl's gyrus. The analyses are convincing due to a large sample size, inter-rater reliability, and corrections for multiple comparisons. The associations in this valuable work might serve as a reference for future targeted-studies on brain lateralization.

    1. eLife assessment

      This study used deep neural networks (DNN) to reconstruct voice information (viz., speaker identity), from fMRI responses in the auditory cortex and temporal voice areas, and assessed the representational content in these areas with decoding. A DNN-derived feature space approximated the neural representation of speaker identity-related information. While some of the neural decoding results are valuable, the overall evidence for general representational and computational principles is incomplete as the results rely on a very specific model architecture.

    1. eLife assessment

      This useful study measured how information about object categories varies with time in EEG responses to object images in human participants and found that real-world size, retinal size, and real-world depth are represented at different time points in the response. The evidence presented is incomplete and can be further strengthened by removing confounds related to other covarying properties such as semantic categories, and by clarifying the partial correlations that are used to support the conclusions.

    1. eLife assessment

      Some delayed rectifier currents in neurons are formed by the combination of Kv2 and silent subunits, KvS. However, we lack the tools to identify these heteromeric channels in vivo. In this valuable study by the Sack group, the authors identify a pharmacological tool that can reveal the presence of KvS subunits as components of the delayed rectifier potassium currents in selected neurons. The experimental evidence presented in the manuscript is compelling and represents an advance that should be of interest to a wide community of neuroscientists and channel physiologists.

    1. eLife assessment

      This work represents a new toolkit for implementing virtual reality experiments in head-fixed animals. It is a valuable contribution to the field and the evidence for its utility and performance is solid. Some minor improvements in the material presented - including clarifying design decisions and providing more details about design features - would improve the readability and thereby potentially increase its impact.

    1. eLife assessment

      In their manuscript, Cummings et al. use in vitro reconstitution to examine the differential activities of tubulin polyglycylases, providing valuable insights into the enzymatic regulation of microtubule glycylation and its mechanistic role in maintaining cilia function and microtubule dynamics. The convincing evidence, supported by well-designed experiments and appropriate controls, significantly advances our understanding of the tubulin code and its biochemical mechanisms.

    1. eLife assessment

      This important work substantially advances our understanding of RNA structure analysis by introducing an innovative method that extends DMS probing to include guanosine residues, thereby enhancing our ability to detect complex tertiary interactions. The evidence supporting the conclusions is compelling, with detailed analyses demonstrating the method's capacity to differentiate structural contexts and improve RNA structure predictions. This work will be of broad interest to RNA structural biology, biochemistry, and biophysics researchers.

    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 the statistical analyses and figure presentation could be improved, and the concrete contribution of the paper and how it relates to previous literature clarified.

    1. eLife assessment

      In this manuscript the authors present high-speed atomic force microscopy (HSAFM) to analyze real-time structural changes in actin filaments induced by cofilin binding. This important study enhances our understanding of actin dynamics which plays a crucial role in a broad spectrum of cellular activities based on solid experimental evidence. Some technical questions, however, remain, making the data interpretation incomplete.

    1. eLife assessment

      The authors provide solid data on a functional investigation of potential nucleoid-associated proteins and the modulation of chromosomal conformation in a model cyanobacterium. These valuable findings will be of interest to the chromosome and microbiology fields. Additional analysis and the tempering of conclusions has helped to improve the work, although further refinement remains possible.

    1. eLife assessment

      This useful manuscript presents an analysis of different factors that are required for release of the lipid-linked morphogen Shh from cellular membranes. The evidence is still incomplete, as experiments rely on over-expression of Shh in a single cell line and are sometimes of a correlative nature. The study, which otherwise confirms and extends previous findings, will be of interest to developmental biologists who work on Hedgehog signaling.

    1. eLife assessment

      This study presents valuable empirical work and simulations that are relevant for the evolution of genetic load linked to self-incompatibility alleles in two Arabidopsis species. The evidence supporting the findings is solid, although it remains to be seen how generalizable the conclusions are beyond the specific system investigated here, not least because the statistical significance varied between the two species. The work will be of relevance to geneticists interested in the evolution of allelic diversity in similar systems.

    1. eLife assessment

      This important modeling work demonstrates out-of-distribution generalization using a grid cell coding scheme combined with Determinantal Point Process Attention. The simulations provide convincing evidence that the model improves generalization performance across several tasks. The generality of the approach is unclear, however, and there is limited comparison to relevant prior work.

    1. eLife assessment

      This important work introduces a method to express fluorogenic DNA aptamers in E. coli, paving the way for genetically encoded fluorescent DNA. The evidence supporting the conclusions is solid, consisting of comparisons of the aptamer's activity in vitro and within bacterial cells. This advancement described in this study is likely to become a standard technique in the DNA aptamer field, and the work will be of interest and utility to researchers in synthetic biology, molecular imaging, and bacterial genetics fields.

    1. eLife assessment

      The authors have developed a valuable approach that employs cell-free expression to reconstitute ion channels into giant unilamellar vesicles for biophysical characterisation. The work is solid and will be of particular interest to those studying ion channels that primarily occur in organelles and are therefore not amenable to be studied by more traditional methods.

    1. eLife assessment

      In this valuable study, Huffer et al posit that non-cold sensing members of the TRPM subfamily of ion channels (e.g., TRPM2, TRPM4, TRPM5) contain a binding pocket for icilin that overlaps with the one found in the cold-activated TRPM8 channel. By examining a body of TRP channel cryo-EM structures to identify the conserved site, this study presents convincing electrophysiological evidence supporting the identification of an icilin binding pocket within TRPM4. This study shows that icilin has modulatory effects on the TRPM4 channel and will be of direct interest to those working in the TRP-channel field, but it also has implications for studies of somatosensation, taste, as well as pharmacological targeting of the TRPM subfamily.

    1. eLife assessment

      The authors combined molecular dynamics simulations and experiments to study the role of ATP as a hydrotrope of protein aggregates. The topic is of major current interest and thus the study potentially makes a useful contribution to the community. In the current form, however, the level of evidence from the computation is considered incomplete, due to several issues such as limited convergence test, analysis, and the very high ATP concentration used in the simulation.

    1. eLife assessment

      This fundamental work provides new mechanistic insight into the regulation of PDGF signaling through splicing controls. The evidence is compelling to demonstrate the involvement of Srsf3, an RNA-binding protein, in this new mechanism. The work will be of broad interest to developmental biologists in general and molecular biologists/biochemists in the field of growth factor signaling and RNA splicing.

    1. eLife assessment

      This study presents a potentially valuable finding regarding the role of cytokine signaling in the mechanism of response and resistance to castration therapy in prostate cancer. The evidence, although solid for some aspects of the work, is incomplete and only partially supports the main claims.

    1. eLife assessment

      This study provides valuable insights into the influence of sex on bile acid metabolism and the risk of hepatocellular carcinoma (HCC). The data to support that there are inter-relationships between sex, bile acids, and HCC in mice are solid, but for the most part, they are descriptive. At this point, there is not enough evidence to determine the clinical significance of the findings, given the differences in bile acid composition between mice and men.

    1. eLife assessment

      The findings are useful for understanding the disease's pathology and immune dysregulation, but the evidence is still incomplete regarding whether these immune changes are directly caused by copper metabolism alterations or are secondary to liver dysfunction.

    1. eLife assessment

      This study investigates BMP signaling mechanisms in the developing chick cerebellum to better understand germinal layer formation, cellular amplification and neuronal differentiation. The data from human tissue is compelling and lends support to the possible links of these processes to medulloblastoma, although this study does raise exciting questions regarding the generalized role of BMP signaling during normal development and malignant growth. Overall, this is an important study with beautifully presented findings.

    1. eLife assessment

      This is an important study on changes in newborns' neural abilities to distinguish auditory signals at 37 weeks of gestation. The evidence of change in neural discrimination as a function of gestational age is convincing, but further analysis of the acoustic signals and control of the infants' language environment is necessary for the results to be used in clinical applications. The work contributes to the field of neurodevelopment.

    1. eLife assessment

      In this important study, the authors explore ER stress signaling mediated by ATF6 using a genome-wide gene depletion screen. They find that the ER chaperone Calreticulin binds and directly represses ATF6, a new and intriguing function for Calreticulin. The evidence presented is convincing, based on CHO genetics and biochemical analysis.

    1. eLife assessment

      This valuable study describes mice with a knock out of the IQ motif-containing H (IQCH) gene, to model a human loss-of-function mutation in IQCH associated with male sterility. While the evidence for interaction between IQCH and potential RNA binding proteins is limited, the human infertility is reproduced in the mouse, making it a compelling model. The paper could be of interest to cell biologists and male reproductive biologists working on the sperm flagellar cytoskeleton and mitochondrial structure.

    1. eLife assessment

      This study builds upon previous work which demonstrated that brain injury results in the entry of a protein called albumin into the brain which then causes diverse effects. The present study shows that prolonged stimulation of a forelimb in a rat leads to albumin entry, and is associated with effects that suggest plasticity is enhanced in the stimulated side of the brain. The strength of evidence was convincing and results are important because they suggest a previously-considered pathological process may be relevant to the normal brain and have benefits.

    1. eLife assessment

      This study provides an important cell type atlas of the gill of the mussel Gigantidas platifrons using a single nucleus RNA-seq dataset, a resource for the community of scientists studying deep sea physiology and metabolism and intracellular host-symbiont relationships. The evidence supporting the conclusions is convincing with high-quality single-nucleus RNA sequencing and transplant experiments. This work will be of broad relevance for scientists interested in host-symbiont relationships across ecosystems.

    1. eLife assessment

      This manuscript provides important information on the calcification process, especially the properties and formation of freshly formed tests (the foraminiferan shells), in the miliolid foraminiferan species Pseudolachlanella eburnea. The evidence from the high-quality SEM images is convincing although the fluorescence images only provide indirect support for the calcification process.

    1. eLife assessment

      This useful modeling study explores how the biophysical properties of interneuron subtypes in the basolateral amygdala enable them to produce nested oscillations whose interactions facilitate functions such as spike-timing-dependent plasticity. The strength of evidence is currently viewed as incomplete because of insufficient grounding in prior experimental results and insufficient consideration of alternative explanations. This work will be of interest to investigators studying circuit mechanisms of fear conditioning as well as rhythms in the basolateral amygdala. (The authors explain why they disagree with this assessment in their author response.)

    1. eLife assessment

      This fundamental study advances our understanding of the role of bacterial-derived extracellular ATP in the pathogenesis of sepsis. The evidence supporting the conclusions is compelling, although not all concerns from a previous round of reviews were adequately addressed. The work will be of broad interest to researchers on microbiology and infectious diseases.

    1. eLife assessment

      This important study advances our understanding of early Cambrian cnidarian paleoecology and suggests that the reconstructed ancestral feeding and respiration mechanisms predate jet-propelled swimming utilized by modern jellyfish. The work combines solid evidence of fluid and structural mechanics modeling, simulating for the first time the feeding and respiratory capacities in a microfossil (Quadrapyrgites), which in turn opens new possibilities using this approach for paleontological research. Assuming that the prior interpretations and assumptions concerning the modeled organism's soft part and skeletal anatomy are correct, the hypotheses that (1) the organism could alternately contract and expand the oral region and (2) such movement increased feeding efficiency seem plausible.

    1. eLife assessment

      This valuable study examines the role of the interaction between cytoplasmic N- and C-terminal domains in voltage-dependent gating of Kv10.1 channels. The authors claim to have identified a hidden open state in Kv10.1 mutant channels, thus providing a window for observing early conformational transitions associated with channel gating. The evidence supporting the major conclusions is incomplete, however, and additional work is required to determine the molecular mechanism underlying the observations in this study. With the experimental conditions clarified and the mechanistic interpretations addressed, this work could be significant in understanding the gating mechanisms of the KCNH family and will appeal to biophysicists interested in ion channels and physiologists interested in cancer biology.