- Jun 2024
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study addresses the question of how certain zooplankton achieve barotaxis, directed locomotion in response to changes in hydraulic pressure. The authors provide compelling evidence that the response involves ciliary photoreceptors interacting with motoneurons. This work should be of broad interest to scientists working on mechanosensation, cilia, locomotion, and photoreceptors.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study elucidates the essential role of the chromatin regulator KDM6B in the establishment and maintenance of neural stem cells (NSCs) in the mouse hippocampus. While the evidence supporting the authors' claims is largely solid, a more comprehensive investigation into the cellular and molecular events underlying the loss of hippocampal NSCs would have further strengthened the study. Nonetheless, the findings will be of interest to biologists studying neural development and NSCs.
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arxiv.org arxiv.org
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eLife assessment
This manuscript makes valuable contributions to our understanding of cell polarisation dynamics and its underlying mechanisms. Through the development of a computational pipeline, the authors provide solid evidence that compensatory actions, whether regulatory or spatial, are essential for the robustness of the polarisation pattern. However, a more comprehensive validation against experimental data and a proper estimation of model parameters are required for further characterization and predictions in natural systems, such as the C. elegans embryo.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work advances our understanding of the foraging behaviour of aerial insectivorous birds. Its major strength is the large volume of tracking data and the accuracy of those data. However, the evidence supporting the main claim of optimal foraging is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Using multiparameter spectral flow cytometry and unbiased clustering analysis, this study provides useful insights into the heterogeneity of antigens-specific circulating T follicular helper cells from children and adults living in malaria-endemic areas of Kenya. Although the study is well-designed, the analysis and interpretation of the potential functional roles for PfSEA-1A- and PfGARP-specific subsets of circulating T follicular helper cells are incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study investigates the role of Caspar (Casp), an orthologue of human Fas-associated factor-1, in regulating the number of primordial germ cells that form during Drosophila embryogenesis. The findings are important in that they reveal an additional pathway involved in germ cell specification and maintenance. The evidence supporting the conclusions is solid, as the authors identify Casp and its binding partner Transitional endoplasmic reticulum 94 (TER94) as factors that influence germ cell numbers. Minor changes to the title, text, and experimental design are recommended.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study investigates the influence of the cingulate cortex on the development of the social vocalizations of marmoset monkeys by making bilateral lesions of this brain area in neonatal animals. The evidence supporting the authors' claims is solid, although including longer-term effects and different social contexts would strengthen the manuscript. The work will be of broad interest to cognitive neuroscientists, speech and language researchers, and primate neuroscientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides an important re-evaluation of modality-specific information processing in the thalamus of trained mice. Using an elegant task design that probes competing tactile and visual stimuli, the authors present convincing evidence that behavioral training reshapes the sensitivity of higher-order thalamic nuclei. Despite the innovative methods and significant findings, the conclusions would be strengthened by deeper analyses of the sensory and non-sensory aspects of the modulation of the higher-order thalamic nuclei.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents convincing evidence of the role of an intestine-released neuropeptide, FLP-2, in the oxidative stress response of C. elegans, as well as for the neural circuit pathway that regulates its release in response to sensing reactive oxygen species (i.e., H2O2). These valuable results advance the understanding of gut-brain signaling and the neural circuit basis of behavioral responses to stress.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study by Franziska Auer and colleagues examines cerebellar Purkinje cells' role in controlling posture in larval zebrafish using the innovative chemogenetic tool TRPV1/capsaicin. This work will interest neuroscientists studying motor control and cerebellar function. Overall, solid evidence is presented showing that disrupting Purkinje cell function impairs balance in the pitch axis and that this cell population encodes tilt direction. At the same time, some conclusions require more data or better statistical analysis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this valuable study, Li et al., set out to understand the mechanisms of audiovisual temporal recalibration - the brain's ability to adjust to the latency differences that emerge due to different (distance-dependent) transduction latencies of auditory and visual signals - through psychophysical measurements and modelling. The analysis supports a role for causal inference in recalibration, though the evidence is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study provides evidence that during learning of a simple detection task, the change in the rate of spike bursts is a signal that is distinct from the change in firing rate, and suggests that the change in bursting is more correlated with learning than other measures of change in activity. However, the evidence for the claim that bursting contributes to learning and attention is currently incomplete, because the authors did not take into account the potentially differential effects of learning-related changes in movement on bursting compared to non-burst spike events, and there is no meaningful way to measure attention in their task. Also, the study used an artificial microstimulation as the stimulus, which limits the generalization of these results to normal sensory-motor learning.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study advances our understanding of how FGF13 variants confer seizure susceptibility. By acting in a set of inhibitory interneurons, FGF13 regulates synaptic transmission and excitability. The data presented here are convincing and combine cell type-specific knockouts and electrophysiology, complemented by histology/RNA studies. Collectively, this research will be of interest to a wide audience, particularly those involved in the study of epilepsy, inhibitory neurons, and ion channels.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presented a valuable inventory in scoring a neuropsychological test, ROCFT. The level of evidence is compelling. The authors constructed large samples from multi-center international researchers and tested the model using internet data with excellent performance. Their deep learning method could potentially apply to neuropsychological tests as well as other related fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing but somewhat incomplete evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is a valuable study on the diffusion rates of drug molecules in human-derived cells, highlighting that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The correlation between pKa and intracellular diffusion is solid and well-supported, but the study would benefit from a more rigorous statistical treatment and a balanced comparison across different types of compounds. Despite these limitations, the findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study draws on published single-cell and spatial transcriptomic data of colon cancer liver metastasis to clarify the pro- and anti-tumorigenic properties of NK cells. The authors discover increased GZMK+ resting NK cells in the tumor tissue and reduced abundance of KIR2DL4+ activated NK cells. However, the evidence is currently incomplete, as the models used to validate the hypothesis and claims are inadequate and lack necessary controls.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study examines the relationship between expiratory airflow and vocal pitch in adult mice during the production of ultrasonic vocalizations and also identifies a molecularly defined population of brainstem neurons that regulates mouse vocal production across development. The evidence supporting the study's conclusions that expiratory airflow shapes vocal pitch and that these brainstem neurons preferentially regulate expiratory airflow is novel and compelling. This work will be of interest to neuroscientists working on mechanisms and brainstem circuits that regulate vocal production and vocal-respiratory coordination.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper reports a valuable new method for creating localized damage to candidate brain regions for functional and behavioral studies. The authors present solid support for their ability to create long-term local lesions with mm spatial resolution. The paper is likely to be of broad interest to brain researchers working to establish causal links between neural circuits and behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work describes a new software platform for machine-learning-based segmentation of and particle-picking in cryo-electron tomograms. The program and its corresponding online database of trained models will allow experimentalists to conveniently test different models and share their results with others. The paper provides solid evidence that the software will be valuable to the community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this study, camera trapping and species distribution models are used to show that human disturbance in mountain forests in the eastern Himalayas pushes medium-sized and large mammal species into narrower habitat space, thus increasing their co-occurrence. While the collected data provide a useful basis for further work, the study presents incomplete evidence to support the claim that increased co-occurrence may indicate positive interactions between species.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides a valuable resource by thoroughly benchmarking multiple sequencing-based tRNA quantification methods. The suggested best practice is supported by solid evidence from in silico experiments in multiple scenarios. The major weakness of the manuscript is the incomplete validation of newly generated experimental datasets.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important study uses a new experimental method to provide compelling evidence on how sense- and anti-sense transcription is differentially regulated. The method described here can generally be used to study the alterations in transcription. This paper will be of interest to scientists working in the gene regulation community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study presents valuable findings on the molecular mechanisms of glucose-stimulated insulin secretion from pancreatic islets, focusing on the main regulatory elements of the signaling pathway in physiological conditions. While the evidence supporting the conclusions is solid, the study can be strengthened by the use of a beta cell line or knockout mice. The work will be of interest to cell biologists and biochemists working on diabetes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work describes a novel affinity interactomics approach that allows investigators to identify networks of protein-protein interactions in cells. The important findings presented here describe the application of this technique to the SH3 domain of the membrane remodeling Bridging Integrator 1 (BIN1), the truncation of which leads to centronuclear myopathy. The authors present solid evidence that BIN1 SH3 engages with an unexpectedly high number of cellular proteins, many of which are linked to skeletal muscle disease, and evidence is presented to suggest that BIN1 may play a role in mitosis creating the potential for new avenues in drug development efforts. Some of the findings, however, remain rather preliminary, lack sufficient replicates and may require additional experiments to definitively support the conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful manuscript extends prior work to identify OVO as a major transcriptional activator of the female germline gene expression program. Using a combination of solid genomic strategies, the authors demonstrate that OVO binds to the promoters of hundreds of genes in the female germline and promotes their expression.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work investigates the role of boundary elements in the formation of 3D genome architecture. The authors established a specific model system that allowed them to manipulate boundary elements and examine the resulting genome topology. The work yielded the first demonstration of the existence of stem and circle loops in a genome and confirms a model which had been posited based on extensive prior genetic work, providing insights into how 3D genome topologies affect enhancer-promoter communication. The evidence is solid, although the degree of generalization remains uncertain.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents important findings on the different polymorphs of alpha-synuclein filaments that form at various pH's during in vitro assembly reactions with purified recombinant protein. Of particular note is the discovery of two new polymorphs (1M and 5A) that form in PBS buffer at pH 7. The strength of the evidence presented is convincing. The work will be of interest to biochemists and biophysicists working on protein aggregation and amyloids.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable strategy to co-deliver peptides and adjuvants to antigen-presenting cells by engineering the Virus-like particle (VLP). The evidence supporting the claims of the authors is convincing, but the antitumour efficacy is unimpressive and would benefit from more antitumor experiments. The work will be of broad interest to bioengineers and medical biologists focusing on cancer vaccines.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents fundamental findings that could redefine the specificity and mechanism of action of the well-studied Ser/Thr kinase IKK2 (a subunit of inhibitor of nuclear factor kappa-B kinase (IkB) that propagates cellular response to inflammation). Solid evidence supports the claim that IKK2 exhibits dual specificity that allows tyrosine autophosphorylation and the authors further show that auto-phosphorylated IKK2 is involved in an unanticipated relay mechanism that transfers phosphate from an IKK2 tyrosine onto the IkBa substrate. These are potentially provocative results but open questions remain due to the nature of the in vitro assays and questions about protein purity and identity. Nevertheless, the findings are a starting point for follow-up studies to confirm the unexpected mechanism and further pursue functional significance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study investigates the sensitivity to endogenous cosolvents of three families of intrinsically disordered proteins involved with desiccation. The findings, drawn from well-designed experiments and calculations, suggest a functional synergy between sensitivity to small molecule solutes and convergent desiccation protection strategy. While the evidence is found to be convincing, the study's conclusions cannot be generalized due to the small number of proteins investigated. This work will be of interest to biochemists and biophysicists interested in the conformation-function relationship of intrinsically disordered proteins.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Based on largely indirect evidence, this study proposes that genomic integration of HIV targets DNA/RNA hybrids called R-loops. The evidence is indirect because the authors do not use relevant models systems to show integration and because they artificially induce R-loops in the critical experiments. There are two interrelated findings: 1) VSVg-pseudotyped HIV-1 induces R-loops in various cell types, and 2) VSVg-pseudotyped HIV-1 targets R-loops for integration in an artificial Hela cell model in which R-loops are exogenously induced. The induction of R-loops by a pseudotyped HIV-1 is a potentially valuable finding. Critically, however, because of the caveats above, the evidence is inadequate to support the primary claims in the title, abstract, and manuscript. Furthermore, if these claims were true, the authors do not provide context for how they could be reconciled with well-established structural data showing that HIV-1 integrase catalyzes the integration of viral DNA into dsDNA as a substrate.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors study how inflammatory priming and exposure to irradiated Mycobacterium tuberculosis or the bacterial endotoxin LPS impact the metabolism of primary human airway macrophages and monocyte-derived macrophages. The work shows that metabolic plasticity is greater in monocyte-derived macrophages than alveolar macrophages. The experimental methods and evidence are solid, and the results and findings are useful for the field of immunometabolism.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study analyzes the roles of post-translational modifications of tubulin by generating a large panel of tubulin mutants and describing their effects on morphogenesis and function of sensory neurons in C. elegans. The work, which is of interest to all cell biologists, in particular researchers with an interest in the microtubule cytoskeleton and neurobiology, presents conclusions that are supported by solid evidence. Demonstrating that all introduced mutations have the intended consequences and exploring their direct effect on microtubules would further increase the impact of the work.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable syngeneic zebrafish model for studying glioblastoma and will be of interest to neuro-oncologists and cancer biologists. Using a feasible in vivo model to study the tumour microenvironment, cell/cell interaction, and immunity, the data are compelling, and opens up new lines of inquiries for future investigation on the impact of efferocytosis on tumor progression and cell of origin in this model as well as assessments of drug resistance mechanisms, using inhibitors to MAPK , Akt and/or mTOR pathway.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Building on on the observation of an increase in miR-182-5p in diabetic patients, the authors investigated the role of miR-182-5p and its target gene LRP6 in dysregulated glucose tolerance and fatty acid metabolism in obese type 2 diabetics. The use of human livers complemented by supporting data in mice and cells are strengths, but the evidence presented remains incomplete. The findings provide valuable insights into the role of miRNAs in the regulation of liver metabolism and insulin sensitivity in individuals with diabetes and fatty liver disease.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides a fundamental advance in palaeontology by reporting the fossils of a new invertebrate, Beretella spinosa, and inferring its relationship with already described species. The analysis placed the newly described species in the earliest branch of moulting invertebrates. The study, supported by convincing fossil observation, hypothesizes that early moulting invertebrate animals were not vermiform.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors report that the neurohormone, bursicon, and its receptor, play a role in regulating aspects of the seasonal polyphenism of the bug, Cacopsylla chinensis. This important study shows that low temperature activates the bursicon signaling pathway during the transition from the summer to the winter form and that it affects cuticle pigment and chitin content, and cuticle thickness. In addition, the authors show that the microRNA miR-6012 targets the bursicon receptor, thereby modulating the function of the bursicon signaling pathway. The study's solid set of experiments and results reveal a role of bursicon signaling in regulating features of polyphenism related to the exoskeleton. Nevertheless, they only incompletely substantiate the authors' claims about the regulation of polyphenism itself.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper addresses a question regarding the low overlap between genetic variants linked to human complex diseases and variants linked to differences in gene expression. Some of the analyses supporting the main claims are convincing, and the key conclusions are valuable and of interest to readers in the fields of human genetics and functional genomics. However, chromatin accessibility QTL (caQTL) also carry the limitation of not identifying the genes that directly mediate the influence on disease phenotypes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work presents elegant experimental data from the Drosophila embryo supporting the notion that interactions among specific loci, called boundary elements, contribute to topologically associated domain (TAD) formation and gene regulation. The evidence supporting boundary:boundary pairing as a determinant of 3D structures is compelling; however, an inability to deplete loop extruders formally leaves open a possible contribution of loop extrusion. This study will be of interest to the nuclear structure community, particularly those using Drosophila as a model.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful work investigates the social interactions of mice living together in a system of multiple connected cages. The approach is interesting as it uses some of the tools developed in physics to investigate animal behaviour. However, , some of the analyses require further scrutiny, leaving the evidence supporting the main claim currently incomplete.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This paper provides a useful analysis of the variation of the burden of strokes across geographic regions, finding differences in the relationship between strokes and their comorbidities. This dataset and the correlations found within will be a resource for directing the focus of future investigations. The statistical analyses are incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important and novel study addresses the challenge of antimicrobial resistance by targeting plasmid proteins that interfere with plasmid transfer as a strategy to limit the spread of antibiotic-resistance genes. The evidence presented and the integration of two approaches to tackle antimicrobial resistance is convincing. This work will interest those working on plasmid transfer and antimicrobial resistance.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
How the triplicate interaction between chemokines with both GAGs and G protein-coupled receptors (GPCR) works and how gradients are created and potentially maintained in vivo are poorly understood. The authors provide solid evidence to show phase separation can drive chemotactic gradient formation. The paper is a useful advance in the field of chemokine biology.
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eLife assessment
This valuable study uses a novel experimental design to elegantly demonstrate how we exploit stimulus structure to overcome working memory capacity limits. The presented behavioural and neural evidence are solid and in line with the proposed information compression mechanism. This study will be of interest to cognitive neuroscientists studying structure learning and memory.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study focuses on the regulation of GLP-1 in enteroendocrine L cells and how this may be stimulated by the mechanogated ion channel Piezo1. The work is innovative and the hypothesis that is being tested may have important mechanistic and translational implications. The data remains incomplete at present and needs a substantial amount of supporting evidence and corrections to be a stronger manuscript and publication.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Efforts to increase the representation of women in academia have focussed on efforts to recruit more women and to reduce the attrition of women. This study - which is based on analyses of data on more than 250,000 tenured and tenure-track faculty from the period 2011-2020, and the predictions of counterfactual models - shows that hiring more women has a bigger impact than reducing attrition. The study is an important contribution to work on gender representation in academia, and the evidence in support of the findings is convincing.
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www.biorxiv.org www.biorxiv.org
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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. The infertility is reproduced in the mouse, making it a compelling model, but the mechanistic experiments provide only incomplete evidence for interaction between IQCH and potential RNA binding proteins, which are prominently mentioned in the title. The paper, which has undergone multiple rounds of review, could be of interest to cell biologists and male reproductive biologists working on the sperm flagellar cytoskeleton and mitochondrial structure.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents an important finding on the function of PLP1+ enteric glia. The evidence supporting the claims of the authors is solid, although the inclusion of additional data showing the mechanisms by which PLP1+ enteric glia acts on Paneth cells would have strengthened the study. The work will be of interest to researchers working on intestinal biology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study provides solid in vivo data that transfer of IL-15/IL-12-conditioned syngeneic NK cells after primary tumor resection promotes long-term survival of mice with low metastatic burden from breast cancer. Also, the authors conducted an investigator-initiated clinical trial that demonstrated that similar NK cell infusions in cancer patients after resections were safe and showed signs of efficacy. Therefore, this study is of interest and value to oncologists in the field of breast cancer research.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study adopted a multi-omics approach to elucidate the regulatory mechanism underlying parturition and myometrial quiescence. The data presented to support the main conclusion remains incomplete. This work will be of interest to both basic researchers who work on reproductive biology and clinicians who practice reproductive medicine.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
In this valuable study, the authors sought to investigate the associations of age at breast cancer onset with the incidence of myocardial infarction and heart failure. Based on results from a series of solid statistical analyses, the authors conclude that a younger onset age of breast cancer is associated with myocardial infarction and heart failure, highlighting the need to carefully monitor the cardiovascular status of women who have been diagnosed with breast cancer.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study combines genetic, cell biological, and interaction data to propose a model of meiotic double-strand break regulation in C. elegans. Comprehensive cataloging of their interactions (physical and genetic) would be valuable information for the field. However, the analyses used in the manuscript are not consistent or comprehensive, and therefore the evidence to support their model is currently incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Using experiments in the white fly, this manuscript provides evidence that the bacterial symbiont Wolbachia can be transmitted from parasitoid wasps to their insect hosts. Characterizing the transfer of Wolbachia between insect species is a valuable attempt to explain the widespread of this intracellular bacterium. This paper is incomplete as it does not furnish sufficient data to support several of its claims for which additional methods and data are necessary.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript presents experiments that address the question of whether the lateral parafacial area (pFL) is active in controlling active expiration, which is particularly significant in patient populations that rely on active exhalation to maintain breathing (eg, COPD, ALS, muscular dystrophy). This study presents solid evidence for a valuable finding of pharmacological mapping of the core medullary region that contributes to active expiration and addresses the question of where these regions lie anatomically. Results from these experiments will be of value to those interested in the neural control of breathing and other neuroscientists as a framework for how to perform pharmacological mapping experiments in the future.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study addresses a fundamental question about how wing morphology and kinematics changed as insect species miniaturized. The authors found no significant correlation between body size and wing kinematics across eight hoverfly species, and instead argue that evolutionary changes in wing size and shape enabled flight in smaller species. However, if the integrative approach to animal biomechanics is strong, the evidence supporting the general conclusion that changes in wing morphology, rather than kinematics, correlate with miniaturization is incomplete and would benefit from more detailed biomechanical analysis and improved methods for phylogenetic comparison.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This article reports an important bioluminescence-based reporter system to evaluate kinase conformations. This assay is applied to four different kinases that have unique, very special regulatory features, thereby indicating that the assay can be used to provide convincing evidence on the conformational state of a large number of kinases. This paper will be of interest to researchers working on kinases and their conformational states.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This study presents a predictive scoring system in DLBCL based on the expression of three tumour microenvironment-related genes. Such a scoring system seems useful for predicting tumour purity levels in DLBCL. The provided evidence showing an association between worse DLBLC prognosis and high-risk score is solid, but it is incomplete to draw a clear conclusion about the links between risk score and drug sensitivity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper describes an important software framework for the curation, retrieval, and analysis of ancient human genomic data and their associated metadata, overcoming long-standing coordination and harmonization issues in ancient human genomics. The resource is built on compelling and sometimes exceptional principles of software engineering and reproducibility, and the authors make an excellent case that their resource will be of practical use to many researchers studying human history using DNA. The main issues include natural uncertainties regarding future funding and maintenance of this resource, as well as deviation from established standards in other areas of genomics.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study presents valuable findings on the role of RIPK1 in maintaining liver homeostasis under metabolic stress. Strengths include the intriguing findings that RIPK1 deficiency sensitizes the liver to acute liver injury and apoptosis, but because the conclusions require additional experimental support, the evidence is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Brain inflammation is a hallmark of multiple sclerosis. Using novel spatial transcriptomics methods, the authors provide solid evidence for a gradient of immune genes and inflammatory markers from the meninges toward the adjacent brain parenchyma in a mouse model. This important study advances our understanding of the mechanisms of brain damage in this autoimmune disease. However, the control mouse groups are not well designed to rule out confounding effects, a limitation that needs to be acknowledged and addressed.
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eLife assessment
This study provides important insight into the mechanisms of proton-coupled oligopeptide transporters. It uses enhanced-sampling molecular dynamics (MD), backed by cell-based assays, revealing the importance of protonation of selected residues for PepT2 function. The simulation approaches are convincing, using long MD simulations, constant-pH MD and free energy calculations. Overall, the work has led to findings that will appeal to structural biologists, biochemists, and biophysicists studying membrane transporters.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study investigates the transcriptional changes in neurons that underlie loss of learning and memory with age in C. elegans, and how cognition is maintained in insulin/IGF-1-like signaling mutants. The presented evidence is compelling, utilizing a cutting-edge method to isolate neurons from worms for genomics that is clearly conveyed with a rigorous experimental approach. Overall, this study supports that older daf-2 worms maintain cognitive function via mechanisms that are unique from younger wild type worms, which will be of great interest to neuroscientists and researchers studying ageing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study combines massively parallel reporter assays and regression analysis to identify sequence features in untranslated regions that contribute to mRNA stability. The strength of evidence presented is generally solid, but providing more details about how half lives are calculated and explaining some aspects of the subsequent choices made for analysis would clarify and strengthen the overall approach. Taken together, this study will be of interest to researchers broadly studying post-transcriptional gene regulation and also to scientists using massively parallel reporter assays.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports a novel mechanism linking DHODH inhibition and subsequent pyrimidine nucleotide depletion with upregulation of cell surface MHC I in cancer cells. The in vitro mechanistic data are compelling, with rigorous methodology and validation across multiple cell lines. The authors also provide in vivo evidence for additive effects of DHODH inhibitors and immune checkpoint blockade. However, the in vivo assessments of the functional relevance of this mechanism remain incomplete, requiring additional analyses to fully substantiate the conclusions made.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study presents the design of a new device to use high-density electrophysiological probes ("Neuropixels") in freely moving rodents. The evidence showing that the system is versatile and capable of recording high-quality extracellular data in both mice and rats is compelling. This study will be of interest to neuroscientists performing chronic electrophysiological recordings.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study is a detailed investigation of how chromatin structure influences replication origin function in yeast ribosomal DNA, with focus on the role of the histone deacetylase Sir2 and the chromatin remodeler Fun30. Convincing evidence shows that Sir2 does not affect origin licensing but rather affects local transcription and nucleosome positioning which correlates with increased origin firing. However, the evidence remains incomplete as the methods employed do not rigorously establish a key aspect of the mechanism, fully address some alternative models, or sufficiently relate to prior results. Overall, this is a valuable advance for the field that could be improved to establish a more robust paradigm.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors report that optogenetic inhibition of hippocampal axon terminals in retrosplenial cortex impairs the performance of a delayed non-match to place task. Elucidating the role of hippocampal projections to the retrosplenial cortex in memory and decision-making behaviors is important. However, the strength of evidence for the paper's claims is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The paper reports the important discovery that the mouse dorsal inferior colliculus, an auditory midbrain area, encodes sound location. The evidence supporting the claims is solid, although how the encoding of sound source position in this area relates to localization behaviors in engaged mice remains unclear. The observations described should be of interest to auditory researchers studying the neural mechanisms of sound localization.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study provides convincing evidence that mutant hair cells with abnormal, reversed polarity of their hair bundles in mouse otolith organs retain wild-type localization, mechanoelectrical transduction and receptor field of their afferent innervation, leading to mild behavioral dysfunction. It thus demonstrates that the bimodal pattern of afferent nerve projections in this organ is not causally related to the bimodal distribution of hair-bundle orientations, as also confirmed in the zebrafish lateral line. The work will be of interest to scientists interested in the development and function of the vestibular system as well as in planar-cell polarity.
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www.biorxiv.org www.biorxiv.org
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eLife assessment:
This important study investigates the contribution of cytosolic S100A/8 to neutrophil migration to inflamed tissues. The authors provide convincing evidence for how the loss of cytosolic S100A/8 specifically affects the ability of neutrophils to crawl and subsequently adhere under shear stress. This study will be of interest in fields where inflammation is implicated, such as autoimmunity or sepsis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study reports that actin-related proteins may be involved in transcriptional regulation during spermatogenesis. The supporting data remain incomplete, and more extensive disentanglement from the canonical role of these actin-related proteins and the experimental validation of in silico predictions are required. This work will be of interest to reproductive biologists and other researchers working on non-canonical roles of actin and actin-related proteins.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents an important finding on the influence of visual uncertainty and Bayesian cue combination on implicit motor adaptation in young healthy participants, hereby linking perception and action during implicit adaptation. The evidence supporting the claims of the authors is convincing. The normative approach of the proposed PEA model, which combines ideas from separate lines of research, including vision research and motor learning, opens avenues for future developments. This work will be of interest to researchers in sensory cue integration and motor learning.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study provides insights into how the brain constructs categorical neural representations during a difficult auditory target detection task. Through recordings of simultaneous single-unit activity in primary and secondary auditory areas, compelling evidence is provided that categorical neural representations emerge in a secondary auditory area, i.e., PEG. The study is of interest to neuroscientists and can also potentially shed light on human psychological studies.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this study, the authors found that a species of aphid that is a known agricultural pest salivated longer and produced more honeydew when feeding at night. The authors identified aphid genes with diurnal expression patterns, including potential saliva-related genes. Silencing these genes reduced aphid performance only on real plants, suggesting a specific role in plant feeding. While this study is valuable for understanding plant-insect interactions in agriculture, it is currently incomplete, as further research is needed to elucidate the function of the identified genes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This fundamental study investigates the transcriptional changes in neurons that underlie loss of learning and memory with age in C. elegans, and how cognition is maintained in insulin/IGF-1-like signaling mutants. The presented evidence is compelling, utilizing a cutting-edge method to isolate neurons from worms for genomics that is clearly conveyed with a rigorous experimental approach. Overall, this study supports that older daf-2 worms maintain cognitive function via mechanisms that are unique from younger wild type worms, which will be of great interest to neuroscientists and researchers studying ageing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This computational modeling study builds on multiple previous lines of experimental and theoretical research to investigate how a single neuron can solve a nonlinear pattern classification task. The study presents valuable insights that the location of synapses on dendritic branches, as well as synaptic plasticity of excitatory and inhibitory synapses, influences the ability of a neuron to discriminate combinations of sensory stimuli. However, the evidence presented is incomplete - the major conclusions are only partially supported by the data presented, and there are identified gaps between the supporting evidence and the major conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors study how cells with lower levels of the conserved steroid hormone signaling component Taiman (tai) are out-competed by neighboring wild-type cells with higher fitness in Drosophila imaginal discs. The findings are useful since they uncover an unexpected link between tai and Wingless signaling in cell competition. The evidence however is incomplete, since the tai loss-of-clone phenotype is based on one allele and the mechanism involved in cell competition through Dlp and Wg lacks adequate supporting data.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The findings are valuable and supported by compelling evidence from deep sequencing and bioinformatics analyses. The strength of this work lies in the comprehensive analysis of different cells representing various life stages, exposing vulnerabilities to EDCs and relating epimutations to specific genomic regulatory regions. Despite the small sample size, the results make a major contribution to the field and provide novel insight into the emergence and correction of epimutations during epigenetic programming and into the processes underlying multigenerational effects of EDCs.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript reports an important finding that the transcription factor Scleraxis regulates regenerative myogenesis by controlling the proliferation and differentiation of muscle stem cells. The evidence presented is compelling and supports the conclusions and the mechanisms by which this gene regulates satellite cell function. These data will be of interest to developmental, transcriptional, and stem cell biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This article describes a novel mechanism allowing the insect Drosophila to combat pathogenic enteric pathogens while preserving the beneficial indigenous microbiota. The authors provide compelling evidence that oral infection of Drosophila larvae by pathogenic bacteria activate a valve that traps the intruders in the anterior midgut, allowing them to be killed by antimicrobial peptides. This important work substantially advances our understanding of pathogen clearance in the insect gut.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study represents valuable findings on the asymmetric connectivity pattern of two different types of CA3 pyramidal cell types showing that while athorny cells receive strong inputs from all other cell types, thorny cells receive weaker inputs from athorny neurons. Computational modeling is used to evaluate the impact of this connectivity scheme on the sequential activation of different cell types during sharp wave ripples. The experimental evidence supporting the authors' claims is solid, although improvements to the modelling aspect of the study would strengthen the study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work describes the activation of astrocytes via the nuclear translocation of PKM2 in an animal model of multiple sclerosis. This study provides solid evidence of the interaction between TRIM21 and PKM2 as the crucial molecular event leading to the translocation of PKM2 and a metabolic shift towards glycolysis dominance, fostering proliferation in stimulated astrocytes. This finding is significant as it underscores the potential of targeting glycolytic metabolism to mitigate neurological diseases mediated by astrocytes, offering a strong rationale for potential therapeutic interventions. However, control experiments and imaging analyses with higher magnification images should be performed to better support the main claims of the study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study reports an important discovery highlighting the essential role of the putative ion channel, TMC7, in acrosome formation during sperm development and thus male fertility. The evidence for the requirement of TMC7 in acrosome biogenesis and sperm function is convincing, although its function as an ion channel remains to be further determined. Overall, this work will be of great interest to developmental biologists and ion channel physiologist alike.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript reports valuable findings on the role of the Srs2 protein in turning off the DNA damage signaling response initiated by Mec1 (human ATR) kinase. The data provide solid evidence that Srs2 interaction with PCNA and ensuing SUMO modification is required for checkpoint downregulation. However, experimental evidence with regard to the model that Srs2 acts at gaps after camptothecin-induced DNA damage is currently lacking. The work will be of interest to cell biologists studying genome integrity but would be strengthened by considering the possible role of Rad51 and its removal.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors use point light displays to measure biological motion (BM) perception in children (mean = 9 years) with and without ADHD, and relate it to IQ, social responsiveness scale (SRS) scores and age. They report that children with ADHD were worse at all three BM tasks, but that those tasks loading more heavily on local processing relate to social interaction skills and those loading on global processing relate to age. There are still some elements of the results that need clarification with future work, but nevertheless, the important and solid findings extend our limited knowledge of BM perception in ADHD, as well as biological motion processing mechanisms in general.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable paper explores the role of translational regulation in the establishment of differential gene expression between neurons and glia in Drosophila. The paper uses Ribo-seq to show extensive variation in the translation efficiency of specific transcripts between neurons and glia. The evidence supporting the model is solid, although only one example (that exhibits very strong differential transcriptional expression between one class of neurons and glia) is studied in detail for translation efficiency.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript presents a valuable model for the field of endosome maturation, providing perspective on the role of the deubiquitinating enzyme UPS-50/USP8 in the process. The evidence presented in the paper is clear, incorporating well-designed experiments that suggest the dual actions of UPS-50 and USP8 in the conversion of early endosomes into late endosomes. Overall, the work is convincing and centers on an intriguing subject.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study reveals an important mechanism, a polyunsaturated fatty acid increases a K+ channel conductance by helping its K+ selectivity filter form a conductive state. Overall, this mechanism is supported by convincing single channel recordings, macroscopic current recordings and mutational analyses, though further clarification of some results seems warranted. These findings are expected to be of interest to researchers studying ion channel gating.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this useful study, the authors investigate the regulatory mechanisms related to toxin production and pathogenicity in Aspergillus flavus. Their observations indicate that the SntB protein regulates morphogenesis, aflatoxin biosynthesis, and the oxidative stress response. In general, the data supporting the conclusions are solid but could be strengthened further through additional analyses of CHIP-seq data.
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www.researchsquare.com www.researchsquare.com
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eLife assessment
The manuscript makes an important contribution to antimalarial drug discovery, utilizing diverse systems biology methodologies. It focuses on an improved M1 metalloprotease inhibitor and provides compelling evidence for the utility of chemoproteomics in pinpointing PfA-M1 targeting. Additionally, metabolomic analysis reveals specific alterations in the final steps of hemoglobin breakdown. These findings highlight the potential of the developed methodology not only for PfA-M1 targeting but also for other inhibitors targeting various malarial proteins or pathways.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Sulphur atoms derived from cysteine are thought to play significant roles in maintaining redox homeostasis in Mycobacterium tuberculosis, which encounters stresses associated with immune cell interactions. In this valuable manuscript, the authors provide solid evidence that the genes encoding cysteine biosynthetic enzymes (cysM and cysK2) are required to maintain full viability of M. tuberculosis under in vitro stress conditions, macrophage infections, and within the lung tissues of mice. The manuscript presents transcriptomic and metabolomic evidence to support the hypothesis that CysM and CysK2 play distinct roles in maintaining cysteine-derived metabolite pools under stress conditions. The work will be of interest to microbiologists in general.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study advances our understanding of the allosteric regulation of anaerobic ribonucleotide reductases (RNRs) by nucleotides, providing valuable new structural insight into class III RNRs containing ATP cones. The cryo-EM structural characterization of the system is solid, but some open questions remain about the interpretation of activity/binding assays and the HDX-MS results that have been newly incorporated compared to a previous version. The work will be of interest to biochemists and structural biologists working on ribonucleotide reductases and other allosterically regulated enzymes.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work examines the potential utility of socio-emotional and socio-cognitive mental training on hippocampal subfield structure and function, and cortisol levels. The authors provide convincing evidence that CA1-3 volume is sensitive to socio-emotional training, with changes related to function plasticity and cortisol levels. Further, the authors provide evidence of change across all subfields and training modules related to stress.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript provides an important advance in our understanding of the molecular events that promote osteoclast fusion. Compelling data support the conclusion that an oxidized form of the ubiquitous protein La promotes osteoclast fusion following enrichment at the cell surface of osteoclast progenitors. These data improve our understanding of the processes that regulate bone resorption and will be of broad interest to researchers in the fields of cell biology and musculoskeletal physiology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study employs an innovative genetic selection-based approach to identify short peptide sequences that target bacterial proteins for degradation. Using random mutagenesis they identified 5 amino acid long "degrons" that target the toxin VapC for degradation permitting survival. They provide compelling data that degrons ending in Ala-Ala are selectively recognized by the ClpXP protease and identify the sequence FKLVA as a particularly significant target. As a whole, there is enthusiasm about the author's findings, although there are also some improvements that could be made to increase the clarity and impact, mostly in the form of revisions to the text.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides valuable scRNA-seq and scATAC-seq data for testicular tissues from patients with spermatogenesis disorders. By examining the transcriptomic and epigenetic changes in Sertoli cells, the authors uncovered key regulatory mechanisms underlying male infertility and identified potential therapeutic targets. While some of the cellular profiling results are convincing, the analyses for differential profiling of NOA cases and epigenomics data remain incomplete in their current form.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study reports that the timing of 'brain-to-gut' signaling influences the lifespan of the C. elegans model. The main finding, that modulating the same neurotransmitter, Acetylcholine, at different ages elicits lifespan shortening - or extending - effects utilizing different receptors, is important and of broad interest to the longevity field as recognized by all the reviewers. The data is largely consistent with the authors' model, but the strength of the evidence is incomplete. The study requires several rigorous experiments detailed by the reviewers to substantiate the main conclusions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on how data quality and data representation are key to obtain predictive machine learning models, even without resorting to complex machine learning approaches. The evidence supporting the claims of the authors is, however, incomplete, as their conclusions are drawn from a single dataset of big size, similarity analysis within and between subsets is lacking, and there are concerns regarding the composition of the training and holdout sets (active:inactive ratio, possible triviality of decoys). If the results were expanded to other quality datasets of different compositions to demonstrate robustness, the manuscript would be of wide interest in the machine learning and drug discovery fields
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work examines the role of the oxidoreductase MftG in Mycolicibacerium smegmatis alcohol metabolism. A solid set of data is presented to show that, in the context of ethanol metabolism, MftG couples electrons derived from the oxidation of redox cofactor mycofactocin to mycobacterial respiratory chain. The theoretical and functional analyses could benefit from more rigour to expand on hypotheses that already exist in the field. This work highlights the metabolic flexibility of mycobacteria, but it will also be of interest to the broader field of bacterial metabolism.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study tests the hypothesis that monocytes purified from tuberculosis patients differentiate into dendritic cells with different migratory capacities. The authors conclude that these monocytes are metabolically pre-conditioned to differentiate, with reduced expression of Hif1a and a glycolytically exhaustive phenotype, resulting in low migratory and immunologic potential. Overall, the evidence provided is convincing, advancing the field substantively and providing novel insights.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript reports important in vitro biochemical and in planta experiments to study the receptor activation mechanism of plant membrane receptor kinase complexes with non-catalytic intracellular kinase domains. Several lines of evidence convincingly show that one such putative pseudokinase, the immune receptor EFR achieves an active conformation following phosphorylation by a co-receptor kinase, and then in turn activates the co-receptor kinase allosterically to enable it to phosphorylate down-stream signaling components. This manuscript will be of interest to scientists focusing on cell signalling and allosteric regulation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reveals the molecular basis of mutualism between a vector insect and a bacterium responsible for the most devastating disease in citrus agriculture worldwide. The evidence supporting the conclusions is compelling, with solid biochemical and gene expression analyses demonstrating the phenomenon. We believe this work will be of great interest to the fields of vector-borne disease control and host-pathogen interaction.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings on the mechanisms underlying a rare brain disease using an organoid system. In this revised version, there are remaining reviewers' comments that are not yet addressed and as such, while the data presented are solid, the evidence supporting some of the claims is deemed incomplete. The work will be of interest to neuroscientists and clinicians aiming to understand and combat similar neurodegenerative disorders.
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www.biorxiv.org www.biorxiv.org
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eLife assessment:
This study describes a new set of genetic tools for optimized Cre-mediated gene deletion in mice. The advances are substantial and will facilitate biomedical research. Although the tools have been validated using solid methodologies, the quantitative assessment of their recombination efficiency is not yet sufficiently described. Evaluating their ability to mediate the deletion of multiple alleles in a mosaic setting would also be a highly valuable addition.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Using a C. elegans/virus system, this important work demonstrates that viral susceptibility can be greatly altered by the bacterial food that C. elegans consumes. The work is rigorous with solid support for the conclusions: the authors show that quorum-sensing compounds play a role in reducing host susceptibility, and they perform control experiments to rule out nutrition and pathogenicity of the bacteria as the cause of impacts on viral susceptibility.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study advances our understanding of how distinct types of communication signals differentially affect mouse behaviors and amygdala cholinergic/dopaminergic neuromodulation. The evidence supporting the authors' claims is solid. Researchers interested in the complex interaction between prior experience, sex, behavior, hormonal status, and neuromodulation should benefit from this study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors' dataset and analysis provide a fundamental new understanding of how cerebellar output contributes to various cerebellar-dependent diseases. The observation that different firing statistics at the level of the cerebellar nuclei directly impart disease-specific phenotypes is quite convincing. The classifier used in the manuscript remains a potential weak-point, showing limited efficacy, particularly for identifying mice with tremor. The concern about classifier accuracy is ameliorated by the fact that the classifier parameters are easily interpretable, and allowed the authors to use these parameters to design stimulation experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important information-theoretic re-analysis of human intracranial recordings during reward and punishment learning. It provides convincing evidence that reward and punishment learning is represented in overlapping regions of the brain while relying on specific inter-regional interactions. This preprint will be interesting to researchers in systems and cognitive neuroscience.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript used the sci-Plex system for screening compounds to improve the Ascl1-induced reprogramming from Müller glia to bipolar neurons in vitro, followed by in vivo characterization of two promising compounds in mice. The findings are valuable for future studies to develop cell replacement strategies for treatment of retinal degeneration. The strength of evidence is solid, featuring a scalable drug screening design, albeit with limited mechanistic insights.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work provides insight into the activity and spatial organization of synapses during early postnatal development in the mouse visual cortex, using state-of-the-art tools to show that synapses are distributed in co-active clusters well before eye opening. The evidence supporting the claims is convincing, and this revised version provides additional methodological details about the experimental paradigm and image analysis.. This work is of particular interest to the field of developmental neuroscience and can also be used by computational neuroscientists studying dendritic integration.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports a novel approach to studying cerebellar function based on the idea of selective recruitment using fMRI. It provides convincing evidence for task-dependent gating of neocortical input to the cerebellum during a motor task and a working memory task. The study will be of interest to a broad cognitive neuroscience audience.
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eLife assessment
This important study presents an original and promising approach to combine convolutional neural networks of visual processing with evidence accumulation models of decision-making. While the methodological approach itself is strong and technically sophisticated, the evidence supporting the conclusions is currently incomplete. The study will be of interest to researchers working in the fields of machine learning and cognitive modeling.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript establishes a sophisticated mouse model for acute retinal artery occlusion (RAO) by combining unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) with a silicone wire embolus and carotid artery ligation, generating ischemia-reperfusion injury upon removal of the embolus. This clinically relevant model is useful for studying the cellular and molecular mechanisms of RAO. The data overall are solid, presenting a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study describes useful mouse models of knock-ins of human STING1 variants and an assessment of these variants' action in mouse immune cells. While the data included in the manuscript are solid, because of the authors' interpretation and conclusions made, the work is currently considered incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study reveals how a rhizobial effector protein cleaves and inhibits a key plant receptor for symbiosis signaling, while the host plant counters by phosphorylating the effector. The molecular evidence for the protein-protein interaction and modification is solid, though biological evidence directly linking effector cleavage to rhizobial infection is incomplete. With additional functional data, this work could have implications for understanding intricate plant-microbe dynamics during mutualistic interactions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript reports a valuable computational study of the effects of axon de-myelination and re-myelination on action potential speed and propagation failure. The manuscript presents solid evidence for the effects of de- and re-myelination in different models of working memory, with potential implications in disorders such as multiple sclerosis. The exposition of the manuscript is targeted for researchers interested in biophysical models of cognitive deficits.
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arxiv.org arxiv.org
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eLife assessment
The authors develop a self-returning self-avoiding polymer model of chromosome organization and show that their framework can recapitulate at the same time local density and large-scale contact structural properties observed experimentally by various technologies. The presented theoretical framework and the results are valuable for the community of modelers working on 3D genomics. The work provides solid evidence that such a framework can be used, is reliable in describing chromatin organization at multiple scales, and could represent an interesting alternative to standard molecular dynamics simulations of chromatin polymer models.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study by Kim et al. is a valuable contribution to the topic of obtaining good channel conductance parameters from electrophysiological recordings. While promising in its ability to rapidly construct newly fitted models using generative adversarial networks, the approach is incompletely described and the generated models often substantially deviate from the dynamics observed empirically. The comparison with existing multi-objective optimization methods is also incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study by Wu and Zhou combines neurophysiological recordings and computational modelling to address an interesting question regarding the sequence of events from sensing to action. Neurophysiological evidence remains incomplete: explicit mapping of saccade-related activity in the same neurons and a better understanding of the influence of the spatial configuration of stimulus and targets would be required to pinpoint whether such activity might contribute, even partially, to the observed results and interpretations. These results are of interest for neuroscientists investigating decision-making.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This paper makes a valuable contribution to our understanding of the tradeoffs in eye design - specifically between improvements in optics and in photoreceptor performance. The authors successfully build a formal theory that enables comparisons across a wide range of species and eye types. The conclusion from the modeling is that resources are split relatively evenly between optics and photoreceptors, and hence that both must be considered in eye design. Evidence for this conclusion is solid, and could be strengthened with a more complete comparison with the experiment.
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osf.io osf.io
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eLife assessment
This important study provides solid evidence that both psychiatric dimensions (e.g. anhedonia, apathy, or depression) and chronotype (i.e., being a morning or evening person) influence effort-based decision-making. Notably, the current study does not elucidate whether there may be interactive effects of chronotype and psychiatric dimensions on decision-making. This work is of importance to researchers and clinicians alike, who may make inferences about behaviour and cognition without taking into account whether the individual may be tested or observed out-of-sync with their phenotype.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work advances our understanding of microglial aging trajectory and heterogeneity. The authors provide an in-depth characterization of microglia in aging and aim to identify molecular checkpoints, that while solid are also deemed incomplete to support all the authors' claims. The study should be of interest to neuroimmunologists and biologists interested in aging.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study showing that sleep deprivation increases functional synapses while depleting silent synapses supports previous findings that excitatory signaling, in particular via AMPA receptors, increases during wakefulness. The consistency with the literature increases confidence in the conclusions, which otherwise are supported by incomplete evidence. An interesting aspect of this manuscript is the inclusion of a model for the accumulation of sleep need that is based upon the MEF2C transcription factor but also links to the sleep-regulating SIK3-HDAC4/5 pathway. As such, the manuscript is as much of a perspective as a primary research paper.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The important study by Ding and colleagues identifies subpopulations of neurons recorded in the monkey subthalamic nucleus (STN) with distinct activity profiles and causal contributions during perceptual decision-making. The combination of neuronal recording, microstimulation, and computational methods provides convincing evidence for a heterogenous neural population that could support multifaceted roles in decision formation. This study should be of wide interest to computational and experimental neuroscientists interested in cognitive function.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study uses calcium imaging to show an increase in the selectivity of the sensory-evoked response in the apical dendritic tuft of layer 5 barrel cortex neurons as mice learn a whisker-dependent discrimination task. The evidence supporting the conclusions is compelling, and this work will be of great interest to neuroscientists working on reward-based learning and sensory processing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment:
This study reported that cold exposure induced mRNA expression of genes related to lipid metabolism in the paraventricular nucleus of the hypothalamus (PVH). The authors provide useful data highlighting the potential role of lipid metabolism in the brain during cold exposure. However, the study is incomplete and would require specific experiments to solidify the claims being made.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study to reveal local circuit mechanisms in the POA that control body temperature and also highlight how neurotransmitter GABA and neuropeptide NTS from the same neurons differentially modulate temperature. This study was carefully executed, providing convincing evidence for the conclusions in this paper. The findings have emphasized the importance of considering multiple diverse functions of the same neuron populations and will be of interest to neuroscientists working on central regulations of energy metabolism and temperature homeostasis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This technical study presents a novel sampling strategy for detecting synaptic coupling between neurons from dual pipette patch-clamp recordings in acute slices of mammalian brain tissue in vitro. The authors present solid evidence that this strategy, which incorporates automated patch clamp electrode positioning and cleaning for reuse with strategic neuron targeting, has the potential to substantially improve the efficiency of neuronal sampling with paired recordings. This technique and the extensions discussed will be useful for neuroscientists wanting to apply or already conducting automated multi-pipette patch clamp recording electrophysiology experiments in vitro for neuron connectivity analyses.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this work, the authors put forward a valuable methodological advancement for imaging deeper in the intact spinal cord of anaesthetized mice. The authors measured blood flow across different vessel types within the spinal cord and observed the cellular responses following venule occlusion. The demonstration is solid, although, a more quantitative comparison with state-of-the-art two-photon excited fluorescence microscopy and a discussion about applicability to functional imaging (e.g., calcium imaging) would have strengthened the study.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study describes an apparatus, workflow, and proof-of-concept data for a system to study social cooperation in marmosets, an increasingly popular primate model for neuroscience. The apparatus and methodology have clear and convincing advantages over conventional methods based on manual approaches. However, the claims of faster social learning or of finer-grained behavioural analysis in their setup require further corroboration.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The neurotrophic factor Neuritin can moderate T-cell tolerance and immunity through both regulatory T (Treg) and effector T cells, promoting Treg cell expansion and suppression while dampening effector T cells to mediate the inflammatory response. Neuritin expression influences the membrane potential, ion channels, and nutrient transporter expression patterns of CD4+ T cells, contributing to differential metabolic states in Treg and effector T cells. These findings are solid and important for understanding immune regulation involving Treg cells and effector T cells.
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www.medrxiv.org www.medrxiv.org
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eLife assessment
This study presents a convincing analysis of the effects of covariates, such as age, sex, socio-economic status, or biomarker levels, on the predictive accuracy of polygenic scores for body mass index; The work is further supported by important approaches for improving prediction accuracy by accounting for such covariates across a variety of association studies. The authors did a commendable job addressing reviewer suggestions and comments. The work will be of interest to colleagues using and developing methods for phenotypic prediction based on polygenic scores.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study develops a new and important method for dissecting out two overlapping cell signaling pathways, phosphoinositide signaling and membrane protein trafficking. The combination of two state-of-the-art spectroscopic techniques provides compelling evidence for a reciprocal influence between an enzyme and a channel. The work will be of interest to the broader cell biology, biophysics and biochemistry communities.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study demonstrates that the Pseudomonas aeruginosa-derived quorum sensing signal, 2-aminoacetophenone, induces immune tolerization in macrophages by perturbing metabolism, particularly in the context of mitochondrial respiration and bioenergetics. The authors present convincing evidence for 2-aminoacetophenone-mediated reduction of pyruvate transport into mitochondria, with downstream effects that result in reduced ATP production in tolerized macrophages. The work will be of interest to those studying host-pathogen interactions.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable work explores the utility of using analyte ratios for improved biological interpretation in a MALDI MSI workflow. The evidence supporting the conclusions is however incomplete, as relevant controls are missing and the novelty of the study has been exaggerated, omitting discussion of key relevant background. The work would be of interest to the mass spectrometry community.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study uses convincing state-of-the-art neuroimaging analyses to characterise whole-brain networks during reward-based motor learning. This work motivates future research to dissociate why the observed changes in neural connectivity occur and how they support reward-based motor learning. The study is highly relevant for researchers at the intersection of decision-making and sensorimotor learning.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study represents a valuable step toward understanding how brain connectivity changes during reward-based motor learning. However, the evidence presented is incomplete. On one hand, the study leverages state-of-the-art techniques to examine brain connectivity; on the other hand, there are potential confounds in the experimental design, some omissions in statistical quantification, and at times, a lack of clarity about the methods used and the motor learning mechanisms being isolated.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a rather valuable finding on the RBM7 function in spicing regulation and uncharacterized role of MFGE8 splicing alteration in breast cancer metastasis. The evidence supporting the claims of the authors is solid. The work will be of broad interest to clinicians, medical researchers and scientists working on breast cancer.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides important findings based on compelling evidence demonstrating that females and males have different strategies to regulate energy consumption in the brain in the context of low energy intake. While food deprivation reduces energy consumption and visual processing performance in the visual cortex of males, the female cortex is unaffected, likely at the expense of other functions. This study is relevant for scientists interested in body metabolism and neuroscience.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript provides important information about the influence of TOR signaling pathway on development and aflatoxin production in the plant and human fungal pathogen Aspergillus flavus. Compared to an earlier version, the authors have addressed most of the concerns of the reviewers, including the convincing demonstration of the essential TOR pathway in this fungus by constructing a xylose promoter mutant strain.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study contributes to the understanding of how parafoveal words are neurally processed during naturalistic sentence reading. Convincing evidence is provided that the MEG response to a word can be modulated by the semantic congruency of a parafoveal target word. The study addresses a classic question in reading using a new Rapid Invisible Frequency Tagging (RIFT) technique, which can separately monitor the neural processing of multiple words during sentence reading.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors utilized scRNAseq profiling of NSCLC patient tumor samples to generate useful insights into the determinants of ICI responsiveness in NSCLC patients. While some of the findings add weight to the current literature, the analysis is incomplete due to the small cohort size and occasional departures from recognized subtype markers. This study would benefit from external cohorts to both validate the findings and to justify the statistical analysis undertaken.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The current version of the study presents important findings on how the RelA/Stat3-dependent gene program in the liver influences intestinal homeostasis. The evidence supporting the conclusions is solid, with new data added compared to an earlier version of the study. The work will be of interest to scientists in gastrointestinal research fields.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work critically evaluates several widely-used assays of transcriptional responses to water limitation in Arabidopsis grown on defined agar-solidified media and, finding inconsistent responses in root transcriptome responses, introduces a new 'hard agar' assay with more consistent responses. The work is valuable as a simple and alternative experimental system that would enable high-throughput genetic screening (and GWAS) to assess the impacts of environmental perturbations on transcriptional responses in various genetic backgrounds. Within this scope, the work is solid, though the debate about whether field-level physiological inferences can be made from such assays remains.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This useful study shows how genetic variation is associated with fecundity following a period of reproductive diapause in female Drosophila. The work identifies the olfactory system as central to successful diapause with associated changes in longevity and fecundity. While the genetic screening and methods used are solid, the approach to assessing diapause is incomplete and could benefit from additional orthogonal experiments.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study presents findings of great practical value, offering fresh insights into natural species distributions across Japan. By combining multiple data sources (including those from non-academic sectors, aka citizen scientists), the manuscript also presents a compelling new tool that can be used to aid conservation agendas, detect species distribution changes, and testing of ecological theories.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The paper illustrates a valuable approach to generating TCR transgenic mice specific for known epitopes. There is some solid evidence for the efficacy of this approach, although only limited evidence is provided that the TCR clone in question successfully recapitulates the functional features of the endogenous response to the same antigen, and the claim that this method is superior to more traditional clone selection methods is incompletely substantiated by the data presented.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript uses public datasets of myelodysplastic syndrome (MDS) patients to undertake a multi-omics analysis of clinical, genomic, and transcriptomic datasets. Useful findings are provided by way of interesting correlations of specific mutations with inflammation and differing clinical outcomes. While the evidence is extensive and interesting, it remains incomplete in the absence of pipeline validation and addressing the potential confounding factors present in the datasets used. When these issues are addressed, this will be of substantive value to hematologists and clinical immunologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This potentially useful study introduces an orthogonal approach for detecting RNA modification, without chemical modification of RNA, which often results in RNA degradation and therefore loss of RNA molecules. The approach might be of particular interest for sites where modifications are rare. However, the false positive and false negative rates are currently unclear, leaving the evidence for broad applicability of the method incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this manuscript, the authors describe a new AlphaFold2 pipeline called PabFold that can represent a useful tool for identifying linear antibody epitopes (B-cell epitopes) for different antigens. This information can be used in the selection of different reagents in competitive ELISA assays which can save time and reduce costs. Several questions, however, remain and the study is currently incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study combines across multiple complementary neuroscientific methods to understand the neural response to visual stimulus complexity in the human brain across lifespan. Lalwani et al., provide solid evidence, drawing from appropriate and validated methodology. A weakness is that key information about methodological details and controls is still outstanding, as is a discussion on how generalizable the findings are. With these elements strengthened, the study would be of broad interest to neuroscientists and biologists interested in aging and sensory processing.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This computational work represents a valuable and long overdue assessment of the potential mechanisms associating patterns of activity of entorhinal grid cells, recorded mostly in rodents, with the population property of hexasymmetry detected in non-invasive human studies. The methodic comparison of alternative hypotheses is compelling, and the conclusions are important for the future design of experiments assessing the neural correlates of human navigation across physical, virtual, or conceptual spaces.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this interesting study, the authors have used light-sensitive mGlu5 negative allosteric modulators to determine the role of these receptors in a chronic pain model. These findings could be useful to the pain field, but the evidence supporting these claims is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a useful examination of dense neuroanatomy in human postmortem medial entorhinal cortex, using a large number of small electron microscopy image volumes sampled from multiple cortical layers and individuals. The authors use solid experimental and annotation techniques, demonstrating the suitability of postmortem tissue reconstructions for analysis and presenting careful, detailed measurements of synapse properties and overall tissue composition. However, there is inadequate support connecting these findings to claims about general connectivity in medial entorhinal cortex, since factors affecting interpretability like noise, the spatial scales examined, and relationships between structural properties and connectivity are not characterized. With a more thorough contextualization, this work would be of interest for studies of cellular neuroanatomy or brain network organization.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on prognostic values of serum CA125, CEA, and AFP for predicting patient outcomes of endometrial cancer. The evidence supporting the claims of the authors is solid, although inclusion of detailed discussion of present results with prior documented findings would have strengthened the study. The work will be of interest to scientists working on endometrial cancer.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important manuscript used state-of-the-art techniques and employed relevant animal models to provide both convincing and solid evidence supporting the regulatory role of microRNA cluster 221/222 in rheumatoid arthritis synovial fibroblast. The findings of this work offer significant advances to current knowledge which will be interesting to a wide range audience in the rheumatology and bone research fields. However, whereas models, techniques, and analyses are solid, certain concepts related to the role of immune and bone cells are limited.
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eLife assessment
How and why nutritional requirements change over development and differ between species are significant questions with wide-ranging implications spanning ecology to health. In this manuscript, Talal et al. set out to address these questions in laboratory and field experiments with grasshoppers and in a comparative analysis of different species. The laboratory experiments are convincing but the field and comparative aspects are not sufficiently well developed. In general, the study offers some evidence of a universal shift from high protein to high carbohydrate intake during ontogeny in animals, but the methods are not clear and/or appropriate to support the goals and conclusions of the manuscript as it is.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is a valuable investigation of how type 5 metabotropic receptor signaling contributes to regulation of striatal circuit dynamics, that focuses on its role in direct pathway striatal projection neurons. The range of methods deployed and levels of analysis undertaken are key strengths but concerns remain that make the conclusions incomplete at present. This study will be of great interest for its unique demonstration of metabotropic receptor regulation of striatal circuit dynamics, physiology and behavior.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides valuable insights into the mechanistic basis of neurological manifestations of RNA polymerase III-related disease by creating a mutant mouse to dissect transcriptional changes. The data are solid and provide compelling evidence for disease progression initiated by a global reduction in tRNA levels leading to integrated stress and innate immune responses and neuronal loss. These observations notwithstanding, additional studies will be necessary to separate the direct and indirect effects of diminished RNA polymerase III transcription on cellular function and neurodegeneration in this valuable mouse model. The work will be of interest to those engaged in the study of chromosome biology, developmental biology and neurodegeneration.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable new behavioral apparatus aimed at differentiating the strategies animals use to orient themselves in an environment. The evidence supporting the claims is solid, with statistical modeling of animal behavior. Overall, this study will attract the interest of researchers exploring spatial learning and memory.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important manuscript describes experimental evolution experiments using a novel genetic system in yeast, showing that solute carrier transporters can incorporate additional functionality through the introduction of point mutations to either the ligand binding site or gating helices. These findings provide convincing evidence to establish that for Amino Acid transporters of the APC-type family, evolution to recognize new substrates passes through generalist intermediates that can transport most amino acids.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The manuscript examined the potential modulatory effects of nitric oxide (NO) on the response properties of mouse retinal ganglion cells (RGCs) using two-photon calcium imaging and multi-electrode arrays (MEA). The data identifying a group of RGCs affected by NO are solid but fall short on the precise nature of the effects and their physiological implications. The findings that there can be cell-specific adaptation effects provide useful new information for the field, and more experiments and MEA analysis are encouraged.
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eLife assessment
This important study describes a new mathematical method to analyze clonal composition of tissues using fluorescent reporters and to estimate the number of precursor cells contributing to tissue homeostasis and regeneration based on statistical variance. The evidence provided is convincing, with rigorous measurement of hematopoietic cell labeling during steady state and regenerative hematopoiesis following insult. It could be further strengthened by exploring the limitations of the binomial assumption, using tools to measure clonality and considering the possible effects of the inducing agent (tamoxifen) on precursor cells. The manuscript not only presents a compelling approach to better understand tissue dynamics, it also challenges some ideas in pathological hematopoiesis, opens new research directions and is thus of broad interest to stem cell and developmental biologists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important work substantially advances our understanding of nocturnal animal navigation and the ways that animals use polarized light. The evidence supporting the conclusions is convincing, with elegant behavioural experiments in actively navigating ants. The work will be of interest to biologists working on animal navigation or sensory ecology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The microRNA lin-4, originally discovered in C. elegans, has a key role in controlling developmental timing across species, but how its expression is developmentally regulated is poorly understood. Here, the authors provide convincing evidence that two MYRF transcription factors are essential positive regulators of lin-4 during early C. elegans larval development. These results provide important insight into the molecular control of developmental timing that could have significant implications for understanding these processes in more complex systems.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important manuscript uses a machine-learning approach to predict and annotate cis-regulatory elements across insect genomes, helping to address a much-needed gap in comparative genomics. This method does not rely on sequence alignments, thereby allowing functional genomics studies of more distant species, including emerging model organisms. There are nuanced views on the strength of the evidence from the predictions: the pipeline appears to be based on solid evidence, but the methods could be better described. We suggest the manuscript would be much more robust if the code used was accessible for review and validated further.
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Local file Local file
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Software developer with 11 years of experience in building e-commerce, enterprise andhigh-performance web applications. Insightful knowledge of Microsoft applications,RESTful API, AWS cloud skills, Microservice architecture, and CI/CD pipeline.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Hartman et al.'s important research examines six commonly utilized imaging-based multiplexed transcriptomic techniques and introduces a novel specificity metric, "MECR," to streamline platform evaluations. The authors highlight the crucial influence of cell segmentation methodologies on outcomes, offering insight into the field. Nonetheless, the substantiation for the principal assertions remains incomplete, as the comparisons across platforms seem uneven due to variations in gene panels.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This is an important study that brings insight into mechanisms that underlie regulation of GABAergic transmission in response to changes in activity. The authors present solid data supporting the premise that action potential firing rather than excitatory synaptic strength is a key determinant of GABAergic synaptic inputs.
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eLife assessment
This study demonstrates that neurons receiving inputs from auditory cortex in the inferior colliculus widely encode the outcome of a sound detection task independant of the presence of auditory cortex. This valuable study based on imaging of transynaptically labelled neurons provides convincing evidence that auditory cortex is necessary neither for sound detection, nor to channel information related to behavioral outcome to the subcortical auditory system. This study will be of wide interest for sensory neuroscientists.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study discovered DBT as a novel gene implicated in the resistance to MG132-mediated cytotoxicity and potentially also in the pathogenesis of ALS and FTD, two fatal neurodegenerative diseases. The authors provided convincing evidence to support a mechanism by which loss of DBT suppresses MG132-mediated toxicity via promoting autophagy. This work will be of interest to cell biologists and biochemists, especially in the FTD/ALS field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Building on previous toolboxes to distinguish 1/f noise from oscillatory activity, this study introduces an important advancement in neural signal analysis to identify oscillatory activity in electrophysiological data that refines the accuracy of identifying non-sinusoidal neural oscillations. Extensive validation, using synthetic and various empirical data, provides convincing evidence for the accuracy of the method and outlines practical implications for relevant scientific problems in the field.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents valuable findings regarding the microstructural basis of brain development in the cerebellum and thalamus of rat neonates using diffusion-weighted MRS. The authors present solid evidence of differential development trajectories in the thalamus and the cerebellum through analytical and morphometric biophysical modelling of the diffusion-weighted MRS data, though some aspects such as the validation of the findings against gold-standard techniques and a detailed discussion of methodological choices require further elaboration. The work will be of interest to developmental biologists and neuroscientists seeking noninvasive approaches to probe in vivo neuronal and glial development in the brain.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study marks a significant advancement in brain aging research by centering on Asian populations (Chinese, Malay, and Indian Singaporeans), a group frequently underrepresented in such studies. It unveils solid evidence for anatomical differences in brain aging predictors between the young and old age groups. Overall, this study broadens our understanding of brain aging across diverse ethnicities.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors use a synthetic approach to introduce synaptic ribbon proteins into HEK cells and analyze the ability of the resulting assemblies to cluster calcium channels at the active zone. The use of this ground-up approach is valuable as it establishes a system to study molecular interactions at the active zone. The work relies on a solid combination of super-resolution microscopy and electrophysiology, but would benefit from: (i) additional ultrastructural analysis to establish ribbon formation (in the absence of which the claim of these being synthetic ribbons might not be supported; (ii) data quantification (to confirm colocalization of different proteins); (iii) stronger validation of impact on Ca2+ function; (iv) in depth discussion of problems derived from the use of an over-expression approach.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The authors provide an important step forward in understanding how brain-derived hormones modulate behavior, using medaka fish as a model system. Knockout lines present convincing evidence from multiple mutant lines, showing that estrogens play a significant role in male social behavior, and that lacking aromatase changes brain gene expression. The conclusions for females are less substantiated, and the conclusions regarding sexual differentiation should be considered carefully.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study reports that glutamate signaling in LepRb PMv neurons is necessary for leptin-dependent fertility. The data supporting the conclusion is solid. This work will be of interest to researchers in the fields of both reproductive and metabolic biology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This work describes important updates to qFit, the state-of-the art tool for modeling alternative conformations of protein molecules based on high resolution X-ray diffraction or Cryo-EM data. The authors provide some convincing analyses of qFit's performance in selected test cases. This manuscript will be of interest to structural biologists and protein biochemists, since the adoption of qFit in structural refinement may lead to new mechanistic insights into protein function.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Urofacial syndrome is a rare early-onset lower urinary tract disorder characterized by variants in HPSE2, the gene encoding heparanase-2. This study provides a useful proof-of-principle demonstration that AAV9-based gene therapy for urofacial syndrome is feasible and safe at least over the time frame evaluated, with restoration of HPSE2 expression leading to re-establishment of evoked contraction and relaxation of bladder and outflow tract tissue, respectively, in organ bath studies. The evidence is, however, still incomplete. The work would benefit from evaluation of additional replicates for several endpoints, quantitative assessment of HPSE2 expression, inclusion of in vivo analyses such as void spot assays or cystometry, single-cell analysis of the urinary tract in mutants versus controls, and addressing concerns regarding the discrepancy in HPSE2 expression between bladder tissue and liver in humans and mice.
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eLife assessment
This important study develops a machine learning method to reveal hidden unknown functions and behavior in gene regulatory networks by searching parameter space in an efficient way. The evidence for some parts of the paper is still incomplete, needing systematic comparison to other methods and to the ground truth, but the work will nevertheless be of broad interest to anyone working in biology of all stripes, since the ideas put forward by the authors extend beyond gene regulatory networks to revealing hidden functions in any complex system with many interacting parts.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Despite the importance of long-lived plasma cells (LLPCs), particularly for the infection and vaccination field, it is still unclear how they acquire their longevity. With a solid genetic approach, the authors demonstrate quite convincingly a requirement for chemokine/chemokine receptor-mediated interaction in LLPC longevity. The data are very valuable for the development of new types of vaccines.
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www.researchsquare.com www.researchsquare.com
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eLife assessment
This study presents an important finding on the molecular mechanism for transduction of environmentally induced polyphenism. The evidence supporting the claims of the author is incomplete due to limited sample sizes and inadequate analysis. This paper would be of interest to those studying aphids wing dimorphism.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study presents a new quantitative imaging pipeline that describes with high temporal precision and throughput the movements of late-stage Drosophila embryos, a critical moment when motion first appears. A new approach is used to explore the role of miRNAs in motion onset and presents solid evidence that shows a role for miR-2b-1 and its target Motor in embryonic motion. The data are well supported even if the mechanistic insight into the emergence of movement remains to be explored.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study makes a valuable empirical contribution to our understanding of visual processing in primates and deep neural networks, with a specific focus on the concept of factorization. The analyses provide convincing evidence that high factorization scores are correlated with neural predictivity. This work will be of interest to systems neuroscientists studying vision and could inspire further research that ultimately may lead to better models of or a better understanding of the brain.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study assesses a novel in silico neoantigen prediction algorithm combined with in vivo validation to determine important parameters of neoantigen immunogenicity and tumor control. The strength of evidence is compelling. This study contributes to the field and will aid in the development of improved personalized cancer vaccines.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study presents a valuable finding on sperm flagellum and HTCA stabilization. The evidence supporting the authors' claims is incomplete. The work will be of broad interest to cell and reproductive biologists working on cilium and sperm biology.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This manuscript highlights single-stranded DNA exo- and endo-nuclease activities of ExoIII as a potential caveat and an underestimated source of decreased efficiency in its use in biosensor assays. The data present solid evidence for the ssDNA nuclease activity of ExoIII and identifies residues that contribute to it. The findings are useful, but some aspects in the study remain incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study offers a compelling molecular model for the organization of rootlets, a critical organelle that links cilia to the basal body, ensuring proper anchoring. While previous research has explored rootlet structure and organization, this study delivers an unprecedented level of resolution, valuable to the centrosome and cilia field. This research marks a significant step forward in our understanding of rootlets' molecular organization.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Hepatocellular carcinoma (HCC) is a particularly aggressive form of cancer, with an increasing number of treatment options approved for use in patients over the past decade. However, the biology of HCC and identifiable therapeutic targets have not been as clear, even in the era of molecular oncology. Likewise, the cellular biology of HCC, including the role of intercellular communication, has not been well elucidated. In this compelling study, Dantzer et al. provide fundamental insight into the role of beta-catenin on intercellular communication occurring via extracellular vesicles, with implications for immune evasion in a cancer increasingly being treated using immuno-oncologic agents.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
The study elucidates a detailed molecular mechanism of the initial stages of transport in the medically relevant Na+-coupled GABA neurotransmitter transporter GAT1 and thus generates useful new insights into this protein family. In particular, it presents convincing evidence for the presence of a "staging binding site" that locally concentrates Na+ ions to increase transport activity, whilst solid evidence for how Na+ binding influences larger scale dynamics.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this potentially important study, the authors report results of QM/MM simulations and kinetic measurements for the phosphoryl-transfer step in adenylate kinase. The results point to the mechanistic proposal that the transition state ensemble is broader in the most efficient form of the enzyme (i.e., in the presence of Mg2+ in the active site) and thus a different activation entropy. With a broad set of computations and experimental analyses, the level of evidence is considered solid by some reviewers. On the other hand, there remain limitations in the computational analyses, especially regarding free energy profiles using different methodologies and the activation entropy, leading some reviewers to the evaluation that the level of evidence is incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This study provides valuable new insights on how a prevailing model of hippocampal sequence formation can account for recent data, including forward and backward sweeps, as well as constant cycling of sweeps across different arms of a T-maze. The convincing evidence presented in support of this work relies on classical analytical and computational techniques about continuous attractor networks.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This solid study assesses a novel mitochondrial inhibitor in combination with the BCL-2 inhibitor venetoclax, with the aim to increase its activity in acute myeloid leukemia. It provides valuable findings of combinatorial efficacy using preclinical models, confirming the overall importance of targeting oxidative phosphorylation to overcome venetoclax resistance in acute myeloid leukemia, and could be strengthened through mechanistic studies demonstrating drug specificity, pharmacodynamic efficacy studies in vivo to test clinical utility and extended statistical analyses of the results. The study is of interest to hematologists because it addresses a key biomedical issue in acute myeloid leukemia (venetoclax resistance) and provides data regarding the safety and activity of a novel inhibitor of the mitochondrial polymerase addressed in combination with venetoclax.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This valuable study aims to present a mathematical theory for why the periodicity of the hexagonal pattern of grid cell firing would be helpful for encoding 2D spatial trajectories. The idea is supported by solid evidence, but some of the comparisons of theory to the experimental data seem incomplete, and the reasoning supporting some of the assumptions made should be strengthened. The work would be of interest to neuroscientists studying neural mechanisms of spatial navigation.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
Notch1 is expressed uniformly throughout the mouse endocardium during the initial stages of heart valve formation, yet it remains unclear how Notch signaling is activated in specific regions to induce valve formation. To answer this question, the authors used a combination of in vivo and ex vivo experiments in mice to demonstrate ligand-independent activation of Notch1 by circulation induced-mechanical stress and provide partially convincing evidence for stimulation of a novel mechanotransduction pathway involving post-translational modification of mTORC2 and Protein Kinase C (PKC) upstream of Notch1. While these findings represent an important advance in our understanding of Notch1-mediated valve formation, data supporting the main claims are incomplete.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this fundamental work, the authors demonstrated that maternal choline supplementation improved spatial memory, reduced hyperexcitability, and restored NeuN expression in a familial Alzheimer's disease mouse model. Interestingly, choline deficiency increased mortality, while paradoxically reduced hyperexcitability. Through behavioral, electrophysiological, and histological measures, the authors present convincing evidence supporting the significant role of maternal choline supplementation in protecting hippocampal functions vulnerable to Alzheimer's disease.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
In this important work, a quantitative analysis method for three-dimensional morphogenetic processes during embryonic development is introduced. The proposed method is a pipeline combining several methods, allowing quantitative analysis of developmental processes without cell segmentation and tracking. Upon application of their method, the authors obtain convincing evidence that ascidian gastrulation is a two-step process. This work should be of interest to a broad range of developmental biologists who aim to obtain a quantitative understanding of morphogenesis.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This important study describes a neural circuit contributing to two behavioral processes affecting pathogen avoidance in the nematode C. elegans. The method used to identify specific contributing neurons is innovative and the experimental evidence supporting the major claims is solid. This study will be of interest to neuroscientists studying behavior, in particular in C. elegans.
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www.biorxiv.org www.biorxiv.org
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eLife assessment
This potentially useful study involves neuro-imaging and electrophysiology in a small cohort of congenital cataract patients after sight recovery and age-matched control participants with normal sight. It aims to characterize the effects of early visual deprivation on excitatory and inhibitory balance in the visual cortex. While the findings are taken to suggest the existence of persistent alterations in Glx/GABA ratio and aperiodic EEG signals, the evidence supporting these claims is incomplete. Specifically, small sample sizes, lack of a specific control cohort, and other methodological limitations will likely restrict the usefulness of the work, with relevance limited to scientists working in this particular subfield.
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