Evaluated articles

eLife assessment

The authors studied the mechanisms by which dead cells are removed from the wounded skin in a process called efferocytosis. By analyzing different cell populations in the skin, the authors find that proteins involved in mediating the cell death and marking the cells as undergoing this process are elevated during distinct times in the wound healing program. Interestingly, these same proteins are elevated even higher in diabetic wounds. Finally the authors demonstrate that blocking the process of efferocytosis alters the wound healing program, thus illustrating its importance in effective wound repair.

eLife assessment

This work is fundamental in providing compelling evidence of mitochondria-encoded RNAs playing a role in controlling nuclear gene expression. How mitochondria and the nucleus communicates is an important but yet not well-appreciated area of biology. Using the iMARI (in situ mapping of RNA-Genome Interactions) technology developed by this team, the authors found that mitochondria-encoded RNAs play an unexpected role in regulating nuclear gene expressions in endothelial cells and intriguingly, depletion or overexpression of a specific mt-caRNA altered stress-induced transcription of nuclear genes encoding for innate inflammation and endothelial activation. Overall, these findings are interesting and supported by experimental confirmation, bulk-RNA-seq, and snRNA and scRNA-seq data and will be of interest to the field studying RNA regulation, gene expression and cell biology.

eLife assessment

This paper presents valuable findings from whole-brain modeling of persistent activity states (underlying working memory) in the mouse brain. The most novel finding is that a spatial gradient of the density of inhibitory neurons supports a corresponding spatial gradient of propensity to support persistent activity. However, the evidence for this finding appears to be incomplete.

eLife assessment

Brodsky and colleagues report here an unexpected cis-activation mechanism of caspase-11. The authors use cellular imaging methods and cleavage site mutants to show that the LPS-induced speck formation by caspase-11 depends on the autoprocessing between two subdomains. This new finding opens multiple doors for further investigating how this non-canonical inflammasome is regulated and activated at the molecular level.

eLife assessment

This important work reveals that increased flux towards one carbon metabolism improves neuronal regeneration after injury in C. elegans. The presented data are solid and provide compelling support for this conclusion. The manuscript can still be improved in order to strengthen some of the specific conclusions made and to increase the clarity of the presentation.

eLife assessment

This valuable study presents a tool for hyperaligning functional brain topography between individuals, which is based on fMRI connectivity data gathered when participants watched different movies. The tool is validated through strong correlations between functional topographic maps generated from a participant's own localizer data and those derived from other participants' data based on this hyperalignment, even when the training and target participants were drawn from different datasets. The study will potentially be of interest to researchers working with a wide range of fMRI datasets.

eLife assessment

The paper introduces a new, important framework for neural modelling that promises to offer efficient simulation and analysis tools for a wide range of biologically-realistic neural networks. The paper's examples provide solid support for the ease of use and flexibility of the framework, but the comparison to existing solutions (in particular in terms of accuracy and performance) is incomplete. With a more careful evaluation of the tool's strengths and limitations, the work would be of interest to a wide range of computational neuroscientists and researchers working on biologically inspired machine learning applications.

eLife assessment

This important study presents a new apparatus and experimental paradigm to examine deficits in finger control in stroke patients, with the goal of understanding their potential (biomechanical and neural) underpinnings. The paper presents solid experimental design and quantitative analyses to characterise these deficits and infer their origin, but a few technical aspects related to data analysis and statistics could be improved, and alternative interpretations of the results considered. In addition to the scientific results, this novel methodology can be used as a starting point for further research on hand function impairments in stroke, which is of significance for theoretical studies in neuroscience and applied research in rehabilitation.

eLife assessment

The manuscript by Jingsong Zhou and colleagues uncovers why the extraocular muscles (EOMs) are preserved while other muscles undergo degenerative changes in amyotrophic lateral sclerosis (ALS). In this work, the authors have used a mouse model of familial ALS that carries a G93A mutation in the Sod1 gene to demonstrate that NaBu treatment partially restores the integrity of NMJ in the limb and diaphragm muscles of G93A mice. The findings of the study offer important information that EOMs are spared in ALS because they produce protective factors for the NMJ and, more specifically, factors secreted by EOM-derived satellite cells. While most of the experimental approaches are convincing, the use of sodium butyrate (NaBu) in this study needs further investigation, as NaBu might have a variety of biological effects. Overall, this work may help develop future therapeutic interventions for patients with ALS.

eLife assessment

This important study investigates various variants of the SARS-COV-2 spike protein using established computational methods, complemented by experimental validation efforts. The evidence, bolstered by an evolutionary approach and protein dynamics, is solid. Placing this research in the broader context of the field could further enrich the manuscript. It will interest biophysicists focused on allostery and protein evolution.

eLife assessment

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

eLife assessment

This important study shows, based on analyses of single-cell RNA-seq data sets of thymus cells, that transposable elements (TEs) are broadly expressed in thymic stromal cells, especially in medullary thymic epithelial cells and plasamacytoid dendritic cells. The authors also show that at least some TE-derived peptides are presented by MHC-I molecules in the thymus. The study provides solid findings supporting a role of TEs in thymic T-cell selection and immune self-tolerance.

eLife assessment

This potentially useful study aims to advance our understanding of the structure of the native form of a viral toxin secreted from infected cells. While some of the findings confirm previous reports, the new claims in this study are unfortunately only inadequately supported by the methods and analyses used. More rigorous approaches are needed to justify the main conclusion that the structure of the viral toxin derived from infected cells in this study is distinct from previously reported structures of recombinantly expressed versions of the toxin.

eLife assessment

This valuable study shows that auxin exposure perturbs feeding behavior, survival rates, lipid metabolism, and gene expression patterns in adult Drosophila flies. The results are solid with proper methods and data analyses, and the evidence broadly supports the conclusions with only minor weaknesses. This work is relevant for fly geneticists who are interested in using the auxin-inducible gene expression system for inducing target protein degradation acutely.

eLife assessment

This useful manuscript explores conditions for epigenetic inheritance by studying the stability of simple network models to permanent and transient perturbations. A novel aspect of the study is that it unifies non-genetic inheritance phenomena across cell divisions of unicellular organisms and in the germline of multicellular organisms. However, the models studied are more a collection of vignettes of numerical studies than a systematic study, therefore the evidence presented remains incomplete. As a first step towards building a more systematic theoretical framework, this work will be of interest to colleagues in the field of epigenetic inheritance.

eLife assessment

This manuscript presents important findings that inform the genetic underpinnings of the model plant Arabidopsis' resistance to turnip mosaic virus (TuMV). The strength of the evidence in the manuscript is exceptional, with very large sample sizes, careful controls, multiple follow-up experiments, and broadening to the evolutionary context. The evidence provides robust support for each of the manuscript's conclusions and could pave the way for functional studies.

eLife assessment

This important study describes changes in excitability in motor neurons of the peripheral autonomous nervous system during aging. The manuscript provides convincing evidence indicating that sympathetic neurons from aged mice show higher excitability compared to neurons from young mice which was linked to decreased activity of KCNQ2/3 potassium channels. This research has implications for understanding the age-related changes that occur in the peripheral nervous system.

eLife assessment

This is an important study that develops a method to fluorescently label peptide MHC complexes on live dendritic cells to enable detection of antigen specific T cells in polyclonal populations. Solid evidence that this can be used to effectively identify antigen specific T cells in vitro and in vivo is provided for one model antigen systems (Ova-OTII). The approach has exciting potential as prior single step methods with directly conjugated single peptides have generally failed due to high background. Thus, this approach potentially moves the state of the art forward, but further work is needed to realise and determine the limits and ultimate utility of the approach.

eLife assessment

This manuscript describes an important NMR investigation of allosteric interactions within Abl kinase. The authors identify helix I as a major element that couples the Abl active site with the myristate-binding pocket. The convincing findings have implications for understanding Abl kinase activation and how to target Abl kinase in diseases.