Evaluated articles

Evaluation Summary:

This article presents molecular dynamics simulations of the pH-gated pentameric ion channel GLIC, which has been the subject of many structural and functional studies. GLIC can be considered as a model system for pentameric ligand-gated ion channels that are responsible for fast chemical-electrical communication between cells in animals. The findings include the solution of open- and closed-like channel forms, intermediates and a "pre-desensitised" state. The approach reproduces modulation by pH and mutation, surprisingly finding a predominance of closed channels, despite activating conditions, and suggest a role for asymmetry in channel gating. Overall, the sampling of channel dynamics is significant and the description of state interconversions sheds new light on pLGIC mechanisms.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This study is of interest to the broad malaria research community and especially those who work on drug resistance. The authors provide a summary of their surveys of African and Southeast Asian Plasmodium falciparum parasites for the Kelch 13 gene, a marker of artemisinin resistance. The contribution of several K13 mutations to artemisinin resistance is investigated in different genetic backgrounds and confirms the lack of a barrier for the potential emergence of artemisinin resistance in African parasites. These findings are of prime importance in the context of public health perspective on managing the risk of resistance appearing in Africa.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

In this paper, Katz and colleagues present an extension of their previous CT methods to now image melanin, a biologically important molecule in melanocytes and melanoma. This work very nicely demonstrates the way in which micro-CT can be applied to very specific biological questions in the context of a whole animal, and will be useful to those working in zebrafish, melanocyte biology and imaging fields.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

The authors examined the Ca-dependence of exocytosis at cerebellar mossy fiber boutons using eectrophysiology, Ca imaging, Ca uncaging and capacitance measurements. The study reveals the presence of a high affinity Ca sensor for exocytosis, a shallow, seemingly non-saturating relationship between Ca and release or Ca and synaptic delay, a high-affinity sensory for priming of vesicles with very low (near basal) Ca levels, a late rate of release that is independent of Ca concentration (presumably due to sensor saturation), and extremely fast peak kinetics of release. This work contributes to a comparative view of synapses. These general approaches have been used at other synapses over many years by Neher and others, and they show intriguing differences among different types of synapse that are likely functionally significant. A strength of this manuscript is the masterful implementation and explanation of the techniques. The recordings at physiological temperatures, pushing-the-envelope for speed of capacitance measurements, the very careful measurement of KDs of indicators, and the unbiased testing of diverse modern-day kinetic models for release, all combine to lend the paper reliability and give it lasting value.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Stress granules are a critical component in the defense against certain viruses. The mechanisms regulating stress granules induced but the NF90 pathway are not well defined. Here, the authors use biochemical, cell-based, and in vivo approaches to make the novel discovery that Tim3 functions as a negative regulator of NF90-mediated antiviral responses.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This MEG pupillometry study investigated the stimulus-specific plasticity in human visual gamma-band activity. The results show that both Gamma-band MEG and pupil size responses to visual stimuli adapt across stimulus repetitions. This work will be of broad interest to readers in the fields of non-human primate and human electrophysiology. The claims are fully supported by the data but the links between behavior, pupil size and MEG signals could be investigated further.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper reports the atomic structure of XKR9, a membrane protein that is implicated in initiating the process to get rid of cells that are undergoing programmed cell death (apoptosis). The protein of interest was originally proposed to be a lipid channel, but the work presented here suggests that it is unlikely to function in this capacity alone. As a first step in this nascent field, the paper should be of interest to membrane structural biologists, and those working on lipid transport and apoptosis.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

Yamagata et al., present a new transgenic mouse where the cells expressing the gene Scn1a also express green fluorescent protein. This new model is an important contribution to the study of Dravet Syndrome- an epileptic disorder, that is often drug-resistant, where ~80% of patients have loss-of-function mutations in SCN1A. This study confirms the well-known presence of Scn1a in interneurons and identifies Scn1a-expressing subpopulations of cortical neurons that could also potentially contribute to the symptoms of Dravet Syndrome.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest to anyone who wants to deliver nucleic acids to specific cell types in whole animals. The work provides a new method to target and deliver of nanodevices to specific cell types and intracellular compartments within live animals. It relies on cell types that can be induced to express a transmembrane protein chimera with a newly developed DNA sequence-specific camelid antibody. In general the data appeared to be of high quality and were well controlled, supporting the authors' conclusions. This work could help pave the way for future advancements in the cell-specific delivery of custom-engineered payloads such as dsDNA nanodevices utilized as quantitative chemosensors and effectors in living cells.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Tracking horizontal gene transfer of mobile resistance genes is exceptionally important in the context of AMR and its burden on public health. An accessible high-throughput technique that provides an alternative to Hi-C or single-cell whole genome sequencing for associating mobile antibiotic resistance genes with their bacterial hosts in complex microbial populations is an important development for the field. The method introduced here, which relies on cellular emulsion and fusion PCR in one step, is an improvement over the previously published epicPCR. In addition, the method can be applied to other studies on complex microbial communities beyond antibiotic resistance.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This study implicates excitatory projections from cholecystokinin (CCK) entorhinal cortical neurons to the lateral amygdala in trace fear conditioning in mice. Behavioral, chemogenetic, optogenetic, and electrophysiological work show that these projections are critical for the acquisition of conditioned freezing to a trace conditioned stimulus. The identification of a novel circuit and genetically defined cell type for regulating fear memory formation important. However, whether this pathway is specifically involved in trace fear conditioning is unclear from the present results and further work is needed to address analytic and interpretational concerns.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

Group living may be beneficial for many reasons, but has costs in terms of increased rates of parasitism, in particular if group members are highly related. In this meta analysis, many original studies on questions related to parasitism, relatedness and group living are brought together in one unifying framework. The authors conclude that living in groups can indeed facilitate the spread of infectious diseases, but that these costs can be overcompensated by the benefits of group living.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript explores the relationship between stiffness of migrating cells and the stiffness of the substrate of which they are migrating. Specifically, the authors show that the actin-bundling protein Fascin limits the levels of activated myosin to alter stiffness of the migratory substrate. This is a well-controlled study, and with some additional clarifications of methods and extensions to some analyses that would strengthen the paper, it will be of broad interest to cell biologists, particularly those studying cell migration.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

The basis for working memory is controversial in terms of any basis related to neuronal or synaptic activity in sensory cortex during maintenance and the involvement of non-sensory areas especially the frontal cortex and hippocampus. This work uses rare human intracranial recordings to examine another aspect, connectivity between areas, and demonstrates connectivity from sensory cortex to hippocampus during encoding in one frequency band and connectivity in a reverse sense during maintenance. The work has the potential to inform models of working memory.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

Kubiniok et al. use published data sets to bioinformatically study the contribution of tissue type and HLA classical class I gene allotype on the immunopeptidome, the repertoire of peptides presented by MHC class I molecules on the cell surface. This is an understudied and critically important question for understanding CD8+T cell tolerance and immunosurveillance of cancer and other diseased cells and autoimmunity, since it enables accurate prediction of peptide targets for vaccines designed to induce or suppress CD8+ T cell responses. Overall, this is a study that draws attention to some of the properties of the antigen processing and presentation pathway that had not been investigated before, namely the known differential gene expression profiles between tissues resulting in the presentation of tissue-specific antigens on HLA-I molecules, which is very valuable. Additionally this study provides avenues for investigation of the involvement of new enzymatic pathways involved in the generation of HLA-I restricted peptides that are presented to CD8+ T cells for immunosurveillance.

Evaluation Summary:

This manuscript provides the first 3D structure of a novel type of RNA processing enzyme recently identified in bacteria. It convincingly uses cryoEM and biochemistry to describe how this small enzyme makes a new type of homo polymeric complex as required for its activity. The manuscript provides important conceptual novelties that will be of interest for a broad readership of biologists interested in gene expression processes.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest to immunologists studying the transcriptional control of innate immune responses. The paper presents a new role for transcriptional regulators in the control of inflammatory properties of cross-presenting dendritic cells that are involved in anti-tumoral and anti-viral immunity. The data support the conclusions but some modifications of the text and additional experiments are required.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper tackles perhaps THE central question in metagenomics: what are all these unknown genes and genomes doing!? The authors use recent advances in high-throughput sequencing clustering and homology detection algorithms to systematically integrate unannotated genes into discovery workflows. The paper's exploration results in a wide array of highly informative summative statistics, together with a simple example of how powerful the provided resource can be in generating hypotheses about the function of unknown genes.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This paper will be of interest to experimental virologists and others following the development of "gene drive" technology to promote the rapid spread of specific mutations through a population. The authors first nicely confirm their prior finding that a gene drive virus can be used to transfer mutations into a normal virus when both are infecting the same cell. They then evaluate a strategy with potential to ameliorate the undesirable but expected emergence of viruses that acquire resistance to the gene transfer. Although the experiments are well done, the data are mostly convincing and accurately interpreted, and the presentation is clear, the studies provide a relatively minor advance in fundamental understanding of this potentially innovative therapy.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Brochet et al. address an outstanding ecological question related to how closely related microbial symbionts co-exist in the gut as stable communities. To tackle this question, the authors use an elegant model relying on honeybees colonized with a defined bacterial community. They provide compelling empirical evidence that a nutritionally complex diet together with microbial metabolic diversity play a key role in enabling co-existence of closely-related honeybee gut microbiota.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)