Evaluated articles

Evaluation Summary:

This paper provides further evidence for hemispheric asymmetry in the cortical control of manual actions based on intracranial (ECoG) recordings in human participants. Specifically, based a linear encoding model, the authors argue that movement encoding is more bilateral in the left hemisphere than the right hemisphere. The paper is well-written and the analyses are largely appropriate for addressing the primary hypothesis, though it would be helpful to detail the variability of electrode placement across individuals (which arises for the clinical intervention being undertaken) and incorporate this variability into the statistical analysis. Given the novelty of this type of human data and the well established question being addressed, this paper will be of interest to both basic and clinical researchers in motor neuroscience.

(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 manuscript uses viral tracing to identify interneurons, throughout the spinal cord, which synapse onto motoneurons innervating pairs of flexor and extensor hindlimb muscles. Importantly, the data identifies single premotor interneurons which travel to, and presumably regulate the activity of, multiple motor pools. It is possible that these premotor neurons are involved in regulating muscle stiffness across a joint.

(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:

It has long been known that nerves regulate the early formation of the blastema during limb regeneration through the promotion of cell proliferation. The manuscript by Wells-Enright et al. provides an interesting new role for nerves during salamander limb regeneration by showing that nerves also determine how much tissue to regenerate. They demonstrate that increased nerve abundance makes bigger limbs while a decrease in nerve abundance generates smaller limbs. Size regulation of organs is a broadly interesting and clinically important problem, which is why this manuscript should be of interest to a large general audience.

(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 will be of great interest to scientists within the fields of developmental biology and evolution, as well as to researchers that generally use the sea urchin as a model system or those employing single-cell mRNA-sequencing technology. The work provides a comprehensive analysis of the cell state specification of a whole deuterostome organism and proof of principle of the use of single-cell sequencing to identity deep homologies of cell type.

(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, #2, and #3 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript studies the alignment of malaria parasites (merozoites) at the surface of red blood cells (RBCs), a key element of their reproduction cycle during the blood stage of the disease. Building on a computational model the authors developed previously, which incorporates the stochastic nature of RBC deformations and adhesive bonds between the merozoite and RBC, it is demonstrated that parasite shape plays a key role in its alignment dynamics. In particular, the authors shed new light on the egg-like shape typically observed in Plasmodium merozoites, which has important implications for how effectively the parasite can survive and multiply.

(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:

This is a strong manuscript due to its sophisticated behavioral analysis and modeling of behavioral output. The system and results provide a framework for future genetic analysis examining the biological basis of sensory behaviors.

(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 develops new software tools to analyze and classify single cells with high throughput based on single cell phenotyping using an existing imaging system. The authors show that tissues can be reproducibly decomposed into clusters of cells based on their feature space and that cell composition dynamics can be reliably detected. The main impact is to make single cell phenotyping more tractable, including for samples and organisms for which sequencing-based or fluorescent-labeling-based approaches are not readily available. Applicability was demonstrated in two research model organisms, zebrafish and freshwater snail.

(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 details coordinated work to both measure and model long-range correlations in the primate brain, during either rest or a reach-to-grasp task. The careful analysis shows that these long-range correlations are modulated by behavioral state, and can exist in the absence of common input or long-range anatomical connections. An analytical model is developed that shows how a disordered system with heterogeneous connections can give rise to this kind of long-range correlations, with only short-range direct connections between neurons.

(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 is of interest to cell biologists studying the signal transduction regulation of RNP granule assembly and its effects on cell growth. The work provides insight into the novel role of Pak1 kinase in the control of mRNA binding protein Sts5 and determines that Pak1 colocalizes with Processing (P) bodies during starvation and has function in P body dissolution after refeeding. Overall, the data are well presented, and support previous known findings.

(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 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

MicroRNAs (miRNAs) control gene expression during development and play crucial roles in disease. Loss-of-function mutations in key pathway components are embryonically lethal. Here, La Rocca et al. establish an elegant mouse model that enables acute and reversible inhibition of miRNA-guided silencing. Analysis of this model has convincingly demonstrated that miRNA activity is dispensable for homeostasis in most adult tissues, with the notable exception of heart and skeletal muscle. This work provides an extremely useful tool for the study of miRNAs in vivo and provides new insights into the roles of miRNAs in adult mammalian tissues. The findings presented will impact many fields given the well-established roles of miRNAs in normal development and diseases.

(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 work is of interest to the field of reproduction. Prior to fertilization, spermatozoa undergo a series of morphological and biochemical changes to become fertilization competent, driven by a rapid and poorly understood signaling cascade, culminating in the acrosome reaction. This latter reaction releases to the outside components from a vesicle, the acrosome, in the spermatozoan head and transforms the head plasma membrane so that sperm can fuse with the egg. The work shows that a G protein modulator GIV/Girdin, influences sperm motility and the acrosome reaction. In so doing it is important for fertilization and is one more strategy to control untimely acrosome reaction. The proposed mechanism is well supported by a variety of different experimental approaches.

(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 will be of interest to scientists across systems neuroscience or to those interested in how one component of a neural circuit contributes to downstream functions longitudinally. This study investigates how increasing feed forward inhibition in the dentate gyrus-CA3 hippocampal circuit impacts the formation and maintenance of context-specific ensembles in CA1 and the anterior cingulate cortex. However not all the claims of this manuscript are fully supported by the data.

(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:

This study aims to measure interpersonal and interethnic variation in human microbiomes and metabolomes in the San Franciso, CA, area. The strength of the study is in the level of robust analysis of the microbiota. It is interesting that diet is not one of the apparent associations in this study, yet the relationship of microbiota diversity to body habitus is strong in Caucasian subjects. Overall, the key results of this work nicely confirm that there are dissimilarities in gut microbiomes related to differences in ethnicity of subjects.

(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:

In this study, Kim and co-workers track the dynamics of a large set of different ATP-dependent chromatin remodelers in living cells by utilizing state-of-the-art single-molecule imaging. They report that the remodelers exhibit very high turnover rates at target loci/nucleosomes, find evidence for cooperativity among the remodelers, and reveal the role of ATP hydrolysis in those interactions. These observations allow the authors to put forward a model for tug-of-war activities that modulate the accessibility of promoter regions for transcriptional activity. This manuscript brings important new information to the remodeler and chromatin dynamics field.

(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 study reports a pivotal role of the conserved edge-strand of the periplasmic metalloprotease BepA in the folding and quality control of an outer membrane protein (OMP), the lipopolysaccharide transporter LptD, in gram-negative bacteria. The authors have discovered that, in addition to proteolytic activity, BepA has a chaperone-like activity and that BepA-mediated quality control of LptD and likely other OMPs occurs during their membrane insertion at the barrel assembly machinery. This result provides new insights into the biogenesis mechanisms of bacterial OMPs and the maintenance of OM integrity.

(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 manuscript is of interest to researchers interested in specification and differentiation of the neural crest. This work presents a small single-cell RNAseq dataset from zebrafish trunk neural crest cells during the early stages of migration that identifies the subpopulations of trunk neural crest cells, new genetic markers and a subset of Rohon-Beard neurons. The paper confirms and extends previous work and reports expression of differentiated pigment cell types in the pre-migratory neural crest populations.

(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 describes a newly developed, publicly available algorithm (iROAR) that was tested on pre-exisiting datasets and is of interest to T and B cell immunologists who perform repertoire analysis via multiplex PCR based techniques. iROAR utilises naturally occurring non-functional sequences to improve and partially correct the amplification bias inherent in multiplex PCR based sequencing technologies.

(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 psychologists and neuroscientist investigating systems memory consolidation. It describes an experimental protocol that allows precise, quantitative behavioural measurements to assess the development and interactions of item and gist memory traces over extended time periods. The study design and hypotheses are elegant and bring together ideas from several other fields of cognitive psychology (working memory, category learning). However, additional analyses, and in particular, comparison of some simple computational models, are needed before the conclusions are justified.

(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 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

This study investigates the effect of copy number variants across all genes in Saccharomyces cerevisiae, and the variation across different genetic backgrounds. Interestingly, apart from universal effects common to most of the genetic backgrounds, the authors also report strain-specific effects related to gene copy number variants.

(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 will be of interest to a wide range of systems neuroscientists seeking to understanding the relationship between neuronal activity and behavior. Building on previous technical advances in brain-wide imaging of neuronal activity (Ca signals) in freely moving animals (Caenorhabditis elegans), it demonstrates that a linear regression model is sufficient reconstruct key parameters of locomotion - velocity and body curvature - from the imaging data and documents differences in activity between freely moving and immobilized worms.

(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.)