Evaluated articles

Evaluation Summary:

This manuscript models a particular class of genetic lesions observed in the imprinting disorder and overgrowth syndrome, Beckwith-Wiedemann syndrome (BWS), using a highly tractable mouse model. Because more than one gene is abnormally expressed in BWS that is caused by loss of imprinting of H19 and IGF2, the authors vary the expression of both genes to investigate the source of the cardiovascular phenotypes and are able to ascribe independent heart phenotypes resulting from IGF2 overexpression and H19 loss of expression.

(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:

Lamm and colleagues explore brain dynamics of empathy in response to facial expressions of simulated versus genuine pain in others. Using a novel experimental fMRI task and dynamic causal modelling, the findings suggest that activation of the anterior insula for genuine pain reflects affect sharing rather than automatic responses triggered by the perceptual salience of events. The paper is of broad interest to an audience of social and affective neuroscientists interested in how humans track the emotional responses of others.

(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:

Martín-Fernández et al. show that Nrp1 acts within the primary somatosensory cortex to control the refinement of axons and the topography of contralateral targeting, particularly with regards to homotopic "matching" of gradients. While this action of Nrp1 has already been discovered between cortical areas, this work elucidates its role within a cortical area, with further insight into the developmental dynamics of projection and refinement also reported. This is impactful to the field of cortical axon guidance and corpus callosum development. The data analysis is rigorous and most conclusions are justified 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Here authors present a robust, high-throughput and genome-wide strategy to identify genes that influence protein localization in individual subcellular compartments. The results profile subsets of genes that are involved in localization of tail-anchored proteins to mitochondrial and endoplasmic reticulum membranes and identify several unexpected regulators. This new tool is adaptable to studying various types of protein trafficking processes to shed light on their molecular 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 #1, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Evaluation Summary:

The paper describes novel structures of a protein recently reported to function as a mechanosensitive ion channel. Surprisingly, the structures and functional data rather support the formerly suggested role of this protein in lipid metabolism. The paper is of relevance for ion channel field and for those interested in fatty acid metabolism.

(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:

Opioids are widely used as pain killers, but present the severe side-effect of respiratory depression. The study from Baertsch et al. provides a mechanistic understanding of the actions of opioids on breathing by elucidating some of the biophysical and synaptic mechanisms by which opioids depress breathing with the goal of identifying therapeutic strategies. The data suggest that opioid-induced respiratory depression (OIRD) is due to both presynaptic hyperpolarization, and reduction of synaptic efficacy. The paper is generally well written and the data presented for the most part advances understanding of the mechanisms of OIRD at the level of central respiratory neural circuits.

(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:

This paper will be of interest to scientists within the field of chromosome biology. The authors take advantage of the Xenopus egg cell free system and combine classical morphological analyses by immunofluorescence with chromosome conformation (Hi-C) analyses to elucidate the contribution of linker histone H1 to mitotic chromosome organization. The authors find that linker histone H1 limits the association of condensin and topoisomerase II to control chromosome length.

(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 applies single-molecule the nanomechanical DNA manipulation together with the direct fluorescent visualization to examine the mechanism of assembly of bacterial partition/segregation complexes by the ParB protein and the ensuing condensation of parS-containing DNA. The experiments specifically show how this assembly and its DNA specificity are promoted by CTP. The authors convincingly show that following association at ParS, CTP-binding allowed ParB to diffusively spread along the DNA. ParB spreading along the DNA was in turn the prerequisite for DNA condensation mediated by this protein. Upon clarification of the ParB diffusive spreading mechanism and its activity under physiological circumstances, this study will be of broad interest to those studying protein-DNA interactions and cell division. The nanomechanical DNA condensation experiments together with the combined direct fluorescent visualization represent a helpful methodological development for future studies of this and similar systems.

(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 excellent manuscript combines molecular, anatomical and behavioral methods to characterize neuron types in the mouse superior colliculus. It will likely be a significant resource to those who study how these circuits integrate sensory information to promote motor output. A diverse set of experiments supports the conclusion that the superior colliculus includes separate circuit modules involved in distinct behaviors: prey capture and predator escape.

(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 investigates the relationship between neuronal spiking and local field potential (LFP) activity recorded on micro-electrodes, and intracranial EEG activity recorded on macro-electrodes using a data from human patients with epilepsy. The dataset is rare and unique in that it is from the human brain and recording neural activity from multiple scales (single neuron, LFP, iEEG) within the same subjects. The study tackles important questions with regards to how ripples relate to broadband LFP activity as well as single neurons in the human brain. This results will be of interest to a broad audience of neuroscientists, and particularly to readers in the field of memory as well as those who perform electrophysiology.

(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:

The manuscript reports the cryoEM structure of a functional E. coli respiratory complex I (proton-pumping NADH-ubiquinone oxidoreductase) reconstituted in lipid nano-discs. The reconstructions and models presented by the authors indicate interesting E. coli specific features of the complex, although there are some concerns about model accuracy. Overall this can be a major advance for the structure of this important respiratory complex from a key model organism.

(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 describes how a small plasmid containing a quinolone resistance determinant changes the cellular response to sub-inhibitory concentrations of Tobramycin. Authors have found that Escherichia coli cells carrying this plasmid undergo nitrosative stress mediated by two previously uncharacterized genes, which leads to induction of the SOS response, a well described stress response in bacteria. These findings are relevant for readers across the microbiology and genetics 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 agreed to share their name with the authors.)

Evaluation Summary:

This study considers how HIV evolutionary dynamics in a multiple drug-treated individual can give rise to the clinical patterns of the accrual of drug resistance mutations, including with understandings of the pharmacokinetics of the drugs in the body to help explain some of the patterns. The subject is of importance both clinically – for the optimal treatment choice for people living with HIV – and scientifically, due to the potential to predict and interpret evolutionary trajectories.

(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:

This is a careful and systematic simulation study that convincingly illustrates a role for intrinsic resonance properties in suppressing the effects of cellular and network heterogeneities in a continuous attractor network model of grid cell firing patterns. The study shows that overly simplified models of neurons can lead to fragility in important network level behaviour and that intrinsic neuronal properties strongly influence relevant network level dynamics. This an important result that likely applies to a broad range of network models. Further investigation into the mechanism, possibly using a simplified model, would substantiate the simulation results and fully exploit the power of models in providing intuition and illustrating the generality of the observations.

(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 article represents a series of behavioral and imaging experiments investigating the effect of cognitive manipulation of beliefs on the explicit perception of other individual's pain and altruistic behavior. The results indicate that manipulations of people's beliefs regarding how much another person suffers alters the way participants rate the pain of others as well as the amount of money participants are willing to donate to the other person. Neuroimaging experiments, using EEG and fMRI, show that manipulating beliefs modulates neural activity in an early time window (P2 component) in response to the emotional expression of the other individual, involving temporo-parietal and medial frontal cortices. While there are some potential concerns about the novelty and implication of these findings, the results are overall clear and consistent throughout the six experiments, integrate with existing data, and are of broad interest to the researchers studying the neurobiology of empathy.

(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 manuscript is of interest to virologists working on SARS-CoV-2, as well as biochemists and biophysicists who perform binding experiments with surface plasmon resonance (SPR), as it provides detailed affinity and kinetics analysis of the effect of mutations in variants of concern in the SARS-CoV-2 receptor binding domain with receptor ACE2 and two 'common' mutations in ACE2.

(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:

Bridges et al., present a timely study on an adhesion G-protein coupled receptor known as GPR1116, which is an important regulator of lung function. The authors performed extensive mutagenesis and functional studies to characterize the structural determinants controlling GPR116 activity. With some additional controls, the conclusions of this study would have far-reaching implications for the development of pharmacological approaches aimed at modulating the activity of this important biological target involved in the maintenance of normal pulmonary functions.

(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:

Garrido-Gomez et al generate a unique dataset profiling the transcriptomes late-stage endometrium of women with prior pregnancies leading to severe preeclampsia (sPE) compared to that of non-preeclamptic pregnancies. Although the question of molecular drivers preeclampsia has been explored at the molecular level directly in the placenta, this study provides a unique view in the endometrium of women years after the pregnancy in question, which is consistent with the fact that a previous preeclamptic pregnancy is one of the best predictors for a subsequent preeclamptic pregnancy.

(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:

After more than 20 years of intensive research the molecular machinery of Resurgent Currents (INaR), a non-canonical identity of currents mediated by voltage-activated sodium channels is still a mystery. In this paper, Ransdell and colleagues advance the conceptual framework with new experimental insight and a new kinetic model of INaR.

(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:

The paper is of interest for those studying tendon development. Starting from a transcriptomic analysis of Drosophila leg tendon cells it identifies a transcription factor, Dar1, required for normal tendon morphogenesis.

(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.)