Evaluated articles

Evaluation Summary:

This paper is based on digital reconstruction of a serial EM stack of a larva of the annelid Platynereis and presents a complete 3D map of all desmosomes between somatic muscle cells and their attachment partners. This resource is of interest to scientists in several fields: motor control, high-resolution anatomy, and network analyses. With the first comprehensive and complete mapping of muscle-to-body connectivity through desmosomes in an annelid larva, it has the potential to close a missing link and make progress towards understanding in a "holistic" way how a complex neural circuitry controls an equally complex pattern of movement/behavior.

(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 is an important study that describes a new mechanism by which Regnase-1 is inhibited upon immune activation, which mediates the efficient synthesis of inflammatory mediators whose mRNAs are normally degraded by Regnase-1. The interaction with 14-3-3 presented here was not known before. This provides an alternative mechanism by which inflammatory mRNAs are upregulated by inhibiting degradation via Regnase-1.

(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:

Pöge at al. present a study of the rod outer segment (ROS). These are specialised cilia of rod photoreceptor cells, essential for sensing light cues and initiating the vision process. The authors apply cryo-FIB milling to generate highly preserved rod samples and report high-quality cryo-tomographic data providing new insights into the ultrastructure of the ROS. The work reveals potential molecular scaffolds both in the lumen of the membrane stacks and on the surface of the stack providing the structural basis for ROS crucial ordered ultrastructure. The data presented here will be highly valuable for the field of phototransduction.

(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 paper reports the results of an analysis of the association between maternal exposure to landscape fire smoke during pregnancy and low birthweight of the offspring. Given the increasing number, intensity, and duration of landscape fires across the globe as well as the impact of low birthweight on public health, the manuscript will be of interest to both scientists and policymakers. The size of the study population drawn from 54 low and middle-income countries makes the paper an important contribution to the literature on the adverse health effects of biomass fire smoke.

(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:

Huang et al. address an intriguing question of pigment cell diversification in vertebrates, namely what is the relationship between (yellow) xanthophores and (red) erythrophores. Their data point to a very close relationship between the two cell types, consistent with the view that they are similar cell types differing principally in the details of their pigment biochemistry. The paper will be of interest to scientists across across a range of the many disciplines within pigmentary biology, including developmental biologists, evolutionary biologists, and those who study the chemistry of pigmentation.

(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 manuscript examines how effort is integrated into economic decisions by recording neural activity from the dorsal anterior cingulate cortex (ACC) in monkeys, while requiring animals to choose between different juice types offered in variable amounts and with different action costs. The ACC is a relevant area because some theories have suggested it is important for evaluating or selecting among potential actions during decision-making, although evidence supporting this idea has been inconsistent. The main results provide evidence against the notion that ACC contributes to evaluation of potential actions. Instead, neurons predominantly coded for post-decision variables, such as cost of the chosen target and the juice type of the chosen offer, but not pre-decision variables, such as offer values. This is in contrast to OFC encoding in the same task (and same subjects), in which neurons encoded the effort associated with choice options. The authors conclude that ACC is unique in representing more post-decision variables than OFC, and in its encoding of outcomes in several reference frames (chosen juice, chosen cost, and chosen action). Together, the results are convincing and highlight potentially unique roles of ACC neurons in learning and decision making.

(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 explores the mechanism of vacor toxicity in neurons. The authors provide exciting and definitive data that vacor drives neurodegeneration by direct binding and activation of SARM1, a potent regulator of axon death. The work elucidates the vacor mechanism of action, provides strong in vitro and in vivo data that toxicity is entirely dependent on SARM1, and will advance the field in terms of how we understand vacor-induced toxicity, and provides a new model for testing anti-SARM1 therapeutics.

(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:

Earlier work demonstrated the inhibition of phage infection by aminoglycosides in Mycobacteria. Following up on this prior work, the authors demonstrate that the acetylated form of apramycin retains its anti-phage activity while blocking its antibacterial activity. The authors observed that MgCl abrogated the anti-phage effects of aminoglycosides and that MgCl can inhibit aminoglycoside uptake leading to the conclusion that antibiotic uptake was likely important for the anti-phage effects. Consistent with this conclusion, the initial stages of phage infection (adsorption and DNA injection) were not impacted by the antibiotics.

(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 adds to an emerging story about the role of activity in the formation of callosal connections across the brain. Previous research of the authors' and other labs had shown that overexpressing the potassium channel Kir2.1, which reduces activity levels in the developing cortical network, blocks the formation of callosal connections almost entirely. Here, the authors show that they can use a TET system to switch off the activity of an Kir2.1 to probe when activity might be necessary or sufficient for the formation of callosal connections. The authors find that artificial restoration of activity with DREADS is sufficient to rescue the formation of callosal connections, and that there is a critical period (somewhere between P5-P15) where activity must occur in order for the connections to form within the cortex. Finally, the authors show that when the potassium channel is removed during the critical period, the cortex exhibits activity, but few highly synchronous events. These results indicate that it is activity in general and not specifically highly synchronous activity that is necessary for the final innervation of the callosal cortex.

(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 examines how cells control their size and will be interesting to scientists studying sizing mechanisms throughout biology. Using yeast cells as a model system, the authors show that an activator of the cell division cycle accumulates as cells grow until a threshold level of activator is achieved. The experiments are performed well, and the high-quality data will be useful for others in the field studying this signaling pathway.

(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 is a rigorous study that confirms the existence of functional KATP and dominant oxidative metabolism in several types of juvenile somatosensory cortical neurons. The authors present multiple lines of experimental results examining the effects of lactate on neocortical neuron types. They also report a mechanism by which lactate is likely to enhance neuronal firing. The data is convincing in supporting the conclusions in the manuscript.

(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 work aims to provide insight into the molecular mechanism by which RNA polymerase separates the two strands of DNA, generating a single-stranded template for RNA synthesis. Using single-molecule analysis, the authors examined two conformational transitions taking place during RNA transcription initiation: DNA unwinding and RNAP clamp movements. Pending addition of some important controls, the paper will help to distinguish between two competing hypotheses within the literature. The work will be of relevance to a wide range of researchers interested in the molecular basis of gene expression and gene regulation.

(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:

The paper describes the development of a mechano-chemical model for plant root development. As such, it presents a significant advance relative to other root models that have focussed predominantly on either the mechanical or auxin patterning aspects of root development, as evidenced by the potential of the model to reproduce a series of hormonal and mechanical perturbation experiments. The current conclusion that a set of minimal principles for self-organized root tip patterning is revealed must be moderated, as patterning inputs are essential to produce the reported 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

Mulholland et al show that there is a very close relationship between the development of excitatory and inhibitory networks in the developing cortex. This paper makes an important contribution to our understanding of the structure of inhibition during an early stage in cortical development. It is therefore of great interest to scientists interested in development, and in computation in cortical circuits. The work has been carefully performed and analysed.

(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 paper demonstrates how MRI can be used to mimic histological measures. This is something that the field of MRI has dubbed virtual histology (or MR-histology) for a while, but to my knowledge this paper is the first convincing demonstration that it can be achieved. The paper combines open access mouse histology data from the Allen Institute with their own multimodal post-mortem MRI, and using deep convolutional networks, are able to build models that map MRI data onto multiple histological contrasts. Some of the results are impressive, such as predicting the outcome of histology on mutant shiverer mice.

(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 study uses a novel rodent surgical model for establishing that dual nerve transfer in the upper extremity improves neuromuscular regeneration in comparison to single nerve transfer. The authors provide a detailed description of how the model is developed and they characterize neuromuscular regeneration through nerve crush, neurotomy, behavioral analysis, and retrograde labeling. The nerve transfer method is clearly delineated for researchers to use in future scientific and clinical applications. The evidence clearly support the main study conclusions. Thus, this manuscript is of great interest to readers in the field of peripheral nerve repair and neural interfaces.

(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 name with the authors.)

Evaluation Summary:

The authors addressed the role of a STING ortholog in antimicrobial defense of choanoflagellates. The analysis of the response of the choanoflagellate Monosiga brevicollis to a variety of bacterial species revealed that exposure of M. brevicollis to Pseudomonas aeruginosa conditioned medium results in choanoflagellate death and the authors found that this is dependent on the newly discovered ortholog of STING. Characterization reveals that the STING response can be induced by 2'3' cGAMP, which parallels the activation of STING in diverse species. In addition, the finding that cyclic dinucleotide treatment induces autophagy also has parallels with the effector pathways observed in other organisms. There are a number of strengths as outlined by the Reviewers. First, the development of a Choanaoflagellate model system to study innate immunity, second with the development of genetics for M. brevicollis, third, the demonstration of a functional STING system in one of the closest relatives to animals and fourth, that cell death occurs in response to cyclic dinucleotides.

(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 presents and evaluates a machine learning method for segmenting and annotating animal acoustic communication signals. The paper presents results from applying the method to signals from Drosophila, mice, and songbirds, but the method should be useful for a broad range of researchers who record animal vocalizations. The method appears to be easily generalizable and has high throughput and modest training times.

(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:

By combining real-time closed-loop EEG-TMS and computational modelling, this study ambitiously examined the causal role of prefrontal cortex in resolving perceptual ambiguity. It impressively demonstrates brain-state-dependent effects on bistable perception.

(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 paper uses controlled exposure to territorial intrusion to show that repeated exposure to conflict between groups compromises fitness in social fish. With a host of results relating to fertility, behavior, and parental investment, its findings will increase confidence in the argument that intergroup conflict is an important factor in social evolution. There are several statistical issues that should be addressed to minimize the possibility of false-positive results.

(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.)