Evaluated articles

Evaluation Summary:

This study investigates oculomotor behavior of cortically-blind patients (with lesions in area V1) performing a saccade and ocular following response toward a cued moving target placed either in their intact or in their blind visual field. Whereas perceptual training led to a good recovery of perceptual performance in the blind field, the ocular following response did not appear to benefit from this training. The authors conclude that V1 lesions result in impaired transmission of signals selectively driving the ocular following response. The manuscript is based on a valuable patient dataset, well written and illustrated, and will be of potential interest to a broad readership of vision scientists, neuroscientists, and clinical neurologists. However, some major weaknesses in the analysis and interpretation of data call into question the conclusion that the selective eye movement deficit reveals a true perception-action dissociation.

(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 paper is of potential interest to psychologists and cognitive neuroscientists studying learning, decision-making, belief formation and metacognition. The authors use a clever, elegant task in which people make decisions with or without control over the information they sample, and link the cognitive processes at play to MEG and pupillometry signatures. The key finding is that when participants have control over information sampling (i.e. are seeking information), they need more contradictory evidence in order to switch their choices, and such switches are made with lower confidence. Anticipatory suppression of alpha-band activity in occipital and frontal regions occurred prior to decision switches, while pupil dilation increased post-switch. The authors propose a computational model to account for behavioral differences between conditions. However, some of the conclusions may not be fully supported by the data and alternative interpretations are possible; therefore further analyses are required to bolster the authors' claims.

(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:

In this study, Phillips et al. report the ancient role of Hippo signaling nuclear effector YAP/TAZ/Yorkie ortholog (coYki) in a unicellular organism Capsaspora owczarzaki. Two major advances of this work include development of genome editing in Capsaspora owczarzaki and characterization of a key gene coYki. The authors found that different from Yki's role in multicellular organisms, the coYki does not contribute to cell proliferation. Instead, it affects cell adhesion to extracellular matrix to ensure the spherical shape of the aggregates. Overall, the presentation of this manuscript is clear with a nice logical flow, and this study should be of interest to the evolutionary cell biology 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 agreed to share their name with the authors.)

Evaluation Summary:

The mechanisms of TGF-beta signaling have been intensively investigated. In this study, the authors reveal a novel mechanism of TGF-beta regulation, which suggests a higher order of signaling complexity. With some stronger experimental support, the paper will be of interest to those studying signal transduction.

(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 results in this report are intriguing in providing evidence that differences in codon optimality in mRNAs can underlie tissue-specific differences in expression and that this phenomenon operates in restricting expression of an evolutionarily young endogenous genes to the testis versus ovaries in a manner important for female fertility in the fruit fly. The scientific quality of the work would be further enhanced by additional experiments to determine whether the differences in expression arise primarily at the translational level or also/rather involve altered mRNA turnover or transcription in response to poor codon usage outside of testis and brain.

(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 readers in the fields of DNA repair, DNA-protein interactions and those employing single-molecule techniques. Using single-molecule methods, the authors discovered that RecX exerts its regulatory effect on the RecA filament through two modes of action: i) by promoting RecA dissociation from ssDNA, and ii) by causing a reversible conformational change of the filament. The latter mode of RecX action is novel and of particular interest. The authors present a plausible model of the RecX-RecA-ATP-ssDNA system that could be further validated in future experiments.

(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 is of great interest to a broad group of neuroscientists including those studying plasticity in the nervous system and in neurodevelopmental disorders such as autism. The current work illustrates the importance of protein phosphorylation in regulating a form of homeostatic plasticity known as synaptic scaling, which has been associated with different neurodevelopmental disorders. In particular, the authors provide compelling evidence that the phosphorylation state of one synaptic scaffolding protein, Shank 3, is a necessary part of a complex signaling pathway mediating synaptic scaling and thus could be therapeutically useful for certain associated disorders.

(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 contributes to our understanding of how a diverse and increasing number of activating adaptors allow the dynein motor protein to move a wide range of intracellular cargoes. Here the authors identify a transmembrane protein called KASH5 as the activating adaptor required for dynein to move meiotic chromosomes, a process that facilitates homolog pairing. Overall, the work is well done and will be of interest to the cell biology, cytoskeletal, and meiosis research communities.

(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 provides insight into how phospholipase C gamma (PLCγ1) becomes activated upon binding to phosphorylated receptor tyrosine kinase, with an analysis of PLC γ1 bound to the soluble kinase domain of FGFR1 (FGFR1K) and/or liposomes containing PIP2. The most interesting finding is that regions of the protein far from the FGFR1K binding site increase in exchange upon binding. This is new information for a large protein that is arguably difficult to study, but it conforms to what has been observed in many other autoinhibited systems with similar SH2 and SH3 domains such as kinases. The results will be of interest to structural biologists and cell biologists with interest in the mechanisms leading to the regulation of phospholipase C activity on membranes.

(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 uses a large dataset on alcohol misuse in adolescents that have been followed up for several years. MRI data are used to test whether the structure and connectivity of the brains of adolescents can predict their alcohol misuse later in their early twenties. The results show that binge drinking can be predicted out of multiple brain phenotypes with a good accuracy, even after control for many confound variables. This study can be impactful as it suggests a reevaluation of studies of the effect of alcohol on the adolescent brain.

(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 study uses both humans and rats to demonstrate that the level of glutathione in the nucleus accumbens correlates with effortful behaviors. The authors provide causal evidence for glutathione in rats by manipulating enzymes involved in the synthesis of glutathione. Although how exactly glutathione regulates effort-related behavior remains to be clarified, overall, the study gives convincing evidence for an important role of glutathione in nucleus accumbens in regulating the willingness to invest effort to obtain reward or escape an aversive situation.

(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 broad interest to readers in the fields of cytoskeletal research, muscle biology and heart disease. By utilizing a combination of quantitative biochemical and biophysical experimental approaches, this work provides critical new insights into the molecular mechanisms of understudied mutations in myosin that cause heart disease. The data are rigorously controlled and analyzed and support the claims of the work.

(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 name with the authors.)

Evaluation Summary:

Plant cells can grow to extraordinarily large volumes; Arabidopsis root cells, for example, can expand beyond 50um long. Vacuole expansion is correlated with cell elongation, presumably to "fill up" the volume of the cell without requiring a tremendous volume of cytoplasm. Here, the authors carefully characterize a new small molecule inhibitor of endocytic trafficking to the vacuole. This new tool will be valuable to researchers studying endocytic trafficking and vacuole biogenesis in plants.

(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:

The authors present an automated system for phenotyping root system architecture based on bioluminescent roots resulting from a constitutively expressed luciferase transgene (GLO-Root). They have developed a robotics-assisted phenotyping platform and an automated image analysis pipeline for high throughput analysis. An impressive array of 93 luciferase expressing Arabidopsis thaliana accessions provides a major resource for understanding the genetic basis for root system architecture variation in response to a range of environmental conditions. The work will be of interest to plant biologists and all those studying genetic variation in plants.

(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 broad interest to scientists who study collective cell migration and cytoskeletal dynamics. The findings of this paper connect proteins involved in planar polarity to the actin protrusive machinery which establishes an axes for polarized collective cell migration. The data presented largely supports the claims of the authors who take advantage of quantitative imaging techniques and Drosophila genetics to establish this connection.

(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:

Synaptic connections are crucial for determining neural circuit function and for storing adaptive changes in the brain. This study performs a highly detailed quantitative analysis of certain excitatory connections in mouse neocortex, and finds that the physical size of these connections has a bimodal distribution. This is an important finding that has implications for our understanding of synaptic plasticity and neural circuit dynamics.

(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 paper will be of interest to lung biologists, developmental biologists, and neonatologists interested in lung injury. In this manuscript, the authors used gene expression signatures to construct a gene regulatory network to identify genes associated with alveologenesis. While reviewers were impressed with the novelty of the approach, questions were raised about the robustness of the results in mice and the validation in human samples.

(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:

Neto et al set out to use Two-Photon FLIM and machine learning to classify macrophages that are polarised along the M1/M2 axis and then subjected to different metabolic stresses classically used to distinguish metabolic strategies of different cell states. Additional information is sought regarding the photophysics of the measurements and if there are an adequate number of photons to fairly compare the three conditions. The work will be of interest to immunologists, physiologists interested in metabolism and engineers looking to translate the 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 #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

This manuscript is interesting to a broad audience in the general fields of RNA and structural biology. It provides detailed and important molecular insight into one of the mechanisms by which ATP-fueled RNA helicases can cause the local destabilisation of terminal base-pairs and eventually contribute to RNA structure remodelling and it is a prime example of how crystallographic high-resolution snapshots of conformational intermediates can be combined with sophisticated NMR techniques and assays into a comprehensive model. The manuscript would benefit from a broader and more explicit comparative discussion including the limitations of the proposed model, because DbpA is a rather specialised RNA helicase and because the double-stranded RNA substrates were specifically designed to exclusively investigate unwinding from the side of a short 5'-overhang.

(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, of interest to neuroscientists in the field of memory engrams, presents novel insights to understand the complex functional network connected with the prefrontal cortex that shape memory-related neuronal ensembles and modulate memory formation in a time-dependent manner. The large data set due to the systematic approach yielded transparent, well analyzed, and clearly presented data. Still, the conclusions require additional support and extended discussion.

(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.)