Evaluated articles

Evaluation Summary:

This study by Wang et al. used a series of carefully designed behavioral experiments to convincingly demonstrate that the attentional blink (AB) could be modulated by higher-order rhythmic regularity. EEG results further support the link between the elicited neural entrainment and the AB modulation effect. They propose that the rhythmic context implements a second-order temporal structure to the first-order regularities posited in dynamic attention theory.

(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:

Binding of cargo to sorting receptors in membrane trafficking is essential to cellular organization. This work is significant because it generates a detailed model of the key residues accounting for specificity and affinity of binding by the KDEL receptor. Interestingly, it is not the affinity per se that accounts for the specificity of cargo binding but rather charge-based exclusion of potentially competing signals.

(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 identifies and describes the functional properties of antennal lobe output neurons towards the response to pheromone odors in the moth brain. This paper will be of interest to neuroscientists investigating how sensory information is organized in the brain. Through a combination of technically challenging experiments, the paper identifies the brain regions that differentially process attractive vs aversive olfactory pheromone signals. While not an exhaustive data set, it provides compelling evidence for one model of how the moth brain interprets complex pheromone olfactory odors.

(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 reveals the existence of a novel Notch-containing signaling hub, organized by Sanpodo and Par3, that operates in Notch receptor signaling during cell fate decisions in the peripheral nervous system of Drosophila. These Notch clusters are modulated by components of the Notch signaling pathway, and are proposed to reinforce Notch signaling by concentrating ligands and receptors. These findings are highly relevant to different areas of biology including membrane biology, cytokinesis, PAR polarity, Notch signaling and cell fate decisions 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This is an interesting and thorough study of the developmental roles of the G-coupled protein receptor Adgr6 in spine development that contributes both to the understanding of spine morphogenesis and the etiology of common types of scoliosis that are of unknown origin. Using conditional mouse knockouts, the authors dissect the contributions of Adgr6 in each spine-associated tissue. In addition to the use of state-of-the-art genetic tools, the authors show beautiful histological and tomography data illustrating developmental processes and phenotypes with great detail. Their results also implicate cAMP signaling and CREB activity in the regulation of mechanical properties of dense spine tissues.

(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 is of interest to scientists within the field of motor control and biomechanics studying human locomotion. The work provides evidence for the optimization of muscle function during locomotion depending on the specific biomechanical constraints. The overall methodology is sound and data are properly analyzed, although the in vivo measurements required a complex experimental setup together with sophisticated modeling which on the one hand conclusively support the key claims of the paper for the experiment within this paper, on the other hand weakens the generalizability of the 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. The reviewers remained anonymous to the authors.)

Evaluation Summary:

This manuscript describes the effects of maternal diet-induced obesity on lipid composition in maternal and fetal serum and the fetal heart, and in the fetal heart transcriptome. This study revealed sex-specific effects of obesity during pregnancy. The results presented provide insight into the still poorly understood processes influencing the long-term health of the fetus.

(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 main strength of the manuscript is the data sets generated by the cell type-specific RNA-seq and TRAP-seq in cerebellar PCs that lack Tsc1. In addition, the bioinformatic analysis revealed several interesting findings, including the observation that FMRP target RNAs are reduced in the Tsc1 mutant PCs and that the translational efficiency of these RNAs is actually increased, likely through compensatory 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 #2 agreed to share their name with the authors.)

Evaluation Summary:

Non-canonical pathways for regulating protein synthesis in animals serve important roles for controlling gene expression in critical developmental pathways. Homeobox (Hox) genes encode many mRNAs regulated at the level of translation. A general feature for many of these mRNAs has been the proposal they are regulated by Internal Ribosome Entry Sites and possess sequences in the 5'-untranslated regions of the mRNA that prevent canonical cap-dependent translation, termed "translation inhibitory elements". Here, the authors focus on two Hox mRNAs and find they use entirely different means to achieve the same end of repressing cap-dependent translation. Overall, the experiments support the major conclusions drawn by the authors, and nail down mechanisms that have been left unresolved since the Hox mRNAs were first discovered to be regulated at the level of translation.

(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 revisits an enduring and central question in population genetics known as Lewontin's paradox: that in contrast to the prediction of the field's null model, which suggests that levels of neutral genetic diversity should be proportional to the census population size, in reality, census population sizes span several orders of magnitude more than the approximately three orders of magnitude spanned by levels of genetic diversity. The manuscript provides a nice review of previous work as well as thought-provoking novel analyses. There are also several issues that make it difficult to interpret the new 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 #1 and Reviewer #4 agreed to share their names with the authors.)

Evaluation Summary:

By using mice lacking the hypoxia inducible factor-1α (HIF1α) in NK cells, the study unravels a previously unknown function of this transcription factor in virus control by NK cells. Mechanistically, the authors provided evidence that HIF1α supports survival of NK cells through an efficient glucose metabolism required for optimal NK cell response to viral infection.

(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 contributes to the fundamental understanding of how a cell grows. It provides a broadly applicable method for dry mass measurement of single cells and, using it, it describe how cell density varies accross the cell division cycle. The key finding of this article is the fact that growth in mass and volume seem to be generally uncoupled, leading to significant density changes.

(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 present paper investigated the role of cortico-cerebellar loops in motor control with high density physiological recordings and by using optogenetics to perturb responses of precerebellar neurons in the pontine nuclei during reaching. The study adds to a long line of work supporting the view that the cortico-cerebellar pathway is required for fine motor control. The experiments are well performed, but a number of revisions in analysis and presentation 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 manuscript describes a critical function for interferons (IFNs) in suppression of spontaneous autoinflammatory disease. The inflammatory disease is seen in mice lacking all types (I, II, III) of IFN signaling and is ameliorated by deficiency in interleukin-17 as well as by antibiotic treatment. The latter result implies a role for the microbiota in disease pathogenesis, but it remains unclear whether or how IFNs regulate the microbiota composition, whether this occurs across genetic backgrounds or housing conditions, or how exactly IFN deficiency leads to inflammatory disease. Nevertheless this work demonstrates a critical regulatory function for tonic IFN signaling in suppressing autoinflammation that serves as a foundation for future studies and will be of interest to a broad audience of immunologists.

(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 will be of general interest to neuroscientists, especially those studying how the brain processes itch stimuli and controls itch-related behavior. The authors show that specific cells in the central amygdala (and their communication with other parts of the brain) play an important role in itching (pruritic) behavior. Overall, the authors provides several lines of evidence to support their conclusions.

(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:

Stephani et al. address the question of how ongoing fluctuations in neuronal excitability, as well as stimulus strength, impact the perception of above-threshold tactile stimuli and the subsequent stimulus-evoked brain activity. The results are puzzling in an interesting way, and while the authors provide a nicely parsimonious explanation rooted in the underlying neurophysiology, editors and reviewers think this study has the potential to further motivate many lines of investigation. This manuscript will be of interest mainly to researchers using electrophysiological methods (EEG, MEG, ECoG etc.), as the authors have produced a very high-quality EEG data-set (including uncommon peripheral measurements).

(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 is an interesting and informative study reporting on the molecular features of reversible hair graying in humans and the connection with psychological stress. The study appears to have been very well conducted and the interpretations are generally supported by the data. While the results are primarily correlative at this stage, this work will set the stage for future more mechanistic studies and represents an important conceptual and methodological advance.

(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 manuscript outlines an epidemiological framework to investigate the relative contribution of different hosts and vectors to the initial spread of a zoonotic disease. It focuses on Ross River virus in Brisbane and collates previously published estimates of abundance, biometrics and viral profiles to highlight the most epidemiologically important routes of transmission.

(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 development of single-cell genomic methods has transformed our understanding of cell types and their attributes across organisms. Here, Tarashansky et al develop SAMap (Self-Assembling Manifold mapping), a graph-based data integration method which builds upon their previously described SAM algorithm to facilitate assignment of homologous genes and cell types across diverse species. As the authors show, this empowers comparative analyses across phyla to facilitate cellular annotation and examine the evolutionary origins of cellular diversity. Overall, the manuscript is well-written and the algorithm has the potential to be foundation for comparative cellular atlasing.

(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 present paper addresses the relationship between the electrophysiological and the anatomical connectomes, utilising a method to describe avalances of activity. The editors feel that this work might be pushing the limits of MEG as a modality, since it implies more spatial precision that most would assume possible, which makes the manuscript particularly interesting to M/EEG researchers. While all reviewers agree that the paper has broad interest and the method is promising, some potential concerns have however been raised that compromise the validity of the results. Most importantly: the issue of volume conduction (proximity) driving the results as opposed to anatomical connectivity, which in the worst case could deemed the results trivial. Other confounds, such as the size of the parcels and their SNR, would also require major review.

(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.)