Evaluated articles

Evaluation Summary:

This study examined the nature of projections from the prefrontal cortex (PFC) to the nucleus accumbens (NAc) and to the ventral tegmental area (VTA). The authors show that PFC projections to NAc and VTA are largely non-overlapping, originate in different layers of PFC, and express different molecular markers. This study provides high-quality data to the long-standing question.

(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 tests the potential of using a combination of mosquito-based approaches, transgenesis and paratransgenesis, for malaria control relative to the use of the individual technologies. The results show that a combination of approaches can be more powerful at preventing the transmission of malaria parasites, opening the possibility of using similar combination approaches to reduce the malaria burden. The findings will be interesting for a broad audience of mosquito biologists and malaria researchers, but as they are limited to a specific transgenic-paratransgenic combination, more work will be needed to determine the true potential of this strategy for disease control.

(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 unexpected observation of selenium exchange into an iron-sulfur cluster cofactor of a component of nitrogenase. The work sets the stage for future mechanistic study of this phenomenon. It also provides a roadmap for the study of sulfide exchange in other classes of iron-sulfur cluster enzymes.

(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 by Luo et al. showed that the cytokine receptor DR3 is selectively expressed on thymic NKT17 cells and DR3 ligation leads to the activation of NKT17 cells in the thymus. Overall, The presented experiment are properly executed, controlled and presented. The finding that DR3 acts as a costimulatory molecule for thymic NKT17 cells is interesting. The mechanism and the functional relevance of this finding remain wanting.

(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:

By using single-cell RNA sequencing, elegant computational approaches, protein validation, and in vitro functional assays, this study characterizes the cellular composition and gene expression profiles of the human placenta in mid-gestation. The findings and dataset provided by the authors represent an important resource for readers interested in human development and placenta biology. However, conclusions require additional experimental support.

(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 interest to cell biologists studying the mechanism of asymmetric cell division and its diversity across species. Building on their earlier work, the authors show that that there is considerable variability in the mechanics of the spindle among six nematode species studied here. While the authors' main conclusion is plausible - that spindle oscillations require high force and low viscosity - stronger support by the data would be needed.

(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 is an extension of previous work by the same authors, which established a two step high-throughput screening approach to monitor germination and growth of fungal spores of the human pathogen Cryptococcus neoformans and identified an FDA-approved drug with antifungal activity (DOI: 10.1128/AAC.00994-19). The current work extends this approach to three libraries of drug-like molecules comprising 75,000 candidate compounds and employs automated image analysis methods to identify classes of inhibition phenotypes. The key result of this work is the identification of 191 inhibitors, of which 76 could be grouped in to 8 classes based on chemical structure - inhibitors that share structural similarities tend to share phenotypic impact.

(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 demonstrates an inactive protease in Pseudomonas aeruginosa, CtpA, is regulated by am outer membrane lipoprotein LbcA. Using crystallization and EM strategies, they also provide a complex structure; however, the precise mechanism of regulation is speculative due to the flexible arrangement of protein domains.

(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 demonstrates that a cysteine residue (C152) in the vWA domain of the type-iV pili tip-associated protein, PilY1 impacts surface sensing, biofilm formation and cyclic-di-GMP signaling in Pseduomonas aeruginosa. Well-executed experiments provide insight into the events that initiate cell adhesion and colonisation, the understanding of which has important implications for human health. The work will be of interest to microbiologists in general.

(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 timely and important for all scientists and policymakers with an interest in producing, using or interpreting estimates of the effective reproductive number, R, as an indicator of epidemic growth when case counts are low (e.g. at the very beginning or end of an epidemic). However, the utility and accuracy of these methods is not evaluated in the context of less-than-ideal surveillance, including time-varying case observation and long delays, which is currently the case in most countries and they fail to evaluate the performance of the metrics in real time.

(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 is of broad interest to readers interested in heterogeneity in immune cell populations with single-cell RNA sequencing, and for students of human T cell biology. It uses and reanalyses published single-cell RNA sequencing data dataset for this purpose. However, it does not adequately address major technical concerns, and therefore the interpretations are not robustly supported.

(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 shows that it is possible to detect high-abundance peptide antigens in nerve cells at the electron microscope (EM) level in sections of formaldehyde-fixed monkey brain after the sections have been stored for several years in an antifreeze solution in the freezer. The topic of utilizing formalin fixed tissue for research, especially with the numerous "brain banks" worldwide, is an important topic especially if one wishes to conduct studies in post mortem human tissue. The authors used antibodies to detect the presence of vasopressin gene-related products (i.e., neurophysin II and copeptin) in the hypothalamus and pituitary of the monkey brain. This paper is of interest to anatomists who work on AVP neurons in non-human primate. Due to issues with tissue quality, methodology and interpretation, the experimental approach described in this paper may not be as useful for studying fixed and archived brain sections as the authors conclude.

(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 uses social media data (namely twitter) to analyse factors of covid-vaccine acceptance. It first trains a classifier to detect whether a tweets pro-vaccine, neutral, or against. Using then a large corpus of accounts, it investigates multiple factors explaining this position in a light counterfactual analysis. The central finding is that the most socioeconomically disadvantaged groups are more likely to hold polarized opinions on COVID-19 vaccines; other findings inclduing that personal pandemic experience has an important impact on acceptance, or that interest in politics modulates acceptance. This study a good example of what machine learning can do with social media data; however it is also a good example of the high data-demands and limitations of a machine learning approach. The correlations found are plausible but the causal implications are not evidenced strongly enough to guide public policy.

(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 paper addresses a subject of potential great interest regarding the evolution of gene regulation and of enhancer landscapes. Available chromatin looping and gene expression data in mouse and human are analyzed to compare diverse properties of genome-wide promoter-centered maps, including associations with gene expression. It is shown that there is conservation of regulatory landscape across the two species, and that the extent of conservation in the TSS-distal landscape is associated with gene expression similarities. These overall results are in agreement with a large body of work in the 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.The reviewers remained anonymous to the authors.)

Evaluation Summary:

This manuscript extends the evidence that ribosomal DNA has substantial interindividual variation, and presents evidence that variants are associated with differences in DNA methylation. The authors show that some rDNA types respond to environmental signals during in utero development, whereas others are changed during the aging process - thus broadening the known communication between development/nutrition/aging and the cellular protein synthesis machinery. These findings have relevance for the influence of such epialleles on gene expression and disease risk.

(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 reports a new approach to the important and challenging problem of predicting T cell receptor:peptide-MHC interactions, one that relies on molecular model building (with previously published tools) followed by feature extraction and machine learning. The strengths of the study are more conceptual than practical: the overall framework and analytical approach; a balanced, critical assessment of the method's performance (which does not shy away from negative results); some observations on TCR:pMHC docking geometry. On the practical side, the classifier does not appear to generalize well to unseen epitopes (neither do the published tools it's compared to), so at the end of the day it's not clear that it will be preferable to simpler sequence-based 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:

In this study, the authors used a chick and a mouse model and human tissues to analyze the role of the conserved protein TALPID3/KIAA0586, previously linked to ciliogenesis, in gut development. Using a multi-species approach, the authors conclude that TALPID3 has an evolutionary conserved role in regulating gut patterning along the radial axis, apparently orchestrated by neural crest cells in a non-cell-autonomous manner and mediated by perturbation of Sonic Hedgehog signaling and the composition of extracellular matrix.

(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 will be interesting for people performing all optical electrophysiology. It describes a new combination of previously available genetic tools to allow simultaneous optogenetic manipulation and optical electrophysiology. The manuscript does not provide a major conceptual advance but provides good evidence that this assay can be employed for large-scale screening in hIPSC-derived 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:

In their manuscript, Eira et al. investigate the role of transthyretin in promoting axon elongation by modulating microtubule dynamics. The data point to a possible role of transthyretin in regulating microtubule dynamics by modulating tubulin acetylation levels during axon outgrowth. With additional support to strengthen this conclusion, the paper will be of interest to those in the neurodevelopment, neurodegeneration, and microtubule cytoskeleton 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.The reviewers remained anonymous to the authors.)

Evaluation Summary:

This behavioural study in healthy participants examines how people trade-off a brief phasic pain stimulus with a monetary reward, reporting a quadratic effect of pain on decision making. It supports and adds to previous findings of a context-dependency deriving from the distribution of rewards, which is a deviation from conventional rational choice theory (which proposes that a particular level of pain should carry the same price, regardless of small context changes). Broadly, the reviewers found the work well executed and the data compelling, but there were some suggestions for alternative explanations that are not ruled out given the current 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.)