Evaluated articles

Evaluation Summary:

The paper is of interest to RNA biologists, especially to those who study small RNAs. The findings deepen our understanding of the rules of DCL3 dicing and explain how 23-nt and 24-nt siRNAs in the RNA-directed DNA methylation pathway are produced. Overall, the data are of high quality and support the paper's 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

This contribution is of interest to molecular phylogeny scientists in particular and to a broad public interested in early evolution in general, as it confirms the long-standing (but recently challenged) assumption that bacteria and archaea are separated by a long branch. It elegantly rebuts a recent study claiming that one of the common markers used for molecular evolution, ribosomal proteins, are actually ill-suited for deep phylogenies and that archaea and bacteria are much closer to each other than previously thought.

(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 authors show that a widely arborizing inhibitory interneuron AL reduces the variability of olfactory responses in at Drosophila Kenyon postsynapses in the mushroom body calyx, which receive inputs from the projection neurons (PNs) in the antennal lobe. The data support a model in which APL neurons, which also receive inputs from PNs, mediate scaled GABAergic feedback to normalize of postsynaptic responses in the calyx. The conclusions, based on detailed analysis of one odorant are mostly well supported 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:

Ribosomal proteins are prone to aggregation. This work provides strong experimental support for a novel mechanism by which the level of the mRNA encoding two different ribosomal proteins is fine-tuned by variation in the abundance or availability of their chaperones. This regulation is proposed to operate through mRNA degradation at the translating ribosome. The data are extensive - from genetic observations that hint at the existence of a feedback loop, through interaction mechanisms, to biological significance. The logical links between the different steps in the analysis are clear, sound and well set out. The conclusions are unanticipated, but convincingly supported and very likely relevant and important for other systems beyond yeast.

(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 name with the authors.)

Evaluation Summary:

This study gives us information about the potential of the endocannabinoid system to become a novel target for the treatment of Williams-Beuren syndrome. The authors found there is an alteration of brain cannabinoid type-1 receptor (CB1R) in a mouse model of Williams-Beuren syndrome (CD mice). Modulation of CB1R by JZL184 treatment improved social and cognitive phenotypes and also cardiac function of CD mice. This study will be of great interest to researchers and clinicians in the field of genetic diseases.

(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 well-executed study looks at the association of urinary metabolites to the types of diets consumed by European children. Using NMR they find four metabolites that are predictive of a Mediterranean diet. This presents both an approach additional to traditional dietary questionnaire methods and potential insights into biological pathways and will be of interest to nutritionists and epidemiologists.

(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 reviewer remained anonymous to the authors.)

Evaluation Summary:

By revealing different conformational landscapes of EGFR when responding to different types of ligands, this study significantly advances our understanding the structural basis for how EGFR generates distinct downstream signaling in response to different types of ligands. This study represents an important advance in the field and paves the way for the comprehensive understanding of structural mechanisms underlying biased agonism in EGFR and other RTKs.

(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:

The authors comprehensively dissected the ontogeny and characteristics of thymic macrophages. These findings are helpful for better understanding of the function of macrophages in thymic tissue environment.

(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 examines whether binding antibodies that cross-react with the spikes of diverse coronaviruses are elicited by SARS-CoV-2 infection. The manuscript is well written, and the figures are laid out in an easy to interpret manner. This study will be of interest to those who are interested in developing pan coronavirus vaccines.

(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:

All three reviewers are in agreement that the study is of potential interest in the field of ER/PR signaling and endometrial cancer and that it contains significant amount of genomic data. However, functional data linking PAX2 to the PR/ER pathway are lacking, and the study is limited to a single model cell line and thus has a relatively narrow scope. There is also a concern that ChIP-seq data appear to be from a single, unreplicated experiment.

(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 present work aims to increase our understanding of marine epizootics caused by the dinoflagelate parasite Hematodinium sp. in crabs. The work includes a large data set of field collected specimens from a wide geographical area. The authors have evaluated presence or absence of this parasite as well as co-infections by several other groups of pathogens and model the main factors that shape crab community structure. The topic of study is very important in the context of current marine pandemics and, therefore, adequate examination of this data set may lead to significant advances in the field. Refinement of the approaches to produce quantitative data is needed in order to reach to more solid 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript addresses outstanding questions about the molecular mechanisms by which the two types of arginine-methylating enzymes affect the processing and fate of transcripts in mammalian cells. This work makes important inroads into these questions, uncovering an inverse effect of the two types of enzymes on intron retention during post-transcriptional splicing, linking the effects to specific target proteins. With better support of some key claims , the paper will provide a lot of new information about the functional consequences of asymmetric and symmetric demethylation.

(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 will be of interest to evolutionary biologists and geneticists, particularly those interested in the evolution of sex determination and sexual conflicts. It provides an unprecedented dataset that enables the authors to show convincingly the presence of three different Y-chromosomes segregating within a species, differential presence of the Ys among ecomorphs, and identifies candidate sex determination genes on the different Ys. Examination of the impact of genetic sex on a male fitness proxy in ecological context provides a compelling case study to explain the stable maintenance of multiple genetic sex determination systems in a species.

(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 name with the authors.)

Evaluation Summary:

The cyst-forming stages of Toxoplasma gondii that perpetuate chonic infections in more than a quarter of the world's human population exist in a metabolically quiescent state. This study provides evidence that metabolic quiescence in bradyzoite cysts is associated with a profound dampening of calcium signalling, including uptake and release from internal stores, which is reversed following bradyzoite egress and exposure to exogenous calcium and carbon sources.

(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 name with the authors.)

Evaluation Summary:

The authors have used the UK bio-bank with sophisticated statistical modeling to predict the risk of type 2 diabetes mellitus development. Prognosis and early detection of diabetes are key factors in clinical practice and the current data suggest a new machine-learning based algorithm that further advances our ability to prevent diabetes.

(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:

Regulation of morphogen diffusion that controls tissue patterning is an important issue in developmental biology. The study deals with the mechanisms that establishes the Wnt gradient combining a mathematical model and experiments considering multiple extracellular components such as receptor and diffusible antagonist. The study revealed that the ligand/receptor feedback enables robust and quick formation of the morphogen gradient and that the diffusible antagonist also plays a role in this process. With some strengthening of experimental data and better explanation of the modeling, this study will be a useful contribution to 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. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

This study investigates the morphological features of dopaminergic (DA) axons in the Nucleus Accumbens using serial electron microscopy (EM) reconstructions of genetically labelled DA axons. The authors report that DA axons (1) show extremely sparse classical synapses, (2) have varicosities with highly diverse vesicle content, and (3) undergo strong remodelling upon exposing mice to cocaine. The volume EM data set on DA axons presented is valuable. The present findings are suggestive of a mode of dopamine signaling that does not involve classical synapses and are potentially important for understanding the biology of DA neurons, whose dysfunctions have consequences on neurological disorders from Parkinson's disease to schizophrenia.

(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 is a very interesting manuscript describing the changes of neurite position in a complex neuropil during development. The experimental system is well chosen because AIB's function within the circuit requires its neurite to be in two different neuropil "neighborhoods". The manuscript includes some technically difficult experiments of imaging neurite outgrowth in C. elegans embryos. The surprising finding here is that neurite position is not solely dependent on its growth cone navigation. In the case of the AIB neuron, the growth cone is anchored after it reaches its destination point and then a segment of the neurite shifts direction towards its final position through a zippering action. They also show that this shift in position is driven by adhesion molecules SYG-1 and SYG-2.

(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 will be of high interest to a broad audience of neuroscientists, as it provides a major advancement of our understanding of cortical circuits. The quality and quantitative nature of the neuroanatomical reconstructions at synaptic resolution are remarkable. Complementing the reconstructions with computational modeling and activity measurements, the study proposes a likely circuit function for a specific inhibitory cell type during 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. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

This paper is of interest to biochemists and those focused on development of novel antibiotics. The authors present two small molecules that specifically target the essential ribonucleotide reductase of the causative agent of gonorrhea, with biochemical, biophysical, and biological data supporting the efficacy of these molecules both in vitro and in mouse models. Overall, this is a comprehensive study providing some interesting insights to guide the development of new therapies for malaria.

(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.)