Evaluated articles

Evaluation Summary:

This paper assesses whether transcriptional signatures in antigen-stimulated peripheral blood mononuclear cells can predict protection from clinical malaria after vaccination with RTS,S AS01 in African children. It adds to the large body of literature looking for immune correlates of protection following RTS,S vaccination and will be of interest to the malaria vaccine community and to those studying in systems vaccinology. An association of malaria risk with monocytes before vaccination may have been uncovered, which will require thorough testing in future functional and mechanistic studies.

(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.)

eLife assessment

This fundamental work substantially advances our understanding of the kidney interstitium and how it influences kidney development focusing on zebrafish as a model organism. The evidence supporting the conclusions is compelling, using single-cell analysis combined with in vivo zebrafish studies to mechanistically explore the functional importance of the discovery. The work will be of broad interest to cell and developmental biologists as well as the kidney community.

Evaluation Summary:

The data and analyses presented in this paper are important for understanding the sources and spread of SARS-CoV-2 across Kenya during the first two waves and are a timely contribution to our understanding of the pandemic in East Africa as a whole. The manuscript provides a clear picture of the viral lineages spreading in coastal Kenya, but sampling biases in the Kenyan and global datasets used make it difficult to evaluate conclusions concerning imports and exports of SARS-CoV-2 into and out of Kenya.

(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 is of broad interest in light of the COVID-19 pandemic. Characterization of how glycosylation affects interactions between the viral Spike protein and ACE2 receptor can inform efforts to inhibit the SARS-CoV-2. The molecular modeling and functional analysis need to be improved.

(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 metabolic, genetic, genomic, and electrochemical experiments described for lactic acid bacteria expand on the recent discovery of extracellular electron transfer in Gram Positive bacteria. The ability to shift and/or accelerate metabolism of lactic acid bacteria capable of extracellular electron transfer may have interesting biotechnological applications, but to what extent this impacts their native physiology is not yet clear.

(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 scientists who think about mechanisms of conformational signaling within transmembrane receptor proteins. It describes a model of signaling by allosteric coupling between individual domains rather than by a concerted conformational change and provides substantial experimental evidence for the model from characterization of over 30 mutational substitutions in the bacterial two-component sensor protein PhoQ. The allosteric coupling model provides a way to understand many diverse observations about signaling by two-component receptors and has the potential to be relevant to conformational signaling by many other transmembrane receptors.

(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:

Magnesium is an essential metal that is involved in vital biological processes. Using a model system, the authors discovered the presence of a conformational equilibrium between different unligated states that may explain the mechanism of magnesium transport. The combination of several different approach support the hypothesis that molecular motion is involved in the transport mechanism of Mg2+ ions.

(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 authors describe the innovative use of a heavy-isotope labeling strategy combined with mass spectrometry analysis to investigate the role of peptidoglycan biosynthesis by an L,D-transpeptidase and penicillin binding proteins in Escherichia coli. They use isotopic labeling of the peptidoglycan following by a chase experiment with label to study how new peptidoglycan is assembled into pre-existing peptidoglycan. The data suggests that new material is inserted one strand at the time on the lateral wall while it appears to be inserted as multiple strands at the division septum. The data are novel and provide important insights, together with notable methodological advances. The study will be of interest to microbiologists studying bacterial cell wall turnover and for drug discovery efforts.

(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 by Guzman-Vilca et al. developed a machine learning (ML) tool to estimate the sodium/salt intake in a pooled database of a WHO surveys entailing more than 45,000 people in low- and middle-income countries. Their ML model based on age, sex, weight, height, systolic and diastolic blood pressure values provided a reasonably accurate estimate of the salt/sodium intake in the population in such countries. While waiting for further validation using the gold standard of 24-hour urinary sodium excretion, as reference, this tool can be important for estimating sodium consumption in low-mid income countries, which cannot afford measurements of sodium in the urine.

(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 will be interesting for understanding how the innate and learned components are synchronized and temporally coordinated in courtship behavior. This study gives the first insight into the midbrain dopaminergic region and its' role in courtship 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 #3 agreed to share their name with the authors.)

Evaluation Summary:

The paper describes improvement in muscle phenotype of a congenital myopathy mouse model by a combined treatment with pharmacological inhibitors of Class IIa histone deacetylases and DNA methylases. The paper demonstrates in principle that there are treatment avenues to pursue but their application could be limited as phenotypic rescue appears to be restricted to particular muscle fiber types.

(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 manuscript presents a well-done integrative analysis of data from many genome-wide technologies for the study of replicative senescence, contrasting the data to non-senescence and acute senescence controls. The time-course study design and the combinatorial analyses have revealed many interesting features of senescence that were previously unknown. Data mining by scientists in the future promises to unlock other aspects of senescence biology and hence this study serves as a great resource to the community. This paper and resource will be invaluable not only for researchers specifically studying the molecular biology of cell senescence but should also be more broadly relevant for researchers studying aging, inflamm-aging, cancer, regeneration, and other fields where senescence plays a role.

(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:

Mickolajczyk et al. report the development of a new optical tweezers-based unbinding-force assay to characterize the interaction between the MIDAS domain of the mechanoenzyme Mdn1 and the ubiquitin-like (UBL) domain-containing ribosomal proteins Rsa1 and Ytm1. The authors show that the bond between MIDAS and Rsa1/Ytm1 can be best explained by a catch-slip bond behavior. The observations suggest that catch bonding between MIDAS and UBL domains plays a key role in the Mdn1-mediated ribosomal biogenesis. The reported results will be of interesting for the ribosomal and single-molecule biophysics communities and the developed DNA-tether-based optical tweezers assay will be useful for characterizing other molecular bonds.

(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 in vitro study proposes to explain why branched actin filament networks, similar to the ones encountered in migrating cells, become denser when they grow against a mechanical load. This question is of broad interest, and has long been waiting for a molecular-scale explanation. Building on their previously published tools and results, the authors perform a series of elegant and clever experiments, and convincingly identify key molecular mechanisms. Importantly, the results also confirm the Brownian ratchet model for actin assembly. This study captures several important features of branched filament networks, and should become a reference on the topic.

(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:

Low voltage-activated T-type calcium channels (CaV3.1-3.3) are important for several physiological processes. It is challenging to distinguish their specific physiological / pathophysiological roles as they share similar biophysical properties, expression profiles and there is a lack of subtype selective pharmacology. This study reports a spider toxin, Pn3a, which exhibits 100-fold selectivity for inhibiting CaV3.3 over CaV3.1 and CaV3.2 isoforms, and which therefore makes for an excellent reagent for the physiological study of CaV3.3.

(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:

Zebrafish strains are typically considerably polymorphic. White and colleagues tested the hypothesis that genes in linkage with a mutant allele might show allele-specific expression differences and thus potentially confound the interpretation of mutant effects. Using a variety of mutant and wild-type alleles with sophisticated analysis of RNA-seq data in zebrafish embryos they demonstrate over-representation of gene expression changes from genes that are in linkage with the mutant allele on the same chromosome. The data are extensive, carefully analyzed and of sufficient depth and quality to support their main claim of frequent occurrence of allele-specific gene expression in outcross experiments. These allele-specific expression differences may impact on the interpretation of differential gene expression caused by a specific mutation. The findings of this study will be of interest to genetics working not only with zebrafish, but potentially also other polymorphic 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 and #3 agreed to share their name with the authors.)

Evaluation Summary:

This study presents new evidence that support a model of aCPSF1-dependent transcription termination in Archaea. Archaeal transcription termination is shown to rely on both poly-U tract terminator signals and the endoribonuclease aCPSF1 of the β-CASP family. This mechanism resembles the eukaryal RNAP II termination process. These new insights fill a gap in our understanding of the mechanism of transcription termination in Archaea and they are of general importance for the RNA biology community.

(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 manuscript reports advances in the image analysis software package MorphGraphX (MGX). designed to capture the developmental dynamics of growing tissues at cellular resolution. This version, MGX2.0, includes new tools for precise quantitation of cellular behaviors, such as cell division and expansion, within the context of positional information in the growing organs. To illustrate multiple functionalities of MGX2.0, various tissues are analyzed. This presentation style highlights the power and broad applicability of MGX2.0, but leads to a somewhat disjointed narrative, and how it can provide insight into specific biological questions is less clear.

(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 work uses large-scale genome sequencing and analysis, mass spectrometry and bioassays to investigate the genomic diversity of Pseudomonas strains and their potential role in plant protection. The authors identified a novel group of cyclic lipopeptides that could inhibit Streptomyces scabies, the causal agent of potato scab, and showed how genomic diversity in closely related bacterial strains can contribute to plant pathogen suppression 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 work reveals the pathway by which an important human parasite synthesizes a nuclear hormone receptor ligand critical for progression through its life cycle and demonstrates the potential therapeutic implications of perturbing this pathway. The experiments are insightfully and expertly conceived, designed and executed, and the data support the conclusions. This manuscript will be of general interest to parasitologists, nematode biologists, and those studying transcriptional regulatory networks governed by ligand-gated nuclear receptors.

(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.)