Evaluated articles

Analysis of the PcrA-RNA polymerase complex reveals a helicase interaction motif and a role for PcrA/UvrD helicase in the suppression of R-loops

1. Inigo Urrutia-Irazabal
2. James R Ault
3. Frank Sobott
4. Nigel J Savery
5. Mark S Dillingham

• Curated by eLife

  Evaluation Summary:
  The resolution of R-loops that form during collisions between replication and transcription machineries is crucial for cell survival. This is exemplified by the lethality of deletion of PcrA, a helicase that appears to be involved in the resolution of such collisions. Here, the authors aim to characterize the critical regions of PcrA/RNAP interactions and determine the function of such interactions. The manuscript's structural work is refined, elegant and leaves little room for doubt concerning the importance of the CTD PcrA-RNAP molecular interactions. This work moves the field forward in a meaningful way and unravels key aspects of PcrA/UvrD function with regards to interaction and function on RNAP. It will be of interest across the wide field of protein-DNA interactions, both prokaryotic and eukaryotic.

  (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.)

Reviewed by eLife

SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway

1. Shahanshah Khan
2. Mahnoush S Shafiei
3. Christopher Longoria
4. John W Schoggins
5. Rashmin C Savani
6. Hasan Zaki

• Curated by eLife

  Evaluation Summary:

  The identification of a novel role of the spike protein expressed on SARS-CoV-2 in directly evoking the host inflammatory responses has a substantial impact in understanding the molecular mechanism of COVID-19 pathogenesis, which may have implication for development of new therapeutics. The elegant analytic approach conducted herein justifies the major conclusions of this work though several additional steps can be made to validate these 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.)

Reviewed by eLife, ScreenIT

Genetic variant in 3’ untranslated region of the mouse pycard gene regulates inflammasome activity

1. Brian Ritchey
2. Qimin Hai
3. Juying Han
4. John Barnard
5. Jonathan D Smith

• Curated by eLife

  Evaluation Summary:

  Genetic differences in outbred species such as humans and differences in the epigenomic structure form the basis of the large variability in the immune response. This work demonstrates that a single nucleotide change in the gene encoding for the universal inflammasome adaptor protein ASC regulates mRNA stability of Pycard and thereby inflammasome function. A particular strength of the work is that the authors managed to show, using genetic alterations, that a single SNP in the Pycard gene sequence (rs33183533) between AKR and DBA/2 mice causes variation in inflammasome activity. Given the relevance of inflammasome for various human pathologies, this work is important for a broad readership.

  (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.)

Reviewed by eLife

Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes

1. Sai Srinivas Panapakkam Giridharan
2. Guangming Luo
3. Pilar Rivero-Rios
4. Noah Steinfeld
5. Helene Tronchere
6. Amika Singla
7. Ezra Burstein
8. Daniel D Billadeau
9. Michael A Sutton
10. Lois S Weisman

• Curated by eLife

  Evaluation Summary:

  The authors investigate the role of the PI3P 5-kinase protein (PIKfyve) in endosome to cell surface recycling. They report that PIKfyve function is necessary for cell migration and endsomal recycling of integrin proteins via the SNX17-Retriever pathway. The findings will be of interest to the endosomal research 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Cooperation among c-subunits of FoF1-ATP synthase in rotation-coupled proton translocation

1. Noriyo Mitome
2. Shintaroh Kubo
3. Sumie Ohta
4. Hikaru Takashima
5. Yuto Shigefuji
6. Toru Niina
7. Shoji Takada

• Curated by eLife

  Evaluation Summary:

  This is an interesting manuscript describing for the first time experimentally the cooperative effects of mutations to individual key Glu residues in the c-ring of ATP synthase. The main result is that mutations in nearby c subunits are less inhibitory than those in subunits further apart in the ring. This is explained on the basis of MD/MC simulations as a shared waiting time for delayed proton uptake in case of neighboring subunits, which appears logical. Overall the manuscript is well presented, but with some caveats. The works will be of interest to specialists in bioenergetics, and to a wider biochemical, biophysical and structural biology audience.

  (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.)

Reviewed by eLife

Slow oscillation–spindle coupling strength predicts real-life gross-motor learning in adolescents and adults

1. Michael A Hahn
2. Kathrin Bothe
3. Dominik Heib
4. Manuel Schabus
5. Randolph F Helfrich
6. Kerstin Hoedlmoser

Reviewed by eLife

Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

1. Samuel Kariuki
2. Zoe A Dyson
3. Cecilia Mbae
4. Ronald Ngetich
5. Susan M Kavai
6. Celestine Wairimu
7. Stephen Anyona
8. Naomi Gitau
9. Robert Sanaya Onsare
10. Beatrice Ongandi
11. Sebastian Duchene
12. Mohamed Ali
13. John David Clemens
14. Kathryn E Holt
15. Gordon Dougan

Reviewed by eLife

An oscillating computational model can track pseudo-rhythmic speech by using linguistic predictions

1. Sanne ten Oever
2. Andrea E Martin

• Curated by eLife

  Evaluation Summary:

  The topic is highly interesting and provides new insights to the ongoing debate about the role of oscillations and predictability in speech recognition. The manuscript is of broad interest to readers in the field of speech recognition and neuronal oscillations. Particularly, the authors provide a computational model which additionally to feedforward acoustic input incorporates linguistic predictions as feedback, allowing a fixed oscillator to process non-isochronous speech. The model is tested extensively by applying it to a linguistic corpus, EEG and behavioral data. It explains variations in speech duration based on linguistic predictability, and recently reported phase-dependency of speech perception, supporting the authors claims. The reviewers agreed that this study provides new insights in the current debate about the role of neural oscillations and top-down predictability in speech recognition, and that it represents an important contribution to the field of language neurobiology. Although they thought that the results support the authors' conclusions, the reviewers each raised a number of questions about the modelling and stated that greater clarity is needed in describing this.

  (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 names with the authors.)

Reviewed by eLife

Cis-regulatory variants affect gene expression dynamics in yeast

1. Ching-Hua Shih
2. Justin Fay

• Curated by eLife

  Evaluation Summary:

  The authors use RNAseq in yeast hybrids to study the effect of cis-variation on evolutionary divergence in gene expression and expression dynamics. Importantly, some of the findings are further confirmed using reporter assays. This is a clever and efficient approach that allows obtaining a genome-wide view of how cis-sequence variation affects expression. What sets this study apart from previous work is that the authors use hybrids across different genetic distances, separate expression levels and dynamics by sampling across different time points during an environmental shift, and also investigate 3' sequences. The main conclusions confirm that SNPs and InDels both affect gene expression as well as dynamics, and that on average, InDels have larger effects compared to SNPs, especially on expression dynamics. Moreover, the results also reflect negative selection on expression levels, with the effect of some cis mutations compensated by other cis variation, which ultimately results in complex interactions between the different cis-acting polymorphisms. Together, the results further our understanding of how cis sequence variation supports divergence in gene expression levels and 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation

1. Filip Sobczak
2. Patricia Pais-Roldán
3. Kengo Takahashi
4. Xin Yu

• Curated by eLife

  Evaluation Summary:

  Pupil diameter is used as an index of the brain's arousal system, and has traditionally thought to be a non-invasive index of specific neuromodulatory activity. It is therefore been heavily used as a measure in neuroscience. More recent data suggests a more complex picture whereby a pupil dilation might track cocktail of different neuromodulators. This paper provides firm data supporting this view, and introduces the new view that the make-up of this cocktail changes significantly over time. Pupil dynamics are linked with different neuromodulatory centers over different intervals of time. This is clearly important data across a broad range of human and animal systems neuroscience.

  (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.)

Reviewed by eLife

Rapid spread of a densovirus in a major crop pest following wide-scale adoption of Bt-cotton in China

1. Yutao Xiao
2. Wenjing Li
3. Xianming Yang
4. Pengjun Xu
5. Minghui Jin
6. He Yuan
7. Weigang Zheng
8. Mario Soberón
9. Alejandra Bravo
10. Kenneth Wilson
11. Kongming Wu

• Curated by eLife

  Evaluation Summary:

  This manuscript will be of interest to a broad audience of researchers interested in microbe-insect interactions and how they may affect adaptation to pesticides. It presents data supporting that infection with a mutualistic virus enhances fitness in a moth, and that selection pressure represented by transgenic crops may be driving the spread of this mutualistic infection in Chinese moth populations. Specificially, infection with a densovirus appears to improve the ability of the cotton bollworm to survive on transgenic cotton expressing insecticidal proteins from Bacillus thuringiensis (Bt). The widely-grown Bt-transgenic crops control insect pests with great reductions in chemical insecticides, and anything that could reduce their efficacy is of relevance to the agricultural biotechnology community and to growers. This work suggests that virus infection of the insect pest can have unexpected interactions with the ongoing selection for Bt resistance that threatens the sustainability of Bt-transgenic crops. The impact of the work would be clearer if there was a better distinction between pest resistance (the evolution of increased tolerance due to genetic changes in the pest population) and other mechanisms of increased pest tolerance (e.g., virus 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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection, and cancer therapy

1. Sierra M Barone
2. Alberta GA Paul
3. Lyndsey M Muehling
4. Joanne A Lannigan
5. William W Kwok
6. Ronald B Turner
7. Judith A Woodfolk
8. Jonathan M Irish

• Curated by eLife

  Evaluation Summary:

  The three reviewers were overly positive about the stated goal of your T-REX method to characterize rare populations by cytometry. The potential applications in the context of analyzing antigen-specific T cells (as identified as tetramer-positive cells) were not missed on the reviewers and the use of the 2 timepoints-cohort of samples from rhinovirus-infected patients was judged clever. However, all three reviewers requested some edits and additional tests to really distinguish T-REX from other methods in terms of performance, and to better understand its analysis power. Reviewer #1 enjoined you to clarify the improvements of your method compared to previous methods. Reviewer #2 requested more stringent tests of your methods against functional datasets. Reviewer #3 inquired about corrections for batch effects, the result consistency for repeated down-sampling as well as the scalability of the method (especially when UMAP is being used).

  (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.)

Reviewed by eLife, ScreenIT

A population-level invasion by transposable elements triggers genome expansion in a fungal pathogen

1. Ursula Oggenfuss
2. Thomas Badet
3. Thomas Wicker
4. Fanny E Hartmann
5. Nikhil Kumar Singh
6. Leen Abraham
7. Petteri Karisto
8. Tiziana Vonlanthen
9. Christopher Mundt
10. Bruce A McDonald
11. Daniel Croll

• Curated by eLife

  Evaluation Summary:

  This study is of potential interest to a broad audience on evolutionary and population genomics, particularly scientists studying genome dynamics, including transposable elements (TE) and their evolution. It takes advantage of genomics datasets from a large population of wheat pathogens collected across the globe at different times (decades) to detect ongoing processes of genome expansion and potential selection mediated by TE insertions. The work provides empirical evidence that drastic demographic processes shape TE dynamics in nature and that these contribute to intraspecific variation in genome sizes, recapitulating the well-stablished association between TE content and genome size observed across the diversity of life forms.

  (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 names with the authors.)

Reviewed by eLife

Identification of neural progenitor cells and their progeny reveals long distance migration in the developing octopus brain

1. Astrid Deryckere
2. Ruth Styfhals
3. Ali Murat Elagoz
4. Gregory E Maes
5. Eve Seuntjens

• Curated by eLife

  Evaluation Summary:

  This is a well-presented study on the development of the central nervous system in the octopus O. vulgaris which is of broad interest to scientists in the field of evolutionary developmental biology. The authors provide an excellent in situ gene expression study of neural genes whose expression is conserved in the developing CNS across the animal kingdom. To identify the origin of neural progenitors in the early embryo, the study furthermore includes cell lineage tracing and the analysis of mitotic activity.

  (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.)

Reviewed by eLife

Multiphasic value biases in fast-paced decisions

1. Elaine A Corbett
2. L Alexandra Martinez-Rodriguez
3. Cian Judd
4. Redmond G O'Connell
5. Simon P Kelly

• Curated by eLife

  Evaluation Summary:

  Corbett and colleagues developed a novel experimental framework to account for value biases in fast-paced decisions. For this purpose, they developed detailed computational models of how value biases can alter the decision-making process and used EEG data to constrain the estimation of model parameters and their comparison. In contrast to existing accounts which describe value biases using a single bias mechanism, they found that a more complex and dynamic pattern of mechanisms best explains the EEG and behavioral 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.)

Reviewed by eLife

Convalescent plasma use in the USA was inversely correlated with COVID-19 mortality

1. Arturo Casadevall
2. Quigly Dragotakes
3. Patrick W Johnson
4. Jonathon W Senefeld
5. Stephen A Klassen
6. R Scott Wright
7. Michael J Joyner
8. Nigel Paneth
9. Rickey E Carter

• Curated by eLife

  Evaluation Summary:

  This work is of interest to clinicians, epidemiologists and policy makers as it raises concerns about under-utilization of convalescent plasma (CCP) therapy during the Covid-19 pandemic, which in turn led to an increased number of preventable patient deaths. The authors demonstrate an inverse correlation between CCP use and mortality per admission in the US. They estimate that reduced use of CCP may have resulted in 29,000 to 36,000 excess deaths over the past year in the US.

  (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.)

Reviewed by eLife, ScreenIT

Motor planning under uncertainty

1. Laith Alhussein
2. Maurice A Smith

• Curated by eLife

  Evaluation Summary:

  This study addresses an important debate in the field of motor control: Can motor commands generated under uncertain conditions be better explained as an average of different candidate motor programs, or by a single motor plan that minimizes the expected costs? The paper provides evidence for the latter hypothesis. Previous studies have provided clear evidence against the motor averaging hypothesis, however the present study provides the most elegant and conclusive examination of these two ideas to date. While some of the interpretation, especially of Experiment 2, requires more nuanced consideration, overall we thought the evidence presented supported the key conclusion.

  (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.)

Reviewed by eLife

Assembly of higher-order SMN oligomers is essential for metazoan viability and requires an exposed structural motif present in the YG zipper dimer

1. Kushol Gupta
2. Ying Wen
3. Nisha S Ninan
4. Amanda C Raimer
5. Robert Sharp
6. Ashlyn M Spring
7. Kathryn L Sarachan
8. Meghan C Johnson
9. Gregory D Van Duyne
10. A Gregory Matera

• Curated by eLife

  Summary:

  The manuscript describes a very detailed mutagenesis analysis of the dimerization / oligomerization behavior of the protein Survival Motor Neuron. Mutations in this protein cause Spinal Muscular Atrophy. Analysis of disease causing mutations show a correlation with their impact on oligomerization. A structural model that includes different domains of the protein involved in oligomerization is built from these analyses.

  This analysis is an excellent source for researchers working in the field of SMN proteins. A mechanistic interpretation of how changes in the oligomerization lead to the disease or impact the formation of membraneless organelles, is however missing. Thus, the manuscript provides an enormous amount of important mutational analysis data but does not lead to a significant advancement in our understanding of the disease mechanism.

  (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.)

Reviewed by eLife

Organelle calcium-derived voltage oscillations in pacemaker neurons drive the motor program for food-seeking behavior in Aplysia

1. Alexis Bédécarrats
2. Laura Puygrenier
3. John Castro O'Byrne
4. Quentin Lade
5. John Simmers
6. Romuald Nargeot

• Curated by eLife

  Evaluation Summary:

  In this report the authors demonstrate convincingly that rhythmic activity in neurons that are part of the feeding CPG in Aplysia is generated via an unusual mechanism, organelle-derived intracellular calcium fluxes. The neurons that are studied (B63 neurons) play an important role in triggering cycles of motor activity and previous work from this group has demonstrated that activity in these neurons can be modified by operant conditioning. The paper was very well received by the reviewers who were impressed by the novelty of the mechanism uncovered as a driver of a fictive motor program and thus likely 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 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Quantitative control of noise in mammalian gene expression by dynamic histone regulation

1. Deng Tan
2. Rui Chen
3. Yuejian Mo
4. Shu Gu
5. Jiao Ma
6. Wei Xu
7. Xibin Lu
8. Huiyu He
9. Fan Jiang
10. Weimin Fan
11. Yili Wang
12. Xi Chen
13. Wei Huang

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to biologists who study mechanisms of cell-to-cell variability in gene expression and those who wish to have a tool to alter variability in mammalian cells. Key regulators of gene expression variability in mammalian cells are identified and noise modulation in a synthetic system is shown. The data quality is high. A model for the origin of the observed noise is proposed, but will require some additional experimental evidence.

  (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.)

Reviewed by eLife