eLife

Latest preprint reviews

1. Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously

   This article has 6 authors:

   1. Christian JG Tessier
   2. Raymond M Sturgeon
   3. Johnathon R Emlaw
   4. Gregory D McCluskey
   5. F Javier Pérez-Areales
   6. Corrie JB daCosta

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper will be of interest to readers interested ligand-gated ion channels and their evolution. The authors show that ancestral AChR beta subunits reconstructed phylogenetically can form homomeric channels that open spontaneously. The work expands our understanding of agonist-independent AChR gating and highlights intriguing aspects of AChR evolution.

     (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.)

   Reviewed by eLife

2. A second DNA binding site on RFC facilitates clamp loading at gapped or nicked DNA

   This article has 4 authors:

   1. Xingchen Liu
   2. Christl Gaubitz
   3. Joshua Pajak
   4. Brian A Kelch

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Replication Factor C (RFC) is known to play a role in both DNA replication and DNA repair by loading a protein clamp called PCNA onto DNA junctions with a 3'-recessed end. The current paper elegantly demonstrates that RFC has a second DNA binding site that recognizes a single strand-double strand DNA with a 5'-recessed junction. The paper reports a series of interesting structures and confirms binding to both short gapped DNA and nicked DNA by RFC, causing local unwinding DNA at the ssDNA/dsDNA junctions. The paper, which is of interest to colleagues studying DNA replication and repair, should be improved through a few clarifications.

     (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.)

   Reviewed by eLife

3. Cytosolic aspartate aminotransferase moonlights as a ribosome-binding modulator of Gcn2 activity during oxidative stress

   This article has 4 authors:

   1. Robert A Crawford
   2. Mark P Ashe
   3. Simon J Hubbard
   4. Graham D Pavitt

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Using mass spectrometry, Crawford et al. identify aspartate aminotransferase 2 (Aat2) as a protein whose polysome-association is increased under oxidative stress in yeast. Aat2 deletion sensitizes yeast to oxidative stress, which is paralleled by an aberrantly elevated integrated stress response, although polysome-association of Aat2 and its effect on oxidative stress response are independent of its aminotransferase activity. This provides evidence that metabolic enzymes may "moonlight" as post-transcriptional regulators. The study will appeal to experts in the fields of biochemistry, genetics, cellular and molecular biology. The presented data mostly support the authors' conclusions, but there are a few technical issues that should be addressed. These include corroborating Aat2:ribosome association and characterizing the effects of non-catalytic Aat2 mutants on the integrated stress response.

     (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.)

   Reviewed by eLife

4. Aminomethanesulfonic acid illuminates the boundary between full and partial agonists of the pentameric glycine receptor

   This article has 5 authors:

   1. Josip Ivica
   2. Hongtao Zhu
   3. Remigijus Lape
   4. Eric Gouaux
   5. Lucia G Sivilotti

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Ivica et al. provide both functional and structural characterization of a relatively unstudied glycine receptor agonist that is structurally in between a full and partial agonist. The combination of cryogenic electron microscopy and electrophysiological approaches allows for complementary structural and functional investigations into the criteria that determine ligand efficacy at the glycine receptor. This manuscript will be of interest to both biophysical and pharmacological investigations of ligand-gated ion channels.

     (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

5. Fuzzy supertertiary interactions within PSD-95 enable ligand binding

   This article has 12 authors:

   1. George L Hamilton
   2. Nabanita Saikia
   3. Sujit Basak
   4. Franceine S Welcome
   5. Fang Wu
   6. Jakub Kubiak
   7. Changcheng Zhang
   8. Yan Hao
   9. Claus AM Seidel
   10. Feng Ding
   11. Hugo Sanabria
   12. Mark E Bowen

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper is of broad interest to investigators studying the function and regulation of protein scaffolds, dynamic protein structure, and the regulation of the postsynaptic density at excitatory synapses. The authors develop an integrated approach using fluorescence-based biochemical methods, disulfide mapping, and discrete molecular dynamic simulations to study the dynamic supertertiary conformation of the synaptic scaffold protein PSD95.

     (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.)

   Reviewed by eLife

6. Neuroscout, a unified platform for generalizable and reproducible fMRI research

   This article has 10 authors:

   1. Alejandro de la Vega
   2. Roberta Rocca
   3. Ross W Blair
   4. Christopher J Markiewicz
   5. Jeff Mentch
   6. James D Kent
   7. Peer Herholz
   8. Satrajit S Ghosh
   9. Russell A Poldrack
   10. Tal Yarkoni

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This paper introduces Neuroscout, a new web-based platform for the analysis of fMRI data with a particular focus on naturalistic stimuli. It describes a new tool that will potentially be of great use to the neuroimaging community, and whose development is already quite mature and has a number of datasets ready to use online. Neuroscout as a tool will be of particular interest to neuroimagers and cognitive neuroscientists, but the conclusions drawn using the tool should be of interest to neuroscientists more broadly.

     (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.)

   Reviewed by eLife

7. Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cells

   This article has 9 authors:

   1. Madeleine L Hart
   2. Evan Quon
   3. Anna-Lena BG Vigil
   4. Ian A Engstrom
   5. Oliver J Newsom
   6. Kristian Davidsen
   7. Pia Hoellerbauer
   8. Samantha M Carlisle
   9. Lucas B Sullivan

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     Hart et al show that loss of mitochondrial complex I rescues succinate dehydrogenase deficient (SDH) cells. The experiments are well performed and the phenotype is potentially very interesting to researchers of cancer metabolism. The authors propose that rescue of SDH deficiency by complex I inhibition is caused by an increase in mitochondrial NADH which leads to a restoration of aspartate levels, which in turn rescues proliferation. To support the model, the authors do demonstrate that there are possible correlations of this phenotype to restored aspartate biosynthesis. However, they do not unambiguously establish a mechanism that fully defines how complex I inhibition rescues the proliferation of SDH deficient cells.

     (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

8. The unmitigated profile of COVID-19 infectiousness

   This article has 6 authors:

   1. Ron Sender
   2. Yinon Bar-On
   3. Sang Woo Park
   4. Elad Noor
   5. Jonathan Dushoff
   6. Ron Milo

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     A pathogen's generation interval directly affects estimates of its transmissibility (R), and the period of self-isolation or quarantine needed to prevent transmission. This study shows that the unmitigated generation interval of the original variant of SARS-CoV-2 is several days longer than previously estimated and that interventions have substantially decreased the effective generation interval. These findings improve our ability to model counterfactual intervention-free scenarios. Overall technically sound analyses support the conclusions, and extensive sensitivity analyses show that the findings are robust. However, sampling or ascertainment bias in this relatively small pre-intervention dataset or biased inputs could affect the accuracy of the reported estimates.

     (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.)

   Reviewed by eLife, ScreenIT

9. Rescue of Escherichia coli auxotrophy by de novo small proteins

   This article has 9 authors:

   1. Arianne M Babina
   2. Serhiy Surkov
   3. Weihua Ye
   4. Jon Jerlström-Hultqvist
   5. Mårten Larsson
   6. Erik Holmqvist
   7. Per Jemth
   8. Dan I Andersson
   9. Michael Knopp

   This article has been curated by 1 group:

   • Curated by eLife

     Evaluation Summary:

     This manuscript describes randomly generated small proteins of <50 amino acids that can rescue the growth of an auxotrophic mutant of Escherichia coli. The authors suggest that these proteins function by binding specifically to a regulatory element in the 5' UTR of the his operon RNA, altering RNA structure to increase expression. The study suggests that functional small proteins can evolve de novo and that newly evolved small proteins can function as regulators by binding RNA. This is an exciting idea, but the suggested mechanism involving the binding of the small proteins to RNA requires 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. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

   Reviewed by eLife

10. Semaphorin3F reduces vascular endothelial and smooth muscle cell PI3K activation and decreases neointimal plaque formation

    This article has 20 authors:

    1. Chutima Rattanasopa
    2. David Castano-Mayan
    3. Chengxun Su
    4. Aaron J. Farrugia
    5. Maria Corlianò
    6. Pakhwan Nilcham
    7. Crystal Pang
    8. Monalisa Hota
    9. Koh Ser Mei
    10. Wendy Lee
    11. Dasan Mary Cibi
    12. Atsu Aiba
    13. Manvendra K. Singh
    14. Siew Cheng Wong
    15. Olaf Rotzschke
    16. Alexander Bershadsky
    17. Han Wei Hou
    18. Elisa A. Liehn
    19. Sujoy Ghosh
    20. Roshni R. Singaraja

    This article has been curated by 1 group:

    • Curated by eLife

      Evaluation Summary:

      The authors provide novel evidence that semaphorin signaling (SEMA3F) is engaged in the vascular endothelium and smooth muscle to confer atheroprotection. They show that SEMA3F reduces the activity of key enzyme Phosphoinositide 3-kinase to decrease smooth muscle cell proliferation, migration, and phenotype switching, which contributes to atheroprotection. The study has significant translational potential and yields a new therapeutic target.

      (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