JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: Interferon-independent STING signaling promotes resistance to HSV-1 in vivo (2021)

Reviewer #1 (Remarks to the Author):
 The authors have made an attepmt to address the points raised, and some of the data added have
 improved the manuscript. However, I find that the most critical points remain unresolved.
For instance the lack of demonstration of STING-dependent autophagy-dependent antiviral activity
is a critical weakness. The authors base part of their arguement on the Yordy paper, where
autophagy in neurons is demonstrated to exert anti-HSV activity. However, neurons do not
express STING. It is hence not likely that the autophagy response shown to be antiviral is
activated through STING.
In addition, regarding the TBK1 dependence, the authors argue that it is the previous finding or
TBK1-independent STING-driven autophagy by Giu et al that is surprising. However, here the
authors ignore two other papers (Cell Death Differ. 2019 Sep;26(9):1735-1749; EMBO J. 2018 Apr
13;37(8). pii: e97858) also showing TBK1-independent activation of autophagy by STING.
Therefore, the authors need to mechanistically explain their observation.
 Finally, the preliminary data on IRF3/7 DKO mice should be consolicated to a conclusive level and
 integrated into the paper
Reviewer #2 (Remarks to the Author):
Reviewer #3 (Remarks to the Author):
 The authors responded my critiques based on new experiments performed. Therefore, I am
 satisfied with the mansucript revised version. The findings are novel and will open a new avenue to
 define the STING-mediated protection to HSV infection independent of type I IFN.
 The authors responded appropriately to my concerns. It is an interesting study that should be
 published.
Peer review of: Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure (2020)


 

REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The additional studies markedly improved the revised report. Some minor concerns remain. 

1. Please define “n/a” and “e” in Supplementary Figure 1a. 

2. Lines 53-56. Reference #6 deals with shock, not heart failure. 

3. Line 64. The word “algorism” is not the correct word. The authors probably meant “algorithm”. 
According to Wikipedia, informally, an algorithm can be called a "list of steps". By contrast, “algorism 
is the technique of performing basic arithmetic by writing numbers in place value form and applying 
a set of memorized rules and facts to the digits” (according to Wikipedia). 

4. Lines 67-69. Reference 11 cited in this sentence is missing the name of the journal (Nature 
Communications), line 539. 

5. Line 89. Epinephrine, not dopamine, is used with caffeine in reference #13. 

6. Lines 95-72. The phrase “lesser mortality” may be better than “better mortality” in the context of 
the sentence. 

7. Supplementary Tables 1-1 to 1-3. LVFS: fractional is spelled as “fractinal”. 

8. Lines 144-146. Although a couple of papers suggested the existence of D1R in human and rat 
hearts, there have been no reports addressing the physiological and pathophysiological function of 
cardiac D1R. The authors cited three articles. Therefore, the phrase “couple of papers” is not 
appropriate. 

9. The word “labeling” (line 148) is also spelled “labelling” (line 69). 

10. The immunoblot analysis section does not include antibody validation. 

11. The D1R gene in humans is DRD1 (line 334); it is Drd1 in non-humans. 

 

 

 

Reviewer #2 (Remarks to the Author): 

 

I am pleased with the responsiveness of the authors. Significant new data and discussion has been 
added. 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors have completed a thorough rebuttal. My concerns have been addressed. 

Just a few minor points below, to clarify some areas of the manuscript. 

 

1. Fig 1d and 2e. Please clarify in the figure legends that these were from n=1 mice per group. 

 

2. Fig 1d. Is “week 0” actually a sham-operated heart, as currently stated in the legend? Or is this a 
pre-operation heart. Please clarify. 

 

3. Fig 1d. Please show on the figure, is there statistical significance, between sham group and any of 
the other time points (1 week, 2 weeks)? 

 

4. Please add a line in the Methods section to clarify that age differences (i.e. between 8-12 week 
old mice) were limited by using littermate controls. 

 

5. Methods section, Line 194, “and was replaced with fresh one two times per week” this is slightly 
confusing wording, perhaps authors can replace with “and was refreshed twice per week”.
Peer review of: Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by (2019)



 

REVIEWERS' COMMENTS: 

 

Reviewer #2 (Remarks to the Author): 

 

Authors have addressed all previous criticisms. 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors made a good faith effort to address most of my requests. I recommend acceptance of 
the revised manuscript. 

I would encourage the authors in future studies to use more robust metrics of UPR activation. BiP 
levels are great, but xbp1 splicing and IRE1 and PERK phosphorylation are better than antibodies 
against spliced xbp1 protein or downstream targets of eIF2a phosphorylation that are not specific to 
just PERK activation.
Peer review of: Functional 3D architecture in an intrinsically disordered E3 ligase domain facilitates ubiquitin (2019)


REVIEWERS' COMMENTS: 

 

Reviewer #3 (Remarks to the Author): 

 

The authors have provided new information and edited their text in part. Most importantly, the 
omitted analysis is now available in Supplementary Figure 24. This data significantly weakens the 
authors claims that the ∆basic RNF4 has a strong physiological effect. The negative control shows 
that while there is a tiny increase in PML bodies in ∆basic compared to WT, comparison to the RNF4 
knockout shows that ∆basic is as significantly different from knockout as is the wildtype, thereby 
revealing that this mutant is not strongly reducing activity. The region of interest in this paper might 
be part of bringing the substrate to the ligase domain but its absence results in an enzyme that does 
the job nearly as good (3 fold difference in biochemical experiments in Fig. 7 and very low effect in 
cells in Supplementary Fig. 24). It thus remains an open question what drives substrate (SUMO) 
ubiquitination by RNF4 and thereby enables its physiological function.
Peer review of: Real-time tracking reveals catalytic roles for the two DNA binding sites of Rad51 (2020)



REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The revised manuscript has addressed all the concerns raised by this reviewer. Only a few typos as 
below: 
 
1. Page 15, line 29; “Swi5-Sr1” should be “Swi5-Sfr1”. 
2. The figure legend of supplementary Fig 4; “Supplementary Fig. 4b” should be “Supplementary 
Fig. 4” 
3. Figure 1a; the shadow of Arg-257 (L1) and Arg-324/Lys-334 (Site II) is misaligned. 
 
 
 
Reviewer #2 (Remarks to the Author): 
 
Authors have done a fine job addressing the previous critique. 
 
The study adds significantly o our understanding of recombinase mechanisms and publication in 
Nature Communications is fully warranted. 
 
 
 
 
Reviewer #3 (Remarks to the Author): 
 
The authors have addressed all my comments and when appropriate, they have modified existing 
figures and added additional information that has improved the manuscript. I have no hesitation to 
recommend the manuscript for publication in his current format
Peer review of: A non-invasive far-red light-induced split-Cre recombinase system for controllable genome (2020)



Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
In this article, the authors describe a far-red light-induced split CRE (FISC) system. This is an 
undoubtedly useful system and the original version of the article contained compelling data. My 
initial review was overall enthusiastic, asking for some clarification of experimental issues, writing, 
and figures. 
In this revision, the authors have carefully addressed my original comments. Specifically, they 
have: 
• rewritten their description of the various constructs using labeling that will be easier for the 
reader to understand 
• clarified, in some cases with new experiments, questions related to the level of basal/dark 
activation 
• provided new experiments to clarify time-dependent SEAP production mediated by the FISC 
system 
• provided new data on the recombination efficiency mediated by the FISC system 
• quantified the time-dependence of recombination after light exposure 
• provided further information on how their plasmid constructs were optimized and provided 
additional clarifying text regarding their design decisions. 
• added citations to relevant related literature in the introduction 
 
Overall, I am satisfied that the authors have addressed my concerns and overall improved their 
manuscript. It is appropriate for publication in Nature Communications.
Peer review of: Multistable and dynamic CRISPRi-based synthetic circuits (2019)


Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The revised manuscript is indeed improved in many ways and I think the authors probably 
appreciate it as well. The explanation for the bistability based on nonspecific binding seems 
plausible and corroborated by a model. nevertheless the title of the Fig3 might more appropriately 
be: Proposed origin of bistability... 
 
With respect to the sequences I would nevertheless suggest to include the sequences of all 
constructs into the Supplementary material rather than at the Addgene submissions. 
 
The only nonresolved issue for this reviewer are the sustained syncronous oscillations. The 
explanation that this is due to the robust inheritance across several cell divisions seems a bit far 
fetched. Without imposing excessive additional experiments to the authors it should be relatively 
easy to test this hypothesis by a simple experiment: chamber should be seeded by a mix of cells 
from two transfections performed with a certain (say 5 h) delay. If their hypothesis is correct they 
should be able to observe a superposition of two oscillations (with amplitude proportional to each 
cell type fraction), which would make the paper even more interesting. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
This new version of the paper improves upon the previous version in many ways, especially with 
the inclusion of a toggle switch and more standard experimental demonstration that it works. 
Other changes made in response to the reviews seem solid to me. I apologize for not being able to 
write a more thorough review at this time.
Peer review of: Dissecting the sequence determinants for dephosphorylation by the catalytic subunits of (2020)



REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

Authors have done excellent work in responding to my comments and criticism. There are only 
minor issues remain gin to be addressed (numbering refers to numbering of the original comments): 

 

1. The schematic figures in 8d,e are very helpful. Meanwhile two important PP2A phosphoproteome 
studies have been published and for the readers sake it would be useful to shortly comment how the 
results of those studies fit to the authors model (PMID: 32400009, PMID: 32071079). Even though 
this is not a review article, again to help the reader, all such studies cited in the paper could be 
referenced together in the introduction after a sentence like this “Several recent studies have 
identified substrates for PP1 and PP2A by different approaches……” 

 

2. It is still not crystal clear from the title that the study focuses on catalytic subunits, but not on 
holoenzymes. Why not to use the protein names of the catalytic subunits PP1C and PP2AC in the 
title instead of PP1 and PP2A? 

 

8. & 13. Authors effort to respond to these comments by gel filtration analyses is acknowledged. 
However, there is some evidence for shift towards higher molecular weight complexes with 
recombinant PP1c and this should be clearly mentioned in the text. 

 

12. The text in the lines 261-263 is still not quite clear. Why not to write out that you mean e.g. 
kinase target motifs with “motif” as it is explained in the response to me. “…a known motif, such as 
kinase target motif…” 

 

-The manuscript is so full of details and complicated data/interpretations that it would be a great 
favor for the reader if the entire manuscript would be proof-read and edited by a professional 
scientific editing service for maximum clarity 

 

- Next time, please label the figures with figure numbers
Peer review of: Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic (2020)


 

 

REVIEWERS' COMMENTS: 

Reviewer #2 (Remarks to the Author): 

This study immunized the mice and elicited two highly potent serotype-specific neutralizing Abs, 
referred to as 6C5 and 4B10, both of which could neutralize E30 infection efficiently by blocking 
viral binding to its two types of receptors. The SPR assays showed the competitive binding results, 
both 6C5 and 4B10 efficiently prevented E30 attachment to the cell surface and could displace the 
viral particles that had already attached to the cell surface in a dose-dependent manner. Using the 
Cryo-EM micrographs to see the E30 in complex with its NAbs 6C5 and 4B10 and define the key 
amino residues for the antigen-antibody interaction. 
This study is very systematic and well define the specificity of 6C5 and 4B10 to E30. 

1. Through the author’s explanation, it is clearly to understand that destabilization is unlikely to be 
the neutralization mechanism. In addition, the structures of E30 in complex (prepared at low 
temperature) with 6C5/4B10 showed bulk densities for RNA genome inside (supplementary figure 
3), which are similar to those observed in E30 mature virion structure, reflecting that binding of 
6C5/4B10 does not trigger viral RNA release for E30. 
2. The authors have followed the suggestion to set a positive/negative control is required to verify 
the assay well set or not and demonstrate that heat-treatment at 55 ° C for 10 min makes E30 
release RNA genome (supplementary figure 2), which can be detected by the dye SYTO9 at room 
temperature. The positive (heat-treatment) and negative (E30 alone) controls as well as 
experimental groups have been re-analyzed and this information is provided in supplementary 
figure 2. 
3. The authors have modified the labels and provided more details in figure legends to present the 
information clearly supplement figures 1. 
4. Accept with no additional suggestions. 

I would like to encourage the authors continue to find the answer why the enterovirus antigenicity 
is so diverse? where is the highly conserved sequences or epitopes among enterovirus? For future 
universal enterovirus vaccine design.
Peer review of: Structures of Echovirus 30 in complex with its receptors inform a rational prediction for (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

This is a very well written, elegant and an important study on the prevalent enterovirus 
Enterovirus 30, causing difficult outbreaks and infections worldwide. The authors show that Fc 
receptor binding causes a collapse of the hydrophobic pocket indicative of uncoating already at 
neutral conditions, while DAF does not induce the same changes. The observed structural 
comparison of full and empty viruses, and the neutralizing antibodies elicited even by the empty 
viruses give hope of their use for effective and safe vaccine production. The structure-based in-
silico algorithm to evaluate the receptor binding area is a novel tool contributing to evaluation of 
receptor usage of different enteroviruses.ew. 

In the revised manuscript, the authors have satisfactorily answered my questions and comments. 
The paper is now acceptable for publication from my point of view.
Peer review of: Influenza A virus is transmissible via aerosolized fomites (2020)


REVIEWER COMMENTS, second round: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have done an excellent job revising the manuscript. The only thing I would recommend 
additionally is to replace "animal model" in the abstract on two occasions to "guinea pig model". The 
contribution of the newly identified route of transmission has yet to be demonstrated in mice, 
hamsters, pigs, ferrets and other animal models.
Peer review of: NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice (2020)


Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have very well replied to my and in my opinion also the other reviewers‘ concerns and 
revised the manuscript accordingly. I have no further comments and suggest publication of this nice 
and important piece of work in Nature Communications. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The points raised by this reviewer have been satisfactorily addressed. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
Authors made a great effort in addressing my concerns, by editing the manuscript, providing more 
background information on safety issues in work with virus, and they performed new experiments that 
strengthen the conclusion that NS forms amyloid to avoid innate immune response. I recommend to 
publish.
Peer review of: Human norovirus targets enteroendocrine epithelial cells in the small intestine (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
I appreciate the authors’ thoughtful and detailed response to my previous concerns 
about this study. I still have reservations with their assertion that “human 
noroviruses preferentially target epithelial cells” based on these data collected from 
a very small sample size of immunocompromised people. The data for EEC infection 
are novel and convincing, and should open up new lines of investigation into how 
noroviruses cause disease. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have more than adequately addressed the concerns of the reviewers 
and have greatly extended their already significant findings with the inclusion of 
additional data. This reviewer has no further comments. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors have answered my questions satisfactorily. There are a couple of 
additional clarification they can make as noted below: 
 
Supplementary video 1 legend – please provide a legend for the various colors in 
the video. 
 
Extended data Fig 4 – please provide orientation to help the reader understand how 
cells identified as epithelial cells
Peer review of: High flavivirus structural plasticity demonstrated by a non-spherical morphological variant (2020)


 
 
 

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
All my comments have been addressed. 
 
 
Reviewer #2 (Remarks to the Author): 
 
The revised manuscript by Morrone et.al., answers my previous queries satisfactorily. I only 
have a minor comment: Figure 1 has numerous panels referring to different experimental 
conditions and referring to them as 'right' and 'rightmost' makes it a bit hard to follow. It 
would be better if the authors could label each panel and refer to them distinctly.
Peer review of: The architecture and stabilisation of flagellotropic tailed bacteriophages (2020)



REVIEWERS' COMMENTS second round: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have addressed my concerns from the earlier version in an adequate manner. 
 
 
Reviewer #2 (Remarks to the Author): 
 
The revised MS “The architecture and stabilisation of flagellotropic tailed bacteriophages “ is a 
much improved article. Thank you for addressing all referee’s comments with such care (with 
figures, accurate citations, etc.). Very impressive and very much appreciated! 
 
I have only two minor comments. Both are carryovers from the previous version. 
1) The figure showing the crystal structure of the free capsomer subunit (Fig. 2b) is tiny. Smaller 
than a postmark it seems. This is rather unfortunate. This compact form of MCP has to be shown 
on a much larger scale. The differences between the free and shell-embedded conformations of the 
MCP must be discussed in greater detail. Would it be possible to discuss the energetics associated 
with this folding gymnastics? I believe that the fact that a structure of an HK97-fold protein is 
known in its free and capsid-integrated forms needs to be put front and center in this MS, as the 
chi MCP might become one of the most important proteins in the field of biophysics of virus shell 
assembly. The chi MCP is a goldmine for people studying protein folding. 
2) Fig. 6a. How was the electrostatic change calculated? Which software used? How were the 
hydrogens added?
Peer review of: Majority sensing in synthetic microbial consortia (2020)


 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have addressed my major concerns and made additions to the main text and 
supplementary file accordingly. Thank you! 
 
The only point that I am still a little concerned by is the large error bars (point 6, Page 11 - Figure 5 
(b)) 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have satisfactorily addressed my raised points.
Peer review of: Prediction-based highly sensitive CRISPR off-target validation using target-specific DNA (2019)


 
 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors successfully addressed all of my concerns, and were able to improve the validity and 
utility of their claims significantly. 
 
 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have improved the study by performing a number of additional experiments and the 
CRISPR amplification method now makes a useful contribution to off-target mutations detection. 
Only a few minor points are suggested. 
 
Minor points: 
1) Line 226-243, “Spacer 8a, 15a” and “Spacer 15A” should be consistent (Supplementary Fig 9-
11). 
2) Please add references for line 73, “in-silico prediction”; line 191-193, “Conventional NGS did not 
allow detection of the off-target indels with frequencies below the detection limit (indel frequency 
~ 0.5)”; line 257-259, “adenine base editor (ABE)”. 
3) Line 190-191, the sentence “and unique indel pattern was detected at off-target site 3 (Fig. 3a, 
b, Supplementary Fig. 6b)” would be better than the original.
Peer review of: SARS-CoV-2 is transmitted via contact and via the air between ferrets (2020)

 
 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have satisfactorily addressed the comments of the reviewer. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
In the revised manuscript “SARS-CoV-2 is transmitted via contact and via the air between ferrets”, the 
authors examine contact and airborne transmission of SARS-CoV-2 in 4 sets of animals intranasally 
inoculated with the virus. The authors have addressed all of the previous concerns. In the revised 
manuscript the authors provide viral titer data and plaque reduction neutralization assays. The low 
viral infectious titer data presented in Supplemental Figure 3 for all animals (donor, direct contact, and 
indirect recipient animals) is surprising and the authors may want to comment on the distinction of 
RNA levels and infectious virus levels. Overall this work is very timely and will be of broad interest.