JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: ABHD4-dependent developmental anoikis safeguards the embryonic brain (2020)


 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors addressed all of points and the manuscript reads well. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The revised version of László et al. addresses the points raised during the previous round of 
review. 
I appreciate the fact that in the present version the authors provide additional data and 
quantifications corroborating and strengthening their original claims. 
 
It is my opinion that the paper in its present form should be accepted for publication. 
 
Only one point should be addressed: there are here and there several typos, that must be 
corrected and edited before publication.
Peer review of: Dynamic remodelling of the human host cell proteome and phosphoproteome upon (2020)




REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The revised version of this manuscript address all the questions and suggestions by the authors and 
in my opinion the majority of the concerns describe by the other reviewer. I believe that the 
inclusion of of additional experimental validations on GBF1 and PI4KB phosphorylation in the 
formation of the replication organelles and the connection of TFEB and secretory autophagy during 
CVB3 infection is interesting finding. I believe the paper has significantly increased in quality and I 
have not additional comments or concerns. 

 

 

Reviewer #2 (Remarks to the Author): 

 

For the revised version of the manuscript entitled “Dynamic remodeling of the host cell 
(phospho)proteome upon enterovirus infection” the authors addressed the majority of my 
comments. The main concerns that I raised included the focus on the previous version on the 
description of the dataset rather than emphasizing what the data tells us about the biology of 
enterovirus infection, the lack of functional follow up studies, and restructuring of the manuscript. 

The authors restructured the manuscript substantially as well as shorten some of the descriptive 
sections, so that it is more intuitive for the reader to follow the major findings of the study. 

In order to address the lack of biological insights extracted from the large scale dataset the authors 
added functional data characterizing the role of mTORC1 inactivation leading to increased TFEB 
activity as well as investigating the role of phosphorylation of host factors involved in the formation 
of viral replication organelles. 

 

I have a few remaining concerns/questions regarding the functional follow up findings: 

1. The authors hypothesize that TFEB activation downstream of mTORC1 affect non-lytic virus 
release vis extracellular vesicles (EV). While the authors show a significantly reduced EV-enclosed 
virus release, but at the same time TFEB ko also reduces the naked virus, even though it is not 
significant reduced, which is likely due to variability in the measurements/experiment. Does this 
result imply that TFEB does not only affect the non-lytic but also the lytic virus release? How do the 
authors explain ths oberservation? 

2. The last sentence of the Result section “These data lend further support to the idea that 
(entero)viruses not only hijack cellular pathways to build their replication organelles but that they 

also rewire them from their regulation in non-infected cells.” seems unclear to me. Please clarify the 
meaning of “…rewire them from their regulation in non-infected cells.”
Peer review of: Visualizing the enzyme mechanism of mevalonate diphosphate decarboxylase (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

I am totally satisfied with the revisions made by the authors, in which all my comments have been 
addressed. Now the reaction mechanism of MDD proposed by the authors is updated appropriately 
and agrees well with recent knowledges of the enzyme. The comparison of the structures of MDD 
solved in the study with the previously known structures of the enzyme and its orthologs, 
considering the effect of crystal packing, makes sense. I still hope the catalytic mechanism of this 
interesting decarboxylase is elucidated by QM/MM study, but it is not necessary in this paper. The 
elucidation will be made in future probably by the authors or other groups. 

Reviewer #2 (Remarks to the Author): 

In the manuscript entitled "Visualizing the Enzyme Mechanism of Mevalonate Diphosphate 
Decarboxylase" by Chen et al. (Manuscript NCOMMS-19-27996A) the authors submitted a revised 
version of their manuscript. 

The revised version has substantially improved. 
(1) The structural comparison of different MDD structures available in the PDB improves the 
understanding of the differences of the structures for example different crystal packing effects and 
hence restricted conformational flexibility of the elements. See also the novel Supplementary 
Figure 7. Here, I just have a minor point: I personally find it useful if the PDB-ID for the displayed 
structure (panel c to e) is provided and/or a reference to the primary citation. This suggestion 
applies as well to Supplementary figures. 

The functional implications are now much better to follow. In particular, the discussion of the 
putative function of Asp282 is now better to understand. By the discussion of the other two recent 
publications, as suggested by the other reviewer, the authors were able to discard the contested 
hypothesis section on the mechanism. It is a very beautiful example how structural biology can 
provide insightful structural information to elucidate an enzymatic mechanism. 

I recommend to accept the current version of the manuscript. 

Minor points: 
- Page 12, line 11: Names of organism should be in italic 
- Supplementary Figure 5: I suggest deleting the primer sequences. They are given in the 
Materials and Methods section.
Peer review of: Ion mobility collision cross-section atlas for known and unknown metabolite annotation in (2020)


 

REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The authors have done a very thorough job of responding to my comments. I particularly welcome 
the additional results, especially those that show the improved performance with real MS/MS data 
(which is, I think, a more common use-case). 

I would be happy to see the manuscript published now.
Peer review of: Complete chemical structures of human mitochondrial tRNAs (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have addressed all my previous concerns and the revised manuscript has been improved. I 
thus strongly support the publication in Nature Communications. 

Reviewer #2 (Remarks to the Author): 

The authors addressed my questions. I have no further questions. 

Reviewer #3 (Remarks to the Author): 

The Authors have addressed all concerns from the original review. The authors have provided a reason 
for why a comprehensive map of human tRNA modifications is important since bovine and human mt-
tRNAs differ fairly significantly in sequence so simple prediction is not sufficient. In addition, the authors 
provide evidence for new modifications, cmnm5U and cmnm5s2U. The authors also add ribosome 
profiling data and protein folding reporter plasmids to provide functional relevance for the findings. 
Based upon these clarifications and additions, the paper has provided novelty and biological insight that 
would be of broad interest in the field of RNA biology. Thus, I recommend the manuscript for 
publication.
Peer review of: Warsaw Breakage Syndrome associated DDX11 helicase resolves G-quadruplex structures to (2010)


 

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
Having read the revised version, we are convinced that the manuscript warrants publication in 
nature communications. This study addresses a key issue in the cohesin field. There have been 
conflicting views about the role DDX11 plays in promoting cohesion establishment during 
replication. The detailed characterisation of the newly identified mutations currently presented in 
figure 8 makes a strong case for the requirement of the helicase activity of DDX11 in order to 
promote cohesion establishment. This is an important observation that alters the outlook for future 
understanding of the molecular mechanism of cohesion establishment during replication. 
 
Our concerns were not intended to belittle the authors efforts in any way, we understand that the 
study is also of interest to clinicians. Comprehensive analysis of independently identified mutations 
associated with WABS and clarification of conflicting effects reported in literature is very important. 
Our view was that the way the manuscript was initially presented was distracting for a general 
reader and more importantly, not enough emphasis was given to the main message of the 
manuscript, namely the importance of the helicase activity of DDX11 in promoting the 
establishment of sister chromatid cohesion. Both our concerns are satisfactorily addressed in the 
revised manuscript and we fully support the immediate publication of the manuscript in nature 
communications. 
 
 
 
Reviewer #2 (Remarks to the Author): 
 
I have carefully read the responses to the Reviewers' comments, including my own. It is my belief 
that the authors have addressed the great majority of the comments in a satisfactory manner. 
Importantly, the revised manuscript is significantly improved. 
Minor comment: References 19 and 79 in the reference list are the same. This mistake should be 
corrected. 
Minor comment: In addition, Reference 22 has not spelled out correctly the name of the late Johan 
de Winter, a leading pioneer in the discovery and characterization of Warsaw Breakage syndrome. 
This error should be corrected. Reference 22 also lacks volume and page numbers. 
Minor comment: Reference 23 lacks volume and page numbers. 
Minor comment: Reference 38 lacks volume and page numbers. 
Minor Comment: Reference 75 lacks volume and page numbers. 
Minor comment: Reference 87 lacks volume and page numbers. 
There may be additional errors in the reference list. The reference list needs to be carefully 
examined and corrections made. 
 
 
Reviewer #3 (Remarks to the Author): 
 
I have looked at the revisions and the justifications provided, including issues raised by other 
reviewers. My criticism that there is still lack of mechanistic insight as to how DDX11 functions in 
cohesion, which the authors do acknowledge. Nevertheless, this is a decent piece of work with 
something of interest to say and the authors have added additional experiments to support their 
case. In this respect they have addressed my concerns satisfactorily.
Peer review of: Isobutanol production freed from biological limits using synthetic biochemistry (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

I was reviewer #1 in the previous iteration. The authors have done an excellent job addressing the 
concerns and comments made. I believe this manuscript is ready for publication and will be widely 
cited as a pivotal study as the cell-free field continues to develop. 

Reviewer #2 (Remarks to the Author): 

The manuscript “Isobutanol production freed from biological limits using synthetic biochemistry” 
described about production of isobutanol by multiple enzymatic reactions without cells. 
The authors responded to all the issues pointed out in the peer review process [redacted] and it is 
considered that the current version of the manuscript is suitable for publication in the journal Nature 
Communications. 

Reviewer #3 (Remarks to the Author): 

Reviewer:3 
Recommendation: Publish after minor revisions noted. 

Comments: 
As the author commented, so far, the cell-free production of isobutanol is not cost competitive 
compared to cell-based fermentation and further studies are required for real application (listed in 
Response to reviewers). However, I agree that this work can be a milestone towards cell-free 
biomanufacturing and thus I feels that the manuscript should attract much attention to the broad 
reader of Nature Communications. 

Minor point. 
In vitro production of isobutanol was performed at 30 °C in both small scale reaction and bioreactor. 
According to the supplementary Fig.2, the activity of SmilvD gradually decreased at 25 °C and SmilvD 
showed almost no activity over 37 °C within 12 h. Based on this thermal tolerance results, I expect 
that SmilvD has low thermal stability and it will lose its activity at 30 °C more rapidly than that at 25 
°C. However, according to the Fig.5c, the residual activity of SmilvD is almost 45 %. In case of KivD-
S, although it had higher thermal tolerance than SmilvD, it showed almost no activity after 70 hours 
of incubation (Fig.5c). In addition, AlsS-p also almost lost its activity after 70 hours of incubation 
(Fig.5c) despite of its high thermal tolerance.
Peer review of: Enhancing intracellular accumulation and target engagement of PROTACs with reversible (2019)


 

 

 
 
 
 
 

REVIEWERS' COMMENTS:  

 

Reviewer #1 (Remarks to the Author):  

 

The authors have adequately dealt with the previous comments that I raised.  

 

 

Reviewer #2 (Remarks to the Author):  

 

The authors have done a nice job to carefully address questions raised by all reviewers by 
performing additional experiments and making new compounds. I found the manuscript now 
acceptable for publication in Nature Communications.
Peer review of: TrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in mem (2020)


 
 

REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
Zhang et al. provide a revised manuscript, which improved in readability and clarity (also about 
the limitations of their study). I am satisfied with most of their replies. The only remaining 
problem for me is the link to physiology. First, it is in no way new that potassium transporters and 
channels in general contribute to the establishment of the membrane potential. However, previous 
studies (general and on TrkHA/KtrBA) clearly showed the link between potassium accumulation 
and membrane potential adjustment (e.g. Kashket & Barker, 1977, Tokuda et al, 1981; Ochromel 
et al, 2011; Castaneda-Garcia et al, 2011), which Zhang et al. appear to question. But, their 
results in the changed membrane potential could as well reflect the disturbed potassium 
homeostasis upon abolishing the effective closure of TrkH. This said, I find the presented data with 
the given discussion, not further detailing what in their opinion happens other than K+ 
translocation, rather meaningless. The authors should either provide further data determining 
intracellular K+ and Na+ as well as the pH or remove the data. At least they should reference 
former papers and relate their suggestion to those publications. Also, I am not in favor of the 
changed title because ‘TrkA alters the membrane potential’ in my opinion is not even describing 
what the authors claim. I understand their argumentation rather as saying that the functional 
TrkHA system is involved in membrane potential adjustment. 
Additionally, there are several sentences that lack a word or have one too much as a result of 
changes to the manuscript (e.g. line 54., line 96, line 123, line 178). The authors should carefully 
revise their manuscript. 
 
 
 
Reviewer #2 (Remarks to the Author): 
 
I am satisfied with the changes made to the manuscript. 
 
I only suggest that the authors revise carefully the text and figures as I found a few obvious 
mistakes. 
For example: 
Supplementary Figure 5a: The two different interfaces are both labeled as HN1. I believe that the 
one on the right should be labeled HN2. 
 
Supplementary Figure 5b: One of the residues is labeled APS44, it should read ASP44. 
 
Legend of Supplementary Figure 11. The authors have chosen to use KtrBA instead of the 
established KtrAB. Although it is understandable to try to harmonize the nomenclature across the 
field (TrkHA and KtrBA), this may cause a confusion among the readers if they try to follow the 
literature. I suggest that either the authors use the established KtrAB or stick to the term KtrB-
KtrA used in the main text.
Peer review of: A dietary fatty acid counteracts neuronal mechanical sensitization (2020)

Reviewers' Comments:
Reviewer #1:
Remarks to the Author:
The authors have made substantial text changes and added new data analyses and results that
greatly strengthen the manuscript. They have directly addressed all of our concerns highlighted in
our initial review. It is our opinion that the data now fully support the claims, and no further
revisions are required.
 Reviewer #2:
 Remarks to the Author:
 The authors have nicely addressed my comments, and further strengthened an already-strong
 manuscript.
 One remaining discrepancy arising from the edits is:
 Lines 331 - 333 (in Discussion): "Our data show that MA does not impair bradykinin-mediated
 sensitization, but rather reduces the mechano-currents similar to the ones measured during
 normal neuronal mechanical response or non-inflammatory-like levels."
seems to be at odds with:
 Lines 84 - 86 (in Introduction): "Importantly, MA decreases PIEZO2 currents potentiated by the
 proalgesic agent bradykinin, indicating that it might be particularly useful for reducing heightened
 touch responses during inflammation."
Peer review of: Redox-coupled proton pumping drives carbon concentration in the photosynthetic complex I (2020)

 
 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The revised version of the work “Redox-Coupled Proton Pumping Drives Carbon Concentration in 
thePhotosynthetic Complex I “ presents a significant improved and corrected version of the 
manuscript. Authors have adressed and/or adressed most of my previous concerns as well as 
those presented by the other reviewers. 
Specifically, they have: 
i) added, as requested, a detailed methodology in the methods section now included as part of the 
main text, which properly describes theory levels and methodology 
ii) Clarified key elements of the three enezymes that are compared in the work (αCA, βCA and 
current enzyme). 
iii) Added proper description that energy calculations correspond to ΔH – TΔS + ΔZPE based on the 
electronic energy and the molecular Hessian. 
iv) Better explained the role of the titrable active site resiudes and pKa calculation 
v) Increased sampling and analysis of the waters present in the proton chanels 
vi) Provided estimate of the Free Energy Profile of CO2 migration along the proposed channel. 
 
Therefore, I believe the present work is suitable for publication. I only have a minor comment 
(described below) related to Figure 2b,. 
 
In the text desribing Figure 2 authors state (starting line 123) “ The CO 2 hydration is initiated by 
proton transfer (pT) from the Zn-bound water molecule followed by a nucleophilic attack.. of the 
hydroxide on CO 2 . In αCA (βCA), the rate limiting reaction barrier of 11 (12) kcal mol -1 is 
connected with pT to His64 (Tyr205), … In CupA, proton transfer from Zn-bound water to Tyr41 is 
slightly exergonic” Therefore, if I understood it correglty, in CupA Zn bound watre (which then acts 
as the nucelophile) transfer the proton to Tyr41 (in αCA /βCA the acceptor being His64/Tyr205. 
However, in Figure 2B, the Zn bound water transfer the proton to ANOTHER water molecule, 
whiwhc then transfers it to Tyr/His/Tyr. So, are there 1 or 2 water molecules?. 
In line with this point in Figure 2A waters are missing. I strongly beliebe they should be shown and 
the issue needs to be clarified. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
I think that the authors have addressed the questions raised by all reviwers adequately, so that 
the revised version of the manuscript can be accepted. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors have answered all questions to my satisfaction and especially the figures have been 
improved considerably. I support publication of the paper.
Peer review of: Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism (2020)

REVIEWERS' COMMENTS second round: Reviewer #1 (Remarks to the Author):
Reviewer #2 (Remarks to the Author):
Reviewer #3 (Remarks to the Author):
 The authors addressed the comments of all reviewers with great care. With regard to my
 comments I can confirm that they were also addressed satisfactorily. I have no further suggestions
 and recommend publication of the manuscript as is.
 The revised manuscript by Ciudad et al. has greatly improved. They have addressed my concerns
 and recommend publication.
 The authors have done a good job of addressing the reviewer concerns. As indicated in my original
 review I think this is an interesting, important, and novel work. I am in favor of publishing the
 revised manuscript as is.
Peer review of: Single molecule secondary structure determination of proteins through infrared absorption (2020)

REVIEWERS' COMMENTS:
Reviewer #2 (Remarks to the Author):
 The manuscript was revised very well.
 I recommend to accept it for publication.
 technical comments:
 - The authors should consider to check if the maximum of signal as given in the text in connection
 with Figure 1 f) is at ~-2kHz off-resonance.
 - Fig S4; "FTIR" is found in the inset and caption, but the axis label is "IR amplitude"?
Peer review of: Polyamine regulation of ion channel assembly and implications for nicotinic acetylcholine (2020)

Reviewers' Comments:
Reviewer #1:
Remarks to the Author:
This paper reports novel discoveries about the role of polyamines in regulating the expression of alpha
7 and alpha 4 beta 2 AChRs but not alpha 6 beta 4 AChRs. Extensive data are provided. The authors
were responsive to reviewer comments. This is an interesting and important paper with substantial
implications for new therapeutic approaches.
 Reviewer #2:
 Remarks to the Author:
 The authors have addressed all the issues that I have raised and inserted them in the revised version
 of the paper.
Peer review of: Kinesin-14 motors drive a right-handed helical motion of antiparallel microtubules around (2020)

REVIEWERS' COMMENTS:
Reviewer #1 (Remarks to the Author):
Reviewer #2 (Remarks to the Author):
The revised manuscript by Mitra et al. has now been greatly improved by editing and new data.
The authors now demonstrated that Ncd can actually generate torque that is large enough to
cause microtubule twisting and coiling. Although the data is qualitative, this demonstration is
highly relevant to the chirality of the mitotic spindle in vivo. All comments of me have been
addressed in great detail to the full satisfaction.
 I have read the answers of the authors as well as new data and find it to be satisfactory. I would
 also like to thank the authors for invested time and effort to improve on their work. I have no
 further objection for the article to be published in Nature Communications.
Peer review of: Cooperative transport mechanism of human monocarboxylate transporter 2 (2020)


 
 
 

REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

I think authors have addressed the issues regarding functional characterization of the transporters to 
a reasonable extent, including new experiements. A pity that pCMBS assays were not possible. 
Structural aspects are beyond my expertise. 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors have adequately addressed most of the comments in particular those concerning 
protein expression levels and localization. At the time, the authors have explained in their rebuttal 
letter that the HEK293 expression system is not fully suitable for all conclusions drawn. In the light of 
this, my recommendation is to appropriately use "might"/"may"/"could" in the respective parts of 
the text to properly indicate uncertainty. Otherwise, the reviewer is satisfied with the revision.