JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: Retention of paternal DNA methylome in the developing zebrafish germline (2020)


REVIEWERS' COMMENTS:  
 
Reviewer #1 (Remarks to the Author):  
 
The authors have satisfactorily addressed my concerns. I would also like to note as an expert with 
WGBS data generation/analysis that the data can be used to estimate genome-wide levels of DNA 
methylation by calculating the percent of cytosines in raw sequenced reads across a range of 
samples. This can be used to estimate DNA methylation levels in any species regardless of a 
publicly available reference genome. The authors used a equally effective approach in their 
response to reviewer 2 and 3 that is more complicated than I think is necessary. Regardless, it is a 
suitable method that reveals their original conclusions are correct.  
 
 
Reviewer #2 (Remarks to the Author):  
 
All my concerns regarding the manuscript by Skvortsova et al have been addressed. This is a nice 
story. 
 
 
Reviewer #3 (Remarks to the Author):  
 
The authors produced an excellent rebuttal and the manuscript is much improved. I only have a 
few minor remaining comments.  
 
1. ‘The active mechanism entails enzymatic oxidation of genomic 5mC by TET (Ten-eleven-
translocation) family enzymes’ – perhaps better described as ‘an active mechanism’. As the 
authors point out, this is not the active mechanism in the zygote or in PGCs.  
 
2. ‘5mC levels reach their lowest point in the blastocyst followed by cell type-specific  
remethylation during gastrulation’. The lowest point of 5mC is in PGCs following epigenetic 
reprogramming.  
 
3. ‘germline is specified during gastrulation’. In mice, it is prior to gastrulation. In humans, we 
don’t know.  
 
4. ‘likely employ more extensive 5mC remodelling only during gonadogenesis.’ – do the authors 
mean gametogenesis?  
 
5. ‘germline-expressed genes are specifically methylated in the early preimplantation embryo, 
between the blastocyst and the epiblast stage’. This statement is incorrect. The promoters become 
methylated shortly after implantation, in the early post-implantation epiblast. The term ‘epiblast 
stage’ is not routinely used in mouse embryology (this would be confusing anyway - as it it 
wouldn't be clear whether the authors are referring to the pre-implantation epiblast (in the 
blastocyst) or the post-implantation epiblast).  
 
6. ‘It is worth noting however, that TET expression is extremely low in pre-gastrula...'.- It should 
be mentioned that any early DNA demethylation could also occur in a TET-independent manner – 
as occurs in the mouse germline and zygote.  
 
7. ‘and suggest that 5mC likely only plays an auxiliary role during germline development’ – I am 
not convinced this statement is backed up by the data shown, and is rather unnecessary. I would 
delete.
Peer review of: Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for (2020)


REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have addressed appropriately the concerns that I raised before 
 
 
Reviewer #2 (Remarks to the Author): 
 
We are fully satisfied with the authors revision and recommend the paper for publication in its present 
form.
Peer review of: Diaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem (2020)


 
 
 

REVIEWERS' COMMENTS: 

Reviewer #2 Remarks to the authors: 

I think their response is OK. The one thing I would do is put the S7G figure in the main figure run as 
part of Figure 6, as an extension to 6H. As presented, the figure includes the experiment that worked, 
but not the one that didn’t.
Peer review of: Characterization of a pluripotent stem cell-derived matrix with powerful osteoregenerative (2020)



 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors should be commended for their efforts to address concerns raised during the initial 
review of their manuscript. These concerns were all addressed in a systematic manner, and in 
many cases the response involved inclusion of new experimental data. Congratulations on an 
excellent study.
Peer review of: Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to (2019)

Reviewers' Comments:
Reviewer #2:
Remarks to the Author:
With regard to the revised manuscript provided by the authors I like to state that the authors have
throughly and now appropriately addressed my latest comments. In particular based the provided IF
data, I do now acccept the statement that Ag85 is present in some CD73 and CD105 positive cells.
However the authors should refrain from exaggerating and overinterpreting their findings. They should
"disarm" and better refine the wording:
 - Terms as "Routinely" and "frequently" ask for quantification, which I do not ask for. Thus, please
 omit these adverbs and let the experienced reader decide.
 - The statement "can revolutionize" reflects the excitement and the enthusiasm of the authors but I do
 not consider this to be appropriate with regard to the science. This is really to much.
 Thus I suggest to end the abstract as follows: "Moreover, MSCs are observed in and around human
 tuberculosis granulomas, harboring Mtb bacteria. We, therefore, propose, targeting the unique
 immune-privileged niche, provided by MSCs to Mtb, can have a major impact on tuberculosis
 prevention and cure."
Norbert Reiling
Peer review of: ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like (2020)



Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
The authors have made no progress in addressing the significant flaws with the manuscript. In 
fact, the only difference in the figures is that old figure 4h has been replaced with a worse version 
(seven days is not sufficient incubation time for neurosphere formation, as pointed out last 
review). 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors addressed my concerns
Peer review of: ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like (2020)



Reviewers' Comments: 
 
Reviewer #4: 
Remarks to the Author: 
Glioblastomas are known to have a myeloid cell enriched tumour microenvironment. 
Understanding how this is shaped by tumour signalling pathways is of great interest - particularly 
given the current failures of immunotherapy to have a major impact on this disease. Yin et al., 
explore the role played by glioblastoma stem cells in altering the phenotype of tumour-associated 
macrophages. 
 
The authors focus on ARS2, a zinc finger transcription factor and suggest this has a major role in 
polarisation of TAMs - i.e. making them pro-tumorigenic. ARS2 is a transcription factor and this 
group suggests MGLL is a key target, which activates beta catenin via glioblastoma stem cell 
activation of prostaglandin. 
 
These findings are potentially interesting, as Ars2 was identified in a Nature paper several years 
ago as a potential key regulator of of Sox2 in mouse neural stem cells. 
 
The authors perform knockdown of ARS2 in patient GSCs and identify MGLL from RNA-seq as a 
potential target gene. They show ARS2 is bound at the MGLL by Chip-seq. 
 
A major concern of Reviewer 2 is: "Is ARS2 necessary for stemness, or for stem cells to induce M2 
polarization, or just for survival of cells in general?” I agree that this is important to resolve. Is the 
self-renewal role critical and immune impact secondary, or both are critical? 
 
Can this not be tested easily by transplanting into NSG mice, which are fully immunocompromised 
and comparing survival rates to the Nude mice transplants. i.e. what is the contribution of the cell 
autonomous self-renewal effects of ARS2 loss, versus the immune modulation role. They could 
easily dissect this. 
 
I also agree that nuclear beta catenin staining and strength of that conclusion (which is difficult to 
infer from ICC) should be toned down or biochemical evidence presented. 
 
Overall these are interesting insights, with a significant amount of experimental data, that 
identifies a role for ARS2 and influence on both beta catenin and TAMs via prostaglandin is both 
interesting tumour biology and has a potential therapeutic relevance. 
 
minor points: 
Macrophage signatures are already well described in the mesenchymal subtype of GBM. This is the 
subtype in which immune cells are increased. So this is not unexpected they see this. 
 
Minor point - in the abstract it is not clear whether beta catenin is activated within the GSCs or 
TAMs or both.
Peer review of: TNFAIP8 controls murine intestinal stem cell homeostasis and regeneration by regulating (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
 
The authors revised the manuscript according to the reviewers’ comments. However, there still 
remain significant issues regarding the evaluation of pAktS473 staining, β-catenin staining, and 
Western blotting of β-catenin.   
 
1.   In the revised Figure 5C, the authors claimed that a different Western with more equivalent 
baselines has been used in the resubmission. It seems that the images for β-catenin and 
β-actin are replaced using the different sample, however, the images for pAktS473 and Akt 
remain exactly the same in the revised images as in the previous images (e.g., we can see 
exactly  the  same  defect  in  the  WT  Akt  bands  in  both  images).  The  authors  will  need  to 
comment on this finding. 

 
Previous Fig 5C                                                      Revised Figure 5C 

 

 
2. 

In Fig E5H, β-catenin cannot be detected in the nucleus. Quantification of nuclear β-catenin 
staining in Fig E5C is not consistent with the staining image in Fig 5H. 
 

3.  There still remains issues evaluating the pAkt staining in Fig 5D, because the background 
staining  for  Tipe0-/-  mice  are  much  stronger  compared  to  that  of  WT  mice.  The  authors 
claimed  that  they  see  this  increased  staining  in  the  muscularis  of  Tipe0-/-  mice  by 
performing IgG control staining. However, this explanation does not justify comparing the 

Tipe0-/-  and  WT  mice  which  have  different  background  staining.  The  staining  strength 
including the background may also be affected by how the samples are prepared (e.g., how 
they are fixed, how long  they are fixed). We strongly recommend the authors repeat the 
experiments  again  to  provide  more  faithful  comparison  of  pAkt staining  between  Tipe0-/- 
and WT mice. 

 
 
 
 
 
Reviewer #2: 
Remarks to the Author: 
Goldsmith and colleagues have nicely addressed all the comments and concerns raised in the original 
review. The manuscript is significantly improved, particularly with most of the images that raised a lot 
of questions now being replaced with higher quality pictures, being removed entirely or modified to 
better illustrate the main message. This much improved manuscript is now suitable for publication. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors properly addressed the concerns raised in the previous review and significantly improved 
the manuscript. However, immunofluorescence stainings for E-cadherin must be improved
Peer review of: SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 (2020)

REVIEWERS' COMMENTS:
Reviewer #2 (Remarks to the Author):
I commend the authors for their thorough and knowledgeable answers to my queries. I accept all
answers as satisfactory but one:
<i> We did not remove the PCR duplicates in our RNA sequencing data. PCR duplicates should be
taken into consideration in DNA sequencing analyses, in that the genome has a definite copy
number (n=2). However, for RNA sequencing, PCR duplicates should be retained in most cases, as
duplicate removal might greatly affect the natural duplicates (expression abundance) of RNA
species. Only when UMIs (Unique Molecular Identifiers), which was usually for analysis of genes of
ultra-low expression, were used in library construction, PCR duplicates could be removed in RNA
sequencing. In our study, we had enough RNAs for library construction and only performed a
conventional RNA sequencing without UMIs.
We did not state our PCR duplicates retaining in the previous submission as we thought this was a
default protocol. We apologize for the negligence and have added the statement in the Method
section of this revision.</i>
The matter of whether PCR duplicates need to be removed or not in RNAseq studies is an open
one, with partial evidence leaning either side depending on the situation. I agree with the authors
in that in the case of high quality, high amount starting material, removal of PCR duplicates can be
neutral or even harmful in the case of very short reads (50bp or below) which is not the case of
this study’s data. Even in the cases (which given the author’s comments would be this case) in
which removal of PCR duplicates is not necessary, evidence for this is required in the form of the
actual average percentage of PCR (and standard deviation) for reviewers and readers evaluation
that this is the case indeed. To be clear: the fact that the percentage is stated does not mean that
they are actually removed from analysis. A sentence in the M&M with average PCR duplicates and
deviation should suffice.
Peer review of: Endothelial cell clonal expansion in the development of cerebral cavernous malformations (2019)


REVIEWERS' COMMENTS:  

 

Reviewer #1 (Remarks to the Author):  

 

The revised manuscript is improved and my concerns were addressed. This is an important 
contribution to the field.  

 

 

Reviewer #3 (Remarks to the Author):  

 

The authors have satisfied all of the comments from this reviewer and the work is highly suitable for 
publication in Nature Comms.  

 

 

Reviewer #4 (Remarks to the Author):  

 

The authors have addressed all but one of the points raised in my review. I continue to find the in 
situ hybridization data presented in Extended Date Figure 3 not convincing.
Peer review of: Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal (2020)

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have addressed all the concerns raised by the reviewers. 

Reviewer #2 (Remarks to the Author): 

Fig. S10. The nuclear beta-catenin does not look convincing, though there is a clear increase of beta-
catenin protein. Please repeat IF staining with confocal microscope, which should give a better quality 
of image showing the nuclear beta-catenin. 

Reviewer #3 (Remarks to the Author): 

Abo et al showed the importance of Erdr1 in the stem cell and TA cells. The paper was nicely written 
and well-organized. I am delight to accept this manuscript.
Peer review of: Chronic bee paralysis as a serious emerging threat to honey bees (2020)


Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The key issue with the paper has been addressed in that they have validated the diagnostics with the 
PCR data. I find the conclusions convincing and think this is important to the honey bee disease field. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
It is a revised version of an interesting manuscript on the epidemiology of honeybee disease: chronic 
bee paralysis. 
The authors are looking at a big picture of a history and spatial distribution of a specific symptom. In 
my opinion it is a good approach. With one important limitation that past infection by a particular 
agent can not be confirmed. 
In the corrected version the question raised were addressed well and in details and the current 
infection by CBPV was confirmed. This of course can at most imply on the past agent/s responsible for 
the infection. 
Based on the fact that there the authors have no practical way to confirm past CBPV infection, I 
strongly suggest the authors to be more careful in their statements. In my opinion, the statement in 
the first opening sentence is too strong! I recommend to replace the word demonstrate chronic 
paralysis... or slightly modify the sentence and its connection with the second one, as the PCR data 
are relevant only for the current situation and not the past. 
Minor comment: in fig 3. Y axis title needs to be more informative not just k value 
 
Overall, the article reads well and in my opinion carries information worthy publishing
Peer review of: Juvenile cleaner fish can socially learn the consequences of cheating (2020)



 
 
 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The MS is greatly improved since the last version. I have no further major issues to raise. 
 
There is a full-stop missing in line 234. 
L430: lunguage?? 
 
Culum Brown 
 
 
 
Reviewer #2: 
Remarks to the Author: 
I first want to apologise for the delay in returning this review I understand that it is very difficult to 
wait for reviewers to get their act togethor but in this case just a number of factors came togethor and 
I've not been able to fulfil many of my commitments in a timely fashion. 
 
However I've now had a chance to review the changes the authors have made in response to my 
comments and I am very happy with the way they have done so - where they have defended their 
positions I am persuaded to give way, since they have taken my main points onboard in a very 
positive way, overhauling their analysis significantly - I think the paper is stronger now and ready to 
be published.
Peer review of: Balancing selection via life-history trade-offs maintains an inversion polymorphism in a (2019)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

I enjoyed reading this manuscript the first time around and had relatively minor comments then. The 
three main points I had were as follows: 
1) More information was needed on the inversion polymorphism and its genomic architecture. This has 
now been reported. 
2) The observation that the excess of αα homozygotes declined as the frequency of the α allele 
increased was, I think, an inevitablility rather than evidence of negative-frequency dependence. The 
authors have acknowledged this and changed the wording as a consequence. I don't think the overall 
conclusions are greatly impacted by this. 
3) I was concerned that the simulations treated available habitats as independent for each individual, 
when in fact they are correlated as e.g. wave action affects all haitats more or less simultaneously. 
The authors have clarified how the simulations were set up, and I am no longer concerned by this. 

Overall, I think the authors have done an excellent job with the revisions, and I am satisifed that they 
have addressed all of the points I raised earlier. I only saw a summary of the other reviewer's 
comments because they were sent confidentially to the editor. Therefore I am unable to judge 
whether that reviewer's concerns were addressed. 

Reviewer #2 (Remarks to the Author): 

Thank you for the revisions - the manuscript reads very nicely now.
Peer review of: Network-based diffusion analysis reveals context-specific dominance of dance (2020)

Reviewers' Comments:
 Reviewer #1:
 Remarks to the Author:
 The authors addressed all my comments and I have no further comments or suggestions.
Reviewer #3:
Remarks to the Author:
I've read the paper through again carefully and reviewed the author's response to my and the other
reviewers comments. I'm satisfied with their response and edits, and I find the paper greatly improved
because of them. It is an exciting study, with a clear and convincing result. I'm happy to recommend
it for publication in its current form.
Peer review of: Nuthatches vary their alarm calls based upon the source of the eavesdropped signals (2020)


REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
I am satisfied that the corrections are completed and, accordingly, this paper would now appear to be 
publishable 
 
 
Reviewer #2 (Remarks to the Author): 
 
Review of: NCOMMS-19-23668A 
 
I have re-reviewed the paper “Nuthatches vary their alarm calls based upon the reliability of the 
eavesdropped signals”. 
 
I think the authors have done a good job at addressing the issues I raised. I do, however, just have a 
few more final changes that would be important to incorporate before publication. 
 
 
 
L78-81: This is direct repetition of L70-73. 
 
L95-96: It is not clear how parameters that differ in their dimensionality (time, frequency) can be 
considered as “similar to each other”. Can the authors clarify here? 
 
L91-98: The authors have definitely expanded on the interaction effect, but I was thinking this could 
be stated more clearly and generally, specifically, that the effect that threat level had on an acoustic 
variable differed based on whether the information was direct or indirect. They can then go on to 
report the exact results of the mixed effects models. 
 
L182: depredation? Why not just predation? 
 
L310: remove additional bracket. 
 
L317-318: Maybe change to “We observed a potential exemplar-order interaction in the data..” 
 
L329: Should that be “Luke”?
Peer review of: Early-exposure to new sex pheromone blends alters mate preference in female butterflies (2020)


Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have addressed all comments and questions clearly, and I find their findings exciting and 
worth publishing in Nature Communications. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
COMMENTS TO THE AUTHORS 
 
I like that you have added a second experiment, and in general I found the manuscript well written 
and interesting. However, I am still not convinced by the transgenerational effects in this research. 
 
Lines 95-96. This sentence is unclear and needs rewording. 
 
Lines 111-119. In this section the you need to explain the differences between the “experiment 1” and 
“experiment 2” you detail later. 
 
Line 134. “innate females” is confusing 
 
Lines 139-140. This does not clarify why it was necessary to use mixed models. It would be better to 
explain here that the mixed models were necessary in order to include family as a random effect – it is 
also confusing as the results you report in the next paragraph are chi-square test results instead. It 
needs to be better clarified that you used both types of tests and why you did so. 
 
Lines 172-174. I understand your point here that it is a small effect size. But you are making a large 
claim here – and it seems to me that in order to demonstrate this effect you need to show that these 
groups are different from each other the way that you do in the maternal generation. In your 
responses to my comments you say: “As suggested we have compared the preference (mating bias) 
of naïve females from the parental generation to the preference (mating bias) of their offspring. In 
experiment1, naïve females form the parental generation and offspring of Wt1-exposed females prefer 
the Wt blend, while offspring of NB1-exposed females don’t show any preference” but I do not see 
these statistics in the manuscript. Looking at the data my guess would be that none of the offspring 
generation preferences would be significantly different from the naïve maternal generation 
preferences. 
 
Line 182: should be “from” not “form” 
 
Line 395: “About 5” can you instead say the range? 3-7?
Peer review of: Comparative analysis of squamate brains unveils multi-level variation in cerebellar (2019)



Reviewers' Comments:  
 
Reviewer #3:  
Remarks to the Author:  
I am pleased that my primary concern, the fixation of tissue samples, was not a significant factor. 
Also, the additional information on methods is greatly appreciated as this resolves a number of 
outstanding issues. Although I disagree with the authors on several of their statements concerning 
morphometric approaches in evolutionary neuroscience, I have no major concerns or criticisms of the 
revised manuscript.  
 
I have a few minor corrections (page and line numbers refer to the marked version of the 
manuscript).  
 
page 2, lines 31-34. This was a bit dense, so I would suggest breaking it up into a couple of 
sentences.  
 
page 4, line 14. I am not sure that "read-out" is the most appropriate term to use here.  
 
page 9, line 5. Replace "have already shown to be" with "is known to be"