JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: Independent regulation of age associated fat accumulation and longevity (2020)


REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
I think the authors have addressed the reviewers comments very well and the revised version is 
further improved. I have no further comments 
 
 
Reviewer #4 (Remarks to the Author): 
 
In the revised manuscript of their paper, Beas et al. addressed all requests and concerns of the 
Reviewers #1 and #3. The manuscript is clearly written and of high technical quality. The claims 
are convincing, fully supported by the experimental data and appropriately discussed in the 
context of previous literature. The authors have been fair in their treatment of previous literature. 
They provided enough methodological details for the experiments to be reproduced by others. The 
manuscript provides a critical step towards understanding mechanisms linking replicative cellular 
aging to age-related and environmentally controlled changes in cellular metabolism. Therefore, in 
its revised form, the manuscript is suitable for Nature Communications, and I recommend 
accepting it for publication.
Peer review of: Multivariate genomic scan implicates novel loci and haem metabolism in human ageing (2020)


Reviewer #1 (Remarks to the Author): 

Thank you for your thoughtful responses, and improvements to the manuscript. I have no further 
comments or concerns, other than that the authors should include the results of a "leave one out" 
analysis in the new iron-related MR section to show the results are independent of HFE 
haemochromatosis (i.e. it is natural variation in iron that is associated - it is not being driven by 
disease-causing variants having an overwhelming effect). 

Dr Luke C. Pilling 

Reviewer #2 (Remarks to the Author): 

The authors have addressed all my concerns. 

Reviewer #3 (Remarks to the Author): 

The authors generally addressed my concerns well. I have some additional comments. 

1) Page 5, line 151, σ12 and σ22 need to be defined. 
2) Page 5, line 159, the formula for SEα is not correct. The denominator of the second term inside 
the square root should be β2all 
3) I have some difficulty to understand the MR results. The authors mentioned that there was 
evidence of violation of the pleiotropy assumption (page 11). However, in Figure S11, the 
intercepts of MR-Egger seem not significantly depart from 0. How the pleiotropy assumption was 
violated? Have the authors performed the outlier test, for example using MR-PRESSO? In Table 
S10, the causal effect estimates were very small (ranged from -0.03 to 0.01), suggesting no 
causal relationship. However, the causal effect estimates were large in Table 3 and ranged from -
0.01 to 0.80. How to explain the results? In general, it has been suggested that interpretation of 
MR results should be caution. (Burgess S, Smith GD, Davies NM, Dudbridge F, Gill D, Glymour MM, 
P. Hartwig FP, Holmes MV, Minelli C, L. Relton CL, Theodoratou E: Guidelines for performing 
Mendelian randomization investigations. Wellcome Open Research 2020.)
Peer review of: The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating (2020)


 
 
 
 
 

Reviewers' Comments: 
 
Reviewer #3: 
Remarks to the Author: 
The authors addressed most of the comments satisfactorily. 
 
Minor comments: 
1. In Figure 1d and l the exact same measurements are shown for WT and KO mice, nonetheless 
the significances differ significantly (p < 0.05 in d and p < 0.001 in l). Is this due to multiple 
comparisons? 
2. The authors were supposed to merge 1d, i and l into 1 graph in order to have a direct 
comparison between transfused and non-transfused mice. Since they do not observe differences 
between WT mice transfused with WT platelets and KO mice transfused with WT platelets, the 
involvement of other cell types can basically be excluded (and the differences are definitely not 
due to remaining KO platelets in the KO mice).
Peer review of: Glial type specific regulation of CNS angiogenesis by HIFα-activated different signaling (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

In this revised manuscript the authors have addressed many of the concerns raised in the previous 
reviews and the paper is significantly stronger as a result. The addition of new data showing the 
efficiency of the genetic approaches and the analysis of direct interactions of HIFa in cells of the 
oligodendrocyte lineage. The paper is more balanced in its presentation and the revisions and new 
data make a more compelling case that stabilization of HIFa in oligodendrocytes activates VEGF but 
does not modulate Wnt signaling. This is an important observation that provided novel insights into 
the role of glial in CNS angiogenesis. 

There are only minor issues that require attention. 
Lines 80-87. It would be good to include the age at which analysis was done. It is in the legend but 
should be in the results. 
Lines 161-170 The revised text could be improved particularly the sentence “We expressed Wnt7a….” 

Reviewer #3 (Remarks to the Author): 

The authors have provided compelling evidence to address all the previous concerns. 

The inclusion of new data in Fig2 has nicely addressed previous concerns as it provides convincing 
evidence against the concept of HIF1a- dependent secretion of WNT7a and its targets in OPC. 

The data in Figure 3 further show the involvement of the WLS secretory pathway in OPC induced to 
express Wnt7A (as they do not express detectable levels in physiological conditions. 

Finally the inclusion of early postnatal data on Aldh1l1-Cre Vhlfl/fl mice and on triple transgenic 
Aldh1l1-Cre Vhlfl/fl Wls fl/fl nicely support the authors interpretation
Peer review of: Alterations of gut microbiota contribute to the progression of unruptured intracranial (2020)


Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
Li et al. seem have addressed most of my comments sufficiently and have provided clear point-to-
point rebuttal. However, I have some concerns about data integrity. I observed the exactly same 
network figure using SparCC (the sup Fig 4) as the previous network figure using Spearman at the 
initial submission (Fig 2). I wish this was just an accident. The inaccuracy was also spotted at the 
initial submission. The authors need to convince me that all data and results are correctly 
presented in the paper firstly. 
 
Furthermore, several statements lack statistical evidence. For instance, UIA-enriched MLGs were 
more highly interconnected than control-enriched 
MLGs. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors have been very responsive to my comments and those of the other reviewers. The 
manuscript is significantly improved. I have no further concerns. 
 
Robert Jenq 
 
 
 
Reviewer #4: 
Remarks to the Author: 
In the response to the reviewers' comments under point 5 that authors discuss down regulating 
taurine in mice to detect a difference in incidence of aneurysm formation, progression and rupture. 
The Figure accompanying point 5, panel c illustrates that the vehicle group incidence of no 
aneurysm, unruptured aneurysm and ruptured aneurysm totals to 105%. This should be corrected 
and probably included in the supplementary material.This further corroborates the critical role of 
taurine production through gut microbiota in cerebral aneurysm pathogenesis.
Peer review of: Using arterial–venous analysis to characterize cancer metabolic consumption in patients (2020)

Reviewers' comments:
Reviewer #2 (Remarks to the Author):
 In the revised manuscript, the authors significantly improve the readability of the manuscript,
 especially for the concept of “VIP” metric and the structure of their main figures. However, there
 are still one minor issue which needs to be addressed before publication in Nature
 Communications:
1. In “Data Analysis” section of the Methods, the author add lots of details related to the
calculation of VIP scores and construction of figures. However, for the concept of VIP scores, the
content is insufficiently mathematically defined for statisticians to rigorously evaluate, nor does it
give an intuitive explanation for readers who are not familiar with it. For the content of figures, the
explanation for figure 2B is mixed with that for figure 2C. I’d suggest to move those contents
related to figures to main text or figure captions to make it more accessible to readers.
2. Please add the full name and definition of TIC. I guess it is concentration of each metabolite? Reviewer #3 (Remarks to the Author):
To me, the author's response to my suggestion to include an analysis of plasma concentration of
2HG upstream (within the arterial supply of the tumor) and 2HG downstream (in the venous
drainage of the tumor) is not sufficient. There are well documented methods for the use of mass
spectrometry to detect 2HG (Santagata et al PNAS July 29, 2014 111 (30) 11121-11126). It
appears that the method the authors have chosen another method using the QTRAP5500 does not
separate 2HG from a similarly sized confounding metabolite.
A bigger problem is that the authors cannot provide even basic genetic characterization of the
tumors they've analyzed. Basic molecular characterization of gliomas is the standard of care in
clinical practice and can certainly not be avoided in a research setting. If the authors no longer
have tissue or samples from these patients, I would suggest a prospective experimental design
where then can collect arterial and venous blood, as well as tissue for basic genetic analysis: IDH
status, ATRX status, 1-19q status. To me a basic experiment showing that 2HG is present in very
low concentration upstream and high concentration downstream is essential. Without this it's very
hard for me to understand the metabolic results being presented here. That said, I still think this
manuscript represents great science- it just needs to be strengthened to ensure the data are
interpretable within the current diagnostic framework used to describe gliomas.
Peer review of: Using arterial–venous analysis to characterize cancer metabolic consumption in patients (2020)

REVIEWERS' COMMENTS:
Reviewer #2 (Remarks to the Author): The authors have addressed my concerns.
Reviewer #3 (Remarks to the Author):
 The response to my suggestions is very nicely constructed. Ideally it would be great to see the
 observation that 2HG levels in venous samples greatly exceed that of plasma or arterial samples in
 a larger series of patients but I am quite satisfied by the data presented and support publication at
 this point.
Peer review of: Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage (2020)

 
 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
my comments have been addressed 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors provide a revised manuscript aimed to determine the relevance of the meningeal 
lymphatic system on the clearance of intracranial erythrocytes after subarachnoid hemorrhage. 
Overall the manuscript is much improved by the additional experiments. 
A few remaining concerns warrant discussion: 
1- The authors refer to the lymphatic zone of the cervical lymph nodes, but more standard 
terminology for lymph node anatomy is suggested. 
2- Why is there parenchymal hemorrhage in the subarachnoid blood injection model (Fig 3G)? 
3- The terminology of M1/M2 microglia is no longer considered straightforward in vivo, and the 
authors should be careful calling the cells M1 or M2 based on 2 markers. Furthermore, it appears 
they are quantifying single positives (CD206 or CD16/32) and ignoring the double positive gate. 
4- The authors should not report the trends or numerical differences when there is no statistical 
significance (see CD206 results of MAZ51 + SAH section). 
 
 
 
Reviewer #3: 
Remarks to the Author: 
The authors have appropriately addressed all of my comments. Good job.
Peer review of: Rhythmic light flicker rescues hippocampal low gamma and protects ischemic neurons by (2020)



Reviewer #1 (Remarks to the Author): 

Zheng et al. presented a revised version of their ms describing the neuroprotective effect of 40 Hz 
flickering light on CA1 neurons, synaptic plasticity of Hp and in vivo cognitive function in a 
2VO+hypotension global ischemia model. The authors have done a good job in responding to prior 
critiques with either new data or useful discussions. I am largely satisfied with the responses to my 
comments. I have only minor requests or suggestions for the authors to consider below: 

1. It would be more convincing to show Fluorojade staining of frontal cortex, striatum and 
thalamus nuclei of mice with 2VO to fully characterize this model. 
2. I suggest to cite ref #46 as the reference for the 2VO model on page 23, since ref #19 was a 
rat study. 
3. For the hippocampal LFP-novel object exploration study, direct evidence in moving velocity 
would be helpful to strengthen the data. 

Reviewer #2 (Remarks to the Author): 

I appreciate the authors' efforts to revise the manuscript, and many aspects have improved. 
However, my concerns regarding the rigor of the statistical analyses were not really addressed or 
were misunderstood. I repeat my concerns again below and try to clarify so that the authors will 
understand what I mean: 

1. Statistics should be clearly described in the text, and statistics should be provided with degrees 
of freedom and exact p-values, not just p-values < 0.05 or whatever. 
2. Main effects in ANOVAs should be reported to justify use of post-hoc tests. 
3. When comparing effects of treatments across groups, all groups should be included in the same 
analysis, with a significant interaction effect shown to back up the claim (for example, in Figure 1, 
authors conclude that different rhythm types are differentially affected by the different types of 
treatment, but do not report a significant interaction effect to back up this claim). It is 
inappropriate to conclude that differential effects of treatments are observed across groups simply 
because p-values are significant for one group and not another (See 
https://www.nature.com/articles/nn.2886). For example, in figure 1, it is inappropriate to conclude 
that only low gamma is affected simply because p-values are significant for low gamma group and 
not for the theta and high gamma groups. 
4. Repeated measures tests should be used when multiple measurements are taken from the same 
slices or animals across time, when different rhythm types are analyzed within the same 
recordings, etc. 

Reviewer #3 (Remarks to the Author): 

Manuscript has been updated with specific reference to reviewer comments. In particular the 
clarity (in particular of methods and results) has improved along with reducing the over 
interpretation of the impact/translational relevance. 

Claire Gibson
Peer review of: Plasma membrane H+-ATPases sustain pollen tube growth and fertilization (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have greatly improved the manuscript and it is now acceptable for publication. 

Reviewer #3 (Remarks to the Author): 

Congratulations to authors for addressing all the comments raised. Really an excellent paper,I 
hope this will form basis to explore other roles of H+-ATPase.
Peer review of: Flexibility of intrinsically disordered degrons in AUX/IAA proteins reinforces auxin co- (2019)


2 

REVIEWERS' COMMENTS: 

Reviewer #4 (Remarks to the Author): 

All comments were addressed in a satisfactory manner and I recommend publication. 

Reviewer #5 (Remarks to the Author): 

The authors successfully addressed both major points regarding the computational part raised in 
the previous round of review and I agree that the manuscript is accepted for publication.

 

Niemeyer et al.
Peer review of: Effect of sequence depth and length in long-read assembly of the maize inbred NC358 (2019)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have addressed most of my concerns and comments. 

Reviewer #2 (Remarks to the Author): 

I thank the authors for the revised manuscript, which properly addresses my earlier comments. This 
manuscript will provide an important reference paper for the application of long-read sequencing and 
assembly of complex plant genomes. 

Reviewer #3 (Remarks to the Author): 

In my initial review of this manuscript, I thought that it was large, comprehensive, insightful, and very 
helpful addition to the craft of creating better assemblies of very complex plant genomes. I had no 
real concerns about the manuscript as it was. My fellow reviewers, having more current experience in 
this field, came up with some reasonable suggestions for improvement and clarification of the text. I 
think the authors have done a good job of addressing the reviewers' concerns, and in the process 
have improved the manuscript substantially. The authors have added some additional analyses, 
addressed specific concerns, clarified some of the language used, and provided a more comprehensive 
background in the introduction. I think the changes should make this manuscript very helpful to those 
deciding on what path to take in generating a genome assembly. Assuming that the other reviewers 
are largely satisfied with the responses, I feel there is no reason to hold back on publication at this 
time. 

Roger Barthelson
Peer review of: Repressive chromatin modification underpins the long-term expression trend of a perennial (2020)



Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

The authors have now provided a much expanded discussion of the derivation of the differential 
equations. This is a big improvement and hopefully readers will now be in a better position to 
understand the assumptions built into the model. There is, however, still one difficulty I have. This still 
stems from the term representing the transition MM->UM. In the original stochastic model this arises 
from multiplying the probabilities together for being in the MM state and being in the An state. 
However, such a product is only correct if the two probabilities are uncorrelated with each other, in 
other words the probability of being in the MM state is independent of being in the An state. I don't 
think this is true in the model the authors propose. At the very least the procedure the authors apply 
is an assumption (technically a mean field assumption) that may not be entirely correct. This 
assumption must at the very least be stated.
Peer review of: Repressive chromatin modification underpins the long-term expression trend of a perennial (2020)

Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

The authors have responded to most of my comments and the manuscript has improved. However, 
one item has not been satisfactorily resolved: the transition MM->UM in the model depends on 
transcription from other loci, including in other cells, and this then affects removal of K27 at MM loci. 
There is no evidence to my knowledge that this is true; only transcription at the individual locus in 
question will affect removal of K27me3, not from other loci. I therefore remain concerned that the 
equations contain a flaw. Just because the experiments and model are constructed at a tissue level 
does not address this particular point. 

Reviewer #2 (Remarks to the Author): 

The authors have addressed my criticisms well during the revision of this manuscript. I have only two 
very minor suggestions for changes in wording. 
1. line 37; I suggest "plants are sessile" rather than "plants live sessile" 
2. line 43-44; I suggest "temperatires greatly fluctuate in the natural enviromnent of A halleri" rather 
than "in the natural population of A. halleri" 

Reviewer #3 (Remarks to the Author): 

It was a real pleasure to read the revised version of the manuscript. The authors have answered all 
points raised in my first revision to my satisfaction. In particular, the extension of the modelling 
approach to the distal nucleation region added novel aspects and provides a mechanism for the 
"ratchet-like" regulation of FLC in perennial Brassicaceae. 

Reviewer #4 (Remarks to the Author): 

No further comments 

Reviewer #5 (Remarks to the Author): 

Thanks for revising the manuscript. I do not have any further comment. I recommend publication.
Peer review of: A mycorrhizae-like gene regulates stem cell and gametophore development in mosses (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have taken the reviewers' comments seriously, and have given them good 
consideration. I am content with the revisions made. 

Reviewer #2 (Remarks to the Author): 

The authors have fully and satisfactorily tackled all of my previous comments. I do not have any 
further remarks.
Peer review of: The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate- (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors addressed all my concerns in their revised manuscript. I recommend publication in 
Nature communications. 

Reviewer #3 (Remarks to the Author): 

I understand the technical difficulty associated with non-model plant materials. I suppose that 
authors responded to all comments sincerely and their excuses are largely understandable. 
One concern is the type of the publication. I would like to leave this point to editor's dealing. 

Reviewer #4 (Remarks to the Author): 

The authors addressed my points to my satisfaction with exception of the timing of the gene 
duplication that lead to DAH. The extended phylogeny nicely clarifies in more detail when the gene 
duplication took place. However, I disagree that the duplication “occured in Menispermaceae plants 
after they diverged from the rest of Ranunculales plants”. The DAH sequences group at the base of 
the Ranunculales FLS-like clade (without bootstrap support…), which presumably includes 
Menispermaceae and other families. This would suggest that the duplication happened early after 
separation of the Ranunculales from other eudicot lineages, but before Menispermaceae separated 
from other lineages (families) within the Ranunculales. If the duplication happened within the 
Menispermacea, the ADH sequences should have been part of a (or the) Menispermacea clade 
within the Ranunculales. It may be helpful to annotate clades within the Ranunculales with 
taxonomic family information. It appears Supplemental Data Table 2 detailing the sequence 
information used for the extended phylogeny is missing.

 
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