JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: E2F-dependent transcription determines replication capacity and S phase length (2020)

REVIEWERS' COMMENTS:
Reviewer #1 (Remarks to the Author):
Reviewer #2 (Remarks to the Author):
I am now fully satisfied with the revisions. The authors have answered all of my questions. Anja Katrin Bielinsky
Reviewer #3 (Remarks to the Author):
I am now satisfied by the newly added data and authors' responses, and recommend this
 manuscript for acceptance
 
Throughout the text authors convey the idea that E2F-depedent transcription controls the
 replication capacity of cells as part of a regulatory mechanism to ensure timely replication
 completion and to optimise replication fork speed:
 P1. “Thus, at its most fundamental level, E2F-dependent transcription determines the replication
capacity of a cell during S phase, controlling the time it takes to duplicate the genome. More
generally, our work shows that controlling replication capacity during S phase is a robust
mechanism to ensure timely completion of DNA replication, which could be at the basis of keeping
replication fork speed within an optimal range independently of fluctuations in replication initiation
events.
P2. “Limiting the replication capacity of a cell would provide an elegant mechanism to regulate the
 global rate of replication during S phase, largely independent of the number of active replication
 forks.”
 P6. “This suggests that E2F-dependent transcription controls the amount of DNA a cell can
 synthesis per unit time in S phase, which we define as replication capacity, likely through
 regulating the expression of limiting factors for DNA replication.”
 P9. “Overall our work suggests that the tight regulation of E2F transcription in S phase is an
 important determinant in DNA replication control and genomic stability, which has important
 implications for basic biology and the understanding of cancer.”
 However, evidence is not provided on what cues would this mechanism respond to in order to be
effective, how E2F-dependent transcription would be modulated to achieve this regulation, or
through what factors would replication speed be controlled. Since the expression of many factors
important for replication depends on E2F-dependent transcription, it is a logical expectation that
increasing E2F-dependent transcription might augment replication rates and the overall replication
capacity. The authors nicely show this in this manuscript and demonstrate this preferentially
occurs through fork speed and not through increased origin firing, but the notion that E2F-
transcription is part of a mechanism controlling replication rates to preserve genome stability
remains premature at this point. Regardless the significant amount of work reported in the
manuscript, in my opinion evidence supporting these claims is required to firmly support its
publication in Nature Communications.
Peer review of: Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination (2020)


 
Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
The authors have done a wonderful job addressing my concerns and I think this is really a 
beautiful paper - congrats to them. 
 
A few minor points for the final version 
- in the abstract, I think the worked "accumulated" instead of "cumulated" is more appropriate. 
- figure 4 g, h - labeling the colors of lines and dots on the figure itself would help
Peer review of: Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton (2020)



 

REVIEWERS' COMMENTS: 

 

Reviewer #2 (Remarks to the Author): 

 

The authors have sufficiently answered all my questions. While I still do not agree that the resolution 
of images is very good, they do support what the authors want to show. Thus, I recommend 
publication in Nature Communications without further revisions. 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors have addressed my criticisms to my satisfaction
Peer review of: Structures of the human mitochondrial ribosome bound to EF-G1 reveal distinct features of (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have made an excellent effort to address all my comments. I would like to thank them for 
highlighting the changes in the text which makes it easier to find the sections (except for the FSC 
criteria which they didn't highlight unfortunately). 

The addition of the small dataset of the control mitoribosome is definitely an important addition. I 
would only ask that the authors clearly describe not just the ratcheted or non-ratcheted state but also 
the conformation of the tRNAs i.e. P/P- and E/E and A/P and P/E, I presume? 

I have only one last minor small point which is that the use of 16S rRNA is a little confusing to readers 
who are not used to mitoribosomes since it is the same size of the 16S rRNA that is in the small 
subunit of bacteria. Maybe it makes sense to use SSU and LSU rRNA or to have both 12S (SSU) rRNA 
and 16S (LSU) rRNA, particular in the figures to avoid any confusion.
Peer review of: Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop (2020)



 


 

REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The authors have addressed most of my comments satisfactorily. Two minor issues remain: 

 

I my first point, I had indicated that in order to accommodate the substrate, the Ct-extension must 
already have moved in the simulation in which only PLP was bound. The authors now show that his 
is not the case, with the Ct-terminal in virtually the same position. What confused me is the 
sentence on page 9: “In order for succinyl-CoA to bind and orientate in the active site, we reason 
that the Ct-extension must change its conformation.” But apparently, you were able to put it in and 
only then the Ct-terminal starts moving? Does this mean that there is overlap between the substrate 
and the Ct-terminal, leading to big forces and hence a distortion of the Ct-terminal? The authors say 
very little about how the substrate was modelled in. A distortion of the Ct-terminal can also just be 
the effect of not placing the molecules too carefully. If I understood correctly, the substrate was 
taken from the scALAS structure, in which the Ct-terminus is in an entirely different position. Could 
that also mean that the displacement of the Ct-terminal is only the onset of a much bigger 
movement, and it will eventually take a position similar to that seen in the scALAS structure? It 
would be good if they can explain also this aspect of the modelling effort in more detail. 

 

The authors show the repeats of their simulations in their response to the reviewers, but in the 
supporting information, they only mention that figures S10 and S11 are a representative example of 
n = 2. What speaks against showing all data in the supplementary material? I think the data shows 
that there is an asymmetry, but also that there is a larger variability between the monomers and 
repeats. 

 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors were very responsive to this reviewer's comments. The Revisions are satisfactory and 
have strengthened the manuscript.
Peer review of: Quantifying CDK inhibitor selectivity in live cells (2020)


 

 

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have done a very nice job addressing concerns from the first submission. In particular, 
the addition of Nanobit is quite nice. 

Minor correction: line 35 has a grammatical error with a period followed by a comma. 

Optional issue to address: New residence time data (starting on line 287) was fit with a one-phase 
association equation in prism. If the authors have data showing these measurements at different drug 
concentrations, then they could extract kon and koff. Having these parameters in the manuscript 
would demonstrate that they can be measured. 

Reviewer #3 (Remarks to the Author): 

The authors did an excellent job addressing all reviewer questions. I fully support the publication of 
this manuscript with these new experimental data. I believe some of the new findings, particularly 
those addressing the reviewer questions below, to be worthy of inclusion in the main figures, but I 
leave it up to the editors and authors on how to address this: 

Reviewer 1 - questions 2, 3 
Reviewer 3 - questions 1, 2
Peer review of: Split Intein-Mediated Protein Ligation for detecting protein-protein interactions and their (2020)


  
  
   
  
 

Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
This is a re-revised manuscript that now deals with a few of the concerns of the original review, 
rather than pointing out that those concerns were unwarranted. The revision represents at least an 
initial effort to establish some degree of a quantitative basis for detecting interactions. In 
particular, some of the Western signals have now been quantified and at least in one case have 
been compared to ELISA results. However, I am still puzzled by how a user establishes that an 
interaction has been detected, even if you accept the authors’ contention that the cutoff value can 
be different for different protein pairs. Indeed, on line 204, the authors cite “a robust 1.5 fold 
increase” in spliced signal after rapamycin treatment as evidence of interaction detection. Lines 
278-281, however, indicate the lack of interaction detection of a different pair because “the signal 
was not significantly enhanced after EGF stimulation” given the density ratio was 1:1.7. Perhaps 
these contradictory statements provide some sense of what is creating confusion about these data.
Peer review of: Light-triggered switching of liposome surface charge directs delivery of membrane (2020)


 
Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
I thank the authors for addressing my questions and concerns adequately. I recommend 
publication. I have no further requests. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The manuscript has been improved. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
In my opinion, the authors have addressed all reviewer comments to a satisfactory extent. I 
consider the manuscript suitable for publication in Nature Communications.
Peer review of: Multiplexed Optical Sensors in Arrayed Islands of Cells for multimodal recordings of cellular (2020)


 
Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
Dear Authors, 
Congratulations to this beautiful work. All my comments have been addressed satisfactorily. 
Sincerely, 
Roland Malli 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have addressed most points adequately. It is regrettable they were unable to include 
biological repeats of their experiments on hiPSC cardiomyocytes and indeed, that only one 
(commercial) source of cardiomyocytes was used. This is correctly the current standard in the field 
since there is biological variability between lines (the authors actually cite the variability in 
conduction velocities they found in the literature for CDI cardiomyocytes) and batches although it 
is appreciated this is more of a "technical approach" paper and not intended to advance the 
biology. It is to be hoped then that the absolute values here are not cited verbatim by others. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
To clarify simultaneously the different response behaviors in cells treated by chemical or physical 
treatment, the authors of this manuscript developed a technique, Multiplexed Optical Sensors in 
Arrayed Islands of Cells (MOSAIC). This method enables parallel sensing for different signaling or 
metabolism species or events utilizing the patterned cells encoded with different fluorescent sensor 
with microarray printing the sensor encoding lentiviral vectors. The special design for motile and 
nonmoyile cells has also been displayed. This technique is a new advance in synchronous sensing 
of cell events in a number of living cells, which provides more accurate same culture conditions 
and timing sequence. It is desirable the rapid publication in this journal. 
Since all my concenrs have been fully addressed, I suggest to publish its without no more revison.
Peer review of: Mapping allosteric communications within individual proteins (2020)



 

REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The authors have adequately addressed our previous comments. Just a couple of very minor 
suggestions to enhance clarity: 

 

p. 7 of merged PDF, lines 165-166: “These results indicate that the allosteric correlation between the 
allosteric site and the active site is generally reversible.” We suggest rephrasing this statement to 
take into account that not all allosteric couplings are reversible as previously shown by E. Freire et al. 

 

Fig. 5A-C: it would be very helpful to add a label for alpha5 in panels A-C of Fig. 5 

 

 

 

Reviewer #2 (Remarks to the Author): 

 

 

The new version of the manuscript, SI and the response to reviewers seem appropriate and have 
successfully answered my questions. I am particularly pleased with the effort to include more 
quantitative comparisons with other methods to demonstrate the advantage of this new 
methodology. I am also satisfied with the response to the other reviewers asking to clarify 
methodological aspects, acknowledge and properly cite previous work and the definition and 
clarification of the work in other systems. 

 

Revisions were extensive and comprehensive with the possible drawback that the SI is possibly too 
long. I think this work deserves to be published and its original contributions are substantial. 

 

 

Reviewer #3 (Remarks to the Author): 

 

I have found the revised version of the manuscript by Wang et al. to be considerably improved. In 
particular, the relevant literature has now been more comprehensively covered and some of the 
computational details have been provided to enable the reproducibility of the findings. Moreover, 
the discussions are now based more on quantitative arguments and comparisons to additional 
measures that determine allosteric sites and residues that control allosteric pathways have been 
included. 

 

Some typos: 

line 352: allostery response -> allosteric response 

line 353: please reword, "...distant allosteric communication at distant site..." 

Table S2: k_cat should not be capitalized
Peer review of: The receptor PTPRU is a redox sensitive pseudophosphatase (2019)


REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The authors have done a largely admirable job at addressing the concerns of the reviewers and 
especially, through editing changes and changes to the figures, made the results considerably more 
clear. 

 

I have only a final concern, which arises, in part, to the significantly increased clarity of the message 
in the current manuscript. The authors argue that the pTyr binding pocket structure is 'disrupted' 
and, particularly, that "This new loop orientation blocks the catalytic cysteine and would directly 
interfere with pTyr binding (Fig. 2e)." and "Our structural data identify multiple features that would 
disrupt both substrate binding and catalytic activity." 

 

Yet, the conclusion of the manuscript is that the function of the protein is to bind and titrate 
phosphorylated substrates from their endogenous phosphatases: "This ability to bind substrates that 
overlap with active phosphatases, combined with the lack of phosphatase activity of PTPRU suggests 
that the likely role of PTPRU in cells is to act as a decoy receptor that sequesters substrates 
protecting them from dephosphorylation". 

 

How are these apparently opposing messages reconciled? 

 

 

Reviewer #3 (Remarks to the Author): 

 

The authors have satisfactorily responded to my critiques of the original manuscript, and I am happy 
to recommend the revised manuscript for publication.
Peer review of: Generation, localization and functions of macrophages during the development of testis (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

While this referee based on own but not published experiments respectfully disagrees on the lack of 
bioavailability of TAM at later time points of development when administered at E13.5 the new labeling 
experiments performed at E8.5 answer my questions. 
Lineage tracing of EMP-derived tissue-resident macrophages is possible by using Tnfrsf11a-cre (Rank-
cre) knock in mice (Percin et al 2018 Nature Communications, Jacome-Galarza et al 2019 Nature). To 
label macrophage progeny of definitive HSCs Vav-cre (Jacome-Galarza et al 2019 Nature) or Flk2/Flt3-
cre (Gomez Perdiguero et al 2015 Nature) lineage-tracing mouse lines can be used. 
The new approaches for depleting embryonic macrophages significantly substantiate the new 
conclusions drawn by the authors! In line with this comment the authors have sufficiently addressed 
and resolved all my concerns. 

Reviewer #2 (Remarks to the Author): 

I find the revised manuscript to be substantially improved. The additional data regarding function of 
these cells in development is interesting and well done. The authors did a great job of addressing my 
concerns. 

Dan McVicar 
Laboratory of Cancer ImmunoMetabolism, NCI 

Reviewer #3 (Remarks to the Author): 

I have reviewed the revised manuscript by Salmi et al. The authors have adequately addressed my 
comments with revisions to the text and additional experimental evidence. Technical limitations (low 
cell counts in younger animals) were also made more clear. The revised article is much improved and 
I have no further comments.
Peer review of: ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic (2019)


 
REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors addressed all the relevant concerns raised by the reviewers. Notably, the availability 
to the community of the results shown in the manuscript has also been improved. I think this 
newer version of the manuscript is suitable for publication in Nature Communications. I only have 
very few minor comments to improve the accuracy of some sentences and/or the overall clarity: 
- Line 161: “Of note, the TOBIAS ‘ATACorrect’ module applies an “expected” intermediate.” I 
understand the message of this sentence by reading the overall paragraph that follows, but per se 
I could not understand the meaning of it; 
- Line 499: “mechanisms” rather than “concepts”? 
- Considering the new versions of figs. 1 and 2, I now see panel 1A as a better fit for fig. 2 (so that 
fig. 1 would be completely focused on introducing TOBIAS, and fig. 2 on the ZGA analysis). 
 
 
 
Reviewer #2 (Remarks to the Author): 
 
All of the reviewer's concerns have been addressed. The paper has improved greatly. It is 
interesting and reads well. The new method and the results presented constitute a significant 
scientific advance. 
 
The sentence in line 119 is unclear: "expected" intermediate ?
Peer review of: Dynamic changes in the epigenomic landscape regulate human organogenesis and link to (2020)



Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
In this revised version of their manuscript, the authors: 
1. Add more in-depth analyses to support their claim regarding the absence of promoter bivalency 
in cell-fate determining genes in human organogenesis.   
2. Include sufficient details on how computational analyses were performed.   
3. Provide the data for their correlation analysis between enhancer activity and gene expression, 
which will undoubtedly be a valuable resource to the research community.   
4. Have appropriately toned down their claims and discuss limitations of their analysis (e.g., 
regarding the analysis of DDDs or the confounding effect of cellular heterogeneity).   
 
Additionally, they generated more experimental data to support the functional relevance of the 
tissue-specific enhancers identified in this study. 
 
The authors have thus sufficiently addressed all my concerns and I recommend this revised 
manuscript for publication.
Peer review of: Mutations in FAM50A suggest that Armfield XLID syndrome is a spliceosomopathy (2020)


 
 
 

Reviewer #3 (Remarks to the Author): 

The authors have addressed all of my concerns. 

Reviewer #4 (Remarks to the Author): 

The revisions added to the manuscript have clarified and enhanced the examination of Fam50A. 
The new data indicating a role of Fam50A in spliceosomopathy is compelling, and has 
strengthened the paper. Some more experiments need to be done, however, to fully address 
Reviewer #2’s concerns. 

Reviewer #2 argues that a zebrafish knockout model is only indirectly informative, and that the 
knockout needs to be rescued with mutant versions of fam50a mRNA. The authors have performed 
this rescue, but only use swim bladder formation as a readout of the mutant phenotype. Swim 
bladder formation is unrelated to any patient-relevant phenotype and is therefore uninformative 
with regards to the effect of the mutations. The cartilage-patterning defects examined in the 
morpholino experiment are of interest, but they only indirectly address the neuronal changes that 
would be expected in an intellectual disability model. To assess the effect of the FAM50A variants, 
the rescue of the knockout should be assessed by huc, her4.1, and a cell death marker
Peer review of: Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation (2020)


 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have satisfactorily addressed all concerns. The manuscript looks good and addresses 
the critical caveats of the model and mechanisms. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have resolved almost all the remaining questions and I appreciate the changes in the 
text, I believe that improves clarity. 
Although, I respectfully still disagree with them, as they disagree with me, in regards to the 
mechanistic link between naïve and cancer, I believe that ultimately this is their manuscript, 
therefore if they are confident of that link they should go ahead with it. That’s how science 
advance, creating discussions and rectifying concepts if necessary eventually. 
 
The overall work is of good quality, they have addressed all other concerns, thus I support the 
publication of the manuscript.