JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: Global translation during early development depends on the essential transcription factor (2020)



Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

The authors have done an excellent job at addressing our comments. However, there are still a few 
issues with the manuscript that should addressed. 

In supplemental Fig 1E, they show the expression of Nanog and Oct4 in the trophoblast of PDRM10 
mutants. There also appears no ICM. However, these images would be greatly improved by including an 
overlay. In addition, the control embryos in this figure do not have a completely normal morphology. Is 
the ICM missing in the mutants missing and the co-expressing ICM/trophbolast genes - this is what 
appears in the figure? How does this fit with the ex vivo culture data? Clearly better staining, for both in 
vivo derived and ex vivo cultured embryos (including the time points shown in bright field), 
quantification of expression and n values are needed here. They should also augment this with more 
extensive analysis of their RNA seq from wild type and null embryos. 

A similar issue exists with respect to the ESC phenotype. In all cases their control cells show gene 
expression trends (e.g. Fig 3d, S3A), why does cell culture over 2 days produce these differences? The 
analysis is quite difficult to interpret as the gene expression changes they see relative to the controls do 
not always appear as significant as the changes between the time course for the controls. They are also 
missing the figure legend for S3e. 

The differentiation experiments in rebuttal figure 3 should be included, but with additional analysis of 
pluripotency genes in differentiation (particular given their ectopic expression in vivo). 

Rebuttal figure 2 on additional translational related targets should also be included in a revised 
manuscript. 

On line 243 there are two different n values for the same 8.7%. Assume this is just a typo. 

Reviewer #2 (Remarks to the Author): 

This is a resubmission in which the authors have added new information to bolster their claim that the 
phenotypic effects of PDRM 10 are through eIF3b. This paper was previously rejected but the authors 
have decided to come back with new data claiming that this link is better supported. 
Figure 4 is completely new and is provided to show that eIF3b is an essential gene in early embryos and 
mESCs, which is good to know but does not strengthen the PDRM10 relationship. 
The panels for new Fig 5 were in the previous MS, so there is no new information here. 
At the end of the day, the fact that a transcription factor regulates an essential translation factor, and 
that translation is affected when you remove the transcription factor is an expected result. The fact that 
you can't completely rescue the translation defect by OE of eIF3b says something else is at play here and 

makes it difficult to get excited about claims of PRDM10 phenotype being "largely mediated though 
eIF3b-dependent effects on global translation". (ABSTRACT).
Peer review of: Unique properties of a subset of human pluripotent stem cells with high capacity for self- (2020)



Reviewers' comments: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have now adequately addressed the reviewer comments. 
 
 
Reviewer #2 (Remarks to the Author): 
 
I don't think the characterization of differentiation potential into the three germ layers is sufficient to 
address the question raised (revised Figure 2d). The data doesn't compare differentiation potential 
quantitatively and the data presented is of low quality and value. More experimentation is required to 
address this important point. 
 
The original comment was 
"Can 'archetypical' cells be differentiated to the three germ layers? Are they pluripotent and how does 
their potential compare to primed cells? 
Is it possible that 'archetypical' cells have a reduced capacity for germ layer formation while having 
increased germ cell capacity?" 
 
 
Reviewer #3 (Remarks to the Author): 
 
No further comments.
Peer review of: Long-term culture of human pancreatic slices as a model to study real-time islet (2020)


 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
To reiterate, I do think that this paper is a major breakthrough in pancreatic tissue long term 
culture of up to a remarkable 10 days, which is of sufficient duration for numerous applications in 
pancreatic islet and exocrine biology, and here the islet capability was applied to understanding 
neogenesis of beta cells using viral mediated lineage tracing in normal pancreas. I strongly believe 
that this technical capability is extremely important and useful to the large community of 
pancreatic investigators and should be disseminated. 
In the revised manuscript and rebuttal, these workers have satisfactorily addressed almost all of 
my concerns, although the new exocrine data is not perfect with regards to histological details, this 
is not the major point of this work. 
There must be an error in Fig. 3t using 10 MICROmolar CCK8, which is highly toxic, and likely they 
were using 10 (or 100) PIDOmolar CCK8. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors have addressed all of my concerns either experimentally or by adding/modifying 
texts. Therefore, I believe that the current version of the manuscript is suitable for publication. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
This reviewer appreciates and acknowledges the hard work of authors to provide additional data 
related to modeling of oxygenation, staining for beta cell maturation markers, glucagon secretion 
data etc. It is noteworthy that the authors have made a genuine attempt to address these 
questions.
Peer review of: LSD1-mediated enhancer silencing attenuates retinoic acid signalling during pancreatic (2020)

 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
We are pleased to see that the authors have addressed all comments very well. There are a couple 
of points where the authors are not sure whether to include or not the data. We would 
recommend: 
1) to keep out the short-term YFP tracing, as suggested by the authors (rev fig 1) 
2) to include the low magnification YFP tracing, showing the recombination efficiency (rev fig 3) 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The authors carefully addressed all my concerns. The work is addressing a timely topic and is well 
suited for publication in Nature Communications. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
This revised manuscript is improved, and the authors have addressed most of my previous 
concerns. Overall this is study represents an important advance in the field providing a 
mechanistic basis for how the duration of transcriptional responses to extracellular signals are 
modulated and how LSD1 can epigenetically decommission enhancers are after the removal of the 
signal. In addition to informing pancreas development this mechanism is likely to impact signal 
responsive transcription in many biological contexts. 
 
Minor point that should be resolved: Showing that LSD1 and FOXA/GATA bind to the same 
enhancers is a nice addition, but it does not demonstrate that FOXA recruits LSD1 – the authors 
should temper this conclusion. 
 
 
 
Reviewer #4: 
Remarks to the Author: 
The authors have been thoroughly attentive to the initial reviews, and their final version nicely 
describes the mechanism of LSD1 function in pancreatic endocrine development. Although there 
are still a few inconclusive areas, these are trivial overall compared to the strength of the data and 
their interpretation. I expect that this work will be of great interest to the pancreas development 
community, and I support its publication.
Peer review of: Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by (2020)



REVIEWERS' COMMENTS: 

 

Reviewer #3 (Remarks to the Author): 

 

By performing additional validation experiments of the Pex19 knockdown, which I suggested, the 
anomalies with the Pex5/Pex14 depleted cells could now be clarified. 

The other issues were also satisfactorily dealt with by the authors.
Peer review of: CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and (2020)


REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors have addressed my concerns. I am happy with the revised manuscript. 
 
 
Reviewer #2 (Remarks to the Author): 
 
I find it strange that the authors could not cluster rare populations (interneurons, astrocytes and 
microglia) using top variable genes. It seems that this is likely due to a technical bias and small 
sample size (less abundant cells with more complex and arborized morphology are less likely to be 
sampled using this technique). 
 
I think that the rational behind the use of prom1 +/- FACS sorted cells for downstream bulk-RNA seq 
is better explained. Considering all the data presented and the thorough functional validations 
performed, I think there is enough evidence support for two progenitor populations giving rise to 
upper and deep-layer neurons. 
 
It is now clearer why the authors chose to use tSNE-NN as it separates the RGC population better for 
them to see the two trajectories. I am more convinced that the two trajectories they presented are 
real. 
 
 
 
 
Reviewer #3 (Remarks to the Author): 
 
We thank the authors for addressing our questions. 
2 points: 
1- In comment 6, the authors state “Thus, our data support the idea that cortical progenitor cells 
commit to neurogenesis before they upregulate Eomes expression.” This is not mentioned in the 
manuscript and would benefit from being explicitely stated. 
 
2- Comment 7, GSEA Hallmark GO terms do not correspond to the ones cited in Figure 5. Please 
correct or explain. 
 
 
 
Page 6 Line 22: “tSNE-NN map map”: correct.
Peer review of: Context specificity of the EMT transcriptional response (2020)


 
 
 
 

REVIEWERS' COMMENTS: 
 
Reviewer #3 (Remarks to the Author): 
 
The authors have provided a rebuttal solely based on rewording some paragraphs. Although they 
have somewhat clarified some of the criticisms raised by the reviewer, it is clear that the present 
study is facing the same issues regarding the heterogeneity of response in part due to the extent 
to which each cell line can engage into EMT. 
Contrary to what the authors claim (lines 125-128), it is not surprising that whatever the EMT 
inducer used in the study, each cell line transcript will always cluster together with the parental 
cell line, since each cell line has a strong gene expression profile linked to its tissue of origin. 
It is also worrisome that the authors have not detected at least Zeb 1 in A549 cells perhaps due to 
the real limitations of the single-cell sequencing technology. The relatively recent technology still 
suffers from several issues in terms of detecting a large fraction of transcripts, even in cell lines. 
Another intrinsic difficulty in single-cell sequencing is that cells are not synchronized and are 
analyzed at different positions of the cell cycle, thus increasing the variability in the 
transcriptomes. The authors should have carried out RNA sequencing for each sample to serve as 
a reference and to determine whether they should have detected important transcripts, including 
EMT transcription factors, in their single-cell sequencing. 
The gene signature derived from this study is of no surprise, since the most expressed genes are 
related to the extracellular matrix and proteases known to be common denominators for all cell 
lines and tumors engaged in EMT. However, in tumors, these genes are mostly expressed by 
stromal cells. This new signature needs to be evaluated in tumors and in cell lines in large datasets 
to evaluate its performance relative to other signatures. 
The drug screen, although potentially interesting, is quite preliminary, as stated by the authors. It 
has not delivered interesting data leading to the identification of potential new targets, aside from 
RIPK1, which can contribute to activation of some EMT modules. 
 
 
 
Reviewer #4 (Remarks to the Author): 
 
Through multiplexed single cell RNA sequencing, the study by Cook et al., provides a 
comprehensive, rich EMT dataset that will be undoubtedly utilized by the broader EMT community 
for cancer related studies. The authors have adequately addressed the concerns that had been 
raised through clarifications in the text, detailed discussion and adding references and requested 
supplementary data. 
Although the study is strong in its approach and analytics,and offers in depth views of EMT 
dynamics - all valuable for future studies - I do feel that the main message, that EMT is a context-
dependent and heterogeneous process, is perhaps not as novel and is already recognized in the 
field.
Peer review of: A broad-spectrum virus- and host-targeting peptide against respiratory viruses including (2020)


 

 

Peer Review File - Reviewers' comments second round 
 
 
Reviewer #2 (Remarks to the Author): 
 
The authors improved the manuscript from Yuen et al. significantly and addressed all questions 
and comments with intensive efforts. From my view this article is now suitable for publication in 
nature communications. 
 
 
Reviewer #3 (Remarks to the Author): 
 
The authors have sufficiently addressed my major points. The revised manuscript has significantly 
improved. One minor point: the survival graphs should be presented as Kaplan-Meier plots.
Peer review of: Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in (2020)


 

 

 

 

 

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

None 

Reviewer #2 (Remarks to the Author): 

All issues raised were very well-addressed. Additional data are provided that further strengthen 
the work. No further comments
Peer review of: Protein–ligand binding with the coarse-grained Martini model (2014)


 

REVIEWERS' COMMENTS second round: 
 
Reviewer #1 (Remarks to the Author): 
 
Review of NCOMMS-19-28960A Revised Paper 
 
The authors have responded to nearly all of my comments satisfactorily in the rebuttal and revised 
manuscript. 
 
In particular, they have expanded the range of their study which helps to convince the reader of 
the potential of the methods they have developed. 
 
I do think that their response to the question of elastic network settings is a bit weak – some 
degree of testing of the effect of varying the elastic network cut-off would be easy to do, and 
indeed they presumably explored this at a preliminary level to decide upon the shorter cut-off for 
GPCRs. However, I do not think this should be a sticking point. They refer to possible advances by 
using Martini 3 + Go-like models, both in the rebuttal and the revised ms. It will be of interest to 
see how this performs for these systems in future studies. 
 
In summary, I think the revised manuscript is much stronger and I would recommend acceptance. 
 
 
 
Reviewer #2 (Remarks to the Author): 
 
This is my second review about the manuscript on the use of MARTINI coarse-grained models for 
protein-ligand binding. I found that the revised manuscript has been improved and the authors 
answered questions and comments appropriately. 
 
Prediction of protein-ligand or protein-drug interactions is one of the central issues in 
computational chemistry. Atomistic approaches can be more reliable if sufficient sampling is 
achieved. But, protein-ligand binding process is slow and atomistic MD simulations may not be 
able to predict the binding process with reasonable computational resources. 
 
The authors proposed in the paper the use of MARTINI coarse-grained models and showed 
successful binding results. Upon the request of the previous review, the authors expanded the 
discussion in the manuscript, even the limitation of current models. I believe that this is a 
significant progress in the field and would contribute to in-silico drug discovery also. I suggest the 
publication of the manuscript in the current form. 
 
 
Reviewer #3 (Remarks to the Author): 
 
The authors have addressed my concerns.
Peer review of: Prolonged tau clearance and stress vulnerability rescue by pharmacological activation of (2020)


REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have addressed all of my comments in full, and I thank them for taking the time to 
provide a comprehensive rebuttal to each of my points. No further comments other than to 
complement them on an excellent paper! 

Reviewer #2 (Remarks to the Author): 

The authors have nicely addressed my concerns, especially around clarification of the selection 
criteria for compound advancement. The key choices are much more transparent.
Peer review of: Multiplex secretome engineering enhances recombinant protein production and purity (2019)

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
Thank you for giving me tho opportunity to review this manuscript by Kol et al. This is a very 
interesting, well designed and comprehensive study that will undoubtedly be of high interest to the 
bioprocessing community. I only have three questions for clarification and comment by the 
authors: 
On page 11, line 312, the authors introduce a comparison based on specific HCP productivity. I 
suspect that this refers to secreted HCPs only - can the authors please clarify in the text. 
 
On page 14, line 373, the authors mention that the bioreactor experiments were carried out, in 
part, to ensure that the reduced HCP content was retained. In Industry this usually involves 
stability studies over multiple generations. Can the authors please clarify if any such stability study 
was carried out and if not, over how many generations stability was assessed. 
 
In a broader context and in relation to the use of model-guided genetic engineering, can the 
authors comment on whether the model simulation results for the KO cell lines were numerically 
accurate. In other words, can the model predict the % reduction of secreted HCP content for these 
cell lines with any accuracy or can it only be used for screening at this stage? 
 
 
 
Reviewer #2: 
Remarks to the Author: 
 
Dear Editor, 
Thank you very much for the opportunity of reviewing the manuscript entitled: “Multiplex 
secretome engineering enhances recombinant protein production and purity “ by Kol et al. 
The manuscript describes the generation via a multiplexed CRISPR/Cas9 knock-out strategy of 
CHO lines that very significantly reduce the production of abundant host cell protein (HSCPs). 
These knock-out clones surprisingly have a superior fitness while producing high titer of antibodies 
in a reduced HSCP secretory background that facilitates the removal of unwanted impurities. 
Overall, the manuscript shows the feasibility and validation to larger multi-gene scale of an idea 
previously shown for single knock-out genes. The data are logically presented, the conclusions are 
supported by the data and the manuscript is clearly written. 
 
Few revisions will further improve the quality of the work: 
 
- The data from Fig. 5 appear to be originated from one single high-producing rituximab clone for 
each the WT, 6xKO and 11xKo lines. At least two additional clones for each genetic condition 
should be tested to show reproducibility of the same findings in multiple clones. 
 
- The conclusion on line 451: “Importantly, the ability to generate high mAb producers was not 
perturbed” is not accurate as rituximab-producing clones from the 14xKO were not obtained, and 
the clone from the 11xKO seems to express lower titer levels than WT or 6xKO (Fig. 5B). Actually 
the Authors should comment on possible reasons why clones from the 14xKO were not obtained. 
 
- The panel Figure S2 (transfection efficiency) does not have standard deviation. Repeated 
experiments should be provided with statistical analysis.
Peer review of: Multiplex secretome engineering enhances recombinant protein production and purity (2019)


Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The revised manuscript is improved in terms of clarity and accuracy. I particularly appreciate the 
acknowledgment of limitations of the experimental design/study as well as the additional work that 
has been carried out to provide evidence of reproducibility. I have no further comments for the 
authors. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
The Authors have satisfactory addressed the concerns.
Peer review of: Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat (2020)


 

Reviewers' Comments: 
 
Reviewer #2: 
Remarks to the Author: 
The manuscript is improved with the inclusion of further data. The interpretation of the data is willfully 
simplistic in this reviewer's opinion, but enough data are included for readers to decide for 
themselves. 
 
 
 
Reviewer #4: 
Remarks to the Author: 
Overall this is a thorough study of two antibodies with different binding specificity to activated protein 
C (APC): a type I active-site binding mAb and a type II mAb binding to an exosite on APC (required 
for anticoagulant activity). These antibodies have potential utility in treating coagulation disorders. 
 
Some small additions in the presentation would improve the readability of the manuscript. 
 
The humanization protocol for Fabs is given in great detail for both the Type I and Type II Fabs. 
However, the data presentation could be improved if the amino acid sequences of the resulting Fabs 
were given, possibly in the Supplementary information. 
 
No description is provided about how the full length antibodies were constructed. Exactly what TPP-
2313 (BAY 1316786) and TPP-4885 (BAY 1896502) are is unclear. Presumably they are hIgG2 but 
that is really only mentioned parenthetically on line 455. What vectors were used for their 
construction? In addition references should be provided for the constant region sequences used to 
construct BO2C11-cyno IgG1. The reference for BO2C11 is for the original hIgG4 antibody
Peer review of: Stereospecific Si-C coupling and remote control of axial chirality by enantioselective (2020)


Reviewers' comments: 

Reviewer #1 (Remarks to the Author): 

The revised version of the paper is in my personal opinion lacking some important aspects. First of 
all, the assignment of the absolute configuration to the stereogenic axis is not correct. The authors 
report that compounds 5 have the M absolute configuration but this is wrong. They have reported 
a structure with a P absolute configuration. But, independently by the drawn structure, they do not 
reply correctly to my question. I wanted to know which is the relative configuration of the products 
5, because in this way, with the absolute configuration of the stereocenter, determined by X-ray of 
3 series, they could easily know the absolute configuration of the chiral axis. Furthermore, the 
revision added on the SI, that is figure S16 wherein the absolute configuration of 5a was obtained 
via DFT calculation, can not be accepted. They used these data to write in the manuscript that 
compounds 5 have a rotational barrier major than 30 kcal/mol. Where is coming from this data? 
From figure S16 I can see that DFT calculation estimates, I repeat estimates, the energy barrier 
for compound 5a to be 27.8 and not 31.7 kcal/mol, as said in the text. You should explain the 
reason why compound 5a decides to rotate following the highest syn-TS? Finally, this aspects 
highlight a scarce knowledge of the atropisomerism phenomena which can not go unnoticed and 
drive me to consider the rejection of the manuscript.