JerMa88/TPR_Peer_Reviews huggingface dataset:
Peer review of: A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction (2020)



REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The authors present a much improved version of the manuscript and have adequately addressed 
most of the reviewer comments. There are still a few outstanding issues to address. 

 

1. The words "providing mucosal immunity" should be removed from the title as they are 
misleading. One would need to conduct animal studies to show mucosal immunity. 

2. A sequence alignment of the CDRs should also be included in the supplement, not just the 
framework regions. 

3. Even with the improved structural modeling the atomic representations in Figs. 2 and 3 of the 
mAb362 bound to RBD should be relegated to the supplement to de-emphasize the confidence in 
the model. The new mutagenesis data is highly supportive of the antibody overlapping the ACE2 
binding site but the accuracy of the model really needs to be validated with an explicit structure. 

 

 

Reviewer #2 (Remarks to the Author): 

 

The authors have made a substantial effort to address all of the points raised previously, and the 
resulting revised manuscript is greatly improved. In particular, the addition of live virus 
neutralisation experiments has strengthened their conclusions. I am mostly satisfied with the 
responses to my specific concerns (many of which were shared by reviewer 1). I would urge the 
authors to take more care when drafting rebuttal letters in future as they refer to the wrong 
supplementary figures on several occasions. 

 

The construct and purification strategy used to obtain the spike ectodomains is appropriate and I am 
satisfied by the ELISA results. However, for the sake of being thorough, I'd like to point out that 
proteins containing multimerization domains, such as T4 fibritin, can often elute at the expected 
molecular weight by SEC even if they are not adopting the desired 'intact' quaternary structure. 

 

Given the degree of sequence similarity to 80R, and the mutagenesis data, I'd say the authors 
homology model is in the right ballpark. By toning down their interpretation of the epitope, the 
results are less overstated. That being said, X-ray crystallography and/or cryo-EM data would 

significantly improve the paper, but I appreciate this is outside the scope of a reasonable reviewer 
request. 

 

Overall, given the important nature of the work, I believe the manuscript is sufficiently improved to 
warrant publication.
Peer review of: A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for (2020)


 

 

 

REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

All my comments have been throughly addressed by the authors. I just have an additional suggestion 
for the point below. 

My first comment: 
The neutralizing 93k antibody presumably acts by binding to the prefusion form of gB and the 
approach to isolate native gB from VZV-infected cells would suggest the possibility to capture gB in 
the pre-fusion conformation. Why the recovered native protein is in post-fusion conformation? Was 
any pre-fusion/antibody complex recovered? 

Authors' reply: Unfortunately, a prefusion gB-antibody complex was not identified with our current 
purification protocol. The cryo-EM data were mined for such complexes, but class averages were not 
identified that resembled a prefusion form of gB in complex with mAb 93k Fab fragments. The 
prefusion form of herpesvirus gB has been challenging to purify for herpesviruses in general. 
Currently, the only evidence of prefusion forms of herpesvirus gB have been in the context of purified 
virions or transiently expressed gB on the surface of exosomes1,2. In addition, specialized approaches 
used for other viral fusogens such as pH manipulation or mutagenesis to ‘lock’ the fusion protein has 
not currently been feasible for herpesvirus gB. 

My suggestion: I think it would be worth to mention this in the paper. It would be expected to have a 
prefusion native gB protein in cells yet all the purified form is in post-fusion even when the mAb 93k 
antibody is added shortly after the first step of purification. This underscores the highly metastable 
status of the prefusion form (confirmed by the absence of even minor classes resembling a prefusion 
form in cryo-EM data) and would suggests alternative approaches to capture the prefusion form. I 
wonder if a cell-permeable nanobody of mAb93k would be helpful in this task. 

Reviewer #2 (Remarks to the Author): 

The raised questions have been approximately addressed by the authors.
Peer review of: Triacylglycerol synthesis enhances macrophage inflammatory function (2020)



REVIEWERS' COMMENTS: 

Reviewer #1 (Remarks to the Author): 

The authors have adequately addressed my concerns. 

Reviewer #2 (Remarks to the Author): 

The authors have made a good effort in addressing my comments. While I believe that a number 
of the key issues are not fully settled. Specifically, I feel it remains well possible that DGAT1 
inhibition has an effect independent of TG production. Time (and additional experiments) will tell. 

Yet, overall this manuscript is interesting, improved and I now support its publication.
Peer review of: Bacterial polyphosphates interfere with the innate host defense to infection (2020)



REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

Overall I am happy with the changes made. While there are lingering questions, much of this is due 
to the state of the field - these are things that can be addressed in the future and not significant 
enough at this stage for me to hold up the timely publication of this important study. 

 

I really enjoyed this work. The authors should be very proud of their accomplishments. 

 

 

 

 

Reviewer #2 (Remarks to the Author): 

 

 

Congratulations to the authors for this well conducted study. All my concerns have been addressed 
in this much improved version. 

 

Nelson Gekara
Peer review of: Ex vivo editing of human hematopoietic stem cells for erythroid expression of therapeutic (2020)



Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The Authors well addressed all my questions and the manuscript has been improved. 
Since inversions are a common outcome when cleaving two adjacent loci with nucleases and the 
Authors cannot rule out this possibility with a low false negative confidence, I would just 
recommend them to indicate in the manuscript that “the detection and quantification of HBA2 
inversions was not possible due to technical issues”. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
Considering circumstances, the authors have made a commendable effort to address the reviewer 
comments, overall improving the manuscript. The design and results are now much clearer. 
Still, concerns over potential genomic rearrangements - shared between both reviewers - remain 
unresolved. Instead, the authors provide published examples of comparable gene editing 
scenarios. While this is not direct evidence, it is understood that analysis of rearrangements in 
duplicated genomic regions can be complex. Therefore, the authors must make it clear in the 
discussion that their data cannot exclude this potential outcome of their editing strategy. 
Regarding the sequence data in Supplementary Figure 2m, the authors may have misunderstood 
my concern. The results state a percentage editing, while the data shown is not the HDR results of 
40 clones, just PCR products for 14 samples and one sequence read. I understand that they may 
have difficulties accessing their lab, however the conclusion must be supported by appropriate 
data (for example, a table of clonal sequencing results).
Peer review of: Preferential inhibition of adaptive immune system dynamics by glucocorticoids in patients (2020)



REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
 
The authors answered my questions and concerns with clear descriptions. The manuscript was revised 
to improve on the presentation of data and to clarify the weaknesses that were noted in the first 
submission. In particular, this reviewer was convinced by the validation data that was presented for 
their signaling studies by CyTOF and by the discussion of their analytical workflow. 
 
 
Reviewer #2 (Remarks to the Author): 
 
The authors satisfactorily responded to my concerns. They now discuss the limitations caused by the 
restriction of the study to elder individuals and the single dosing of MP, and also provide some 
confirmatory data concerning my former concern. Although Suppl. Fig. 4 is still very small, it is now 
readable. In this respect, my only suggestion would be to enlarge the asterisks indicating statistical 
significance since they are easily confounded with data points. The statement concerning the inhibition 
of NF-kB activity by GCs has been revised. I accept that providing additional data on functional 
features of immune cells would probably go beyond the scope of the current manuscript. I now 
recommend publication of this work. 
 
Holger Reichardt
Peer review of: Bile acids drive the newborn’s gut microbiota maturation (2020)

EVIEWERS' COMMENTS:
Reviewer #1 (Remarks to the Author):
The authors have extensively revised the paper by adding bacteria data in the colon, and addressing the major criticisms. My major concerns that limit my enthusiasm for an otherwise valid result are the results are focused on BA metabolism and microbial changes mainly in the small intestine. The authors rationalize this as it impacts the immune system, but this isn’t a focus of the paper. Additionally, the correlation involving UDCA and GCA is puzzling since glycine conjugated bile acids are in trace amount in mice and their effect on gut microbiota and bile acid reabsorption in the colon is likely minimal at such low concentration.
The observed kinetics for the predicted BSH activity and the gene expression are different (predicted BSH activity peaks at PND21-PND28 whereas the bile transport and FXR regulatory axis gene expression rises continuously until PND56) and do not parallel.
If one accepts these limitations the paper is much improved.
Jacob Friedman
Reviewer #2 (Remarks to the Author):
Van Best et al present a revised description of the development of neonate mice gut microbiota and the changes in bile acid production during the same period, which also includes an experimental oral administration of bile acids that caused microbiota to mature more quickly. I would like to thank the authors for the clarifications in their revised manual. I have only a few points that I feel the need to insist on.
Former Major point 4: I am sorry that I was unclear in my previous comment. Your methods section does not provide detail on the number of samples, the breed of mice, or their relationships and I'd like to see this omission mended.
Former Major point 7: Thank you for the clarifications on the methods. I don't completely buy your rationale for the use of OTUs, however. A) The results presented in Figure S3 and lines 141-144 would clearly benefit from the highest possible resolution. B) Overestimation of microbial diversity is a problem that is more severe for some 97% OTU clustering methods than the exact sequencing variants methods (e.g. 10.1371/journal.pone.0227434, 10.7717/peerj.5364). However, since you've picked the OTU clustering method with the lowest introduction of spurious OTUs, I would not want to make you redo the whole sequence analysis and pretty figures for a minor detail. Maybe you can adjust the wording in the relevant section and methods description?
I also appreciate the additions made in response to reviewer 1's questions and wish you good luck with the publication.
Reviewer #3 (Remarks to the Author):
Authors answered all my comments satisfactorily and made a diligent effort in revising this manuscript.
Peer review of: The CD153 vaccine is a senotherapeutic option for preventing the accumulation of (2020)



 

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
This is an interesting study that suggests that vaccination against CD153, a T cell marker, 
improves metabolic homeostasis in the face of a high fat diet. The manuscript is revised and the 
authors did a thorough job doing the requested additional experiments, including multiple 
additional in vivo studies. 
My expertise is in senescence and senolytic therapies, not immunology. My concerns are: 
1) What is the rationale for a vaccine as opposed to simply treating with an antibody against 
CD153? 
2) The experimental design addresses the prevention of accumulation of CD153+ T cells during 
high fat feeding rather than their removal in for example an aged, obese, diabetic organism. 
3) What is a senescent-associated T cell? Is it senescent itself? Or associated with senescent cells 
of non-immune lineages in tissues? SA-T is a very confusing nomenclature. 
4) The main concern is that the title and manuscript are riddled with statements about senescence 
and apoptosis/cell death. These are both measurable entities. Yet neither are measured anywhere 
in this body of work. Thus, no statements about senotherapeutics or the impact of the vaccine on 
senescent cells can be made. 
 
 
 
Reviewer #2: 
Remarks to the Author: 
All comments are addressed properly. in my opinion this is an interesting proof of the concept 
study, showing senotherapeutic effect of proposed vaccine against CD153 positive cells and will be 
interesting for readers. 
 
 
 
Reviewer #4: 
Remarks to the Author: 
The authors have addressed all of my concerns.
Peer review of: The CD153 vaccine is a senotherapeutic option for preventing the accumulation of (2020)



Reviewers' Comments: 
 
Reviewer #1: 
The authors have been quite responsive to my comments. However, I still have some reservations 
as outlined below. You are welcome to transmit my reservations to the authors directly or with 
modification. 
1) The definition of senescence-associated T cells remains poorly defined. "Senescence-associated" 
implies associated with senescent cells of a different origin (than T cells). It appears that in fact 
the T cells themselves could be senescent. Thus, the descriptor "senescent associated" is 
misleading. Nevertheless, the phrase is in the published literature, whether accurate or not, so the 
authors should be allowed to use it, regardless of its accuracy (although I am hesitant to 
propagate inaccuracies). 
2) There is still something jarring about the paper. Paragraph 1 talks about the value of targeting 
senescent cells therapeutically. Then paragraph 2 jumps in to describe a vaccination approach to 
killing senescent cells. Senoptosis/senolysis as an approach to targeting age-related decline is still 
in debate. Thus, it would be valuable to justify vaccination vs. other therapeutic approaches like 
small molecules or antibodies. 
3) To determine if senescence-associated T cells are in fact senescent, the authors measured p16 
and gH2AX in WAT section by IHC. While the representative images look reasonable, the 
quantitation of p16 signal does not reach significance (Sup Fig 11). This is most likely because it is 
well known (although not clearly published) that none of the commercially available antibodies 
against p16 work in mouse tissue. There is a signal on WB or IHC, but the same signal occurs in 
analysis of tissues from p16KO mice. I do not recommend including this data for that reason. qPCR 
to measure p16 expression is much preferred. 
So while the study is innovative, addresses an important topic , demonstrates efficacy in terms of 
metabolic outcomes, it remains unclear in my mind what the vaccine is targeting precisely and the 
mechanism by which it works
Peer review of: MG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor- (2020)



REVIEWERS' COMMENTS: 

Reviewer #2 (Remarks to the Author): 

The Authors have answered by queries. The manuscript is now acceptable for publication. 

Reviewer #3 (Remarks to the Author): 

The reviewer appreciates the revisions to the manuscript. The authors have satisfactorily 
addressed the concerns of this reviewer.
Peer review of: A STING-based biosensor affords broad cyclic dinucleotide detection within single living (2020)


  

Reviewers' Comments: 
 
Reviewer #1: 
Remarks to the Author: 
The authors have thoroughly responded to every point raised and clarified all the major points of 
confusion. As a first-generation sensor, BioSTING has been well characterized, the practical 
advantages and disadvantages are discussed, and the proofs-of-concept are compelling for the 
applications of interest. There are no additional concerns for this manuscript. 
 
 
 
Reviewer #3: 
Remarks to the Author: 
For comment 8. The authors compared FRET signal in bottom 50% BioSTING expressing cells to 
top 50% expressing cells. They claim that "We did not see significant differences between these 
two populations suggesting that, as long as BioSTING can be detected by the flow cytometer, the 
level of BioSTING expression is not severely altering results." This analysis is not included in the 
text. 
 
From the authors' analysis, it seems like the expression level does have an effect on FRET signal. 
While the differences may not be statistically significant, in each of the three cGAMP delivery 
methods presented (nucleofection, extracellular, and CT-DNA transfection), the FRET signals of the 
two populations consistently separate. This suggests that for experiments utilizing BioSTING, 
expression of the reporter should be tightly controlled. At the very least, the authors should 
include the analysis of the low/high populations in the manuscript and indicate that controlling 
reporter expression levels is important when comparing FRET signal between samples. 
 
We are happy with how the authors addressed the rest of the comments and this manuscript 
should be published after the authors make the changes indicated above.
Peer review of: Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by (2020)


 

 

Reviewers' comments: 

 

Reviewer #2 (Remarks to the Author): 

 

The authors have answered the criticisms and the questions I had and the manuscript is substantially 
improved. It is a very important paper. Alexander Khoruts, MD 

 

 

Reviewer #3 (Remarks to the Author): 

 

The manuscript represents a transfer from a sister journal where I previously reviewed the first 
submission. The authors have responded to my comments, , however there are only very few 
additional experiments to answer any of the questions, although I find it hard to compare the 
documents without a clearly marked revised version. I agree with the authors that the level of 
mechanistic insight can be lower at this stage, however I still stand with the following comments: 

1. The selection of just a few "microarray mice" is problematic, the authors state in their response 
that they -by 25 years of clinical experience- selected the most contrasting mice for analysis. 
Although I disagree with that procedure, it should at least be clearly noted in the M&M section. 

2. The microbiota analysis as it stands in the main part of the manuscript is below standard, 
respective suppl data figures are informative and necessary to go into the main part, with depiction 
of statistical differences (not just in another supplemental table). The respective inoccula must be 
included in the analysis and not just in the rebuttal letter. 

3. The IRF3 story is has remained more or less unaltered, as differential roles for IRF3 in different cell 
types have been reported, I still find the use of MEFs as a model system a very strange selection. The 
authors do not discuss the fact that IRF3 KO has been reported to protective in several sepsis models 
including CLP. I agree that different model systems can lead to different outcomes however this 
must be openly discussed. 

4. The pIRF3/IRF3 protein level evidence is underwhelming, as it shows n=1 and just ubiquitous 
brown staining in liver /SI. In the current form this cannot support the claim and must be removed. 

5. I still stand with the notion that the term MDR healthcare pathogen infection is confusing, as it 
suggests that MDR pathogens relevant to healthcare can be reduced to 3 bacteria and Candida 
isolated from a single patient. In fact, the Candida strain shows no resistance to antifungals and the 
Enterococcus strain is sensitive to most clinically applied antibiotics including Vanco. I would give a 
strong advice to thus change the nomenclature of the model. 

6. The additional OTU analysis is very interesting, however the rationale and exact algorithm is not 
sufficiently described in the manuscript , is this based on an indicator OTU analysis , how did the 
authors set the thresholds for OTU identification ? The Figure itself contains very small and 
repetitive text, with strange technical lingo and abbreviations , this should be simplified.
Peer review of: Transplacental transmission of SARS-CoV-2 infection (2020)


 
 
 
REVIEWERS' COMMENTS: 

 

Reviewer #1 (Remarks to the Author): 

 

The authors have adequately addressed this reviewer's comments. 

 

 

Reviewer #2 (Remarks to the Author): 

 

thank you for revision of the manuscript. it has improved significantly. 

 

further comments to address: 

Abstract: 

1. Last sentence – replace “consistent” to “similar”. 

Text: 

1. The agein hours at first blood gas analyses will be useful to know as it can help to satisfy that 
neonate was not asphyxiated. 

2. Reference to “placenta was extremely positive” should be changed – there is nothing like 
“extremely” or not extremely – it was positive. 

3. Presence of viral gene in placenta could still be contaminated by blood. Need to soften this 
finding. 

 

Discussion: 

1. Paragraph 1 will need to be revised based on one published case with similar placental findings. 
https://www.cmaj.ca/content/early/2020/05/14/cmaj.200821 

2. Suggest to remove the concept of “viral replication” in placenta as it is possible that the high viral 
load in placenta may just reflect stagnation of blood and thus virus from maternal circulation. There 
is no evidence of replication based on the investigations performed. Inflammatory findings do not 
mean replication.
Peer review of: Androgens predispose males to monocyte-mediated immunopathology by inducing the (2020)



 

Revision 2 NCOMMS-19-26999A 
REVIEWERS' COMMENTS: 
 
Reviewer #1 (Remarks to the Author): 
The  authors  have  comprehensively  answered  the  concerns  from  the  prior  review  and  the 
manuscript is improved as a result. I have no further critiques. 
 
Reviewer #2 (Remarks to the Author): 
The authors adequately addressed my major concerns.  
A few modifications that the authors should consider: 
1.  I  would  not  use  a  slang  term  like  'trans'  in  a  manuscript.  Replace  with  'transgender'. 
2. In Figure 5g, the conceptual cartoon image would benefit from showing how androgen receptor 
signaling  interacts  with  TLR4 signaling to  make the  cartoon  more  relevant  to  this  manuscript. 
3. In Figure 7d and related text, I would suggest replacing 'lymphocyte isolation' with 'immune cell 
isolation' because monocytes are not lymphocytes. 
 
Reviewer #3 (Remarks to the Author): 
The manuscript has improved. However, to still use student t test for small sample groups is not 
acceptable and inconsistent even if the authors now used another test to evaluate potential normal 
distribution in small samples. Non-parametric test must be used for these groups with lees than 
10-20 animals/independent samples.