Structural Specificity of Polymorphic Forms of α-Synuclein Amyloid
Round 1
Reviewer 1 Report
Thanks for recommending me as a reviewer. In this paper, the evaluation of the influence of these factors was analyzed based on a modified fuzzy oil droplet model considering the influence of factors other than water that affect the characteristics of external forces. If the authors complete minor revisions, the quality of the study will be further improved.
1. The introduction is well written, but the theoretical background is not sufficient. If the authors describe the introduction section more abundantly, it can help the reader's understanding.
The introduction is well written, but the theoretical background is not sufficient. If the authors describe the introduction section more abundantly, it can help the reader's understanding.
2. In Table 1, references must be entered in order.
3. In the conclusion, it would be helpful to the reader if the authors add the limitations of the study.
Author Response
REVIEWER I
Dear Reviewer
Many thanks for comments and suggestions as to the correction of our paper.
We did our best to follow your advices.
We hope the final form of our paper shall be found as acceptable for publication.
Sincerely yours;
Irena Roterman
Open Review
( ) I would not like to sign my review report
(x) I would like to sign my review report
Quality of English Language
( ) English very difficult to understand/incomprehensible
( ) Extensive editing of English language and style required
( ) Moderate English changes required
( ) English language and style are fine/minor spell check required
(x) I am not qualified to assess the quality of English in this paper
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Does the introduction provide sufficient background and include all relevant references? |
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Are all the cited references relevant to the research? |
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Is the research design appropriate? |
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Are the methods adequately described? |
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Are the results clearly presented? |
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Are the conclusions supported by the results? |
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Comments and Suggestions for Authors
Thanks for recommending me as a reviewer. In this paper, the evaluation of the influence of these factors was analyzed based on a modified fuzzy oil droplet model considering the influence of factors other than water that affect the characteristics of external forces. If the authors complete minor revisions, the quality of the study will be further improved.
- The introduction is well written, but the theoretical background is not sufficient. If the authors describe the introduction section more abundantly, it can help the reader's understanding.
The introduction is well written, but the theoretical background is not sufficient. If the authors describe the introduction section more abundantly, it can help the reader's understanding.
The shord introduction to applied method has been added (text in red)
- In Table 1, references must be entered in order. - CORRECTED
- In the conclusion, it would be helpful to the reader if the authors add the limitations of the study. – COMMENT ADDED (given in red)
Reviewer 2 Report
The manuscript presented from rena Roterman et al., is interesting, original and well written. The authors clearly presented results and discussion. However I would suggest the authors to insert an extension of the introduction, in detail they should extend the neurodegenerative disease - related to a-syn. Also because the special issue also focus on pathology.
Author Response
REVIEWER II
Dear Reviewer
Many thanks for comments and suggestions as to the correction of our paper.
We did our best to follow your advices.
We hope the final form of our paper shall be found as acceptable for publication.
Sincerely yours;
Irena Roterman
Open Review
(x) I would not like to sign my review report
( ) I would like to sign my review report
Quality of English Language
( ) English very difficult to understand/incomprehensible
( ) Extensive editing of English language and style required
( ) Moderate English changes required
( ) English language and style are fine/minor spell check required
(x) I am not qualified to assess the quality of English in this paper
|
Yes |
Can be improved |
Must be improved |
Not applicable |
|
|
Does the introduction provide sufficient background and include all relevant references? |
( ) |
(x) |
( ) |
( ) |
|
Are all the cited references relevant to the research? |
(x) |
( ) |
( ) |
( ) |
|
Is the research design appropriate? |
(x) |
( ) |
( ) |
( ) |
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Are the methods adequately described? |
(x) |
( ) |
( ) |
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Are the results clearly presented? |
(x) |
( ) |
( ) |
( ) |
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Are the conclusions supported by the results? |
(x) |
( ) |
( ) |
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Comments and Suggestions for Authors
The manuscript presented from rena Roterman et al., is interesting, original and well written. The authors clearly presented results and discussion. However I would suggest the authors to insert an extension of the introduction, in detail they should extend the neurodegenerative disease - related to a-syn. Also because the special issue also focus on pathology.
The appropriate fragment added in Discussion (given in red).
Reviewer 3 Report
In the present study, the authors investigated the external factors that affect the formation of A-Syn amyloid fibrils. In the first part, the authors aimed to show proteins of different status in respect to FOD-model, in the second part, the model was applied to amyloid transformation. However, I have no idea what the purpose of the entire article was. The authors concluded that the presence of micelle-like amyloid observed by A-Syn seems to be specific for this protein and that the proposed model for A-Syn amyloid transformation cannot be generalized to other known examples of amyloid proteins. If these are true, the reliability of FOD-M model cannot be verified by other amyloid proteins. Although the topic falls into the category of pathogenesis mechanisms of diseases, the present article relies only on the computational technique. I am personally interested in this kind of article, but at the same time, I am afraid that it may not be of interest to the readers of this journal. Thus, I strongly recommend the authors to submit to other journals dealing with more biophysical aspects.
Author Response
REVIEWER III
Dear Reviewer
Many thanks for comments and suggestions as to the correction of our paper.
We did our best to follow your advices.
We hope the final form of our paper shall be found as acceptable for publication.
Sincerely yours;
Irena Roterman
Open Review
(x) I would not like to sign my review report
( ) I would like to sign my review report
Quality of English Language
( ) English very difficult to understand/incomprehensible
( ) Extensive editing of English language and style required
( ) Moderate English changes required
( ) English language and style are fine/minor spell check required
(x) I am not qualified to assess the quality of English in this paper
|
Yes |
Can be improved |
Must be improved |
Not applicable |
|
|
Does the introduction provide sufficient background and include all relevant references? |
( ) |
(x) |
( ) |
( ) |
|
Are all the cited references relevant to the research? |
(x) |
( ) |
( ) |
( ) |
|
Is the research design appropriate? |
( ) |
(x) |
( ) |
( ) |
|
Are the methods adequately described? |
( ) |
(x) |
( ) |
( ) |
|
Are the results clearly presented? |
( ) |
( ) |
(x) |
( ) |
|
Are the conclusions supported by the results? |
( ) |
( ) |
(x) |
( ) |
Comments and Suggestions for Authors
In the present study, the authors investigated the external factors that affect the formation of A-Syn amyloid fibrils. In the first part, the authors aimed to show proteins of different status in respect to FOD-model, in the second part, the model was applied to amyloid transformation. However, I have no idea what the purpose of the entire article was. The authors concluded that the presence of micelle-like amyloid observed by A-Syn seems to be specific for this protein and that the proposed model for A-Syn amyloid transformation cannot be generalized to other known examples of amyloid proteins. If these are true, the reliability of FOD-M model cannot be verified by other amyloid proteins. Although the topic falls into the category of pathogenesis mechanisms of diseases, the present article relies only on the computational technique. I am personally interested in this kind of article, but at the same time, I am afraid that it may not be of interest to the readers of this journal. Thus, I strongly recommend the authors to submit to other journals dealing with more biophysical aspects.
The specificity og A-Syn in context of FOD-M model appears unique. Other amyloids (ABeta, transthyretin, V-domain of IgG) represent the status described by high RD and K values. It is shwon in ref [15]. Two paths for amyloid transformation are proposed:
- The native forms of the protein represent the structure close to micelle-like structuralisation while their amyloid forms are described by high RD and K.
- The native – biologically active form of A-Syn represents the status characterised by very high RD and K values while its amyloid form resembles micelle-like structuralisation (low RD and K).
High RD and K values express the status influenced by external factors, while structure of low RD and K seems to the result of water influence. A-Syn loosing the target construction adopts the structuralisation characterist for water. The amyloid forms of transthyretin, V domain shall meet changed conditions to loose the water-directed structure and keep the form influenced by external factors.
The next paper (in preparation) will be submitted to journal of more biophysical specialisation. Many thanks for this suggestion.
Round 2
Reviewer 2 Report
The authors improved the quality of the manuscript
