https://orcid.org/0000-0002-4299-2488
Peer Review History
| Original SubmissionDecember 17, 2021 |
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Dear Dr. Johnston, Thank you very much for submitting your manuscript "Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection" for consideration at PLOS Pathogens. Your manuscript was reviewed by members of the editorial board and by several independent reviewers. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations. Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out [2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments. Sincerely, Xiaorong Lin, Ph.D. Section Editor PLOS Pathogens Xiaorong Lin Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** Reviewer Comments (if any, and for reference): Reviewer's Responses to Questions Part I - Summary Please use this section to discuss strengths/weaknesses of study, novelty/significance, general execution and scholarship. Reviewer #1: I was reviewer 1 in the previous submission: "Gibson and Bojarczuk et al present a very interesting manuscript describing how intravascular growth of Cryptococcus neoformans (Cn) correlates with the appearance of endothelial damage and preceding Cn invasion out of the vasculature. They make excellent use of dual fluorescent Cn to correlate individual instances of intravascular growth with localised pathologies. The second half of the manuscript focusses nicely on the Cnendothelial interaction and drills down into VE-cadherin junctional stiffness as a mechanistic determinant of tissue invasion" Reviewer #2: The revised manuscript from Gibson et al. has added new data from dextran permeability experiments and immune cell localization that provide further evidence for the major findings of this manuscript. They have also expanded the text in a number of important ways that further contextualize their work. Together, these new additions to the manuscript have provided further support for their findings and their importance within pathogenesis. This work is well done and will be of broad interest within the pathogenesis community. ********** Part II – Major Issues: Key Experiments Required for Acceptance Please use this section to detail the key new experiments or modifications of existing experiments that should be absolutely required to validate study conclusions. Generally, there should be no more than 3 such required experiments or major modifications for a "Major Revision" recommendation. If more than 3 experiments are necessary to validate the study conclusions, then you are encouraged to recommend "Reject". Reviewer #1: The authors have addressed all of my concerns with either new experimental data, reinterpretation of existing datasets, or acceptable technical reasons why the experiments are not possible. Reviewer #2: (No Response) ********** Part III – Minor Issues: Editorial and Data Presentation Modifications Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. Reviewer #1: None. Reviewer #2: Line 224-225 – ‘infected blood vessels were larger relative to blood vessels in the same location in control animals’ this is a little confusing as the vessels/endothelial cells themselves aren't directly infected. Maybe something like 'vessels containing cryptococcus cells' would be more clear. Line 213-225 - From the text, the distinctions from the results from experiments in Figure 4C and 4 G, H are not clear – expanding a bit to explain the distinctions here might be useful. Line 304-310 - While I appreciate the efforts you have made to soften the language around endothelial junctions, the passage still gives the sense that the VE-cadherin/Gal4;UAS/Teal transgenic is providing some sort of readout of vascular integrity that was missed with the previous flk1 transgenics. However, since both of these reporters ultimately end up using an endothelial specific promoter to drive a cytoplasmic fluorescent protein, it doesn’t seem like this line is offering much new information on cell-cell junctions, particularly since VE-cadherin is also regulated in a number of ways not captured by this reporter (e.g. localization, posttranslational modification etc.) and even if its expression is regulated, with the long half-life of FPs in the cell, changes in VE-cadherin transcription may not even be visible within the time frame of these experiments. I think it’d be best to focus on intact and disrupted vessels alone and leave out any discussion of junctional integrity. Line 309-310 – It would be useful to further explain the criteria for intact vs. disrupted vessels. Line 758 – ‘Kymograph’ – this isn’t a Kymograph but rather a graph of width over time at a single point. Line 802-803 the legend describes ‘Intact endothelial junctions’ – but as mentioned in the previous review, the transcriptional reporter doesn’t really capture the status of the junctions themselves. Line 703-704 ‘1000/25 cfu of a 5:1 ratio’ what does 1000/25 cfu mean in this context? Line 706 – ‘1000 cfu ratio of KN99’ missing a ratio. Fig. 3 – There are some overlayed word outlines (DPI etc.) that appear in panels B and D. Fig. 4D and E – Perhaps width of cryptococcus masses rather than ‘C. neoformans mass width’ ********** PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Stefan Oehlers Reviewer #2: No Figure Files: While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. Reproducibility: To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols References: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. |
| Revision 1 |
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Dear Dr. Johnston, We are pleased to inform you that your manuscript 'Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection' has been provisionally accepted for publication in PLOS Pathogens. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Xiaorong Lin, Ph.D. Section Editor PLOS Pathogens Xiaorong Lin Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** Reviewer Comments (if any, and for reference): |
| Formally Accepted |
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Dear Dr. Johnston, We are delighted to inform you that your manuscript, "Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection," has been formally accepted for publication in PLOS Pathogens. We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens |
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