Physiological consequences of Aldolase C deficiency during lactation

James A. Votava; Jing Fan; Brian W. Parks

doi:10.1371/journal.pone.0315719

Peer Review History

Original SubmissionJuly 24, 2024
18 Sep 2024 Decision Letter - Mohd Akbar Bhat, Editor PONE-D-24-31001Physiological consequences of Aldolase C deficiency during lactationPLOS ONE Dear Dr. Parks, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Nov 02 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please include a separate caption for each figure in your manuscript. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Overall, the study appears to have been well conducted and provided interesting results, but there are issues to consider. Introduction: - The purpose of the introduction is to give a scientific background to the main topic of the study. - The last paragraph of the introduction should state the rationale and hypothesis of the study. - Line 113: "Deletion of Aldoc did not impact pregnancy or litter size,……" The introduction is not the appropriate place to present the results of the study!! Materials and Methods: - It is very confusing and makes the results and figures difficult to follow and understand. - It is advisable to provide a representative flowchart of the study protocol. - Before rushing into the details of biochemical analysis or staining method, you should first clearly define the experimental groups, the number of mice/group and the parameters being measured and in which sample. - Please specify the dates of milk collection and the biochemical parameters being analyzed. - Explain the rationale behind choosing L3, L10 or L14, and why not all parameters are analyzed on the same date. Statistical analysis: - Did you check for normality of data? - It is not clear which test was used to compare the means of two different groups, and which test was used to compare the means of the same group at different time points (e.g. L3, L10). - The two-tailed Student's t-test is used to compare two different groups only. Please check the statistical analysis of your data. Results: - Line 197: The word "Aldoa and Aldob" was repeated twice in the same sentence, Please correct. Reviewer #2: The manuscript presents valuable and novel findings on the physiological role of Aldoc in lactation. It is well-executed, and the results are robust. To improve the clarity of the manuscript, I would recommend authors to address the following comments: Abstract: Consider adding a brief sentence on how these findings could impact broader fields, such as human lactation research. Introduction: The background on Aldoc's regulatory role in cholesterol and lipid metabolism is relevant. It will benefit from adding a paragraph emphasizing the knowledge gaps about its role in lactation specifically. Methods: The methods section is detailed and well-organized, providing sufficient information for replication. The use of multiple techniques (e.g., lipidomics, histology, and gene expression assays) is a strength. However, the section could benefit from a clearer explanation of how some decisions were made regarding time points for analysis (e.g., why L3 and L10 were chosen). Discussion: Clarify the distinction between previously published data on Aldoc in other tissues and this study’s findings in the mammary gland and avoid repeating points about metabolic coordination in lactation. Add a brief conclusion summarizing the implications of Aldoc deficiency in lactation and suggestions for future research directions. Overall, this manuscript presents significant and original research on the role of Aldoc in lactation. After addressing the minor suggestions above, I recommend that this study be published. The work is a valuable contribution to the field of metabolic regulation during lactation. ****** 6. 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: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment 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. Registration is free. 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Revision 1
4 Oct 2024 Author Response Response to Reviewers Reviewer #1: Overall, the study appears to have been well conducted and provided interesting results, but there are issues to consider. Introduction: - The purpose of the introduction is to give a scientific background to the main topic of the study. In the manuscript, the introduction provides detailed background on the role of de novo lipogenesis within the mammary gland as well as the transcriptional regulation of this process and known information on aldolase C. - The last paragraph of the introduction should state the rationale and hypothesis of the study. In the revised manuscript, we now provide a concise rationale and hypothesis in the last paragraph of the introduction. - Line 113: "Deletion of Aldoc did not impact pregnancy or litter size,……" The introduction is not the appropriate place to present the results of the study!! In the revised manuscript, we have removed specific results and now include an overall statement of findings. Materials and Methods: - It is very confusing and makes the results and figures difficult to follow and understand. In the revised manuscript, we have added relevant information to materials and methods to clarify experimental groups and milk collection time points. The birth dates and milking dates are provided in the supplementary minimal dataset. - It is advisable to provide a representative flowchart of the study protocol. A flowchart is included in figure 1D. Additionally, we have added more details to the various groups of mice used in this manuscript. - Before rushing into the details of biochemical analysis or staining method, you should first clearly define the experimental groups, the number of mice/group and the parameters being measured and in which sample. In the revised manuscript, we have defined experimental groups, numbers/group, and parameters measured to help clarify. - Please specify the dates of milk collection and the biochemical parameters being analyzed. In the revised manuscript, we have included a statement indicating all milk collection was performed within a four-month timeframe and provided exact dates in the supplementary minimal dataset. - Explain the rationale behind choosing L3, L10 or L14, and why not all parameters are analyzed on the same date. In the revised manuscript, we have added details and rationale behind choosing lactation day 3 and 10 for milk collection and analysis. As we collected milk from the same mice a multiple time points (L3 and L10), it is not possible to do this on the same date. However, all biochemical milk composition analyses were conducted on same date. Statistical analysis: - Did you check for normality of data? Yes, the data within this manuscript is normally distributed. - It is not clear which test was used to compare the means of two different groups, and which test was used to compare the means of the same group at different time points (e.g. L3, L10). We apologize if this wasn’t clear. In the revised manuscript, each figure legend now indicates the statistical test used and is included in the statistical analysis section of the materials and methods section. - The two-tailed Student's t-test is used to compare two different groups only. Please check the statistical analysis of your data. For all of our statistical analyses, we are comparing two groups (Aldoc+/+ vs Aldoc-/-), unpaired two tailed students t-test is the appropriate test for these analyses. Results: - Line 197: The word "Aldoa and Aldob" was repeated twice in the same sentence, Please correct. This is now corrected. Reviewer #2: The manuscript presents valuable and novel findings on the physiological role of Aldoc in lactation. It is well-executed, and the results are robust. To improve the clarity of the manuscript, I would recommend authors to address the following comments: Abstract: Consider adding a brief sentence on how these findings could impact broader fields, such as human lactation research. We now include a sentence on the impact on human lactation within the abstract. Introduction: The background on Aldoc's regulatory role in cholesterol and lipid metabolism is relevant. It will benefit from adding a paragraph emphasizing the knowledge gaps about its role in lactation specifically. In the revised manuscript, we have modified the last paragraph of the introduction to clarify the knowledge gaps, rationale for study, and hypothesis we are testing. Methods: The methods section is detailed and well-organized, providing sufficient information for replication. The use of multiple techniques (e.g., lipidomics, histology, and gene expression assays) is a strength. However, the section could benefit from a clearer explanation of how some decisions were made regarding time points for analysis (e.g., why L3 and L10 were chosen). In the revised manuscript, we now include rational for milk collection at lactation day 3 and 10. Discussion: Clarify the distinction between previously published data on Aldoc in other tissues and this study’s findings in the mammary gland and avoid repeating points about metabolic coordination in lactation. In the revised manuscript, repeated points about metabolic coordination have been removed and previous findings of the role of Aldoc in regulating plasma cholesterol and triglycerides have been clarified. Add a brief conclusion summarizing the implications of Aldoc deficiency in lactation and suggestions for future research directions. In the revised manuscript, we have added a conclusions section. Overall, this manuscript presents significant and original research on the role of Aldoc in lactation. After addressing the minor suggestions above, I recommend that this study be published. The work is a valuable contribution to the field of metabolic regulation during lactation. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0315719.r002
1 Dec 2024 Decision Letter - Mohd Akbar Bhat, Editor Physiological consequences of Aldolase C deficiency during lactation PONE-D-24-31001R1 Dear Dr. Parks We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Mohd Akbar Bhat, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have revised this manuscript and incorporated all the recommended suggestions; therefore, I recommend this paper for publication. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #3: (No Response) Reviewer #4: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #3: Yes Reviewer #4: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: Yes Reviewer #4: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #3: Yes Reviewer #4: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #3: Yes Reviewer #4: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #3: the authors had addressed all required revisions no more comments are needed to be fulfil the article is much been improved Reviewer #4: The authors have addressed all the suggestions raised by the reviewers. Hence, the manuscript can be accepted for the publication. ****** 7. 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 #3: Yes: amany A. Saleh Reviewer #4: Yes: Shiwali Goyal ******** https://doi.org/10.1371/journal.pone.0315719.r003
Formally Accepted
3 Dec 2024 Acceptance Letter - Mohd Akbar Bhat, Editor PONE-D-24-31001R1 PLOS ONE Dear Dr. Parks, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Mohd Akbar Bhat Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0315719.r004

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