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My View Points on SCI papers and Review Process

My View Points on SCI papers and Review Process. Hui Cai , M.D. Renal Division Emory University School of Medicine May 29, 2011. Your reseach interests. Your grant application You are completing your work as proposed. Surprising findings Basic frame of your manuscript (MS)

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My View Points on SCI papers and Review Process

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  1. My View Points on SCI papers and Review Process HuiCai, M.D. Renal Division Emory University School of Medicine May 29, 2011

  2. Your reseach interests • Your grant application • You are completing your work as proposed. • Surprising findings • Basic frame of your manuscript (MS) • Personal habits • Collaboration work • Collegial discussion

  3. Where do you submit your MS • This is very important!! • Research area • Pure basic sciences vs clinical research vs translational research • Familiar with mission of each Journal • Specialty vs General • Productivity vs Quality

  4. High profile journals

  5. High Profile clinic papers

  6. Basic Review Process • After submission according to Journal’s requirments. • Editorial review processing: Can turn down your paper within 7-10 days without even sending out you paper. • Assign the reviewers: Usually assign two reviewer and but most 3 reviewers. In latter case, associate editor or chief editor will be serves the third reviewer. • Review usually takes 2-3 weeks to completion. • Editorial decision • Then lthey will send a letter to you.

  7. Editor Decision • Editorial level rejection • Reviewer assignment • How to choose the reviewer? • Final decision

  8. Review Criteria • Overall Manuscript Rating (Required): TOP 10%, 25%, 50%, 75%Significance of Research Findings (Required): TOP 10%, 25%, 50%, 75%Novelty of Findings (Required): TOP 10%, 25%, 50%. 75%Experimental Design and Quality of Data (Required): TOP 10%, 25%, 50%, 75%Recommendation (Required): Reject, Major revision, Minor revision, Accept

  9. Review Criteria cont • Has the author stated that they have IACUC, IRB, or equivalent approval, if the study involves animals or humans? (Required): Yes, or NoIs there any question of violation of APS's Guiding Principles in the Care and Use of Animals? (Required): Yes, or NoIs the manuscript the right length? (Required): Yes, or NoAre all of the figures and tables necessary? (Required): Yes, or NoIs the use of figure color scientifically necessary? (Required): Yes, or No

  10. Cover Letter • Very important. • It should include the following components: • Your title of MS • Brief introduction of paper: new or novel. • Suggesting reviewers for reviewing your MS including reviewers’ name, title, contact information. • Suggesting reviewers that you don’t want them to revise your MS.

  11. Sample of Cover letter for 1st submission

  12. Sample of Cover letter for 1st submission Cont

  13. Sample of Cover letter for 1st submission Cont

  14. Cover lettre format • Dear Editor： • Thank you for your prompt review of our work. We wish to thank the reviewers for their constructive comments. We appreciate the opportunity to improve our manuscript and found the comments and suggestions very helpful in revising our manuscript. In response to your E-mail from February 10, 2008 concerning the manuscript—MS #2008-12-1275, entitled “***************”, we have made a great efforts to address all the concerns raised by reviewers. •  The following are the changes made in the revised manuscript: •  To address the physiological relevance of our study, we have performed additional experiments including immunohistochemistry, western blot and RT-PCR to show endogenous sortilin expression in the kidney, •   We have performed additional experiments to determine the effect of 。。。. These new data are incorporated into the revisedFigure 2A and 2B. • We have provided a complete negative control for Co-IP showing that EGFP-tag itself does not immunoprecipitate NCC. The new data will be added to the revised Figure 3B. The original Figure 3B is replaced by new Figure 3C. • In addition, we have revised parts of the introduction, results, discussion and methods highlighted in red font according to the new data and reviewers’ suggestions in this revised manuscript. •  Our point by point responses to the comments of the reviewers follow. The reviewer’s comments are shown in italics and are followed by our responses. •  We believe that the above mentioned efforts have significantly improved this revised manuscript and hope that it is acceptable for publication in your journal. Thank you in advance for your efforts on this revised manuscript. •  Sincerely, •  Name

  15. Sample of Cover letter for revision • Dear Dr. Siegel: • Thank you for your prompt review of our work. We wish to thank the reviewers for their constructive comments. Although editor and reviewers found our work interesting, the manuscript was not acceptable for publication without major revision. We greatly appreciate the opportunity to improve our manuscript and found the comments and suggestions very helpful in revising our manuscript. In response to your E-mail from February 10, 2009 concerning the manuscript—MS JASN-2008-12-1275, entitled “WNK4 enhances the degradation of sodium chloride cotransporter (NCC) through the lysosomal pathway via sortilin, a novel lysosomal targeting receptor”, we have made a great efforts to address all the concerns raised by reviewers. Given the need for new experiments to response to reviewer concerns, I called Ms. Bonnie O'Brien in JASN editorial office and requested the extension of times for revision. The due day for the revision was extended to the end of June 2009.

  16. Sample of Cover letter for revision Cont • The following are the changes made in the revised manuscript: • To address the physiological relevance of our study, we have performed additional experiments including immunohistochemistry, western blot and RT-PCR to show endogenous sortilin expression in the kidney, especially in distal convoluted cells. These new results are added as new Figure 6 in the revised manuscript. • We have performed additional experiments to determine the effect of sortilin WT and sortilin TRU on NCC protein expression in the absence of WNK4 to serve as additional control groups. These new data are incorporated into the revisedFigure 2A and 2B. • To more carefully examine the effect of sortilin on NCC protein expression and avoid the concerns of type 2 error, we have performed more experiments and re-done the statistical analysis by ANOVA as suggested by reviewers. The new data are shown in the revised Figure 2D in the revised manuscript.

  17. Sample of Cover letter for revision Cont • We have provided a complete negative control for Co-IP showing that EGFP-tag itself does not immunoprecipitate NCC. The new data will be added to the revised Figure 3B. The original Figure 3B is replaced by new Figure 3C. • Based upon the suggestion by reviewer #2 we have re-done immunostaining experiments with quantitative analysis to compare the control group with the WNK4 group and shown that WNK4 does increase NCC colocalization with the lysosomal marker in the presence of lysosomal inhibitors, Leupeptin and E64, indicating that WNK4 promotes NCC targeting to lysosome for degradation. The original Figure 6 has been replaced by new Figure 7 in the revised manuscript. • As suggested by reviewer #2, original Figure 7A has been omitted and the statement concerning interaction between WNK4 and sortilin has been modified in the text. The Figure 7B is re-labeled as new Figure 8 in the revised manuscript.

  18. Sample of Cover letter • In addition, we have revised parts of the introduction, results, discussion and methods highlighted in red font according to the new data and reviewers’ suggestions in this revised manuscript. • Our point by point responses to the comments of the reviewers follow. The reviewer’s comments are shown in italics and are followed by our responses. • We believe that the above mentioned efforts have significantly improved this revised manuscript and hope that it is acceptable for publication in JASN. Thank you in advance for your efforts on this revised manuscript. • Sincerely, •  M.D. • Assistant Professor of Medicine and Physiology

  19. Accepted Letter • Dear Dr. On behalf of Editor-in-Chief Eric Neilson and Associate Editor, Dr. Alfred George, I am pleased to inform you that your manuscript is now suitable for publication without further revision and will appear in the nextavailable issue of the Journal of the American Society of Nephrology (JASN) following receipt of the final manuscript files.We aim for the papers we publish to be accessible to a wide readership and have been paying particular attention to the titles and abstracts. Titles should be 10-12 words long without colons, and abstracts devoid of unnecessary jargon and detail. Please check through these parts of your paper once more before uploading the final files. The editors reserve the right to modify the title and abstract further as needed to improve readability.  Please make sure to check the revised versions on your proofs for any errors.

  20. Accepted Letter cont • The final version of your manuscript will need to be uploaded into Manuscript Central as a revised manuscript. Please submit the text and tables in one Word file.  Your figures will need to be uploaded as a TIFF or EPS file.   We do not in general allow any modifications to the figures unless those modifications have been requested by the editors or reviewers. Any other changes must be requested and granted before the paper is accepted for publication.It is a pleasure to receive and publish manuscripts of this quality in JASN.  I deeply appreciate your support of the journal, and we look forward to the opportunity to consider further manuscripts from your group.Sincerely yours,Vivian Siegel, PhDExecutive Editor, JASN

  21. Minor revision letter • Dear Dr. • The review of your manuscript that was submitted to the JASN is complete and the Associate Editors and referees have provided us with an assessment of the paper. • The Editors and Reviewers find the work interesting and potentially appropriate for publication in JASN. However, a number of concerns have been raised by the reviewers, which preclude us from publishing the manuscript in its current form. We would like to be able to reconsider the manuscript and hope you can successfully address the concerns outlined below by the reviewers. • Among these, the issues of most importance to address in a revised manuscript are the reviewers’ comments regarding the need to test a second structurally unrelated Epac agonist, and better explanation for certain disproportionate effects (e.g., lack of proportional correlation between degree of transporter phosphorylation and urea permeability).

  22. Minor revision letter cont • We hope you will be able to address these issues and submit a revised manuscript to us. Please let me know how you choose to proceed. If you choose to resubmit, we request that the revised manuscript be submitted electronically according to the "Instructions for Authors" available on our web site (www.jasn.org). The revised manuscript must be submitted within three months of receipt of this letter. If we do not receive the revision by that time, you will need to submit the paper as a new submission. • The Editorial Team of the Journal of the American Society of Nephrology thanks you very much for the opportunity to review this interesting work. Please contact me if you have any questions, or wish to discuss timing of the resubmission. •  Sincerely, •  Vivian Siegel, PhD • Executive Editor, JASN

  23. Major revision letter • Dear Dr. : Experts in the field have carefully reviewed your manuscript titled, "RAS-GRP1 STIMULATION ENHANCES UBIQUITINATION AND ENDOCYTOSIS OF THE SODIUM CHLORIDE COTRANSPORTER," and, although they found merit in your study, they have raised a number of serious concerns that preclude its acceptance in the present form. Concerns were raised regarding data interpretation and presentation. However, I invite you to respond to the reviewers' comments and revise your paper accordingly. The revised version will be reevaluated by the original reviewers. Please be aware that this invitation does not guarantee eventual acceptance of your manuscript.The revision is due by 5th Mar 2010, six (6) months from today. If you do not request an extension to this deadline or submit a revised manuscript within 6 months, we will consider the manuscript withdrawn from submission to American Journal of Physiology - Renal Physiology. However, if you wish to submit the manuscript to another journal within the 6-month time frame, you must officially withdraw your manuscript from the journal American Journal of Physiology - Renal Physiology. Please contact at dpisconte@the-aps.org if you wish to withdraw your manuscript.To successfully submit a revision, follow the instructions below.Regards,MDEditor-in-ChiefAmerican Journal of Physiology: Renal Physiology

  24. Reject letter • Dear Dr. Your manuscript has been reviewed by referees who specialize in the subject matter addressed by the submitted material. The general and specific comments of the referees are below. Although the referees felt the study was very interesting, I regret to inform you that the reviewers raised serious questions about several aspects of the study and submitted low priority ratings. In particular, both referees had the folowing concerns: 1) that the data quality was not always adequate, 2) that some of the conclusions drawn were not supported fully by the data given, 3) that additional controls are needed, 4) that some of the data appears internally inconsistent and 5) that the study lacks focus. Accordingly, I must reject your manuscript for publication in the American Journal of Physiology - Renal Physiology. I hope that the reviewers' comments will be of assistance to you if you decide to submit your work elsewhere. If you choose to rewrite your manuscript and resubmit it to AJP: Renal Physiology, you must resubmit it online as a de novo manuscript where it may be assigned to a new Associate Editor and new reviewers. It will not be treated as a revision. You must complete all required submission forms and pay the $50 submission fee. No exceptions will be made. I thank you for submitting your work to the American Journal of Physiology - Renal Physiology, and hope that the outcome of this particular review will not discourage you from sending future manuscripts to us.Regards,Associate EditorAmerican Journal of Physiology - Renal Physiology

  25. How to respond to reviewer’s critiques • Rule of thumb: • Answer all the questions. • Carry out 4/5 suggested additional experiments for Major revisions • For minor revisions, answer all the questions and usually perform the suggested experiments rather easily. • Again, cover letter is very important and needs to lay out what you have done in the revised MS. • Use the itemized bullet to tell reviewer what you have done to address their concerns.

  26. Some Examples • This study describes the regulation of inner medulla urea transport by EPAC. Although the data on UT-A regulation and function are novel, I have some concerns. • 1) The manuscript contains very limited data and I feel that more can be done to increase the novelty of the manuscript. For example, the authors concentrate on UT-A1, but what are the effects on UT-A3? Are they similar, or are there different pathways? The authors have shown previously the phosphorylation sites in UT-A1 - are these the same sites regulated by EPAC - if so then would they effect UT-A3? • Response: • Do we have any phosphorylation or biotinylation samples left that could be probed for UT-A3? If not, do we say it is a separate study or just do these experiments? • The PKA phosphorylation sites in UT-A1, S486 and S499, are not in UT-A3. The PKA sites in UT-A3 are unknown, except that it is not either of the PKA consensus sites (ref: Smith).

  27. Some Examples • 4) The very small difference in functional measurements is hard to interpret, with such small numbers of observations the data must only just reach significance. The addition of AVP would result in approximately a 300% increase in urea permeability, whereas the EPAC stimulation results in 26%; not that big a change. • Response: • We agree with reviewer 3 that there are no structurally unrelated Epac agonists. As an alternative approach, we perfused tubules with H-89 to inhibit PKA, then stimulated with forskolin, which should primarily stimulate Epac when PKA is inhibited. Forskolin did significantly stimulate urea permeability following H-89 pre-treatment. • We can address the different response to Epac and AVP through rewriting.

  28. Some Examples • These are well performed and well described studies that demonstrate an important role of the Epac pathway in vasopressin and cAMP regulation of urea transporters in collecting duct. Multiple systems are used to make a compelling story, and all appropriate experiments and controls have been performed. The authors may wish to comment on the fact that Epac stimulation raises urea permeability by 25%, while raising phosphorylation of the transporter by 90%. This lack of proportionality may provide further mechanistic insights. Another interesting issue that is clearly beyond the scope of this paper, but which begs for resolution, is how a single cell type upregulates urea and water transport in response to vasopressin, and does so with distinct time courses and kinetics, while apparently using the same downstream signaling pathways. • Response: • We can address the lack of proportional correlation through rewriting. • I am inclined to simply agree that it is an interesting issue that is beyond the scope of the current paper.

  29. Some Examples • 1.  The physiological relevance of these observations is not clear.  As noted by the authors, sortilin was identified in brain and has been shown to be expressed by several tissues.  The authors, however, neither cite information nor provide direct evidence themselves that sortilin is expressed by DCT cells.  To make this story physiologically compelling, the authors need to present evidence that sortilin and NCC (and WNK4) are co-expressed in vivo. • Response: We agree with the reviewer that the physiological relevance of our work is not clear. Although sortilin was originally identified in brain tissue it is also expressed in many other tissues and cell lines including Cos-7 (Ref. 25). To address this concern we have performed additional experiments including immunohistochemistry, western blot and RT-PCR demonstrating that the endogenous sortilin does express in the kidney, especially in distal convoluted tubular (DCT) cells along with NCC. These new results have been added as new Figure 6 in the revised manuscript. We also show WNK4 mRNA expression in the mouse DCT cell lines (new Figure 6D) given the fact that no good antibody against WNK4 is commercially available. However, there is the evidence demonstrating that WNK4 is expressed in DCT (Ref. 2).

  30. Some Examples • In Figure 7A there is an unexplained large band on the "-" IP lanes. It runs around the same MW of NCC. It should at least be commented on. And again there is no explanation for what the "-" lane is. Is it just protein A/G beads with no ab? No statement one way or another in methods, fig. legend or results. This must be clarified. • Response: Our apologies on the confusion. The large band in sign (-) lane is likely a non-specific band in original Figure 7A. The sign (-) lane is a negative IP control for monoclonal myc antibody using protein A/G beads only without adding any antibody. We have eliminated this section of Figure 7 and altered the remainder as described below.

  31. Some Examples • 6. Finally, the manuscript would be strengthened by showing effects of sortilin on the activity of NCC, as assessed by radiotracer uptake. • Response: We agree that the manuscript might be strengthened by including the effect of sortilin on the activity of NCC assessed by radiotracer uptake. However, the functional assay of NCC by 22Na uptake has been carried out and published previously (Ref. 3 and 4). These studies showed that WNK4 wild type (WT) reduced NCC sodium uptake corresponding with reduction of NCC surface expression. We previously showed that WNK4 reduced NCC surface expression primarily due to a decrease in NCC total protein expression and an increase in NCC degradation, likely through a lysosomal pathway (Ref. 6). We believe that additional 22Na uptake assay would probably not change the conclusion from our current work. Thus we would not plan to perform this functional assay for this manuscript.

  32. Some Examples • In this regard, how much do you think that the mannose-6-phosphate receptor (M6PR)-mediated mechanism participates in this process? • Response: We think that M6PR-mediated mechanism might be also involved in this process because M6PR contains similar domain structures as sortilin. We agree that this question might be important in the regulation of NCC. However, we would like to address this question in the future as a separate topic.

  33. Some Examples • The authors have addressed many of my previous concerns and the manuscript is now much improved.  There are a couple of remaining issues, however. • Response: We thank the reviewer for his/her positive comment on this revised paper. • A recent paper provided further evidence that WNK4 diverts the NCC to the lysosome and also found that it stimulates association with AP3.  This work should be cited in the discussion, as it is very relevant to the current results and the discussion on page 12 describes AP1 and 2 as possible partners, but not AP3.  • Response: We agree with reviewer’s suggestion. A recent relevant paper is cited and AP3 as a partner of WNK4 is discussed in the revised manuscript (Subramanya AR et al. J Biol Chem 284(27):18471-80, 2009, ref ?).

  34. Some Examples • Overall this is a novel hypothesis regarding the mechanism of regulation of NCC by WNK4. Regulation of this key effector of blood pressure homeostasis is an essential area of research. • Response: We appreciate very much for reviewer’s comment on the novelty of our work. • There are a number of minor grammatical and spelling mistakes.  The presentation would be strengthened if they were corrected. • Response:We appreciate reviewer’s suggestions.The grammatical and spelling mistakes are corrected accordingly in the revised manuscript.

  35. Thank You • GOOD LUCK WITH YOUR PAPER SUBMISSIONS !!!

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