From Mice to Men: An Evolutionary Conserved Breakdown of the Epidermal Calcium Gradient and Its Impact on the Cornified Envelope
Round 1
Reviewer 1 Report
Here is my review report for the ms cosmetics-312433 from Streubel and co-workers entitled: From mice to men: An evolutionary conserved breakdown of the epidermal calcium gradient and its impact on the cornified envelope.
In this paper, the authors present convincing results about the differential distribution of calcium ions as a sign of skin ageing conserved among human (their previous work) and mice (this paper), evidencing the possibility to use mouse a model to study the impact of this age-dependent differential distribution of calcium.
The introduction provide sufficient background. The methods is adequately described. The figures are of good quality and the legends provided sufficient details to easily understand it. The conclusions are logical and supported by the results. The results are well discussed.
For all these reasons, I recommend the present work for publication in Cosmetics pending the following minors’ revisions:
L20 western
L136-137 different character fonts
L145 start of paragraph 3.1., change numbering after
L158 “Figure 1B”, there is no “B” in Figure 1
L170 “Figure 2B” is mentioned before “2A” (at line 175)
L226-241 different character fonts
L277 protein
L279 “p” (p-value) in italic
L293 nothing or anything?
L326 “the” not in italic
Author Response
Dear Reviewer,
thanks a lot for your nice review and for your careful reading. We improved the following things:
1: L20 western was changed
2: L136-137 fonts were adapted
3: The numbering was added by the journal. We will take care that the numbering is correct in the final version.
4: L158 We removed B
5: L170 We changed Figure 2 (switched the order of A and B)
6: We adapted the fonts
7: L277 W corrected „“protein“
8: L279 “p” was changed to italic
9: L293 We chose „anything“
10: L326 “the” is not italic anymore
Reviewer 2 Report
It is quite interesting paper but there are some problems in writing.
3. Results
Author described human data into one paragraph and describe mice data with subheading. Author should provide subheading to human data parts.
In text, there are figure 1A and figure 1B. However, there is no figure 1A, 1B in figure legends.
It needs more method how the 3-fold, 12 fold, and 60 folds are produced. Are 3 folds not significant? How? It means that there are big variations but SD bar is not big enough in Figure 2.
In general, author did not provide numerical data or way of calculation. It need to be provided with statistical data.
Add arrow in Figure 3 for easy understaning. It is difficult to follow.
Add arrow in figure 4 also for easy understaning.
There is no data for p value. Provide it.
There is no primer information for aquaporin in table 1.
Figure 1. Change “year of birth” to “sex/age” (example: F/35)
Figure 2. A: upper panel middle aged lower panel: old-; change old- to old aged
Discussion
Line 293: nothianything: what it mean?
Line 304: filaggrin another protein: writing error?
Author Response
Dear Reviewer,
tthanks a lot for the careful reading of our manuscriopt. Your suggestions really helped to improve the manuscript.
The following changes were applied:
1.Author described human data into one paragraph and describe mice data with subheading. Author should provide subheading to human data parts.
Subheadings were added in the Results setion
2. In text, there are figure 1A and figure 1B. However, there is no figure 1A, 1B in figure legends.
B from Figure 1B was removed.
3. It needs more method how the 3-fold, 12 fold, and 60 folds are produced. Are 3 folds not significant? How? It means that there are big variations but SD bar is not big enough in Figure 2.In general, author did not provide numerical data or way of calculation. It need to be provided with statistical data.
According to your suggestion the p-values for filaggrin and AQP3 were added to the main text. According to our analysis (student t-test) loricrin is not significantly different. In four of the five analyzed old eyelid samples loricrin is down-regulated (in one sample no effect was seen). BUT: One sample had an extreme high regulation,especially for aquaporin. If this single sample would be removed the down-regulation of aquaporin would change from 60-fold to 45-fold, but the p-value would greatly improve (from ~0.05- to 0.0009)). The p-value of loricrin would also greatly improve and would be close to significance. After heavy diuscussions we decided not to remove this sample, although we believe that it was inflammed. A description for the calculation of the fold change is summarized in the RT--PCR section (Methods section of the manuscript).
4. Add arrow in Figure 3 for easy understaning. It is difficult to follow.
An arrow was added to Figure 3B. An explanation for the arrow was added to the Figure legend.
5. Add arrow in figure 4 also for easy understaning.
An arrow was added to Figure 4. An explanation for the arrow was added to the Figure legend.
6. There is no data for p value. Provide it.
The graph in figure 4C is a quantification of the western blot in 4B. In one case we found a 3-fold decrease (male) , in the other case a 17-fold decrease. Although highly regulated statitstics claim no significance because of the bog difference.
7. There is no primer information for aquaporin in table 1.
Sequence information of AQP3 was added.
8. Figure 1. Change “year of birth” to “sex/age” (example: F/35)
Date of birth was replaced with age. In the figure legend it is now clearly stated that only females were analyzed.
9. Old was changed to old age
10. Line 293: nothianything: what it mean?
Sentence was corrected
11. Line 304: filaggrin another protein: writing error?
Sentence was corrected
Reviewer 3 Report
The paper is very interesting and ,in my opinion ,it could be useful to go on by this kind of research .to further confirm your hypothesis .An observation :when you write in the first page for first time CE it could better to specify the meaning,I.e.corneocyte envelope because not all the readers could know its meaning .
Author Response
Dear Reviewer,
thanks a lot for your supporting words. According to your suggestion we tried to include a brief explanation of the cornified envelope upon its first appearance in the introduction section.
