Referee 1's review:

This is a review on a research topic of high interest in literature focusing on the existence of water at two different polymorphic structures in various systems with biological relevance: low-density (LDW) and high-density (HDW) structures.
My criticisms and corrections concern the things that are not shown or those are not clear. A more thorough approach will make this a much clearer review for the reader.

Main comments on the review:

1) It is difficult for the reader to follow the manuscript's structure and to understand the text, which is unclear and suffering from a poor discussion of the figures. For instance, Figures 2-5 are not mentioned in the text. Figure 4 mentioned in page 4 to show that the neutral salts had dramatically non-linear effects upon water structure in dextran sulphate solutions. However, the captions of figure 4 (page 41) present data on glass beads.

2) In different sections, there is discussion of results from literature and concluding remarks without adding references to the text (see the parts mentioned in pages 21-35). Thus it will be difficult for the interested reader to understand the arguments. For instance, it was written in page 29 without adding suitable references: 'We have used this method for freezing stem cells, platelets and jurkat cell lines with good recovery of cells. In the controlled freezing method using DMSO or glycerol, cooling and warming are generally rather slow. In the method using solutions devoid of chaotropes freezing must be rapid'.
3) Some parts are unclear. For instance, the first paragraph in the part of Resolution of the conflict (see page 7), and the first two paragraphs of the part Problems of interpretation (see page 11).

4) In page 15, first paragraph of section Superposition of the several compensations for osmotic pressure gradients. What are the five different modes mentioned in the fist line?

The review has to be very clear, and the arguments have to be very well presented. I am suggesting that there is need to shorten significantly the review and to focus only on the behavior of water in few examples of processes with biological relevance, in which there are evidences from literature that LDW & HDW are playing a very important role. A revised clear review will be suitable for publication in PLoS ONE due to the high interest of exploring the crucial role of water in biological systems.

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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.