Wikipedia:Peer review/Protein C/archive1

Protein C
This peer review discussion has been closed.

This article is on its way to WP:FAC. What do you think it needs? (I've also nominated it for WP:GAN, which I think it should pass comfortably.) -- Rmrfstar (talk) 01:22, 17 September 2010 (UTC)

Comments by Cryptic C62

 * "plays an important role in managing blood clotting, inflammation, cell death and the permeability of blood vessel walls" First, what does "managing" mean in this context? Second, does the protein "manage... the permeability of blood vessel walls" or does it "play an important role in ... the permeability of blood vessel walls"?
 * Reworded.


 * "proteolytically inactivating proteins Factor Va and Factor VIIIa." The purpose of the subscripted "a"s is not clear to me.
 * As far as the reader should be concerned (at this point in the article), those are just the names of the proteins which protein C inactivates. I've included them in the wikilink to make this clearer.


 * "given the risk of bleeding associated with treatment." I feel like there should be an adjective in front of "bleeding". Perhaps "external", "internal", or "excessive".
 * I understand. I've put in "serious". Does that satisfy?


 * "that eluted from DEAE-Sepharose ion-exchange chromotograph." Not entirely sure what this means, but I think there should be "a" or "the" before "DEAE-Sepharose". Or perhaps "chromotograph" should be pluralized.
 * Fixed.


 * "cDNA cloning of protein C was performed in 1984 by Beckmann et al. which produced a map of the genes responsible for producing protein C in the liver" Was this the first cloning of protein C? If so, I suggest adding "first" before "performed".
 * Fixed.


 * "Also in 1984, inherited protein S deficiencies were proposed as cause for a case of familial thrombophilia, since protein S is a cofactor of protein C and the latter's malfunctioning is associated with thrombosis." Not sure why this is included. It seems to be more relevant to protein S than to protein C, and it isn't made clear from the surrounding prose whether or not this proposal was ever accepted as fact.
 * Took it out.


 * "in baboons infused with lethal concentrations of" I don't know a whole lot about this area of knowledge, so I could be wrong here, but I don't think "infused" is the most accurate word here. It makes me think of tea.
 * The word is perfect. A linked the term to the appropriate page.


 * "Two years later, the Gla-domainless APC was imaged at a resolution of 2.8 angstroms." The what? Without a link or an explanation, I don't think many of our readers will know what "Gla-domainless" means.
 * Added a note.


 * "In 1998, a study was performed mating mice which were heterozygous for a protein C deficiency after the gene was specifically targeted for inactivation. Their offspring exhibited clear signs of the serious symptoms associated with homozygous deficiencies." So what? Without some sort of explanation, this appears to be nothing more than an insignificant factoid.
 * I commented this bit out.


 * "an amino-terminal leader preceding a propeptide." What kind of leader? I don't understand.
 * Linked "amino terminal" and made "leader" go to leader peptide.


 * "epidermal growth factor (EGF)-like domains" This is an awkward-looking and somewhat confusing construction. Why not just "EGF-like domains"?
 * I'd say that the acronym "EGF" is too obscure, yet too relevant.


 * "The light chain contains the Gla- and EGF-like domains. The heavy chain contains the protease domain." What about the aromatic segment and the activation peptide? Are these not on either chain?
 * Fixed.


 * "If either of these two proteins is absent in murine specimens, the mouse dies from excessive blood-clotting." First, what does "murine" mean? Second, this seems to be a sweeping generalization. Even if there is a strong association between the absence of these proteins and death in the specimen, the wording of this sentence implies that removing one causes automatic death, which is a bit silly.
 * "Murine" means mouse-related. I changed the wording slightly and added a source for each deficiency.
 * Perhaps your edit wasn't saved correctly; the wording of the sentence in question has not changed. --Cryptic C62 · Talk 01:33, 1 October 2010 (UTC)
 * My mistake. I added the qualification this time.


 * "The activation of protein C is strongly promoted by thrombomodulin" Just going off my gut here, but would it be correct to insert "the presence of" before "thrombomodulin"?
 * The presence itself is not enough: the thrombomodulin must bind to thrombin to create the complex. Anyway, it'd be slightly more idiomatic, but unnecessarily wordy.
 * Then why is it used later on in the paragraph: "The presence of thrombomodulin accelerates activation by several orders of magnitude" ? The importance of the binding is not made clear in the text. --Cryptic C62 · Talk 01:33, 1 October 2010 (UTC)
 * In that case cutting the prepositional phrase would make the language rather stilted. These are just stylistic choices which change emphasis and flow in a subtle fashion.
 * Regardless of the stylistic choices, you've hinted here that the thrombomodulin must bind to thrombin to create the complex which promotes the activation of protein C. This is not made clear in the text. --Cryptic C62 · Talk 18:47, 2 October 2010 (UTC)
 * A couple of sentences down: Because of the accelerating effect of thrombomodulin on the activation of protein C, the protein may be said to be activated not by thrombin but the thrombin-thrombomodulin (or even thrombin-thrombomodulin-EPCR) complex.


 * "One particular exosite augments protein C's ability to efficiently inactive Factor Va" This sentence is missing a verb. I'm guessing that "inactive" should be switched with "inactivate".
 * You are correct.


 * "The biologic instructions for synthesising protein C" I had never heard the word "biologic" before now. A quick google search shows that biologic is used far less frequently than biological. Any objections to switching the word?
 * "Biological" is redundant; and scientists, I believe, tend to use "biologic"... it's an adjective already.


 * "The gene's symbol is "PROC" from "protein C"." This seems a bit out of the blue, as it doesn't indicate what system of symbols is being used.
 * Fixed.


 * "anticoagulation and cytoprotection (its direct effect on cells)" If the parenthetical comments is intended to clarify the meaning or relevance of "cytoprotection", perhaps an explicit statement of what cytoprotection is would be more helpful than the non-descriptive "direct effect". Otherwise, I'm not really sure what the purpose of the parenthetical is.
 * The purpose of the parenthetical is to allow someone reading the article straight through to avoid following the the wikilink to cytoprotective, which should be unnecessary given the importance of the sub-topic. The parenthetical, I think, provides enough information on what "cytoprotection" (in fact nearly useless jargon) is, accompanying the word's first significant use, to allow said reader not to stop but continue reading.


 * "To a degree, APC's anticoagulant properties are independent of its cytoprotective ones" Not sure what this means. My first guess is that APC cannot perform both functions at the same time, which seems obvious given that the presence of EPCR determines which function takes effect, but if that's the case then why does the sentence start with "To a degree"?
 * That's not what that meant: I've reworded it. Also, "independent" does not mean "exclusive" but literally "not dependent".


 * "The protein C may be up-regulated by platelet factor 4." As far as I can tell, this is the only instance of protein C being referred to as "the protein C", which suggests that there may be a missing word. If there is a missing word, I suggest un-missing it. If there isn't a missing word, I suggest deleting "the" for consistency.
 * Fixed.


 * "concentrations around 70 nmol/L; the activated protein C is found at only 40 pM/L (2.3 ng/mL). Protein C levels in a healthy term infant average 40 IU/dL." Why are there so many different unit systems being used here? It's absolutely impossible to form any comparisons.
 * I'm working on this. Unfortunately, "IU" are about the stupidest units of all time, I can't find a way of converting them to moles: protein C has its own conversion factor, and I can't find out what that is. I do know that 100 IU/dL is approximately 70 nm/L, but not accurately enough yet. I fixed it.


 * "In addition, proteins released from cells can impede protein C activation, for example eosinophil, which may explain thrombosis in hypereosinophilic heart disease." Perhaps I may be asking for details that aren't entirely necessary, but how exactly do these proteins impede protein C activation? The previous regulators were all accompanied by explanations of why/how they regulate the activation.
 * I wrote a note.
 * Good, but the phrase "excess eosinophil specific granule proteins" is... a mouthful, to say the least. It's not clear what "specific" is referring to, and I suspect there is a missing hyphen. Perhaps "excess eosinophil-specific granule proteins" ? --Cryptic C62 · Talk 03:15, 13 October 2010 (UTC)
 * Yup.


 * "Last, Protein C is inhibited by protein C inhibitor." Starting this sentence with "last" is a tad confusing, as it implies that this is an item in a list, which it is not. I see no problem with removing it entirely.
 * There is a list: a list of substances which up- or down-regulate protein C.
 * Yes, but the other substances mentioned are not preceded by listy terms, such as "first," or "also,". I don't see any reason why they should be treated as list items, but if so, they should all be consistent. Having a paragraph of non-listy terms and then one random listy term is awkward and confusing.
 * I've replaced "last" with "in addition". Does that work for you?


 * "The half-life of Factor VIIIa is only around two minutes unless Factor IXa is around to stabilises it." Besides the obvious typo of "stabilises" instead of "stabilise", the use of "is around to" is both informal and vague. Perhaps "is present to stabilise" would be better?
 * Fixed.


 * "either of which is sufficient to disable Factor VIIIa and convert it to Factor VIIIi" Is there any difference between "disable" and "inactivate" in this context? Assuming the two terms are interchangeable, the inclusion of "and convert it to Factor VIIIi seems somewhat redundant. "either of which is sufficient to inactivate the activated Factor VIII and convert it to the inactivated form of Factor VIII."
 * I just wanted to make clear what inactivation actually is.


 * "APC inactivates activated Factor V" It would be more concise to say "APC inactivates Factor Va", and indeed this is how the paragraph on Factor VIII is introduced. Is there any reason not to use this notation?
 * It's clearer, I think, if sometimes the full notation is employed.
 * While that may be true in some cases, I think the two consecutive instances of "activate" will be confusing. My !vote is still "APC inactivates Factor Va". --Cryptic C62 · Talk 17:05, 13 November 2010 (UTC)
 * OK.


 * "Treatment of cells with APC demonstrates its gene expression modulation effectively controls major pathways for inflammatory and apoptotic behaviour." I'm not sure that I'm interpreting this sentence correctly, but if I am, I think it would be much clearer if there were a "that" after "demonstrates".
 * Yup.


 * "though other cellular functions are also affected." Such as?
 * Nothing interesting. I've removed the offending phrase.


 * "APC's mechanism for altering gene expression profiles are not well-understood" Subject-verb disagreement. Should be either "APC's mechanisms for altering gene expression profiles are not well-understood" or "APC's mechanism for altering gene expression profiles is not well-understood".
 * Yup.

Editing break
Here are some comments on the article's prose:


 * "Thrombin itself may also have an effect on the levels of EPCR." This is somewhat vague. I'm assuming it means that the presence of more thrombin decreases the levels of EPCR, but I suppose it could be a positive correlation too. Which is it?
 * I can't track down (though I've made an incomplete effort) what it does exactly. I think it's not relevant enough to matter anyway.


 * "A genetic protein C deficiency, in its mild form associated with simple heterozygosity" Heterozygosity of what? Suggest adding "of the PROC gene".
 * "there may be a presentation of purpura fulminans, severe disseminated intravascular coagulation and simultaneous venous thromboembolism in the womb" It's not clear if these are three separate conditions or just a long explanation of purpura fulminans. If the former, I suggest employing the serial comma and changing the "and" to "or". If the latter, I suggest employing an em dash after "fulminans".
 * "No racial nor ethnic biases have been detected" How about gender bias?

More to come. --Cryptic C62 · Talk 21:59, 22 September 2010 (UTC)
 * Much appreciated, as always. -- Rmrfstar (talk) 00:30, 23 September 2010 (UTC)
 * Glad to see you're back! I thought you had been eaten by bears. --Cryptic C62 · Talk 17:05, 13 November 2010 (UTC)
 * It's not bears one has to worry about. -- Rmrfstar (talk) 01:37, 17 November 2010 (UTC)