Wikipedia:Featured article candidates/Serpin/archive1
- The following is an archived discussion of a featured article nomination. Please do not modify it. Subsequent comments should be made on the article's talk page or in Wikipedia talk:Featured article candidates. No further edits should be made to this page.
The article was promoted by Ian Rose via FACBot (talk) 13:03, 11 March 2016 [1].
Contents
- 1 Serpin
- 1.1 Comments from delldot ∇.
- 1.2 Comments from Jfdwolff
- 1.3 Response from T.Shafee(Evo﹠Evo)
- 1.4 Comment on lead from Aa77zz
- 1.5 Comments from User:Seppi333
- 1.6 Comments from User:jcwhizz
- 1.7 Response 2 from T.Shafee(Evo﹠Evo)
- 1.8 Comments from Opabinia
- 1.9 Response 3 from T.Shafee(Evo﹠Evo)
- 1.10 Coord note
- 1.11 Source and image review by Cas Liber
- 1.12 Closing comment
- Nominator(s): T.Shafee(Evo﹠Evo)talk 03:40, 1 January 2016 (UTC)[reply]
This article is about a protein superfamily that is significant to both fundamental science (protein conformational change and enzyme inhibition) and applied science (mutations cause a wide array of Genetic disorder). It has been a Good Article since 2007, and has been significantly improved since then (particularly images, layout, readability and accessibility to lay audience). There are relatively few high-quality articles on protein superfamilies currently, so it would be good to have an FA example. T.Shafee(Evo﹠Evo)talk 03:40, 1 January 2016 (UTC)[reply]
Hi Evo & Evo, looking good so far, although I'm only partway through. Thought I'd leave these comments to let you get started. Mostly minor copy editing stuff:
Might it make sense to add into the first sentence or para what organisms they occur in? e.g. "Serpins are a superfamily of proteins with similar structures, found in all kingdoms of organisms, that were first identified for their protease inhibition activity."
- Done - Good point, although I've put their occurrence second in the sentence since it seems the subsidiary point of the sentence.
I dunno if you can do anything about this, but the first para says "inhibit" so much the word starts to lose its meaning.
- Done - I've
inhibitmanagedinhibittoinhibitreduceinhibittheinhibitoccurencesinhibitainhibitlittle. A keen eye could perhaps excise one or two more.- I replaced one with 'acts on', now that's a normal number of 'inhibits'! delldot ∇. 06:38, 6 January 2016 (UTC)[reply]
- Done - I've
In History, why is this a new para? "Examples of cross-class inhibitory serpins..." My understanding is short paras are discouraged.
- Done - (suspect you mean Activity section) I've combined the paragraphs, since they were clearly discussing the same topic.
- Citations needed: "It is presently unclear whether any mammalian serpins function to inhibit caspases in vivo." "Structural biology has therefore played a central role in the understanding of serpin function and biology." "Around the same time, the first structures were solved..." and "The structures indicated that the inhibitory mechanism involved..."
- I'll address these over the next week. Some are easy. A couple I'll have to look up.
- Done - The caspase sentence has been removed, since it was an overemphasis on caspases, which held no particular significance in that section. The rest have had references added (or reviews repeated from elsewhere)
- I'll address these over the next week. Some are easy. A couple I'll have to look up.
In Protease inhibition, the last sentence seems like a non sequitur. Could there be transition wording or could it be incorporated elsewhere? "In Caenorhabditis elegans, all serpins lack signal sequences..."
- Done - I think it was originally included as an example of intracellular serpins, but it's was simultaneously over-specific and vague so I'v moved it down to the Distribution section.
In structure, Reactive Centre Loop is inconsistently capitalized.
- Done
Why the switch from plural to singular? "Serpins are classed as irreversible inhibitors and a suicide inhibitor"
- Done
Can you replase one 'basis' with another word? "The understanding of the molecular basis of this interaction formed the basis of the development..."
- Done - definite improvement
- in Latent conformation, does this exist only in proteins that do not have the described in the previous section, or do some proteins do both?
- To the best of my knowledge, latency and activation are relatively rare and no serpins have been described that show both. Jcwhizz may know more.
- Ah so this is instead, not in addition. Does that go without saying, or should that be indicated? delldot ∇. 06:38, 6 January 2016 (UTC)[reply]
- Done - Aha, antithrobin can do both (convert to latency, and be allosterically activated by a cofactor). I've therefore updated the section to make clear that both are possible for the same serpin.
- Ah so this is instead, not in addition. Does that go without saying, or should that be indicated? delldot ∇. 06:38, 6 January 2016 (UTC)[reply]
- To the best of my knowledge, latency and activation are relatively rare and no serpins have been described that show both. Jcwhizz may know more.
- The section Deficiency is very short. Could it be fleshed out with any examples?
- In progress
- I'm not a stickler for the cosmetic stuff so I won't object to the two-sentence paragraph, but it would be good to have examples of the conditions that can result, as the other subsections have. delldot ∇. 06:38, 6 January 2016 (UTC)[reply]
- Done - Whilt looking for more examples it became clear that deficiency almost invariably refers to deficiency due to polymerisation. The few examples of null mutants or less active mutatnts I've now grouped together into a single subsection. I've made clear at the beginning of the Disease section and Polymerisation subsection that polymerisation is the most common mechanism of serpin-caused disease
- I'm not a stickler for the cosmetic stuff so I won't object to the two-sentence paragraph, but it would be good to have examples of the conditions that can result, as the other subsections have. delldot ∇. 06:38, 6 January 2016 (UTC)[reply]
- In progress
Inconsistent spelling of α-Antitrypsin deficiency.
- Done
Unclear: "Each monomer of the serpin aggregate in the relaxed conformation (RCL inserted into the A-sheet)."
- Done
Unnecessary 'in'? "The domain-swapped trimer (of antitrypsin) forms in via the exchange of..."
- Done
I think 'and / or' is discouraged. Would 'and' work just as well by itself here? "Lung and / or liver transplantation is also used to treat"
- Done - Hadn't noticed that one! "And" is definitely sufficient.
"gene targeting in induced pluripotent stem cells has successfully been deployed to correct the Z-antitrypsin defect..." This is the only mention of the Z-antitrypsin defect, can it be described or linked?
- Done - I think the term can be safely removed and left as the more descriptive "antitrypsin polymerisation defect"
In general I have no major complaints! Well done making this tough-to-comprehend topic understandable! delldot ∇. 04:28, 4 January 2016 (UTC)[reply]
- Thanks for the points so far. I've addressed most of them. the ones that require some more reading I'll try to get to over the week. T.Shafee(Evo﹠Evo)talk 11:41, 4 January 2016 (UTC)[reply]
- Looking good so far! I replied to a couple of your replies. (Oh, BTW, I think the {{done}} template is discouraged on this page, see the blue box up top). I will be back soon with more input. delldot ∇. 06:38, 6 January 2016 (UTC)[reply]
- Thanks for the points so far. I've addressed most of them. the ones that require some more reading I'll try to get to over the week. T.Shafee(Evo﹠Evo)talk 11:41, 4 January 2016 (UTC)[reply]
A few more:
"Antitrypsin augmentation therapy is approved for severe..." Could this sentence be expanded a bit to explain what Antitrypsin augmentation therapy is? Do they just pump a bunch of it into you?
- Done - turns out basically yes, not even recombinant currently, jut purified from donor plasma.
In Degradation, I think it might help to add a topic sentence up front to help introduce and transition to the new topic. Something like, "once a serpin has successfully formed a complex with its target enzyme, it must be broken down and disposed of."
- Done
- I think the Signalling section needs to be fleshed out a bit. It might also make sense to move it above Degradation, since wouldn't it seem more logical for the latter to come at the end? But do these really need to be separate sections? What if Conformational change in non-inhibitory function were broadened to be, like, Other things that serpins also do? The signalling seems like it could follow that para. Then the whole article might flow better: How they function in cells, why it's bad when they don't, evolution. Not sure if this would work, just an idea.
- Done - I added some more information, then realised that it's really two different phenomena that already have logical places to merge. Where signalling is merely due to the cleave of signalling cascade proteases, I've merged the info into the Function section. Where signalling is due to direct binding of the R-conformation, I've merged it into the Conformational change in non-inhibitory functions section. Degradation is now under the normal functioning, before the Disease section.
Gotta sleep, more later! delldot ∇. 07:13, 6 January 2016 (UTC)[reply]
Last few:
In Human, might it be better to spell out 'about' or 'roughly' rather than a tilde? "analysis of ~500 serpins from 2001".
- Done
I like the idea of hiding the massive table in a navbox collapsed. Might it look better like this rather than having the column headers showing in the title bar?
- Done - I've implemented your formatting and moved PDB codes to the end.
In Insect, does 'toll' need to be capitalized? Should this be hyphenated, Toll-mediated? "...which results in Toll mediated signaling..."
- Done - lower case is correct, and hyphenated is appropriate
In Plant, could "the most well-studied example" be written "the best studied example"? delldot ∇. 01:54, 7 January 2016 (UTC)[reply]
- Done
Nice job so far! Just one additional comment:
- "The presence of serpins in plants has long been recognised,[166] indeed, an abundant barley grain serpin (barley protein Z) is one of the major protein components in beer." I think this sentence carries a false implication, that recognising serpins and putting them in beer are linked. I'm picturing like the ancient Egyptians or whoever going "aren't these serpins great? Let's put them in beer!" I think just splitting into two sentences and removing the 'indeed' would fix this.
Anyway, ping me when you're done with all my comments, looks like you're super close! delldot ∇. 07:13, 10 January 2016 (UTC)[reply]
Excellent work, everything above is addressed. I read it again so of course I now have more comments (don't worry, there's fewer each time!).
- Is this supposed to be capitalized? "a large Extracellular multiprotein complex" I changed one before noticing this one and being overcome by self-doubt. also, maybe a link for extracellular?
- Done - must have been a copy-paste error some time back
- The Non-inhibitory roles section is smallish. Is there another sentence that could be said about this? "heat shock serpin HSP47 is a chaperone, essential for proper folding of collagen." What role does it play?
- Done - elaborated on HSP47 and added in ovalbumin to make the section cover all non-inhibitory serpins with reasonably well-established function
- Is this correct hyphenation? "In some serpins, the S-to -R transition"
- Done
- "polymers are slowly removed via endoplasmic reticulum associated degradation." Should this be "endoplasmic-reticulum-associated" or "endoplasmic reticulum-associated"?
- Done - wording order change improves clarity anyway
- The ref Acosta 2015 uses semicolons instead of commas between author names. Same with Mushunje 2004 and Walenga 2002 (also names not initials) and Fermi 1984 (and aren't you supposed to fill a parameter for what language the source is if it's not English?) Also some titles capitalize every word (e.g. de Serres 2002 and Egeberg 1965) and most don't.
- Are there semi-automated editing help tools? I'll go through the ref formatting manually if not, but it might be more efficiently done by others!
Real minor stuff. It's promotable now, so I'll go ahead and give my support now on the assumption that you'll do whatever's best with these last few. I did some minor copy editing, you may want to double check it though. delldot ∇. 18:51, 14 January 2016 (UTC)[reply]
I'm impressed by the current state of the article (I created its first version in March 2004...) Well done to Evolution and evolvability (and of course to Jcwhizz who has contributed significantly to the content). This is well outside my professional scope so my comments will be limited. JFW | T@lk 16:47, 4 January 2016 (UTC)[reply]
- My main concern is about the decision to use primary sources as support for many statements. For clinical articles we are quite strict about secondary sources, although I am fully aware that this is less of a concern for the basic sciences. Is there any scope for increasing reliance on secondary sources? I am worried that claims about transcortin deficiency "caus[ing] chronic fatigue" might be misinterpreted, and I would suggest that all associations with human disease are supported with WP:MEDRS-compatible secondary source whenever possible.
- I see your point (particularly the megatable, which contains almost 50% of the total references). I'm not usually involved in MED articles, but the disease section and table of human serpins definitely fall within the remit of WP:MEDRS, so I'll put that as a priority. For these sections (and much of the rest of the article), there are a half dozen or so extensive reviews cited that can be used to support more of the paragraphs to increase the weighting of secondary sources.
- Done (maybe) - I've replaced all lead citations with major secondary sources. I've also made sure that all main points made in the Disease section are supported by a secondary source as well as any primaries. Finjally, I've addeed the two main secondary sources for the megatable in its heading. In fact the megatable has a high degree of overlap with the tables presented in both of those references. If appropriate, I'd prefer to keep the primary refs in the table, mostly so that as new functions are discovered, they can be easily added. I'd particularly value your opinion on the use of the main secondary sources in the column name of the the deficiency column of the megatable.
- I see your point (particularly the megatable, which contains almost 50% of the total references). I'm not usually involved in MED articles, but the disease section and table of human serpins definitely fall within the remit of WP:MEDRS, so I'll put that as a priority. For these sections (and much of the rest of the article), there are a half dozen or so extensive reviews cited that can be used to support more of the paragraphs to increase the weighting of secondary sources.
- Other point: consistency of capitalisation in the "Decription" column of the "Table of human serpins", and occasionally in "Common name" and "Disease / Effect of deficiency".
- Done - I've gone though and made a stack of clarity and consistency edits. I find it easy to miss those sorts of things in tables.
- In the same table: what is "Angiodemia"?
- Done - wow, it's amazing how long a typo can go unrecognised.
Response from T.Shafee(Evo﹠Evo)
edit@Delldot and Jfdwolff: I've gone through all of the comments above! Let me know if you think the responses sufficient, or if you recommend any further changes. The article is already much improved from your suggestions. One final question is what are your opinions of the External links section? Lists of laboratories seem to be common in science articles, but I'm never sure how well they are kept up to date, or weighted by significance. Finally, I've taken the liberty of emailing the lab heads on that list to see if any are willing to cast their eye over the article before it finishes review. T.Shafee(Evo﹠Evo)talk 11:46, 14 January 2016 (UTC)[reply]
Comment on lead from Aa77zz
editWhy is it considered necessary to have citations in the lead of this article? The usual practice is to include citations only for direct quotations. See WP:LEADCITE. Aa77zz (talk) 12:18, 15 January 2016 (UTC)[reply]
- I must admit, I was unaware of the WP:LEADCITE policy! The citations are the broadest academic reviews on the topic, a decision based the decision on WP:MCB articles like DNA, gene and enzyme. It seems to be relatively common for science articles to use the lead to place important general references (list of WP:MCB articles of FA-class). However, given this isn;t anything close to official policy, I'm happy to go with consensus of a few editors (delldot, Jfdwolff - any opinions?). T.Shafee(Evo﹠Evo)talk 23:45, 15 January 2016 (UTC)[reply]
- My understanding is there is no rule against putting citations in the lead, and you need them if the info is not cited elsewhere in the article, but they're optional as long as it is. I can't think of any reason to keep them out, but I'm not worried either way. delldot ∇. 02:18, 16 January 2016 (UTC)[reply]
Comments from User:Seppi333
edit- Support promotion to FA – this is one of the best formatted FA candidates that I've gone through in terms of article layout and text formatting. I've manually checked the article source for MOS:NUMERAL, MOS:NBSP, and MOS:IMAGE (specifically, MOS:ALT and MOS:CAPTION) compliance and made a few minor tweaks. I also used AWB to group named refs together and used 2 scripts to standardize MOS:DATEFORMAT and MOS:DASH formatting. I also made a few minor copyedits to the article text. As far as I can tell, the text/source formatting is fully MOS-compliant at the moment.
- Here is a summary of my changes.
- I'm not entirely familiar with the subject matter of the article, so I'm not particularly comfortable with doing a thorough review of the article text; however, on a cursory read-through the text does appear coherent and well-written. Seppi333 (Insert 2¢) 14:15, 16 January 2016 (UTC)[reply]
Comments from User:jcwhizz
edit- Support promotion to FA – I declare a conflict of interest in that I contributed to earlier versions of the serpin page. I work in the serpin field, and I can confirm to the best of my knowledge that the data in the page is a high quality and accurate reflection of the field and is up-to-date. I'd also like to say that as a total non expert in terms of creating and editing wiki pages that I'm incredibly impressed with how the community (and in particular User:Evolution and evolvability) have worked on this page to make it more attractive and accessible! All the best, James Whisstock.
Response 2 from T.Shafee(Evo﹠Evo)
editThank you to the recommendations, and edits delldot, Jfdwolff, Aa77zz. I believe that all the major points above have now been resolved (or at least discussed). Please let me know if there are any outstanding points you'd like further addressed. T.Shafee(Evo﹠Evo)talk 05:47, 28 January 2016 (UTC)[reply]
- Evolution and evolvability I'm still not very happy with some of the sources. Only secondary ones are suitable for medical associations. The "chronic fatigue" reference is unchanged... JFW | T@lk 21:05, 28 January 2016 (UTC)[reply]
- @Jfdwolff: Ah yes, I'd thought that putting the secondary refs up in the header would be sufficient. I might need I've made a few alternative referencing formats of the megatable in a sandbox page:
- Version with only secondary sources in header, primaries in cells - new functions easily added when discovered
- Version with both primary and secondary source for each cell - messy, but ensures that anyone who looks at the primary source ref is fully aware of the secondary source
- version with secondary references in header only - removes temptation to rely on primary sources, but I can imagine new functions being added to the table with no sources at all
- Originally, I was keen to retain the primary sources in addition to the secondary and so preferenced #1, but I guess that any 'new functions' should only be added once there's a suitable secondary review of them anyway! Additionally, the wording of functional descriptions could be made more specific, e.g.:
Deficiency may cause chronic fatigue
→Deficiency-causing mutations associated with chronic fatigue
- What do you think of the different table versions and wording suggestion? Thanks for your help! T.Shafee(Evo﹠Evo)talk 02:04, 30 January 2016 (UTC)[reply]
- @Jfdwolff: Ah yes, I'd thought that putting the secondary refs up in the header would be sufficient. I might need I've made a few alternative referencing formats of the megatable in a sandbox page:
- Evolution and evolvability I don't think we need the primary sources mentioned at all, provided the secondary source provides the serpin-disease association. I am happy to yield to a second opinion, but formally speaking WP:MEDRS applies. Sorry to be such a nuisance! JFW | T@lk 17:24, 31 January 2016 (UTC)[reply]
- Incidentally I agree with the wording change. Association does not prove causation. JFW | T@lk 17:26, 31 January 2016 (UTC)[reply]
- @Jfdwolff: Not a nuisance at all, it's important to get it right. I've implemented the secondary source only table in the article I'll store the current version of the table in this talk page for reference in case anyone needs to chase down a primary reference for some reason. T.Shafee(Evo﹠Evo)talk 12:16, 1 February 2016 (UTC)[reply]
- Sorry but I really, really disagree - fair enough cite a secondary source for medical condition, but in in a lot of cases the primary citations ARE important and relate to scientific findings where primary sources can and should be cited - the maspin entry for example is now incorrect, and removing valid information that actually is useful to the community simply because one doesn't want to cite a primary source seem odd and non-helpful. User:Jcwhizz - James Whisstock.
- OK - I'm not expert enough a user to undo all that has been done to the table without causing utter mayhem! I think it is essential that primary sources in the table are cited for scientific findings - these make reference to valid peer reviewed papers that usually are published in high profile journals. I am happy for secondary sources to be cited for diseases. So we don't get into a game of tennis and prior to attempting to re-reference the table does this seem reasonable to all?. User:Jcwhizz - James Whisstock.
- @Jcwhizz and Jfdwolff: I've had a think about this and I have a possible solution. I agree that it would be a shame to sacrifice the utility of the references for the non-medical statements by just citing secondary sources. What's more, the main secondary sources ([1][2]) are from a biochemistry research angle rather than a medical angle, so aren't actually ideal for WP:MEDRS anyway.
- What I suggest is to ensure that all medical claims are kept only in a "Human disease" column, and are only kept if good secondary/tertiary sources can be found for them. Mouse models etc should be kept in a different column so that their relevance to humans is clearly distinguished (and primary sources are still permissible). That way the statements that need to be WP:MEDRS-compliant are more clearly delineated within the table. I've implemented what I mean in the article for now, with disease statements removed until I find good sources for each. I'll add them back in as I go. T.Shafee(Evo﹠Evo)talk 12:19, 5 February 2016 (UTC)[reply]
- Evolution and evolvability Thanks, and sorry for the hassle! JFW | T@lk 12:26, 5 February 2016 (UTC)[reply]
- I think it's important, and worth it to get it right for an FA. Given that the superfamily has such biochemical and medical relevance, it's actually pretty unique as an FA. I hope that resolving it will set a good precedent for other similar articles in the future. T.Shafee(Evo﹠Evo)talk 12:32, 5 February 2016 (UTC)[reply]
- OK I have some more thoughts for the ones that you need support for. SERPINB6 - this is pretty clear cut. First of all KO in the mouse results in hearing loss - see PMID: 23669344, so that at least can be cited and mentioned in the table. There are about 4 different studies on various populations that show association of SERPINB6 with human hearing loss - all primary I guess - maybe also cite PMID:20451170 and PMID:25817395 in effect of deficiency section. SERPINB7 was a major discovery and actually very interesting - there are a couple of reviews - PMID: 25029323 and PMID: 24635962. SERPINC1 is antithrombin - heaps and heaps of reviews to choose from here - PMID: 21781239 would be a recent one, but it is one of the best characterised serpins to date. SERPENT (PAI-1) is clearly controversial - think leave this one out in the disease column. SERPINH1 got a cracker here - PMID: 25007323 and PMID: 23145505 - very high profile reviews - again really interesting and unexpected discovery as well. SERPINI1 - very well known if rare disease (FENIB) - see PMID: 12112652 for e.g. or PMID: 19164889. Finally PMID: 25660269 for SERPING1 or PMID: 24125136 - again this should not be controversial - G1 is complement C1 inhibitor - well known in angiodemia. PMID: 17768101 for macular degeneration. By the way I do apologise that I'm simply not adding these things by myself - I just feel that I'm likely to do more formatting harm than good!!!!! As soon as my grant writing season is over I'll try to relearn how to do wiki pages properly. OK - over and out will look at the remainder later. User:Jcwhizz - James Whisstock.
Thanks for the medical review references James. I've integrated them into the megatable, in addition to a good review of the SERPINF2 (α2-antiplasmin). The remaining serpins (A10, B8, I2) seem to have only primary references at the moment. similarly, SERPINA10 (PZI) still seems highly contentious. It's reviewed in '07,[3] but an '08 meta-analysis disagrees.[4]. We should probably leave them out for now, until their disease role is reviewed in the medical literature. T.Shafee(Evo﹠Evo)talk 05:13, 21 February 2016 (UTC)[reply]
- Hi - I am really really happy with all this - it is great - all my concerns have been addressed!!!! User:Jcwhizz
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References
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Comments from Opabinia
edit- Support! I've been meaning to read this forever and it looks like everyone else has beaten me to criticisms of any substance :) Well written and illustrated as usual, and very deserving of an FA star. Minor nitpicks/suggestions below. Opabinia regalis (talk) 06:29, 23 February 2016 (UTC)[reply]
- A few instances of "conformation change" - to my ears it should always be "conformational".
- History section says
The name "Serpin" was first coined in the 1980s when it became clear that they formed a large superfamily of related proteins that also included non-inhibitory members
- which gives the impression that the name was chosen due to the non-inhibitory members - but the lead says the name is from "serine protease inhibitors", the opposite implication. - In the protease inhibition section,
preventing modulating activity of protease
is awkward. - It sounds as if the key to this inhibition mechanism is the kinetics: the conformational change happens faster than acyl hydrolysis. Have the rates actually been measured? Are there mutants that are slow switchers and therefore ineffective inhibitors?
- Degradation of extracellular serpins is mentioned, but not intracellular - is there anything interesting to say about how these are recycled? (It would be kind of cool if there were a ubiquitination site only exposed post-transition...)
- Parallelism in the distribution subheads ("fungal", "prokaryote" - pick either nouns or adjectives)
- Done - Thanks! I've addressed the wording suggestions. As for the kinetics question, you're completely correct. For wild-type serpins, the relative rates of (inhibition)/(hydrolysis)≈1 i.e. inhibition is so much faster than hydrolysis that the relative rates can't be measured. I get the impression that it's at least 103-fold faster given the accuracy of the methods used to measure, but I can't find a secondary source that makes the statement. I've added a sentence highlighting the significance of the kinetics. There are plenty of mutants with reduced conformation change rates, but I think that those details are probably too much for the article. V. interesting though! It also turns out that there are multiple, definable sub-steps in the conformational change. [1] T.Shafee(Evo﹠Evo)talk 21:09, 24 February 2016 (UTC)[reply]
- Interesting, thanks! I guess one thing I learned today is that acyl hydrolysis is slower than I would've thought. Opabinia regalis (talk) 02:51, 25 February 2016 (UTC)[reply]
- Done - Thanks! I've addressed the wording suggestions. As for the kinetics question, you're completely correct. For wild-type serpins, the relative rates of (inhibition)/(hydrolysis)≈1 i.e. inhibition is so much faster than hydrolysis that the relative rates can't be measured. I get the impression that it's at least 103-fold faster given the accuracy of the methods used to measure, but I can't find a secondary source that makes the statement. I've added a sentence highlighting the significance of the kinetics. There are plenty of mutants with reduced conformation change rates, but I think that those details are probably too much for the article. V. interesting though! It also turns out that there are multiple, definable sub-steps in the conformational change. [1] T.Shafee(Evo﹠Evo)talk 21:09, 24 February 2016 (UTC)[reply]
References
- ^ Gettins (2002). "Serpin Structure, Mechanism, and Function". Chemical Reviews. 102 (12): 4751–5504. doi:10.1021/cr010170+. PMID 12475206.
Response 3 from T.Shafee(Evo﹠Evo)
editThank you again to all delldot, Jfdwolff, Aa77zz, Seppi333, Opabinia regalis, and Jcwhizz. I think I've now addressed everyone's key recommendations and criticisms. In particular, I think the combination of primary/secondary sources for scientific points with med-secondary and tertiary sources for medical points has made the page more robust. Again, let me know if there are any additional issues, or if you feel I've not fully addressed the issues already raised! T.Shafee(Evo﹠Evo)talk 21:20, 24 February 2016 (UTC)[reply]
- Suppport FA. Great work. Could I recommend one slightly different source for the clinical correlate of SERPING1 deficiency: doi:10.1016/j.autrev.2015.03.006. The source currently supporting the link with hereditary angiooedema is mostly a cohort study. Otherwise very good work and ready for the star. JFW | T@lk 06:05, 25 February 2016 (UTC)[reply]
Coord note
editT.Shafee(Evo﹠Evo), is this your first FAC? A belated welcome if so -- we will need a spotcheck of sources for accurate use and avoidance of close paraphrasing in that case. Also source review for formatting and reliability, and image licensing review. All these can be requested at the top of WT:FAC. Cheers, Ian Rose (talk) 23:14, 27 February 2016 (UTC)[reply]
- @Ian Rose: Thanks, FAC is surprisingly different to the GA system! I've added a source audit request at WT:FAC. Are there any other steps I need to take, or will the rest of the process run its course automatically if the article passes source review? Thanks again, T.Shafee(Evo﹠Evo)talk 15:03, 28 February 2016 (UTC)[reply]
- Hi, per my initial comment, pls add "image review" to your list of requests at WT:FAC (unless the licensing has already been validated and I missed it). As long as all these checks come back clean (or any issues found can be actioned in reasonably short order) then there should be nothing more to do before the article can be promoted. Cheers, Ian Rose (talk) 22:59, 28 February 2016 (UTC)[reply]
- P.S. I note several duplicate links in the article. Given the length and technical nature of the article, some of these might be justified but pls review in any case (you can install and run this script to highlight the duplicates). Cheers, Ian Rose (talk) 23:10, 28 February 2016 (UTC)[reply]
- Thanks. I've corrected the request. I've also done a run through removing duplicate wikilinks (certainly those in the same section). Some concepts are introduced broadly in e.g the lead or mechanism, but then discussed in more detail in a later section, so the duplicate link is occasionally useful. T.Shafee(Evo﹠Evo)talk 18:05, 29 February 2016 (UTC)[reply]
- P.S. I note several duplicate links in the article. Given the length and technical nature of the article, some of these might be justified but pls review in any case (you can install and run this script to highlight the duplicates). Cheers, Ian Rose (talk) 23:10, 28 February 2016 (UTC)[reply]
- Hi, per my initial comment, pls add "image review" to your list of requests at WT:FAC (unless the licensing has already been validated and I missed it). As long as all these checks come back clean (or any issues found can be actioned in reasonably short order) then there should be nothing more to do before the article can be promoted. Cheers, Ian Rose (talk) 22:59, 28 February 2016 (UTC)[reply]
Source and image review by Cas Liber
editOk, taking a look....
- Refs should all be formatted the same - hence the authors of refs (using this version for reference) 8,11, 12, 53, 156, 157 and 163 (and some others) should all be "Smith J, Jones F, etc"
- pageranges in refs should be consistent - hence ref 105 has "1269–1275" and ref 40 has "579–586" (also ref 101) - where in most other places you seem to have a two digit page range (e.g. ref 100 has "237–45")
some dates are written "2013-07-01" and some are "March 2002" - I'd comform them all.- Dates have been standardized to DMY. Seppi333 (Insert 2¢) 17:46, 10 March 2016 (UTC)[reply]
- FN 1 used 5 times - material cited and faithful to source
- FN 19 used 3 times - material cited and faithful to source
- FN 66 used 6 times - material cited and faithful to source
- FN 190 used twice - material cited and faithful to source
- FN 192 used once - material cited and faithful to source
Regarding images, if File:Serpin (stressed).png is actually the synthetic scorpion toxin linked to, should it not say that in the description?
- Same goes for File:Serpin and protease.png and File:Serpin equilibrium.png
- Eep, my mistake: PDB: 2K9O should be PDB: 1K9O! T.Shafee(Evo﹠Evo)talk 23:25, 10 March 2016 (UTC)[reply]
Closing comment
editI'm going to promote but pls note there are several duplicate links in the article; some may well be justified given the article's length and detail but pls review and lose whatever's superfluous. This script can be installed and invoked to highlight the duplicates. Cheers, Ian Rose (talk) 13:01, 11 March 2016 (UTC)[reply]
- Closing note: This candidate has been promoted, but there may be a delay in bot processing of the close. Please see WP:FAC/ar, and leave the {{featured article candidates}} template in place on the talk page until the bot goes through. Ian Rose (talk) 13:03, 11 March 2016 (UTC)[reply]
- The above discussion is preserved as an archive. Please do not modify it. No further edits should be made to this page.