Talk:Histamine N-methyltransferase

GA Review

This review is transcluded from Talk:Histamine N-methyltransferase/GA1. The edit link for this section can be used to add comments to the review.

Reviewer: Esculenta (talk · contribs) 15:29, 9 April 2021 (UTC)

@Esculenta - we had discussions in 2023 that, if you had time in 2024, you will be able to review the revised article, if no one reviews it by that time. Could you please do that? Thank you in advance. Maxim Masiutin (talk) 12:08, 19 January 2024 (UTC)

Hi, I'll review this article. I'll need a day (or few) to post a full review, but on first glance I notice that the article is missing historical background, i.e., who discovered the enzyme, when, why, etc. Also missing is any information about the enzyme structure. How big is it? Is it made of subunits? What is the nature of its active site, etc., etc. These aspects will have to be added to the article for it to meet WIAGA criteria 3a ("it addresses the main aspects of the topic"). There's 1000's of hits for this topic on Google Scholar, including several review articles published in the past years that haven't been used as sources, so it shouldn't be difficult to find this kind of information. I see the article is listed as A-class, but I can't find a link to an A-class review ... could you kindly point me to that? Esculenta (talk) 15:29, 9 April 2021 (UTC)

Thank you, I will address the issues that you have raised. There were no A-class review :-( Maxim Masiutin (talk) 19:02, 9 April 2021 (UTC)

Ok, I read through the article and it seems to me like it is quite a ways from GA-standard.

• the lead is too short and does not adequately summarize the article’s contents
• the lead should briefly explain what histamine is and why it is important, which would help give context for the reader about the importance of the enzyme
• the lead says MNMT is involved in histamine metabolism, which is of course true, but I get few hints from the article that it inactivates histamine - this should be more explicit
• should link gene, chromosome 2
• could we have a reaction equation somewhere in the article? see here for an example
• first paragraph of “Function” needs a citation
• ”In brain of mammals histamine neurotransmitter activity is controlled by Nτ-methylation” please explain how neurotransmission is “controlled” by methylation
• ”As about the biologic species” not sure what this phrase adds, can it be left out?
• ”Whereas DAO metabolizes extracellular free histamine, be it either exogenous came with food or mostly endogenous released from granules of mast cells and basophils[8] as a result of allergic reactions, in view of the fact that DAO is mainly expressed in the cells of intestinal epithelium, HNMT is involved in metabolism of the persistently present intracellular primarily endogenous histamine, mainly in kidneys and liver, but also in bronchi, large intestine, ovary, prostate, spinal cord, spleen, trachea[9] and peripheral tissues.” This is a really long sentence that’s hard to parse and would benefit by being broken up.
• ”The most studied genetic variant is T allele at rs11558538 (c.314C>T, p.Thr105Ile),” where in the two cited sources does it support the assertion that it is “the most studied genetic variant”? The first source says it “has been the matter of several case–control association studies”, while I cannot find any such assertion in the second cited article. The shorthand jargon (c.314C>T, p.Thr105Ile) is incomprehensible for the average reader and should be explained. Also, the frequency of this allele should be mentioned (“occurring in an estimated 5 to 10% of the healthy Caucasian population” according to PMC5058861)
• why is the website for the diagnostic testing company IMD Labor Berlin used as a source? Surely a neutral secondary source could be used to cite these basic facts.
• ”In a study of 48 adults, median enzyme activity was significantly lower in subjects with the CT or TT genotype than in those with the wild-type CC genotype (485 versus 631 U/mL of red blood cells).[13] In another study of 195 subjects, the C314T variant also showed an association with serum Interleukin-8 (IL-8) levels — individuals with the CT or TT genotype had lower levels of IL-8 (1.2 ± 0.7 versus 2.1) and higher levels of histamine (107.0 ± 53.9 versus 85.6 ± 45.7 ng/mL) in comparison with individuals with the CC genotype.” This is far too detailed for a Wikipedia article – the average reader doesn’t need to know the number of study participants, nor the experimentally determined concentrations (complete with standard deviations). Additionally, reference 13 is a pilot study (i.e. a primary study) from 2006, and shouldn’t even be used in an overview article like this (see WP:SCIRS)
• per WP:SEEALSO, links already in the article shouldn’t be repeated here, so this could just be removed
• any rationale for inclusion into the lengthy “Further reading” section? Some are older primary studies
• Missing stuff:

• basic info about HNMT’s enzymology: what’s its EC number? is it inhibited by its reaction product in a negative-feedback loop? Kinetic data comparing the standard form of the enzyme with the common Thr105 variant? (e.g. what is the difference in activities between standard and Thr105 variant?)
• mention of the association with defective HNMT (i.e. SNPs) and Parkinson’s disease, ADHD, mood disorders, or decreased intellectual ability
• mention of HNMT’s role in regulating the airway response (e.g. doi:10.1152/ajplung.1994.267.3.L342
• research into use of HNMT as treatment for meth overdose doi:10.4137/DTI.S38342
• there’s an image of HNMT’s structure in the infobox, so presumably this enzyme has been crystallized. When and by whom? Are there interesting aspects of its structure that have been revealed by this work? Does it have a structure consistent with other S-adenosyl-methionine-dependent methyltransferases (e.g. a standard AdoMet binding domain)?
• only human HNMT is discussed in the article. Any info on this enzyme from other animals? Is it highly conserved? % amino acid identities?
• has there been any work done with HMNT knockout mice?
• methylhistamine is one of the products of the enzyme reaction; perhaps a few words could be said about its resulting pharmacologic activity … is it active at histamine receptors?

For these reasons, I think the article needs quite a bit of work to meet the GA criteria, specifically criteria 1a, 3a, and 3b. I think this would be best worked on outside of the time contraints of the GA review, so I am closing this review, but hope to see it back at GAN after the issues above have been addressed. Esculenta (talk) 16:34, 15 April 2021 (UTC)

@Esculenta:Thank you very much! I will edit the page to address all the issues that you have described, and will then apply again. Thank you for your time and your carefully made, valuable observations! Maxim Masiutin (talk) 20:37, 15 April 2021 (UTC)

@Esculenta: thank you very much for your detailed feedback that I hope should contribute to the article improvement. I made updates and additions to the article based on your suggestions and observations. I hope that your contributions were not in vain. Thank you very much for your attention and you help.

the lead is too short and does not adequately summarize the article’s contents

Expanded the lead.

the lead should briefly explain what histamine is and why it is important, which would help give context for the reader about the importance of the enzyme

Done.

the lead says MNMT is involved in histamine metabolism, which is of course true, but I get few hints from the article that it inactivates histamine - this should be more explicit

Done.

should link gene, chromosome 2

Done.

could we have a reaction equation somewhere in the article? see here for an example

Thank you for this suggestion, I made a similar illustration, but an improved one: emphasized the transfer of the methyl group.

first paragraph of “Function” needs a citation

Now all the paragraphs have citations except the lead that does not contain claims on its own: all the claims made in the lead are repeated in the article, with appropriate references.

”In brain of mammals histamine neurotransmitter activity is controlled by Nτ-methylation” please explain how neurotransmission is “controlled” by methylation

Explained in the lead that HNMT controls histamine neurotransmitter activity "By degrading and regulating levels of intracellular histamine...."

Also explained in the body that "In the central nervous system, HNMT plays an essential role in degrading histamine, where it acts as a neurotransmitter, since HNMT is the only enzyme in the body that can metabolize histamine in CNS, ending its neurotransmitter activity."

”As about the biologic species” not sure what this phrase adds, can it be left out?

Thank you, clarified that.

”Whereas DAO metabolizes extracellular free histamine, be it either exogenous came with food or mostly endogenous released from granules of mast cells and basophils[8] as a result of allergic reactions, in view of the fact that DAO is mainly expressed in the cells of intestinal epithelium, HNMT is involved in metabolism of the persistently present intracellular primarily endogenous histamine, mainly in kidneys and liver, but also in bronchi, large intestine, ovary, prostate, spinal cord, spleen, trachea[9] and peripheral tissues.” This is a really long sentence that’s hard to parse and would benefit by being broken up.

Thanks, split that sentence.

”The most studied genetic variant is T allele at rs11558538 (c.314C>T, p.Thr105Ile),” where in the two cited sources does it support the assertion that it is “the most studied genetic variant”? The first source says it “has been the matter of several case–control association studies”, while I cannot find any such assertion in the second cited article.

I removed the claim about "most studied".

The shorthand jargon (c.314C>T, p.Thr105Ile) is incomprehensible for the average reader and should be explained.

Thank you! Explained that.

Also, the frequency of this allele should be mentioned (“occurring in an estimated 5 to 10% of the healthy Caucasian population” according to PMC5058861)

I rather mentioned it based on information from dbSNP, for global population, to avoid discrimination (Caucasian vs rest)

why is the website for the diagnostic testing company IMD Labor Berlin used as a source? Surely a neutral secondary source could be used to cite these basic facts.

Sorry, I removed reference to this testing company and instead put the references to reviews in journals that gave the same information. For example, from a study on "Two polymorphic forms of human histamine methyltransferase" I took the claim that "Methylated histamine metabolites are excreted with urine" because it is the easiest source for such a claim, however, the study itself is not related to metabolism of histamine or its excretion. It just gave this claim in the introduction, still, this claim was peer-reviewed, making this article a secondary source.

”In a study of 48 adults, median enzyme activity was significantly lower in subjects with the CT or TT genotype than in those with the wild-type CC genotype (485 versus 631 U/mL of red blood cells).[13] In another study of 195 subjects, the C314T variant also showed an association with serum Interleukin-8 (IL-8) levels — individuals with the CT or TT genotype had lower levels of IL-8 (1.2 ± 0.7 versus 2.1) and higher levels of histamine (107.0 ± 53.9 versus 85.6 ± 45.7 ng/mL) in comparison with individuals with the CC genotype.” This is far too detailed for a Wikipedia article – the average reader doesn’t need to know the number of study participants, nor the experimentally determined concentrations (complete with standard deviations). Additionally, reference 13 is a pilot study (i.e. a primary study) from 2006, and shouldn’t even be used in an overview article like this (see WP:SCIRS)

Sorry. I removed the description of studies.

There are some references to research articles, but these articles are used as secondary sources, i.e. I do not use research findings of these articles, but use commonly accepted claims not explicitly dependent on article reseach. Therefore, this research article becomes secondary source for those claims.

per WP:SEEALSO, links already in the article shouldn’t be repeated here, so this could just be removed

OK, thank you, removed that section.

any rationale for inclusion into the lengthy “Further reading” section? Some are older primary studies

It was a legacy section that existed before I started work on this article. I removed this section.

Missing stuff: basic info about HNMT’s enzymology: what’s its EC number? is it inhibited by its reaction product in a negative-feedback loop?

Thank you, it is indeed inhibited in a negative feedback loop. I mentioned that in the article and gave a reference.

Kinetic data comparing the standard form of the enzyme with the common Thr105 variant? (e.g. what is the difference in activities between standard and Thr105 variant?)

I removed the jargon and explained in simpler way.

mention of the association with defective HNMT (i.e. SNPs) and Parkinson’s disease, ADHD, mood disorders, or decreased intellectual ability

OK, I mentioned that based on reviews.

mention of HNMT’s role in regulating the airway response (e.g. doi:10.1152/ajplung.1994.267.3.L342

I mentioned that mucosa of bronchus is affected based on reviews, however, those reviews did not explain the details, still, that study that you mentioned is a primary one, so I was afraid to mention it. There was a mention at https://www.uniprot.org/uniprotkb/P50135/entry but it relied on a case report, which, in turn refers to a review that describes the process.

research into use of HNMT as treatment for meth overdose doi:10.4137/DTI.S38342

Thank you for pointing that out, I mentioned it!

there’s an image of HNMT’s structure in the infobox, so presumably this enzyme has been crystallized. When and by whom? Are there interesting aspects of its structure that have been revealed by this work? Does it have a structure consistent with other S-adenosyl-methionine-dependent methyltransferases (e.g. a standard AdoMet binding domain)?

I mentioned that the crystallographic structure was first described in 2001 and gave the reference to the publication of the articles where the researchers described it (primary study), as well as to secondary study. I also mentioned that it has a classic fold found in many other methyltransferases. Thank you for bringing the attention!

only human HNMT is discussed in the article. Any info on this enzyme from other animals? Is it highly conserved? % amino acid identities?

I made a brief description on HNMT in other animals, but did not describe in detail, as research on animal HNMT was mainly focused on understanding human HNMT, not as a biological field of study per se.

has there been any work done with HMNT knockout mice?

Yes, I mentioned the findings on a few studies given in a review article (mice were aggressive, etc.).

methylhistamine is one of the products of the enzyme reaction; perhaps a few words could be said about its resulting pharmacologic activity … is it active at histamine receptors?

Thank you, I explained that.

Thank you very much for such valuable contributions to the article! Maxim Masiutin (talk) 01:07, 30 November 2023 (UTC)

A quick review - looked at the old GA feedback.

@Maxim Masiutin

The GA feedback - not sure every point was covered nor if every point was ever super relevant - against the GA guidance.

1. There is a section in here that explains how information from a gene becomes a protein. I know I often comment about target audience, but in this case I think it is rational to point to the WP article that talks to this really major subject - Gene expression I could see some light preamble but the topic is about the protein and this description of GE takes up discussion space - one has to assume the reader has some base knowledge.
2. I think some of the language might be in parts very clunky - entering the bloodstream and such. I am happy to take a run at some of this - but likely later in the week.
3. I thought the structure of the steroid-21-hydroxylase article was really better - building from an expanded lede - gene - to protein - to actual enzymology dialog - role in pathologies (if any) - history of discovery - as we talked about - I think the target audience should be a UK A level Biology student - what they are exposed to is online.
4. I did not check the references - but looking at https://www.uniprot.org/uniprotkb/P50135/entry it looks fairly accurate.
5. Again seeing this as a unique protein - should be lots of data on how one describes a protein.
6. The enzymology part can get deep - and kinetics, active sites, substrate binding, I think it is easy to get trapped in CLOP - reflecting on this, I almost think making the discussion shallow has merits, again the S21H article was fairly good as to general balance - I think this one swings the other way.
7. Not sure if this helps - but I would not re-submit yet, there are some typos and spacing issues also.

Dr. BeingObjective (talk) 01:06, 28 November 2023 (UTC)

Yes, thank you! I will not resubmit yet. There is a schematic still missing.

As for the lead, I did not write it until we complete the body.

The lead should be based on the body, so I left it for later.

Let me think hot to link to the Gene expression better.

Should I have some other ideas or find typos, I will find them.

Should you also notice something or have ideas, please contribute.

Thank you! Maxim Masiutin (talk) 01:32, 28 November 2023 (UTC)

Not a problem - I'll take a look in the morning.

BeingObjective (talk) 01:37, 28 November 2023 (UTC)

I have resolved all the issues described by the reviewer and that you raised here, thank you very much! I resubmitted the article for the GA review. Maxim Masiutin (talk) 01:21, 30 November 2023 (UTC)

General Flow etc. Seeking to understand - so I can add value.

@ Maxim Masiutin

I looked at the structure of the S21H article, I understood this likely follows a prescribed format? Perhaps I am mistaken - logically, I can see a flow that would be.

Lede/Overview - I think it is LEDE oddly -- Gene -- Protein -- Activity -- Pathologies -- History -- etc. I think the species/distribution are oddly placed -- IMHO -- the function/mechanism - is low in the article - clinical sig. -- but if this maps to some guidance - I understand it is a requirement.

I noted a lot of data in the infobox structure - I assume it is a template - and I stated - my molecular biology skills are like a decade or more out of date.

It might seem irrelevant but left to my own professional devices - I'd likely have gone for:

Lede/Summary -- History -- Gene Info. -- Protein Data -- Chemical Functionality/mechanism -- Distribution -- Clinical Sig.

About the degree of detail and target audience:

1. Gene Info/gene expression - mixed feelings - S21H has no deep discussion on gene expression and I think any attempt to really expand this might make this article not align with other similar articles in WP - as mentioned - pointing to a fairly elaborate description article is good enough. So deleting out the current explanation - makes sense - I was going to do this - but wanted to ensure you are in agreement.
2. The functionality/mechanism and equations - this is where I wonder who this is again targeted to - it is very detailed in S21H - I think this can be simplified - this is really fairly detailed.
3. There is a very good article - Methyltransferase. I think your opening likely will be 'Histamine N-methyltransferase (HNMT; Molecular Interaction Map # 605238) is a cytoplasmic protein that belongs to the methyltransferase superfamily and is one of two enzymes involved in the metabolism of HA....'

Just a few late night mumblings - BeingObjective (talk) 07:22, 28 November 2023 (UTC)

We cannot change the order of the sections much in the article on 21-Hydroxylase and on Histamine N-methyltransferase. Although we can move between certain sections, we cannot put the History section to the beginning. Whereas articles in peer-reviewed journals usually start with the History, in Wikipedia, History is among the last sections. Probably, this is because in Wikipedia, there is a rule that the most important information should come first; I don't know the rationale, but we cannot put History section to the top.

I would suggest to improve the content of the sections rather than move the sections between them for 21-Hydroxylase and for Histamine N-methyltransferase I like the proposed order of sections in WP:MEDMOS.

I do not agree on deleting current information in the "Gene" section for 21-Hydroxylase: the CYP21A2 gene is unique comparing to other genes because it is located in a multimodular cluster, and it should be explained. Even researchers do not understand this topic. I saw many articles where researchers wrote that the CYP21A2 gene is accompanied by CYP21P1 pseudogene, but it is not always the case. In an unimodular structure of RCCX, there is no pseudogene. Quote: In a monomodular structure, all of the genes are functional i.e. protein-coding, but if a module count is two or more, there is only one copy of each functional gene rest being non-coding pseudogenes with the exception of the C4 gene which always has active copies.

As for the HNMT, there is the following 3 pieces of information mentioned in the Gene section:

1. Three transcript variants have been identified for this gene in humans, only one has histamine-methylating activity.
2. The cDNA of Hnmt was initially cloned from a rat kidney and has since been cloned from human, mouse, and guinea pig sources.
3. In the human genome, six exons from the 50-kb HNMT contribute to forming a unique mRNA species, approximately 1.6 kb in size. This mRNA is then translated into the cytosolic enzyme histamine N-methyltransferase, comprising 292 amino acids.

Do you prefer to move this information to the "Species" section? I think that the "Species" section is more on biodiversity, whereas the "Gene" section is more on exons and intron and other things specific to a gene. I think it will be unfair to delete it.

On the functionality/mechanism and equations - I would suggest to keep it as it is for CYP21A2. As for HNMT, yes, there is room for improvement here. We should explain the chemical reaction and give the schematics, and probably also explain more on pathways of histamine metabolism. So, there is lot of work to be done on this section.

I will look at Methyltransferase, thank you! Maxim Masiutin (talk) 07:59, 28 November 2023 (UTC)

I will also try to delete "These variants arise due to a process called alternative splicing, which allows a single gene to code for multiple proteins by including or excluding particular exons of a gene in the final mRNA produced from that gene"

because it makes things complicated to follow, I agree with your observation. Maxim Masiutin (talk) 08:01, 28 November 2023 (UTC)

Perhaps a little confusion - I think the CYP genetics - critical, I might have miscommunicated - I totally agree, this is really good data and I had no intention of messing with it - the pseudogene information defines the section - not sure what I stated - but just a misunderstanding.

I did not make any changes to it recently. I did mention the activity was highly detailed but it all checks out.

Section 3 could be in gene or protein - I tend to think of amino acid counts to be a descriptor of an unfolded protein - but I am old fashioned and I think a molecular biologist would not see it that way.

Yes, if it is a required WP format it is fine - a little odd, but I assumed it was defined. BeingObjective (talk) 08:22, 28 November 2023 (UTC)

I agree that certain paragraps or sentences can be tossed around sections. If you find a good candidate to move, please feel free to do so! Maxim Masiutin (talk) 09:11, 28 November 2023 (UTC)

I moved something to "Species", deleted some common stuff, but left all stuff on substance, so now the "Gene" section is concise. Maxim Masiutin (talk) 08:11, 28 November 2023 (UTC)

Yes, this makes sense. BeingObjective (talk) 08:23, 28 November 2023 (UTC)

Function discussion.

@ Maxim Masiutin

I think you stated you might have materials that express this section in a more diagrammatic way - it is text dense, an is arguably a very important section - I looked at the S21H activity area - and a lot of work was done to represent this schematically.

I need to understand the ways other articles work this section - the S21H is especially detailed, I am not totally convinced one has to be that intricate in every article about an enzyme - I guess it depends on the source materials available.

BeingObjective (talk) 14:28, 28 November 2023 (UTC)

I think that BogHog may be familiar with the matter. Maxim Masiutin (talk) 15:15, 28 November 2023 (UTC)

The WP:MCBMOS gives a few article links as examples:

• Reelin
• Estrogen_receptor
• Alcohol_dehydrogenase

These articles are very good on substance, but I don't know whether they fully comply to various Wikipedia rules, I didn't check. Maxim Masiutin (talk) 15:21, 28 November 2023 (UTC)

I think this is the very essence of the matter - an article is good - by what real measure?

With respect to GA editors - they are following a fairly basic checkbox, and there is still a lot of subjectivity in interpreting GA requirements - sure some aspects are 'clean' assessments - is it appropriately sourced and the like.

But, especially on a very technical article, it is a challenge - as you state, the articles that WP:MCBMOS invokes as exhibits, you feel are not compliant - is rule following inhibiting good article production? I have no answer, though being too literal in interpreting what really was only intended as guidance - might be the actual issue.

BeingObjective (talk) 17:18, 28 November 2023 (UTC)

Yes, that makes sence. I will now try to make drawings for SAM-e and SAH and will try to make drawings of histamine metabolism by HNMT. Maxim Masiutin (talk) 18:13, 28 November 2023 (UTC)

GA Input --The lead is too short and does not adequately summarize the article’s contents

There seems a little concern on what should be in the lede of this article based on the aforementioned GA review.

I think it worth capturing on the article talk page - the original dialog was on my talk page and will get lost in time.

Guidance states 'most' content - I think there is merit in not be too literal, in the following circumstance.

1. When an enzyme is part of a superfamily of enzymes and a robust article already exists talking about the broader family. I think mentioning this in the lede - makes perfect sense - and linking to the parent article.
2. It does not need to be repeated nor deeply discussed in the article body, this seems to add no value - the article is about one member of the enzyme group - mentioning this fact in the lede can hardly violate any guidance - and this is guidance only.
3. The GA review did state the article's lede was light - I think the reviewer was also too literal -
4. One could move it into the body, but it is worth no more than a few sentences no matter where it lives - this applies to any topic when something is a subset of a bigger thing - I think this seems simple common sense - and hardly worth me typing this little diatribe.

Cheers -

BeingObjective (talk) 16:56, 28 November 2023 (UTC)

Please see whether this illustration is Histamine_N-methyltransferase#Function? Maxim Masiutin (talk) 20:17, 28 November 2023 (UTC)

Well, it is sourced to https://www.rcsb.org/structure/2aot

Is there a concern this is not?

BeingObjective (talk) 20:38, 28 November 2023 (UTC)

I mean the chemical reaction, not the protein structure.

Maxim Masiutin (talk) 20:42, 28 November 2023 (UTC)

Where did you conjure this from? I only note your name and no authoritative academic source.

SAM is a cofactor sure - I noted a very similar image in the methyltransferase article - also with no formal academic attribution - did you just take this and put the structures described from the text? Are you sure this is actually compliant with WP policies?

Surely you must need to cite this and if understand how you created it - what are you going to cite?

Simply not sure about this, if you cannot find a source to cite - it might be prudent not to even include such a diagram - or simplify it so that it is clearly a gross simplification - tricky.

BeingObjective (talk) 21:44, 28 November 2023 (UTC)

What do you mean by academic attribution? Do you mean that we should back up a claim that histamine goes to N-methylhistamine and SAM-e goes to SAH? I will find source for that. Maxim Masiutin (talk) 22:48, 28 November 2023 (UTC)

The reaction is described here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030376/

quote: HNMT inactivates histamine by transferring a methyl group from S-adenosyl-L-methionine (AdoMet) to the Nε2 atom of the imidazole ring, yielding methylhistamine and S-adenosyl-L-homocysteine (AdoHcy).

We referenced this article when we explained the reaction. Should we also reference it near the drawing, this is what you mean? Maxim Masiutin (talk) 22:57, 28 November 2023 (UTC)

There is another source, quote: "Histamine-N-methyltransferase (HNMT) methylates histamine by transferring a methyl group to the imidazole ring, using SAM as the methyl group donor, yielding methylhistamine and SAH. HNMT: SAM + histamine = SAH + N(tau)-methylhistamine""

PMID 34893161

it is a review, therefore, more preferred as a source Maxim Masiutin (talk) 23:09, 28 November 2023 (UTC)

If you are happy with this, it is fine. Truly.

You actually asked me for a 'reality check' - yes?

I do not want to offend you and I am happy to continue a working collaborative relationship - we do not have to agree on every single thing. You have helped me a great deal.

I am not sure I can support the way the graphic came to be, perhaps I am totally wrong - recall, I am new and just another general editor - we are not working as collaborators in a formal academic environment.

As you stated to me, WP has no 'editor in chief' - if you think this is fine, then has to be.

The document is currently FAR better - so let's leave it at that.

I would have strongly preferred a schematic with clear provenance - it is not the case - both schematics are 'own work' - I would have liked 'Dr. xyz, UCLA, Biochem, as I communicated to you. I think my concerns were really very clear -

Kind Regards Dr. BeingObjective (talk) 00:09, 29 November 2023 (UTC)

I don't understand what you mean, frankly. Maxim Masiutin (talk) 01:03, 29 November 2023 (UTC)

@Boghog: Can you please help? - can you please help.

I saw schemes of histamine methylation by HNMT at these works: PMID 33310825,

PMID 30744146, PMID 34893161 and drawn a scheme using Inkscape. To get molecules, I took SMILES from ChEBI and converted them to SVGs and then pasted these SVGs around a sheet, made captions and arrows, and colorful ovals, then put this drawing to the page on Histamine N-methyltransferase, citing those works where I saw similar scheme. Still, Dr. BeingObjective asks about formal academic attribution as required to Wikipedia. There is probably a misunderstanding, can you please help us? Maxim Masiutin (talk) 01:19, 29 November 2023 (UTC)

@BeingObjective I guess I wrote about HNMT all I could. Thank you also for your contributions and comments. Should you have suggestions, let me know. Maxim Masiutin (talk) 06:41, 30 November 2023 (UTC)

According to Wikipedia:Image use policy: Wikipedia encourages users to upload their own images. The providence of images uploaded to Wikimedia commons is clear when the "created myself" option is used. Using figures downloaded from the web would require a Wikipedia compatible license which is often difficult to find. Also a lot of what is available on the web is low quality. At the same time, it is important to include a source (preferably secondary or tertiary) that confirms what is in the image is accurate. For the reaction catalyzed by histamine N-methyltransferase, one could use KEGG whose layout closely resembles File:HNMT-methylation-of-histamine.svg. Boghog (talk) 04:36, 29 November 2023 (UTC)

Thank you! I will put KEGG as a reference. Thank you again for your help! Maxim Masiutin (talk) 04:39, 29 November 2023 (UTC)

I will also put these KEGG figures to the image metadata on Wikimedia commons. Maxim Masiutin (talk) 04:40, 29 November 2023 (UTC)

@Boghog - I think this part of your response "For the reaction catalyzed by histamine N-methyltransferase, one could use KEGG whose layout closely resembles File:HNMT-methylation-of-histamine.svg." - is at the heart of the concerns I expressed to @Maxim Masiutin.

Thanks for the explanation, though still - 'I beleive this looks like what happens', and that is how I read the aforementioned statement you made, seems at odds with WP:RS.

This was published without any provenance, despite the robust prior dialog - I was asked in this thread 'does this 'look okay' - and I still would state - why are you even asking me after it was published?

Provenance is the correct word, this is really not like stating something and then dropping a robust PMID in to support it.

I could not find materials that satisfied my concerns on this 'my own work' issue - and I do not think this requires any further dialog - it is perhaps just a reality of WP.

BeingObjective (talk) 14:48, 29 November 2023 (UTC)

I think that the term "own work" in this context should be considered from the point of view of the copyright legislation, i.e. the person who drew lines and arranged figures. Underlying information, such as the order of reactions in a chemical process is not copyrightable. Therefore, the term "own work" is applicable here as the term "own work" is understood in the copyright legislation. If you see the image metadata, everything there was about copyright: license, author, whether it is a derived work or an original work, etc. Ideas are not copyrightable, so if I saw similar schemes and draw my own one from scratch it is not considered a derivative work, but my own work. Also, electrocardiogram images are not copyrightable. But if you put an arrow as an explanation, this becomes a work protected by copyright. Maxim Masiutin (talk) 15:00, 29 November 2023 (UTC)

I suspect you will not convince me on this matter - KEGG ref. or not - an ECG exhibit is not the same thing and it is nothing about CR - more about Wikipedia:Reliable sources

Cheers BeingObjective (talk) 15:04, 29 November 2023 (UTC)

Apologies - the link should be: Wikipedia:Reliable sources.

I just see this a weird conflict of the ethos expressed here - even the KEGG ref is a form of weird nebulous editorializing - the credibility of any articles needs to take the editor out of the thing being talked about - is this not the essence of WP?

Enough perhaps. BeingObjective (talk) 15:01, 29 November 2023 (UTC)

(edit conflict) I really don't see what the problem is here. KEGG is a reliable tertiary source. File:HNMT-methylation-of-histamine.svg is supported that source. Hence my statement is completely consistent with WP:RS. Full stop. Ideally the source should have been provided at the same time graphic was inserted into this article, but better late than never. The provenance of the graphic is the editor (Maxim) who created it. KEGG is not editorializing, they are simply summarizing the scientic literature. Boghog (talk) 15:22, 29 November 2023 (UTC)

Let's terminate this dialog, enough on the matter.

BeingObjective (talk) 15:39, 29 November 2023 (UTC)

I already mentioned KEGG and 3 Pubmed sources yesterday in the reference behind the image. Will try to be more specific. Maxim Masiutin (talk) 15:47, 29 November 2023 (UTC)

References

Pushing electrons

@BeingObjective, @Boghog Can you help me with chemistry? There is a ting that I don't fully understand. In chemistry, a curved (curly) single-headed arrow is used to depict the movement of a single electron from one place to another, either in resonance or in a mechanism. However, in a hystamine methylation, curly arrow on the sources I given (via PMIDs) is from SAMe to SAH. There also a hydrogen atom relesed, but it is not shown on reaction. However, I couldn't find any specific information about the use of a curved arrow to distinguish a cosubstrate transformation from the main substrate transformation. Does the electron move from SAMe to SAH in this reaction? Maxim Masiutin (talk) 15:15, 29 November 2023 (UTC)

It is important not to confuse a biochemical reaction schematic (where the arrows can either be straight or curved), and an "electron pushing" reaction mechanism, where the movement of a pair of electrons is represented by a curved double barbed arrow and the movement of a single electron is represented a single barbed arrow. File:HNMT-methylation-of-histamine.svg is a biochemical reaction schematic and the curved arrow in it does not imply the movement of a single electron. Boghog (talk) 15:35, 29 November 2023 (UTC)

Is there a nomenclature described on biochemistry? It is not a coincidence that 3 sources used curly arrow for cosubstrate transofrmation? Where can I read about it? Maxim Masiutin (talk) 15:46, 29 November 2023 (UTC)

Oops, hydrogen is released in case of diamine oxidase reaction (DAO aka AOC1) on histamine, not in case of HNMT. Sorry for confustion. Maxim Masiutin (talk) 15:49, 29 November 2023 (UTC)

From my quick googling, it appears that most methyltransferases (including histamine N-methyltransferase) catalyze the classical (non-radical) S_N2 mechanism where histidine acts as a nucleophile and SAM acts as a electrophile. There are a few methyltransferases that catalyze a radical mechanism that requires a [4Fe-4S] cofactor. Boghog (talk) 15:58, 29 November 2023 (UTC)

There is an interesting notion at https://bio.libretexts.org/Bookshelves/Biochemistry/Fundamentals_of_Biochemistry_%28Jakubowski_and_Flatt%29/01%3A_Unit_I-_Structure_and_Catalysis/06%3A_Enzyme_Activity/6.05%3A_Enzymatic_Reaction_Mechanisms

See Figure 6.5.2 : Class I methyltransferase mechanism alternative arrow pushing

There is a description of the use of arrow in a reaction from SAMe to SAH, still, a bit complicated convention Maxim Masiutin (talk) 16:01, 29 November 2023 (UTC)

It seems that I have to make arrow from methyl group probably. Let me try. Maxim Masiutin (talk) 16:02, 29 November 2023 (UTC)

Some more information is here which shed light on this arrow conventions: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491745/ Maxim Masiutin (talk) 16:07, 29 November 2023 (UTC)

Another way of thinking about it, in a reaction schematic, the arrows point at molecules that are consumed or created. In a reaction mechanism, the arrows point a individual atoms and the arrows themselves represent a flow of electrons, where a single barbed arrow represents the movement of a single electron and a double barded arrow represents the movement of a pair of electrons. Boghog (talk) 16:32, 29 November 2023 (UTC)

OK, that makes sense. I just made the two arrows connect each other to show that it is a single reaction. Maxim Masiutin (talk) 17:13, 29 November 2023 (UTC)

Can you please now review the caption behind the image in the "Function" section of the article (Histamine_N-methyltransferase#Function). I hope that it is now more than reasonable, both on citing sources and on explaining what the arrows mean. Maxim Masiutin (talk) 17:19, 29 November 2023 (UTC)

GA Review

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

---

This review is transcluded from Talk:Histamine N-methyltransferase/GA2. The edit link for this section can be used to add comments to the review.

Nominator: Maxim Masiutin (talk · contribs)

Reviewer: Sammi Brie (talk · contribs) 22:25, 23 March 2024 (UTC)

GA review (see here for what the criteria are, and here for what they are not)
It is reasonably well written. a (prose, spelling, and grammar): b (MoS for lead, layout, word choice, fiction, and lists): It is factually accurate and verifiable. a (references): b (citations to reliable sources): c (OR): d (copyvio and plagiarism): It is broad in its coverage. a (major aspects): b (focused): It follows the neutral point of view policy. Fair representation without bias: It is stable. No edit wars, etc.: It is illustrated by images, where possible and appropriate. a (images are tagged and non-free images have fair use rationales): b (appropriate use with suitable captions):
Overall: Pass/Fail:
· · ·

Some reference issues. Britannica needs to be excised, and I need some explanation on the blood serum line. I also want to see Esculenta's comments if they materialize soon. Ping me when done; I may still hold for Esculenta to determine if the issues from GA1 still linger. Sammi Brie (she/her • t • c) 02:26, 24 March 2024 (UTC)

I removed the reference to Britannica and put different sources for the sentence "DAO is primarily responsible for metabolizing histamine in extracellular (outside cells) fluids, which include interstitial fluid (fluid surrounding cells) and blood plasma". If you still find these sources problematic, we can support particular parts of this sentence or remove it at all, as this sentence is about a different enzyme, other than what is covered in this article, so this sentence is not essential in this article. I will reply to your other issues soon. Maxim Masiutin (talk) 13:45, 24 March 2024 (UTC)

Did you know? If you fancy doing so, I always have plenty of GA nominees to review. Just look for the all-uppercase titles in the Television section. Reviews always appreciated.

I also saw that Esculenta was previously requested to provide feedback on this article at some point. Feel free to join in. Sammi Brie (she/her • t • c) 01:53, 24 March 2024 (UTC)

Copy changes

Lead

• Research on knockout mice lacking the Hnmt gene Is this styling appropriate for the gene in mice?
• Genetic variants affecting HNMT activity have also been implicated in various neurological disorders like Parkinson's disease and attention deficit disorder, still, as of 2024, it remains unclear whether alterations in HNMT are primary causes or secondary effects of these conditions. The first comma should be a semicolon. WP:CINS

Protein

• 33kDa Link this unit and add a space after "33".
• It has a classic fold found in many other methyltransferases, and consists of a seven-stranded beta-sheet surrounded by three helices on each side. Remove comma after "methyltransferases" (CinS)

Species

• Consider consolidating into fewer, longer paragraphs.
• Italicize or don't italicize the gene acronym consistently.

Function

• Reintroduce "diamine oxidase (DAO)" on first mention in the body of the article.
• DAO is predominantly expressed in the cells of the intestinal epithelium and placenta, but not in the central nervous system (CNS). Remove comma (CinS)
• Link "central nervous system" on first mention and de-link it later.

Clinical significance

• It is presumed by some scholars that in the case of flawed HNMT activity, the most affected organs are the brain, liver, and mucous membrane of the bronchus, consequently, flawed HNMT activity can lead to chronic forms of HIT Another comma splice; the comma after "bronchus" should be a semicolon.
• The exact mechanisms by which deficiency or impaired activity of HNMT causes HIT are not fully understood but are hypothesized to involve genetic factors: variations in genes encoding for HNMT have been presumed as potential contributors to increased susceptibility to allergic diseases and more severe courses of conditions like atopic dermatitis and allergic rhinitis: while deficiencies in DAO may be considered the primary cause of HIT, variations in both DAO and HNMT genes could play a role in its development; the interplay between these enzymes may influence effectively histamine is broken down and cleared from the body, but the reliable studies to confirm these hypothesis are lacking. Split this very, very long sentence, possibly in three.
• cause of aggravate should be "cause or aggravate"
• Studies predict that one such inhibitor can be metoprine, which crosses the blood-brain barrier and can potentially increase brain histamine levels by inhibiting HNMT, still, as of 2024, treatment of methamphetamine overdose by HNMT inhibitors is still an area of research. Semicolon, not comma before "still"
• It can bind to histamine receptors, still, NMH has a lower affinity and efficacy than histamine for these receptors maybe It can bind to histamine receptors, but NMH has a lower affinity and efficacy than histamine for these receptors
• Still, NMT, being a produce in a reaction catalyzed "product"

Sourcing and spot checks

• 4: PubMed search for mouse in the infobox, not a typical reference. Instead doing
  • 6: List of isoforms in UniProt. One mentions that it has no histamine-methylating activity. Your article says that only one has it. Which is correct?
• 16: Trends in Biomedical Sciences article. The 230 figure is in [15]. This article is about convergence of different types of MTases. Y
• 26: Find a new reference that meets RSMED for the definition of extracellular fluid.
• 28: The DAO protein is stored in plasma membrane-associated vesicular structures in epithelial cells of kidney and intestine and is secreted into the circulation upon stimulation ... The highest expression of DAO has been observed in the intestine, kidney and placenta Y
• 45, 47: Can you help me find the claim in these references? I don't see "blood serum" anywhere.
• 61: p534 Since the key metaboliteNτ-methylhistamine, like all other metabolites, is inactive at the different members of the histamine receptor family Y

Images

The visualization is published under CC-BY license, as is the methylation diagram. Encouragement: Consider alt text, probably "Refer to caption", for the latter.

Nominator replies

Gene name capitalization

User:Sammi Brie, there is a convention for the molecular biology articles (Wikipedia:WikiProject_Molecular_Biology/Style_guide_(gene_and_protein_articles)) that human genes should have all characters capitalized whereas other species genes should only have the first letter capitalized, referring to gene nomenclature that is followed by peer-reviewed articles. Maxim Masiutin (talk) 14:04, 24 March 2024 (UTC)

@Maxim Masiutin I kind of thought this was the case but was not immediately sure. The italicization was still inconsistent, though. Sammi Brie (she/her • t • c) 15:41, 24 March 2024 (UTC)

@Sammi Brie I was very careful to italicization. Italicized word means gene name whereas non-italicized means protein name, according to the same convention. Maxim Masiutin (talk) 16:53, 24 March 2024 (UTC)

Thank you for explaining. Sammi Brie (she/her • t • c) 17:05, 24 March 2024 (UTC)

I also tried to write sentences in a specific way to use terms for which wikipedia articles exist with that name, to avoid using pipe characters in wikilinks, as suggested by MOS:PIPE. Maxim Masiutin (talk) 22:41, 24 March 2024 (UTC)

Earlier review

User:Sammi Brie, on December 1st, 2023, I asked User:Esculenta to review the article again, just for your information. [1] Maxim Masiutin (talk) 17:56, 24 March 2024 (UTC)

Lead section

1. On gene name capitalization and italicization, that particular instance was correct, but you were right that there were some places of inconsistency, that I fixed today, overall, I hope that I addressed this issued in the #Gene name capitalization subsection of this talk page.
2. Replaced comma to semicolon on the sentence that had ", still, ". I also did this replacement in two other places in the article.

Maxim Masiutin (talk) 17:56, 24 March 2024 (UTC)

Protein section

1. On 33kDa, I slightly reworded the sentence so that removed abbreviation from the unit, added wikilink to it and made it explicit that it was a unit of mass, so that the new sentence is friendlier to a reader who is not a specialist in the domain.
2. Removed the comma before "and consists of".

Maxim Masiutin (talk) 17:56, 24 March 2024 (UTC)

Gene section

1. Consolidated into fewer longer paragraphs, by topic.
2. Checked the case/italic appropriateness.

Maxim Masiutin (talk) 17:56, 24 March 2024 (UTC)

Function section

User:Sammi Brie,

1. On sourcing: I removed the reference to Britannica and put different sources for the sentence "DAO is primarily responsible for metabolizing histamine in extracellular (outside cells) fluids, which include interstitial fluid (fluid surrounding cells) and blood plasma". If you still find these sources problematic, we can support particular parts of this sentence or remove it at all, as this sentence is about a different enzyme, other than what is covered in this article, so this sentence is not essential in this article.
2. Reintroduced full "diamine oxidase" on first mention.
3. Removed the comma in the sentence "DAO is predominantly expressed in the cells of the intestinal epithelium and placenta but not in the central nervous system (CNS)."
4. Linked "central nervous system" on first mention and de-linked it later in this section, however, I added one wikilink to CNS in one of subsequent sections to "remind" the reader on the abbreviation.

Maxim Masiutin (talk) 17:56, 24 March 2024 (UTC)

Clinical significance section

1. Replaced comma to semicolon after bronchus.
2. Split that long sentence and removed some text that was excessive, combined two paragraphs into one after the deletion.
3. Resolved the "cause of aggravate" issue by keeping only "aggravate".
4. Replaced comma to semicolon before "still"
5. In the sentence that starts with "It can bind to histamine receptors", I analyzed your suggestions and come up with a probably better variant: "NMH can bind to histamine receptors, but has a lower [...]".
6. Fixed a typo in the word "produce"

Maxim Masiutin (talk) 22:14, 24 March 2024 (UTC)

Sourcing and spot checks reply

1. As for the mouse in the gene infobox, I have no control over the data from the article. I only use {{Infobox_gene}} template, and it finds the gene from the wikidata and further collects information from databases. What I can do is to remove the infobox at all. Do you think I should remove the infobox?
2. You asked the following: "List of isoforms in UniProt. One mentions that it has no histamine-methylating activity. Your article says that only one has it. Which is correct?". When I went to https://www.uniprot.org/uniprotkb/P50135/entry and scrolled down to "Sequence & Isoforms", I saw three isoforms listed there: P50135-1 This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.; P50135-2 Note Has no histamine-methylating activity.; P50135-3 Nothing is mentioned about histamine-methylating activity. My understanding is that only the P50135-1 has histamine-methylating activity, while P50135-2 and P50135-3 have no histamine-methylating activity. UniProt is vague, but at least it does not contradict to the information presented in the article, because UniProt mentions that at least one isoform does not have histamine-methylating activity, while the article mentions that only one isoform has histamine-methylating activity citing a source that explicitly mentions that.
3. On definition of extracellular fluid: I added PMID 22686593 that mentions Extracellular fluid is distributed in two major sub-compartments: interstitial fluid and plasma and I also found specific articles that mention that DAO exists in specifically interstitial fluid and specifically in plasma, I added those references.
4. You also asked "45, 47: Can you help me find the claim in these references? I don't see "blood serum" anywhere." -- I added two references after "blood plasma" that should be more explicit.

Maxim Masiutin (talk) 22:14, 24 March 2024 (UTC)

@Maxim Masiutin There is no need to remove anything. The source you have added covers the Britannica replacement. Sammi Brie (she/her • t • c) 17:57, 25 March 2024 (UTC)

@Sammi Brie I didn't know that Britannica is not WP:MEDRS Maxim Masiutin (talk) 18:10, 25 March 2024 (UTC)

Images -- reply

TBD

No issues with images: no need to reply. Sammi Brie (she/her • t • c) 18:27, 24 March 2024 (UTC)

Thank you, I didn't know about the MOS:ALT feature, I added the attribute and viewed the page source and there was indeed <img alt="Histamine inactivation by HNMT" src=.

I hope I addressed all the issues that you raised. Should there be more issues, please let you know.

Thank you very much for your thorough observation, especially on grammar and style. Maxim Masiutin (talk) 22:16, 24 March 2024 (UTC)

@Sammi Brie - do you have any further observations or concerns? A couple of days ago I made all the changes that you suggested. Maxim Masiutin (talk) 17:43, 26 March 2024 (UTC)

The article has status "On hold: this article is awaiting improvements before it is passed or failed", however, I already implemented all the improvements that you have suggested. Maxim Masiutin (talk) 18:47, 26 March 2024 (UTC)

I'm reading through. I think I understand the isoforms and blood serum issues (isoform 3 has the same missing pieces as 2, blood serum is because of where HNMT is found vis-a-vis DAO). This is ready. Sammi Brie (she/her • t • c) 19:04, 26 March 2024 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Britannica as a source

@Sammi Brie - I have a follow-up question. You wrote that Britannica is not a good source. Can you please provide the reasoning for that? Thank you! Maxim Masiutin (talk) 16:10, 28 March 2024 (UTC)

Did you know nomination

This subsection is transcluded from Template:Did you know nominations/Histamine N-methyltransferase.

The following is an archived discussion concerning one or more templates or modules. Please do not modify it. Subsequent comments should be made on the appropriate discussion page (such as the template's talk page or in a deletion review).

The result of the discussion was delete.

The following is an archived discussion of the DYK nomination of the article below. Please do not modify this page. Subsequent comments should be made on the appropriate discussion page (such as this nomination's talk page, the article's talk page or Wikipedia talk:Did you know), unless there is consensus to re-open the discussion at this page. No further edits should be made to this page.

The result was: promoted by AirshipJungleman29 talk 21:13, 21 April 2024 (UTC)

(

• Comment or view
• Article history

)

• ... that histamine N-methyltransferase enzyme regulates essential brain functions and sleep-wake cycles in humans? Yoshikawa T, Yanai K (September 2016). "Histamine Clearance Through Polyspecific Transporters in the Brain". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 241: 173–187. doi:10.1007/164_2016_13. ISBN 978-3-319-58192-7. PMID 27679412.
  • ALT1: ... that histamine N-methyltransferase is the only enzyme in the human body responsible for metabolizing histamine within the central nervous system, playing a crucial role in brain function? Yoshikawa T, Yanai K (September 2016). "Histamine Clearance Through Polyspecific Transporters in the Brain". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 241: 173–187. doi:10.1007/164_2016_13. ISBN 978-3-319-58192-7. PMID 27679412.
  • ALT2: ... that histamine N-methyltransferase plays a crucial role in sleep-wake cycles as the only histamine-metabolizing enzyme in the human central nervous system? Yoshikawa T, Yanai K (September 2016). "Histamine Clearance Through Polyspecific Transporters in the Brain". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 241: 173–187. doi:10.1007/164_2016_13. ISBN 978-3-319-58192-7. PMID 27679412.
  • ALT3: ... that histamine N-methyltransferase is the only histamine-metabolizing enzyme in the brain, and its activity helps maintain arousal and sleep functions? Yoshikawa T, Yanai K (September 2016). "Histamine Clearance Through Polyspecific Transporters in the Brain". Handb Exp Pharmacol. Handbook of Experimental Pharmacology. 241: 173–187. doi:10.1007/164_2016_13. ISBN 978-3-319-58192-7. PMID 27679412.

• • Reviewed:
  • Comment: This is my very first DYK nomination. User:Sammi Brie: since you are the DYK expert, if you have suggestions, or you noticed that I did something wrong, please help.

Improved to Good Article status by Maxim Masiutin (talk).

Number of QPQs required: 0. Nominator has less than 5 past nominations.

Post-promotion hook changes will be logged on the talk page; consider watching the nomination until the hook appears on the Main Page.

Maxim Masiutin (talk) 21:15, 28 March 2024 (UTC).

• I struck ALT2 as it is too long (318 characters). ALT1 is 198, near the limit of 200. By the way, Maxim Masiutin, the source you should link to in a DYK nomination is the cited reference in the article for the hook fact. I can't review since I handled the GA nomination, but I wanted to flag those two things. Sammi Brie (she/her • t • c) 21:38, 28 March 2024 (UTC)

ALT1 could perhaps be streamlined a bit more to "... plays a crucial role in sleep-wake cycles as the only histamine-metabolizing enzyme in the human central nervous system?" JoelleJay (talk) 06:05, 7 April 2024 (UTC)

Regarding the new sources, I would definitely advise against citing Scientific Reports or Frontiers for this, especially the former as it is also a primary source. Per MEDRS we should reflect what secondary review sources say on a topic, and I think for statements made in wikivoice in a high-profile venue we need much more reputable sources than Sci Rep and Frontiers. They can still be used in the article, but ought to be accompanied by additional supporting sources. This Physiological Reviews article could serve as a replacement for the claim that it's the only neuronal enzyme degrading histamine, while this Sleep review touches on HNMT's role in aggression and indirectly on sleep. The Handbook cited in ALT4 also works for all of these claims (though a lot of the HNMT info is just the authors reviewing their own work; not necessarily a problem, but something to keep in mind). Note that the first two state it is acting in the extracellular space, which is in contrast to the mechanism put forth in the last. Regarding ALT4, this could easily be read as "HNMT is the only enzyme in the brain that maintains arousal and sleep functions, which it does by degrading histamine", which is incorrect, rather than "HNMT is the only histamine-metabolizing enzyme in the brain, AND its activity helps maintain arousal and sleep functions". JoelleJay (talk) 16:46, 7 April 2024 (UTC)

Please let me explain on why I don't agree with your statement that the cited study is a primary study for the claim it backs up. For that particular claim, it is a secondary source. This is not a primary source for the particular claim that "(HNMT) is the only histamine-metabolizing enzyme in the brain, and its activity helps maintain arousal and sleep functions". This source makes synthesis what already was known about HNMT in its introductory statements. It is not the source that figured out that "(HNMT) is the only histamine-metabolizing enzyme in the brain, and its activity helps maintain arousal and sleep functions". It may be a primary sources for the other claims which were the subject of the study of this publication, but not for the quoted claim. Let me give you another example. Consider a study on whether ketotifen increases appetite in mice that claims that ketotifen is an antihistamine. For the claim that ketotifen is an antihistamine medication, that study is is a secondary. For the claim that ketotifen increased appetite on mice, it is a primary sources. Frequently, research research articles such as invitro studies or animal model studies give some synthesis on earlier research for some introductory statements, making them secondary research for that statement. Maxim Masiutin (talk) 02:29, 14 April 2024 (UTC)

I changed the sources as you suggested. I removed sources that the plugin marks by yellow background and found a source that the plugin doesn't mark as yellow. It marked MDPI publications yellow, but didn't mark the Springer book yellow.

Maxim Masiutin: Please respond to the above. This is technically the oldest unreviewed nom, so I would otherwise review it, except I know virtually nothing about WP:MEDRS and refs 7, 8, 11, 18, 20, 32, 39, 40, 43, 51, 52, 53, 54, 55, 56, 57, 60, 61, 63 all come up yellow on WP:UPSD.--Launchballer 15:52, 13 April 2024 (UTC)

Launchballer: I have a plugin that shows them yellow too, I don't know why it shows this way. The sources are fully WP:MEDRS. These requirements are not that complicated, essentially, the source should not be primary, it should be at least secondary, i.e. the source that mentions source rather than the source mentions the information. Maxim Masiutin (talk) 21:24, 13 April 2024 (UTC)

All the MDPI links should be axed; it is not considered a reliable publisher. Frontiers journals should also not be cited, although they're somewhat less problematic. JoelleJay (talk) 22:23, 14 April 2024 (UTC)

I removed the MPDI links from this template, but if you mean that I should remove all MDPI links from the HNMT article for it to qualify for DYK, otherwise my DYK nomination will fail, I will regret about it, I didn't know that MPDI source prevents an article from be a DYK. I used MPDI articles that are in compliance with WP:MEDRS, they are also indexed in PubMed. I also use MPDI with care, for example, I didn't quote a health claim or something extraordinary from MDPI, only some undisputed pieces of general information, that MDPI quoted from other sources which are very reliable. For example, I used MDPI to support the statement that "HNMT does not have promoter cis-elements, such as TATA and CAAT boxes". The MDPI article has the following statement (quote): "Its gene is poorly characterized and lacks canonical promoter cis-elements such as TATA and CAAT boxes" that it cites from Reyes-Palomares, Armando; Montañez, Raúl; Sánchez-Jiménez, Francisca; Medina, Miguel Ángel (4 August 2011). "A combined model of hepatic polyamine and sulfur amino acid metabolism to analyze S-adenosyl methionine availability". Amino Acids. 42 (2–3): 597–610. doi:10.1007/s00726-011-1035-7. PMID 21814788.. If you noticed a particular MDPI reference that falls of this principle, please let me know. Still, I would be unable to remove all linkst to MDPI for the reasons I mentioned. Maxim Masiutin (talk) 22:40, 17 April 2024 (UTC)

If you wish, I can augment references to MDPI with references to the sources that they cite, but keeping only these sources as a replacement for MDPI should not be sufficient due to the rules of WP:MEDRS, formally.Maxim Masiutin (talk) 22:45, 17 April 2024 (UTC)

MDPI is listed as "questionably reliable" on RSP, and so doesn't meet the high quality requirements of MEDRS. It's unfortunate this was not brought up during the GA. Anything that is "general knowledge" should easily be citable to non-MDPI secondary sources. I'm more concerned with the MDPI journal Int J Mol Sci cited 16 times... JoelleJay (talk) 23:41, 19 April 2024 (UTC)

For future reference, how do I tell these at a glance?--Launchballer 05:56, 15 April 2024 (UTC)

The citation script will highlight them yellow, and also the journals often have single-word pluralized titles like "Catalysts" or "Biomolecules" so when I come across journals with that theme I check the publisher. JoelleJay (talk) 22:56, 15 April 2024 (UTC)

Launchballer: I nominated DYK based on the recent GA review, I didn't add any new source since the GA review, and the GA review should also follow WP:MEDRS - the completion that the article fullfilled and the condition verified by the GA reviewer. This is my understanding of the situation. Maxim Masiutin (talk) 21:26, 13 April 2024 (UTC)

Launchballer: I have nominated several articles in the past for GA, some passed, and I have done some GA reviews in the past. As for the DYK, this is my first ever DYK nomination. I don't yet fully understand the DYK process. Therefore, I will did some techincal errors in the DYK, please help me resolve them. Thank you in advance! Maxim Masiutin (talk) 21:35, 13 April 2024 (UTC)

You do only have to ping me once. I'll review this properly in the morning.--Launchballer 22:24, 13 April 2024 (UTC)

Thank you, I replied to the initial objection as you suggested, thank you again! Maxim Masiutin (talk) 02:29, 14 April 2024 (UTC)

Long enough, new enough. ALTs 0-3 cited, short enough, and interesting, however all four should lose "(HNMT)" per WP:DYK200, and I'd expect a more merciless prepbuilder to truncate ALT1 at "system". Article is devoid of maintenance templates and neutrality issues. Is there another way of writing "In mammals, histamine is metabolized by two major pathways"?--Launchballer 07:06, 14 April 2024 (UTC)

I rewritten the sentence that starts with "In mammals, histamine is metabolized by two major pathways" the following way: "In mammals, there are two main ways to inactivate histamine by metabolism: one is through a process called oxidative deamination, which involves the enzyme diamine oxidase (DAO) produced by the AOC1 gene, and the other is through a process called N^τ-methylation, which involves the enzyme N-methyltransferase. In the context of biochemistry, inactivation by metabolism refers to the process where a substance, such as a hormone, is converted into a form that is no longer active or effective (inactivation), via a process where the substance is chemically altered (metabolism)." Did I understand correctly your concern about this sentence and addressed your concern adequately? Maxim Masiutin (talk) 22:24, 17 April 2024 (UTC)

You also mentioned lengths. Can you please help me and modify the sentences to fit the length where it violated the length limitations? Maxim Masiutin (talk) 22:25, 17 April 2024 (UTC)

Please give me one day to address current issue raised. I wanted to resolve them yesterday, but didn't manage to do that, sorry for the delayed answer, just give me one day please. Maxim Masiutin (talk) 07:16, 16 April 2024 (UTC)

Sure, take your time. Make sure you remedy both mine and JoelleJay's concerns.--Launchballer 07:20, 16 April 2024 (UTC)

I hope I addressed all the issues mentioned except removal of links to journals published by the MDPI publisher. I gave reasons. If you still think that links to all MDPI journals should be removed, could you please request a second opinion from a editor with Wikipedia medical sources experience? However, the other editors of Wikipedia medical articles thought that I am competent enough in sourcing, and they appreciated it via barnstars, see my user page for those barnstars. Maxim Masiutin (talk) 22:52, 17 April 2024 (UTC)

Still, I am new to DYK and your help in any form will be appreciated by me, and it will definitely be helpful for potential readers; for example, if you could suggest a better ALT or let me know how can I further improve the article. Maxim Masiutin (talk) 22:56, 17 April 2024 (UTC)

If you will agree on my proposal to ask opinions on capable editors on sourcing, I can suggest several candidates. Just let me know how to proceed. Maxim Masiutin (talk) 22:56, 17 April 2024 (UTC)

Article length is fine and hook length is fine, they just can't have "(HNMT)" or any contents in brackets in them, and my copyright concerns are resolved. (If I was feeling particularly Bolshie, I might reword the hooks so that the article would be linked via "the only enzyme in the human body responsible for metabolizing histamine" or similar, therefore taking the title out of the hook, but that is absolutely not essential.) I could be wrong on this, so pinging JoelleJay to double check, but if my understanding is correct, then articles in predatory journals are self-published, and should not be used for almost all claims.--Launchballer 06:29, 18 April 2024 (UTC)

There are no articles in predatory journals cited in HNMT. If you could point a particular cite, please let me know ASAP. By predatory journals I mean journals listed at least one of the following: (1) Template:Predatory open access source list; (2) Wikipedia:Potentially unreliable sources. The script User:Headbomb/unreliable.js uses yellow background for the sources that this script considers "borderline", i.e. as defined by [2] is "situated at or near a border", but in a good set, i.e. is compliant to WP:MEDRS. Still, if there are a few source that raise your concern, I can address them one-by-one, but I don't think that finding alternative sources for all MDPI articles is appropriate just because the script considers them "borderline". The Wikipedia article MDPI mentions: MDPI was included on Jeffrey Beall's list of predatory open access publishing companies in 2014[25][26] but was removed in 2015 following a successful appeal[23][25] while applying pressure on Beall's employer.[27] Some journals published by MDPI have also been noted by the Chinese Academy of Sciences and Norwegian Scientific Index for lack of rigor and possible predatory practices.[28][29][30] This Wikipedia article has a detailed discussion on what MDPI is, but it is in no way currently predatory.Maxim Masiutin (talk) 20:35, 18 April 2024 (UTC)

• There's nothing intrinsically wrong about articles published in MDPI: each case needs to be judged on their merit. Other journals are more dangerous. MDPI journals may publish research which is less novel and ground-breaking, or in other words more suitable as source for introductory text on a topic. In the specific case, I see that Nutrients articles are cited in support of a rather mild statement that «It is presumed by some scholars [...] the most affected organs are [...]», so it's not a case of extraordinary sources being needed. If we look at the first authors, we see for example an associate professor at the University of Padua. There's no reason to outright discard such a source. The sentence in the DYK snippet should not be attributed to doi:10.1007/164_2016_13 («Brain histamine plays a role in diverse physiological functions such as anxiety, sleep-wake cycles, appetite, and learning and memory (Haas et al. 2008)»), but to the source they attribute this statement to, i.e. doi:10.1152/physrev.00043.2007 (also archived). Note that some of the sources for very similar statements, like doi:10.3390/ijms2003073, are actually referring to the brain of mice, so when replacing sources better check that the new source actually supports the statement, or we end up doing original synthesis which is a far worse problem that the hypothetical issues with one publisher. Nemo 17:24, 19 April 2024 (UTC)

Nutrients is among the MDPI titles that have been specifically called out as unreliable. See e.g. the mass editor resignations due to acceptance of poor articles, ongoing accusations of unethical practices leading to a boycott by 1100 professionals, lack of rigor in validating CoIs... The tide in the last few RSP discussions about MDPI has also been strongly on the side of avoiding their titles as much as possible. I still think these citations should be replaced, though I don't know if that's a requirement for DYK. JoelleJay (talk) 00:01, 20 April 2024 (UTC)

Hmm... now I see this isn't the first time you've advocated on behalf of MDPI against the strong general sentiment at RSP and WikiProject Medicine that the publisher has major problems and shouldn't be cited... JoelleJay (talk) 00:36, 20 April 2024 (UTC)

Thank you, JoelleJay, for the detailed explanation, your arguments definitely make sence. Even if I may disagree with you on some points, I think it would be better to remove all links to Nutrients from the HNMT article, because it is always better to spend time in replacing bad sources with good or act as a "Wikipedia exclusionist" than spend time arguing :-) -- if we are not time-bound, give me a few time to get rid of Nutrients, as other editors may later point attention to Nutrients again, so better prevent troubles Maxim Masiutin (talk) 02:21, 20 April 2024 (UTC)

Also, if we are not time bound, let me try to get rid of all "yellow" sources as shown by the script, but it may be a challenge Maxim Masiutin (talk) 02:23, 20 April 2024 (UTC)

I can help with the source replacements -- I added a couple alternatives today, some of which might be usable for the other MDPI citations. Thanks for understanding my concerns! JoelleJay (talk) 04:01, 20 April 2024 (UTC)

Thank you very much for your contributions at [3], I saw them, but haven't read your message back then, so I hope I already removed all the "yellow" sources as displayed by the script. Let me check the other articles to which I contributed, I will try to remove yellow sources there as well; let us also wait what the other editors think about the HNMT article if they eventually provide any feedback, that's where you help may be needed. Maxim Masiutin (talk) 08:03, 20 April 2024 (UTC)

In response to your feedback, I've revised the article. I've included superior sources to substantiate the claim that the brain, liver, and bronchial mucous membrane are the most impacted organs due to defective HNMT activity. I've also made more obvious that the references to the MDPI Nutrients journal were not used to back up particular conclusion on health, but to illustrate the views of certain scholars. These scholars, as cited in Nutrients, propose that adverse reactions to dietary histamine could be classified as a distinct medical condition, termed "histamine intolerance". While mainstream medicine does not recognize this as a separate condition, there is consensus among all scholars and practitioners that such reactions can result in symptoms like itching and flushing. The citation of Nutrients was intended to highlight this ongoing academic discussion. The term "histamine intolerance" is used in mainstream media, so I thought it is important to explain what is it. Maxim Masiutin (talk) 20:40, 19 April 2024 (UTC)

Here is an example of the use of the term "histamine intolerance" in mainstream media: [4]. Maxim Masiutin (talk) 20:42, 19 April 2024 (UTC)

I removed all links to MDPI; they have open access text which referred the same sources are more trustworthy but paywalled sources available via a library susbscription of by payment. If you cannot get access to some of these sources and like to access the context for the purpose of the DYK review, please let me know so I could send you relevant snippets via WikiPedia email. I also rewritten for clarity the section on histamine intolerance. I you think that there left some other parts to rewrite, let me know. Maxim Masiutin (talk) 07:52, 20 April 2024 (UTC)

I hope I done everything to address the issues raised so far. What do you think? Is there any action required from me so far? Maxim Masiutin (talk) 08:10, 21 April 2024 (UTC)

Looks good to me.--Launchballer 16:04, 21 April 2024 (UTC)

The above is preserved as an archive of the discussion. Please do not modify it. Subsequent comments should be made on the appropriate discussion page (such as the template or module's talk page or in a deletion review). No further edits should be made to this section.

Explanation of uncommon terms

Hello, User:AstonishingTunesAdmirer, User:AryKun, User:David Eppstein, I followed your suggestions at https://en.wikipedia.org/w/index.php?title=Wikipedia_talk:Good_article_nominations&oldid=1217067219#Hard-to-understand_terms_in_the_lead and replaced uncommon terms in the lead and in the body that you pointed out. Can you please provide your feedback on the following changes:

1. Removed the word "cytoplasmic" from the lead and added description to the "Protein" section on what is the cytoplasmic protein and what is a cytoplasm. The word "cytoplasmic" did not add value to the lead section. It was not essential. The lead without this word did not lose any value.
2. Replaced the term "biogenic amine" in the lead to "biomolecule", because it was not essential in the lead to qualify "histamine" as a "biogenic amine". Even without such qualification the lead did not lose its value. Instead, I made a description on what is a "biogenic amine" in a later section, and defined a biogenic amines as "substances, produced by a life form (like a bacteria or an animal) that has an amine group (−NH2)."
3. Explained the term "knockout mice" in the lead, the following way "genetically modified mice lacking the Hnmt gene".
4. Explained the term "histaminergic neurotransmission" in the lead and in the body.
5. Also explained a few terms in the sections.

See https://en.wikipedia.org/w/index.php?title=Histamine_N-methyltransferase&diff=1217089317&oldid=1215724083

Maxim Masiutin (talk) 18:59, 3 April 2024 (UTC)

In my opinion, it is easier to understand now for an average reader. Nice job! Also I believe you meant to ping @AirshipJungleman29. AstonishingTunesAdmirer 連絡 19:30, 3 April 2024 (UTC)

Replace first#/last# to vauthors

Hello, @Boghog! Can you please help with editing this article by replacing all instances first#/last# to vauthors? Thank you in advance! Maxim Masiutin (talk) 08:06, 20 April 2024 (UTC)