Wikipedia:Featured article candidates/Tumor necrosis factor/archive1

Tumor necrosis factor

Tumor necrosis factor (edit | talk | history | links | watch | logs)

As of 4 November 2024, 22:44 (UTC), this page is active and open for discussion. An FAC coordinator will be responsible for closing the nomination.

• Featured article candidates/Tumor necrosis factor/archive1

Nominator(s): AdeptLearner123 (talk) 05:40, 8 October 2024 (UTC)

This article is about a chemical messenger that mediates the immune system and is a key factor in several autoinflammatory conditions. This article passed GAR a few days ago, so I am now nominating it for FA status.

AdeptLearner123 (talk) 05:40, 8 October 2024 (UTC)

• Hi AdeptLearner123, any chance of some response to the outstanding reviewer comments? Thanks. Gog the Mild (talk) 16:29, 29 October 2024 (UTC)

  Yup I will take a look today and address outstanding comments. AdeptLearner123 (talk) 17:06, 29 October 2024 (UTC)

• The paragraph beginning ‘In 1975, Elizabeth Carswell and…’ is unsupported. - SchroCat (talk) 06:34, 8 October 2024 (UTC)

  Fixed after rewrite of History section AdeptLearner123 (talk) 00:20, 13 October 2024 (UTC)

Image review

• Suggest adding alt text

• All images past the lead should be scaled up

• All images past the lead also need sources for the data presented. Nikkimaria (talk) 05:11, 9 October 2024 (UTC)

Done, lmk if the images should be scaled up more, and if the references are valid. AdeptLearner123 (talk) 19:26, 12 October 2024 (UTC)

Ajpolino

Hi AdeptLearner123, welcome to FAC. I'm glad to see you're interested in continuing to improve this article. I'll work my way through the article and try to summarize feedback below. Right now I think the article needs quite a bit of work to meet the FA criteria, which are a higher bar than the GA criteria. Unfortunately we don't get many molecular biology FACs; in fact I can't recall one in the several years I've had a lazy eye on FAC (though someone cleaned up PfEMP1 for WikiJournal of Medicine in 2017, so perhaps that's a decent model to consider). I'm still going through the article, and of course you're most welcome to ignore me, but my suggestion would be to withdraw the nomination and start a WP:Peer review to try to solicit more feedback on improving the article to the FA standard. At the same time, keeping an eye on – and participating in – the FAC process will help you move through the process yourself. Alright comments below, separated by FA criterion. All are suggestions, rather than demands.

First-round of commentary

1c. Well researched - Sourced to high-quality, reliable sources History - We try to build our articles from secondary sources (i.e. we are volunteer non-experts summarizing experts who are summarizing the literature). You may be used to writing academic science articles where the goal is slightly different (there your name/institution/reputation establishes you as the expert, and you wield your expertise to summarize a topic). So instead of summarizing key papers and citing those papers, find reviews on the history of TNF and summarize those. That way the established experts are guiding us as to which moments in history are important, rather than the reader trusting that a Wikipedia editor has curated the history appropriately. You might find Help:Wikipedia editing for medical experts a useful skim. History#Isolation - "When TNF was ... weight of 45,000 kDa" I'm not a biochemist, but I think the distinction in the paper is that in the first case they denatured what came off the HPLC column with SDS PAGE (and so you get the monomer). In the second they used non-denaturing conditions (and so you get the trimer). If I had to summarize reverse phase HPLC in a few words (which no one would trust me to do) I'd say "which separates molecules by their hydrophobicity". Your summary "which breaks proteins into constituent molecules" would be my short summary of tandem mass spectrometry. The publisher MDPI has a checkered reputation, and is often (though not always) a place authors will publish if they lack the results, prestige, or mainstream acceptance to publish elsewhere. Since our goal is to summarize the best sources available, we often avoid MDPI journals, or at least carefully consider why each adds irreplaceable and reliable information to the article. You cite three articles in International Journal of Molecule Science. Ditto Frontiers Media journals, though my personal opinion is that folks are less wary of Frontiers journals than MDPI journals. 1a. Well-written, "Prose is engaging..." Lead - I'm not sure if "mediates the immune system" will have much meaning to most readers. Could we clarify to something like "... messenger produced by immune cells that induces inflammation." Lead - "target receptors" not sure target contributes any meaning. Lead - Is there a difference between "immunocytokines" and "cytokines" (which this redirects to)? Lead - "without dependence on the synthesis of other proteins." I'm not sure this distinction needs to be in the lead. Lead - "include... [list]... among others" is redundant. Lead - "TNF plays a role... such as contributing to..." the grammar is a bit weird. "Roles... such as..."? Or if that's the only non-immune role you can just drop the "such as". Lead - "Excessive production of TNF is a key factor in inflammatory disorders..." you already told us this at the end of paragraph 1. Lead - "Due to the important and complex role of TNF in the immune system..." you can probably cut that. We know it from the rest of the section. Reads as editorializing. History#Isolation - "with the protein-rich segments identified by their absorption of 280nm light." this seems an unimportant detail. That's just how protein chromatography works. History#Isolation - I think the experimental detail in this section could be trimmed a bit without losing the thread of the TNF story (e.g. do we care that they used a 42 bp probe?) History#Physiological - "June 1981" it reads odd to mark every discovery with just a year, except for this one which gets a month. Do we care that this discovery was in June? History#Physiological - "The accumulating evidence...cancer treatment" reads as editorializing, and comes as a surprise since it seems poorly related to the rest of the section (which is a walk through history). In general, the history section is a choppy read. "In year X, this happened. In year Y, this happened. Etc." And the steps back in time for each subsection are a bit unnatural. It would be great if the section could run chronologically instead, as is typical for histories. That said, I appreciate that there are several semi-overlapping lines of research; so perhaps a chronological story isn't possible. Gene#Expression - "TNF is denoted as TNFSF2 in the tumor necrosis factor superfamily" what does this have to do with gene expression? Gene#Enhanceosome - "The composition... compatible binding site" This feels like unnecessary detail. Gene#Enhanceosome - "The CRE and ... and transcription machinery." I don't really follow the distinction you're drawing here between core and anchor complexes. Is this a common concept in gene regulation? Gene#Other - "The transcription factor NF-κB ...to the promoter" seems to have more detail than is necessary for the TNF story. Gene#Regulation - "Several studies... Other studies" is WP:WEASEL WORDS, or maybe just scientist speak. You could start every sentence in the article with "Some studies have shown..." Gene#Regulation - "have also been found to regulate" = "also regulate" The latter is shorter and clearer writing. Evolution - maybe this is personal preference, but I think Evolution could be elevated to a full-blown section. The material really relates to TNF as a whole, moreso than the rest of the Gene section. Protein - I think the beginning of this section could be written more clearly. E.g. you tell us it's a type 2 TM protein with no definition. Then a few sentences later you define the orientation. Might be clearer to just give us the orientation and save the jargon. It doesn't need to be readable to a full layperson, but it should still be readable and interesting to a university student studying biology. Protein#Transmembrane form - "N-terminal is... C-terminal is" unless this is a regional thing, the grammar isn't quite right here. You could say "N-terminus is..." or "N-terminal end..." Protein#Soluble form - The prose here is sufficiently boring that I thought "Gee, I bet a crystallographer wrote this" and sure enough the text is lifted in places from the cited paper. The sentences/fragments are similar enough to the copyrighted text that I think it's a problem: "similar to the "jelly-roll" structural motif of viral coat proteins" vs the source "similarity to the "jelly-roll" structural motif characteristic of viral coat proteins" "The upper β-sheet consists of three long β-strands supplemented with a loop of two additional β-strands, while the bottom β-sheet consists of five β-strands of steadily decreasing length. The middle β-strand of the bottom β-sheet contains the last 9 residues of the C-terminal, locking it into position." vs. the source "The upper sheet (sheet 1) is kinked with three long strands supplemented... by a loop of two additional strands. The lower sheet (sheet 2) comprises five strands of steadily decreasing length. The middle strand of this sheet consists of the last 9 C-terminal resides." "the inner surface" I was momentarily confused thinking this meant the core of a monomer, and was surprised. I see now instead "inner surface" means the monomer surface that touches the other two monomers in the trimer. Maybe you could word it more clearly. "Inner surface" sounds almost oxymoronic. Continuing, just have to step away from the computer for a bit! Stay tuned. Ajpolino (talk) 20:44, 9 October 2024 (UTC) I'm going to stop here for now, and stick to my recommendation above. If you're interested in further improving this article to the FA standard (which I recommend! It's rewarding!) and would like further feedback, please let me know and I'm happy to help. All the best, Ajpolino (talk) 19:47, 11 October 2024 (UTC)

Thanks for the comprehensive feedback! I have rewritten the history section using secondary sources, which omit experimental details. I noticed that the referenced article, Plasmodium_falciparum_erythrocyte_membrane_protein_1, cites primary sources and includes experimental details in its Discovery section. As such, I'm confused what is the proper scope of a protein history section. Any guidance around this would be appreciated! AdeptLearner123 (talk) 01:33, 13 October 2024 (UTC)

I've revised the Gene and Protein sections. Let me know how it looks now, and if anything else should be changed. I'm also wondering if the Function section contains too many details about cell signaling that should be moved to the TNFR1/TNFR2 pages. AdeptLearner123 (talk) 07:35, 13 October 2024 (UTC)

Great! Will take another look. Beginning presently. Will wrap it up asap.

1c. Well-researched

• Evolution - "before the Agnatha and Gnathostomata split" any chance the source gives some sense of when this was?
• Evolution - "This ancestor gene was dropped from the Agnatha ancestor but persisted in the Gnathostomata ancestor" - I'm not well-versed in evolution things, but at a glance it looks like the paper is suggesting there are TNF family members in Agnatha, and several (nine in Fig. 3) TNF superfamily members. Also "this ancestor gene" it looks like they're proposing a bunch in the vertebrate ancestor. The OG TNF gene would be somewhere way above this.

1a. Well-written

• Lead - "TNF also contributes to homeostasis in the central nervous system" is there anything more specific we can say here? This is kind of like saying "it does some stuff in the brain".
• Function - I feel this section gets so focused on the details of how TNF signals that we miss the bigger picture of what TNF does and why. Think about what the main messages you want someone to get out of a TNF Function section are, and make sure the material is organized in a way to make those clear. I'd suggest the main messages are something like (in order of importance) (1) immune cells make TNF in response to signals of infection/damage, (2) TNF is an inflammatory signal; it activates other immune cells, (3) it does this by a signaling pathway that leads to NF-kB et al., (4) if a pathogen blocks elements of the pathway, the immune cell kills itself to release inflammation-triggering molecules... I don't know anything about the reverse signaling, the CNS role, or the reason that non-immune cells express and signal through TNFR2 so you'll have to sort out how those fit into the overall story. At a minimum I'd suggest moving the "Immune response" subsection to the top of the section. I'd gently suggest reorganizing the section by function rather than TNF receptor, but I'm not super confident on that. Within the current text, some trimming and clarifying is probably in order, but I suggest you deal with the bigger changes first.

Nitpicks:

• Lead - "by the immune system that induces inflammation" is it fair to say "by immune cells to induce inflammation"? I think it slightly snappier and more precise.
• Lead - "assemble together" redundant
• Lead - "effectively treated" the adverb isn't carrying its weight ("can be treated" implies "effectively")
• History - "Studies on recombinant TNF confirmed the anticancer potential of TNF" a bit redundant, maybe "Studies... confirmed its anticancer potential"?
• Evolution - "believed to be descended" science-speak filler words. you could write "believed to be" before every fact in an article.
• Protein - "Remarkably" is best avoided as editorializing (see MOS:EDITORIAL).
• Protein - "Small molecules... present a potential mechanism for inhibiting TNF." seems speculative for the Protein section. Maybe this would be better in a Research section (or cut)?

Made it through Protein. Will make it through everything by the weekend's end. Ajpolino (talk) 21:42, 25 October 2024 (UTC)

Evolution - Doesn't look like the source gives a time for when the split occurred. TNF is one of many proteins in the TNF superfamily. The ancestor gene referred to is the TNF/lymphotoxin gene (TNFSF1/2). In Figure 3 of the source, the 1/2 gene is present in the vertebrata ancestor, and then deleted in the agnatha ancestor. AdeptLearner123 (talk) 03:34, 30 October 2024 (UTC)

Function - I'm thinking that the specific cell signaling pathways should be moved to the articles specific for those TNF receptors, whereas the TNF article can just summarize each receptor. What do you think? AdeptLearner123 (talk) 02:40, 1 November 2024 (UTC)

Draken Bowser

My pre-clinical knowledge is in a state of decline, so I had "the professor" take a look, which generated some of the following suggestions:

• binding to its receptors on other cells. - suggest spelling out "TNF receptors" and wikilinking.
• and TNF-blocking drugs are often employed to treat these diseases. - I think it's a little early in the lead to start talking about applications and suggest we leave this to the final paragraph.
• endotoxin shock - isn't it usually endotoxic? And suggest wikilinking.
• This led to the approval of the first anti-TNF therapy for rheumatoid arthritis in 1998. - I think we should name infliximab (and etanercept?) here.
• stimulated in macrophages by antigens. - suggest "antigen exposure" alt. "exposure to antigens".
• Consider inverting TNF is produced rapidly |in response to many stimuli <> by multiple cell types|.
• Suggest adding a sentence early in the "protein"-section clarifying that TNF is synthesized in the ER.
• reverse signaler - doesn't appear anywhere on the web outside this article.
• OVLT - suggest using the full term in lieu of the abbreviation.

That's it for the first pass. Regards. Draken Bowser (talk) 14:54, 20 October 2024 (UTC)

WikiOriginal-9

This article had 79 references before the recent edits. Now it only has 40. Is this even an improvement? The article is shorter now. AdeptLearner123 also cut down Crohn's disease from 257 references to only 45. ~WikiOriginal-9~ (talk) 03:17, 4 November 2024 (UTC)

Coordinator note

This has been open for well over three weeks and has yet to pick up a support. It also has unaddressed reviewer comments nearly two weeks old. Unless all reviewer comments are addressed within the next 48 hours and it attracts considerable movement towards a consensus to promote over the next three or four days I am afraid that it is liable to be archived. Gog the Mild (talk) 16:18, 2 November 2024 (UTC)

Four weeks in and no movement towards a consensus to promote, so I am timing this out. The usual two-week hiatus regarding further FAC nominations will apply. Gog the Mild (talk) 19:13, 4 November 2024 (UTC)

• Closing note: This candidate has been archived, 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. Gog the Mild (talk) 19:13, 4 November 2024 (UTC)