the cake is offline on Nostr: npub1gmx4v…jatcq I would like to have loud words with evolution about the fact that ...
npub1gmx4vz0z4waf3ff40j7vdy7stdn4c0gne6lkd0pwtae46lzph4mqajatcq (npub1gmx…atcq) I would like to have loud words with evolution about the fact that Psoriasis, metabolic syndrome (and thus type II diabetes), psoriasis, rheumatoid arthritis, AND several flavours of autism are all caused (in whole or in part) by alterations to ONE FUCKING GENE.
Mutations in this gene co troll the ACMSD proteine, which is part of everything from tryptophan recycling to the kynurenine pathway (lipid metabolism, schizophrenia, etc) through to the glutamate pathway (thanks, exon 12!). The glutamate pathway, of course, being wrapped up in autism, various autoimmune disorders etc.
One change to this godforsaken gene and all of a sudden you're producing way too much NAD, which leads to too much MNA, which leads to an excess of 2PY and 4PY. One of those two (I cannot remember which) stimulates ER stress in the TD4+ cells resulting in excess production of IL17 and IL23. These in turn lead to an overproduction of (amongst other things) TNF-alpha.
TNF-alpha, of course being responsible for inflammation, both systemically and locally, and thus leads to psoriasis (local response) AND psoriatic arthritis (system response)! This same mechanism also makes you prone to fatty liver, GLP dysfunction and splenomegaly.
But of course if you've one mutation to the ASMCD proteine, you might just have another. (Hi, exon 12!) So you jave psoriasis and all these other inflammation-related diseases, but also your glutamate pathway is all fuckity-boo, which now gives you MORE auto-immune diseases. And probably autism/ADHD.
Autism/ADHD cause altered brain development in multiple regions, making you statistically far more likely than average to have no upper pain threshold. This means you can NEVER stop feeling your psoriasis. EVER.
So why do these mutations persist in our genome, and why are them more prevalent amongst Europeans? Because mutations to this gene alter the ASMCD proteine, which alters two major subcellular metabolic pathways that influence immune response. And it just so happens that several of the mutant immune responses that otherwise cause disease are strongly protective against the Black Death. Some mutations to this gene even provide enhances resistance to cancers (see: alteration of the TNF-alpha response) as well as HIV.
So because this one stupid gene made my ancestors better able to withstand the black death I have to deal with endless itching and pain with no upper pain threshold.
Fuck you, evolution. You're an asshole.
Mutations in this gene co troll the ACMSD proteine, which is part of everything from tryptophan recycling to the kynurenine pathway (lipid metabolism, schizophrenia, etc) through to the glutamate pathway (thanks, exon 12!). The glutamate pathway, of course, being wrapped up in autism, various autoimmune disorders etc.
One change to this godforsaken gene and all of a sudden you're producing way too much NAD, which leads to too much MNA, which leads to an excess of 2PY and 4PY. One of those two (I cannot remember which) stimulates ER stress in the TD4+ cells resulting in excess production of IL17 and IL23. These in turn lead to an overproduction of (amongst other things) TNF-alpha.
TNF-alpha, of course being responsible for inflammation, both systemically and locally, and thus leads to psoriasis (local response) AND psoriatic arthritis (system response)! This same mechanism also makes you prone to fatty liver, GLP dysfunction and splenomegaly.
But of course if you've one mutation to the ASMCD proteine, you might just have another. (Hi, exon 12!) So you jave psoriasis and all these other inflammation-related diseases, but also your glutamate pathway is all fuckity-boo, which now gives you MORE auto-immune diseases. And probably autism/ADHD.
Autism/ADHD cause altered brain development in multiple regions, making you statistically far more likely than average to have no upper pain threshold. This means you can NEVER stop feeling your psoriasis. EVER.
So why do these mutations persist in our genome, and why are them more prevalent amongst Europeans? Because mutations to this gene alter the ASMCD proteine, which alters two major subcellular metabolic pathways that influence immune response. And it just so happens that several of the mutant immune responses that otherwise cause disease are strongly protective against the Black Death. Some mutations to this gene even provide enhances resistance to cancers (see: alteration of the TNF-alpha response) as well as HIV.
So because this one stupid gene made my ancestors better able to withstand the black death I have to deal with endless itching and pain with no upper pain threshold.
Fuck you, evolution. You're an asshole.