--- Log opened Thu Jul 25 00:00:03 2024
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01:24 < hprmbridge> Eli> Yes, some people are claiming this is downstream of all antidepressants. Biotech is working on compounds now to target it. If their hypothesis is correct it would potentially have fewer side effects than other antidepressants. The claim is that BDNF is released via the trkb/mtor binding.
01:29 < fenn> "all antidepressants" meaning the ones that actually work?
01:37 < hprmbridge> Eli> By all, I mean all types. SSRIs, psychedelics, etc … the claim is that trkb is downstream of all of them
01:49 < hprmbridge> Eli> I think there are a lot of questions to be answered but you can see the section on antidepressants in this paper https://www.cell.com/trends/biochemical-sciences/fulltext/S0968-0004(24)00037-9
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06:18 < kanzure> http://collapseos.org/
06:36 < L29Ah> http://collapseos.org/civ.html the guy seems to be living in some parallel reality; i admit though that his hobby is probably more useful than arguing about galaxy colonization at this point
06:44 < kanzure> yeah it's a bit schizo, but at the same time kinda useful that someone is thinking about how to wrangle chips in case we can't manufacture chips any more...
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08:38 < Lando-HoloNet> HACK THE PLANET
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13:44 < docl> a forth os? cool
13:44 < docl> wonder if eleitl is a contributor
13:47 < docl> looks like all one guy going by the sr.ht recent changes 
13:49 < docl> forth is a great autism concentrator, no surprise there's a schizo side to it
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15:22 < L29Ah> https://www.scientificamerican.com/article/nasa-cancels-its-viper-moon-rover/
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16:57 < fenn> it's not schizo, it's doomer
16:58 < fenn> "begin quantifying the odds on your list" where have i heard this sort of thinking before~
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17:57 < docl> .m https://x.com/GarrettPetersen/status/1816571499895292064
18:00 < docl> apparently people on ozempic are noticing improvements in IBS, chron's, etc. so he thinks something in the food might be working as a 'GLP-1 supercharger'
18:01 < docl> anyone manage to make a brewer's yeast culture with semaglutide byproduct yet?
18:02 < docl> ah, engineered yeast is the standard process
18:03 < docl> https://www.ema.europa.eu/en/documents/assessment-report/ozempic-epar-public-assessment-report_en.pdf
18:03 < docl> The manufacturing process for semaglutide active substance consists of a fermentation process in yeast cells, recovery and purification of semaglutide precursor. The semaglutide precursor is subjected to a synthetic modification process and purified. All steps have been described and explained.
18:05 < docl> https://www.science.org/content/blog-post/compounded-and-counterfeit-semaglutide
18:10 < docl> what could be good at the population level is a genegeneered (or evolved?) gut bacteria that emits small amounts of a GLP-1 agonist. the features for longer half life and so on aren't necessarily important if you have a factory in your gut
18:15 < fenn> wow it's 10x more expensive in the US
18:16 < docl> hmm, maybe instead of a dietary change directly affecting glp-1 in the body, it exerts selective pressure somehow on the microbiota and they produce it (or something complex like sending a signal out to make the body more responsive to it)
18:16 < docl> I mean, it's a way for the microbe to get more food right?
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19:23 < docl> Here's a crude way to offset the selection pressure: Embed a small device in the gut which releases antibiotics whenever you eat something overly calorie-rich. This can dissolve and be replaced every few weeks (with a different antibiotic each time, so resistant strains aren't favored).
19:26 < docl> The mechanism by which the microbiota stop you from overeating doesn't matter. They could produce a semaglutide-like GLP-1 agonist, reduce inflammation, lose the bad feature where they make you extra hungry, whatever.
19:29 < docl> https://journals.asm.org/doi/10.1128/mbio.02032-23 // Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases
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21:29 < hprmbridge> Eli> You can already buy a probiotic that does this
21:34 < hprmbridge> Eli> Here: https://pendulumlife.com/products/glp-1-probiotic?utm_source=google&utm_medium=paid&utm_campaign=acquisition_dsa_akk_1bcc44150a619c442152af3559d59a18&utm_term=&gbraid=0AAAAACnR2jjyXX4R_zwdiIftNjS7d_KVX&gclid=EAIaIQobChMIsvbGoPDDhwMVnM_CBB1diR7UEAAYASAAEgLuf_D_BwE
21:35 < docl> Interesting
21:54 < docl> Expensive. I wonder if I can get 1 bottle and amplify it somehow. Drop a pill in sterile sugar water and wait a bit?
21:59 < docl> This idea of doing selection in the gut is interesting. You could in principle select for bacteria that emit nootropics
22:01 < docl> Also the gut is big enough you could do an insulated marble sized device that sterilizes its contents by heat, so no antibiotics needed.
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22:32 < fenn> "an 84 kDa protein, named P9, that is secreted by Akkermansia muciniphila. Using L cells and mice fed on an HFD, we show that purified P9 alone is sufficient to induce GLP-1 secretion and brown adipose tissue thermogenesis. Using ligand-receptor capture analysis, we find that P9 interacts with intercellular adhesion molecule 2 (ICAM-2)"
22:32 < fenn> .t https://pubmed.ncbi.nlm.nih.gov/33820962/
22:32 < saxo> Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice - PubMed
22:34 < fenn> you probably want to do sterile culture instead of just dropping a pill in. streak a plate with diluted pill-juice, pick a colony, then put that into the sterile culture broth
22:39 < fenn> "the optimal ratio of chitosan: L-rhamnose: sialic acid: galactose as 1:1:2:1 with a concentration of 1.25%, thereby providing strong support for the efficient proliferation of Akkermansia"
22:40 < fenn> plus "brain heart infusion broth" which sounds yummy~
22:42 < fenn> Enriched medium: 1 g/L L-cysteine hydrochloride, 50 mL/L animal protein peptides, 0.2 g/L KH2PO4, 0.53 g/L Na2HPO4, 0.3 g/L NH4Cl, 4 g/L NaHCO3, 0.4g/L KH2PO4, 0.0005 g/L C12H6NNaO4.
22:45 < fenn> so basically soy sauce, doritos, and sugar
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22:45 < fenn> maybe you can figure out what the mystery food additive is by seeing what kills off this naturally occuring fecal bacterium
22:46 < fenn> the hypothetical food additive
23:42 < hprmbridge> Eli> From what I understand, even if you have correct QA, the issue is getting the probiotics into the gut. From my recollection, it's not the same as just swallowing magnesium or something.
23:47 < hprmbridge> Eli> Honestly, I would not do personally mess with the gut unless I had a serious issue that I wanted to correct for. That's a whole ecosystem in there. You can really screw things up when you introduce an invasive species. Because it's a complex system, you don't really know what the outcome will be.
23:47 < hprmbridge> Eli>
23:47 < hprmbridge> Eli> If you have IBS or metabolic syndrome, both of which will cause you to die early, then go for it. I'm going to wait for the RCTs before I would trust anything. Same with using antibiotics. Our a priori should absolutely be to never use them if possible. There's more bacterial cells in your gut than cells in your body. Taking antibiotics is like an asteroid hitting the earth and causing a mass
23:47 < hprmbridge> Eli> extinction event. You don't know how the system will respond. And we understand too little about everything.
--- Log closed Fri Jul 26 00:00:04 2024