--- Log opened Tue Dec 12 00:00:56 2023
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06:36 < docl> a fast nano rna synesizer at the core of every cell would let you test genemods safely. you could turn yeast cells into monkey embryos that grow to term in sugar water
06:43 < kanzure> yes except nobody knows how to build that
06:52 < fenn> this is why i was onto laser controlled enzymatic DNA synthesis in the first place
06:54 < fenn> also as stated it's not right because you'd need self replicating nanotech to go along with the self replicating cells
06:54 < fenn> but self replicating DNA is given
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07:04 < docl> I was a bit sloppy with my wording there (as technically the existing dna system *is* a fast rna synthesizer). technically this could work by adding mass produced synthetic cells (which could be small initially) rather than self replication.
07:05 < kanzure> you could insert symbiotes
07:05 < docl> but yeah a computer controlled rna synthesizer small enough to fit (along with a computer and optical I/O) in a standard nucleus is what I have in mind. there are other plausible ways though, an external organelle somewhat analogous to mitochondria perhaps?
07:06 < docl> that's a good thought. probably how nucleus and mitochondria originated in the first place
07:07 < kanzure> docl: as usual a few minutes in the library saves a few years in the lab https://diyhpl.us/~bryan/papers2/bio/Intracellular%20silicon%20chips%20in%20living%20cells%20-%202010.pdf
07:07 < docl> will read
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07:15 < kanzure> united therapeutics leading with the most knock ins and knock outs in an animal https://twitter.com/antonioregalado/status/1681313634327359489
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07:49 < docl> more recent work citing that one: https://scholar.google.com/scholar?as_ylo=2019&cites=13378460311474728172
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08:25 < docl> https://www.biorxiv.org/content/10.1101/2023.12.08.570879v1.supplementary-material // some cool looking renders of biological structures made with unreal engine
08:25 < docl> .tw 1734550998926909579
08:25 < docl> .tw https://twitter.com/alexjamesnoble/status/1734550998926909579
08:25 < kanzure> (.m)
08:26 < docl> .m https://twitter.com/alexjamesnoble/status/1734550998926909579
08:26 < AugustaAva> ​twitter: <alexjamesnoble> Muyuan has been working on this for some time, it's cool to see a manuscript: How to create full, atomic resolution scenes of biomolecules in Unreal Engine and fly around them in real-time. Really cool stuff with untapped potential. http://eman2.org/unreal_render <biorxiv.org/content/10.110… https://t.co/oRDsvwECgj>
08:26 < AugustaAva> ​https://video.twimg.com/ext_tw_video/1734550922636779521/pu/vid/avc1/1280x720/FXBLFK4w-zIn0qj4.mp4?tag=12
08:26 < docl> bot syntax keeps changing :/
08:34 < fenn> very cool
08:42 < fenn> "Two specific systems were showcased: the infection of a salmonella cell by bacteriophages and the inner workings of a eukaryotic cell involved in photosynthesis and carbon fixation. With more than a billion triangles to render"
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08:57 < docl> I wonder if you could replace the nucleolus (small structure inside the nucleus) with a symbiote/organelle, at least in the role of ribosome production. that might result in less wear and tear on chromatin.
09:07 < docl> there's a stress response mechanism where the nucleolus swells to increase ribosome production. might explain how stress accelerates aging. the nucleolus is tied mechanically to all the chromosomes most of the time (disappears during mitosis and reforms after). slow aging seems tied to having a smaller nucleolus
09:11 < docl> however, you probably can't just use bacterial ribosomes because they are less accurate than human ones. might be able to do some directed evolution work to get something comparable though?
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09:13 < docl> https://www.labroots.com/trending/cell-and-molecular-biology/25038/revealing-striking-differences-human-bacterial-ribosomes
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09:51 < docl> oh, there's heterogeniety in ribosomes. a dedicated symbiote might need to produce several variants to replace nucleosome function properly
09:51 < docl> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092941/ // The discovery of ribosome heterogeneity and its implications for gene regulation and organismal life
09:54 < docl> > Although Crick overshot ribosome heterogeneity with his original “one gene-one ribosome-one protein” model, the hypothesis of ribosome specialization has been resurrected. A more accurate though less pithy summary would be “one mRNA regulon-one ribosome-one protein network,” as each type of specialized ribosome appears to translate mRNAs, demarcated by particular cis regulatory elements, 
09:54 < docl> encoding proteins in a common pathway.
10:05 < hprmbridge> Eli> Certainly, I don't consider myself smart enough to be donating my sperm. With regard to intelligence, it seems like it is one measure of evolutionary fitness. A better match to the environment.  Why not use selective breeding to create humans that are a better match to modern day society? You can already choose your sperm donor based on phenotype, no?
10:06 < docl> hmm. I read somewhere that smart people in a population tend to produce way more in positive externalities (economic growth overall) than gains to income (present but more modest)
10:10 < docl> had an inkling ribosome heterogeniety might be the case (because there's room for it to be the case). biology is such spaghetti code. I retain some hope it's navigable though (maybe even rationally exploitable, e.g. ribosomes specialized to given protein networks being something you can manipulate optically).
10:11 < hprmbridge> Eli> Perhaps instead of "smart", I should use the phrase "less of an evolutionary mismatch to our environment". Evolutionary mismatch is the cause of a lot of the pain in society. For example, most Americans will die of obesity related causes (unless Semaglutide changes things). But having cognitive disability is also devastating to peoples ability to contribute to society and take care of themselves.
10:11 < hprmbridge> kanzure> people already do voluntary selective breeding; if they are not picking a trait you prefer, then I think you need to compensate them or otherwise make arrangements
10:13 < docl> my theory as to why smart people make externalities is they tend to grasp exponential outcomes better and take more interest in them. that can also help avoid things like promoting a pyramid scam (the downside of which is obvious if you think in exponents) or trying to direct savings to reinvestment instead of rent extraction schemes.
10:14 < hprmbridge> Eli> For sure. That's why the voluntary aspect of offering it for people who are already seeking sperm donors is important. People seeking donors are already more likely to have thought about the future of having the baby. Anyway, sometimes I often run thought experiments of what the best way to invest in humanity would be if I had a billion dollars. I don't really know why
10:15 < docl> one needs far-mode thought experiments as mental exercise IMO. just need to balance it out
10:17 < fenn> "if they are not picking a trait you prefer, then I think you need to compensate them" lol
10:17 < fenn> is there a name for this age-old practice
10:18 < fenn> smart people make externalities because capturing value is hard
10:19 < fenn> (and this is good)
10:19 < docl> fair
10:19 < fenn> if i sell copper for $1/lb, it's worth more than $1/lb to the buyer
10:20 < fenn> much harder to think about with intellectual goods
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10:21 < hprmbridge> Eli> Seems to agree: https://journals.sagepub.com/doi/10.1177/0956797612457784
10:21 < fenn> .t
10:21 < EmmyNoether> HTTPError: HTTP Error 403: Forbidden (title:75)
10:22 < fenn> "Youth identified before age 13 (N = 320) as having profound mathematical or verbal reasoning abilities (top 1 in 10,000) were tracked for nearly three decades. Their awards and creative accomplishments by age 38..." [conclusion vague and unclear]
10:22 < hprmbridge> kanzure> let's just give a bunch of people hypermemory and see what happens.
10:25 < hprmbridge> kanzure> retelling of a classic https://twitter.com/big_gelatin/status/1733734580828668196
10:30 < fenn> looking at the figures in "who rises to the top?", the genius kids mostly turn into math/cs/physics/engineering but there's a very clear wordcel/rotator split too
10:30 < hprmbridge> Eli> "In total, 11.3% of participants had earned tenure at accredited institutions; 7.5% had tenure at researchintensive institutions (Carnegie Foundation, 2010). This latter percentage is many, many times the base-rate expectation, given the 2% base rate for doctorates in the United States and the fact that only a tiny fraction of the individuals with doctorates have tenure at research intensive
10:30 < hprmbridge> Eli> institutions." – this seems high tho
10:31 < fenn> http://fennetic.net/irc/who_rises_to_the_top.png
10:34 < docl> kind of funny how bio is a wordcel discipline
10:34 < fenn> have you read a bio paper
10:35 < fenn> sonic hedgehog is all i have to say
10:35 < docl> uh, a few. might have linked some today
10:35 < docl> lol yeah
10:36 < fenn> https://en.wikipedia.org/wiki/Sonic_hedgehog_protein
10:37 < fenn> physicists pull this shit too but you can mostly ignore it
10:37 < fenn> there are only a few dozen particle names to memorize
10:46 < hprmbridge> nmz787> 3rd time in the past month my kindergartner is sick
10:46 < hprmbridge> nmz787> Ugh
10:48 < hprmbridge> kanzure> what you need is incremental kindergartner immune exposure therapy
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10:58 < docl> astronomers are also pretty prone to naming stuff creatively (was mainly greek mythology refs initially, but now it's all the mythologies)
10:59 < docl> not like the neat conlang chemists use
11:00 < fenn> astronomy is mostly obscure numbers and letters in star catalogs, or processes which share terminology with ordinary physics
11:00 < fenn> nobody is talking about tiny moons of jupiter
11:01 < docl> I'm thinking more about asteroids. they do at least have numeric refs too
11:01 < fenn> it's really math and data heavy
11:03 < fenn> really this diagram shows a pareto frontier
11:03 < fenn> we want to be in the upper right quadrant
11:05 < fenn> i wonder who the badass art critic outlier is
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11:13 < fenn> A potential inhibitor of the Hedgehog signaling pathway has been found and dubbed "Robotnikinin"
11:15 < docl> > The problem of the "inappropriateness" of the names of genes such as "Mothers against decapentaplegic", "Lunatic fringe", and "Sonic hedgehog" is largely avoided by using standardized abbreviations when speaking with patients and their families.
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11:24 < docl> I wonder if it's well established whether the nucleolus enlargement in progeria patients is directly responsible for the accelerated aging vs the downstream effect of producing more proteins?
11:29 < docl> https://www.frontiersin.org/articles/10.3389/fmolb.2023.1270285/full // Chromatin: the old and young of it
11:30 < docl> > Chromatin is typically organized with dense heterochromatin anchored to the nuclear periphery and euchromatin in the nuclear interior, however the structure at heterochromatin as well as the organization of euchromatin can change during aging.
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11:45 < zxrom> Hey!
11:47 < docl> hello
11:53 < fenn> zxrom: nope, go away
11:55 < zxrom> Why?
11:56 < fenn> i don't wanna deal with your BS
11:59 < fenn> go on, shoo
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12:02 < fenn> well perhaps i could have been more diplomatic
12:02 < hprmbridge> kanzure> i must have missed something
12:02 < docl> https://www.youtube.com/watch?v=YVmcHclAzrc // talk about ribosomal heterogeniety
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12:26 < docl> hmm. main distinction seems to be which ribosomes form under which forms of stress, not whether they act the same way. some specific differences like where the peptide tunnel exits the structure though. and it seems to be generally thought that ribosomes regulate protein formation (IOW somewhat selective as to which mRNA get turned to protein)
12:37 < docl> main reason I'm thinking about this (recapping a bit) is that it might be a low hanging fruit option to introduce a symbiote (or mitochondria like organelle, in the sense of having its own DNA) to each cell to fabricate ribosomes (so the nucleolus can be shrunk down, slowing aging). that's harder to make a case for if the symbiote has to pick one of hundreds of possible ribosomes to make based on 
12:37 < docl> current cell conditions. in the best case we would have just one nice ribosome design that has a nice low error rate and decent speed. then release that at a certain carefully regulated rate into the cell, at which point the nucleus can just focus on doing mRNA expression (and occaisional mitosis).
12:59 < docl> (that doesn't give you full control like a general purpose computer controlled mRNA synthesizer, but might slow down aging)
13:02 < fenn> how would a nucleolus cause aging?
13:06 < docl> it swells up in stress conditions, causing it to produce more ribosomes. and it's attached directly to each of the chromosomes. so my thinking is that makes chromosomes more easily damaged. if you look at the picture in the chromatin article it shows the strands getting stuck in the unpacked state. I think that process might tend to be accelerated by the nucleolus swelling up, and slowed if it's kept 
13:06 < docl> smaller.
13:07 < docl> there's some empirical evidence too, like small nucleolus being associated with slow aging
13:07 < fenn> "The nucleolus directly regulates p53 export and degradation" which induces cellular senscence apparently
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13:07 < docl> the alternative is that synthesizing more proteins contributes to aging directly
13:08 < kanzure> beep boop
13:08 < fenn> i'm not sure we can equate DNA damage with aging so easily
13:11 < docl> true. I'm thinking in terms of the complexity load, but it's obviously not as simple as that. long lived animals like elephants express more copies of p53
13:20 < fenn> .t https://www.nature.com/articles/ncomms16083
13:20 < EmmyNoether> Small nucleoli are a cellular hallmark of longevity | Nature Communications
13:20 < docl> bowhead whales apparently have a mutant version of p53 suspected to play a role in their (2x other cetaceans) lifespan. could be more that with the cancer less of an issue some other lifespan limiting factor(s) (short telomeres being one candidate, but not necessarily the only one) can be selected out more, i.e. could be more evolutionary pressure based than functionally related
13:22 < docl> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395165/ // The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity
13:40 < docl> I guess the null hypothesis is that increased protein turnover rates cause aging by a separate mechanism, and these also cause a big nucleolus since you need more ribosomes to express more proteins. but hmm. the nucleolus yanking the dna around in a relatively less protected state might be relevant? I wonder if it's feasible to introduce a symbiote into a yeast cell that releases ribosomes, then knock 
13:40 < docl> out the yeast cell's nucleolus activity
13:46 < docl> oh, now this is interesting: http://haolab.ucsd.edu/zhou_science_2023.pdf // Engineering longevity—design of a synthetic gene oscillator to slow cellular aging
13:48 < docl> apparently they found toggles for mitochondrial decline and nucleolar decline and switched back and forth between the two
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14:54 < Ashstar> fenn, the ageing process is just not DNA damge over time but also a break down of functional proteins like enzymes, heme
14:55 < Ashstar> there are DNA repair mechansims too
14:55 < Ashstar> functioonal protein enzymes
14:57 < Ashstar> our optic lens is a protein and it breaks down for many reasons, cataracs
14:57 < Ashstar> not all areas and organs age equally
14:58 < Ashstar> too
15:10 < docl> producing heme in a symbote is definitely doable. probably would need to do a lot of different proteins this way to get measurable life extension though
15:11 < docl> https://www.sciencedirect.com/science/article/pii/S1096717621000781 // Improved production of human hemoglobin in yeast by engineering hemoglobin degradation
15:12 < docl> in that case they are taking it all the way to hemoglobin
15:12 < docl> seems like you could probably have an intestinal microbe that pumps out heme
15:14 < fenn> you could just eat heme
15:14 < Ashstar> dracula
15:14 < docl> thing is, the genes that produce heme are presumably still there in the aging cells. it's mitochondrially produced, I think
15:15 < docl> https://impossiblefoods.com/heme
15:15 < Ashstar> I wonder, does Dracula sereotype his victims blood?
15:15 < Ashstar> Rh +/-
15:16 < Ashstar> taste different
15:17 < Ashstar> ?
15:18 < docl> genetically engineered yeast that produces soy leghemoglobin is an option. although you can also make regular human hemoglobin in yeast, so you might just use that
15:19 < docl> I wonder if a low heme diet is better though, since veganism apparently causes life extension? could be a biofeedback thing where eating more heme makes you stop producing as much sooner
15:20 < fenn> i'd be very skeptical of the veganism claim
15:20 < fenn> not saying it's true or false, but there are huge political pressures to make it come out one way or the other
15:25 < docl> eh, it's noisy enough I could see it either way. I weakly lean towards it being true though. might not have anything to do with heme consumption, could just be less caloric intake in typical cases
15:28 < Ashstar> well, there are some pluses to having a meatless diet. We need good high digestible source of Aminos
15:29 < Ashstar> the main issue with too much meat is the length of our gut
15:29 < Ashstar> coupled with the digestibility
15:30 < Ashstar> (amino acid dissasembly)
15:31 < Ashstar> red meat has connective tissue with makes it hard to adequately dissaamble before reaching our lower intestine
15:31 < Ashstar> it's otherwise got all the complete protein
15:32 < Ashstar> the second problem with undigested protein n food reaching our gut
15:33 < Ashstar> is the bi-products of microbial action
15:33 < Ashstar> n shit, like ammonia, alkylating compounds
15:33 < docl> well, this sounds engineerable at the gut microbe level
15:34 < Ashstar> which is why I eat a lot of lactic bacteria
15:35 < Ashstar> there is lot or high surface per protein
15:35 < Ashstar> in the fermented milk'
15:35 < Ashstar> L. bacteria'
15:36 < Ashstar> what goes through helps regulate our gut biome
15:38 < Ashstar> sorry to go on, I will say one last thing. People do not realise how important our gut is
15:38 < docl> optically rewritable genomes in yeast or bacteria would let you do a lot at that level. insulin, testosterone, free amino acids, heme, whatever. you could get an LED implant to make the changes.
15:38 < Ashstar> it has over 500 million neurons
15:39 < Ashstar> mybea
15:39 < Ashstar> our gut is a fermenter
15:39 < Ashstar> that has a permiable cross membrane
15:41 < Ashstar> that's why there is a continuous production of stuff that our liver needs to detoxify
15:41 < Ashstar> like ammonia, etc
15:41 < docl> you could set it up so that each time you deliver an update it creates a subpopulation with a unique code that can trigger the microbe to self destruct. then to kill off the previous population to make room for new one, deliver the previous code as light pulses.
15:43 < Ashstar> well, I got to change a pump valve, switchin wine
15:59 < docl> hmm, converting ammonia into amino acids is something gut bacteria could be optimized to do. you could take a lot of load off the liver and kidneys that way I'm guessing, and dramatically decrease protein consumption requirements
16:11 < docl> .wik Glutamine_synthetase
16:11 < EmmyNoether> "Glutamine synthetase (GS) (EC 6.3.1.2) is an enzyme that plays an essential role in the metabolism of nitrogen by catalyzing the condensation of glutamate and ammonia to form glutamine: /  Glutamate + ATP + NH3 → Glutamine + ADP + phosphate  /  Glutamine synthetase uses [...]" - https://en.wikipedia.org/wiki/Glutamine_synthetase
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19:28 < hprmbridge> kanzure> https://archive.is/TX4zV
19:35 < hprmbridge> nmz787> I always just think of Frank Grimes re elon's baby mama
19:35 < hprmbridge> nmz787> Grimy as he liked to be called
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--- Log closed Wed Dec 13 00:00:57 2023