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kanzure | .title http://www.sciencemag.org/content/350/6256/94.abstract | 02:32 |
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yoleaux | Somatic mutation in single human neurons tracks developmental and transcriptional history | 02:32 |
kanzure | "Neurons live for decades in a postmitotic state, their genomes susceptible to DNA damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs) in the human brain. We identified thousands of somatic SNVs by single-cell sequencing of 36 neurons from the cerebral cortex of three normal individuals. Unlike germline and cancer SNVs, which are often caused by errors in DNA replication, neuronal mutations appear to reflect ... | 02:33 |
kanzure | ... damage during active transcription. Somatic mutations create nested lineage trees, allowing them to be dated relative to developmental landmarks and revealing a polyclonal architecture of the human cerebral cortex. Thus, somatic mutations in the brain represent a durable and ongoing record of neuronal life history, from development through postmitotic function." | 02:33 |
Stskeeps | hang on | 02:34 |
Stskeeps | arr.. stupid lag | 02:34 |
archels | kanzure: but is it actual damage, or just some still unknown mechanism with a functional role? | 02:36 |
kanzure | not sure, there has already been various results about prions/methylation for memory engram tracing | 02:37 |
kanzure | http://diyhpl.us/~bryan/papers2/neuro/DNA%20methylation%20in%20memory%20formation%20-%20emerging%20insights%20-%202015.pdf | 02:37 |
kanzure | ah looks like someone finally cited that review | 02:39 |
kanzure | .title http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548453/ | 02:39 |
yoleaux | Dynamic DNA methylation in the brain: a new epigenetic mark for experience-dependent plasticity | 02:39 |
archels | yeah but this is not epigenetics, this is SNPs | 02:40 |
kanzure | maybe some changes are edited into the genome, dunno | 02:43 |
kanzure | .title https://www.youtube.com/watch?v=pfX6z9Z4sAk | 02:50 |
yoleaux | Disney's Mars & Beyond 5 of 6 - Life on Mars - YouTube | 02:50 |
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kanzure | cryoresuscitation is going to suck for a long time until things get really good at being cryonics-adapted | 06:12 |
kanzure | e.g. probably multi-week recovery period | 06:12 |
kanzure | and probably long-term damage ("oops that joint doesn't work any more" and such) | 06:13 |
poppingtonic | more like a 3mm^3 region in the anterior cingulate cortex suffered damage due to thawing cracks so the patient now has debilitating brain damage | 06:15 |
kanzure | that brain damage was already there | 06:16 |
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kanzure | besides, brain damage is the spice of life | 06:37 |
archels | that's purely based on correlational evidence | 06:40 |
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JayDugger | Good morning. | 07:14 |
kanzure | http://diyhpl.us/~bryan/papers2/longevity/young-blood.txt | 07:16 |
kanzure | some snarks stuff https://bitcointalk.org/index.php?topic=1201029.0 | 07:27 |
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kanzure | so if you are bothering to make a large-scale facility for selective breeding to get cryonics-adapted animals, there are other interesting traits that are near-term accessible on the genetic landscape | 12:37 |
kanzure | there are traits and functions that are biologically-plausible but not usually found by natural selection | 12:37 |
kanzure | trivial example is stuff like organ xenotransplantation compatibility, or even simpler self-transplantation compatibility (e.g. ability to heal from the critter's kidney being surgically removed and then patched back in) | 12:38 |
kanzure | "young blood" could be a fascinating target- i expect that young blood has some minor beneficial effect in general, but hard to measure, or it might depend on too many unrepeatable factors | 12:39 |
kanzure | but you could select for young blood that happens to heal older animals | 12:39 |
kanzure | i guess that's sort of an anti-aging thing, but it's much faster than just waiting 20 years to decide your mice are extremely long-lived | 12:40 |
kanzure | other nearby targets are things like digestability | 12:42 |
kanzure | delinquentme says, "just throw a femur into a bioreactor and figure out how to keep the hemotopoetic stem cells alive + producing" | 12:42 |
kanzure | "so treat it like one and figure out if we can use the femur as some kind of abstraction to keeping the haemotopoetic cells alive and producing" | 12:43 |
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kanzure | also- if the young blood selection trick happens to work, once you see improvements in aged animals becoming de-aged, you could then start selecting for cross-species young blood benefits | 12:49 |
kanzure | in a less practical but more explorative area i suppose you would want to select for talkative mice that chirp to each other, and then mice that chirp to each other while looking face-to-face, and then for mice that collaboratively solve mazes while chirping. but this is a poor substitute for having an actual selective criteria for cognitive ability. (sorta mimicing stuff from human history.) | 12:54 |
kanzure | you could select for memory resistance to hemispherectomy, eventually have brained animal that continues to function normally with 95% of brain matter removed, allowing you to more easily study the remaining tissue. | 13:01 |
kanzure | (although i would expect hemispherectomy resistance would require multiple competing mutations and directions instead of just one technique that the population stumbles into; otherwise the benefits of 50% hemispherectomy resistance might not translate to 80% hemispherectomy resistance) | 13:02 |
kanzure | "heterochronic parabiosis" | 13:05 |
kanzure | in fact; i think you can take blood from multiple members in a population, inject into older animal, then if there's any effect at all, you select all of the members of the population that you used. | 13:10 |
kanzure | i vaguely remember someone using a method like "take blood from multiple members of population, inject into single target" but i have no idea what for | 13:12 |
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drethelin | Anyone want to order a sample of FuGENE HD? | 13:26 |
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maaku | kanzure: you hear back re: alcor conference? | 13:43 |
kanzure | nope | 13:43 |
kanzure | max is prolly v. busy this week anyway | 13:43 |
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drethelin | seriously, is there anyone in here who does transfection? | 13:59 |
kanzure | yeah there's a few, they just don't sit around on irc all day waiting i guess | 13:59 |
kanzure | juul, ParahSailin, yashgaroth, a handful of others.. | 14:00 |
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delinquentme | drethelin: what kind? | 14:05 |
delinquentme | i got a car battery and a cuvette | 14:06 |
drethelin | the kind that uses reagents | 14:10 |
kanzure | updated http://diyhpl.us/~bryan/papers2/longevity/young-blood.txt | 14:11 |
delinquentme | wheres that homoerectus ParahSailin to shoot my thoughts apart when i need it | 14:24 |
delinquentme | questionmark | 14:24 |
delinquentme | AFM DNA assemblya | 14:24 |
delinquentme | colocate long chain dna strands and simply force the ends together with mechanical means | 14:25 |
delinquentme | why problematic | 14:25 |
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kanzure | hard to attach to single nucleotides, hard to attach/deattach at specific times, hard to keep dna molecule straight and extended | 14:26 |
kanzure | hard to position things precisely | 14:26 |
kanzure | tool tips are hard | 14:26 |
kanzure | (afm tool tips) | 14:26 |
kanzure | er, tooltips. whatever. | 14:26 |
kanzure | http://diyhpl.us/~bryan/papers2/nanotech/A%20minimal%20toolset%20for%20positional%20diamond%20mechanosynthesis.pdf | 14:26 |
delinquentme | we have single nucleotide attatchement solved | 14:26 |
delinquentme | we have synthesis | 14:27 |
delinquentme | Im saying make an AFM that takes long chain oligos | 14:27 |
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delinquentme | and smashes them together? | 14:27 |
delinquentme | lolol | 14:27 |
delinquentme | fuck im so bad with question marks | 14:27 |
kanzure | halcyon molecular, and some research groups i think, were working on scanning electron sequencing of dna. and at least one group was trying afm sequencing of dna. but not synthesis. | 14:29 |
delinquentme | yeah sequencing. | 14:29 |
kanzure | dunno, check if people have figured out afm tooltips yet | 14:29 |
kanzure | might be something new on google scholar for 2015. i hvaen't looked this year. | 14:30 |
maaku | delinquentme: see the tooltips in the above referenced paper | 14:30 |
maaku | and see if you can construct a chemistry for attaching them to nucletides | 14:30 |
maaku | (if so, we've got molecular nanotechnology, booyeah) | 14:31 |
kanzure | you could maybe get away with something like afm pick-and-place of small dna fragments, like a 4^n library where n is the length | 14:31 |
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kanzure | but then need array of 4^n dna molecules on a surface somewhere, meh | 14:31 |
delinquentme | we have prescident for picofluidic channels placed through AFM tips | 14:31 |
kanzure | yashgaroth: see today logs about young blood stuff, tell me what you think | 14:31 |
delinquentme | would be a good place to start | 14:31 |
kanzure | "placed"? | 14:32 |
kanzure | pick-and-place carbon nanotube channel..? or what | 14:32 |
delinquentme | i dont recall the mfg process . lemme see if I can find pics | 14:32 |
delinquentme | http://www.nanowerk.com/spotlight/id27760_1.jpg | 14:34 |
delinquentme | there we go | 14:34 |
kanzure | well dna has a width of like 1-4 nm at most | 14:36 |
kanzure | kinda forget | 14:36 |
delinquentme | 2nm | 14:37 |
yashgaroth | so, selectively breeding mice that have better-rejuvenating blood? you could select for healing effects pretty quickly, but the evolution on the donors will still be slow | 14:37 |
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kanzure | yea kinda slow, but increase size of population | 14:37 |
kanzure | i know it's not a direct tradeoff between population size and number of required generations but.. i think you get something. | 14:37 |
yashgaroth | unless you feed them mutagens and/or have a few leads on genes to tweak, in order to enhance the effect | 14:38 |
delinquentme | fabricated with a FIB | 14:38 |
kanzure | yes i would assume lots of mutagenesis, i didn't state as much, but it's important | 14:38 |
yashgaroth | can't be any harder than physically mashing dna strands together | 14:39 |
yashgaroth | oh also bad news I got another job, so this is my only week of freedom | 14:40 |
delinquentme | yashgaroth: thats what I was hoping to hear . And thats kinda what I was thinking | 14:41 |
kanzure | yashgaroth: describe new job | 14:41 |
yashgaroth | medical biosensor startup, 40% payrise, stock, free lunches | 14:42 |
maaku | yashgaroth: well done | 14:42 |
kanzure | small molecule biosensors? | 14:42 |
maaku | milk it for as long as it lasts :) | 14:42 |
maaku | (though expect the stock to be worthless) | 14:43 |
kanzure | maaku: usually 40% is congrats-worthy but let's be honest, yashgaroth was probably underpaid like every other biologist ever. | 14:43 |
maaku | true | 14:43 |
yashgaroth | heh | 14:43 |
yashgaroth | some small molecule, some protein, mostly circulating blood factors and such | 14:43 |
maaku | yashgaroth: non-invasive? | 14:44 |
yashgaroth | ya, some cheek swabs, some finger pokes, but not like implanted or anything...depends how you define invasive | 14:44 |
delinquentme | butthole probe is how i define invasive | 14:44 |
maaku | yashgaroth: I was thinking non-prick | 14:45 |
maaku | e.g. continuous raman spectroscopy of near-surface blood | 14:46 |
yashgaroth | nah it's the usual biosensors, antibodies stick to target in solution, react with something, you measure that thing | 14:46 |
delinquentme | so how does one affix or grab the ends of the DNA | 14:48 |
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delinquentme | i’d imagine overcoming vanderwalls isnt too difficult … and once you’re past that they’re adjoined .. no? | 14:49 |
nmz787_w | delinquentme: that guy kanzure was emailing you and I about mentioned the physical forcing of atoms together... obv problems are getting a forcer that is the right geometry | 14:49 |
delinquentme | nmz787: smashing the ends of long chain DNA together | 14:49 |
nmz787_w | ya | 14:49 |
delinquentme | yeah he wanted to do sequencing though | 14:49 |
yashgaroth | umm mutate an exonuclease and conjugate it to something you can interact with? then the ends are still kinda capped with the protein though | 14:49 |
nmz787_w | nah he mentioned synthesis many times in the slides | 14:49 |
delinquentme | you got the slides :D | 14:50 |
delinquentme | lel. | 14:50 |
nmz787_w | you were in that email chain | 14:50 |
nmz787_w | did you not notice before? | 14:50 |
delinquentme | I ignored most of what was said in there as soon as it started to seem more like scientific outerworld prognostication than “ hey we have a product “ | 14:50 |
nmz787_w | also his specific method seemed flawed, but the general idea seems legit enough | 14:51 |
nmz787_w | drethelin: I used to transform cells... but I always preferred reagentless like electroporation | 14:51 |
delinquentme | yashgaroth: exonuclease would be leaving a staggered end though right? | 14:52 |
delinquentme | To be determined: whether a staggered end or a straight ended DNA would take best to smashing | 14:52 |
yashgaroth | wait how are you getting the two strands to meet under the AFM tip in the first place? | 14:53 |
delinquentme | thats the big problem that first comes to mind | 14:54 |
delinquentme | dna combing was mentioned by a friend | 14:54 |
delinquentme | affxing the dna to a surface … but then how to get the dna attached to the functional tip of whatever is doing the forced press | 14:54 |
nmz787_w | nanotunnel, with two pistons on either end | 14:55 |
delinquentme | HMMMM! | 14:56 |
delinquentme | nmz787_w: +1 | 14:56 |
yashgaroth | hire a maxwell's demon | 14:56 |
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delinquentme | lel | 14:57 |
delinquentme | demonpore | 14:57 |
delinquentme | yashgaroth: Its funny bc thats the name of the basically defunct startup I was working at doing mechanical nanopores | 14:57 |
yashgaroth | a subsidiary of satansystems | 14:58 |
delinquentme | omg. i kinda wish i could have shared the naming discussions we had | 14:58 |
delinquentme | 2am + alcohol with 4 dudes living in a warehouse space in downtown sf stacked to the gills with electrical equiment? | 14:58 |
delinquentme | yeah thats was heaven | 14:58 |
nmz787_w_ | carbon nanotube with two oligos, one just shorter than the other... turn on electrphoresis at end of tube, electrophoresis force pulls shorter one into longer one ??? | 14:59 |
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yashgaroth | .wik Ku (protein) | 15:03 |
yoleaux | "Ku is a protein that binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Ku is evolutionarily conserved from bacteria to humans. The ancestral bacterial Ku is a homodimer (two copies of the same protein bound to each other)." — https://en.wikipedia.org/wiki/Ku_(protein) | 15:03 |
nmz787_w_ | pfft, no one synthesizes BOTH strands | 15:06 |
nmz787_w_ | that notahelix guy actually responded twice to my emails... I have yet to get back to him | 15:06 |
nmz787_w_ | his last email was something like 'do you know anyone with an EM'... so I need to tell him I've got one, and know some local peeps too with TEM (which is likely required for his ideas) | 15:07 |
delinquentme | Fuck I love the hivemind of ##hplusroadmap | 15:07 |
justanotheruser | Fuck I love the hivemind of ##hplusroadmap | 15:13 |
delinquentme | ^ | 15:18 |
justanotheruser | ^ | 15:21 |
kanzure | delinquentme: see old things here https://groups.google.com/group/enzymaticsynthesis | 15:21 |
nmz787_w_ | what is the schematic symbol for a chicken? | 15:24 |
delinquentme | 2 crossed drumsticks | 15:25 |
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nmz787_w_ | it just occurred to me that chickens wouldn't be able to participate in the phenomena known as 'planking'... | 15:31 |
nmz787_w_ | (I guess you could argue becoming chicken strips...) | 15:32 |
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kanzure | "I was inspired by a journal article published in Applied and Environmental Microbiology by a Stanford/Berkeley group describing the successful creation of a whole-cell uranium biosensor that fluoresces in the presence of micromolar concentrations of uranium (http://www.ncbi.nlm.nih.gov/pubmed/17905881). The coolest part was that the researchers managed to get the signal strong enough to be seen with the naked eye after 4 hours of ... | 17:35 |
kanzure | ... exposure and with only a standard UV flashlight (shown in the figure I attached)." | 17:36 |
kanzure | https://groups.google.com/d/msg/diybio/aOSvLwFi7FE/F3iXUyl4CQAJ | 17:37 |
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-!- mode/##hplusroadmap [-q erasmus!*@*] by kanzure | 17:44 | |
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kanzure | anatoly brouchkov has been injecting ancient bacteria into his bloodstream for some crazy reason, i thought it was just random tabloid nonsense (and it is i think) | 17:46 |
kanzure | apparently he runs the geocryology department at moscow state university | 17:46 |
kanzure | "Similar bacteria were discovered by Siberian scientist Vladimir Repin in the brain of an extinct woolly mammoth preserved by permafrost." | 17:49 |
kanzure | "'We did a lot of experiments on mice and fruit flies and we saw the sustainable impact of our bacteria on their longevity and fertility,' said Dr Brouchkov. 'But we do not know yet exactly how it works." | 17:49 |
maaku | wait we had a preserved wholly mammoth brain that someone thawed? grrrrrr | 17:49 |
kanzure | "The bacteria not only stimulates growth, but increases frost resistance. The seeds sprouted at a temperature 5C" | 17:51 |
kanzure | http://moscowstate.academia.edu/AnatoliBrouchkov/Papers | 17:52 |
maaku | permafrost brains are the only chance we have at recovering pre-historical memories | 17:52 |
kanzure | they probably thawed it because that's what humans do with meat- they heat it | 17:53 |
-!- mode/##hplusroadmap [+o kanzure] by ChanServ | 17:57 | |
-!- mode/##hplusroadmap [+ooo fenn maaku Burninate] by kanzure | 17:58 | |
@fenn | erasmus: you have never contributed anything useful to the channel and have harassed and threatened multiple channel members. i hope you make friends elsewhere and good luck with your neurofeedback project | 18:00 |
-!- mode/##hplusroadmap [+b *!*esb@unaffiliated/erasmus] by fenn | 18:01 | |
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abetusk | guess there was some drama in pm? | 18:03 |
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fentel | fenn TAKE YOUR MEDS | 18:11 |
fentel | YOU SHORT, UGLY, BALD LOSER | 18:11 |
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fentel | CHEW ON A LIGHTSABER YOU STUPID, UGLY LITTLE SHITBAG. | 18:17 |
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@kanzure | maaku: mammoth brain https://pbs.twimg.com/media/B1NYYy7CYAAmgvS.png | 18:22 |
@kanzure | http://content.science20.com/files/images/article-2124991-12775A2A000005DC-298_634x339.jpg | 18:23 |
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@kanzure | heh "brouchkov@hotmail.com" | 18:25 |
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@kanzure | https://en.wikipedia.org/wiki/Category:Research_institutes_in_Russia | 18:28 |
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@kanzure | oh i guess this would be the better version https://ru.wikipedia.org/wiki/%D0%9A%D0%B0%D1%82%D0%B5%D0%B3%D0%BE%D1%80%D0%B8%D1%8F:%D0%9D%D0%B0%D1%83%D1%87%D0%BD%D1%8B%D0%B5_%D0%B8%D0%BD%D1%81%D1%82%D0%B8%D1%82%D1%83%D1%82%D1%8B_%D0%A0%D0%BE%D1%81%D1%81%D0%B8%D0%B8 | 18:30 |
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@kanzure | huh, surprisingly hard to find recent research in russia | 18:37 |
@kanzure | https://scholar.google.com/scholar?as_ylo=2015&q=%22Moscow+State+University%22&hl=en&as_sdt=0,44 | 18:37 |
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-!- mode/##hplusroadmap [-o kanzure] by kanzure | 18:38 | |
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kanzure | "collapse now and avoid the rush" cathal and eleitl must be best friends by now | 19:21 |
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CaptHindsight | you kids sure get some weird ass threats from way past neurotic types | 20:01 |
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kanzure | CaptHindsight: the inkjet industry doesn't attract schizos?? | 20:38 |
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CaptHindsight | kanzure: inkjet is pretty crazy that's why I'm only on the fringes of it | 20:43 |
CaptHindsight | and they generally threaten with lawyers vs Star Wars references | 20:47 |
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--- Log closed Tue Oct 06 00:00:49 2015 |
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