immunology & stem cell biology- tissue culture in startups and basic research
๐บ๐ธ๐ฎ๐ช๐ซ๐ฎ citizen- reading, running, climbing, paleontology, folk harp etc
has there ever been a problem in science where the solution hasn't been "it's far more nuanced, complex, & context dependent than we thought"
just once it would be nice for overwhelming complexity to suddenly simplify itself with additional understanding from a new discovery
I know renting is essentially setting money on fire but every time I hang out with a friend who recently bought a house it reminds me that home ownership is really the modern form of adam & eve eating from the tree of knowledge and falling from grace
it's a well-kept secret but the actual reason people get married & make fewer friends in their late 20s and early 30s because a decade of adulthood is the point where the overall narrative gets too convoluted to explain to new people
what are examples of eerie unexpected heritability in your life if you're privileged enough to have a good relationship with your family
mine was finding out my dad and I ate the exact same thing during undergrad all nighters without ever discussing it & they're v odd choices
also if you ever need a paper behind a paywall that's not on scihub- dm me- I have journal access, a family of NAS professors who raised me to hate elsevier, & a friend circle of researchers who all support open science- am more than happy to be captain hook the science pirate
did y'all know NASA was legitimately worried that the moon wasn't going to have a hard surface to land on and decided to just go for it due to the similarities between observed topography and the valles caldera
are c-sections unnatural or is it actually really cool that our species came up with a solution for our big heads using our big heads
(can already feel the maternal microbiome ppl coming for me w/pitchforks)
ever since I learned sharks are older than the north star, I've been trying to figure out exactly when in earth's history the north star appeared in our sky with no avail just to see if it coincided with anything cool in evolution
this is 300% not scientific, I just want to know
how wild is it that so much of our biochemistry fluctuates with the seasons which we only have due to a giant rock slamming into us billions of years ago to create the moon
I still can't believe we don't teach biology primarily as history- like my brain kind of broke when I realized HMGB1 is something we have from when we were archaea
one time I took 25mgs of zinc for a month just to prove to my GP that iron and zinc do in fact share the exact same absorption & storage pathways and it's kind of insane to see all the anti-iron rhetoric right now in the public without mention of this
expected 0 answers & unintentionally got a comment section full of uplifting ones that give hope
I feel like the discovery of AIRE too would also qualify
@MasterTimBlais
hi it's me
tl/dr: company was selling cells as induced pluripotent stem cells (reprogrammed somatic cell) when in reality they had a contamination and were selling embryonic stem cells
the ncardia cell contamination scandal-
so CDI (in the v red until fujifilm bought) sells a product called iCells cardiomyocytes that are iPSCs diffed into CMs and sold at a super high price and theoretically you can use them to make cardiac constructs (1/n)
I deleted most of my spicy tweets to make this account more professional and every day I regret it more and more
anyway, there are none/fund basic research
I've heard colloquially that there's something in development that can turn on that makes the likelihood of being L vs R handed 50/50 and I know nothing else
@jasoncbenn
@bryan_johnson
oh that candidate gene study failed to replicate
anecdotally I'm homozygous for the "short sleep" version of dec2/rs121912617 and usually fully need an 8 hours
oh crucial context being I'm a c282y hfe homozygote and my ferritin and TF% shot back up
anyway biochemists who name proteins after specific metals when they really aren't selective sort of nerf a lot of fields
@MasterTimBlais
I have so much more like 7/10 lung cancer cell lines have iron regulation mutations, K562s express embryonic zeta globin, people using bone marrow cancer lines KNOWN for donating mitochondria reparatively as cardiac fibroblasts, and using HeLa cells in a paper = astrology
the ncardia cell contamination scandal-
so CDI (in the v red until fujifilm bought) sells a product called iCells cardiomyocytes that are iPSCs diffed into CMs and sold at a super high price and theoretically you can use them to make cardiac constructs (1/n)
the cilia of your respiratory tract are pretty much identical to the cilia of your reproductive tract- evolutionarily where do you predict it first arose
@MasterTimBlais
none of this was related to contamination which also runs amok because EVERYONE SHOULD BE DOING CONFIRMATORY SEQUENCING ALWAYS
Merrick is great and you should all subscribe to his substack
I'm sorry but there is nothing as good as path twitter
bored on a first date? path twitter
preparing for parenthood? path twitter
bored waiting to finish staining? path twitter
shutting down the cytometer? path twitter
etc
@kapahi_pankaj
if they're an actually interested trainee they'll see this and know
there's so many great candidates out there I would move on but my mother's foreign postdocs have been using chatgpt to basically bandaid their difficulties with English as a 2nd/3rd language & that would be myโฆ
Easy to dunk on (and I did) but itโs a generic problem in modern science that people are using not just code, but reagents and methods whose proper use and more importantly limitations they donโt understand and often donโt have any straightforward way to understand.
fun fact: a human specific gene duplication of SRGAP2A allows antagonism of the original which promotes spine maturation & this allows human pyramidal neurons to have increased spine density, radial migration, & allows emergence of the our neocortex
tl/dr: these were CMs diffed from Rues2 ESCs not iPSCs
moral: sequence everything always, store your cells in the vapor phase w/internally threaded cryovials, label
(9/n last)
credit to
@a_manifolder
for giving this to me weeks ago which if you know me irl you know I annoyingly never stop talking about MOR in immunology & neurodevelopment
does anyone know what SPECIFIC species of worm thrives in the layer of fat & rotting material in bubbly creek in chicago/the remnants of the stockyards of upton sinclairs jungle
@StearnsLab
biotech is super bad right now!!! xbi is low, everyone is getting laid off, private capital investment is low, people are realizing the basic research gaps holding back any downstream technology development & wanting to work on them
/test drugs which I did and they're industry standard - however a lab in germany ran scRNAseq and found them all to be transcriptionally homogenous with fibroblast markers instead of any atrial vs ventricular markers (2/n)
Anyway, iCells are stupid expensive & you have to preplate because the initial die off is unacceptably variable & it's all around a scam- just diff your own CMs (Wu lab protocols). nCardia wanted to break up this monopoly and started selling a line of iPSC-CMs called Cor.4U (3/n)
around 2017? Anyway, not to start a DFW footnote but in the US there's v strict regulations on use of ESCs vs iPSCs and you have to fill out infinite paperwork for the former & you couldn't get federal $ during the Bush admin (thx obama but actually) & the latter is chill (4/n)
Scientists starting using Cor.4U in cardiac stem cell papers as iPSC-CMs until one day in 2021 someone decided to do confirmatory sequencing on the cells (I actually don't know who did this, if you do lmk)... (5/n)
When the confirmatory sequecing was done on the iPSC-CMs from nCardia (Cor.4U) - it turned out instead of iPSCs they were actually RUES2 ESCs that had been diffed into CMs and major contamination had happened at some point- instead of iPSCs, everyone was actually using ESCs (7/n)
@SamuelVernon14
I feel like I didn't truly appreciate that in middle school when we read it for english
gerda weissmann klein's all but my life left a much bigger impression on me/still influences my consistent practical footwear choices
@manorlaboratory
clone, transform dh5alpha magic cells from zymo, confirm sequence, inoculate a mega culture or just a buncho 4 mL cultures, maxiprep with thermo genejet- it's as good as macharey nagel for getting LPS & endotoxins out for downstream txns for making virus
so like 2 days and aโฆ
@evolscientist
@mbeisen
did you know they inherit their mitochondria from both their mother & father and it's used in their sex determination
wait you probably definitely know that
And it was a scandal and nCardia obviously stopped selling them and any paper that used Cor.4U CMs had to issue corrections/errata clarifying that they were actually RUES2 CMs (8/n)
eg:
Now we're back in NYC at beautiful Rockefeller University which is a close to Hogwarts as you will ever get on earth where a prodigous stem cell researcher produced a line of ESCs (not iPSCs) called RUES2s & made them widely available & they diff into CMs like a dream (6/n)
We speculate that these rapid, cell type-restricted changes are poised physiological adapations that are triggered by birth, e.g. gluoconeogenesis in the liver (cut off from mom), thermogenesis by fat (the real world is cold), etc. 14/n