PhyBits: Doppel, Chronic Wasting Disease & More!

[@phylumchannel]

Some of you have had the interesting hypothesis that the mutation in the hunters could be acting synergistically with CWD - this is an interesting hypothesis and I honestly didn't think of it when I was making this video. If you are brave enough - evidence addressing that question can be found here: wwwnc.cdc.gov/eid/article/30/6/23-1568_article This an open access paper so I will DEFINITELY do this as a journal club stream in the future - why not subscribe and turn notifications on to learn when I go live with this paper?

[@OhhCrapGuy]

Could there instead be separate cause we haven't noticed that's originally caused or encouraged the spread of CWD by causing a mutation in deer, that also caused a similar mutation in those hunters? You know the old adage, when you hear hoofbeats, think horses, not zebras? Sometimes I wonder how often we "see hoofprints" and instead of horses or zebras, we end up looking for rocks, ignoring all the zebras, horses, and other ungulates because we're convinced the depression in the dirt looks like a weird shaped rock. (Metaphorically)

[@phylumchannel]

​@@OhhCrapGuy It is an interesting thought! However, any model of /directed/ mutation by some environmental factor would be pretty big news - the equivalent of discovering CRISPR, but for mammals instead of bacteria. Not saying there isn't a universe in which you are correct, but as of right now, no model more complex than "mutation happens randomly and natural selection keeps that in check" is needed. There are viruses that can integrate at specific locations in the human genome, but none that I know of that can swap DNA base pairs in a targeted way. I do love the thought! It's been quite fun reading the comments.

[@noahcole6856]

@@phylumchannelwhat are the stream rules?

[@jansenart0]

OH, so it WASN'T "everything" you knew about Prions!

[@phylumchannel]

Never let 'em know your next move

[@costlycoffee4234]

Own the fraud! :P

[@MandrakeFernflower]

​​@@phylumchannel any chance for a video on naegleria fowleri and it's weird fetish for acetylcholine?

[@phylumchannel]

@@MandrakeFernflower never say never!

[@pebble312]

@@jansenart0 sad part is this is unironically how ridiculous some people are in comment sections lol some people actually complain about stuff like this as if its a “gotcha” moment, its nuts 🤣

[@rand5106]

Please more prion disease videos... they're a special interest of mine and it's so hard to find info that is 1. Digestible and 2. NEW. It's so rare I learn new information, but I've learned a lot of new info from your videos! And you communicate the info so well!

[@ikosaheadrom]

This protein turned out to be more interesting tban i thought it was

[@ouroboros8529]

prion diseases have been my greatest fear ever since learning about CWD at like 9 years old. truly life-changing experience I'm convinced that they will be the cause of the zombie apocalypse, that or the cordyceps that infected that one guy

[@torrvest]

@@ouroboros8529 nah I'd take care of it dw bro 👍

[@gaiawillis]

I don't think any cases of human cordyceps infections have happened.

[@ouroboros8529]

@@gaiawillis they have just this year actually!! it's a really interesting read, look up "human cordyceps infection india" and you should be able to find some articles on it

[@pwnedbyfishies]

earlist of byords acquires the wyrm

[@wyslink9354]

wormy enzymes and NAC

[@Foxtr0t1337]

The relation between doppel and prion is so messed up.🤨

[@billcipher4368]

I mean when you think about it ... the brain is the biggest sex organ most animals have...

[@liesdamnlies3372]

I’m not sure if I should be reassured or extra concerned when the CDC is like “we have zero idea if it’s possible but it’s be so scary if it is that you really shouldn’t even take the chance.”

[@GameDesignerJDG]

0:55 I actually happened to guess that. My guess wasn't even really a joke. I was like, 'he can't be talking about any cells that are even remotely related to neurons, otherwise he'd not be as fascinated or be asking us to guess. Sperm cells were as far removed as I could think of.

[@NerakanDrac]

the old guys who got CJD. they both had a mutation that in and of itself is probably not a functional issue, but perhaps made them/their proteins uniquely susceptible to cross species prion hijinks. how common is this point mutation in the general population? maybe only some of us are prone to this kind of cross infection

[@phylumchannel]

Met129 is one of the most common ways to get CJD, meaning hypothetically, they did not need to be eating CWD to have come down with CJD as M129 prion protein can aggregate. Whether or not a M129 human prion protein can be misfolded by a CWD deer prion is an interesting question!

[@MandrakeFernflower]

​@@phylumchannelperhaps the cwd prion can work as a seed for human prion fibrils to form around? Should be as easy as mixing the deer and human prion proteins and then some cyro em

[@phylumchannel]

@@MandrakeFernflower see the pinned comment!

[@mahwiiiife408]

I KNEW IT WAS GOING TO BE SPERM!!! The genetic code for something so cherished by evolution as myelin sheathes, a doppel would likely have a similar important function. And what could be as important as procreation and the continuation of species.

[@phylumchannel]

spoilers!

[@alexdrockhound9497]

@@mahwiiiife408 i too called it

[@user-nk8zx1yw8s]

SAMEE

[@jude6027]

These videos are so high quality I didn’t even notice you’re a smaller channel! I loved your prion and rabies videos

[@syndipirate2598]

I find prions endlessly fascinating! Actually, do we know of the development of prions throughout evolutionary history? If prions can kinda sorta reproduce, does that make them alive or dead? (Kinda like a virus) Now that I think about it, would a self replicating protein not be an ideal candidate for the origin of life? One where in some deep thermal vent a collection of amino acids accumulate into proteins, but one of those proteins refolds the others to be like itself. Those proteins then theoretically act according to natural selection, perhaps giving rise to dna or rna?

[@phylumchannel]

they don't quite "reproduce" they "convert" other prions to fold in a funky way. There's some research into PNAs - peptide nucleic acids, that might fit the description of what you're saying, as a precursor to the biomolecules we know and love today.

[@syndipirate2598]

@@phylumchannel Ah, understood! Thanks for the clarification! Would love to see your take on an “origin of life” video from the perspective of a biochemist! Keep up the good work! Hopefully soon you’ll be amongst the big shots of educational KZbin soon!

[@omegahaxors3306]

You're either protein or antitein

[@phylumchannel]

bro...

[@raffishrabbit]

i forgot that i had notifications turned off and didn't realize that my original cwd comment had replies. i should have been more clear in presenting my anxiousness about consuming deer meat as pure conjecture based on my own ignorance as a layman on the topic of prion disease.(i do not want to unintentionally spread misinformation online) one of the studies that really interested me was "Lack of Transmission of Chronic Wasting Disease Prions to Human Cerebral Organoids" where it states "even after direct exposure of human central nervous system tissues to CWD prions, a substantial resistance or barrier to the propagation of infection exists". i've read through the paper a few times, though it contains a lot of specialized language that i don't fully understand (im also currently running on no sleep), but it seems like their cjd positive control also didn't show any major changes with the exposure to cwd prions? my initial thought was that, in the case of the two hunters, the mutation could potentially create an "in" for prion mischief. if i am reading the paper right, which i am not fully confident of, it's possible the two hunters homozygous for m129 might not have been more likely to develop cjd due to their exposure to cwd prions? it's a neat line of exploration

[@phylumchannel]

very relevant paper that, because it is open access, i will cover in a journal club one day.

[@fmleverynameistakenx]

the two men with cjd might just have had the same healthcare provider who had this diagnosis on their mind. cjd as a cause of dementia in elderly probably is underdiagnosed, so someone keeping out an eye for this actually might actually find it once in a while. plus, maybe a somewhat conserved gene pool making the mutation more common in that region?

[@direwolf2562]

Thank you for the great video! I learned a lot. Keep making these please!!

[@binhminhnguyen7751]

1:15 when he asked that the first thing that came to mind were balls lol. No freaking way I got that right

[@LeThrowawayAccount]

My hypothesis for why different mutations in the prion gene cause different diseases is that the RNA created from the PrP gene undergoes alternative splicing, so maybe different cells produce slightly different proteins from the prion gene, and the exact mutation on the PrP gene determines which of these versions of the protein is pathogenic.

[@phylumchannel]

That's a great hypothesis! Didn't think of that one!

[@nile_prince7498]

just stumbled upon your channel and I love your videos! I have a suggestion for a fascinating topic: Plasmodium, Malaria and the evolution of sickle cell trait.

[@phylumchannel]

One day!

[@icecream6256]

Why arent this channel getting more recognition ?, honestly all your vids that i watch are entertaining and informative to layman like me. Hope more people can see your videos. Ghonorea was scarry though 😂

[@theunknown4834]

Just finished the prion video and saw this pop up. Yay scary diseases, sleep is overrated anyways.

[@TheFbalperfb]

I've just discovered your channel. I love the animation style and your voice over. I hope you achieve whatever goal you've set for yourself and keep making juicy molecular biology content for us

[@Panjy_]

started giggling behind my keyboard when i saw that Phy dropped a vid

[@SOOKIE42069]

I’ve found your videos so much clearer than other microbiology videos i’ve seen. maybe you can finally help me understand this: through what physical mechanism/action does dna lead to the production of proteins? and how does a protein being expressed physically cause particular traits or processes to occur in your body? i’ve seen a lot of videos take a long time to say what i just said to summarize my question, but never any clear description or visualize of the actual physical or chemical machinery that is required for those processes to occur

[@phylumchannel]

It'd take a bit too long to write out in a comment - but you can look up "Transcription & Translation". The TL;DR of it is, DNA is "read" to make messenger RNA from ribonucleotides, which are freely available in the nucleus. The mRNA is then sent out of the nucleus and is threaded through the ribosome, which helps align the mRNA with tRNAs that bring amino acids to the party. A video does way more good than a comment though. Your second question is much harder to answer because traits are a combination of a ton of different genes. To have a simple explanation - take a look at microbes. E.coli have a gene that makes the enzyme lactase (protein), which breaks down lactose. If a mutation broke that gene, that bacteria would no longer be able to grow in media that contains only lactose as a source of energy (trait). Hopefully that helps a little bit!

[@peytoia]

any chance you’d consider doing a video on how toxoplasmosis works? it’s probably my favorite pathogen ever. truly fascinated by its behavior

[@NickGarcia1519]

Super excited for a tau/amyloid beta followup

[@sipbipmip7381]

What if the CWD prion can't interact normal human prion proteins but can induce misfolding of the mutated prion proteins present in the hunters?

[@phylumchannel]

see pinned comment!

[@user-xj8wy4uu1q]

Perhaps the hunters already had the mutation but eating cwd contaminated meat triggered the prp protein to start aggreagating

[@phylumchannel]

see pinned comment!

[@nahometesfay1112]

I was straight up chanting sex before you revealed that it was infact related to sex. Immaturity wins everytime

[@suikarbus]

1:12 dunno, liver maybe? 4:20 maybe prion protein has several active sites but only select few are used in each part of the brain? Or there is just alternative splicing happening so some amino acid sequences are missing in one part but present in another 6:53 for selective upregulation I think it is possible to do nreve cell rna transcriptomics assay. For “nucleation” maybe do bunch of double deletion mutations? I am not sure how positive results would look like though 🤔

[@wrenross5315]

Have you found any papers about upregulating Doppel in the brain? If they're truly antagonists, could Doppel possibly have a protective effect or at least slow down the progression of prion disease? Or it could go the other way around and, because of their structural similarity, prions would be able to misfold Doppel as well. It feels too easy so it's probably not viable, but if it is then it would have been tried already because Doppel was discovered over 20 years ago... any thoughts? I did find a paper about Doppel overexpression in AML/myelodysplastic syndromes, but it seems to me like it's just collateral damage, it doesn't do anything in the bone marrow except signal that there is something structurally wrong with chromosome 20 to us.

[@arthurghahramanyan3279]

Was it comfirmed that the mutations in Hunters were spontaneous??

[@__sunspot23]

You should look into the work of Dr. Manuelidis at Yale. Her lab has some significant time invested into alternative hypothesis that considers protein miss folding as a side effect / immune response mechanism of an as yet unknown infectious agent involved in CJD

[@user-bz9qz7fg4u]

Great video!

[@superieur11407]

How did you time the upcoming ad?

[@phylumchannel]

skills (to pay the bills)

[@llawliet666]

Good video 👍

[@richardg7485]

Have you considered doing a video on LUCA or FUCA? Im not knowledgable on biology at all but it seems like there is some potential content there?

[@osmosisjones4912]

Microgroglia look more like micro neurons

[@strayorion2031]

If I had to propose a way the deer prion caused the disease in the two hunters, I would propose that both of them were already genetically predisposed to prion disease because of the mutation in their genes, and than the deer prion just triggered it by interacting with the mutated protein but that the deer prion isn't able to do the same with the normal protein

[@chickadeestevenson5440]

I mean there's a chance they're related maybe? (somebody's pa wandered maybe?)

[@phylumchannel]

see pinned comment!

[@user-gi5zy8jy3z]

I was actually thinking Doppels would be related to sex cells, since they have copies of a lot of DNA.

[@KingdomOfDimensions]

I find it unlikely that prions will cause a grey goo protein apocalypse. The prion protein is ancestral in mammals, so it's at least a few hundred million years old. Mutations leading to prion disease are nowhere near rare enough to only be occurring now, meaning they've probably had just as long to build up in the environment. Add in exponential growth and this apocalypse would have ended complex life the moment it started.

[@Valgween]

5 comments not including this one 76 views 15 minutes ago. also was this inspired by that person talking about it in the previous video

[@ThomasTheThermonuclearBomb]

11:26 omg i know that guy

[@whlewis9164]

Dang - I have been saying pry-on this whole time. 😢

[@Thesnakerox]

"I like CWD-positive meat" - ClownCore

[@user-pr6ed3ri2k]

Oh my god i guessed sperm and changed my answer to somethintg digestion related 🎉

[@osmosisjones4912]

When The body' wants to talk to the Brain The take The call is the thalmus. So maybe singles from sperm is factor

[@brovid-19]

Doppledo sounds like a my little pony character

[@passerby4507]

Obviously, it's a plot from big deer.

[@johannbauer2863]

damn, never been this early before :O

[@The_Variable1]

Yey

[@setoman1]

You are what you eat.

[@bmanpura]

"Deer prion disease" Deer lord I can't escape from shikanokonokonokokoshitantan someone help

[@skaldlouiscyphre2453]

YOU DEER 🦌

[@2bertlh1connu43]

Tell us more, now😡

[@LordWaterBottle]

I guess something liver function! Nope, Sperm of all things.

[@maxdoner4528]

Gunt

[@matthewzibinwong7731]

First

[@Thetaproductions19]

third comment owo

[@SynthRockViking]

Stop putting googly eyes on them, I assume they don't actually have eyes 🤨

[@rubentandy7654]

to assume is to make an ass out of u and me

[@wyslink9354]

sus you spending all this time instead of just telling people they need to be taking anti-SARS-COV-2 enzymes, acids, and cyclodextrins