#and also a bit envy
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dummycatgirl · 1 year ago
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personally Maddie and Simon are one of the best friendships (between a man and a woman) I’ve seen on screen
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tragicvampireromanceisland · 3 months ago
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anyone else remember this weird little show that toon disney used to air back in the nineties?? inside out focused on the lives of the emotions inside the mind of thirteen-year-old riley andersen, as they worked together to guide her through each day. while essentially just being a workplace comedy, the show quickly garnered praise from critics and fans alike for its unique premise, strong and relatable characters, and positive messaging on emotional regulation for its young audience.
at first, it looked like the show was going to become a staple saturday morning cartoon. season 2 even added four new emotions to the original cast of five! unfortunately, it seemed like disney had other plans. clocking in at 52 episodes, inside out only managed to reach around half of the golden standard of 100 episodes for rerun syndication before it abruptly got cancelled. the reason why has been the subject of speculation in hundreds of online forum threads over the past thirty or so years. but who knows! if we drum up some more conversation about it, maybe we can get a reboot!!
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whattheheckisatazelwurm · 2 months ago
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Gifed this because I never noticed this small moment before, until I saw art of it 🥺
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alicenpai · 8 months ago
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whoever asked for more rozen maiden dolls it's your lucky day i got you bro (gender neutral)
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dykedvonte · 1 month ago
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Do you have anything you've been thinking on but just haven't made a post about it yet? Also I'm really enjoying your fic!
I have a few things but it's likely mostly headcanons that I consider somewhat disconnected from my analysis.
Curly's parents had him old, only child, died shortly after he graduated and got the pony express position. It was the last big thing they saw him do which is a reason he stayed for so long.
Doesn't admit how much their death affected him
Jimmy has a largish family. One of the cases of too many kids to keep tract of, parent never really noticed any of them nor their behaviors
Anya lived in a lot of houses growing up, regular supportive family that just struggled to support themselves.
Became a nurse largely to avoid their financial struggles but mostly because she felt too many people weren't being cared for and advocated for in the world properly
Swansea likes high top sneakers most. Likes how snug they fit and how they shield his ankles at work
Curly has a bit of a caffeine problem since he can’t sleep. Can occasionally be found wandering the ship at “night” when he had some too late or just couldn’t sleep.
Daisuke knows a little about a lot of things. Starts conversations with “did you know” a lot but please don’t ask him deeper questions
Curly has known Jimmy longer but has worked with Anya and Swansea longer, met them during his middle years, met Jimmy shortly before college.
Swansea rents a house, Daisuke’s family lives in a big nice apartment, Curly has a condo, Anya live in a small one bedroom apartment and Jimmy has a studio.
Curly's home is very disconcerting. It's too normal to a like uncanny degree.
Anya is ambidextrous but prefers her left.
Anya and Curly are both not native English speakers so occasionally they forget words and bond over the mutual mocking they get from the rest of the crew. Daisuke knows some Japanese but is still learning, never picked it up as a kid
Only Swansea and Daisuke know how to drive, Earth in my mind is very post capitalist so only older people and like the extremely wealthy can afford cars.
It's also like walkable just due to how many businesses are in your face. Probably strict living vs shopping districts
I have more but the way that I headcanon about them is like too long.
#im still trying to figure out voiceclaims like I think Curly is the most generic lost his accent his accent like swedish or eastern european#guy cause he was raised by old immigrants and anya never had a thick accent but she talks with the cadence of one shes like slavic and east#asian to me. Swansea at most is like irish or italian but just an old white guy and Jimmy just has a bit of olivish skin like hes just whit#i think people should make them all weirder too like I think Anya loves showing the fucked up diagrams and pictures from premed and everyon#has to nod and act super supportive and not horrified cause Anya thats a guy with his leg broken in seven places it is not facinating to th#rest of the crew but she loves it cause fyi to go to med school you have to pass pre-med she has a BA if not a BS in nursing or bio atleast#Swansea randomly talks about shoe politics and its like hes talking about regular politics. Curly doesn't sleep walk but he pauses at weird#times or places and will just stand leave and not tell anyone anything cause even he forgot#Jimmy is himself ig and Daisuke always has some media drama they are too old for to get invested in and teach them about youth slang Anya#kinda gets it#also i think people make Curly and Jimmy way too old? Like In my mind Curly is sorta his late 20s- early 30s like he's in the settling#part of his life hence the fear about settling here anya is likel mid 20s to 30 cause she at least finished college we dont have the years#of how long shes been working and maybe Jimmy is just a bit older and feels weird envy about missing that introspection Curly is having.#Daisuke is like 19-22 in my mind like hes an adult but a kid by their standards#like Curly was recruited and its much easier to get younger people plus getting someone young is a good investment like they either got him#right after school and its like all he's known and it scares him#mouthwashing#mouthwashing game#anya mouthwashing#curly mouthwashing#jimmy mouthwashing#swansea mouthwashing#daisuke mouthwashing#ask#anon
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oogaboogaspookyman · 4 months ago
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Soooo a reply in the most recent Oil Is Thicker Than Blood release (by @dronebiscuitbat ) gave me an idea! And threw my impulse control out of my window!
BE WARNED: this contains a more than implied spicy Nuzi scene, which is canon in the universe of Oil Is Thicker Than Blood. I also tried my best to finish this so be also warned for potentially sucky writing lmao
Edit: I FOUND THE GUY THAT INSPIRED THIS SHIT IT'S @/makiyu23 THANK YOU DUDE THIS WAS SO MUCH FUN I WOULDN'T HAVE MADE THIS WITHOUT YOU
[EAVESDROPPING]
That red eyed freak... She's gonna pay.
Crawling in the vents. She always loved crawling around, whether it's the roof, the walls, or the ventilation systems, it always felt so good and satisfying.
This time didn't feel good the usual way now. It felt good like a revenge. Fitting.
While she's doing that, she found a few trinkets along the way! Neat! Things to look at instead of her glasses! She always disliked looking at her own glasses out of boredom, it brings memories she doesn't have consent for... Y'know what else she didn't consent to?
...
Let's not joke about that time, V...
...
Anyway! Back to searching through the vents! And sending those updates on the red thing stuff too!
"robo-god i fucking love crawling it's satisfying like-..." She stops for a moment... Then sighs... "Let's not ramble about these things alone V, you'll seem crazier than you already are..."
After long minutes of crawling around in the vents and sending updates on the search, she started to hear something...
Talking?
There's people talking...
There's people talking.
"Look, i'm just sayin', we can't have these Murder Drones in 'ere at all, ya know their body count? As someone who like- counts the deaths and missing drone cases, i say they're up to like- the THOUSANDS!"
"You know Khan's orders and announcement, they're living with us now, end of. We cannot keep having this conversation, Sean..."
"Susan please just- just understand what i'm trying to say here!"
"We can't keep up a relationship if all you're gonna ramble about is the Murder Drones wanting to make amends."
A Worker with an irish accent... Rambling to another, 50% masculine 50% feminine and 100% tired sounding, about the fact that she and N are living in the bunker with them and how he's against it. Of course. If she could drop down right then and there... She would. But she can't, she made a promise... Stupid promise but hey, she cares about that idiot.
...
Stupid feelings, stupid concept of caring, stupid core, now she feels all mushy and gross...
Ughh, get back to work you trauma bag!
Beep. Update sent. And as she crawls around the vents, a message for Lizzy. Heehee Lizzy she cute- SHUT UP BRAIN.
SD-V: yo liz i caught two people talking while i crawled in the vents, wanna hear?
A few seconds later...
Lizthequeen: OMG yes!!! drop the gossip gurl!!!
SD-V: so theres these two workers talkin shit about me and n for obvious reasons and apparantly these two workers are also a dumb lovey dovey couple
Lizthequeen: oh shiz you talking about sean and susan??? oh theyre having constant problems with their relationship i heard!!
SD-V: thats what im saying. theyre in constant problems with their relationship yeah
Lizthequeen: they are fr?? daaayyuummm gurl...... are they breaking up now???
V stopped to look back and crawl a little backwards to hear...
"... Susan- Susan please don't do this to me-"
"No no no no you know what? You know what? We're done here, all you ramble about is your racism, fuck you and fuck off"
"Susan please!"
Then a slam... Then a sigh...
"... WELL GOOD RIDDANCE I FUCKING GUESS!"
She began crawling forward again... God damn.
SD-V: yup
Lizthequeen: RN????? HOLY SHIT?????
SD-V: yup
Lizthequeen: they finally broke up........ thank you for sharing the info bestie i owe u so much
SD-V: yeah you owe me a good hanging out
What the FUCK. WHY DID YOU SEND THAT WHY DID YOU SAY THAT
V immediately stopped messaging in flustered frustration, yellow filling her visor and embarrassment filling her... Everything. Fuck's sake.
...
...
...
Lizthequeen: what do u mean by that ;3c
SD-V: nothing shut up buzz off im busy anyway BYE
Then to the right goes the program...
...
...
...
That was stupid.
...
...
Okay that's processed.
As she crawled by, she began to hear more chatter... Right, people exist.
"Guy imma need to talk to ya"
"Oh no. My name in b flat. I'm in trouble"
"More like i wanna discuss something with you regarding the whole Khan's daughter and N thing..."
"... Am i in trouble?"
"Stop saying you're in trouble, i just wanna talk"
PFFFFT
"“Stop saying you're in trouble” yeah shut up before you get in trouble hehehehehe-"
"What the HELL was that?!"
V squeaked in surprise, then yelled back, attempting to threaten the two into submission.
"YOU BETTER NOT TRY ME OR I WILL DROP DOWN AND RIP YOU TO SHREDS YOU TOASTERS!!"
...
...
"Okay, no need to yell lass, we would've listened anyway"
"Yeah what Han said"
V sighed in relief and kept crawling and sending updates. Situation avoided.
...
...
Crawling by crawling by, crawling by for the sake of your life~
This is getting really boring, i fucking hate this now i wanna go home~
She sang as she crawled in the vents, sending updates every few as she found new things and new gossip, making herself laugh a little as she crawled... She needed those laughs and those moments. She needed a break from the tension and the fear. The dread. That red eyed freak...
...
That red eyed freak.
...
"You want me to lead?" She heard, faintly, as she crawled about...
What in the god damn?? Uzi??
"Lay down then"
What????????
She crawled forward and stopped to hear the possible new gossip...
...
What the fuck are they doing down there.
"Relax, okay?"
"O-okay..."
Uzi?? N?? What are they...
...
Oh they can't be.
"I-i'm not t-that insteresting"
"You're gorgeous, actually"
"Shouldn't i be saying that to y-you?"
Nuh uh they're not i don't believe... N would be a bottom though.
A little more of hearing from inside the vents, it becomes clearer as every second passes. She can't move.
She jerks a leg forward, yet it's stiff. She can't move.
She tries the same with one arm, it's stiff too. She can't move.
She tries to at least launch herself forward, but her whole body is stiff. She can't move.
She sighs... I can't move... I can't stop hearing...
"Ngh... Uzi..."
JUST MOVE LET THEM BE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOVE MOV
She jerks an arm, trying to continue crawling.
Again.
And again.
And again.
And again.
And again.
And again.
FINALLY.
She manages to continue crawling by...
After ceaseless crawling, ending up finding nothing, and having heard quite the event... You think she'll have a word or two for them about it?
She's laid down across the ground, alone in her nest in the spire, seemingly dissociating after the events that transpired...
"Well... Damn." Her last words said in surprise.
...
...
...
...
...
We never got to go far in our relationship.
She swapped her hand up with the submachine gun and aimlessly let loose a barrage of bullets, drowning her thoughts in noise. Drowning her sorrows in noise.
Heavy breathing, panting.
...
"Let's not think of that, V..."
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thegreatyin · 3 months ago
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good job scoundrel! you've successfully ruined yourself!! again!!!
at this point, it's one of their best talents.
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em0puppy · 12 days ago
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sign petition here to let n say fuck
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gomzdrawfr · 23 days ago
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One day I need to figure out the one drink/food that can sustain me when im extremely exhausted
Ya panda is rawdogging life by sheer will because:
1. Coffee makes me sleepy (or give me a head splitting headache no in between)
2. Tea works although not too long
3. Music also work sometimes but not consistent
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aimasup · 8 months ago
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sure i COULD ramble about how ai is one of the multiple things that check all the marks of humanity's seven deadly sins but would that be extreme
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^^^ possibly insufficiently educated
#the pride the hubris of believing you can do better than innovation and nature by playing god and not in the fun way#the lust it's being used for in so many awful cases#the sloth the way its encouraging everyone to check original sources less before believing anything. Also to not take time to develop skill#the greed its being used for profit without consideration for ethics or fair labour#gluttony. we always have to be faster. shinier. better. no matter if it ends up being less convenient or wonky#the wrath it sows in between people creating more differences to be frustrated over. more hatred#the envy how it takes and takes. always trying to be as clever as the best humans. as beautiful as a real forest or sunset.#do you think the ai wants itself#if this were a scifi movie would we be the bad guys#but this is not a movie and the ai cannot love us. so we cannot love it. and there's that#my post#personal stuff#thinking aloud just silly yapping n jazz 没啥事做就这样咯~#( ̄▽ ̄)~*#when i was in primary school our textbooks for chinese had short stories and articles to learn about#there was a fictional scifi oneshot about a family in the future going to the zoo#the scifi zoo trip was going great until the zoo's systems went offline for a moment#and it was revealed that all the animals roaming in their enclosures were holograms#the real ones went extinct ages ago#when the computers came back online the holograms returned and there they were#honestly at first I thought it was a bit exaggerating#but I still think about it once in a while
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gophergal · 6 months ago
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ok so a doodle with a target audience of one before I go to bed
Just some team fort characters cast as characters in the Seven Deadly Sins vocaloid series by MOTHY. Here we have the Administrator in Judgement of Corruption (Greed), Demoman in The Muzzle Of Nemesis (Wrath), and Medic in Gift From the Princess Who Brings Sleep (Sloth)
ok night
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mars-ipan · 8 months ago
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they're so GROSSSSSS (<- desperately wants what they have)
alt color under the cut:
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re-colligere · 4 months ago
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Sorry didnt see you said unlikely pairs uhhhhhhh envy and fear
OHH it's all good don't worry! :D I can do any pair, I just thought it'd be fun if people got creative with the pairings hehe
IN the meantime...I've thought about Envy and Fear before, because a bunch of my fanfic ideas take some time to focus on their friendship. With that said, I'm still a little unsure how to write Envy even if she's a fascinating character on her own. Alsoooo it's a little bit hard to tell how they'd interact because canon doesn't give us a lot to work with, but it's really fun to think about KDJFHSJKDFH
I do think Envy looks up to Fear (pun intended), in the way that he's smart and quick-thinking. In turn, I think Fear would really appreciate her words. He'd also be the type to carry Envy around and goof off with her (or at least look after her if she's getting rowdy--she's so small, after all). I think Envy would be a good motivator for Fear to try new things their friends are doing, maybe inspire him to get out of his comfort zone! And Fear's there to be careful and temper that desire if things get a little scary or dangerous, and if Envy's going too far.
If they wind up on the same page, though, I feel like they could make a special brand of insecurity. Envy's constant comparisons with others could really enhance Fear's hold on Riley's self-esteem, and maybe even on his own self-esteem. Because as much as Envy loves pointing out the things she likes about others, she's also just as prone to point out the things she likes that aren't there...would it be such a stretch to say that even she doesn't have great self-esteem herself? She's either a yes-man (trying to impress someone/hopefully get respected) or she can convince someone that her motivations are correct and beneficial (and she usually believes she's doing something good). Fear's a solid voice of reason but again, highlighting his (or Riley's) flaws could really get his gears going a mile a minute. This COULD be a good drive for self-improvement, if they don't make Riley so nervous and feel inadequate she couldn't do anything. Whoopsies.
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Has it been long enough that I can safely say I relate to Eddie Munson without it being social suicide
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cellarspider · 9 months ago
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13/30 Science interlude!
(Previous) | (Index) | (Next)
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We return to Prometheus, where I am taking a break to ramble about my job. A thing that I love. It will be a nice change. Also: weird blood!
I have been informed that some methods of accessing tumblr do not play well with long alt text rambles. To keep the flow between the main text and alt text separate, I’ll be copying the longest ones below the main text and citations. Captions that I think are going to be long enough to need this treatment will be marked with “Overflow Ramble [number]”, so they’ll be slightly easier to find. It’s not a perfect system, but Tumblr is not a perfect website.
And I am going to need the overflow space this time, because we’re getting into genetics!
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After electrocuting a decapitated alien head until it exploded into a shower of green gore, the creatures that claim to be scientists stuck a bit of the goop in some sort of very science-y DNA machine, leading to this:
“Let's have a look at its DNA. Isolate the strand. Okay. Compare it to the gene sample?”
“[Overlay… Processing… Processing… DNA MATCH.]”
“Oh, my God. It's us.”
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I want this preserved for posterity, because this made me absolutely hoot. They avoided fake science technobabble by going so far in the other direction that it becomes equally meaningless.
What the scene is trying to say is “this alien shares the vast majority of its genetic material with humans, indicating that they are in fact related.” 
I will get to how one would actually determine that, but first: The head turned into green goop. Green goop. Humans are notably not prone to turning into green goop. Otherwise Nickelodeon would’ve probably been shut down within a week.
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(Image credit: Rich Fury/KCA2021/Getty Images for Nickelodeon)
This annoyed me so much that years later, I dug up a possible explanation that backfills this with cool biology.
Humans, and almost all vertebrates have hemoglobin-filled blood. And on a tangent that I must follow: The only vertebrate that doesn’t is the icefish Channichthyidae family, commonly known as the white-blooded fish. 
You’ll never guess what’s special about them. 
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Yes, somehow these fish manage to live without hemoglobin, their blood only having 10% of the oxygen carrying capacity of their red-blooded cousins. Hell, most of them also lack myoglobin, which stores oxygen in muscle. The loss of myoglobin isn’t just a one-off event either, genetic studies have shown that these icefish have seen four distinct branches of their family tree lose myoglobin independently of each other. They have a wild series of adaptations to permit this, but basically they were already in such cold oxygen-rich water and moving so slow that they didn’t need all that extra oxygen-having stuff. They lost it, kept going, got bigger hearts, weirder muscles, and just. Kept. Going. They’ve actually expanded their range in the past 30 million years or so!
I love them! Evolution is wild. You know what’s also wild? There’s green-blooded vertebrates. Yes. You read that right. Yes, they still have hemoglobin. What they also have are staggering levels of biliverdin, which human bodies only produce when breaking down hemoglobin–when a bruise takes on a greenish hue, it’s because the dismantling of the blood under your skin has created biliverdin. While it’s generally been thought of as just a breakdown product, some research suggests that it also has protective effects against a number of diseases. In moderation, though. If you have enough of it to actually turn a bit green, you’ve got jaundice, which is not a thing you want to have. 
But for a number of fish species, bush frogs, and skinks, they have way more biliverdin. 
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(Austin, C. C., & Jessing, K. W. (1994). Green-blood pigmentation in lizards. Comparative Biochemistry and Physiology Part A: Physiology, 109(3), 619-626.)
Humans usually don’t have much circulating biliverdin at all, so the table above compares someone with untreated jaundice to a number of other species–fish with two to fourteen times that amount, and the green-blooded skinks have twenty-two times as much! These creatures have green blood and turquoise-colored bones, and we still don’t know why. Maybe it’s protection against diseases, maybe it’s protection against parasites like malaria, maybe it’s to make them really blend in with foliage. Could be all of those at once, could be none of them, we don’t know! What we do know is that, as with the icefish, the green-blooded skinks in particular have independently evolved this feature four different times. (Rodriguez, Z. B., Perkins, S. L., & Austin, C. C. (2018). Multiple origins of green blood in New Guinea lizards. Science Advances, 4(5), eaao5017.)
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(https://australian.museum/blog-archive/amri-news/amri-three-tiny-green-blooded-frogs-sing-like-birds/) 
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(https://web.archive.org/web/20180619143048/https://blog.nationalgeographic.org/2013/09/30/why-do-mysterious-lizards-have-green-blood/) 
We have no mammals identified with biliverdin-filled green blood, you would need a lot of tweaks to how our bodies function to make this work. But it’s not literally impossible, like I thought in the theater! I’m quite sure the prop department didn’t do this level of research on the subject, but think about it! 
I love biology! It’s! So! Weird!
And because I love biology, you’re not getting rid of me yet. My chosen field is genetics. This movie has presented me with a laughable sci-fi depiction of what we do. 
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So! What do we actually do, when we want to find out how related we are to another species?
I’m going to get into excruciating detail, so here’s the top-line summary: We extract the DNA, mash it up into readable little chunks, use some wicked cool machines to do the actual reading, and then we compare the target DNA with our DNA, and do some cooler stuff the movie isn’t aware of. A competent analysis would not only be able to tell you how much overlap two genomes have, but also be able to estimate how long the two species have been genetically distinct. 
Is this way more than the movie needed for this plot point? Yes. But they didn’t actually have to do this at all, they could’ve just said the truth that science fiction usually ignores for budgetary reasons: “there’s no way these beings independently evolved to look so much like us, we have to be related.” 
(Although even Star Trek, despite being the classic example of “putting a rubber thing on an actor’s forehead to make them an alien”, actually does acknowledge this. Precisely once. TNG s6e20, “The Chase”. It has never been mentioned again in the main line series, possibly because Rick Berman didn’t like it.)
Now. Time for me to take you all on a grand tour of DNA sequencing and phylogenetic analysis. You are all getting into the Willy Wonka boat with me. You have no choice.
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So! You have a sample you’ve taken from a non-human mammal, one that’s never been genetically analyzed before. You are very lucky. You get to do fun stuff.
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But before you get to sequencing, you have to purify any DNA in the sample. Your sample is full of all sorts of other biochemical gunk, and when cells are happy, DNA is packed away in the nucleus–you need to crack those open to get at the DNA. 
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Next, you need to break the DNA into chunks, that’s #1 on the diagram above. For most of the past twenty years, this has meant chunking DNA down into pieces 25-50 letters long–just enough to probably get something unique over most of the genome, though you will have some areas that look identical at that tiny scale. In recent times, we’ve been getting better and better at what’s called “long read sequencing”, which at this point means fragments of several thousand DNA letters in length–though that’s still pretty short, compared to human chromosomes though: the average length of a human chromosome is 134 million letters long.
Depending on the sequencing technology and its needs, the sample may also need “amplification”: getting copied over and over using a protein originally harvested from hotspring-loving bacteria (#2). I always love that bit just as a concept: it’s one of many places where the modern study of genetics uses the microscopic, biological machinery of proteins for our own use! 
After everything’s prepared, Then the sequencing itself can occur. That too is wild–the most common versions these days use tiny little fluorescent proteins to tag each letter of the DNA and read the sequence of lights (#3!). Some use infinitesimally tiny electrical modulations as DNA passes by a microscopic reader. There’s loads of different ways, anything works, so long as it can be read by a computer.
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All this takes place in machines that are either small enough to fit on a countertop, or big enough to look like a fridge, and come in Apple White or Cheap Plastic Appliance.
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Because you have a new species, you’re building what we call a reference genome. This tries to capture as much of the entire genome sequence as possible. Here’s an interesting wrinkle, though–A lot of samples won’t be just DNA from your target species! You might be picking up microbial DNA along the way as well. That can be really interesting and worth knowing about, though! Some people spend their whole careers studying the genomes of microbes found on people’s skin, or in their bodies. You’ll be computationally sorting out which sequences are in contiguous, mammalian chromosomes, which are from mitochondrial DNA (those cute little powerhouses have their own genomes!), and which come from microbes.
At the end of it, you have sequenced an entire genome. Because you want to find out how related it is to humans, you compare it to our reference genome–The human reference genomes we use is an assembly made from multiple individuals.* We use the reference genome as a common point of comparison that we refer to when studying genetic variation.
*Though if you’re working with data form the Genome Reference Consortium as is usually standard, one anonymous African-European donor, RP11, is still the backbone of the reference, accounting for 70% of the latest assembly.
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(https://mk.bcgsc.ca/telomere-to-telomere-human-genome-assembly/posters.mhtml)
So, we’d compare this new mammalian genome to our own–how much overlap would we find? A lot. How you define our similarities and differences from other species can change the answer, but you’ll expect a lot of overlap. Some areas of the genome diverge faster than others, others are highly conserved–generally the more stable it is, the more important it is for our function. 
Through many, many, many studies and corroboration with the archaeological record, we’ve worked out how to estimate how long ago two species diverged from each other. Actually, you’d rarely be comparing between just two species at this stage–get out all the other relevant reference genomes you’ve got! Compare them all! Build a phylogenetic tree–the modern version of that “tree of life” idea that Darwin popularized. Then you’ll have a more accurate sense of how your mystery species relates to everything.
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(https://www.embl.org/news/science/a-new-tree-of-life-allows-a-closer-look-at-the-origin-of-species/) 
I’m going to go off on a tangent to end this post, because that’s just the start, taking the entire genome of a single individual. This is what most people think is what we always do. But no! That’s expensive overkill for most experiments. Once you’re familiar with a species, and you’ve sequenced DNA from many individuals, you can identify areas where lots of them have sequence variants. These can be completely benign, differences that make us all unique, or make an individual more susceptible to disease. This allows us to target what we want out of DNA sequencing: Are we trying to diagnose an illness? Identify a person from a tissue sample? Or are we doing something more exploratory?
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Depending on what you want, you select anywhere from a handful of locations, up to tens of thousands. The closest many people have gotten to this stuff is through ancestry services like 23andMe, which uses this kind of sequencing.
But that’s not all! There’s so many different targets to choose from, depending on what you want to do! So many techniques to get DNA in different ways! And we still haven’t gotten to the part that I actually work on.
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I’m a computational geneticist. I get all the gigabytes of data that comes out of these experiments and I get to dig into the details, the patterns that emerge between genetic code and the details of the organisms we study, the connections between genome sequence and other, wilder things we can collect data on, the dizzying complexities of what goes on every microsecond of every day in every cell in your body.
I love my job. 
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Citations for alt-text rambles:
1. https://www.youtube.com/watch?v=O_YuTMDkWfI 2. https://doi.org/10.1242/jeb.116129 note: this source lists the image as credit to “J.M.B.”, which is not how I’m used to seeing images credited. Those are the initials of one of the authors, but I thought it meant “Journal of Molecular Biology”, so I went on a half hour wander around the internet trying to find where the hell this fish blood came from. 3. https://www.thebhs.org/publications/the-herpetological-journal/volume-13-number-4-october-2003/1729-01-hyperbiliverdinemia-in-the-shingleback-lizard-tiliqua-rugosa 4. https://doi.org/10.1111/j.1439-0264.2009.00952.x 5. https://en.wikipedia.org/wiki/Mandrill#Characteristics 6. https://www.vogue.com/article/dune-part-two-costumes-jacqueline-west-interview 7. http://dx.doi.org/10.13140/RG.2.2.29564.08327 8. https://www.researchgate.net/publication/357946568_New_approaches_and_concepts_to_study_complex_microbial_communities 9. https://karobben.github.io/2023/10/30/Bioinfor/PacBio/ 
Overflow Ramble 1
 the fuckin “DNA MATCH” machine. I already wrote a 380-word alt-text about this thing last time. I’m not doing it again. I’m going to talk about things I like instead. Such as Dune: Part Two! Yes! I mentioned it last week and then didn’t ramble about it after seeing it. Well, NOW I WILL. tl;dr it’s good, go see it. I only vaguely remember the book, but I liked the changes they made to center the fact that no, Paul becoming Lisan al-Gaib is not actually a good thing.
Man, it’s nice to see a movie where the costumers and set designers got good time to work on their craft. (cite 6) Even the generic Harkonnen soldiers looked great–reminded me a lot of my beloved Warframe, probably because the costume designer was using H.R. Giger for inspiration there. Everything felt real. Even the stuff that definitely wasn’t–the gigantic spice harvesters and ships felt like living, physically present beings. The sand worms looked great. The movie did a fantastic job visually communicating the massive size of so many things. Especially because the camera remains restrained: no weightless zipping around, the camera itself follows paths and finds locations that make sense. 
Chakobsa continues to be a fantastic conlang, now the work of both David and Jesse Peterson. It’s heard a lot more in this movie, and there are some great flourishes with it. While there isn’t as much Arabic vocabulary in it as in the original books, I remember from DJP’s work streams that he definitely was using the grammar of Arabic as one of his touchstones. Most key words remain Arabic though–jihad was removed, but it made me double-take in the theater when Stilgar referred to Paul as the Mahdi.
I’m of two minds about lowering the Arab influences on the Fremen–on the one hand, missing representation, which included some explicit ties to real world anti-imperial struggles in North Africa and the Middle East. On the other, these first two movies are about how the Fremen are manipulated by a colonial power, using their adherence to a faith that was manipulated by a different colonial power. They become both hapless victims and also perpetrators of colonial violence, with only Chani seeing through it.
I think the general decisionmaking process on cultural changes was motivated by a desire to remove some of Frank Herbert’s bad ideas–particularly around the Harkonnens, thank fuck. That seems to have been the thinking around altering the Fremen a bit as well. Did it succeed? Not my place to say. On all other notes, I have no reservations recommending the movie. It’s a very earnest attempt to bring that world to life, and I think it succeeds.
Overflow Ramble 2
A figure showing the basic steps of the standard Illumina sequencing method (cite 7). It is broken into four sub-figures:
Library Preparation. The genome is snipped into small fragments, then adapters are attached (“ligated”) to stabilize the molecule and make it behave. This creates a “library” of DNA that will be read from.
DNA library bridge amplification. The adapters on DNA fragments stick to a prepared plate, which is covered in little clusters of molecules that specially attach to those adapters. Biochemical processes are then carried out in repeated cycles to duplicate (or “amplify”) those fragments in such a way that the clusters on the plate are all filled with copies of just one DNA fragment.
DNA library sequencing. The DNA is modified so that the four letters it’s made out of all glow a specific color, with each DNA letter shining in sequence. This is pure awesome and I love it.
Alignment and data analysis. Because of some details on how step 1 is done, you have lots of fragments that create an overlapping patchwork of sequences. This allows (most of) the genome to be pasted back together by looking for overlaps (“contiguous sequences”, or “contigs” for short).
Congratulations! You have just attended an abridged graduate-level introductory lecture on Illumina sequencing.
Overflow Ramble 3
A diagram of PacBio Systems’ sequencing technology, Single Molecule, Real-Time Sequencing, or SMRT Sequencing, because scientists love acronyms. Pretty much every step is different from how Illumina does it. I cannot find a diagram that’s both brief and also good at explaining what it’s showing, so this is the best I could find. It’s split into four parts with attendant text, which I’ll try and explain as well.
“SMRTbell template. Two hairpin adapters allow continuous circular sequencing.”
Library preparation basically involves taking a longer chunk of DNA and splitting it in half lengthwise, in such a way that the two strands of DNA will form a single-stranded loop. This is called a SMRTbell library. Why? I have no idea! 
“ZMW wells. Sites where sequencing takes place.”
Then, these are fed into SMRT Cells, which contain zero-mode waveguides (ZMWs). I was once told what this means, and I have completely forgotten, but it sounds like something from Gundam.
“Modified polymerase. As a nucleotide is incorporated by the polymerase, a camera records the emitted light.”
What I do understand is that at the bottom of each of these little holes, they stick a molecule which the DNA sticks to. This molecule, a polymerase, has precisely one job: make more DNA, an exact copy of what it’s latched onto. So you give it this loop of DNA, feed it a soup of free DNA letters, and it starts cranking out a new strand. 
“PacBio output. A camera records the changing colours from all ZMWs; each colour change corresponds to one base.”
Each one of the DNA letters given to the polymerase has a special modifier, on it which flashes a color when the polymerase slots it into the new strand it’s making. A camera picks up this flash. And, because the DNA is a circle, the polymerase doesn’t know where to stop–it just keeps going and going until something breaks or it runs out of letters to work with. This means that even if the camera misses a flash the first time, it will have more chances to see it, and confirm what it already saw.
Wait what in the fuck this figure was from somebody’s thesis (cite 8), but that wasn’t what actually got this into search results. What got it there was a github page with a vtuber avatar sitting in the corner?? What??? (cite 9)
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many-a-cringe-interests · 5 months ago
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Bro (me) thought he was onto something 💀
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