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SeptimusHeap from Switzerland (Edited uphill both ways) Relationship Status: Mu
#2426: Jan 20th 2024 at 11:45:01 AM

Looks like an earthquake swarm is underway in Tyrol (Austria). Nothing in terms of fatalities or damages, but it's now two days of seismic activity.

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman
SeptimusHeap from Switzerland (Edited uphill both ways) Relationship Status: Mu
#2427: Jan 30th 2024 at 8:31:17 AM

A bit of a thought experiment: How easy/difficult is it to genetically engineer a human person to bioluminesce, akin to the example given here for plants? A few considerations, partly from easier to harder, some chemical jargon inbound:

First, obviously one needs to encode the necessary enzymes of the pathway - not just luciferase, but also caffeoylpyruvate hydrolase, hispidin synthase and hispidin 3-hydroxylase. You may consider changing the pathway, say by having caffeoylpyruvate coupled to acetoacetyl-CoA rather than malonyl-CoA, especially since the latter is a signalling molecule that is pointedly not present in actively catabolizing cells.

Second, you need a way to produce the luciferin. Animals don't produce caffeic acid, so you need to include the two biosynthetic enzymes (tyrosine ammonia lyase and coumarate 3-hydroxylase) as well. Analogously, you'll need the other biosynthetic enzymes if you use a different luciferin. And you'll need a new malonyl-CoA synthesizing enzyme to solve the aforementioned problem.

These are the easy parts. The third part is how to get controllable luminescence out of it. The main way I can think of is to genetically engineer the development of skeletal muscle cells in the skin, at the embryonic stage. That means including a signal (probably a stochastically induced transcription factor) that causes a fixed proportion of skin cells to differentiate into muscle cells. These would then induce the development of nerves, and then children learn to control it the same ways they learn to walk. However, these modified/hijacked muscle cells ought to lack key motor proteins so that they don't move; this can be done easily via RNA interference processes.

The fourth part is the melanin issue. You don't want these cells to contain melanin but at the same time such anomalous muscle-like tissue will have stem cells associated that need it lest they become cancerous. So you probably need to induce melanin-transporting proteins so that during the cell growth, it is constantly repositioned to the stem cell. And you'll need extra tumor suppressor genes. Might also want to add skin dissolving enzymes so that the muscle-like tissue is located under a thinner layer of skin.

All this needs to be done pre-natally; connecting to the nervous system will almost certainly not work post-natally. Such glowing skin might be very susceptible to sunburn and/or injury, depending on how part four is arranged.

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman
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#2428: Jan 30th 2024 at 8:43:07 AM

The fifth one is running away from the law when you try it. tongue

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SeptimusHeap from Switzerland (Edited uphill both ways) Relationship Status: Mu
#2429: Jan 31st 2024 at 3:46:21 AM

Depending on the law in question, mind you - as the case of the Russian and Chinese scientists who edited babies' genomes in 2019 show, this kind of gene editing is a legal grey zone in many countries. There are some practical uses to being able to light your skin, e.g for technicians. And if the glow is powerful enough, as an easily controlled weight loss device (not treatment, as we are talking about pre-natal genetic engineering). I'd worry about the race issues more: Glowing skin is a thing where skin colour makes a major difference, as too light a skin and the modified cells are at risk of cancer, too dark and the light can't get out. Speaking of skin colour, most luciferins including this one have colours which would alter the skin colour.

Anyhow, sleeping over this the key difficulty to overcome is how to induce muscle tissue in embryonic skin, unlike bones there is no easy "inject substance, bones grow" device here. When that is sorted, all that's needed is to express the artificial chromosome you used for engineering in these cells

    More biological details for any biochemistry anoraks 
The chromosome in question probably needs an hypoxia-sensitive repressor, since a) you can't make light without oxygen, anyway, b) oxygen permeates through skin, if there isn't enough oxygen it's probably being expressed in the wrong place and c) the metabolic engineering pathway I suggest below would result in the buildup of the hypoxia mimic succinate if the cell is stressed, creating a negative signalling system.

The chromosome needs the six genes of the light cycle: Luciferase, hispidin-3-hydroxylase, hispidin synthase, caffeoylpyruvate hydrolase, tyrosine ammonia lyase and coumarate hydroxylase. They need calcium activability too. You might need a seventh gene (a phosphopantheteine transferase) to activate the hispidin synthase.

Three other genes are needed to recycle the pyruvate and to produce malonyl-CoA and NADPH. The latter two can be done with an acetyl-CoA carboxylase and a transhydrogenase, probably calcium-dependent and with some way to get the products out of mitochondria (acetylcarnitine as mentioned below). For the latter, you might have to decide between the cancer-promoting effects of reduction to lactate or the reductive stress inducing conversion to acetyl-CoA. Or you convert that lactate to alanine somehow. Part of the pyruvate won't be reduced for lack of reduction equivalents, then it can be transaminated or included

Two or three genes are needed for melanin handling; the stem cells need it, the modified muscle cells don't want it, the melanin that builds up anyway ought to cluster close to the neuromuscular junction.

One or five genes are needed for modifying the muscle cells. The obligatory one to suppress the actual functionality as muscles, e.g by preventing myosin (de)phosphorylation. The optional ones to suppress glycolysis, citric acid cycle and complex I activity in mitochondria, and induce fatty acid oxidation. The citric acid cycle part may also be needed to enhance the malonyl-CoA export (via acetylcarnitine?). Thus you can run the entire cycle on a two-acetate unit, with one of the two NADH used to form NADPH for hispidin-3-hydroxylase and the other for pyruvate->lactate conversion. The acetates are both used by hispidin synthase, the flavins for the mitochondrial complex II.

There are other biosynthetic pathways but they are all considerably more involved than this. One alternative would be coelenterazine, which requires 1 calcium-activated luciferases (aequorin or obelin), optionally 1 colour-determining protein (green fluorescent protein), probably 1 luciferin biosynthetic protein (an iron-dependent isopenicilline-N-synthase), 2 "maintenance" enzymes (a sulfatase and a sulfotransferase), and a few recycling enzymes. One might need 4 (dehydrocoelenterazine synthase, dehydrocoelenterazine reductase, a hydroxyphenylacetate serine transferring enzyme, and one glycolate-acetate coupling one)

Edited by SeptimusHeap on Feb 1st 2024 at 5:56:58 PM

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#2430: Feb 12th 2024 at 10:07:44 AM

I wonder if there is a way to grow trees out of paper, like some ultimate recycling method.

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#2431: Feb 12th 2024 at 2:13:49 PM

Do Cassowaries have one huge claw on each foot as a direct holdover from raptor dinosaurs having one huge claw on each foot? Like, did that trait just never evolve out, did it evolve out and then come back, or are Cassowaries not even direct descendants of those kind of raptor dinosaurs, and they evolved it convergently?

Edited by PushoverMediaCritic on Feb 12th 2024 at 3:14:31 AM

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#2432: Feb 12th 2024 at 2:41:09 PM

Cassowarries and other Big birds like them (Emus and Ostriches) are likely descendants of Terror Birds like Gastornis or Phorusrachus, who convergently evolved to share the same niche as Raptor dinosaurs in their era.

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#2433: Feb 12th 2024 at 3:38:56 PM

@Pushover Media Critic

Birds are paraves, which is a group that contains various "raptor"-type dinosaurs. So it is the right type of dinosaur, yes. In essence, birds are small, flight-adapted raptors.

Ratites like the Cassowaries are essentially bird evolution recreating the Mesozoic raptor using birds. Largely successfully in the case of Cassowaries, which are a basically a middle finger to anyone who makes jokes about T. Rexes and Chickens. Indeed, they bluntly create some amount of Fridge Horror when you realize that the Mesozoic had what are basically giant, deadlier, carnivorous, cassowaries in it.

In essence, they're to Mesozoic Raptors what Bioshock is to System Shock: a good spiritual successor made by the same dev team.


Regarding the claws specifically: I'm having trouble determining if it's a "trait that they never fully lost", "trait they re-evolved", or a combination of the two.

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SeptimusHeap from Switzerland (Edited uphill both ways) Relationship Status: Mu
#2434: Feb 13th 2024 at 4:08:18 AM

Mmm, given that cassowaries are related to tinamous and kiwis, both of which have unremarkable claws, I figure that it evolved anew.

"For a successful technology, reality must take precedence over public relations, for Nature cannot be fooled." - Richard Feynman
DeMarquis Since: Feb, 2010
#2435: Feb 13th 2024 at 8:03:22 AM

They aren't the only species that have dew claws, after all.

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#2436: Feb 14th 2024 at 9:22:58 PM

Okay, so this might be a weird question, but are there any species of spiders whose venom has medical properties?

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SeptimusHeap from Switzerland (Edited uphill both ways) Relationship Status: Mu
#2437: Feb 14th 2024 at 11:17:18 PM

A modified black widow toxin is used in science.

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#2438: Feb 15th 2024 at 12:23:21 AM

What kind of science?

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#2440: Feb 15th 2024 at 5:53:57 AM

So basically there isn't much scientific basis for Spider venom being used in medicine besides experimental stuff.

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#2441: Feb 15th 2024 at 5:55:40 AM

I'd imagine they could be used to make antivenom.

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#2442: Feb 15th 2024 at 5:58:20 AM

I asked because a recent movie came out where it's a plot point that a spider's venom could cure a neurological disorder as well as grant super powers.

...Even tho the entire point of a spider's venom is to kill it's prey. So I decided to double check if there's any actual basis for that sort of thing.

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#2443: Feb 15th 2024 at 6:01:15 AM

Venoms generally are used as basis for medicine, not straight up medicine. Coagulent/Anticoagulent ones are used as blood thinners/thickeners, neurotoxins can be used to deal with certain neural disorders, that sort of thing.

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#2444: Feb 15th 2024 at 6:06:51 AM

Yeah but the venoms usually have to go through modifications so it's not lethal right?

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#2445: Feb 15th 2024 at 6:10:44 AM

Yeah, this isn't homeopathy. Scientists will work to isolate the molecules in the venom that have the desired properties.

Many things that we use for medicinal purposes today are directly adapted from toxins and venoms. Botulinum toxin is one of the most well-known, as it is used to treat muscle spasms, sweating disorders, and facial wrinkles.

Edited by Fighteer on Feb 15th 2024 at 9:13:12 AM

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Protagonist506 from Oregon Since: Dec, 2013 Relationship Status: Chocolate!
#2446: Feb 15th 2024 at 6:13:23 AM

@Red Hunter 543

I asked because a recent movie came out where it's a plot point that a spider's venom could cure a neurological disorder as well as grant super powers.

...Even tho the entire point of a spider's venom is to kill it's prey. So I decided to double check if there's any actual basis for that sort of thing.

I'd actually say that there is some small basis to that. There are poisons in nature that find beneficial uses to humans.

For example, it might be designed to kill something that isn't humans, and has a different effect on humans. Caffeine would be an example of this in real life: it's very dangerous to insects, but a mild stimulant to humans.

On the flipside, a poison might have medical applications in controlled doses or in the right context. While not the best example: Botox injections actually contain small amounts of the most deadly poison created by any organism on Earth.

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#2447: Feb 15th 2024 at 6:20:32 AM

yeah humans love their deadly substances that they weren't meant to consume for some reason

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#2448: Feb 15th 2024 at 6:54:38 AM

Like Artifically made Trans fats and PUF As.

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nova92 Since: Apr, 2020
#2449: Feb 15th 2024 at 8:26:59 AM

Yeah but the venoms usually have to go through modifications so it's not lethal right?

Not necessarily. If the venoms act by binding to a specific enzyme in the prey, for example, and humans don't have that enzyme/the active site is shaped differently, it may not work on humans. Or the lethal dosage may be different, and it could have beneficial effects at sub-lethal levels.

DeMarquis Since: Feb, 2010
#2450: Feb 15th 2024 at 4:57:48 PM

Isn't that basically the basis of chemo-therapy (not spider venom specifically, but something that would normally be toxic to us)?


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