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GODSPEED JOHN GLENN posted:No sir, I've thought about it and I don't want no toxins. We've all seen your sigs, and we know better.
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Apr 21, 2019 03:03
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prepuce repurposed posted:toxic aunt crew I have a few of those!
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Apr 21, 2019 03:04
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prepuce repurposed posted:toxic aunt: you wore one of the two sweaters I made you for christmas!
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Apr 21, 2019 03:17
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prepuce repurposed posted:toxic aunt: you wore one of the two sweaters I made you for christmas! haha |
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Apr 21, 2019 05:01
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prepuce repurposed posted:someone told me alcohol is a neurotoxin is this true Sorry I missed this one! Yeah - alcohol is a neurotoxin, it's a toxin because it's produced from a natural source and it has neurotoxic effects. That said 'neurotoxic' or 'neurotoxin' are basically just functional categorizations of toxins - a toxin or even a single component of that toxin can be a neurotoxin and also a myotoxin (we'll encounter this particular circumstance later on at some point). Alcohol could also just as readily be called a 'hepatotoxin' cause it damages the liver or a 'cytotoxin' because it damages cells. I'll deal with this a little more at the end of the next effort post for reasons that will become clear 
Stoner Sloth fucked around with this message at 09:57 on Apr 21, 2019
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Apr 21, 2019 09:46
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Meanwhile, some scary toxin stories of a wasp injecting venom into a cockroach brain (not really a brain, because you know, insects don't have those, but an important thing in the head called supraesophageal ganglion) to turn it into her servant. https://www.youtube.com/watch?v=-ySwuQhruBo Goons Are Gifts fucked around with this message at 14:46 on Apr 22, 2019
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Apr 22, 2019 14:43
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Goons Are Great posted:Meanwhile, some scary toxin stories of a wasp injecting venom into a cockroach brain (not really a brain, because you know, insects don't have those, but an important thing in the head called supraesophageal ganglion) to turn it into her servant. Nice find - such pretty but mildly terriffying creatures these were the ones that made me think about those vampire ants maybe being able to judge the health of their larvae through tasting of haemolymph!They're still trying to figure out exact the molecular mechanisms by which jewel wasp venom managed to 'zombifie' the host cockroach but from what I'd read there's certain somewhat eerie similarities between these the state of these 'zombie' roaches and human patients with some forms of neurological disorder. Basically after the grooming bit they sort of simplify things by saying it's 'stupefied' but the reality is that the instead manage to reduce the ability and/or drive of the roach to self-initiate locomotion - it's not paralyzed obviously can't start movements on it's own. It's correlated with an insensitivity to dopamine suggesting that the wasp's venom disrupts the normal dopamine-dependent signalling in the roach's nervous system. This can be seen as not unlike severe Parkinson's disease and particularly patients who survived the early 20th century sleeping-sickness epidemic - they weren't paralyzed technically but were essentially frozen in place until an appropriate external stimulus happened. For example, these locked in patients could perfectly catch and return a ball thrown to them. Thanks for this GaG and feel free to post more about our venomous hymenopteran frens anytime! Stoner Sloth fucked around with this message at 09:59 on May 7, 2019
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Apr 22, 2019 15:12
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the jewel wasp is fascinating. reminds me of this, (srry if this is an ant crew trigger, i can't figure out how to spoiler vids. if its a problem ill take it down) https://www.youtube.com/watch?v=XuKjBIBBAL8 hope this is a cool addition, idk if its toxicology take the moon fucked around with this message at 22:06 on Apr 22, 2019 |
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Apr 22, 2019 21:56
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Nah I think spiders were problematic sometimes, but ants should be fine. Didn't have any complains in the ant crew about posting pictures there and we even had nasty parasites and body snatching monstrosities. This even gives chills despite Attenborough narrating it. Fungi are absolutely insane organisms in almost every way, really. Resilient and large in numbers like plants, but cunning and adaptable like animals. I don't think it's fully known how those fungi work, especially the mind control part is largely a mystery, as we can't even really know how this kind of stuff works for humans, not to say about animals that do not have a centralized nervous system. It is very much likely that the fungus produces some kind of toxin to, similarly to the cockroach part, induces some kind of stroke situation in the brain, causing neurological damage that leaves only the basic functions alive, while triggering movement towards a certain direction. However, brain science is one hell of a science and pinning that kind of stuff down on insects seems like a really tough challenge, so who knows what magic works there!
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Apr 22, 2019 22:09
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cool video - I read a few things about this despite not having much of a background in fungi. It's a pretty complex process that we're still in the infancy of understanding. An interesting (read horrifying) thing about these fungi is that for the most part they don't invade or damage the brain of the ant other than in really specific areas - instead they grow through the muscle fibers of the ant, connect up and then start releasing chemicals that damage the motor centers of the brain but otherwise leave it untouched. Then they use chemicals to control the muscles of the ant... basically the ant is a prisoner in it's own body until the fungi finally kills it. https://www.theatlantic.com/science/archive/2017/11/how-the-zombie-fungus-takes-over-ants-bodies-to-control-their-minds/545864/ seems like a good, brief, not overly technical summary.
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Apr 22, 2019 23:39
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Goons Are Great posted:Fungi are absolutely insane organisms in almost every way, really. Resilient and large in numbers like plants, but cunning and adaptable like animals. (some) fungi are friends indeed, try to imagine life without yeast |
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Apr 23, 2019 03:44
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Manifisto posted:(some) fungi are friends indeed, try to imagine life without yeast  thanks fungi!Lichen is another vital fungi - and pretty amazing, apart from being a symbiotic composite organism of fungi (sometimes two types) and algae or cyanobacteria (can be multiple types per lichen) but they can also form other symbiotic relationships with microorganisms as if they're an entire microscopic ecosystem themselves. They're also responsible for much of the world's fertile soil, since they're able to break down rocks into minerals that they and other things can use, and probably created the first soils suitable for life to grow in on land since they're in the fossil record for an amazing 2.2 billion years. Individual lichen are also exceptionally long lived - an arctic species has examples of it that appear to be 8,600 years old and may be the oldest living organism on the planet. Oh and also at least two species of lichen can not only survive in space for at least 15 days but can do so without resorting to the sort of tricks that waterbears do and can then be planted back on earth and can still grow, photosynthesize and function normally. Another experiment suggest that they could keep functioning and photosynthesizing on mars for at least 34 days. Only a few species are toxic (mostly yellow ones), containing high amounts of vulpinic or usinic acid - both of which show great potential as antibiotics and are formed seemingly exclusively in lichenized fungi, but they're still very cool! Without them life on land may never have been successful.
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Apr 23, 2019 05:13
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Cnidaria 2  Time to talk about corals - beautiful, "sea flowers" that are surely harmless right? Well as I stated in part 1, ALL Cnidarians are toxic and corals are no exception - far from it as we will see. Zoanthidea (taxonomists also refer to this as Zoantherea) are our first stop - a soft coral that has species ranging from deep sea enviroments to tropical coral reefs to the shells of marine invertebrates. these are often vibrantly colourful and charismatic corals are also often sold to amateur aquarium owners and hobbyists because they're relatively easy to keep, being durable and used to many different marine environments, and because of their beauty:     Like most corals they are symbiotic with a type of dinoflagellates known colloquially as Zooaxanthellae (genus Symbiodinium) - single celled, photosynethic organisms that also are often at least thought to be responsible for the production of a variety of marine toxins (bacteria infecting may be at least partially responsible in many cases). In the case of Zonathidean corals this results in some of them concentrating a toxin called Palytoxin (or PTX). PTX is an extremely powerful vasoconstrictor and one of the most toxic non-protein substances known to science. Because of it's exact mechanism of targeting the sodium-postassium pump present in and vital for the continuing operation of every cell in a verterbate organism it is toxic through almost any source of exposure - be that contact, an open wound, ingestion or even inhalation of fine particles or vapor. It has a "relatively" high ingested LD 50 in mice of around 510-767 micrograms per kilogram but its intracheal or respiratory value is only 0.36 micrograms per kilogram. Worse still an intravenous LD50 in mice is only 0.045 micrograms per kilogram. If it were the same level of toxicity in humans then this would suggest that only a couple of micrograms (millionths of a gram) would be necessary to kill even a large human being. In reality we're probably slightly more resistant than mice but not nearly enough to make this anything other than an extremely lethal toxin. Given the sheer number of routes of exsposure here it's not surprising that human envenomations and even fatalities have occured through numerous routes - eating parrotfish that have gnawed on and eaten these corals, cuts on hands while handling corals, cutting up or otherwise disturbing these corals in an aquarium or even just inhalation of vaporized toxin and water have all cause fatalities. Symptoms vary as does time taken by route of envenomation ranging from flu like symptoms to skin symptoms like rash or dermatitis to gastrointestinal or even ocular symptoms if exposure is through the eyes. However in severe cases neurological, cadiac or muscular symptoms tend to be present as well and can lead to muscle breakdown, kidney failure, coma and death from cardiac or respiratory failure. The molecular chemistry of palytoxin is outstandingly complex - I won't go too deeply into it unless anyone's remotely interested but there are approximately 10 to the power of 21 different "variant" arrangements of this molecule (stereoisomers). It, like other dinoflagellate (or possibly bacteria infectingthem) toxins such as tetrodotoxin (TTX), saxitoxin (STX and responsible for Paralytic Shellfish Poisoning), is highly toxic. However even compared to most of these its in a class of its own - exceeded only by maitotoxin (MTX) in terms of toxins from dinoflagellate origins. TTX, which we met earlier when talking about the distinction between toxins and venoms, you'll remember is the lethal toxin used by both blue ringed octopus and many species of pufferfish in different ways. It is probably the least lethal of these at an intravenous LD50 of 8 micrograms per kilogram in mice (remember 0.045 for PTX) - this compares to an intravenous LD50 of 2.6 MILLIgrams per kilogram for deadly potassium cyanide! In other words TTX is more than 300 times as lethal by this measure and PTX is more than 57,500 times as lethal as potassium cyanide! There is no antidote. If all this weren't enough evidence suggests that in sublethal doses palytoxins may promote tumors. You may at this point have second thoughts about handling coral while not wearing thick gloves or eating reef fish, you have my blessing to do so. ---------- Nightmare fuel aside corals are of course venomous in other ways - they use a variety of venoms injected by their stinging cells to catch fish and other small creatures - some rely solely on this although most practice symbiosis with photosyntheic dinoflagellates as mentioned earlier. There is however another aspect of corals that is less obvious - many are silently and constantly waging chemical warfare against other corals on a massive scale. This is especially prevalent in species that mostly reproduce asexually - corals will use a variety of toxins dispersed in the water currents to attempt to kill or stall the growth of other, unrelated coral so that its offspring may replace them. While most toxins are for predation or defense this and other forms of intraspecific venom use as competition for resources is probably the most common minor use of toxins (though of course there are many, many other niche uses) by venomous organisms. Moving on from corals we'll take a look at the most complex of cnidarians - the Cubozoans or box jellyfish. Now everyone reading has probably heard of the most well known of these, the 'sea wasp' or often just 'box jellyfish' - Chironex fleckeri but we shall leave this aside for just a moment. The class of Cubozoans are defined by their cube shaped medusae (duh) and there are over 50 different known species the majority of which, while obviously venomous, are not a threat to human beings. These advanced Cnidaria are all capable of independant movement and have a large number of eyes - interestingly some of which are simple light detectors but others of which are more advanced 'true eyes' featuring retina, cornea and lenses. In addition to this the possess gravity sensing cells allowing them to detect their orientation in the water as well as the ability to propel themselves through contraction of their bodies. They all display complex behaviours and can avoid obstacles and predators as well as actively hunting prey courtesy of a far more complex neural structure than other Cnidarians exhibit. We'll start here with the little guys of the Cubozoan world - Irukandji:   Irukandji, as they were termed by an Australian group of indigenous people, are actually a number of different species of Cubozoan or box jellyfish. They represent the smallest known species of this class. Ranging in size from a bell of about 5 millimetres to 25 millimeteres and with four tentacles ranging in size from a few centimetres up to 1 metre in length. While the 'body' of these creatures can be less than the size of a thumbnail, they can inflict fatal envenomation on human beings despite targeting nothing more than small fish and crustaceans. Often the effects of envenomation can take 2-12 hours to fully appear and where fatal result from cardiotoxic effects such as hypertension, pulmonary edema or tachycardia. And finally we take a look at our old friend the 'sea wasp' or 'box jellyfish', Chironex Fleckeri:   Quite a large Cubozoan, the 'sea wasp' can have up to 16 tentacles each with a maxmimum length of over 3 metres. All up this adds up to quite possibly the most venomous organism on the planet - capable of inflicting severe evenomation that targets a broad range of molecular targets and can cause severe inflammation, pain, neurotoxic, haemotoxic, cytotoxic, cardiotoxic, myotoxic and dermnonecrotic (kills skin cells through lysing <bursting> them) effects. It's a sledgehammer in terms of venom and should be compared to the venoms of most sea snakes or cone shells which can be described accurately as almost purely neurotoxic. To add insult to injury the 'sea wasp' or 'common box jellyfish' can kill a human being faster than almost any other venomous organism - 2-5 minutes on average from a serious envenomation before cardiac arrest sets in. Even in less serious cases permanent scarring is a certainty. We'll leave it here for now, hope you've enjoyed this episode of Toxin Crew. PS peeing on jellyfish stings is unlikely to help - it seems that while it deactivates untrigged nematocysts, it also makes those already injected increase the dose of venom to a victim. It's mostly recommended because it allows scraping off the tentacles more easily but you can safely do that with a glove or even thick piece of cloth. Vinegar and other weak acids face the same problem. Please don't take this as professional medical advice but if someone is stung by this jellyfish the best thing to do is seek urgent medical attention and worry more about keeping their heart and lungs working than pissing on them. Again, not a doctor. Stay safe out there! Stoner Sloth fucked around with this message at 17:20 on Apr 24, 2019
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Apr 23, 2019 18:21
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Stoner Sloth posted:PS peeing on jellyfish stings is unlikely to help  v good post ty. |
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Apr 23, 2019 18:50
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take the moon posted:
ty - figured I'd go for the human interest angle
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Apr 23, 2019 18:54
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this is what 'sea wasps'/'box jellyfish' stings that are relatively minor look like:   this sort of scarring is likely to last a lifetime. e: it's also possible that peak Big Disney movies have led us to optimistically believe that peeing on thigns will help, usually it does in fact not Stoner Sloth fucked around with this message at 19:23 on Apr 23, 2019
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Apr 23, 2019 19:08
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another very interesting post, thank you! I remember hearing that the pain from some jellyfish stings can last for over a year or more, that sounds decidedly unfun |
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Apr 23, 2019 19:59
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Manifisto posted:another very interesting post, thank you! thanks for reading friend! glad you're enjoying!!yeah, some pain inducing venoms can last for a considerable length of time - the worst culprit there (imho and ruling out testing on myself) is funnily enough a mammal but we'll get to that one soon enough
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Apr 24, 2019 02:19
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Gonna let anyone interested have a say in what we look at next: a) continue on with toxic marine animals, looking at molluscs next b) something completely different, look at toxic mammals next c) delve a bit deeper into how toxins work I'll tally up the results and go from there
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Apr 24, 2019 10:09
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Those are some drat sexy corals. That's SpongeBob porn
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Apr 24, 2019 11:05
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Personally I'd be very down with c
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Apr 24, 2019 11:06
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Goons Are Great posted:Those are some drat sexy corals. That's SpongeBob porn yeah - they're definitely beautiful. Looking for pictures of coral reminded me of diving on the Great Barrier reef when it was still in quite a healthy condition - they still don't do it full justice but gave me a pleasant trip down memory lane at least Goons Are Great posted:Personally I'd be very down with c and one vote for c noted! and don't worry, I'm intending to cover all of these topics and plenty more eventually so feel free to vote whatever you'd like to see first ppl and don't worry too much about missing out on the others!
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Apr 24, 2019 15:21
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Stoner Sloth posted:Gonna let anyone interested have a say in what we look at next: I'm down for anything, I am sort of fascinated/horrified by cone snails but the toxin aspect is only a piece of that picture
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Apr 24, 2019 15:25
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Manifisto posted:I'm down for anything, I am sort of fascinated/horrified by cone snails but the toxin aspect is only a piece of that picture I've got some good stuff on them that I think you'll definitely find fun/horrifying/fascinating then! But c will easily segue into a or vice versa and I can work with doing the same with b so any choice is a good one
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Apr 24, 2019 15:28
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I vote for c, but any of the three is fine, and will undoubtedly be interesting. Also, this thread 
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Apr 24, 2019 16:05
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Barking Gecko posted:I vote for c, but any of the three is fine, and will undoubtedly be interesting. thank you mate! and that's 2 votes for C so far possibly one for A too but wasn't sure if I am counting Manifisto though wasn't entirely sure if he was voting. We'll count it just to be safe though I think.
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Apr 24, 2019 16:10
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in order I am b, c, a * stands for it doesn't matter I am down to learn about w/e
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Apr 24, 2019 17:01
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take the moon posted:in order I am b, c, a excellent! well that's 2 for c, one for b, one provisionally for a - the mammals stuff will be fun too, there's quite a few of them that most people don't realize are venomous I'm gonna give it a about 6 more hours to let anyone else have a chance to cast a vote and then I'll do a final tally in the mornin' and get to writing up the winning topic
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Apr 24, 2019 17:22
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gonna extend voting hours a little cause i gotta go visit a sick friend and brink him some smonkables - so if anyone who's interested still wants a say then they're more than welcome, otherwise it's looking like we're delving deeper into the nature of toxins!
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Apr 25, 2019 02:00
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Stoner Sloth posted:gonna extend voting hours a little cause i gotta go visit a sick friend and brink him some smonkables - so if anyone who's interested still wants a say then they're more than welcome, otherwise it's looking like we're delving deeper into the nature of toxins! oookay well that took longer than I thought but was fun - think the votes have been decided, more toxicology 420 and then we can take another vote after on mammals and molluscs!! not sure if I'll write up the next post tonight or tomozz - either way it should be soon.
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Apr 25, 2019 12:44
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Stoner Sloth posted:oookay well that took longer than I thought but was fun - think the votes have been decided, more toxicology 420 and then we can take another vote after on mammals and molluscs!! Sorry for being a bad OP - I swear that I'll post more soon, life's just been being a bit crazy and the next bit is a bit more complex than earlier sections so having to put in a bit more effort to make it worth reading. But fear not, i have not forgotten you toxin crew!
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Apr 30, 2019 03:49
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Stoner Sloth posted:Sorry for being a bad OP - I swear that I'll post more soon, life's just been being a bit crazy and the next bit is a bit more complex than earlier sections so having to put in a bit more effort to make it worth reading. But fear not, i have not forgotten you toxin crew! great to hear! but don't stress too much about keeping the effortposts on a schedule, as a wise sage once said, this is byob and you can hang with me, you can chill out relax and smoke a bong with me
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Apr 30, 2019 04:43
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Manifisto posted:great to hear! but don't stress too much about keeping the effortposts on a schedule, as a wise sage once said, this is byob and you can hang with me, you can chill out relax and smoke a bong with me thank you friend, those are words of wisdom to live by 
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Apr 30, 2019 05:22
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Okay let's get this back thing back on track! Rule 4 - more classification stuff, as I mentioned earlier the nature of a toxin's attacks on the body can be catergorized functionally in terms of the nature or form of the attack. This as previously mentioned not a mutually exclusive thing as some toxins or components of toxins can attack in more than one way as we shall see. However these terms are handy to have in one place so as you can instantly check the meaning of them. Neurotoxic - a neurotoxin attacks the nervous system either destructively or by interfering with the function of the nerves. Typically this is done by interfering with the neurons control over ion concentrations across the cell membrane or with communication between neurons across a synapse. Neurotoxicity is one of the more important types of toxicity due to it's capacity to be rapidly lethal. Myotoxic - often related to neurotoxins structurally, these peptide and proteinaceous toxins bind to the muscle fibres and cause progressive destruction of muscle cells leading to release of breakdown products from the cells. This process often takes hours to become apparent... by which time tissue is irreparably damaged. The release of the cell contents can also lead to toxic levels of myoglobin and/or potassium in the blood, leading to kidney and/or heart failure. Cardiotoxic - affects the hearts function, damaging it or causing arrhythymia. These can be through direct action on the heart function or more commonly through indirect effect - for example myotoxins damage muscle tissue which can release sufficient potassium into the blood stream as to interfere with the function of the heart potentially leading to arrythymia or cardiac arrest. Hepatotoxic -targets the liver through a wide variety of mechanisms, this of course also damages the body's ability to defend against toxic substances. A good example of this kind of toxin is that of the Amanita phalloides or death cap mushroom... it works by selectively inhibiting RNA Polymerase enzymes and thereby causing problems with protein synthesis of various sorts. By the time effects from the destructive hepatotoxic effects become symptomatic, the liver (and often kidneys) are often damaged irreparably and this has made this species the most deadly of mushrooms. Cytotoxic - targets cells. This is a very broad category naturally and includes our own immune systems cells toxins! They can cause necrosis, thereby losing integrity of the cell membranes and rapidly resulting in death through lysing (bursting) of the cell. Cytotoxic components can alternatively or also cause cessation of cell growth and division or activate a genetic program of cell death (apoptosis). In the case of apoptosis the cell will eventually become necrotic and burst though this follows more slowly than in purely necrotic toxins. Haemotoxic - also referred to as hemotoxic or hematotoxic, these substances destroy red blood cells, disrupt clotting and/or cause organ degeneration and generalize tissue damage. They tend to be very painful as well as generally destructive and as a result can often be found in venoms - in some cases these can kill with similar frightening speed to neurotoxins!! Nephrotoxic - damages the kidneys through a wide variety of mechanisms both direct and indirect. As mentioned above this can be simply the result of destruction of other cells causing a buildup of cellular breakdown products in the bloodstream in levels too high for the kidneys to cope with. There are other forms of toxicity including such things as ototoxicity (toxic to the ear/hearing systems) and infamously mutagens which cause genetic damage. These however are probably beyond the immediate scope of our look into the world of toxins, at least for now. Rule 5 - there are two more forms of classification/groupings that we'll discuss but these WILL have immediate relevance. You can divide toxins, like any other chemical, into organic and inorganic substances. An organic substance is one containing Carbon - Hydrogen bonds, an inorganic substance is one that does not. While this may seem abstract it's relevant because C-H bonds allow immense complexity, far beyond that displayed in the inorganic world. This is because C-H bonds can form long chains of carbon that can have other functional groups attached. Living chemistry is, as we far as we know, dependent on this complexity that can only come from carbon chemistry. It should be no suprise toxins are organic chemicals - inorganic chemicals may well be toxicants but living things tend to rely on organic chemicals for poisons and venoms. The second, and more important, classification is one I'd like to talk a fair bit more about. Chemicals can be soluble in polar (basically meaning that eletrical charge on the molecule is unbalanced resulting in negative and positively charged ends) or non-polar (balanced charge means no poles of charge present) solvents. Like disolves like is one way of putting it since polar molecules dissolve in polar solvents (water being the most important one) while non-polar substances tend to dissolve in non-polar solvents (such as ethanol or more importantly lipids such as fats and oils). This has profound consequences for toxicity of a substance. It's easy to envision this distinction - imagine you're making a salad dressing with olive oil and water base. This will form an emulsification, a mixture of two substances that can't be blended together permanently. When left to settle they'll form a layer of the less dense oil on top of the water because they cannot be blended. Now if you add things to this salad dressing like salt or sugar, these will dissolve almost entirely into the water alone. Alternatively if you add things like vanilla or mint extract they'll dissolve into the oil without almost any trace of them in the water component. If we take our salad dressing and shake it after adding whatever components to it then these differently soluble components will be mixed almost entirely into the oil or the water - or they won't dissolve at all and be found sitting at the bottom of the container. So based on these two distinctions we can divide up every chemical into one of five categories - water soluble organic, water soluble inorganic, lipid soluble ogranic, lipid soluble inorganic and insoluble (organic or inorganic). An insoluble compound is basically toxicologically inert - if it can't dissolve into water or lipids then it cannot be absorbed into the body and cannot reach target sites to cause a toxic effect. This leaves 4 relevant categories of which another can be crossed out - lipid soluble inorganics are basically in practice not toxicologically interesting. So we're down to three possible categories of toxic substance of which we'll primarily be exploring the two organic types. To look at why the dichotomy between lipid and water solubility is so important we need to first take a close look at where the chemicals literally bump up against biology: the cell membrane. Stoner Sloth fucked around with this message at 13:47 on Apr 30, 2019
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Apr 30, 2019 13:44
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Solubility and the Cell Membrane Before we look at the absorbtion of toxic compounds from the environment via a variety of means, let's take a moment to consider the nature of individual cells. Ask someone to draw a picture of a cell in only a couple of seconds and without fail they'll draw a closed circle - in essence they are drawing the cell membrane. While the nucleus, mitochondria, golgi aparatus and other cell organelles might be vitally important to the life of a cell, it is the cell membrane that separates the inside from the external world - essentially defining what is the cell and what isn't. The cell membrane is composed of a double layer of phospholipids (lipids that contain a phosphate group shockingly enough!) that are arranged in such a manner that, in the outer layer, the phospholipids polar heads all point outwards from the cell and their large, non-polar tails all point back in towareds the cytoplasm (interior of the cell). The innner layer is the reverse of this - polar heads pointing into the cytoplasm and non-polar tails pointing outwards to form a double layer of non-polar tails in the middle of and separating two polar layers. The polar heads are critical here - within each of them lies a negative and a positively charged region. Since like charges repel and opposite charges attract this in effect forms an impenetrable barrier to diffusion for any charged inorganic or organic ion. This relative impenatrability creates a problem however; the inner cyctoplasm cannot wall itself off from vital water soluble compounds entirely. Many essential inorganic ions such as calcium, sodium or chloride as well as organic polar substances such as glucose cannot readily migrate through the cell membrane. So how do they get in? Well with the help of proteins, a wide variety of which stud the lipid bilayer. These proteins act as pores or carriers that can ferry polar molecules across the cell membrane. The more active a cell or organelle inclosed behind a biological membrane, the more proteins are found studding the membrane. For a toxic response to occur, the chemical in question needs to reach it's target - this is sometimes a receptor, other times a protein or nuclear DNA, but in general the target is either within the cell, embdedded within the cell membrane, or is the cell membrane (lipid bilayer) itself. As such, for many toxic chemicals the route to biological activity has to cross the cell membrane and this is where solubility of the chemical reenters the picture. Water soluble compounds obviously can't readily cross the lipid bilayer unless they have help in the form of a protein gate, pore or carrier. As such, water soluble compounds are controllable and many - such as the inorganic ions sodium, chloride, potassium and calcium - are maintained in strict concentrations within the cell. Interestingly however while this system has evolved so that these ions can be closley regulated, the system is not so fine tuned as to guarantee that mistakes do not occur. Ion channels or gates might allow for the precise regulation of inorganic and organic ions but also often allow for the inappropriate uptake of toxic ions from the blood into the cell. Transporters for the micronuterients copper and zinc, for example, cannot differentiate between these essential metal ions and other, more insidious metals such as cadmium, silver and mercury all of which are toxic. While water soluble toxic chemicals engage in a game of mistaken idenity, being allowed into the cell via channels whose function is to allow the transport of necessary chemicals, toxic lipid-soluble compounds are engaged in a very different process. These chemicals simply do not see the lipid barrier as a boundary at all and as such can move around within an organism without constraint or regulation. They basically are able to entirely avoid the carefully evolved cellular regulation and organization inherent within living cells as one of their defining features. Now since solubility is clearly such an important thing in understanding the absorbtion and ultimate fate of molecules within the body, we need a way to quantify it. If we go back to our earlier salad dressing metaphor then all we'd need to do to measure the solubility of an unknown added component is to shake the oil and water mixture and then measure the concentration of our mystery compound in the water vs the oil. Expermentally the oil we use isn't delicious olive oil of course but rather octanol and the resulting numeric determination is referred to as the octanol:water partition coefficient or Kow. If we think about different molecules ranging from highly water soluble, such as table salt, and highly lipid soluble, such as cholesterol, how different are there Kow values? It turns out that they are very, very different indeed. It's not unusual for a water soluble compound to be a million times more soluble in water than in octanol, nor is the reverse uncommon either. In fact the numbers are so large that logarithmic expression becomes necessary - the Kow of a lipid soluble substance may be 1,000,000 (106) or expressed as log Kow = 6. The difference between solubility of a lipid and water soluble compounds may exceed 1012, such that the lipid soluble compound is more than a trillion times more soluble into the lipid bilayer than the water soluble compound is relative to that same bilayer. So, to summarize, a chemical that is water-soluble is, by definition, not lipid-soluble and as such will not be able to dissolve into the membrane. As such its rate of diffusion across the barrier will be minimal. Without the aid of carrier proteins, the uptake of chemical will be minimal - as will it's ultimate toxicity. In contrast to this, a compound that is soluble in oil or fat will easily be absorbed across the lipid bilayer and as such will have a greater potential for eliciting toxic action. With a high log Kow a substance will readily solubilize into the lipiid bilayer and it's rate of diffusion into cells will be much higher. This is perhaps the fundamental dichotomy within toxicology - the behaviour of virtually every toxic compound is dictated by the fundamental split betwen water and lipid solubility. It influences absorbtion from the environment, delivery in the blood, diffusion into target tissues, excretion from the target tissue, metabolism, sequestration and whole-body elimination. All of these properties are influenced more by solubility rather than size or shape of the molecule. e: Just for simplicity sake - we'll call this Rule 6 - the nature of a chemical's effect on an organism is heavily dependent on it's polar vs non-polar solubility. Stoner Sloth fucked around with this message at 15:02 on Apr 30, 2019
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Apr 30, 2019 14:48
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So uh yeah, hope that all made sense and wasn't too dry. The toxicology stuff is a little abstract sometimes and hard to find illustrations for. Got another decent sized bit to come and then I'll put things up to another vote to see where we head from there - thank you for reading and hope you're finding it interesting friends e: and as always happy to answer questions too!!
Stoner Sloth fucked around with this message at 17:15 on Apr 30, 2019
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Apr 30, 2019 17:12
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it's pretty interesting to me, you're bringing back things from long-ago classes. there is this old trope about building up immunity to poisons by taking small doeses and gradually increasing them, e.g. "iocane" in princess bride. I imagine this works okay for some toxins and doesn't work at all for others (e.g. people subtly poisoning others with heavy metals by giving trace amounts over time). do the distinctions you're drawing play into whether tolerances can be increased for various substances?
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Apr 30, 2019 17:26
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just wanted to add that amanitas can be v beautiful  good postings imo |
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Apr 30, 2019 17:35
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Manifisto posted:it's pretty interesting to me, you're bringing back things from long-ago classes. there is this old trope about building up immunity to poisons by taking small doeses and gradually increasing them, e.g. "iocane" in princess bride. I imagine this works okay for some toxins and doesn't work at all for others (e.g. people subtly poisoning others with heavy metals by giving trace amounts over time). do the distinctions you're drawing play into whether tolerances can be increased for various substances? This is an excellent question - short answer is yes, they do. Longer answer will have to wait for another post but I promise you will get as complete an answer as I can adequately give on this but we've got a ways to go before we get there. "Iocane" is obviously fictional but it does, as presented, bare a decent similarity to tetrodotoxin (TTX) which I'm guessing inspired it and can certainly be found in Australia (and many other places - some newts in north america I believe make use of it). But yeah - in very basic terms it effects things like how the body tries to excrete stuff and also what gets stored in the body over longer periods - heavy metal poisoning or pesticide poisoning being excellent examples of substances excreted only slowly. The body has quite a few tricks up its sleeve but in the case of lipid soluble stuff which get stored long term (water soluble stuff obviously being pretty easy to excrete through urine) what is happening is that the body is trying to chemically alter the substance in question into a water soluble form. This can backfire too as we'll eventually see - sometimes this can increase the toxicity of a substance. The body can also produce specific anti-bodies which can breakdown or disable a chemical, try to reduce the number of target receptors in some cases or try to reduce the effectiveness of carrier proteins for water soluble toxins. It gets even weirder - there is are people out there who have formed a subculture of trying to immunize themselves from snake venoms - for reasons varying from the pseudo-scientific to the mystical to simply believing it will keep them safe from snake bites to protect them from their hobby/profession of handling snakes. This is extremely dangerous and I would not recommend it to anyone for a number of reasons, starting with the fact that many of these venoms are so toxic that the slightest miscalculation could kill you - also the treatment for such miscalculations could kill you to. In principle though building resistance is possible in many cases, particularly with venoms, hell it's the basic principle of why we use large animals to produce anti-venoms. In practice any resistance built up may be useless in the face of the overwhelming toxicity of the venom in question - what use is it in resisting 1/100th the bite of a coastal taipan? Stoner Sloth fucked around with this message at 18:04 on Apr 30, 2019
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Apr 30, 2019 17:42
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Took me a while to catch up here, but I really like thisw details! Since I have some academical history with biology this stuff naturally attracts me and reading how this stuff works in detail is so fascinating. brb injecting myself tons of snake venom to prepare for my next australia visit
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May 1, 2019 20:48
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