Great video, quite detailed surprisingly, except for at 11:12 - the mechanism of one-hit vulnerability of TP53 is NOT a 'not fully understood mechanism'. It is due to hetero-oligomerization of the wild type p53 protein with the mutant p53 protein that results in the dominant negative effect of a single mutation in this tumour suppressor gene. I understand it might be difficult to include this aspect in the video but it is a well known phenomenon, so saying otherwise seems misleading. References: Lane DP. p53, guardian of the genome. Nature. 1992;358(6381):15-16. doi:10.1038/358015a0. Brosh R, Rotter V. When mutants gain new powers: News from the mutant p53 field. Nat Rev Cancer. 2009;9(10):701-713. doi:10.1038/nrc2693
One thing I don't get though, is why at 12:38 he pushes away meat... That doesn't really fly with me as being particularly cancerous. I saw my mother get permanent iron deficiency because she gave up eating meat. Now she sometimes needs an iron infused shot. What should've been on his plate was something loaded with chemicals like fried fastfood, not some pristine piece of lean steak.
@@Yezpahr maybe it was cured pork or even just overly red meat? The salts used for curing pork are really bad for us. In most of Europe there's now labeling on pork products that show the curing process hasn't made use of these bad salts.
Your body is actually pretty good at finding and eliminating cancer. It's the ones that your body doesn't detect, that spread fast enough to be harmful but slow enough to not burn out, that jump between different types of cells, that are dangerous. And yet, all these minuscule on minuscule on minuscule chances cancel out with the number of cells just right so that it's on a human scale.
@@jtgd It's not your cell if it's aberrant it's your immunity that is too much sickened for not being able to understand the difference between them.. Or to restore a non Aberrant Genetical patterns..
@@antoniopacelli ok wtf man stop spewing bs. You try to sound smart but you aren’t. You really just googled big words and shoved them in there. First guy is right.
Great video! But using the paper at 1:52 to claim that we go from 500 mutations per cell as an infant to 3000 per cell as an adult is confounded by the fact that they only looked at B cells. B cells are unique immune cells because they are able to select themselves to detect antigen by mutagenizing themselves, and the B cell receptor locus goes through 10k to 100k times more mutation than normal...so it's probably not the best cell type to use to make this claim.
How can a simple educational channel be soooo good!! This is mindblowingly unboring! I just love the animantions! And the topics will always keep me hooked. This channel deserves 1 million subs :)
all those tiny molecular robots grinding a way day after day just so I can watch this video and not have cancer. thanks tiny robots :) awesome video as always!
Man you are one of the channels I click immediately no matter what the upload is about! Your explanatory and animation skills are off the charts and I can listen to you all day long! you deserve a billion subscribers, everyone should go through at least a couple of your vids, the content is so rich and diverse!
I learned about the P53 gene from Metal Gear Solid. In the game, if you make Snake smoke, he'll get a call warning him about cancer while mentioning the gene.
Cancer took my beloved Boston Terrier away from me too soon. He was only 9 years old and we had to put him down because he had lymphoma and could barely breathe. He couldn't sleep because if he laid down, his chest cavity was too full of tumours to get a full breath so he had to sit up all the time. Poor lil' guy. He suffered too much, but he was still such a happy guy despite never sleeping. We gave him a nice last day with steak and presents and he was euthanized in front of our fireplace and Christmas tree. He's now buried in the backyard woods in an aluminum truck tool box. He's at peace now, but I still feel intense guilt for not being able to save him. Chemo would have been his only option but the percentage of survival was so low that it would've just caused him extra suffering during his last few weeks with us. But part of me wishes I had tried. It was just snuck up on me so suddenly but when I think back, the warning signs were there. Like he used to love going into pet stores with me because he'd go and pick a toy out himself and we'd buy it. The last few times I went in with him, he headed over to the pet medicine section, almost trying to tell me that he needed something that wasn't toys. But the biggest warning signs that there was something wrong was that he stopped wanting to go on walks. He'd always made funny breathing noises because he was a Boston Terrier and brachial (short-snouted) so when he was making extra breathing noises, it didn't register. It wasn't until the desire to go on walks (which he loved like all dogs) stopped completely that made me take him to the vet. Once I told the vet that, she ordered X-rays. I remember the vet coming back and telling me "We found something" and then a bunch of science talk, then telling me that he had only a few weeks to live and we need to think about euthanizing because it'd be cruel to make him suffer longer than he has to. This was on Thanksgiving Day. Well he didn't make it to Christmas, sadly. He really did only last a few weeks. We tried to pump him full of codeine and other medications to keep him comfortable, but it was just hard to deal with knowing he'd be on his way out. If you have to euthanize your dog, I highly recommend you do a home visit from your regular vet. You do not want your dog to be scared at the final moment, so hold back your tears until later, which is easier said than done. I had to lie to my dog and tell him that the vet was coming to fix all his problems, and I knew he understood a bit of what I was saying because he understood the word "fix" to mean solving his ailments throughout the years. He might've thought something was up in the final weeks because we cried a lot more and were taking more pictures than normal. But I know that final day was a good one for him. I still feel awful about lying to him. I have adopted another dog now--a rescue. She was a puppy just 8 weeks old when I rescued her from one of the many shelters in my city. There are SO many puppies needing rescuing. PLEASE do not go and buy a specialty breed because you want a chic, specific breed. There are just so many dogs that need saving out there. And if not you, then some lowlife who enjoys dog fights comes and "rescues" them and they end up having such a terrible life. No love. No toys. Only abuse. Please rescue a dog. Even if they're mutts, even if they're older. They will love you all the same. I can't stress just how many there are. SO many. And little tiny puppies. They're just abandoned. They have no idea what's going on in life and are stuck in crates and the shelters are SO loud with barking. I at least rescued one. Her name is Rory and she's a handful being a puppy that was abandoned from her mother, but the love she gives makes up for all the housetraining and other training stresses associated with puppy ownership. It's always worth it if you remember where the rescue came from and what circumstance might have awaited them had you not intervened.
I really love the style and content of your work. Please don't stop if you can comfortably keep it up, I'm sure the rest of your audience feels exactly the same.
9:27 Another unexpected Fermi Paradox, life is inherently subject to mutation which is probably what kickstarted life in the first place, but it could have just as easily killed itself off before it mutated a mutation that unmutates mutated mutations.
I love these videos. Your clear and concise explanations paired with the very fun yet amazingly detailed animations make these videos a pleasure to watch. I can’t wait until the next one!
Absolutely breathtaking Your videos are the best on RU-vid The attention to detail, the lack of watering down, your examples, everything makes these videos beautiful
Brilliant, as I have come to expect from you. Highly impressive. One question: The bit about "only a little over 8% of our DNA has useful information" ( 03:10 ish). I thought that was a myth? Or at least a miscommunication, as in "only bits get expressed in each cell, so overall only a small amount (~8%) of the total DNA in your body is actually expressed -> useful? I know that evolution is far, far from being a perfectionist, but are we really carrying that much baggage? Best regards!
Great question. Basically the old much higher estimate was about protein activity on the DNA. Here's a quote "[The ENCODE project] counted all pieces of DNA on which some protein activity occurred, whether or not that activity was useful to the cell," Ponting told Live Science. "The difficulty is that protein activity occurs on all DNA, such as when it is replicated just before cell division." A better method is just comparing our DNA with similar species and observing the similarities. Essential DNA won't change much since our last common ancestor but we expect junk to freely mutate without much recourse. That method yields the ~8% that's important figure.
@Yooless ENCODE noted that 8% of our DNA are for functionally for proteins, which counts the cDNA (1.8%), and proximal transcription(cis)-regulation sequences, but it doesn't include distal (trans)-regulation sequences and mechanisms for DNA expression (e.g., RITS via miRNA, lncRNA) as well as regulation sequences for what is known as jumping genes in our genome. Jumping genes are sequences that can induce translocation and mutations to other regions in the human genomes and in some cases cause cancer. Arguably, the 8% better represents our knowledge about sequences that has a direct downstream effect on gene expression, but doesn't account the numberous upstream regulators. Indeed, when ENCODE reaccount for these sequences in 2012, 80% human genome seemed to be biochemically active and might therefore be functional/have molecular effects on a given cell. (www.pnas.org/content/111/17/6131)
@@jerrywang8945 Thank you for the response, and this interesting link :) I'm not sure if I understand the "upstream/downstream" part of your comment though. Could you explain this further? Reading through the publication you linked, I am surprised to find no mention of a statistical approach to finding out which parts of the genome are "functional". Since it was my first idea, I assume that there's a reason they are not doing it, but I don't see it. My idea would be to compare genomes of different species at varying distance from each other, genetically speaking. I believe that certain test organisms like mice, fungi, tube worms, etc. are well sequenced. Commonalities between these should indicate either convergent "junk", or relevant sequences. The distance from us in relation to the likelihood of occurrence per sequence could also be insightful, especially if one has more understanding of some of the sequences in question, allowing further inference. This could at least help to constrain the possibility space they are working with. But perhaps this is so commonly in use that they didn't consider mentioning it^^ Or do you see a problem I missed? Have a great day ;)
@@EliasMheart So when I talk about downstream gene regulations, we are talking about the protein mechanisms that regulate initiation/continuation of transcription (so promotors, transcription factors, enhancers, silencers, etc.). Downstream regulations tend to be restricted to a limited number of genes and protein products and occur in all forms of life Further upstream gene regulation utilize non-coding regions that regulate can many genes simultaneously, and generally invoke RITS mechanism and/or epigenetic histone-coiling of whole regions of DNA. It only occurs in linear-DNA organisms, so eukaryotes and archaea, but not prokaryotes (they have circular-DNA), contrasting that of downstream regulation. For instance, X-silencing is controlled by upstream gene regulation mechanisms via Xist lncDNA Also @But Why? Comparative genomics to look for functional genes is a good approach, but limitation includes that fact that upstream gene regulation mechanism also tend to be non-specific, so non-conservation doesn't necessarily imply that the section of DNA is useless. To quote the paper below, "More generally, alignment methods are not well suited to capture substitutions that preserve function, such as compensatory changes preserving RNA structure, affinity-preserving substitutions within regulatory motifs, or mutations whose effect is buffered by redundancy or epistatic effects. Thus, absence of conservation cannot be interpreted as evidence for the lack of function." www.pnas.org/content/111/17/6131
Just found your channel and very happy I did! I'm just binge watching all your videos right now and really enjoying it. Thank you keep up the exceptional work!
You should have millions of subscribers. Keep up the good work because "But Why?" Is one of the most important channels on RU-vid. The animations make understanding the subject so much easier.
2:35 it is such a mind blowing and humbling realisation that such a remarkable cellular machine appeared in nature on its own just through nature processes although not 100% accurate. You always wish had there been some more "error correction" mechanisms, may be in future there could be a way that human intelligence could improve the cellular machinery but for now I will suggest lifestyle modification like fasting which will trigger autophagy in your cells which have any DNA damage preventing chances of cancer. Also try to avoid processed meat
That relocation mutation thing feels like it'd happen more if you shake the cell during it happening. And oh boy it feels like misreprecenting the scales at which it happens at but i cannot not feel like it would. Life pro tip. When you feel your cells doing a division, sit really still so it happens correctly...
It makes sense TP 53 is one hit vulnerable: its activity is entirely determined by the concentration of the ATM, that means that if one half of the synthesized TP 53 proteins is nonfunctional, you'll need twice the concentration of ATM to reach the threshold for apoptosis, and ATM probably never reaches twice that concentration because it didn't evolve to be effective at such wide ranges of concentrations, so the regulatory sequences won't ever allow such accelerated production.
What a great video! Thank you so much for your hard work. There are definitely many people that your videos helped and inspired, like myself. Please keep making such wholesome videos!
There are even the cellular elimination mechanism of cancer (e.g., cytotoxic immune cells) even after the molecular mechanism in a given cell fails. Indeed, chances are there are cancerous cells in your body right now. But you will never hear from them simply because they will be removed swiftly automatically and without issue. Even when some are not removed, most are benign cancers. Only when all of the above is surpassed can a cell line become dangerous at the organ and human scale.
Could a treatment consist in making the cells more likely to kill themselves when they detect mutations rather than try to fix themselves? I suppose Its not as simple as that but surely some medicine can put to sleep the medium fixer proteins or make the killer proteins more agresive/abundant/whatever. Other issue could be more cell division which in term leads to more mutations, but It wouldnt be hard to calculate if this treatment is beneficial or not in the net amount of mutations. The base idea is that in nature is useful to try to rescue every cell because we need to save up resources but now thats not an issue. There are probably many systems that take place in our bodies with the idea of saving resources for the sort term at the expenses of long term performance.
Wow, fascinating. The amazing complexity of these analogue molecules almost make me believe creationism. Alas no, science is my true religion. So please tell us some of the less obvious nasty habits we have that speed up the mutations. Great channel. Subscribed!
In the outro you say "Cut down on those guilty pleasures" while showing a steak. Is eating a steak correlated with DNA mutations? I'm not sure how this relates to the topic, otherwise a great insightful and educational video! Thanks :)
Did you really showed an mRNA at 4:39 to 4:43 double stranded!!!! plus polymerases don't do protein synthesis, the entire animation between 4:39 to 4:43 is wrong, this is a glaring mistake in this video. I don't think it's rectifiable now. But otherwise the entire video is well made and highly informative. I am giving this video a like nonetheless. [DiowE]
The right transcription of DNA by Polimerase, the right Homeostatic balance, the Perfect Innate Immunity bringing to a perfect DNA's damage response, and Symbiosis among every body's cells.. This is something that can be applied to everyone.. but not with a Warfare tipe of Healthcare like nowadays public standards.. [Cannabinoids Receptors activations from Natural Compouds and consequential increase in CBr Expression would naturally leading to at least 2 of this predetermined conditions]
@@iseriver3982 Conspiracy theorists talking about Conspiracies to others putatively chosen conspirators... A Classic. Read again.. you might have missed something. I stated that it's applicable not that is provided nor that isn't forbidden in the majority of the world. If Real Science it's banned by people like you all that is left (as you yourself are making noticing) It's our nowadays HeLacare standards.. You sad just because you fighting me instead to fighting the problem.. Let do like this I add a specific Information that might gonna make you understand better.
"This is bad news bears..." 3:30 I had to replay that a couple times trying to figure out WTF you were talking about. Try to keep the cuteness to a minimum.
“Loci” is pronounced with an S sound. The 92% of dna that supposedly does nothing does a lot of something. There might not be any “junk dna”, but rather it is non protein coding epigenetic control dna. So those mutations might be very significant.
