STEMology s1e38

[00:00:00] Sophie: Welcome to episode 38 of stem ology.

[00:00:03] David: This is the grand finale for 2021.

[00:00:06] Sophie: STEMology is a podcast sharing some of the interesting fun, and sometimes just patently bizarre news in science, technology, engineering, or maths.

[00:00:15] David: Your hosts are Dr. Sophie Callabretto and Dr. David Farmer.

[00:00:19] Sophie: This is the final episode for 2021

[00:00:22] David: And in today’s episode, we’ll be chatting about Snap tacular fingers, necro-fungal-philia,

[00:00:28] Sophie: cerebellar belly and little baby, baby embryo.

Snaptacular fingers

[00:00:34] Sophie: Dave, can I start this story by reading you maybe my favorite line in an abstract that I’ve ever seen before? And this is the first line in the abstract. Are you ready?

[00:00:45] David: yeah. Go for it.

[00:00:46] Sophie: The snap of a finger has been used as a form of communication and music for millennia across human cultures. However, a systematic analysis of the dynamics of this rapid motion has yet to be performed.[00:01:00]

[00:01:00] Uh oh

[00:01:01] David: I know. Oh, No

[00:01:03] Sophie: No one has looked at the dynamics of, and so this is snapping fingers. I would say I was going to ask you, Dave, it’s clicking fingers to me. In Scotland, you click or do you snap your fingers?

[00:01:14] David: click your fingers. I don’t know. I think, I don’t know. Cause I’m a bastard child of the Americas as well.

[00:01:18] Sophie: Oh, you are

[00:01:19] David: they would say snapping. Um, so I’m not sure maybe it is clicking fingers in Scotland. I’m not sure.

[00:01:25] Sophie: But yeah. So finally someone has sorted out the physics of snapping your fingers. Fantastic.

[00:01:31] David: Yes. And specifically they figured that how friction plays a critical role in generating the sound and the fact that It happens very, very, very quickly

[00:01:41] Sophie: It happens very, very, very quickly also seems to be inspired by the film Avengers Infinity War in a way

[00:01:49] David: I loved.

[00:01:50] Sophie: really troubling.

[00:01:52] David: I love it in this press release. They spend not half the time, like not an equal amount of time, but maybe 10 to 20% of the press

[00:01:59] Sophie: [00:02:00] I would say 30, 30 plus Dave, maybe 30 to 40, like there is a, a huge amount of time apparently. So we’ve got some issues here. So as you said, Dave, we’ve got what causes the snapping sound also like we’ve looked at how fast this is, but apparently this particular group earlier on has developed a general framework for explaining the kind of surprisingly powerful and ultra fast motions of like observed in living organisms.

[00:02:23] And they felt like that framework seemed to naturally apply to snapping your fingers. Cause I guess what you do is I’m going to snap. I’m going to snap old episode is going to be.

[00:02:32] David: Yeah. It’s going to be.

[00:02:33] Sophie: Irritating, but yeah, so like you, you’re very quickly accelerating your little finger. It’s hitting your other fingers, making a snap sound.

[00:02:40] But the problem is Dave, in Avengers Infinity War. I have not seen any of the Avengers films. I presume this person is called Thanos or.

[00:02:49] David: Thanos.

[00:02:49] Sophie: Thanos.. Our villainous character apparently seeks to obtain six special stones and places them into his metal gauntlet. After collecting [00:03:00] them all, he snaps his fingers and triggers that universe wide consequences.

[00:03:03] The issue is they’ve said, what are you even be able to snap his fingers wearing the metal gauntlet?

[00:03:08] David: And there’s actually a, did you watch the little video? There was a little video with the article.

[00:03:12] Sophie: No, I didn’t.

[00:03:13] David: where the students are, that it’s a, student who developed the, who led the study, which is really, really cool. And apparently they went to see this movie of a Friday night and then they went and were just chatting about it.

[00:03:22] And they got into this heated argument about whether Thanos would actually be able to snap his fingers, where he wearing a metal gauntlet. And that led to this just really beautiful curiosity, inspired piece of work. Where they’ve worked at exactly what it takes to create a snapping of the finger. So as we’ve said, it involves the movement of the fingie against the other fingie and if you change the amount of friction between the fingers, that seems to have a big effect on whether or not you can snap. So they explored this by looking at, what happened if you cover the fingers with different materials and the ones that I came across were rubber metal and loop

[00:03:59] Sophie: Yep. That’s [00:04:00] basically it

[00:04:01] everything for a fun Friday night. No,

[00:04:03] David: There’s actually in the video, there’s a video of them snapping their fingers while the thingies have got live in the loop, kind of sprays over the wrist. And it’s very,

[00:04:10] I dunno how I

[00:04:10] Sophie: Is it visceral or is it very

[00:04:12] David: It was visceral?

[00:04:13] It was very visceral. and so they found with the metallic symbols, which was to simulate the effects of trying to snap with a metal gauntlet,

[00:04:22] you couldn’t produce a snap. And they said, this is because of the contact. Area between the fingers is different, which doesn’t allow you to load force in the same way as your nice supple load bearing fingy pads do.

[00:04:35] Sophie: Yeah, which makes sense. Cause if you think about it, it’s like, you know, using a thin ball, it’s kind of like, just like touching the tips of your fingers together. But like when you actually snap your fingers, you’re pushing, you know, your thumb and your middle finger against each other, like pretty hard and you are creating like a much larger surface area.

[00:04:51] but yeah. What they did is, as you said, they had, so we had five snaps from three different people for each of the surfaces you’ve just described.[00:05:00] and then what I have to myself here is a note that says Gollum tracking, but it’s like, you know, when, uh, they turned Andy Sirkes into Gollum and they did the little dots all over him.

[00:05:09] That was my reminder. Yes. So they basically did something very similar. So they put these like, sort of quite bright dots in various places on the hands. And so it meant that then when they looked at it with a high-speed camera, they could, you know, work out accelerations and all these different kinds of things and they found, so yeah, in terms of speed, like this is where it gets really crazy.

[00:05:25] So say we’ve got bare fingers and our ordinary snap, apparently the maximum rotational velocity. Uh, 7,800 degrees per second. Right. Which is insane, but that is not faster than the rotational velocity of a baseball player who’s pitching. Right? So the velocity per for snapping velocities, and not faster than the fastest known rotational motion of humans, but the acceleration is. So apparently the rotational accelerations, you get [00:06:00] 1.6 million degrees per second squared. And then apparently that’s three times faster than the rotational acceleration of a professional baseball pitchers arm, which is like 1.6 million degrees per second square is nuts,

[00:06:17] David: and just to put that in perspective, if you don’t follow baseball or if that seems a bit abstract to you, cause this seems a bit abstract to me, the fastest ever baseball pitch was 170 kilometers/hour So the result of that acceleration is to remove something, the mass of a baseball, the massive size of a baseball, 170 kilometers per hour.

[00:06:35] And this acceleration is three times faster than that acceleration

[00:06:39] Sophie: Yeah. And I think, yeah, and I think you know, part of the thing is that, so a finger snap occurs in only seven milliseconds, which is more than 20 times faster than the blink of the eye, which takes more than 150 milliseconds. So I think that’s where obviously you’re getting a lot of that fast

[00:06:54] acceleration because it’s happening over a, such a short period of time. and so they [00:07:00] did that where they had got everyone to snap and they looked at these things and they also came up with this mathematical model and I’ve

[00:07:06] David: Tell me about the model because the models are always wasted on me and then you always illuminate them for me.

[00:07:11] Sophie: Well, let’s see, I’m going to illuminate and maybe criticize some of our pattern matching,

[00:07:15] David: Alrighty. Let’s go.

[00:07:16] Sophie: so the way that they modeled it was really great. So they’ve looked at this, particular finger snapping is what they’ve called a latch mediated spring actuated system. So basically think of your middle finger as the, the spring.

[00:07:29] Your middle finger is the spring. So like you can

[00:07:31] David: Well, I use my ring finger, but I will continue to think of it as this spring.

[00:07:35] Sophie: Oh, wow. People use different fingers. I didn’t even think about that. Okay. So you, your finger that you’re thrusting into the Palm of your hand, that is the that’s the spring that’s spring loaded, that accelerates super fast. And so if you move your thumb out of the way, what you just doing is hitting yourself in the hand with one of your fingers, right?

[00:07:52] But if you bring your thumb in that’s the latch. So the spring activation, basically your spring is being mediated by [00:08:00] the latch. So if you were to put your thumb in the wave, your finger and not move it out of the way, you really just pressing then your thumb and your finger really hard together. But then if you move your thumb away, like a lap, like really quickly as in like a latch has been deployed, then that finger is going to snap down and hit you in the hand.

[00:08:16] So what they’ve really done is they’ve basically monitored as a spring. So. You know, as anyone would physically model a spring, you’ve got like a spring, constant, all these things, and then they’ve got the little latch, which is movable. And so that’s what they’ve done is then yeah. they created this model, which physically looks good.

[00:08:31] And then they’ve, I think they just use MATLAB to solve it. So that’s very like simple. I couldn’t actually find the model. I went into the notes and they gave me all their MATLAB code, which I didn’t run.

[00:08:39] David: Yeah, that seems reasonable.

[00:08:41] Sophie: and then they said that they got good qualitative agreement between that and the data, but what they did is, as I

[00:08:47] David: That means, they looked at it and went, oh, that looks pretty good.

[00:08:50] Sophie: And if you look at, and I was like, I was looking at the paper where they compared the data and there was from what I can tell from one graph where, you know, as we said, they had, was it five steps from [00:09:00] three different people. And then they measured all those times and speeds and all those things and they enforces and everything.

[00:09:06] And they kind of looked at that one as like one data point with like an arrow. For like each, you know, basically person material, and then they just plotted those. So they don’t have that many data points. Cause we’ve only had a few different materials and a few different people. So basically what you have is this model that they’ve done and they’ve got like five data points on it and I’m going like disagree. Great. But the thing that bothers me is that we’ve got this, like apparently there’s these two different phases. So one of them where you kind of unleashing and then like it’s settling linked down to an equilibrium. So you kind of got to curve up and then a flatbed and they just put like one dot on the bottom of the curve at zero and then one dot on the flat.

[00:09:44] But I just like, there’s a lot of, I think we’re pushing it to say that we get good quantitative agreement, but I would say that the model that they’ve used books solid. I think, I just think we may be needed to in the discussion section comment more about like, this is really data fitting [00:10:00] and you’ve modeled this way and it looks kind of okay like that, but yeah, that was my main issue.

[00:10:05] David: The The thing, that would have really rammed it home for me. So they say that,

[00:10:07] like, so the metal doesn’t work because you’re reducing the amount of friction and the loop doesn’t work. So you’re reducing the amount of friction. And then they go on to say that if you cover the fingies with rubber, that doesn’t work either because the friction is so high that you’re dissipating the stored energy as

[00:10:23] Sophie: instead

[00:10:23] David: than

[00:10:24] Sophie: stuck, right?

[00:10:25] David: Speed and noise. So what would have been really appealing would be to cover the thingies and something that has a similar friction coefficient as skin and show that you still get a snap that would have really knocked it out of the park for me.

[00:10:37] Sophie: Yeah, I agree. Cause at the end it was funny. Cause in the, um, the press release, they say that surprisingly increasing the friction by covering the fingertips with rubber, like also didn’t result in a snap snap. And I was like, I don’t know if that’s surprising, like that’s quite intuitive. Like if I put rubber on my fingers, Like I’m going to rub.

[00:10:55] Yeah. I guess I’m thinking of like a rubber thimble. And I was like, if I put a rubber thimble on my finger and [00:11:00] thumb, there’s no way I can click my fingers. But yeah. So basically what they’ve discovered is, you know, we’ve sort of got this sweet spot in the middle where, you know, the friction is, there’s not too much, there’s not too little.

[00:11:11] Your surface area is nice. but also the, I think the really surprising thing that comes out of this as just those rotational accelerations, like they are just absolutely insane.

[00:11:23] David: Yeah,

[00:11:23] Sophie: it’s all in your little fingers.

[00:11:25] David: your little fingers and just apologies to the reader. We kind of oscillated between two different nomenclatures there. We used fingers and fingies. Those both mean the same thing. want to

[00:11:34] Sophie: clarify.

[00:11:34] They’re in an equivalence class for the purpose of this podcast and that, that story. But yeah, so, and apparently they’ve said that this will be good because, you know, we’re, getting into a world where our prostheses are getting more and more complicated. And now that we sort of understand this mechanism, wouldn’t it be good to, to make things that actually can make

[00:11:51] fingers hands that can replicate what a human can do. But then they also said that the, their model can help understand how other animals such as [00:12:00] termites and ants, snap, their mandibles, which I like.

[00:12:03] David: Nice. And I also liked rationally bio inspired actuators for engineering applications. That’s just a fantastic bit of jargony sentence rationally. Bio-inspired So, looking at something how it works, how a piece of biology works and then applying it to something cool in engineering.

[00:12:19] Sophie: Yeah. So,

[00:12:19] David: yeah, it was

[00:12:20] a lot of good, a lot of

[00:12:21] Sophie: Avengers, infinity. Well, yeah, I really enjoyed it, but I loved that that was the inspiration. Just people having an argument about whether or not you could snap your pens fingers, wearing a metal gauntlet. And the answer is no. Stop lying to us Thanos..

Necro-fungal-philia

[00:12:36] Sophie: Okay, this is my favorite story that we’ve ever had ever on the history of STEMology ever, ever,

[00:12:47] David: week.

[00:12:48] Sophie: not even though.

[00:12:49] Cause I was thinking, I know I say every single week, but I’m going to say the most I can think of another one. I did really enjoy the fisting hiccups draw that I needed last night. But apart from the fisting hiccups straw, I [00:13:00] would say that this one just ticks all of the boxes for me, Dave.

[00:13:03] David: We talk about some gross stuff on the show, but this is pretty, pretty gross. So we’ve got a deadly fungus for a start. It controls the minds of houseflies, which are themselves pretty gross before consuming them from the inside out, which is gross. And That’s just for start Sophie.

[00:13:20] Sophie: That’s just the starters and you know, I think I can say categorically. I don’t think we’ve spoken about necrophilia on STEMology before and no time like the present.

[00:13:29] David: No time, like the last show of 2021 to be talking about necrophilia on the podcast.

[00:13:34] Sophie: yeah. So

[00:13:35] then yeah. So I go, Dave, you were

[00:13:37] David: please, please. No, it’s your favorite? I insist.

[00:13:40] Sophie: I think, yeah, let’s, you’ve broken it down really nicely, but apparently we’ve got this, our fungus, which is, oh, I’ve not tried to say this out loud before. Entomophthora muscae.

[00:13:51] David: Yeah.

[00:13:51] Yeah.

[00:13:53] Sophie: so as you said, yeah, it infects the flies. it controls their minds is mind control fungus in flies. I really love the way that they described [00:14:00] the general death of the flies, where apparently this fungus compels flies to climb to an elevated surface, like a tall plant stem or twig.

[00:14:08] And then basically the zombie fly clings and dies there with their wings out stretch, basically like I’m getting like a little bit of like a crucifixion imagery. Like I’m seeing fly, like up on a kind of cross. The reason that the wings are outstretched in a, like a bit of a crucifix waste, but a dispersed fungal spores sprouting from their bodies.

[00:14:29] But the beautiful bit that we have not said explicitly yet, is those beautiful fungal spores, what they do is they emit chemicals resembling those produced by females when they’re ready to mate and so that sexy scent attracts healthy males and prompts them to mount dead females, males in turn become infected, and then fly off to spread their fungal spores among their friends and family.

[00:14:52] So we’ve got fungus that like controls the flies, kills them and then sometimes makes them have sex with dead flies.[00:15:00]

[00:15:00] David: It’s just it’s gross. just gross

[00:15:04] and fabulous. Isn’t mother nature disgusting?

[00:15:07] Sophie: She has a real problem person sometimes. And I love that they, um, so this all came about because they’d been doing previous stuff and it was like the quote from the, it was just the press release. But, scientists were previously surprised to see healthy male flies in the lab were unusually interested in mating with dead infected females.

[00:15:25] And I was like, yeah, like that’s either like, mates,

[00:15:28] David: That does seem Yeah. But also to be in a position where your job is to notice that by happenstance is a special position to be in. I think like, whoa, these flies are doing it with the dead flies more often than usual. Wonder what that’s about.

[00:15:44] Sophie: It’s just a bit much. And so then they did this, it was a little experiment where they tempted male flyers with an assortment of female cadavers, some infected, some not. And they found that, the males were more more often they tried to mate with the infected corpses, but at a later [00:16:00] stage.

[00:16:00] So apparently. you we’ve got our dead female, who’s emitting these like smells. And, in the very beginning they found that, it wasn’t that popular. I think in fact, some of the male flies went up and like touch the non-infected corpses as well. They’re just investigating these like dead women hanging around.

[00:16:17] David: well, I looked at the, if you look at the data, so the crucial statement is that the male flies tried to attempt to mate with the infected flies more often, they were still having a go at the normal uninfected flies.

[00:16:30] Sophie: yeah, I agree, Dave. They really had a go.

[00:16:33] David: they had a go and they had a go more often at the infected ones. And you’re absolutely right. So they talk about this process called sporulation.

[00:16:39] Sophie: Yes.

[00:16:40] David: so this is basically when the fly dies, that’s when it starts to creep out and buds and kind of make this weird. I think they talk about it as a halo or a Corona or something on the dead female fly. And as that process advances, the female becomes more appealing to the male fly.

[00:16:58] Sophie: Yeah. and they quoted in terms of the [00:17:00] SRN 25 to 30 hours after death. That’s like the sweet spot for having sex with a dead female fly. And they said that 73% became infected after exposure to late sporulation cadavers, which is your 25 to 30 hours compared to 15% of males exposed to early sporulation

[00:17:18] David: and then they

[00:17:19] They said about the how. some beautiful experiments. So they do, what’s called, this is something, I learned a word that I learned, electoral antenography..

[00:17:28] Sophie: Yep.

[00:17:29] David: So this is where you measure the electrical activity of. They basically take off the antenna of a fly.

[00:17:35] And keep it alive and then measure the electrical activity across it and showed that the electrical activity increase in the presence of the smell from the infected female flies.

[00:17:44] Sophie: Yeah, I didn’t a thing you could do.

[00:17:47] David: I did not either. So apparently in the house fly the antenna is their smell organ. So it responds to the dead female infected flies.

[00:17:55] and then they start to get into what it is that the animals smelling that’s [00:18:00] attractive and they show a couple of things. The first thing they show is that there’s some attraction to the fungal spores itself and they did that with a, what they call a trap test. So you had sticky traps and one was like inoculated with the fungal spore and one wasn’t.

[00:18:13] And they found that more flies went to the fungal spore one onto the other, but then they also do, they profiled the volatile cuticular hydrocarbons, which I’m interpreting as the gases that come off the skin of the flies. Right. And they did gas chromatography coupled to mass spectrometry.

[00:18:33] So basically they use a device that looks at it sorts out molecules based on their atomic weight. Right. And they showed that the infected female flies have this particular profile of gases that they emit, which they say the attractive ones are probably in this gamut of chemicals.

[00:18:52] Sophie: Yeah.

[00:18:53] And they, I think they highlight, or at least the press release highlights, ethyl octonate. Yeah, I’m going

[00:18:59] David: some kind of [00:19:00] Ester probably smells fruity or gross.

[00:19:02] Sophie: Fruity. Oh, gross. Oh, both a thing has happened. Um, and then a group of chemicals known as, cesquiterpenes.

[00:19:10] And apparently they’re both known for their insect learning ability. So they think that those are two important ones to make the, um, the corpses smell alluring to a male flies. I’ve got a few of my favorite quotes from the paper that I’ve down. Dave. Indulge me. So one of, them’s not quote, it’s just a fact.

[00:19:27] So apparently all the house, what they did in terms of like getting this fungus is that they got a house fly from a cow stable that was infected. And then they do just use that do to infect everyone else. So they didn’t even have to like, do like raise their own fungus’s and need to, or anything. They just got with some filthy fly from like a cow stable,

[00:19:46] David: Some filthy street, fly some filthy farm fly.

[00:19:48] Sophie: That’s right. So for science, but this one I really liked, the behavior of the male fly was filmed and monitored for 40 minutes. And behaviors related to sexual attraction were noted in the software BORIS, [00:20:00] the software called BORIS. I stands for something it’s all capitals, but it’s BORIS v. 6.2.4. Which I love there’s just some dude BORIS he’s like, tell me about old behaviors related to sexual attraction and these flies I’ll note down for you.

[00:20:13] David: This fly is having sex with this fly.

[00:20:16] Sophie: And then there was this thing that I could not find any information about. And they said the standard definition of housefly mating behavior, a mating strike was used as previously described by, and there’s like listed some papers and I went in there and I just couldn’t. I wanted, cause if you look at fly mating strike, it tells you about fly strike in sheep because you know, like they get all like fly blown because yeah. And I’m, that’s not what I was after. They just the internet ignore the word mating, even though I asked it not to, but apparently I just wanted to know what, yeah, the standard definition of how flies mating never known about it before and mating strike was used a previously described anyway.

[00:20:52] So I liked that. Because of course, you know, this is science, so everything needs to be defined properly. And then I learned, I tried to, yeah, just Google fly mating and [00:21:00] it turns out it’s actually quite complex. And I just wanted to know what a mating strike was. It just sounded very like, like a bit violent.

[00:21:06] David: Yeah. So apparently occurs mid air or can occur mid air, which Yeah. So they say it’s more like a jump, but jump doesn’t describe it well, because.

[00:21:15] Sophie: Yeah.

[00:21:15] David: They’re in air. but that’s like, let’s really looking at, a page of search results as opposed to anything that we would require to be, you know, it’s not an authoritative

[00:21:25] Sophie: Oh, and at that stage, we should say that this work is, are available in the bio archive, but it has not been published yet. And hence has not been peer reviewed. Um, whereas if I were reviewing this paper, I’d give it 10 out of 10. it.

[00:21:38] David: Yeah. absolutely disgusting and gross and fabulous, disgusting mother nature for the win.

[00:21:44] Sophie: So just be thankful. You’re not a fly.

Cerebellar hunger

[00:21:46] David: Sophie

[00:21:57] Sophie: Yeah.

[00:21:58] David: we’ve discovered a [00:22:00] completely new seat for hunger in the brain.

[00:22:03] Sophie: Yes. This is really interesting.

[00:22:05] David: not you and I, we, but we, we as species.

[00:22:08] Sophie: I guess I am, I’m not part of the university of Pennsylvania, so I would agree with you.

[00:22:13] David: exactly. So we’ve done this by looking at people with Prader-Willi syndrome. And this is a genetic disorder and people who have this syndrome have an insatiable appetite. So no matter how much they eat the heartiest meal, going the biggest Turkey, no matter what, doesn’t matter, they still have this insatiable

[00:22:29] Sophie: really horrible. Like I’ve seen some reason, there are UK documentaries about it, but it’s like, you have these poor kids and it’s like, the kid feels like they’re being starved, but they’re in fact, you know, like almost morbidly obese and all this is it’s because I guess something is broken somewhere and they’re just hungry all the time and they just want to keep eating, but like their bodies have had all the food they need. It’s really terrible.

[00:22:50] David: Yes. So according to this new study, that constant hunger has a seat in the brain because hunger is a behavior, which means it must be driven by the brain. because we use our [00:23:00] brain to do all of the things that we do basically. and that seats surprisingly is in the cerebellum because we traditionally associate the cerebellum with things like fine motor control, so that people that are born without cerebellums, they’re basically fine, but they struggle.

[00:23:12] They have kind of jerky motion with their hands and their legs. So that’s more what we associate the cerebellum with, but this study is telling us that it has something to do with hunger and satiety, which is the feeling of being full.

[00:23:23] Sophie: Yeah. And so what they basically didn’t cause this, this is brain stuff, Dave, I’m going to say then you can say the real brain thing, but basically they found these neurons, cerebellar neurons and what they found is when they activated these neurons in mice, basically.

[00:23:40] It would like the effect was enormous. Right? So you’ve got these mice, they ate just as often as typical mice, but when these neurons were activated, their meals were 50 to 75% smaller

[00:23:52] David: Yes.

[00:23:52] my understanding too. And so the way that they got to this, so it’s quite a lovely progression of, ideas and things. So they started [00:24:00] off with an FMRI study. An FMRI study, tells you where blood flow is going in the brain and response to a stimulus. And what that tells you is the blood tends to go to the areas that are being activated by whatever it is that you’re doing, because those regions are energetically active, so they need more blood.

[00:24:14] So what they did was they looked at people with Prader-Willi and they looked at people who were just control people, standard issue, people, humans, and they looked at them in two states. So they looked at them when they were fasted and they looked at them after feeding. And basically what they did was they stuck them in the FMRI machine and then showed them images of food and what they saw in both populations of the Prader Willi patients.

[00:24:37] And the controlled patients was that if they were fasted, you saw this increase in activity response to images of food. But after they’d been fed. This activation was notably less in the controlled patients, whereas it was still elevated in the Prader Willi, people and the area that was lighting up

[00:24:55] was this area and the cerebellum that has not traditionally been associated [00:25:00] with hunger. And so then they went and did the next thing. They were like, okay. So these sales are of interest. If we look at the equivalent cells and the mouse, and we feed the mice and look at the cells before and after what you see is that they express this molecule called Homer one alpha, is not a molecule I was familiar with, but apparently Homer one alpha gets expressed when the neurons are switched on.

[00:25:21] So. If you have mice that are facet and you look at their cerebellum and you see no Homer one, and then you feed the mice and see that the Homer one alpha is expressed. It tells you that area of the cerebellum is being activated.

[00:25:33] Sophie: Right.

[00:25:34] David: And then they did what you said, which is this. They did some fancy optogenetics to show that if they activate these cells, with a light stimulus using a virus and this fancy optogenetic thing that I think we’ve talked about on

[00:25:46] Sophie: I think we did. Yeah. I remember. Yeah. Like fancy viruses and light. And cells being activated.

[00:25:52] David: Yeah. so then what happens is, yeah, the meal sizes go down. So we’ve got three lines of evidence already. The FMRI [00:26:00] study, the activation of the cells the mice, passively in response to the feeding And then also activating them, reduces food intake. So you’ve got these kinds of three combining coalescing.

[00:26:10] This constellation of evidence that says these are the cells that are important. It’s lovely.

[00:26:14] Sophie: and even said, when they then, did the reverse and when they inhibited the neurons, the mice ate larger than normal meals. So you just like, well, that’s, that’s good. Like that’s what you’d maybe expect.

[00:26:24] David: in terms of causation, that’s very appealing and it then gets very complicated talking about the reward pathways and I really start to struggle to be honest. but what’s interesting about this as well, is that, Traditionally speak well, not traditionally, but in the past, the areas that have been studied in the brainer and the brainstem and the hypothalamus, these are the areas that we think are involved in driving, feeding behaviors, and in processing the signals that come from the body when we’re satiated. So full, so typically what will happen is, short-term regulation of hunger tends to happen when you get like blood levels of nutrients drops. So you that’s [00:27:00] detected by the brain and that drives this food seeking behavior, and then your, glucose goes up and that gets sent back to the brain and that kind of triggers you to stop eating another things that happens is that, the actual act of putting food into your belly, because it stretches your guts that actually inhibits hunger as well. And those signals have all been studied very well in terms of the hypothalamus, which is in the brainstem. So this is a completely different part of the brain that nobody really would have suspected was involved in this process at all, which is probably why it’s gone into nature. I think.

[00:27:31] Yeah.

[00:27:31] Yeah.

[00:27:32] it’s lovely, lovely stuff.

[00:27:33] Sophie: Yeah. and then, you know how, when I don’t know what’s going on scientifically in a paper, I like to find a fun facts. It was quite hard in this one. That was a lot. The paper was just hard for me all around Dave. But, I did like the specificity of when they’re talking about food intake with the mice, they gave them me three grand pellet of chow was provided the food intake was measured over a period of one hour by weighing the remaining food accounting for crumbs.

[00:27:56] So I thought that was good.

[00:27:57] David: Oh, that’s very rational. All kinds of for [00:28:00] crumbs.

[00:28:00] Sophie: Yeah, cause it’s just like, you know, mice, they’re just chewing up their little pellet, they going crumbs everywhere and you’ve got to count that as not eaten food. but yeah, apart from that, it was terrifying paper, but like amazing result.

[00:28:10] David: Terrifying paper, amazing results. Just an astonishingly long list of collaborators involved. Yeah. Lovely paper loved Loved the bits that I read and understood.

[00:28:20] Sophie: Yeah. and I really hope that this can then be used to help people. You know, people who suffer from Prader-Willi syndrome and stuff, and they can work out what’s happening with the neurons. They can turn things on and off and they can, help them manage their uncontrollable hunger, which I think would just be terrible.

[00:28:35] David: Yes, I think that would be terrible. And also like, presumably this can be applied more broadly. So like the brain stem, like the pharmacological, treatment options that target that hypothalamic pathway has been very disappointing and in treating things like obesity.

[00:28:49] So presumably if we’ve got these new cells, if we can determine something on then that can be targeted for treatment, that might, that’s another avenue that can be explored to, you know, really broadly for [00:29:00] anyone who has any kind of, eating disorder. So good stuff.

[00:29:03] Sophie: Great work.

Little Baby Baby Embryo

[00:29:04] Sophie: Teeny weeny little baby embryo is the teeniest of the baby embryo.

[00:29:18] David: How much smaller could they be? And the answer is only slightly more is tiny.

[00:29:21] we’re talking about embryos before they’re differentiated, we’re talking about pre embryos really, aren’t we?

[00:29:27] Sophie: Yeah.

[00:29:28] David: pre embryos in that transition phase to becoming embryos

[00:29:32] Sophie: just like an egg and like a sperm. And they’ve just been like hanging out for a little bit, but they haven’t quite worked out what they’re doing.

[00:29:39] David: Yeah.

[00:29:40] So we’re talking about this. This is research. That’s looked at human embryo at three weeks of age, which is about a week older than we typically get to see human embryos at, ethical reasons. Right. And it’s a, it’s an embryo. That’s been isolated from a medical termination of a pregnancy, and which is why it’s been accessible.

[00:29:57] And because it’s illegal to, if you [00:30:00] grow an embryo from scratch to grow it past two weeks.

[00:30:02] So one’s a week, a week past that, and that gives us an opportunity to look at something fascinating that we’ve never seen before, which is this transition phase from basically an undifferentiated mass of cells, like a, just a massive epithelial cells that then start to differentiate and become all of the cells that are going to make up all the body parts, that human being has.

[00:30:23] Sophie: Yeah.

[00:30:24] And is that the that’s called gastrulation? Is that Dave? I’d never heard of the specific role, but yes, apparently two weeks after fertilization, this gastrulation process starts. And as you said, all this human cells start to take on their specific roles. Like, am I going to be brain meadow or am I bone tissue or my own nose,

[00:30:43] David: exactly, and even things as fundamental as, okay, this is a blob of cells, but now this blob of cells has a front and a back end. Like this is going to be the head and this is going to be the tail and this is going to be the left. And this is going to be the right, like really fundamental stuff that an organism has to have in order to be called, you know, [00:31:00] a complex organism.

[00:31:01] Sophie: Yeah. And so, and the issue it to the two week thing from my understanding arises because sort of up until now, we’ve used samples from mice and non-human primates to kind of better understand that process. And in mice, at least it’s at around two weeks at the nervous system starts to form. And so that’s when they said like, okay, no more, but what they’ve found out is that it doesn’t happen in people.

[00:31:25] David: Yeah. that’s my understanding too.

[00:31:26] Sophie: It happens later on.

[00:31:28] David: They’ve seen key differences. So basically what’s happened is we’ve used this as an opportunity to say how relevant our experimental models are. So if we compare what’s happening to this cell at three weeks to very compared to what’s happening on most, how good is the comparison?

[00:31:41] And they’ve also looked, I think, primates and a few other kinds of animals. and Yeah.

[00:31:45] they find that there are key differences. One of the differences is how, as you mentioned, the nervous system hasn’t started to form yet. And that’s an important one because that might lead to a raising of this threshold for when we can continue to study which

[00:31:57] would presumably yield valuable information [00:32:00] about how we differentiate complex things. Another one apparently is that human beings show earlier development of blood vessels. The cells that are going to turn into blood vessel cells than do the mice. I’m not sure what the significance of that is, but apparently it does happen.

[00:32:15] Sophie: We just love blood Dave.

[00:32:17] David: We bloody love blood. and basically the way that they did this was, this is one of those ones where it sounds like it’s going to be really complicated because what did was single cell RNA sequencing, but basically what they did, first of all, it’s impressive because they did a bit of manual dissection.

[00:32:33] So this embryo is smaller than a poppy seed by my, estimation. So a four week old embryo was apparently the size of a poppy seeds. And this one is a week younger than that. So it was going to be considerably smaller than a poppy seed, but it was manually dissected using tungsten needles. And what they did was they took off the yolk sac and then they managed to. Basically, they divided it into and said, this is the head end. And this is the tail end. And we’re [00:33:00] going to look at all the cells in these different compartments and see if we can spot some differences between them. And then basically what they did was they dissociate the cells. And when you dissociate the cells, all that means is that you stop them from coming in together and the way that they’ve been clumped together, and you caused them all to spread out uniformly.

[00:33:17] So, and then you centrifuge them down so that they’re all, you can divide them into the various compartments of the cell, not compartments of the cell. You can divide them into the various cell sizes

[00:33:28] you can redistribute that into a solution. And then basically you’ve just got all these cells free floating in a kind of cell soup. And then you can basically take one cell, and what they looked at was RNA sequencing. So they were looking at the RNA profile of each individual cell and they could tell whether it came from the head end or the tail end of the body. And RNA is basically the middle ground between DNA and protein.

[00:33:53] So you have your genetic structure, your genetic sequence, which is the same for all the cells. And then you [00:34:00] make RNA, which is translated into protein. And protein is ultimately what gives you cell function. Proteins are the things in your cells that do all the things that cells do protein. So looking at the RNA, tells you very specifically not what genes the organism has, but what genes are being expressed, what ones are actually you know, going to lead to function and this particular cell.

[00:34:22] Sophie: I’m glad you knew that Dave.

[00:34:25] David: Yeah.

[00:34:27] Sophie: but yeah, so I thought that was really, and yeah, like it’s potentially going to be like quite important. And they’ve hoped that as we’ve said before, this is gonna raise that two weeks to maybe three weeks. Cause apparently the lab got this particular embryo that as we said, someone has donated the sample.

[00:34:44] They spent five years on a waiting list and, you conducted their genomic tests and physical examinations to determine that it was a good sample, but what they really need is potentially more samples. Right. Because what we’re doing is drawing a lot of conclusions from one embryo, which you’d think [00:35:00] is okay, but you know, in science it’s maybe better to do it a few times.

[00:35:04] and they’re saying that yeah, if they were to wait on this waiting list, again, like even the chances of getting another one in another five years are pretty slim.

[00:35:12] So this,

[00:35:13] David: Imagine the pressure. Imagine being the person who did that manual dissection, like with their hands. So they detected this clump of cells with their hands.

[00:35:20] Sophie: Yeah. Don’t

[00:35:21] David: person who had to do that

[00:35:22] do not make a mistake yet.

[00:35:26] Sophie: Dan do a better job. but yeah, so hopefully this can, it means that they can at least grow embryos to three weeks. Later on. Maybe I say that, you know, it, there’s lots of things that have to happen before that is a possibility, but you know, it is good that we know, at least in general, the, the mouse model is quite a good model for humans, except for, as with the blood and the nervous system.

[00:35:49] But I’m, it is crazy

[00:35:50] David: again, fascinating that we are so similar to mice at this early stage of development and fascinating that we have a yolk SAC at this early stage of development as well, which I mentioned in passing. [00:36:00]

[00:36:00] Sophie: Yeah.

[00:36:00] David: there you

[00:36:01] have it. Little peek at the baby, baby, baby, baby, baby, baby, baby embryo.

[00:36:06] Sophie: Yeah, the little wee baby, baby embryos, the babiest of the babies,

Outro

[00:36:11]

[00:36:19] Sophie: And thank you for listening to another fun episode of stem ology.

[00:36:22] David: be sure to check out all the links to these great stories on our show notes. Go visit www.stemology.com.au

[00:36:29] Sophie: Your hosts have been Dr. David Farmer and Dr. Sophie Calabretto. This is a podcast from Ramaley media.

[00:36:35] David: Be sure to hit subscribe on your favorite listening apps so you never miss our episodes.

[00:36:39] Sophie: This is the final episode for 2021. If you’ve loved this show, please let us know, drop us a note on Ramaley media socials, or email our producer, Mel.. The address is mel@ramaley.Media

[00:36:51] David: We’ve loved presenting the show every week and we hope you’ve enjoyed us sharing the latest in all things. Science, technology, engineering, and maths.