Nature Podcast 11 January 2007
Introduction
This is a transcript of the 11 January edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com
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Chris Smith: In the Nature Podcast this week, what's the best way to store high-level radioactive waste? Should we just encase it in something hard and bury it?
Ian Farnan: What we've measured is the number of atoms which are displaced when an alpha particle is emitted from plutonium. It's 5,000 atoms, which is four or five times higher than previously estimated. This means that materials will become severely radiation-damaged much faster than previously assumed.
Chris Smith: Also, our researchers have uncovered the link between glucose, fats and diabetes.
Enrique Saez: We have discovered a glucose-activated sensor, a protein that combines glucose directly and serves as a switch to turn on the conversion of excess glucose in the liver into fats that can be stored in adipose tissue.
Chris Smith: And how scientists have found evidence that embryos containing just four cells have already decided what those cells are going to turn into.
Magdalena Zernicka-Goetz: The cells in the mammalian embryo start to differ from each other earlier than it was thought before. Already by the four-cell stage you may have some cells which have a temptation to differentiate prematurely.
Chris Smith: And Magdalena Zernicka-Goetz will be unlocking the secrets of embryonic development for us later in the programme.
Chris Smith: Hello, I'm Chris Smith. Happy New Year and welcome to this, the first edition of the Nature Podcast in 2007. First up, the subject of what to do with the world's nuclear waste. The favourite option at the moment is to mix things like plutonium with a synthetic material to form a hard ceramic crystal that can then be buried. But Cambridge University's Ian Farnan has found that the radioactive decay emitted by the stored substances severely damages the crystal structure, making it amorphous and leaky. But it's not the radiation that does it. It's the decaying nucleus recoiling after it kicks out an alpha particle. The recoil knocks other atoms in the crystal out of place. Nature 445, 190–193 (11 January 2007)
Ian Farnan: What we're trying to do, Chris, is to understand how materials are damaged by alpha-decay events. These are the radioactive decay events that occur naturally when you have heavy elements like uranium or plutonium within a material.
Chris Smith: And this is relevant, of course, because we want to store these materials because they're the products of radioactive waste in power stations and things?
Ian Farnan: That's correct. They are generated primarily through re-processing nuclear fuel rods and also they are contained as contaminants within general process wastes.
Chris Smith: What sorts of materials are they mixed in with, the radioactive wastes, in order to immobilise them so they can be safely stored?
Ian Farnan: Well, the favourite materials... these are candidate materials at the moment, nothing is actually used, are mineral-based ceramics and one of these could potentially be the mineral zircon, which is what we've been working on. Other materials are zirconate pyrochlores or titanate pyrochlores.
Chris Smith: And how long do we hope that they're going to be stable for, because that's a key question, isn't it? We're going to put this stuff in the ground. It's got a very long half life?
Ian Farnan: Yes, well, if you think of ten half-lives of plutonium 239, then you're talking about 241,000 years.
Chris Smith: Okay. And, so obviously we have to be sure that this material is robust enough to survive for that length of time at least?
Ian Farnan: That's what we would hope.
Chris Smith: So how have you set about testing whether these materials are up to the job?
Ian Farnan: What we've been doing is taking some natural minerals which have been proven to retain uranium and thorium over geological timescales, putting quite small quantities... so up to about 1% of these elements, and we've then compared how they behave with synthetic materials which were made about 25 years ago and these contain plutonium 239.
Chris Smith: So these are real waste deposits that you've analysed?
Ian Farnan: These are research ceramics which we're considering the material as a disposal matrix.
Chris Smith: And how do you analyse them to see what's going on at the ultrastructural level?
Ian Farnan: Well, the novelty of what we've done is we've managed to implement what we call a radiological nuclear magnetic resonance experiment. We spin the sample extremely fast to get higher resolution. We then can identify the magnetic resonance signal from damaged parts of the crystal and from undamaged parts of the crystal and, in fact, we can quantify that by saying exactly how many atoms are in the crystalline phase and how many atoms are in the amorphous phase. And then, from that information, for different doses, we can extract out the damage per event.
Chris Smith: Now I see you've brought in a sort of computer here with the simulations that you put together running on it, so if I just orientate people, what it looks like here is a massive sort of grid of dots which are... those are the atoms presumably? That's the crystal matrix that you put there?
Ian Farnan: Exactly, yes.
Chris Smith: And there's one bigger dot which is the uranium sitting there, so presumably that uranium's going to do an alpha decay? And we're going to see the consequences of that? So, would you just mind talking us through, Ian, exactly what's going to happen?
Ian Farnan: I should just say for the moment, this is a simulation that's been done by my colleague Kostya Trachenko, in conjunction with Martin Dove and Ekhard Salje at Cambridge. But what happens is that the uranium atom will emit an alpha particle in one direction. That's highly energetic and basically rips through the structure, but only causes in general ionisations in the structure, so it kicks electrons out of the structure, but not atoms so much. But as the nucleus that's emitted the alpha particle recoils, that causes a significant amount of disruption to the crystal structure and that's what we've measured, the amount or the number of atoms that are displaced when you get the recoil of the heavy nucleus which has just emitted an alpha particle.
Chris Smith: Shall we run it?
Ian Farnham: Yes. So if I press the button there, you can see...
Chris Smith: Oh, good grief! The whole crystal's gone out of shape!
Ian Farnan: Exactly. I'm only showing a central portion of the crystal in this simulation, so that you're surrounded by more pristine crystal here, but this is a low...
Chris Smith: But that's... I mean, for the people who can't see this, literally what was a nice orderly crystal structure, a matrix, is completely now... it looks like literally someone's blasted it to pieces. And that devastating change is just the nucleus recoiling and it's smashing into all of the other atoms in the crystal structure and dislocating everything?
Ian Farnan: Yes. It creates a cascade of collisions of atoms which then collide with other atoms and eventually it's dissipated.
Chris Smith: On the basis of this model that you've put together, how long do you think the material will last in a reliable form before it begins to show quite significant deterioration?
Ian Farnan: Well, for the case that we've particularly measured here, which is zircon, we would say that we've passed what's called the percolation point. That's where damaged regions within a crystal will start to join up across the crystal and then the material will start to swell and potentially crack. That would occur after 210 years, and the whole crystal structure would be destroyed so the material would be amorphous after 1,400 years. So that's not good enough.
Chris Smith: So, way short of what we need?
Ian Farnan: Yes. Now what we're saying is that what we've developed is a screening process to now look at other materials. You see, those time scales were quite specific and that's because we have quite a quantitative understanding now of the number of atoms that are displaced in this particular material. Hopefully, the number of atoms which are permanently displaced in other materials will be fewer and therefore the material will last for longer.
Chris Smith: A man who's certainly working on a hot topic, Cambridge's Ian Farnan ith an elegant way to work out how well a crystal structure can withstand the long-erm effects of radioactive decay. Now from the body of a crystal to the human body and how it detects glucose. Enrique Saez has found a receptor in the cell nucleus called LXR which alters gene activity according to how much sugar there is present. And because it's also involved in fat metabolism, it might explain why diabetics are prone to arterial disease. Nature 445, 219–223 (11 January 2007)
Enrique Saez: We have discovered a glucose-activated sensor, a protein that combines glucose directly and serves as a switch to turn on conversion of excess glucose in the liver into fat that can be stored in adipose tissue.
Chris Smith: It's just in the liver, is it? Or would you expect to find this throughout the body?
Enrique Saez: We have seen the fat in the liver and we have focused our studies on the liver, but we have also examined the intestines and seen that, in that tissue which also faces a significant amount of glucose influx, such as for example after a meal, LXR also serves as a glucose sensor.
Chris Smith: And where is this receptor? Does it sit on the cell surface or is it inside the cells?
Enrique Saez: LXR belongs to the family of nuclear receptors. It sits inside the nucleus of the cell directly regulating gene expression. We don't know the exact details of the interaction. That will necessitate the resolution of the crystal structure and we're working on that. But we know that it binds directly in what is called a ligand-binding pocket of the nuclear receptor family and that it's probably more than one molecule of glucose that is found inside that LXR LBD.
Chris Smith: And how did you track them down in the first place?
Enrique Saez: Well, we were originally studying LXR as a target for atherosclerosis because the nature LXR ligands described to date were oxidised forms of cholesterol and LXR is known to play an important role in cholesterol metabolism, but when we fed mice synthetic LXR activators, we saw interesting effects on glucose metabolism. In particular we saw that the activators decreased production of glucose by the liver and also enhanced clearance into peripheral tissues of glucose.
Chris Smith: It's very interesting that you say that LXR can respond to both cholesterol and forms of cholesterol and also glucose, because if you look at people who are diabetic, they often also have problems with raised blood lipids and they have atherosclerosis, so do you think this could be the common pathway?
Enrique Saez: Well, you are correct. Atherosclerosis and type-2 diabetes, or insulin resistance, occur together very frequently. We don't know yet whether LXR will be the link. However, it is very suggestive given that it is the only known protein, the only known transcription factor known to bind both LXR and glucose. We're asking the ultimate physiological question which is, what relevance does this have to humans, by looking at human populations that are obese and diabetic and hyperlipidaemic and we're trying to see whether LXR levels are different or LXR alleles are different among those populations.
Chris Smith: Enrique Saez who's from the Scripps Institute with the discovery of the glucose receptor LXR in the cell nucleus.On the way, how researchers have discovered that embryos make decisions about what their cells are going to turn into when they consist of just four cells. First, though, to a new way to disentangle food webs and to put some numbers on the impact of agriculture on local ecology. It stands to reason that if the natural environment's replaced with crops, there must be knock-on effects for other species. But if we could quantitate those effects, we might be able to find more fauna-friendly forms of agriculture. Jason Tylianakis and his colleagues have done just that, but with some surprising results. Nature 445, 202–205 (11 January 2007)
Jason Tylianakis: All over the world humans are clearing land to make way for agriculture and even in the tropics alone, it's nearly six million hectares of rain forest are cut down every year. There's growing evidence that this land use change drives a lot of extinctions of a variety of species, but what was much less clear was the effect on the species that still remain. So how do the interactions between the surviving species change as land-use gets changed for agriculture?
Chris Smith: But that sounds like quite a difficult thing to do. How do you do that? I mean, what's the mechanics involved in doing a study like this?
Jason Tylianakis: Well, in our case, we used some traps that were simply made with PVC tubes and some reeds inserted inside them, like bamboo tubes. And we have about 432 of these traps all over a region of Ecuador and within these traps, bees and wasps that build their nests in cavities in wood, built their nests within these traps, and we were able to see how often they were eaten by their different natural enemies.
Chris Smith: And having done this, I mean, what did you find, first and foremost?
Jason Tylianakis: Well, we looked at over 7,000 nests of these bees and wasps and what we found was the frequency with which they were eaten by each of their enemies changed quite considerably as land-use intensity increased. So we have a gradient of land-use types from forest right through to coffee and then really intensive agricultural, like rice and pasture, and what we found was that with increasing intensity of agricultural management, the food webs became much less even in their structures. So they started to become dominated by one interaction, which was one parasitic wasp. This species actually becomes much more specialised in the managed habitat. So whereas in a natural habitat it attacks a variety of different prey, in the highly modified habitats, the host species it attacks becomes much more common because it's a bee that requires a lot of weedy flowering plants. Now, as this bee becomes more abundant, the parasitic wasp has a much larger host resource and it doesn't need to focus on other host species. It just attacks only this one species.
Chris Smith: So, were there any surprises that came out of this, apart from finding the dominance of the parasites?
Jason Tylianakis: Well, the biggest surprise was the extent to which the food-web structure changes. If you look at the shape of the food web, it's a completely different sort of structure to the ones in the natural habitat. But another surprise was that coffee agroforest, which is just coffee plants growing within a relatively natural forest, were not significantly different in food-web structure from the ones of natural forest. So this implies that agriculture needed necessarily go against the natural food-web structure and it is possible to have compatible agriculture and conservation.
Chris Smith: That's certainly a very surprising find. Do you know why you saw that?
Jason Tylianakis: Well, coffee, at least superficially, strongly resembles native forest, at least from the outside. The understorey is cleared quite frequently from weeds, but nevertheless it is a relatively natural kind of habitat and there has been some evidence from a variety of studies showing that birds and insects are almost as diverse or sometimes just as diverse in coffee plantations as they are in forests. So, to some extent, it's not surprising that their interactions would be similar, but it was nice to actually confirm this, that they don't just superficially resemble forest, but they are, to some extent, performing the same function.
Chris Smith: That was Jason Tylianakis from New Zealand's University of Canterbury describing how he's found some interesting changes in how food webs hang together when you add various forms of agriculture to the equation.This is Nature's podcast from 11th of January edition of Nature with me, Chris Smith. Now to the developing embryo and Magdalene Zernicka-Goetz, who works at Cambridge University's Gurdon Institute. She's found that embryos containing just four cells have already determined what those cells will subsequently turn into and they do it by adding chemical tags known as methylation to the histone proteins which are associated with the DNA in the cell nucleus. The more methylated the DNA is, the more potent the cell, in other words, the more different tissue types it can produce. Nature 445, 214–218 (11 January 2007)
Magdalena Zernicka-Goetz: The question which we tried to address in the lab is when and how the very first cells of the embryo start to differ from each other. The old view of development of the mammalian embryo was that initially until two-and-a-half days of development, all cells are identical and only when the cells take different positions within the embryo... and this means that some of the cells will go into the inside part of the embryo, while others will stay outside, and this position of the cells will influence where they go. What we've found out is that even earlier, at the four-cell stage, when all of the cells have the same position, and there are only four of them, there are already differences between those cells.
Chris Smith: And what are those differences?
Magdalena Zernicka-Goetz: So what starts these differences, we have only now a hypothesis which we'll be testing for a number of years to come, but what we identify in describing this paper, that there are specific epigenetic modifications that occur in some of the cells and specifically identify a methylation of one of the histones on specific residues, the arginine residues, which are very high in those cells which are fully pluripotent and relatively low in those cells which start to differentiate earlier.
Chris Smith: And how did you prove that?
Magdalena Zernicka-Goetz: First, we just correlated it. These levels of methylation vary between cells and vary in a perfect correlative way with the potency of the cells, but the question is, is it really that important? And to be able to address this question, you have to change the level of this methylation and ask the question whether now you change the fate and potency of the cells? And this is what we did, and we showed that indeed it is the case. So we upregulated this modification, so we overexpress enzyme in just one part of the embryo which governs this modification, which put methyl groups on these specific arginine residues, and we found out that the older daughters of these cells were now behaving as a group of pluripotent cells.
Chris Smith: What are the implications given that you've found these differences so early on, for, say, embryonic stem cell technology?
Magdalena Zernicka-Goetz: Well, the question is, is this particular modification also will help embryonic stem cells to retain pluripotency and this is something which we will be testing now. But we know that this particular modification does exist in pluripotent stem cells.
Chris Smith: And to take a more clinical sort of standpoint on it, what happens if you have monozygotic twins because do we presume then that those cells... or even triplets might be a better example, those cells have divided and some of them will be more methylated than others. Does that have an implication?
Magdalena Zernicka-Goetz: I think not because when you have monozygotic twins or when you have to separate cells within the embryo, I think they all have an enormous plasticity to re-program themselves. So what you would do is that you actually... you cannot treat anymore an embryo as like a quarter of the embryo, but you have a quarter of the embryo which starts to behave as a whole, so it's important to remember that all of these cells in different circumstances will have a full potential to develop.
Chris Smith: Magdalena Zernicka-Goetz explaining how she's found that chemical tags applied to DNA of early four-cell embryos determine the fate of the cell that carries them.And now heartening news for Australians, because they seem to make up about 90% of the world's backpackers. Larry Rome from the University of Pennsylvania has come up with a hip-, back-, ankle- and energy-saving rucksack. Nature 445, 1023–1024 (21 December 2006)
Larry Rome: We all think that backpacks are a fantastic invention and, in fact, they are, but they can be improved greatly.
Chris Smith: What, you mean more space? Or more comfortable to carry?
Larry Rome: Exactly, more comfortable to carry things, because the problem with the backpack is when you walk that moves your hip up and down about 5 cm and since the backpack is attached to your hips, you move the load up and down 5 cm, and that causes the load to put a lot of force back on you, making it uncomfortable.
Chris Smith: But it must also burn off an enormous amount of additional energy? It must be very inefficient?
Larry Rome: That's right. That's precisely right, because you have to lift this load for every step you take.
Chris Smith: So what are you proposing to do instead?
Larry Rome: Right. What we wanted to do is find a way to keep the load stay at constant height above the ground, because we knew if we could do that, then you would not have these extra forces on the body. If you carry a 50 lb load it will exert 50 lbs of force on you, but when you start to move, even though the average force will still be 50 lbs, when you walk the peak force will now be 85 lbs and if you run with the load, the peak force will be three times more than the actual weight of the pack, or 150 lbs.
Chris Smith: Okay. So you've said you can get round this problem if you can hold the load in one position vertically relative to the body. So how are you going to do that?
Larry Rome: Right. So what we have to do is to suspend the load from the frame of the backpack, so as the frame goes up and down with your hips, the load doesn't. So we have to have a very long bungee cord which attaches the load to the frame and with this long bungee cord, as you move up your hip by 5 cm, the bungee cord essentially just stretches by 5 cm and keeps the load at constant height from the ground.
Chris Smith: How much energy will this actually save someone who's going on a hike with a big heavy rucksack?
Larry Rome: It saves about 40 watts of metabolic energy and to put that into more real terms, with our backpack you can carry 60 lbs for the same energetic cost that you'd have to expend for carrying only 48 lbs in the normal backpack.
Chris Smith: So it's a considerable energy saving then, Larry?
Larry Rome: Oh, sure, yeah, quite right. You're able to essentially walk with 12 lbs extra of load for free.
Chris Smith: Does it also spare you some orthopaedic injuries though? Will your back and hips wear out less quickly because you're not exerting this vertical force down on them with every step?
Larry Rome: Exactly. With our backpack we knock out about 85% of this extra force you need to accelerate the load, but where it will be extremely protective, for instance, if you jump off a rock and then land on the ground from several feet in height, then you can actually break your ankle quite easily because when you hit the ground, you have to decelerate not only your mass, but the mass of the load of the backpack. But with my backpack, when you hit the ground, the load keeps on sliding down inside the frame and hence you are able to spread that force out over a longer period of time. And this is actually a problem that US Marines have when they jump out of high trucks with a very loaded backpack. They break their ankles sometimes.
Chris Smith: Larry, where can I get one?
Larry Rome: Well, hopefully in one to two years we'll have them on the market.
Chris Smith: Larry Rome's ankle-friendly energy-efficient backpack.Well, that's it for this week's and thank you very much for listening. I hope you can join me next time, when Ill be finding out about the flu. In the meantime, all of the reports we've covered this week are available from our website at http://www.nature.com/nature. And if you'd like to send us some feedback about this programme, the address to write to is mailto:podcast@nature.com. For more audio scientific stimulation, this week's edition of the Naked Scientist podcast explores the science of red wine and finds out why it's better for you than grape juice or white wine. Also under the microscope are the effects of another of our favourite drugs, which is caffeine, and we'll also be hearing how the bacteria living in your intestines help you to make the most out of meal times. That's the Naked Scientist podcast that's freely available from http://www.thenakedscientist.comThis programme was produced by me, Chris Smith, with Anna Lacey. Until next time, goodbye.
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