Nature Podcast 24 May 2007

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Chris Smith: This week, a strange glow in the sky, but what could it be?

Shrinivas Kulkarni: This explosion is about 100 times fainter than the faintest supernovae ever found. It is about 100 times brighter than the brightest novae ever found. The best explanation for this event is the merger of two stars.

Chris Smith: Shri Kulkarni will be explaining how he came across that phenomenon in just a moment. Also, a historical hurricane record. Scientists have found a way to look back longer than ever before and discovered that El Niño can actually help to ward off bad weather.

Jeffrey P. Donnelly: We have been able to go back over five thousand years. It seems as though sea surface temperatures are not the only story. When you get lots of strong El Niño events you get very few intense hurricanes in the North Atlantic.

Chris Smith: And is this the mouse that could show researchers what kindles cancer?

Lynda Chin: DePinho and his group have shown by engineering a mouse they have shortened shortest telomere and eventually those mouse cells experience telomere-base crisis and this has been shown to occur in human cancer cells.

Chris Smith: More from Lynda Chin coming up later. Hello, I am Chris Smith. Welcome to the Nature Podcast. First this week a story of special significance to anyone who is a Virgo because that is the part of the sky where Shri Kulkarni recently spotted something very unusual. It was a very short-lived red glow. It was too dim to be an exploding star or supernova and it was too bright to be a nova, which is when a star obtains some fresh fuel and transiently flares up. So, what could it be? Well, it might be the first glimpse that astronomers have ever had of two stars merging together. Nature 447, 458–460 (24 May 2007)

Shrinivas Kulkarni: We reported a discovery of an entirely new type of explosion, which occurred in a nearby galaxy in the Virgo cluster. This explosion is distinctly different from the supernovae and novae family of explosions. Supernovae are explosions of stars when they are dying or about to die. The star basically shreds itself to pieces, sometimes leaving a black hole or a neutron star. Novae, on the other hand, are explosions which occur on the surface of a White Dwarf. So, these two types of explosions have been studied extensively since there were recognition of explosions in the sky over, let us say, about 100 years ago.

Chris Smith: So, how does that one that you have seen actually differ from these and how did you spot it in the first place?

Shrinivas Kulkarni: I hate to say this, but we found it entirely accidentally. Every night, there is a telescope near San Jose, California that is run by the University of California System and they scan the skies looking for supernovae and last year we found that one of the sources that looked very dim to be a supernovae and therefore it was rejected by the supernovae groups, but I thought this might be very interesting because it was very dim. It is a much more gentle explosion. Also the colour is quite different. Both novae and supernovae are quite blue to our eyes at their maximum light. In contrast, our explosion is red, perhaps infrared. Furthermore, this explosion, and this is the fun part, is about 100 times fainter than the faintest supernovae ever found. On the other hand, it is about 100 times brighter than the brightest novae ever found. So, this is a new type of beast in the heavens.

Chris Smith: Have you got any ideas as to what sorts of stellar convulsions could have actually triggered something like that?

Shrinivas Kulkarni: The current data are not good enough to absolutely and decisively say this is the particular model, although we do think that the best by explanation for this event is the merger of two stars. About half the stars in the sky, you may be surprised to know, are in fact binaries, i.e., they have a companion star. Over time, one of the stars evolves and usually gets larger, just like people do as they get old I suppose, and the material from that larger star spills onto the smaller star.

Chris Smith: For you to have thought, given, you are saying that half the stars in the sky are like this, you would have thought this kind of event would be very common and you would have seen this before and actually we have not so much have we? So how do you account for that?

Shrinivas Kulkarni: Yes, that is always a question one asks when you find something new and then it turns out they are common. As I mentioned, it is a supernova reject that became our prized finding. So, there may well be and I would in fact claim that there probably are a number of such objects in supernovae surveys that have been routinely ignored, but after this I am sure that people will be looking rather eagerly. The other thing you have to bear in mind is these events live for a rather short time. For example, this event lived only for a month and the chance of finding something which lasts only for a month is actually not that high. In any case, my prediction is that the weight of these objects is probably no different than that of supernovae and further searchers, especially if one is diligent, will start uncovering more of these sources.

Chris Smith: Shri Kulkarni from the California Institute of Technology with what could be the merger of two stars. Well, a more down to Earth's story now, quite literally, because Jeff Donnelly and his team have been collecting sediment core samples from the lagoons on islands in the Caribbean. Because these lagoons are separated from the sea by a ridge, it takes a really big storm like a hurricane to push sand and rock grains into them. These grains are piled up in layers with each layer corresponding to a different storm some time back in history. The team have married up this record with other measures of past climate activity to gain vital clues to what conditions might trigger hurricanes and what might be in store for us in the future. Nature 447, 465–468 (24 May 2007)

Jeffrey P. Donnelly: Well, we are trying to understand how hurricane activity varies on long time scales. We do not have very good records going back more than 150 years or so, which is a fairly short amount of time. So, what we are trying to do is extend that instrumental and historic archive back as far as we possibly can and in this case we are coring in lagoons in the Caribbean and getting records that expand our knowledge of these intense hurricane strikes going back many millennia.

Chris Smith: So what are the sorts of hallmarks then in a core sample of a hurricane having arrived?

Jeffrey P. Donnelly: What happens during an intense hurricane strike is that surging waves usually over top the barrier, beach and wash sand and gravel and shells and all sorts of material from the beach and near-shore environment into these muddy environments in the back-barrier lagoons. And so typically what we will see is very fine grained or organic-rich, black, stinky mud with sand layers deposited in them during the event.

Chris Smith: And can you get some clues as to how powerful the storm was depending upon how much sand is in each of the bands that must correspond to the storm and also the size of the particle, the actual physical material that must be being moved by the surge?

Jeffrey P. Donnelly: It is a bit difficult to say just based on the thickness of the layer how intense the storm was, but the more intense the storm, the larger the waves, the more distance the particles are able to be transported and so by looking at the distribution of those particles laterally across the lagoon we can actually say something about the intensity of the event.

Chris Smith: So, you have actually taken multiple cores from multiple locations across one of these, sort of backwater lagoons?

Jeffrey P. Donnelly: Right, that is right.

Chris Smith: And then, you can build up a profile?

Jeffrey P. Donnelly: And basically map out these layers in three dimensions across the entire lagoon to figure out exactly how far they extend and what material the layer is composed of.

Chris Smith: So, as far as the first 150 years or so for which we do have records, you can compare that directly with your cause and then after that you are on your own?

Jeffrey P. Donnelly: Exactly, right. We have a historic archive that we can draw on to try to see you know which historic storms left a layer at this particular site and that gives us some sense for at least what that site is sensitive to at least in the last 150 years, but prior to that we can date the sediments with radiocarbon and know when the layer was deposited, but we obviously do not know any information about storms prior to Europeans arrival in the new world.

Chris Smith: And how far back in time were you able to go with this sort of mud and core sample time capsule then?

Jeffrey P. Donnelly: In this particular work on the archives we have been able to go back over five thousand years, which is one of our longest records. Typically, we have been certainly able to go back at least two to three thousand years at other site.

Chris Smith: It is a long time.

Jeffrey P. Donnelly: Yes.

Chris Smith: Now, in the past, sort of in the last 12 months in fact, we have seen papers, in which people have suggested that hurricanes are getting more intense in the last 50 to 100 years and also that rising sea surface temperatures are going to drive more intense and more numerous hurricanes. Now does that sit correctly with what your data suggest?

Jeffrey P. Donnelly: It certainly makes sense in terms of the physics. We know that the fuels for the hurricanes are the sea surface temperatures and the warmer sea surface temperatures are going to potentially spawn more of these intense hurricanes. In our work, it seems as though sea surfaces temperatures are not the only story. What we have been able to show is that when you get lots of strong El Niño events you get very few intense hurricanes in the North Atlantic. So, that is one phenomenon. The other thing that correlates really well is the strength of the West African monsoon. It seems as though you are getting more convective storminess going on in Africa when you are getting more intense hurricane strikes in the Caribbean.

Chris Smith: So, putting all that together, what does this suggest we are going to be seeing in the next, I do not know, 5 or 10 years over the US, who have been somewhat wind lashed recently, have not they?

Jeffrey P. Donnelly: Yes, certainly we need to be wary of how sea surface temperatures are warming and what role that might play in driving intense hurricane activity in the west and north Atlantic. But it is really key that we understand how El Niño and the West African monsoon are going to change over the coming years if they are going to have any predictive power whatsoever.

Chris Smith: Jeff Donnelly from the Woods Hole Oceanographic Institute with a 5000-year-old hurricane record and all thanks to sand washed into a lagoon.JingleNature's podcast, bringing the world of nature to life.End Jingle

Chris Smith: This is the Nature Podcast, 24th of May edition of Nature with me, Chris Smith. In a moment, the mouse model that is showing scientists how cancers get going. But first, you know that feeling when you open a present expecting it to be something you really want and it is not. Well, now scientists have pinpointed the part of the brain that might be responsible for that sensation of dysphoria. Using trained monkeys, Okihide Hikosaka has found that a small brain region at the back of the brainstem called the lateral habenula nucleus sends inhibitory signals to brain areas that use the nerve transmitter dopamine, which is the brain's reward chemical. Dopamine is also involved in a number of movements in psychiatric conditions and so understanding how these connections work might also give us fresh insights into how to tackle these problems. Nature advance online publication 23 May 2007

Okihide Hikosaka: The purpose of our study was to find out the source of inputs to dopamine neurons, which are thought to play a key role in learning. There are many brain areas that anatomically may project to dopamine neurons, but it is unknown which brain area is critical for that purpose.

Chris Smith: Why is dopamine viewed as so important for learning and that kind of thing?

Okihide Hikosaka: Dopamine neurons encode reward information. Specifically when reward is given more than you are expecting, the dopamine neurons are excited, whereas when reward is given less than you are expecting, dopamine neurons are inhibited and this signal is thought to enhance your behaviour or impede your behaviour.

Chris Smith: So, that explains the positive aspect of the loop. Things go as you expect and they are even better and you get even more dopamine, you get rewarded. What about when the opposite happens and things do not go according to what you think is going to be the outcome?

Okihide Hikosaka: When the reward is less than expected, dopamine neurons are inhibited. One theory is that inhibition of dopamine leads to the suppression of your behaviour. This is where probably the lateral habenula plays a key role.

Chris Smith: So, what did you actually do to try and dissect out what the dopamine neurons are doing under the circumstances of things not going according to plan and working out what contribution the habenula nucleus makes to this?

Okihide Hikosaka: We first trained monkeys to make an eye movement to a small dot and dot starts from the centre and steps to the right or to the left. And on each trial, the rightward or leftward movement comes randomly, but the trick in our experiment was to give a reward only when the dot steps to the right and the monkey makes eye movement to the right. And there is no reward when the dot steps to the left. And we repeat these kinds of trials for maybe 20 to 30 trials and then, suddenly this arrangement was reversed so that now left target indicates reward whereas right target indicates no reward.

Chris Smith: And as this was going on you were presumably recording with electrodes what the dopamine circuits and also the lateral habenula nucleus circuits were doing?

Okihide Hikosaka: Yes, we recorded from the lateral habenula and also dopamine neurons the electric activity of single neurons in each area while the animal is performing this task.

Chris Smith: And the key part of the experiment is obviously is that switch around when suddenly the animal goes getting a reward when it moves its eyes to the right to suddenly not getting a reward and under those circumstances that is when the dopamine circuit is presumably show their maximum change. So, what actually do you observe?

Okihide Hikosaka: When the reward position contingency was switched, the reward or no reward was unexpected. In this occasion, the dopamine neurons are activated by the unexpected reward and inhibited by unexpected no reward.

Chris Smith: And what about the lateral habenula nucleus?

Okihide Hikosaka: The lateral habenula neurons are excited by unexpected no reward and inhibited by unexpected reward.

Chris Smith: And how does the time of their activity compare with the timing of the dopamine signal? Does the lateral habenula come first?

Okihide Hikosaka: In case of no reward, the lateral habenula neurons are excited earlier than when dopamine neurons are inhibited. So, that timing relationship suggests that lateral habenula activity is causing the suppression of dopamine neurons.

Chris Smith: So, what does this add to our understanding of the entire field of things like addiction, learning, and motivation, which we all think are powered by dopamine?

Okihide Hikosaka: It has been suggested that the lateral habenula is related to different kinds of psychiatric disorders including drug addiction, but also depression or schizophrenia. So, our study may suggest that the lateral habenula to dopamine neuron connection is the source of such psychiatric or drug addiction disorders.

Chris Smith: Okihide Hikosaka from the NIH National Eye Institute describing how the lateral habenula nucleus shuts off dopamine signals when you get the opposite of a pleasant surprise. Now, finally this week to a new way to study the evolution of cancers. This has always been very difficult because current mouse models of cancer do not accurately mimic the gross genetic abnormalities that we see in human tumours and the genetic noise created by these gross changes also makes it very difficult for researchers to dissect out the key genetic instigators that actually drive the development of tumours. To resolve the problem, Ronald DePinho and his team have made a mouse, which carries genetic mutations in three key anticancer genes including the tumour-suppressor gene p53, a DNA checkpoint gene called atm, and the mTERC gene which is concerned with controlling the length of the chromosomes telomeres, these are the end caps that are eroded every time a cell divides. The mice have created, have a tendency to develop lymphomas and they also show a severe genetic instability, which closely resembles what happens in human cancers. Lynda Chin, who is one of the co-authors, thinks that mice like this could be used as very effective filters to screen out the genetic noise and home in on the key cancer players. Nature advance online publication 21 May 2007

Lynda Chin: It is well known that most of the tumour in the mouse have very stable genome, in other words, there is relatively few alteration on the DNA level in contrast to human cancer, which will look like a bomb had gone off at the chromosome level everything is scrambled. So, the point is whether we can engineer a mouse model that would help at that level of genomic alteration or complexity that looks more like a human cancer.

Chris Smith: So, how did you actually make the mouse behave in a similar way to the human?

Lynda Chin: The mouse was made in such a way to introduce a level of chromosomal instability into the genome. So, what DePinho and his group have shown is that by engineering a mouse they have shortened shortest telomere and eventually those mouse cells experience telomere-base crisis and this process has been shown to occur in human cancer cells.

Chris Smith: So, I suppose now you can make a mouse do this. It gives you a lot of clues as to how the process must evolve in humans, because when we get a human cancer obviously we have arrived at the endpoint of cancer and this will mean you could do it in a sequential surge you could study how these tumours evolve in time?

Lynda Chin: Yes, with this kind of mouse model we can now go back, for example, and look at time point before the tumour becomes prominent or even when the cells in the mouse were still normal phenotypically and we can examine on the molecular level where other changes are already beginning.

Chris Smith: I suppose that a major problem with studying any cancer is dissecting out the noise from the real hard and fast changes which drive that cancer and by being able to study it in the mouse like this it will facilitate that. Wouldn't it?

Lynda Chin: Yes, when we see evolution conservation of a particular event it is more likely that that event is biologically important and based on that rational we can use the mouse as a way of focusing on things that are more likely to be real in the human cancer evolution.

Chris Smith: Are there any hang-ups with doing this though or we kind of overlook anything by using the mouse model alone? Will there be any cancers it does not represent very well?

Lynda Chin: Each single model will only represent a subset of human tumour. So, we cannot just use one model and try to apply that to every processes in human, but these state our ability to engineer different genetic areas into the mouse on top of that introduce the genomic alteration and that will allow us in the end to generate a model that will represent a pretty broad spectrum of human cancer, but by looking at the comparison between mouse and human and showing that these share similar alterations I think we can conclude from their one important point, which is mouse and human cells indeed share a common biological process during the evolution of tumour genesis.

Chris Smith: Harvard's Lynda Chin describing the mouse that might gives us clues to the way to tackle tumours in future. Well, that is it for this week. Do join me next time when I will be getting cold feet when it comes to pain sensations, ouch! Until then, do tune into this week's Naked Scientist Podcast, which explores the impact the volcanoes can have on human health, finds out why water is such a powerful greenhouse gas and looks at the chemistry of ozone and the clever way to make hydrogen on demand. That is the Naked Scientist Podcast and you can get it free from our website at In the meantime, if you would like to send us some feedback, you just write to This week's program was produced by Azi Khatiri and Sabina Michnowicz and I am Chris Smith. Until next time, good-bye.


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