The team discovers how being a silver surfer can help you keep your marbles, how proteins can be used in burglar alarms and the results of National Hand Washing Day are revealed.

Plus in 'Stuff and Non-Science', is it true that a duck's quack is the only sound that won't echo.

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Chris Smith: Hello and welcome to the Naked Scientists: Up All Night which is produced in association with the Open University. I'm Chris Smith. In this week’s show, how scientists have linked part of a plant with part of a bacterium to produce a light sensitive switch.

Kat Arney: They’ve created a protein that basically works like a light sensor, like the ones you get in burglar alarms. So when you switch the light on, the enzyme’s activated, but when you switch the light off, the enzyme shuts off, and it's all about how they glued the two proteins together, so there’s quite a lot of impressive molecular engineering behind this.

Chris Smith: Indeed, and you can find out how they did that very shortly when we'll also be hearing how researchers may have found a way to get patients with spinal cord damage moving again.

Chet Moritz: And in those types of conditions, the brain is in good condition and the muscles are also in good condition but the pathway that joins those two, that normally joins those two, has been disrupted, and so our goal was to create a method by which we could reconnect signals from the brain, signals which can be consciously controlled, and use those signals to stimulate muscles in order to restore movements to a previously paralysed limb.

Chris Smith: Chet Moritz, whose team have built a system to allow the brain to communicate with previously paralysed muscles, and is it true that a duck’s quack doesn’t echo? The answer’s on the way in this weeks Stuff and Non-Science. That’s all coming up on this week’s Naked Scientists: Up All Night. First up, let’s take a look at some of this week’s top science news stories from around the world, and to bring us up to speed, here’s our science regular Kat Arney. So Kat, everyone knows that smoking isn't good for you but now it looks like there’s yet another adverse effect that nicotine can have on your health?

Kat Arney: Well yes. We all know that smoking causes lung cancer, and it also causes several other types of cancer as well, things like mouth cancer, pancreatic cancer and oesophageal cancer, but one of those that wasn’t thought to be on that list was breast cancer - well until now. Because a new study by researchers at the Beth Israel Deaconess Medical Centre, published in the journal Cancer Research, suggests that nicotine, that’s the highly addictive chemical that we get in tobacco, could actually be involved in the development and spread of breast cancer.

Chris Smith: But how do you know it's the nicotine and not the thousands of other chemicals that are in the cigarettes that are doing it?

Kat Arney: Well that’s a very good question. Now Dr Chang Yan Chen and her team, they did experiments on breast cells that were predisposed to turn into cancer cells, and they actually looked at breast cancer cells as well that had been grown in the lab, and they found that they had parts of the nicotine receptor. This is the nicotinic acetylcholine receptor as it's known to scientists, and this is usually found on nerve cells, and it's this receptor that responds to nicotine, and although the receptor, or at least certain parts of it, are known to exist in other tissues of the body, it's not really known what they do. But in these experiments, at least, it seems that activating this receptor that’s found in these breast cells on precancerous or cancer cells can actually send signals in the cells, potentially increasing the levels of cell growth and movement by bypassing some of the normal check points that control them, and both these processes are really important in the development of cancer.

Chris Smith: So why have the breast cancer cells got a receptor that’s normally found on a nerve cell on them anyway?

Kat Arney: Well that’s what we don’t know. You know, we know that these receptors are found in various parts of the body, we don’t really know what they do. And what’s really interesting about this research is that although it doesn’t show that nicotine alone can actually cause cancer but it looks like, through these experiments at least, that nicotine may be enhancing the effect of other cancer-causing agents or fuelling the growth of cancers that have already started. So obviously the next step for these researchers is to try and unpick it and study the interaction of nicotine with other cancer-causing genes.

Chris Smith: Do you think it's because cancer is a genetic disease and the chromosomes in cancer cells are all messed up and therefore they start to make the receptor accidentally?

Kat Arney: That may be one thing. I mean all sorts of genes get switched on and off in cancer cells. But, as I said, we do know that these receptors or at least parts of them are found in other parts of the body, maybe they do have some role in growth and maybe in cancer activating them can just trigger that overgrowth that leads to cancer and leads to cancer spread.

Chris Smith: So does this mean then that if you are diagnosed with breast cancer and you smoke, that you should stop smoking?

Kat Arney: Certainly anyone who smokes would definitely be well advised to give up smoking. It's the best way to reduce your cancer risk anyway. And certainly giving up smoking if you’ve been diagnosed with cancer would be a very good idea anyway regardless.

Chris Smith: So no smoking mirrors there - sound advice from Kat on not smoking if you have breast cancer. Now this is interesting because as you get older, people worry about losing their marbles and their brain not functioning quite as well as it could but becoming a silver surfer it seems could be one way to offset that.

Kat Arney: That’s absolutely true and searching the web, something that many of us do on a daily or even an hourly basis, I mean I'm every minute on the internet. But researchers at the University of California, at Los Angeles, have found that a spot of Googling can stimulate the brain activity in middle age and older people, and it may actually help to improve their brain function, and this is because actually internet searching is really quite a complicated task. Now it's been thought for some time that engaging the brain in complex tasks like crosswords or chess can help to stop you going gah-gah as you get older, even warding off diseases potentially such as Alzheimer’s, but nobody’s really looked at the role that new technology could play.

So to uncover this link, Dr Gary Small and his team studied twenty-four volunteers, they were aged between fifty-five and seventy-six, half of them were your savvy silver surfers and the other half were web virgins, and the researchers asked the volunteers to carry out web searches or just read a book while they were in this brain scanner, something called a functional magnetic resonance imaging scanner. And this looks at the intensity of brain cell function by measuring the blood flow in different areas of the brain.

Chris Smith: And what did this reveal?

Kat Arney: Well, unsurprisingly, the team found that when all the volunteers were reading a book, they showed significant brain activity, but when it came to searching the web, the researchers found that, although all the volunteers showed brain activity in the same areas that you see when you’re reading, experienced web users, the silver surfers, showed a lot of activity in other parts of their brain too - these are the parts that control decision making and complex reasoning. So the team think that basically internet searching appears to engage the brain to a much greater extent than just reading but only if you’re used to using the internet and understand how it works.

Chris Smith: Do you think it's a valid comparison reading a book versus actually interacting with a computer and a website?

Kat Arney: Well this research certainly shows that the two things are very different. Obviously, the internet is a much more interactive medium. And what this research certainly shows is that that interaction with it, having to make decisions, think about what are you looking for, pointing, clicking, all of that really gets the circuits engaged in your brain, and certainly what these researchers think is that this extra brain stimulation, the sort of thing that you get by doing crossword puzzles or playing chess, the activities that we know are good for the brain, searching on the web could actually help to be protective in the brain in older people.

Chris Smith: But to be honest, Kat, I'm a bit sceptical because a few years back scientists showed that peeling an apple also engages those very executive centres at the front of the brain, the areas that people have been proven to benefit from activating in terms of not losing their marbles as they get older, so do you really think that the internet is a good way to stave off dementia?

Kat Arney: Yes, this is really the first study that’s ever been done so it is pretty early to make a sweeping generalisation and say that all grannies should surf. But it's certainly very interesting because really people have not looked at the role that technology and increasing technology in our lives and especially as we all get older, what role that might have in protecting or destroying our brain function.

Chris Smith: I guess we'll have to wait until we’re all older to find out. Now this is a very interesting story, which is that scientists have managed to make a light sensitive molecule?

Kat Arney: Yes, this one’s great. A team of researchers from Penn State and the University of Texas South Western Medical Centre have discovered a way to use light to activate enzymes - those are the proteins that catalyse biological reactions. And led by Professor Stephen Benkovic, the research has started by designing something called a hybrid protein or a fusion protein which basically consists of a light sensing protein from an oat plant, as plants are sensitive to light, stuck onto an enzyme found in the gut bacteria e.coli, so they kind of did molecular genetics kind of glued the two together, and found that basically you could regulate the levels of activity of the enzyme just by shining light on the other half of it, the light sensitive part of the protein.

Chris Smith: How does it work because you’ve got two proteins that are not normally linked together, and now one’s controlling the other, so what’s going on?

Kat Arney: It really is a very elegant piece of science because they’ve created a protein that basically works like light sensor, like the ones you get in burglar alarms. So when you switch the light on, the enzyme’s activated, but when you switch the light off, the enzyme shuts off, and it's all about how they glued the two proteins together. So there’s quite a lot of impressive molecular engineering behind this. So they had to study the shapes of both the proteins, the enzyme and the light sensing protein, to figure our what’s the sweet spot when you glue them together, the changes in the light sensing protein when it senses light, because that’s how protein sense light, they change shape, changing their kind of molecular properties, how that would affect the enzyme and make sure that it could get switched on when there was light there and switch off. I mean this is all fairly esoteric stuff, to be honest, but in the future it could have some very exciting implications. For example, making nanoscale switches for molecular machines or even switching on or off proteins in cells in people with diseases.

Chris Smith: Which is terrific if you’re worried about people trying to steal your e.coli as well, for example.

Kat Arney:Exactly.

Chris Smith: And talking about e.coli, have you washed your hands before coming to talk to me? I hope so.

Kat Arney: I certainly did. I washed them with soap and water. That’s because I’ve just come off a train so it was not very pleasant. But yes, it's very important to wash your hands after you go to the toilet, and this has been highlighted by a survey by researchers at the London School of Hygiene - funnily enough - and Tropical Medicine, and they found that the further north in the UK you live, the more likely you are to have bacteria from faeces - that’s poo basically - on your hands, and that’s especially if you’re a man, Chris. So to find this out, the team swabbed commuters’ hands outside train stations in Newcastle, Liverpool, Birmingham, Euston and Cardiff, and they found that overall a staggering one in four people had poo bugs on their hands, and people up in Newcastle were three times as likely to be contaminated as Londoners.

Chris Smith: Why is there that geographical difference?

Kat Arney: Well basically they’re not really sure. This is a survey to find out. But it does look like may be people aren't washing their hands so much in the North. But there’s nothing for us southern softies to be smug about here because they found that women living in London were actually three times as likely as men to have mucky paws, and women down in Cardiff were twice as likely to be grimy.

Chris Smith: Terrific. I now know who I should and shouldn’t shake hands with at least if I’ve got some alcohol hand-rub with me. But why are they doing this? It sounds to me a bit unnecessary.

Kat Arney: Well they’ve done it as part of the dirty hand study - great name there - which is aiming to provide a snapshot of the nation’s hand hygiene, and this is part of the world’s first global hand washing day which was on October the 15th, and it is important because the bacteria that the researchers were looking for in this study are all harmless, they’re all found in the gut. They don’t normally cause disease but they do reveal that your hands have not been washed properly after going to the loo, but it's important because if anyone has a tummy bug, and they’re not in the habit of washing their hands properly, that’s how these things get spread. So at the risk of sounding like your mother, make sure you wash your hands.

Chris Smith: Thanks Kat. That was Kat Arney with a round up of some of this week’s top science news stories. And if you’d like to follow up on any of those items, they’re on the web at open2.net/nakedscientists. In just a moment, a new way to tackle TB, scientists have unpicked the workings of a key bacterial enzyme, and what they’ve found could hold the key to a host of new antibiotics. First though, to a brain computer interface that could offer new hope to patients with spinal cord injuries and nerve damage. Worldwide, these sorts of injuries affect millions of people and, typically, the damage is permanent because nerves in the brain and spinal cord can’t regrow when they’re injured. That’s part of the reason why brain injuries are so devastating. And if the injury involves the spinal cord, the brain can no longer communicate with the muscles that we depend on to move and that’s what causes paralysis. But now, working with monkeys, Chet Moritz and his colleagues have developed a way to eavesdrop on the neurological chatter that goes on amongst the brain cells that control movements and then relay those signals to a muscle directly, restoring movement.

Chet Moritz: So we’re trying to develop a treatment for individuals with motor paralysis, and that could result from, for example, spinal cord injury or stroke, and in those types of conditions the brain is in good condition, and the muscles are also in good condition, but the pathway that joins those two, that normally joins those two, has been disrupted. And so our goal was to create a method by which we could reconnect signals from the brain, signals which can be consciously controlled, and use those signals to stimulate muscles in order to restore movements to a previously paralysed limb.

Chris Smith: So does someone who has a spinal injury yet still retains obviously a normal brain, to all intents and purposes, do they have the ability to have signals that you can use for movement?

Chet Moritz: They do, as a matter of fact. Just last year or the year before, John Donahue and colleagues published one of the first studies recording in the brain of paraplegic or tetraplegic patients and discovered that they have quite a number of signals that can be extracted, still under volitional control. And for example, in those patients, imagine moving their hands which have long been paralysed for several years at least, the activity in their brain looks very similar to the activity of that when a healthy person or a healthy animal either makes movements or imagines movements.

Chris Smith: So in this present study, what did you actually do?

Chet Moritz: We began by recording neurones and motor cortex, and that’s the part of the brain that’s responsible for initiating movements, and routed the activity of those neurones through a computer and used that activity to stimulate muscles. Now the crux was developing a method to temporarily paralyse the muscles. So we developed a method whereby we could inject an anaesthetic which made the arm become numb and paralysed for several hours while we carried out these experiments. Then we essentially taught monkeys to play a video game with their paralysed limbs. So the monkeys knew how to play this video game where they moved their wrist back and forth to drive a cursor on a computer screen in the predefined targets. And once they were paralysed, of course, they could no longer move their wrist. But they very rapidly learned to use the activity of these individual neurones, which we connected to a muscle stimulator, to stimulate their own muscles and precisely grade the force that they could produce in order to again play this video game and acquire these targets presented on the screen in front of them.

Chris Smith: How many nerve cells in the brain do you think you’d need to record from to get the kind of resolution of movement that would enable people to do reaching and perhaps grasping movements which are so important to just doing simple things like doing up a button?

Chet Moritz: Certainly, it's an open question exactly how many neurones we need. If the movement is fairly reproducible like closing the hand which involves somewhere in the order of thirteen muscles all in a precise balanced a group of muscles contracting together, it's possible that just a single neurone or a small group of neurones could turn that grasping activity on or off and grade the proportion. Now if you’re talking about individual finger movements, then obviously you need more neurones to actually activate each one of the individual fingers. So it depends on how simple the movements are, how reproducible they are and how much flexibility in the end we’re able to give the patients, that’s going to directly determine the number of independent signals that’ll have to be recorded from the brain.

Chris Smith: And how do you get the signals that come out of the computer back into the muscles because we've talked so far about stimulating muscles but that isn't trivial in itself, is it?

Chet Moritz: We use a technique called functional electrical stimulation, or FES, and that’s actually been around for several decades. But essentially you’re passing electrical current either through a muscle or on the surface of a muscle, and that causes the muscle to contract. We also think of a promising future approach may be to stimulate directly in the spinal cord because we find that we can often activate groups of muscles in these very functional synergies. So, for example, grasp, all fourteen muscles needed to produce grasp can be stimulated in a very balanced and precise way by stimulating in the spinal cord.

Chris Smith: So if you wanted to extrapolate this to a person who’s had a spinal injury, how would see it actually being used?

Chet Moritz: Certainly, the clinical application of this is several years in the future and perhaps even decades has many hurdles that we need to overcome but if we can dream wildly and assume that all those hurdles will be solved in the next several years, which I think is certainly possible, this type of technology could be used for individuals, for example, who suffer a spinal cord injury and are not able to move their limbs to produce at the simplest perhaps grasping of the hand under volitional control by their brain.

Chris Smith: Chet Moritz. He’s from Washington University in Seattle and that work’s published in this week’s Nature. And now from repairing damaged nerves to inflicting some damage of our own on bacteria. Antibiotic resistance is now a major issue in every Western country, and bacterial problems that were once easily solved are now coming back to haunt us. One example is TB which affects about one-third of the world’s population and kills over one million people every year. The problem has got a lot worse recently because now drug-resistant strains of bacteria have appeared, meaning that our existing antibiotic arsenal just isn't working any more. Thankfully scientists at Rutgers University in the US have found a new way to attack the bugs by disabling an enzyme called RNA polymerase that the bacteria rely on to copy their DNA. By studying the structure of the enzyme, the team have developed a new antibiotic molecule called myxopyronin which can lock onto a critical part of the enzyme and prevent it from working. Here’s Richard Ebright.

Richard Ebright: My laboratory studies the cellular machine that’s responsible for the first step in gene expression. The molecular machine has a structure that’s reminiscent of the structure of a crab craw with two prominent pincer-like projections that surround a central cleft. DNA is held in that central cleft and one of the pincers must open to allow DNA in and then must close to hold DNA in place. The DNA is the form in which a cell stores genetic information. You can think of it as a vault, a storage place of genetic information. In order to access that information, a copy must be made which is then transferred out of the storage vault and used to serve as instructions for synthesis of proteins and other cellular components.

Chris Smith: And is that true in both our cells and say micro organisms, bacteria?

Richard Ebright: It is true in all living organisms of bacteria and humans. Each of them has a complex molecular machine to carry out this reaction. Those machines are similar in structure, they’re similar in mechanism, but they differ enough in sequence that it is possible to identify compounds that inhibit the bacterial version of the machine but not the human version of the machine.

Chris Smith: Why is this viewed as such an important target then? Is it because it's so essential to life because there must be lots of machines like this in cells that you could target?

Richard Ebright: It's essential for life. It carries out this first step in gene expression. And it's essential for life in all states of the cell, both rapidly growing bacteria and resting, slowly growing dormant bacteria. This is a matter of particular importance in that for some bacterial infections, such as tuberculosis, there are important states in which the infecting bacterial cells are in a resting effectively dormant state.

Chris Smith: And yet, despite their dormancy, they’re still nonetheless using this enzyme RNA polymerase albeit at a reduced level and that’s why there’s an opportunity to tackle these dormant bacteria with new agents?

Richard Ebright: Absolutely. In a tuberculosis infection, the dormant cells, the resting cells are called persisters. Very few biochemical activities occur inside persisting cells. As a result, there are very few vulnerabilities of persisting cells. There are very few reactions that could be inhibited in order to kill persisters. RNA polymerase is an example of a molecule that’s required for survival of these dormant cells. Therefore if one interferes with the function of RNA polymerase, one is able to kill dormant cells, one has a vulnerability that one can exploit.

Chris Smith: So you can now go out there and either look for molecules that exist in nature or you can make some rationally, just start from first principles and build some chemicals that fit the structure that you now understand in order to block this but not in human cells so we have some brand new agents with which to tackle these kind of bacterial infections?

Richard Ebright: At this point, we have one compound, myxopyronin, that we know has broad spectrum activity against many bacterial species. It has good potency against many bacterial species. It is not toxic in animal tests, even at high doses. And for this compound, we have a structure that defines exactly how the atoms of the compound, the atoms of the antibiotic, interact with their target. We can look at the structure, identify changes that could be made to the atoms of the antibiotic in order to increase potency. There is every reason to believe that we will be able to identify analogues with higher activity and optimal priorities over the next year or two years or three years. Any such analogues would then go into animal tests and then into clinical trials. Overall, the timeframe, perhaps five years, perhaps seven years, if successful.

Chris Smith: Richard Ebright from Rutgers University unpicking the workings of the essential enzyme, RNA polymerase. That work’s published in this week’s edition of the journal Cell. This is the Naked Scientists: Up All Night with me Chris Smith and time now for this week’s Stuff and Non-Science where we massacre myths and bash bad science, and going absolutely quackers for us, here’s Diana O’Carroll.

Diana O’Carroll: This week’s 'Stuff and Non-Science' was sent to us by Michael Oran. The myth is that a duck’s quack is the only sound that won't echo. Is this true? Here’s Trevor Cox from Salford University to put things straight.

Trevor Cox: It might be popular to say that a duck’s quack doesn’t echo, but I'm afraid, as with all sounds, you can get an echo and it can be heard. It kind of depends a bit what an echo is, and we think of echoes as may be standing on the hillside doing a huge yodel and hearing the sound coming back off a large wall, off a large cliff. So we think of echoes as being the reflection of sound off a large surface meaning we can hear sound twice. The first one we make it and the second one it bounces back off the wall. From a physicist point of view, an echo is that reflection from the wall so the echo always exists. But from a psychoacoustics’ point of view, it's actually whether the sound is audible or not.

And that’s where the story with the duck gets slightly more interesting. Because the reality is a duck’s quack may bounce off the wall but it might not be audible. And the reason for that is very simple. First of all, the duck tends to quack rather quietly. So any reflection is naturally going to be rather quiet and difficult to hear. And the second reason is a duck’s quack goes qwaaak - it's got a rather long end to it. So the chances are the reflection mixes with the end of the direct quack making it all rather difficult to hear. The real story should be, a duck’s quack does echo but it's rather difficult to hear but maybe that isn't quite so catchy.

Diana O’Carroll: Trevor Cox there from the Acoustics Audio and Video Department at Salford. It turns out everyone can hear you step on a duck in an auditorium. If you have any science myths that are non-science, do let me know by emailing at diana@thenakedscientists.com.

Chris Smith: Thanks Diana, and that’s Diana O’Carroll with this week’s Stuff and Non-Science. That’s it for this time. We’re back next week with another round up of the latest findings from the world of science. The Naked Scientists: Up All Night is produced in association with the Open University, and you can follow up on any of the items you heard in the programme by visiting the Open University’s website at open2.net/nakedscientists. You can also follow the links there from the BBC Radio Five Live Up All Night webpage. Production this week was by Diana O’Carroll from the nakedscientists.com and I'm Chris Smith. Until next time, goodbye!

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Paul Gabbott investigates a new hope for those with paralysis.

Background

Here's the research used by the team to make the programme.

In the news

‘Surface Sites for Engineering Allosteric Control in Proteins’
by Jeeyeon Lee et al
in Science 322 (5900), p438

The Dirty Hands study
conducted by London School of Hygiene & Tropical Medicine

‘Nicotine Promotes Mammary Tumor Migration via a Signaling Cascade Involving Protein Kinase C and cdc42’
by Jinjin Guo et al
in Journal of Cancer Research

UCLA study finds that searching the Internet increases brain function
Study by Gary Small, Teena Moody and Susan Bookheimer
in American Journal of Geriatric Psychiatry

Interviews

‘Direct control of paralysed muscles by cortical neurons’, by Chet Moritz, Steve Perlmutter & Eberhard Fetz in Nature

‘The RNA Polymerase “Switch Region” Is a Target for Inhibitors’, by Jayanta Mukhopadhyay et al in Cell 135