Cluster-Flock Fatigues Pigeons

27 June 2011
Presented by Ben Valsler.

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In this week's Naked Scientists NewsFlash, a new TB vaccination that stands out on it's own, how babies make sense of broken toys, and why flying in a flock may be exhausting for pigeons. Plus, how a nap in a hammock leads to deeper sleep.

In this episode

Mycobacterium tuberculosis (TB) bacteria seen under scanning electron microscope (x15000)

00:27 - TB Booster Better Off Alone

A new study has shown that a breakthrough vaccine against tuberculosis may be more effective when given alone, rather than alongside other vaccines.

TB Booster Better Off Alone

A new study has shown that a breakthrough vaccine against tuberculosis may be more effective when given alone, rather than alongside other vaccines.

Mycobacterium tuberculosisA study by Martin Ota and colleagues on 4-month old West African infants, found that a next-generation TB vaccine, known rather unspectacularly as MVA85A, is significantly less effective when given alongside other, conventional vaccines.

TB is a major health problem worldwide, and the existing vaccine, Bacille Calmette-Guérin, or BCG, named after its inventors, is not entirely effective. The rise of drug-resistant TB strains is making the need for a top-up vaccine in addition to the BCG ever more pressing.

This was the aim of a team at Oxford University that created the MVA85A vaccine. They started with a strain of vaccinia virus - that's the poxvirus which was used as a vaccine to immunize against, and ultimately eradicate, smallpox. The so-called 'Modified Vaccinia virus Ankara', or MVA, was then manipulated genetically to express a protein found on Mycobacterium tubercolosis, called 85A. The immune response against 85A protects against tuberculosis, as it primes the immune system to target the TB-causing bacteria.

The modified vaccinia virus is important because it biases the immune system towards generating killer cells that attack pathogens directly, rather than using soluble molecules like antibodies. This so-called 'cell-mediated' immunity is essential to fighting off TB effectively.

Martin Ota and colleagues at Oxford had already demonstrated that MVA85A is safe and effective at boosting TB immunity in animal models, and preliminary studies on people in Africa and the UK are showing promise. In this latest study, the authors randomly divided a sample of 4-month old children from the Sukuta Health Centre in Gambia into three groups: one group received the standard selection of vaccines called the 'Extended Program of Immunization', or EPI, recommended by the World Health Organization. This includes vaccines against Hepatitis B, diphtheria, tetanus and others. The second group received the EPI plus the new TB vaccine - MVA85A. And the last group received just the MVA85A alone, without the other vaccines.

The scientists then measured the amount of Interferon-gamma (IFN-γ) produced by the participants of the study, at 4 and 20 weeks post vaccination. IFN-γ is a signalling molecule that pushes the immune system towards cell-mediated, rather than antibody-mediated, immunity (and remember that was important for combating TB). They found that MVA85A was significantly better at inducing IFN-γ, and so promoting cell-mediated immunity, when given alone, rather than when given alongside the other vaccines.

This may be because the other vaccines induce antibody responses in the immune system, rather than the killer cell-mediated immunity, and the two immunological strategies are known to inhibit one-another.

So, the study shows firstly that this new TB vaccine is safe, and could work at boosting cell-mediated immunity against TB, and secondly that public health experts may have to re-evaluate how multiple vaccines are given together to children in the developing world.

And that work was published this week in the journal, Science Translational Medicine.

04:08 - Is it Me? Decision Making Babies

Also in the news this week, 16 month old babies can use limited evidence to decide if they have been given a faulty toy, or are just using the toy incorrectly, according to a study published this week in the journal Science.

Is it Me? Decision Making Babies

 Also in the news this week, 16 month old babies can use limited evidence to decide if they have been given a faulty toy, or are just using the toy incorrectly, according to a study published this week in the journal Science.

In order to achieve goals, we need to learn to make this important distinction between faults with ourselves and faults with our environment. For example, if a light switch doesn't work, is it because we pressed the wrong button or because the bulb is broken?

BabyScientists from Massachusetts Institute of Technology designed some clever experiments where infants watched an adult pressing a button on a green toy to produce a sound. Next, the baby was handed either the green toy, or an otherwise identical yellow toy, neither of which worked when the baby pressed the button. The infants had to make a decision: were they making a mistake, for example not pressing the toy hard enough? Or was the toy itself broken?

When they were presented with the green toy, which they had previously seen working well, babies tended to hand the toy to their parents once they failed, possibly deciding that the fault was with themselves, and their parents would be more successful.

But when they were given the yellow toy, babies were more likely to discard the toy and reach for another, a red one placed nearby. As the babies had no evidence that yellow toys worked at all, they were more likely to believe the fault was with the object, and have another go with a different toy.

But researchers wanted to rule out alternative explanations. Could the babies given the experimenter's toy be less likely to want a new toy? Or were they handing toys over because they thought their parents might be able to fix the toy rather than show them how to use it?

So experimenters showed the babies the green toy again, but this time the babies watched as the same experimenters sometimes succeeded and sometimes failed with the toy, suggesting the fault was with the toy itself. Babies picked up on this, and were more likely to give up on the familiargreen toy and reach for the new red one.

Next, babies watched two different adults - one who consistently failed to produce the noise when they pressed the green toy, and one who always succeeded. After this, babies tended to hand the toy over to their parents, suggesting that the babies were aware there was a 'knack' to it that theyjust hadn't mastered.

These fascinating results show that from a very early age, babies can make evidence based decisions about which response to failure, seeking help or exploring alone, will be most likely to lead to future success. They understand the important distinction between faults with themselves or the worldaround them.

Flock Flying Tires Pigeons
Dr Jim Usherwood, Royal Veterinary College

Ben -   A new analysis of the way that pigeons flock suggests that it actually costs them energy to do so.  It's actually more efficient for them to fly on their own.  To find out what this could tell us about bird behaviour I spoke to Dr. Jim Usherwood from the Royal Veterinary College.

Jim -   Birds fly around in flocks quite a lot.  That's something we know about birds.  They like to be together.  The question has been there for awhile - what are they getting from it?  They could easily not fly around in flocks. In the background of bird world we think of lots of rather large birds flying around in Vs.  Things like pelicans and geese fly around in nicely ordered Vs.  Previous work has shown some kind of benefit from flying in the V.  You flap at a lower rate and your heart rate goes down.  Indeed, if you fly airplanes in a nicely ordered V they reduce fuel consumption.  So, you can fly in such a way that you save energy.  Now most birds don't fly around in well structured Vs.  Pigeons are a good example of a normal flock termed a 'cluster flock'. Why might they be flying around as a group?  We simply didn't know whether they're getting any kind of aerodynamic or energetic benefit from it.  What we went about doing is putting, in effect, a Satnav and some internal sensors on every pigeon.  A lot of the same kit as you get on an iPhone on every pigeon of the flock. We then got them to fly around we worked out that these birds are probably getting some kind of energetic cost from flying close together. This leads the biologists in us to look for why on earth would you fly in a flock? We need to look for different answers to that now.

Ben -   So what were the conditions under which they were flying?  Could they have been flocking in response to something that they saw in the environment?

Jim -   That's the beauty of these new sensors now, you can leave them on animals. They can wake up when the animals are doing something, and you can let the animals roam free, doing exactly what they would normally be doing.  These were put on my flock of racing pigeons which were allowed to do whatever they wanted for 3 days.  They're flying around sometimes at 6 o'clock in the morning when nobody was around here.  They take off, fly around in flocks for 5, 10 minutes, tens of thousands of flaps, pulling 2G as they go around in circles. They are then  sitting down and having a bit more breakfast.  They're doing this quite spontaneously.  It's very much like a wild flock would do.  They are in free flight, but we can take the effects of going up and accelerating, and going around corners into account because we've got so many flaps.

Ben -   So how many pigeons were you following and how many wing beats did you actually manage to capture?

Jim -   We wired-up up to 20.  Not all 20 flew all the time.  We're talking about a quarter million of flaps, 400 pigeon kilometres, that we measured. This is just so awesome.  It's the sort of data volumes that you would just dream of.  If you were trying to do this in a wind tunnel just imagine trying to do that.

Ben -   The other question of course is, for all of these pigeons, they have a bit of technology strapped to their back that they wouldn't normally have.  Is it possible that the way that you're measuring this is actually having an impact?  Is that leading to the fact that they need to fly with greater energy?

Jim -   Anything you add to an animal is likely to influence it a bit, especially when it comes to aerodynamics, little bumps sticking up could do untold things with drag.  Having said that, they were flying voluntarily and watching from a ground point of view, they were flying around in a flock like they always do.  So we've got no particular reason to think they're doing something completely out of the ordinary.  Also whatever the effect of having a logger on is presumably the same for all of them.  I don't say it's a huge issue but of course, there's always a call for lighter, smoother, better loggers.

Ben -   Why are you looking at pigeons in particular when we have other birds that have this glorious V formation or those incredible flocks of starlings that seem almost liquid in the air?  Why pigeons?

A Feral Pigeon or Rock DoveJim -   Pigeons are pretty useful in that they represent typical flocks.  They also have a great advantage that they can carry a fair old payload.  These pigeons are quite happy to fly carrying a payload of 30 grams and they come back. So we can just walk up to them in the shed afterwards, pull out an SD card and get a gigabyte of data off them. That makes things a lot easier.

Ben -   And what impact did flying in a flock actually have compared to a bird just flying free on its own away from other birds?

Jim -   It's actually quite a large difference.  If you think of a pigeon flapping along at 8 hertz then as it gets into a flock you've got to 8.1-ish hertz.  That doesn't sound much, but if you compare that with how much it changes to flying uphill.  If it's flying uphill, it's 4 metres a second.  That's a similar kind of change in flap frequency.

Ben -   What advantages do you think there may be in flying in a flock?  We were saying there's strength in numbers, but then if that strength is counteracted by the fact that you need to put more energy into flight, then it seems that it would be something that would be selected against.

Jim -   Yes, so we've got this slight issue that they're presumably primarily flying in order to take exercise here because they're not going anywhere in these flights.  They're getting up from their loft, they stream around, and then they're going back for more breakfast.  So, is it necessarily a bad thing that they flap a bit harder?  Then the prime thing that people will always think of when considering flocks is some kind of a protection from attack.  The evidence for that is fairly strong in that when there's a sparrow hawk or something like that around, they tend to bunch in a much greater flock.  So, there's probably some advantage of being in a tight flock in terms of being difficult to catch.

Ben -   Is this information only really interesting to biologists?  Is it only useful for people studying birds or studying flocks?

Jim -   Well of course, I'm coming at it from the biologist point of view. There's more and more interest in these autonomous or unmanned air vehicles drones. Flocks of them are becoming more and more useful now. They're always interested in making things more efficient.  If you can get a little bit more out of your drone then that's very useful. This would point to not flying your drones around as a flock of pigeons, but keeping in a goose-like structure if you can.

Ben -   Jim Usherwood from the Structure and Motion Lab at the Royal Veterinary College in Hertfordshire. You can read about that work in the journal Nature this week.

Cracking Histamine's Crystal Structure

Good news for hayfever sufferers - by cracking the crystal structure of the histamine receptor, scientists are on the road to developing more effective antihistamine drugs to treat allergy and inflammation.

Pollen viewed under electron microscopeHistamine is a molecule produced by special immune cells in response to certain foreign bodies and potentially dangerous pathogens. It has a variety of effects depending on which of the four types of histamine receptor it binds to, named H1 to H4.

Histamine signalling, particularly through the H1 receptor, is known to play a crucial role in a variety of allergic conditions, including hayfever, asthma, food allergies and the itchy response to insect bites.

Conventional antihistamines, such as cetirizine and acrivastine (that's Benedryl Once a Day and Benedryl Allergy Relief respectively), work by blocking the H1 receptor.

 Using X-ray crystallography, Tatsuro Shimamura and colleagues unravelled theG-protein coupled receptor molecular structure of the H1 receptor, with a resolution of 3.1 Angstroms, or 0.00000031mm. So that's very fine detail!

All four of the histamine receptors are part of a much larger family of 'G-protein coupled receptors', or GPCRs, which includes thousands of different proteins. Shimamura's group showed that the first generation antihistamine, Doxepin, interacts at a particular site in the H1 receptor that is found in most G-protein coupled receptors. This explains why doxepin was so non-selective, and hence why it had so many side-effects, including sedation, dry mouth and heart arrhythmias -  because as well as blocking H1 receptors, it blocked many other GPCRs as well. In addition, doxepin could cross the blood-brain barrier and block signalling in the brain, adding to the sleepiness.

 Second-generation antihistamines, like cetirizine and acrivastine, have far fewer side effects and are considered 'non-drowsy'. The X-ray crystallography suggests that this improvement is due to a second interaction with a different site on the H1 Receptor, in addition to the one that older antihistamines bind to. This second site is not found in other G-protein coupled receptors, which, combined with their reduced uptake across the blood-brain barrier, helps explain their greater selectivity and reduced side effects.

This detailed look at the H1 receptor and its interactions with antihistamines could help guide future drug discovery, so antihistamines used to treat allergies like hayfever may become more effective and with fewer side effects even than current medications.

And that work was published this week in the journal Nature.

Ben -   So it's a bit like the old antihistamines where a sort of skeleton key that would fit all of these different receptors and it's only now that we really know the structure can we design exactly the right key that will only interact with the histamine receptors and that should enable us to block hay fever without all of these nasty, sleepy side effects.

Will -   Absolutely.  The old antihistamines just acted on so many different receptors and it went straight into the brain and so, it had a very blanketing effect on the whole of the brain.

16:58 - Rocking to a Good Night's Sleep

Researchers from France and Switzerland have discovered that the rocking motion found in cradles and hammocks not only lulls people to sleep more, but also encourages deeper sleep...

Rocking to a Good Night's Sleep

Katrina -   This week has seen breakthroughs into the mysteries of sleep, helping us understand the ancient tradition of rocking babies to sleep, and why we need our shut-eye at all.

Researchers from France and Switzerland have discovered that the rocking motion found in cradles and hammocks not only lulls people to sleep more quickly than lying still, but also encourages deeper sleep.

A couple in a Hammock.

They asked volunteers to have a 45 minute nap in their 'experimental hammock', which was either still or gently rocking, while an electroencephalogram, or EEG, was used to monitor the waves of activity in their brains.

The study, published this week in Current Biology, found that the rocking motion helped volunteers fall asleep more quickly, with a shorter period of stage 1, or light, sleep. The rocking caused more stage 2 sleep, and increased the number of sleep spindles. These are important patterns of brain activity that seem to be needed to refresh our ability to learn after our sleep.

So rocking helps send us to sleep, and helps deepen our sleep in an afternoon nap. The next step will be to see if the same thing applies for a full night's sleep, and to see if the sleep changes caused by rocking help with learning and memory consolidation. Perhaps rocking beds will soon be standard options in all furniture shops!

But why we need to fall asleep at all? Also in the news this week, fruit flies have taught us more about the role of sleep in refreshing our minds so that they can lay down new memories.

Researchers publishing in the journal Science used fruit flies that were genetically modified to fall asleep if the temperature rises above 31 degrees centigrade. Armed with this ability to induce sleep on demand, they wanted to investigate the 'synaptic homeostasis model', the idea that new connections between nerves are continuously formed when an animal is awake, and these are downscaled during sleep to prevent an overload of circuits.

They showed that flies in a socially enriched environment, with exposure to 90 other flies, formed lots of new connections between nerves. This meant that they were unable to lay down long term memories when researchers tried to train them to suppress their mating rituals. Flies that had been socially isolated, on the other hand, formed fewer new connections between their nerves, and later performed well on the long term memory task.

But can sleep 'refresh' the brain, and abolish the effect of the social enrichment? The researchers used temperature to allow the flies 4 hours of sleep after their social enrichment. This did indeed restore the ability of the flies to form new long term memories, supporting the idea that a period of

sleep simplifies neural connections and leaves the flies better able to learn.

Ben -   Is there a bit of a risk with this sort of experiment, similar to that we see with bending animal behaviour experiments that we're actually imposing our own judgment in what they're doing, and it's very, very hard to say exactly why a baby does something, just like it would be hard to say why a bird does something or why a monkey does something?

Katrina -   There certainly is that risk, yes and all you can really tell from this study is that there was definitely a significant difference in the decisions that the babies made according to how the experiment has reacted and what toys they were given.

Ben -   It would be very interesting and I'm sure there are lots of new parents around who would love to know exactly what their babies are thinking.

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