Raindrop Traps and Microbes for Immunity

25 June 2012
Presented by Chris Smith, Helen Scales.

BACTERIA-CELLS

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This week, how microbes make for a healthy immune system, how pitcher plants use raindrops to trap their prey and a new way to block degenerative diseases such as Huntington's disease. Plus, we go online to identify the most influential people in the World around us and discover the transmission potential of H5N1, how natural selection is being used to compose music and the world's first 50 gigapixel camera!

In this episode

00:21 - Microbes maketh a healthy immune system

Any old bacteria won't do: to be healthy, an animal requires a unique consortium of microbes in its intestines, US scientists have revealed.

Microbes maketh a healthy immune system

Any old bacteria won't do: to be healthy, an animal requires a unique Intestinal bacteria (green) are maintained at a distance from the epithelial surface (blue).consortium of microbes in its intestines, US scientists have revealed.

It's been known for some time that mice raised in a sterile environment, meaning that their intestines remain uncolonised by microorganisms, are paradoxically less healthy than equivalent animals reared in a natural, germ-laden environment.

Some species even depend absolutely upon microbial colonisation in order to develop and reproduce at all. Without the help of the cholera-relative Vibrio fischeri, certain tissues don't develop in squid, for instance, and tsetse flies that fail to team up with the bacterium Wrigglesworthia glossindia lack key vitamins required for fertility.

These and other observations have led to the formulation of the human "hygiene hypothesis", which holds that rising rates of allergy and autoimmune diseases amongst western populations reflect an obsession with sterility and a failure to engage effectively with the microbial world. This, scientists say, hampers the development of the immune system, putting people into a pro-allergic state.

But now, new research presented this week in the journal Cell by Harvard scientist Dennis Kasper and his colleagues suggest that just mere exposure to a microbial milieu isn't sufficient. Instead, what organisms require is colonisaton by a unique collection of highly-specific microorganisms unique to a given species.

The team made the discovery by colonising initially germ-free mice with either normal mouse or human intestinal microbes. A third group of animals were left uncolonised as controls.

Both colonised groups developed similar levels of bacterial loads in their guts, the team found. But when they compared the immune systems of the two, the animals colonised with human flora had fewer white cells known as lymphocytes in their small intestines, they secreted lower levels of defensive antibodies and proteins, and they had fewer immune presenting "dendritic" cells in the gut lining.

And compared with the animals colonised with normal mouse bacteria, those carrying human microbial flora were also highly vulnerable to Salmonella enterica infection. In fact, the human-bug colonised animals were equivalently unhealthy and as vulnerable as the germ-free uncolonised mice.

As Hachung Chung, one of the research team puts it, "Despite the abundant and complex community of bacteria that were in the human flora mice, it seemed like the mouse host did not recognise the bacteria."

The interaction also appears to be highly specific since repeating the experiment even with rat, rather than human, bacteria produced the same result, suggesting that millions of years of co-existence between microbes and hosts has produced animals pre-programmed to depend upon the presence of certain bugs for the immune systems to develop and function normally.

"This raises serious questions regarding our current overuse of antibiotics, as well as ultra-hygienic environments that many of us live in," says Dennis Kasper. "If the bacteria within us is specific to us and necessary for normal immune system function, then it's important to know if we are in fact losing these vital bacteria. If that is the case, then this is yet further evidence that the loss of the good bacteria is partly to blame for the increased rates of autoimmunity that we are now seeing."

Pitcher plant and ant

04:34 - Pitcher plants use raindrops to catch ants

Scientists have uncovered a new way that carnivorous plants catch prey, using rain power to help them.

Pitcher plants use raindrops to catch ants

Scientists have discovered a new way that carnivorous plants catch their prey, using the power of raindrops to flip insects into their trap.

Tropical pitcher plants have evolved specially adapted leaves that form a deep bowl, partially filled with digestive fluids, and with a little lid projecting over the top to stop the plant from getting filled up with rainwater. The plants produce nectar to attract insects and set various traps to catch them - the inner wall of many pitchers is covered in platelet-shaped wax crystals that become extremely slippery when wet.

The pitcher plant, Nepenthes gracilis, is unusual because they also produce crystals on the underside of their lids - and researchers wondered whether the lid itself is involved in helping to trap prey. After all, for an insect to cling upside down, right over the trap, is a very precarious position to be in.

Watching these plants in northern Borneo, Ulrike Bauer of the University of Cambridge and her team, saw ants happily walking upside down on the pitcher plant lids and not falling in. Then, during a rain shower, they happened to spot a ladybird crawling beneath the pitcher lid to take shelter only to be flicked by a raindrop into the trap.

To test whether lids really are helping to trap prey when it's raining, the team took some pitcher plants and ants into the lab and doused them in showers of artificial rain.

They found that around 40% of all the ants visiting the pitcher were caught when it rained. And when the rain was switched off, no ants fell into the traps showing that the lids aren't becoming more slippery with increased humidity after it rains.

Performing the same tests on pitcher lids cut off and mounted with a paper clip gave a very similar result. When it's raining, ants find it much harder to hang on.

Back in the field, adding a smear of anti-slip silicon to the underside of pitcher lids made them much less efficient at catching prey in the rain.

The paper appears in the journal PloS ONE and is accompanied by video clips of the ants having a tough time getting to grips with the pitcher plants in the rain.

So it seems that Nepenthes gracilis has evolved to be a lid specialist - they make more nectar in their lids than other pitcher plants, and the team also found the crystals on their lids have a different microscopic structure than other plants, letting ants hang on in dry conditions, but the vibration of raindrops is enough to catapult them into the digestive juices. It's thought that the ants that escape when its dry act as scouts returning to their colony and bringing back lots more ants. And living in very rainy places, chances are that when the ants return, they could find that the heavens have opened and the pitcher plant is a much more dangerous place to be.

07:40 - Identifying the Influential

Are you a leader or are you a follower? An intriguing new study shows how you can identify influential people from their activities on Facebook...

Identifying the Influential
Prof. Sinan Aral, New York University

Chris -    Are you a leader or are you a follower?  An intriguing new study shows how you can identify influential people from their activities on Facebook.  Sinan Aral is at the New York University Stern School of Business.  He's with us now.  Hello, Sinan.

Sinan -   Hi.

Chris -   So first of all, what were you trying to prove with this study?

Sinan -   Well, in essence, finding influencers or as you said influential peopleA computer is sort of all the rage today.  Companies like Klout are trying to measure influence scores for people on social networks like Facebook and Twitter, but beyond marketers, managers and policy makers are more generally interested in how behaviours spread through society.  In this paper, we present a general method for measuring influence susceptibility in networks and the main contribution of the method is that it avoids known biases in current methods such as homophily bias.  Homophily means that we tend to make friends with people like ourselves.  For example, if two friends adopt a product or a behaviour one right after the other, current methods have a hard time distinguishing whether it's because of pure influence; one friend influencing the other, or if friends simply have similar preferences and thus, behaves similarly.

Chris -   And obviously, the world doesn't work like that because an influential person isn't just influencing their friends.  They have the ability to influence a range of different demographics.

Sinan -   Exactly, so what we did was we applied this general method to measure influence and susceptibility in the adoption of a commercial product on Facebook among 1.3 million users and we were able to recover influence and susceptibility scores that aren't subject to these known biases like homophily bias.

Chris -   Okay, so can you talk us through what you actually did?  How did you recruit the people and then what actually happened to discover this?

Sinan -   We worked with a company that developed a commercial movie application where you can rate movies and buy movie tickets, and read about directors and actors.  And as people adopted this application, we randomly assigned them to send messages to their friends in a random manner.  So, every time you did something on the application like rate a movie or talk about a celebrity or something like that, it would randomly select a subset of your Facebook friends to send a message to.  And this randomization removed the selection bias of people selecting friends with similar preferences or selecting people who they knew would be specifically susceptible to influence.  And with this randomization, we were able to measure, for example, how your characteristics or your traits, your age, your gender, your relationship status on Facebook or anything that we could observe about you on Facebook, was correlated with your likelihood of responding positively and adopting this application upon receiving this influence mediating message.  And because the messages were randomised, we could make causal inferences about whether this message was causing you to adopt or not.

Chris -   What about the other way around because that's looking at people how they respond to receiving the message?  What about in terms of the people who actually send the message?  Are you inferring whether they're influential or not based on what the response of the recipients is?

Sinan -   Exactly, so we estimated a statistical model that estimated both influence and susceptibility simultaneously while these random messages were being sent to people from their friends.

Chris -   So, spill the beans then.  What makes someone highly influential?  Is it just that they're very well connected or is there something special?  Is there some special recipe that means that if they say something on Facebook, everyone's going to be talking about it?

Sinan -   We found that it's not just how many people you're connected to and lots of people have been focused on that in the past, how many followers you have, but more importantly, it's whether you persuade your followers to change their behaviour.  What we found was that in the context of this particular movie application when we applied this method, that men were more influential than women, that women influence men more than they influence other women, that older people are more influential and less susceptible to influence than younger people.  Married people are the least susceptible to influence and influence and susceptibility trade off.  Meaning, people who are more influential tend not to be susceptible and people who are susceptible tend not to be influential.

Chris -   Isn't this just what we see in politics though?  If you take a look at the Houses of Parliament here in the UK or you look at Congress in America, do you not already see this playing out we're just basically proving what we already know?

Sinan -   Not exactly.  So, it's not clear whether or not influential people should be more susceptible or whether older people should be more influential than younger people, and my intuition is, that as we begin to apply this method across different behaviours and products, that we're going to see different types of influence emerging in different contexts.  In a different context, it could be that women are more influential than men or that younger people are more influential than older people - the opposite of what we find here, and the value of this paper is it provides a method to measure this in any context.  I'm really excited to see what we might find for other types of products or behaviours.

Chris -   If we could just look at the question of the men and the women, do you think the fact that it was movies might have led you to conclude that men were more influential than women in this context?  Do you think if you've done something on a subject that women are regarded as more authority figures in, you'd have seen the flip side of the argument?

Sinan -   It very well could be true, absolutely.  So, you could imagine other contexts in which women might be more potentially influential than men, but this, in every context is an empirical question and the benefit of this measure is that we can now talk more scientifically, more rigorously about influence and susceptibility in a causal way.

Chris -   And do you see this being applied to job interviews any time soon in a sense that you come from your job interview and someone decides they want management material or they want someone who'll be well-trained and toe the line and it subjects you to this sort of analysis and you can put people into those sorts of categories?

Sinan -   Yes, I think that it could certainly be applied to those types of situations, but I actually think it's much broader and it's interesting for other types of question as well.  For instance, it's not only about targeted advertising or jobs.  We're also now working on applying these same methods and the same science to promote HIV testing in Africa by trying to understand how we can use peer to peer influence to spread positive behaviours in society - diet, exercise, political awareness and like I said, HIV testing in South Africa.

Coronal image of the human brain at the level of the caudate nuclei demonstrating marked reduced volume in keeping with the patient's known diagnosis of Huntington disease.

15:12 - Blocking degenerative brain disease

Huntington's Disease, a fatal inherited degenerative brain condition, can be controlled in animals using DNA technology, suggesting it might be reversible in humans too.

Blocking degenerative brain disease

Huntington's Disease, a fatal inherited degenerative brain condition, can be controlled in animals using DNA technology, suggesting it might be reversible in humans too.Huntington

Huntington's, which affects about 1 person in ten thousand, is a genetically-transmitted disease of the nervous system that leads to behavioural changes and abnormal movements. These symptoms usually begin after the age of 40.

The nervous systems of sufferers show loss of grey matter, with the brain shrinking by up to a third of its volume once the disease has run its course.

The cause of this degeneration appears to be the accumulation inside nerve cells of a substance called polyglutamine. This occurs because, in carriers of the condition, the gene linked to Huntington's - called huntingtin - contains a repeating sequence of three genetic letters - CAG - that has been abnormally duplicated, making it much longer than it should be.

Repeated CAG signatures like this tell a cell to link glutamine molecules together; unfortunately these glutamine chains are then not easily disposed of, so they inexorably accumulate within the cell with ultimately toxic effect.

But now a paper in the journal Neuron has shown that the application of a technology that won a recent Nobel prize - RNA interference - to the problem can potentially arrest the disease.

University of California San Diego scientist Don Cleveland and his colleagues have been working with mice endowed with a copy of the abnormal human Huntington's gene.

These animals manifest a similar degenerative disease to human sufferers, developing abnormal movements and behavioural deficits from a young age.

The UCSD team constructed and infused into the cerebrospinal fluid around the brains of these animals an RNA sequence that is the genetic mirror image of part of the Huntington's gene. When taken up by cells, these short pieces of genetic material pair up with the products of their matching gene, in this case the huntingtin gene, and cause the genetic message to be shut off so the gene is not expressed.

When administered to the test animals over a two week period, the therapeutic genetic sequences produced a 75% reduction in the levels of expression of the abnormal gene and an improvement in symptoms and disease progression that was still measurable months later.

Tests on a rhesus monkey also suggest that the approach could be delivered to humans using a spinal cannula like that employed to deliver epidural pain relief during labour.

Concluding their paper, the researchers point out that "transient suppression of huntingtin can be sufficient to ameliorate disease for an extended period of time... this finding opens up the provocative possibility that transient suppression of huntingtin can lead to a prolonged effect in patients."

17:46 - Transmitting H5N1 and A 50 Gigapixel Camera!

How just 5 mutations could create a transmissable form of H5N1, the 50,000 megapixel camera providing insight never seen before, how noise affects birdsong in our environment and the naturally selecting the best music...

Transmitting H5N1 and A 50 Gigapixel Camera!
Ron Fouchier, Erasmus Medical Centre; David Brady, Duke University; Steve Nowicki, Duke University; Bob MacCallum, Imperial College London

Transmitting H5N1

Sneeze 4The H5N1 bid flu virus could evolve into a form that is transmissible in humans according to research published in the journal
Science.

In this controversial project, Ron Fouchier from the Erasmus medical centre in the Netherlands infected ferrets with versions of the virus that were genetically modified to increase their affinity to mammalian cells and monitored how the virus continued to mutate upon infection.

The team found that just five mutations in total were enough for an airborne and transmissible strain of the virus to develop.

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A 50,000 Megapixel CameraAWARE-

A 50,000 megapixel camera has been created by scientists at Duke University in the US.

Using improved optical elements, electronics and processors, the camera uses an array of 98 microcameras within a spherical lens each capturing visual information from a specific point. Computer processors then stitch the information together to create images covering a 120 degree field of view with 5 times greater resolution than the human eye.

David Brady led the work published in
Nature.

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Songs through the Noise

SparrowThe calls learned by songbirds vary in response to noise in their environment.

Publishing in the journal
Biology Letters, Steve Nowicki from Duke University investigated how noise from nature and humans affects the calls learned by baby songbirds by raising 9 male swamp-sparrow nestlings in a sound-proof room and exposing them to recordings of song types sung by adult males of their species.

The songs played were either clear...

Click this button to hear the clear birdsong 

Or degraded...

Click this button to hear the degraded birdsong

The team found that when the birds matured and began to sing, only the clear recordings had been learned.

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Selecting your Music

And finally, the process of natural selection has been used to compose and refine pieces of music enjoyed by the masses.

The website Darwin tunes, which has been online since 2009, invited online users to listen to a range of short audio loops and rate them, with the highest ranking then combined to produce the next generation of sounds for rating again, resulting in over 2500 generations in their paper in the journal
PNAS.

One of the more popular loops was...

Click this button to hear the popular song

Each successive generation created more recognisable and rhythmical versions of the tunes enabling the sounds to evolve from noise to music.

Bob MacCallum from Imperial College London led the work published in the journal PNAS.

If you'd like to add to the next generations of music, which has now reached nearly 4200, visit
darwintunes.org.

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