Cloned tissue cure Parkinson's Mice

Scientists have used cloning technology to cure mice with the symptoms of Parkinson's Disease, using their own cells.

Writing in Nature Medicine, Sloan-Kettering Institute researcher Viviane Tabar and her colleagues collected skin cells from the tails of mice with an experimental form of Parkinson's. They then "cloned" the mice by injecting the DNA from the tail cells into mouse eggs that had previously been emptied of their own DNA.

When the mouse embryonic clones began to develop the resulting embryonic stem cells were then harvested and cultured in a dish with a cocktail of growth factors to trigger them to turn into nerve cells that produce the transmitter chemical dopamine, which is missing from the brains of Parkinson's patients. 100,000 of these cells ere then injected back into the brains of the affected mice. One group of animals got their own genetically compatible cells, whilst a second group of animals were injected with cells derived using DNA from an unrelated mouse. The aim was to test whether using genetically compatible tissue would affect the success rate of the treatment.

Mice that received brain cells made using their own DNA showed significant improvements in their disease symptoms, and analysing their brains subsequently revealed that, on average, 20,000 of the injected nerve cells had survived and wired themselves into the brain.

The animals that received incompatible grafts, however, showed little improvement, and only about 200 surviving cells were visible in their brains later. This result shows for the first time that it's possible to tailor-make genetically-compatible tissue to repair the diseased brain, and that self-derived cells generated like this are likely to be far better received by the body than tissue from elsewhere.

30th Mar 2008

Sharp Beaks Stick to Soft Squid

Could you carve a roast dinner using a knife that had no handle?  Well this is almost what a squid has to do every time it uses its beak.  Scientists at the University of California at Santa Barbara have discovered how a squid’s sharp, hard beak attaches to its soft, squidgy body, leading the way for new materials which can perform more than one task.

Squid beaks are very strong; in fact it’s one of the hardest and stiffest wholly organic materials known.  But it’s never been fully understood how this stiff, hard material can attach to the soft material that makes up most of the squid’s body.  In order to bite down on prey, the beak will exert huge forces on to the soft skin, and - like carving a roast using a knife with no handle – should do almost as much damage to the squid as it does to its prey.

Writing in Science, Ali Miserez and colleagues spotted a clue in the colour of the beak – it fades from black at the tip to almost transparent near where it attaches to the body.  They took slices through the beak of the Humboldt Squid, Dosidicus gigas to look at how things change as you go along this colour gradient.  By using different chemicals to remove either the proteins or pigments, they noticed a distinct gradient in the amount of water, chitin (which is a bit like the protein Keratin – which makes up horns and fingernails) and proteins which include a substance called Dopa - as you go along the beak.

So the very tip, the sharpest, stiffest bit of the beak, called the rostrum, there is far more dopa-containing protein – and these are able to form cross bonds to make the rostrum much tougher.  As you move away from the tip, the amount of protein decreases, but the amount of both chitin and water greatly increases.

This is a great example of nature joining together two mis-matched materials, so we can learn from nature’s example and use these techniques to attach biologically active components to materials.  So we can develop better anti-fowling coatings for boats, but also new and better ways to test how biological systems will react to chemicals.  In fact, knowing how dopa polymerizes has already helped to develop mussel-inspired glue, and should allow us to attach multi-functional coatings on to almost any surface.

30th Mar 2008

Bad memories lost to the ether

A new study has shown that a whiff of anaesthetic might be able to wipe away bad memories and even prevent post-traumatic stress disorder.

Writing in PNAS, UC Irvine scientists Larry Cahill and Michael Alkire describe how they gave volunteers either small amounts of the inhalational anaesthetic sivoflurane, at a dose one-tenth of that needed to induce unconsciousness, or a placebo. The subjects were then asked to look at a batch of 36 photographs. Some of the images were of a harrowing nature, showing severed limbs for instance, whilst others were relatively humdrum, such as a cup of coffee.

A week later the volunteers were asked to recall as many of the images as they could. Placebo-treated individuals remembered 29% of the harrowing images and 12% of the more boring ones, but the sivoflurane group recalled just 5% of the harrowing pictures and 10% of the boring ones. Brain scans show that sivoflurane can interfere with communication between the amygdala - the part of the brain concerned with emotion and fear - and the hippocampus, where new memories are laid down, thus explaining why the anaesthetic-treated group recalled far fewer of the emotionally-harrowing images than volunteers given the placebo.

The team suggest that understanding how blocking this pathway affects memory formation could also be used to treat people at risk of developing post-traumatic stress disorder, a condition in which patients experience vivid and emotionally-charged flashbacks of frightening or stressful situations.

For people who already have the condition though the problem might be more difficult to solve, although New York University researcher Joseph LeDoux has  found that rats that have learned to associate a sound with receiving an electric shock can be pursuaded to forget the association if they are played the sound whilst under the influence of a drug that can affect memory. This suggests that, in the same way, perhaps PTSD patients could be prompted to re-live their ordeals whilst under the influence of a low dose of an anaesthetic to help them to forget their unpleasant experience.

30th Mar 2008

Rule Learning Rats

It seems that rats are even smarter than we thought – they can learn a set of abstract rules and apply them to completely new situations – something we thought previously only humans, other primates and one or two species of bird can do.

When a toddler learns to speak and understand language, they don’t have to learn the meaning of every possible word combination.  Instead, they learn the ‘rules’ of the language, and apply these rules to new words as they learn them.  Now, I’m not suggesting that Rats learn to speak, but they do seem to be capable of the same kind of rule transfer.

Writing in Science, University College London ‘s Robin Murphy and colleagues conditioned rats to expect food after being played a certain sequence of tones – this is called Pavlovian conditioning and the rats responded as you would expect, looking for food after the right sequence.  They were fed after hearing the sequence ABA, and BAB, but not after the sequence AAB, BBA, BAA or ABB.

They were then tested again using different tones –if they responded to the right sequence, regardless of what tones they were, they would have transferred the sequence rule to a new set of conditions.  It’s been shown that songbirds do not recognize a song that has been transposed by an octave, so different tones should be treated as a completely new situation.

They were played sequences of CDC, DCD, CCD, DCC, DDC and CDD – and the researchers again measured how long the rats spent looking for food after each sequence.  The rats spent much more time looking for food after the sequences they had learned with different tones – in this case CDC or DCD.  This shows that rats are able to apply abstract rules to a novel situation, a key element of problem solving.

So both rats and humans have evolved a mechanism to transfer abstract rules to new situations, a key skill for the development of language which seems to set us so far apart from the rest of the animal kingdom. This ability makes up part of the neurological ‘toolkit’ we have for solving problems, probably part of why both rats and humans are successful almost everywhere on Earth.

30th Mar 2008

Great Ape Gambles

Chris - Sarah Heilbronner is a researcher at Duke University in the US and she been giving chimps and bonobos (an animal related to chimps) a choice between taking a safe bet and being more adventurous. Hello Sarah.

Sarah - Hello

Chris - What did you do in your experiments? What did you find?

Sarah - We were interested in the execution of decision making strategies and particularly the strategies about risk. As you said we looked to our closest evolutionary relatives, chimpanzees and bonobos, for help. The task that we used has a very intuitive human analogue and so I’ll describe that first. If I put you on a gameshow and gave you a choice between what’s behind door number 1 and what’s behind door number 2 and said that you could keep whatever was behind the door you chose. I’d also told you that behind door number one there was definitely $40 or £40..

Chris - It’s a bit of a low-budget gameshow then?

Sarah - Well, I never said it was going to be a very exciting gameshow but you’ve got on it for free so it should be ok.

Chris - And door number 2?

Sarah - Door number 2, there’s a 50% chance that you’ll get $10 and there’s a fifty percent chance that you’ll get $70. The expected value of door number 2 is the same as the expected value of door number one. As you suggested in your introduction, because you’re a human you’re gonna prefer door number 1. You’re going to prefer the safe bet to the gamble.

Chris - Do we know why people tend to be safe betters? Why aren’t we more adventurous in our betting?

Sarah - This was exactly the type of question we were interested in asking. Instead of asking it about humans we asked it about chimpanzees and bonobos of the great apes. But of course chimpanzees don’t regularly work with money nor do they open doors. Instead they were choosing between what’s underneath bowl number 1 and what’s underneath bowl number 2. We used grapes instead of money. Bowl 1 always covered four grapes. Bowl 2 50% of the time covered one grape and 50% of the time covered 7 grapes. What we found was pretty surprising. The chimpanzees who are our closest relative actually preferred to gamble. They didn’t show the same type of preferences as humans. The bonobos were actually very much like humans and they wanted the safe bet as opposed to the gamble.

Chris - So the chimpanzees were always being very adventurous. They were taking the high adrenaline option and gambling even though sometimes they got less fruit even if they picked the bowl they knew had just four pieces of fruit under it?

Sarah - Exactly. Now over time, chimpanzees and bonobos got the same amount of fruit because they were doing this over and over again. They both had these strong but opposite preferences.

Chris - Have you any clue as to why, Sarah? Do you know why they were behaving like that?

Sarah - The big question is why. We went back and did some investigation into what they eat in the wild. We were studying captive chimpanzees and bonobos in the zoo but if these chimpanzees and bonobos had been in the wild the chimpanzees would have been taking much more uncertain, much riskier food sources than bonobos. I’ll give you a couple of examples. One is that both of them feed on fruit trees but the fruit trees that bonobos are feeding on are much more consistent in their environment and they tend to be larger. They’re a much less risky option. An easier one to understand maybe is that chimpanzees are sort of unique in that they hunt colobus monkeys. They go out in big groups and they search for colobus monkeys and they invest a lot of time and energy into doing this. If they manage to bring a colobus monkey down they get a lot of calories. It’s a high payoff but high loss possibility there.

Chris - What you’re saying is that because they have a high-risk lifestyle then evolutionarily speaking they’ve grown up to gamble which is why they do it even when you put them in an experiment.

Sarah - This is exactly right so even when they’re in an experimental situation and all the conditions are the same they’re still going to maintain the types of preferences that they had back in their evolutionary situation.

Chris - So coming back to us, humans for a second, what are the implications for the fact that we are gambling on the stock exchange, we go to the betting, we bet on the Boat Race (Cambridge lost, unfortunately-that’s bad news for us). Are we applying the kind of logic that would have guaranteed in our ancestry that we would have filled up the fridge to a modern economy and there’s therefore a flaw in how we process our decisions?

Sarah - It’s a hugely interesting question because much of behavioural economics over the past few decades has shown that humans are not rational actors even though we like to think of ourselves as extremely rational beings. Especially when we’re making big decisions about money but these types of results do suggest that actually we are making decisions, at least partially, based on what we faced during our evolutionary history and the most important thing then was not money. Money is a relatively recent invention. The most important thing was food so I think these results suggest even for us, humans, a rational actor (Homo economicus). Even for us, we’re probably making decisions based on strategies that were used in our evolutionary path to get food and we might not even be aware of that.

Chris - Thank you very much for explaining that to us, Sarah. Basically, put simply, next time you choose a safe bet over a risk you’re probably behaving more like a bonobo than a chimp.

March 2008

Fizzy Yeast

Find out what makes bread rise and champagne fizzy in this simple kitchen science.

What you need

What to Do

What may Happen

You should find that the mixture becomes frothy, and the balloon inflates.
If you leave the mixture for a couple of hours and then shake it, you should find that it froths up like a fizzy drink.