Stem Cells Muscle InScientists have shown that, contrary to prevailing wisdom, muscles contain stem cells that can repair, replace and strengthen injured tissue. Writing in Nature Stanford researcher Helen Blau and her colleagues have identified a collection of chemical markers that can be used to identify a population of muscle stem cells.
The team made the discovery by genetically labelling the cells with a coloured marker protein before injecting them into mice with damaged leg muscles. This technique enabled the researchers to follow the progress of the same mouse over a period of time by using a sensitive camera that could pick up the increasing intensity of the coloured stem cells as they grew. "We were able to show that the injected cells increased their own numbers, contributed to existing muscle and also produced entirely new muscle in these mice," points out Blau. The results are very exciting because now researchers are able to readily identify the muscle stem cells they can turn their attention to discovering ways to activate them in people with muscle-wasting diseases, or use them to repair muscles in trauma patients. "That's the next step," says Blau.
21st Sep 2008 ‘Baby’ Fat may Beat ObesityIt’s something that many of us struggle with – fat. But where does it come from? Researchers in Dallas have finally tracked down the location of immature fat cells, which hide out waiting for the extra calories that turn them into flab.
21st Sep 2008 Fungi are world's fastest fliersScientists have discovered the fastest fliers in nature and, somewhat surprisingly, they're fungi!
Writing in this weeks PLoS ONE the team have successfully made fungal ballistic measurements of spore trajectories to reveal that these organisms are firing their microscopic projectiles, which measure just a fraction of a millimetre across, at speeds exceeding 25 metres per second and at rates corresponding to 180,000 times the acceleration due to gravity. This is sufficient to propel the spores up to 2.5 metres away from the parent dung pile. The team were also able to get a handle on how the organisms achieve their fungal feat. A concentrated mixture of sugars, alcohols and other metabolites inside the fungus and its fruiting body pulls in water by osmosis, priming the gun at a pressure about four times that of the atmosphere. At the right moment the structure ruptures and the pressure drives out the spores. According to the researchers the images of these fungal ejaculations are so pretty that they've set them to music and plan to post them on YouTube!
21st Sep 2008 Plant Sugars Provide PetrolWe all know that the days of fossil fuels are limited, so researchers are trying to find alternative fuels. Biofuels have risen in popularity in recent years – fermenting plant material to make ethanol is already being used to produce fuel in several countries around the world. But ethanol is a long way, chemically speaking, from the petrol (or gasoline for our US listeners) and diesel that are currently used in car engines.
21st Sep 2008 Surprise Attack - Stopping Bacteria from Sensing your Immune ResponseVanessa Sperandio, Southwestern Medical Centre, University of TexasChris - Some bacterial infections, like E. coli 0157 which is a cause of food poisoning and can also damage your kidneys, seem to get a lot worse when you give patients antibiotics, instead of getting better. It seems that this is because the bacteria enter a sort of high-alert state in response to the treatment. They fight back by becoming a lot more virulent. Researchers at the Southwestern Medical Centre, University of Texas have come up with a drug that can stop the bacteria from sensing the chemicals in your body that tell the bacteria your body’s gearing up to fight them. Dr Vanessa Sperandio is in Dallas and she joins us to tell us a bit about this research. Hello... Vanessa - Hello Chris.
Vanessa - They sense two stress hormones that you have: adrenaline and noradrenaline, and they use those two hormones as cues to know they are inside of you. When they sense that through a receptor in the bacteria they activate production of the virulence trait. By doing that they can actually make you sick and turn on everything that will cause disease. Chris - It’s intriguing to think that these bacteria are eaves-dropping on our own inflammatory signals. They’ve learned or evolved, I should say, to detect the signals our body uses to fight them. Vanessa - Yes, and those are very primal types of signals. That’s at the core of your immune system and it’s the core of gauging how well – how healthy or not you really are and how stressed you are. Chris - How did you get a handle on what the bacteria were doing and then try to work out how to stop them? Vanessa - We figured out many years ago that they were using the signals and then in 2006 we were able to identify one of the bacterial receptors for this signal. What we’ve done now is to develop drugs that will bind to the bacteria receptors and prevent the receptors from seeing the host’s stress hormones. In this way the bacteria passes blindly through the host without being able to know where it is and activate it virulence traits. Chris - So you’ve managed to come up with a drug molecule that can block up the ability of the bacteria to see adrenaline or noradrenaline so the bacteria don’t effectively know they’re in the body. Vanessa - Yes. Chris - How could this molecule be used and is it safe? Vanessa - So far the molecule is safe. Of course, this is in the lab of proof of principle. We did do some preliminary toxicology in mice and so far it looks to be safe. It also does not signal to human adrenergic receptors, which is important. It can be used either to treat infections or hopefully we want to try to use this to prevent infections.
Vanessa - It can be very useful for something like E. coli 0157 which, right now, has no treatment. We also did look at this drug to treat salmonella infections which can cause gastroenteritis and typhoid fever. We looked into tularaemia which is a bioterror agent. In between these bacteria there are several important pathogens that have this sensor. This could be used hopefully to treat some of the communal infections especially for patients in ventilators. Bacteria like klebsiella, acinetobacter, pseudomonas who are important in this class of patient s which do not have a lot of treatments and antibiotics against and are quite resilient to the biotic treatments. They all posses this signalling system. Chris - When do you think that we might be seeing this going into humans in clinical trials? Vanessa - We’ve got money from the National Institute of Health to develop this drug to pre-clinical in five years which means in five years we want to be able to have everything pre-clinically, toxicology and safety done. Hopefully in five years we’ll start the first safe trials in humans. Chris - Thank you Vanessa. September 2008 Fizzes from peroxideUse the power of catalysis to create oxygen and relight a piece of wood, and we give the same reaction a more explosive twist. What you need
What to DoWarning - Hydrogen peroxide is a weak bleach, it will irritate the skin, and you really don't want to get it in your eyes, so wear some form of eye protection. You are dealing with burning objects which may burn quicker than you expect. This experiment should be done by an adult. Pour about 1-2cm of hydrogen peroxide into a jar. Add some potato, what happens? Try the same thing with a small piece of liver. Try lighting a splint and then blowing it out so it is still glowing, and putting it into the jar. What may HappenYou should find that the hydrogen peroxide sits there quietly until you add the potato when it will bubble gently. When you add the liver it should froth violently and if you carefully feel the jar, you should notice that it gets warm. The splint should relight when you put it in the jar, showing that you have made some oxygen.
Just to make it a bit more interesting we thought that we would try to use this principle to power a lemonade bottle rocket, using the oxygen produced to pressurise the bottle. Do not try this at home, you are pressurising bleach, it could spray everywhere!
Thanks to Ian Russell for the idea. What is going on?
Hydrogen peroxide has a molecule very like water but instead of being H2O it has an extra oxygen molecule to form H2O2. This extra oxygen is the reason that hydrogen peroxide acts as a bleach and an antiseptic. The Hydrogen peroxide can react with many different organic molecules oxidising them, which is equivalent to partially burning them. Many coloured molecules are particularly susceptible to oxidation, so they tend to be damaged first so a material will loose its colour long before it is seriously damaged. If you add hydrogen peroxide to a living cell it will Oxidise molecules at random, causing all sorts of biochemical chaos and seriously damage or kill the cell which is why hydrogen peroxide and other bleaches are very good antiseptics. This is also why most biological cells have mechanisms to get rid of the hydrogen peroxide, which is made as a biproduct of several metabolic processes, as quickly as possible. One of the mechanisms is using an enzyme called catalase. Hydrogen peroxide will decompose into water and oxygen in sunlight, very slowly over a period of days, so it is sold in dark brown bottles to keep the light out. However catalase is an enzyme - a biological catalyst which speeds up the reaction thousands of times without being used up itself causing oxygen to be released fast enough to form bubbles.
The liver is used to remove toxins from the body so there is a particularly high concentration of catalyase there so liver will decompose hydrogen peroxide particularly quickly.
Why does the splint relight?Burning is just the reaction of a fuel with oxygen, the more oxygen there is the faster the reaction, so the faster and hotter the fuel will burn. A glowing splint is still burning slowly, so when you put it into the oxygen the reaction speeds up so it gets hot enough to start burning with a flame again. How do catalysts speed up the reaction?Catalysis is a hugely complex subject and still somewhat of a black art, but one way that catalysts, particularly biological catalysts (enzymes), can work is by holding molecules in the right orientation. This helps because for a reaction between two molecules you need them to collide, with enough energy and in the right orientation. If the catalyst holds them in the correct orientation, this can hugely increase the likelyhood of them reacting. Written by Dave Ansell The Problem with Clostridium difficileSani Aliyu, Addenbrookes HospitalChris - Dr Sani Aliyu is a consultant doctor at Addenbrooke’s, one of Cambridge University’s teaching hospitals. He’s with us this evening. Hi, Sani. Welcome to The Naked Scientists. Sani - Hello, Chris. Chris - So C. difficile, what is it?
Chris - Where do we tend to get it then? Does everyone carry C. diff? Sani - Well, no. As an organism it’s quite ubiquitous. In other words it survives in the environment. The spores themselves are quite hardy organisms. You can acquire them from the normal environment as well as from domestic and animals and farm animals. More frequently it tends to be in hospitals because you have patients that already have this infection and they’re producing a lot of the organism and are contaminating the environment. Patients can easily pick up the infection from that. Is it just gut infections it causes or can it also get to other bits of the body? Sani - Well, predominantly gut infections what happens is the gut produces a lot of inflammation within the gut. As a result it can result in quite severe damage to the bowel, perforation, dehydration, severe diarrhoea and subsequently end-organ damage: including death. Chris - Because it’s triggering diarrhoea I presume it’s so easy for it to spread because it’s making people go to the toilet a lot. Every time they go to the loo they’re shedding more of these tiny spores into the environment and that makes it very hard to treat. Sani - Absolutely. Patients with diarrhoea can excrete as much as up to a million bacteria per gram of faeces. It can be quite profuse, really. Chris - Once you’ve got the spores coming out into say, a hospital ward or a toilet how do you get rid of them? Sani - Predominantly by good cleaning, really. The spores themselves are quite hardy organisms. We know that they respond – they are quite sensitive to chlorine-based products. Using alcohol, for instance – alcohol gel – in hospitals wouldn’t get rid of the spores. Chris - Why is it mainly old people who tend to suffer with this? Why is it people our age – I know that as a percentage of the population there’s fewer of us lot in hospitals – but when you look at people in hospitals the proportion of old people getting C. diff is usually higher. Is that just because they’re more vulnerable anyway?
Chris - In other words your body’s own bacteria effectively take up the available space. There’s nowhere for the C. diff to fit in. If you kill those bacteria with a dose of antibiotics or just because that bacterial flora changes with age anyway it makes openings or niches that C. diff can then get into more easily? Sani - Yes. In fact the normal bowel flora as we call it prevents the overgrowth with C. difficile by depriving the organism of micronutrients which means it can’t establish an infection. Chris - In terms of why it’s such a problem now, because ten years ago it was a few cases, now we’ve got 7000 deaths a year. Why s the graph going up exponentially like that? What’s happening? Sani - It’s partly due to improved reporting. Over the last few years we’ve put in place mandatory reporting processes which means that if you have a case of C. difficile you have to report it. The testing has also changed. In the past we used to test in individuals that are over the age of 65 but nowadays anybody having diarrhoea above the age of two. You have a more virulent that first emerged in Canada about 5 years ago and has since occupied the niche that used to be occupied by the more sensitive strains. Chris - When you say more virulent what do you mean by that? Sani - More virulent in terms of producing more toxin, causing more diarrhoea, causing more illness and probably more deaths as well. Chris - Do we know why this has come about? Is it just because it was a random mutation? It just appeared and because it was so much more prolific in terms of its production of diarrhoea and its ability to spread that it just went all over the world? Sani - I think it’s fairly different from other strains of Clostridium difficile in that it has a deletion in the gene. There’s a gene that negatively regulates toxin production. This particular ribotype called the autosomal ribotype has a deletion in that gene which means it can produce much more toxin and it can germinate for a longer period of time than other ribotypes of Clostridium difficile. Therefore you tend to have more spread as well, more environmental contamination as a result of a more severe disease. Chris - What can we do about it? Sani - In the first place we can restrict antibiotic use. A lot of times we use a lot of antibiotics in the community as well as in hospitals that we probably don’t really need. That’s one. Secondly, by improving cleaning and making sure that you interrupt the transmission process from patient to patient either by washing our hands, isolating patients promptly, putting them inside rooms, avoiding contamination of hospital equipment – that will go a very long way to reduce the infection. Chris - Lastly, how long do you think it’s going to take before we get a handle on this problem and can bring it under control? Sani - I think we will. It might take another –being on the optimistic side – another five years. There are new things coming up like vaccines which we hope will probably reduce the incidence of infection. We’re having new agents as well coming in which at the moment look quite promising. September 2008 Keeping Bacteria Off SurfacesProfessor Joanna Verran, Manchester Metropolitan UniversityKat - Whether or not bacteria stick around in your local hospital isn’t always down to local conditions or cleaning. Sometimes it’s the microscopic structure of the surface you’re cleaning that dictates whether you’ll manage to get the bugs off. If we can understand better how bacteria stick to surfaces we could make food factories, bathrooms, kitchens and hospitals much cleaner. A team at Manchester Metropolitan University have been looking into this. Professor Joanna Verran joins us now. Hello. Why is a wipe down with a bit of bleach not enough to get rid of bacteria? Joanna - I think if you think of the surfaces that you’re wiping they may well not be particularly smooth so the bugs can get wedged in defects and scratches. It’s not so easy to get them off that way. Kat - These surfaces, how big are the scratches? Most surfaces look fairly smooth. What size are we talking about?
Kat - Is there a difference in the types of surfaces? Surfaces can be made of all sorts of things. Are there any that are particularly hard for bacteria that you’ve found? Joanna - I think softer surfaces, ones which scratch more easily are going to get more rough and therefore get harder to clean but hygienic surfaces like stainless steel are actually quite hard. They don’t scratch particularly badly. What we’ve shown actually is if stainless steel surfaces wear it doesn’t really make it harder to get the bugs off of those. Part of the problem with them as well is that food material and other material gets stuck in the cracks too. Again it helps the surfaces retain soil and that helps the bacteria stick to them. It’s not just trying to get the bugs off, it’s actually making sure that you get all the organic material off as well. Kat - I know that one of the things you’re really interested in is titanium. Tell me about titanium and how you’re trying to use it to fight off bacteria. Joanna - There’s one aspect of titanium that is nanotitanium. This isn’t so much on our hygienic surfaces but it’s a photo-catalyst. As you’ve been talking about earlier with reactive molecules, nanotitanium is very small particles of titanium dioxide. When light shines on it, it activates the titanium dioxide and particles are released from the surface. These particles react with things like oxygen and form extra active super oxide molecules. They hit the bacteria and start to break down bacteria. These active molecules can also break down organic compounds as well so they are called photo-active surfaces, light activated. Kat - So they’re essentially self-cleaning? Joanna - That’s right. There are quite a few self-cleaning surfaces with nanotitanium in them already. There are glass and lots of ceramic tiles but we were looking at paint formulations particularly. We were interested in seeing whether we could get paint formulations that you could just paint indoors which would be activated by fluorescent light. We were looking at E. coli actually, Escherichia coli – not 0157. Kat - I know that many paints already have titanium dioxide in. Is that special or do paints not normally work in this way? Joanna - Titanium has got different functions. Some of the larger titanium particles are just pigment so it’s white. Titanium dioxide is often used in paints and cosmetics, toothpastes but we’re looking at the nanotitanium because those smaller molecules are better photo-catalysts. Kat - Would that be very expensive though? It sounds like a fantastic idea if you can paint this paint indoors. It’s activated by normal fluorescent lights. Is it going to be too pricy to be practical? Joanna - I don’t really know what the prices might be. We’ve started looking – we looked particularly as E. coli and the reason that we started with E. coli is because that’s where standard tests for testing how good these antibacterial properties are. You would want to then look at other micro-organisms as well and see whether you’ve got a broader spectrum of activity. I’m afraid I don’t know anything about the prices of them. Kat - Brilliant, maybe that’s something to look into. September 2008
A Vaccine for MRSAGerald Pier, Harvard Medical SchoolGerry - The major work has been on infections caused by bacteria. We focussed on two specific types: Staphylococcus aureus (of which one form is MRSA) and another organism called Pseudomonas aeruginosa which is a quite common organism. It’s found in water but fortunately only in certain situation does it really cause a bad infection. Chris - Why is Staph and MRSA such a problem?
Chris - How many people have got it? Gerry - About 30% of people are carry Staphylococcus aureus in their nose. A smaller percentage – maybe around 2-5% carry MRSA. That’s more than it used to be. Even though that sounds like a small number when you think of all the people out there it’s really a large number of people overall. Chris - What are you doing to try and stop that? Gerry - One of the factors that has been very useful in making vaccines has been to extract the materials that bacteria put out on their outer surface. That allows us to immunise individuals and get immune responses, usually antibodies, that can cause the bacteria to be killed. We’ve discovered that there is a specific type of surface material that’s actually a sugar molecule. Scientists call it a polysaccharide that if we chemically change it somewhat it causes a very good immune response. Those antibodies are then capable of killing the Staph and preventing infections or perhaps limiting infections so that they don’t become as severe. Chris - What you’re saying is that people who don’t have this vaccine – there’s something about the surface of the Staph that stops you making an immune response normally. Gerry - Correct. It turns out that one of the ways that bacteria avoid causing an immune response that would kill them is to trick your body into making the wrong kinds of antibodies. The bacteria don’t care you don’t have those antibodies because they don’t harm the bacteria. Our job has been to try and figure out how to get the right kinds of antibodies that will kill the bacteria. Chris - Do you know how they fought the immune system in that way? Gerry - It’s a little bit complicated because it involves looking at this very detailed structure of this sugar molecule that coats the bacteria. In general what we find is that the sugar molecule has projections from the sides and those projections are involved in causing the non-killing or bad antibodies to form. Those antibodies bind to the bacteria ok but they don’t cause other factors of the immune system to stick to the bacteria. These other factors are essential for killing. It’s the structure of this sugar molecule overall that gets the wrong kinds of antibodies mostly made. What we’ve done is we’ve changed the structure so we get antibodies that then bring in these other factors that are needed to kill the bacteria. Chris - So you’re just injecting people not with bacteria but with chemicals from the surface of the bacteria that drive this response? Gerry - So far we’ve only injected mice, rabbits and monkeys. Although we’re fortunate that there is movement towards making this into a human vaccine, optimistically we’d hope perhaps within two or three years we’ll see our first humans immunised with this material. It’s going in the right direction but so far we only have data from animals. Chris - Will the same chemical trick work on other infections because it’s not just Staph that make us ill, is it? Gerry - We’re fairly optimistic that is the case. We’ve shown with our laboratory studies that the same vaccine can be effective against E. coli which is also another common cause of infections in a hospital. The bacteria that causes whooping cough also makes this. The organism that causes plague makes it. There’s a lot of other organisms that have become quite problematic in the hospital setting because they’re very resistant to the antibiotic drugs that we commonly use to treat infections. In some cases we don’t have any antibiotics at all. We’re hoping our vaccine or perhaps antibodies we make in the lab might be effective against these microbes as well. Chris - Do you think there’s any risk that the bacteria could, once you start treating large numbers of people with this, could become resistant? Bacteria change very rapidly. They’ve become resistant to lots of antibiotics. Could they thwart your vaccine? Gerry - This is always a possibility. What one tries to do when you make a vaccine is to make it our of something that the organism has to have. If it stops making it then it no longer causes infections. In our laboratory studies we’ve shown that if staphylococcus doesn’t make this material it’s much less able to cause an infection. We’re hoping that’ll be the case but we’re still a ways away from knowing that with any certainty. September 2008
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