Why do Men's Bits Shrink in the Cold?

In a move that could make a critical contribution to forensic investigations, scientists have developed a powerful new technique to predict a person's age from a sample of their blood.

Writing in the journal Current Biology, Erasmus MC Medical Centre, Rotterdam, researcher Manfred Kayser and his colleagues demonstrate that it's possible to age a blood donor with a precision of plus or minus nine years by studying the DNA present in the donor's T lymphocytes, which are a type of white blood cell.

The technique makes use of an observation that T cells contain additional small, circular pieces of DNA known as signal joint TCR excision circles - sj TRECS for short.  These are produced when the cells rearrange their DNA in order to mount a targeted immune response and there are usually a large number of them, although, critically, this number declines with age in a predictable fashion.

What the Dutch team do is to quantify the number of sj TRECS and then work out how much DNA is present overall in order to standardise the count.  This enables them to make their prediction of the age of the person who produced the blood, which might be the only sample found at a crime scene.

According to Kayser, this is currently the most accurate ageing method currently available. But where it will really come into its own is that it can be combined with other DNA techniques that can now make predictions as to a person's appearance based on their genetic make-up.  However, knowing roughly how old a victim or perpetrator is can be used to dramatically improve the power of such techniques because more accurate descriptions can be produced.

Commenting on the work, Kayser points out that "conventional DNA profiling applied in forensics can oly identify persons already known to the investigating bodies, because the approach is completely comparative.  Hence, every forensic lab is confronted with cases where the DNA profile obtained from the evidence material does not match that of any known suspect tested, nor anybody in the criminal DNA database, and such cases therefore cannot be solved so far.  In such cases, it is expected that appearance information estimated from evidence material will help in finding unknown persons..."

Chris -   Wednesday, December the 1st is going to be World Aids Day and 2011 actually marks the 30th anniversary of the discovery of HIV - the agent that causes AIDS.  So it's very timely that this week scientists have announced that they have solved one of the big outstanding questions that surrounds HIV infection, which is why the virus is so damaging to the immune system.  Professor Warner Greene is the Director of the Gladstone Institute of Virology and Immunology at the University of California in San Francisco.  He's with us now.  Warner, hello.  Welcome to the Naked Scientists.  First, can you give us a brief potted history of what actually happens during HIV infection?  In other words, how does the virus get into cells and what's its life cycle?

Warner -   Good evening, Chris.  I'm happy to do that and it's too bad as we're celebrating the 30th World AIDS day that we haven't ended this epidemic but the number of new infections are in fact declining markedly throughout world which is very good news.  In terms of the life cycle of HIV, HIV binds to the cell surface, micro-injects its RNA genome into the cytoplasm of the cell, and then converts that RNA into DNA, a double-stranded version of the DNA, hence, the name retrovirus - reverse flow of genetic information.  The DNA is then integrated into our own chromosomes, the DNA is then expressed into new proteins and RNA which is packaged into new virions which bud from the cell, and starts the entire infection process over again.

Chris -   And the cells that are targeted are white blood cells, CD4, they carry that marker on their surface, T-cells, without which the immune system can't function properly.  So one logical conclusion is the virus infects the very cells that orchestrate the immune response.  So if you damage them then the immune system is harmed.

Warner -   Correct.  But the real question is, how are these CD4 T-cells dying?  It was quite clear that the number of cells productively infected with HIV could not explain.  In other words, direct killing could not explain the massive CD4 T-cell loss that occurs during HIV infection.  Then a theory was advanced that it's not the directly infected cells but cells surrounding the infected cell, bystander cells, that are dying.  Our study now shows for the first time that in fact, it is these bystander cells which are the principal cause of CD4 T-cell loss, but they themselves are becoming infect but in an abortive manner, an incomplete infection that arrests early after the virus begins the reverse transcription process.

Chris -   How did you do this work?  How did you prove that?

Warner -   Well the first key was to use a primary lymphoid tissue.  We used tonsil and in this tissue, we were then able to use each of the different types of new HIV drugs that interfere with precise steps in the viral life cycle.  We were able to interrupt the life cycle with these drugs and ask whether or not, CD4 T-cell killing was blocked or not.

Chris -   Ingenious.  So, by adding a different drug that works on a different aspect of the life cycle, you interrupt at that stage, see if the cell dies.  If it doesn't die, that tells you that the effect that you see, the bystander death, in an infected patient must lie downstream of that blockade.  If the cell does die, it's upstream of where the drug works and that confines a bit of the viral life cycle that must be doing the damage.

Warner -   Right.  We were able to narrow-in the death window - as we called it - to a step during the reverse transcription process, whereby, the DNA is elongated into a chain longer than 150 base pairs.  One of the real surprises in our study was, it's not the virus that's causing the CD4 T-cells to die, but rather, it's the host cell's response to the occurrence or to the accumulation of cytoplasmic DNA in the cell cytoplasm.  That's what triggers a defensive response in the cell.  In an attempt to protect the host, the CD4 T-cell commits suicide.

Chris -   So this is something we've acquired through evolution to defend us against viral attack.  Cells that sense this cytoplasmic DNA, genetic material in the cell where it shouldn't be, tells the cell, "I'm infected with a virus.  I'll kill myself to protect the rest of the body."  Unfortunately, when you've got the scale of infection going on like you have with HIV, this has deleterious effects then.

Warner -   Right and the other twist of the story that was a real surprise was that these cells do not die silently, but rather they are dying a fiery death with the release of what's called pyroptosis which is the release of inflammatory cytokines.  The entire cellular contents of the cell are dumped which increases the inflammatory response. We now know that there is a close relationship between HIV and inflammation, that these two go hand in hand, dictating disease progression.

Chris -   What is the implication of this, just to finish this up?  Does this mean that we're now closer to understanding how to intervene in the viral life cycle better, so people who are infected with HIV don't lose all their immune cells in this way?

Warner -   Well, one of the great milestones in modern medicine is the creation of a panoply of anti-retroviral drugs, 26 FDA approved drugs for HIV therapy at last count.  All of these drugs can interfere with this death pathway.  However, the new link to inflammation, a death with inflammation, now allows us to explore the possibility of removing that inflammatory component which might allow the virus to grow in a non-pathogenic way.  This might be important for certain clinical settings.

Chris -   Let's hope so.  Warner, thank you very much.  That's Warner Greene who is Professor of medicine, microbiology and immunology at the University California, San Francisco.

One of the most unusual things about the Earth is the large amount of oxygen in its atmosphere, which isn't stable and is only there because plants keep producing it.

The Cassini probe orbiting Saturn has discovered that Saturn's moon Rhea has an atmosphere made of mostly oxygen, and 30% carbon-dioxide. Unfortunately this doesn't mean that captain Kirk could beam down there and be comfortable in his polyester jump suit, and it doesn't indicate that there is a colony of plants down on the surface photosynthesising.

' alt='Saturn's moon Rhea' >Rhea's surface is mostly made of water ice at -180C, and it is getting irradiated by particles of solar wind trapped by Saturn's magnetic field. This breaks up the water releasing oxygen, which is forming the atmosphere. There is also some carbon dioxide being released, possibly from deeper within the moon. Whilst the atmosphere is 100km thick there are still only a few tonnes of oxygen spread out over the whole moon, which if it was on the earth would just fill a large building, so compared to earth's atmosphere it is immensely tenuous.

So this certainly isn't the big story it first sounds like, but it does show that when looking for life you have to be careful when interpreting what atmospheres are made of as there are lots of strange forms of chemistry that can go on without life being involved at all.

Chris - Bone marrow is found in the bone marrow cavity of bones, so if you cut across a bone and have a look, you'll see there's a sort of hole in the middle with lots of plates of bone which jut out into that hole, and those plates in healthy bone are covered in stem cells. These stem cells are dividing very, very fast to produce new blood cells. In fact, the body destroys something like 1011 cells every single day and makes another 1011 cells every single day, and that's just red blood cells. In fact, we worked out over the course of lifetime, that you make a quarter of a million kilograms -a quarter of a ton of new red blood cells over the course of a whole lifetime, so it's a very fast process. And these cells are just dividing all the time and pumping out daughter cells which then slowly, over a course of maturations, turn themselves into the new blood cells. This includes platelets as well. You have big cells called megakaryocytes and those megakaryocytes bleb off little bits of their cytoplasm, the stuff inside the cell, which become these little bits that floats around inside the blood, and they're what causes you to be able to clot if you have a hole in the blood vessel, the platelet would stick on, and it causes the blood to clot. And then you have white blood cells as well, lymphocytes. They're also made by stem cells in the bone marrow which then go out from the bone marrow, go around the body, and turn into mature immune cells.

Diana - The NHS claims that actually, yeah head lice do prefer clean hair, but we were talking about it earlier and from an evolutionary perspective, it seems to make much more sense that lice might have developed and evolved with humans before they'd invented shampoo. So I think it's just as likely that they like dirty hair and I'm sure there are lots of people with filthy hair that have lice in their hair as well.

Dave - Unless of course we're secreting something which kind of slows them down or makes it harder for their eggs to stick to hair or something. I don't know anything about this, but human hair oils might actually be quite good at slowing down head lice.

Chris - And your argument would be, if you wash the hair with shampoo, you actually wash away that natural protective effect and the consequence of that would be that the nit would find it easier to infest you.

Dave - Yeah.

Chris - In other words, if you've got clean hair.

Dave - And purely because we've been living with them for so long, it would make sense we've evolved in some way of discouraging them.

Diana - It's quite possible.

Diana -   In July this year, five devastated a Surrey beauty spot.  Fire fighters from three counties tackled the blaze on Frensham Common but 86 acres of heathland were reduced to a scene of blackened devastation.  It may take up to five years for the affected land to recover, but not everyone views fire as a destructive force.  Planet Earth podcast presenter Sue Nelson joined Paleobotanist Andrew Scott from the Royal Holloway University of London on the charcoaled remains of the blaze, to find out how fire can also bring the past to life...

Andrew -   You can notice as we're walking, your feet beginning to crunch although it's a bit damp today.  Lots and lots of different sizes of charcoal here.

Sue -   Now you've just put a trowel into the ground there.  It almost looks like the sort of beautiful dark and composty peat that you might buy from a garden centre.

Andrew -   Yeah and so, you'd probably think, "This is terrible stuff."  But in fact, this is preserving the plant material as charcoal.  What I consider fire as, is that if you like a preservational mechanism for fossil plants because in many cases, this charcoal now is the cell walls have been converted to nearly pure carbon, and that material can get buried and survive for millions of years.  Not only that.  The anatomy of the plants are still preserved in the charcoal.

Sue -   It's hard to see how anything could be preserved in what looks like the remains of a fire grate.

Andrew -   Yes, I know.  It's sort of almost counter intuitive, isn't it?  If you take this back, and we will, we'll take it back to the lab and look under the microscope.  You'll see that all of the different tissues of the plants are preserved.  I'll collect a bag of the material so that you can actually see that I'm telling you the truth.  One of the problems of course is that this material, as you commented, who would think of collecting that stuff?  And so, one of the things we have to do is persuade people that this is incredible material.  It tells us not only that there was a fire here, but we can tell what was being burned.

...

Sue -   A short drive away and we're now in Andrew's offices.  We've brought some of the charcoal with us, and you've got a microscope here.

Andrew -   So I'm just going to take some of the sample out.

Sue -   A spoonful there.  A bit like spooning out some tea, isn't it?

Andrew -   Sometimes they're often called fossil tea leaves, I think for some people anyway.

Sue -   Oh my goodness!  You can see textures, almost like tiny seeds.

Andrew -   This is rather wet and clumped together, but one that I collected earlier and dried out, I think if I show you this under the microscope...

Sue -   You're using a very fine tipped paintbrush now to sort through the powdered charcoal.

Andrew -   Yeah.  I'll just turn it around.

Sue -   That looks like a clove in that it's got a little stick and a roundish head with two little pins-like protrusions from the top.

Andrew -   That's a charred heather flower.

Sue -   Gosh!

Andrew -   So let me find you another bit of the heather.  This is another one of the flowers that's actually opened up.

Sue - That almost looks like a miniature black rose bud.

Andrew -   Yeah, it's amazing.

Sue -   So the charcoal is a treasure trove as far as you're concerned, but why is it important to examine the remains of these plants?

Andrew -   Our thoughts about charcoalified flowers started with the discovery by Else Marie Friis and colleagues in Sweden of some cretaceous material, in which they discovered these tiny little flowers preserved as charcoal.  This was a period when flowering plants first started.  We know that many of the flowering plants were small, shrubby, weedy forms, and they survive well in disturbed habitats.  But the other thing to know is of course, fire is a major disturbance and if you've got regular fires, then these weedy plants can do very well.  They come back very quickly.  If the fire return interval is quick enough, you prevent any trees growing.  But the question is, why in the cretaceous and why is it so interesting?  We know from experiments that if you have changes in atmospheric oxygen, that can affect fire.  Because if atmospheric oxygen falls below 15% you don't get fire, it gets put out.  If you have much above the present level, you can begin to burn wetter and wetter plants.  So the idea we had was that if you look in ever wet environments, if you have increasing amounts of charcoal, it may indicate that oxygen levels are increasing.  So we've just published our research which tries to use this as a proxy of atmospheric oxygen through time.  Now it turns out that the cretaceous, this period when flowering plants first got going, was a time of high oxygen.  So we believe that there were many more fires that could burn.  They promoted, if you like, the spread and diversification of early flowering plants.

Diana -   Andrew Scott from Royal Holloway University of London, talking to Planet Earth podcast presenter, Sue Nelson.

Diana - It sounds like you've got a right-handed shell there which is called a dextral shell. You do get other shells which are left-handed and they're more sinister called the sinistral shells, but there's no real obvious reason why you get more right-handed shells right now than you do get left-handed shells.

Many people think that if you have all shells within a certain population, which are the same "handedness", it's much easier for them to mate with each other.

So, therefore, if you get one turning up that's left-handed, it's going to be difficult for the right-handed one to mate with it.

But looking back over paleontological records, you do get periods when more left-handed shells appear and then you get periods when more right-handed shells appear, and it just seems to be something that fluctuates and changes with time.

At the moment, we're getting mostly right-handed shells...

Chris - Giant hogweed produces a chemical which is actually used to treat psoriasis, and that chemical is psorolene. Psorolene gets in through the skin. In fact, if you take it into the body, it goes all around the body and goes into pretty much every cell in the body. But it's a photosensitising agent which means that a cell that's got it in can absorb light of certain wavelengths, and it produces a toxic chemical when it's interacting with light, and that toxic chemical can kill the cell.

So, this is why, if you take it into your body or you get it into contact with your skin, the skin cells where the contact occurred become very photosensitive, and then when you go out into the open, there's enough ultraviolet light, just even at low levels on even a cloudy day to interact with the drug that's in the skin, damage cells in the skin and it gives you an exaggerated sunburn.

That's actually an interesting phenomenon because people have now been able to take that out of nature and apply it to a medical condition, psoriasis, in order to get rid of some of the psoriasis lesions by putting people in basically a sun bed, and a dose of psorolin into the sun bed, and the rapidly dividing cells are more sensitive than normal cells, and so they tend to die off faster. And so, that's how you treat your psoriasis.

Chris - Oh yes, they certainly will be. After Saddam Hussein pulled out of Kuwait - when he first invaded Kuwait, if you remember back at the first Gulf War, there were actually a number of people who got killed by people who went out in the streets and fired their guns straight up in the air. And the bullets that came back down again killed people. And you'd might think, "Well, why? They're just falling bullets." But the point is that the bullet is given a degree of energy by the gun and that bullet will convert that energy as it goes up into the air, into gravitational potential energy and it will slow down in the process. But then it's got enormous amount of potential energy. It will then fall back down to Earth and there will be some losses because the bullet is interacting with the air which will have frictional effects, and slow it down a little bit. But at the same time it will end up coming back to the ground, because bullets are pretty streamlined, at almost the same speed it left the gun. So it will come cannoning down into your head if you're underneath it, at the same speed it left the gun. You're effectively being shot from above, so very, very dangerous. Never do it.

Diana - Well the answer is, we don't really know. It's something that palaeontologists have argued over and argued over for years and years, and years. But it all hangs around a thing called division of labour. The idea of that is you have certain groups of people doing certain types of jobs, and if you can divide people according to certain rules say, their gender or their age, or something like that then it might mean that they do a specific job. But of course, finding that in the archaeological record is actually really difficult because you'd have to have a certain group of people fossilised along with the job they were doing, and you'd have to have it repeated over and over to show that it was happening in this society. So the answer is, we don't really know what was happening all those years ago because it's in pre-history. You can look at cave art perhaps, but even then, how do you interpret some figures as male or female? Quite often, the cave art isn't very easily identifiable in terms of gender. There was one theory that one guy came up with a few years ago who said that the Neanderthals actually became extinct because the women took part in hunting far too much and therefore were not able to bear children because they got killed off.

Chris - Rather likely archaeologists in palaeontology that probably made that comment, who were probably blokes, I would think!

Diana - Yeah. This was definitely a man who said this, but I mean, it's certainly possible that women in Palaeolithic times did take part in hunting. We don't know that they were busy making babies all the time. It looks like population was actually quite low.

Dave - Can you compare it with modern Stone Age peoples?

Diana - You'll get into trouble for calling them Stone Age, but yeah, I know what you mean.

Dave - I'm sorry.

Diana - They do make comparisons. It's called ethnographic comparisons. So what you do is you look at hunter gatherer groups in say, South Africa, or South America, or in Papua New Guinea, and look at how they divide up their labour. And actually, it's quite a mixed picture. Sometimes you get very matriarchal societies where the women are in-charge and the women go out and hunt and gather, and sometimes you get patriarchal societies, societies where the women stay at home and the men do do the hunting. So, who knows?

Chris - Well let's assume your skyscraper is standing in isolation, so it's not going to get your view blocked by an adjacent building for instance, so there's no get out clauses like that. It's a building in isolation in the middle of nowhere. There's a sort of approximation for distance to the horizon, which is 1.23 times the square root of the height of your eyes above the ground in feet. So you could work out, using that little rule, how much further you're going to see if you go up the height, in feet, of one storey in a building, and then you could keep doing that to work out how much further you're going to be able to see to the horizon from the top of the building than the bottom, for example.