Stem Cells and Sexy Smells

18 January 2010

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This week, we hear about a new way to grow stem cells from umbilical cord blood, find out why rare things are hard to discover how the scent of a fertile woman affacts male testosterone levels. Plus, we explore the geology of a natural disaster to find out what caused the recent earthquake in Haiti...

In this episode

Growing umbilical cord blood stem cells

Scientists have discovered a way to dramatically boost the numbers of stem cells used for bone marrow transplants.

The technique uses stem cells known as CD34 cells, which are present in the blood of a developing baby.  Cytomatrix_with_stem_cells_growing A small number of them can be harvested from the umbilical cord immediately after a baby is delivered and, in recent years, companies have begun to provide storage services so that parents can preserve these cells in case their child ever needs a source of stem cells in the future.  They can, for instance, be used as a bone-marrow transplant if the individual develops leukaemia later.

Unfortunately, the numbers of cells that can be harvested like this is often only about 10% of the number needed for a successful bone marrow transplant.  The obvious solution - trying to grow the cells in a dish - invariably causes them to lose the ability to behave as stem cells, rendering them useless.  But now, writing in Nature Medicine, researcher Colleen Delaney, who's based at the Fred Hutchinson Cancer Research Centre in Seattle, together with colleagues at the University of Washington, has found a way to expand the numbers of these stem cells without causing them to lose their important stem cell-like behaviour.

The researchers have found that a key chemical signal, called Notch1, which normally helps to control the growth of bone marrow cells in the body, can be used to induce CD34 stem cells to grow in the dish.  Critically, Notch1 makes the cells divide, increasing their numbers up to 164-fold, but without sacrificing their key stem cell properties.

Using this technique, the team showed, initially in mice and then in a small group of humans with life-threatening leukaemias, that cells produced this way can be used for bone marrow transplantation.

Most importantly, they found in the human subjects that the transplanted bone marrow "took" and began to produce new blood cells ten days sooner than patients treated with conventional bone marrow transplant techniques.  This could make a significant impact on survival which, previous studies have shown, is strongly linked to how quickly a patient recovers the ability to begin producing new blood and immune cells again following a bone marrow transplant.

Why rare objects are harder to find

Scientists have uncovered the scientific reason why hunting for a needle in a haystack is so hard - and often fruitless.

If you're a little bit scatterbrained when it comes to organising things and often spend an evening rifling through bits and pieces which, of course, were filed away in a "safe place", Haystackyou can probably identify with the premise of this study. 

It's said that when you're looking for unusual objects you're not as good at finding them.  So, if you're on the security staff at an airport and you have 600 bags to scan, of which 15 contain some sort of weapon, you're much less likely to find all 15.  Proportionate to the number of things, searchers will make more errors if the object they're looking for is rare. According to lead researcher Jeremy Wolfe, "If you don't find it often, you often don't find it." 

The reverse is also true if you're looking for something that occurs more often, such as sun lotion, in which case you might think you can see it when it isn't there.

In Current Biology this week, the researchers from Harvard have been looking at why this happens.  They used two groups of between 12 and 13 volunteers to search through some computer-generated bag contents.

Common sense might tell you that, because something's rare you need to look through more boxes or bags and your brain just gets used to saying 'it's not there' all the time.  And so you start to miss the thing you're looking for.

But the new study shows that it's actually the "Ooh, it's there!" response, which happens more slowly with rare objects.

This is an adaptive behaviour so that, in terms of our ancestors, if you were foraging for food you'd be more likely to stay in areas where it was plentiful and less likely to stray into areas where it was rare.

The findings of the study could be useful, say the researchers, in training security staff at airports or even for helping radiologists to spot more tumours on scans.  According to the team, if people doing these sorts of jobs spend a couple of minutes doing a simulated search for common weapons or tumours, they might then do a better job at really finding rare ones for the next 30 minutes or so.

Spiking Cells

A living cell is an immensely complicated chemical machine, working with thousands of interacting molecules, and we haven't got an instruction manual.

A nanosensor probeUsually, if you're given a machine you don't understand, you prod it and see what happens.  One of the biological equivalents of this is to introduce new molecules into a cell, and then study the consequences.

Unfortunately for biochemists, a cell is bounded by a membrane, which is deliberately structured to filter the molecules entering or leaving the cell.

Scientists already have ways to get around this by genetically altering cells so that they produce certain molecules, by doing some clever chemistry or even by injecting molecules directly into cells by hand.  But these are very laborious processes and sometimes only work for certain types of chemicals.

Now, Alex Shalek from Harvard University and his collegues have developed a far easier method.  They have taken vertical silicon nanowires, essentially a forest of little silicon spikes a few tens of nanometres across and about 100 nanometres high, and covered them in molecules they want to inject into the cells.

Then they put cells on top and they slowly settle down over about an hour and are penetrated by the nanowires. Once this has happened, whatever was covering the nanowire is now inside 95% of the cells. The cells seem perfectly happy in this state and have been grown for several weeks with no apparent ill effects, despite being impaled on multiple silicon spikes.

The team have used this technique to successfully inject DNA, RNA, peptides, proteins, and small molecules into many different types of cells and also detected the effects of the molecules within these cells.  The technique means that it's also possible to experiment on hundreds of cells at once so you can get good statistical data on the results.

More recently the team have even been able to ink-jet print hundreds of small patches of different chemicals, and combinations of chemicals at different concentrations, onto a slide. This has allowed them to do hundreds of different experiments all at once and even remove the cells, intact, at the end of the experiment, opening up the possibility of doing multiple experiments on the same cell.

It is unlikely this approach could be used therapeutically, but instead it provides a very powerful way to learn about living cells.

Fertile females increase male testosterone levels

Scientists have found that the male arousal hormone, testosterone, peaks in line with a woman's fertility.

Writing in the journal Psychological Science, Florida State University researchers Two hands forming a heart shapeSaul Miller and Jon Maner recruited 37 male students aged 18-23 and four non-pill-using females aged 18-19.

The men, who did not know the purpose of the study, were asked to sniff T-shirts that had been worn by the women for three nights at points straddling ovulation on days 13-15 midway through their cycles, when fertility peaks.

The group were also asked to smell a second set of T shirts worn by the same women, also for three nights, but this time towards the ends of their cycles (days 20-22). A set of unworn T-shirts were also included as a control, and the females were asked to use only neutral-smelling soaps and to avoid wearing perfumes or consuming  foods with strong odours during the study.

Before and after the men smelled the shirts, saliva samples were collected to determine testosterone levels. They were also asked how "pleasant" they found the shirt odour in each case.

The analysis showed that the men rated the smells of the shirts worn around the time of ovulation as more pleasant, and the average testosterone level was also significantly higher compared with when they smelled control shirts or shirts worn by the women towards the ends of their cycles.

This suggests, say the researchers, that some sort of smell "cue" is produced by women to broadcast their fertility and that this has the effect of raising male testosterone levels, which is linked to libido and arousal...

Copper-powered carbon sequestration

We've heard about carbon sequestration, deep beneath the Earth, but now here's another way of dealing with the CO2 problem - with copper.

Part of the reason that CO2 is a problem is that it's quite tricky to extract it from the air as it's quite a stable molecule, at least compared with oxygen. And so most of the time gaseous oxygen will bond to a metal, for example, before carbon dioxide does.

But this new copper complex, reported in the journal Science this week, can ignore boring old O2 and go straight for CO2.

A team of researchers, led by Elisabeth Bouwman at the Leiden Institute of Chemistry, say that typically, the problem with oxygen is that it will gain an electron more readily than CO2. CoppersBut this copper complex will happily donate electrons to carbon dioxide instead.

So, to extract CO2 from the air, they put this copper complex into solution. Atmospheric CO2 to which it's exposed is then absorbed. Next, to remove the captured carbon, they just added a lithium salt solution, apply a low voltage - 0.03V - across it, and the carbon precipitates as an organic compound.

As a bonus, this by-product can be converted into useful compounds which can be used in cleaning products and things like wood preservation.

But what's really useful is that the copper complex can be cleaned at the end of the reaction and re-used. The researchers report that they managed to do this six times in seven hours.

Also, compared with other methods of sequestration, it's actually quite cheap although there is a possibility that accessible copper ores might run dry not too far into the future!

13:33 - Geology of a Natural Disaster

We discover the geology behind the recent devastating earthquake in Haiti...

Geology of a Natural Disaster
Dr Paul Mann, University of Texas at Austin’s Jackson School of Geosciences

Chris- You couldn't really have escaped the coverage this week of the disaster that's happened in Haiti.  We've heard lots and lots of reports from Port-au-Prince, the capital city in Haiti where they had the earthquake earlier this week.  It was said to be magnitude 7 on the Richter scale and the number of people who may be dead or injured runs into many thousands.  Loads of those reports have looked at the humanitarian crisis, but very few of them have actually looked to what's going on geologically.  So, we've invited Dr. Paul Mann, a Geologist at the Institute for Geophysics at the University of Texas at Austin, to join us and fill us in a bit more.  Paul, welcome to The Naked Scientists.

Paul -   Okay, thank you for having me.

Chris -   It's a pleasure.  Could you first of all, in practical terms explain to us what a magnitude 7 quake is?

Paul -   Okay.  The term magnitude refers to the Richter scale which is a way to assign a number to quantify the amount of seismic energy released by an earthquake.  It's a logarithmic scale, so an earthquake with a magnitude 5 on the Richter scale would be 10 times larger than a magnitude 4.

So just to tell you what the effects of these different magnitudes might be as a person, the 0 to 2 level is not felt.  The magnitude 3 level would be felt, but there's no damage.  Magnitude 4 you have shaking with limited damage.  Magnitude 5, you're talking major damage.  Magnitude 6 is considered a strong earthquake and that can cause destruction especially in populated areas.  Just to give you an idea of how many magnitude 6 earthquakes there are per year, there's about 120.  Magnitude 7, which is the size of the Haiti earthquake is considered a major earthquake with damage over large areas.  There's about 18 magnitude 7 events per year.  Remember that most of them are occurring in unpopulated areas, so that the Haiti event is unique in that respect, in that it occurred in a very densely populated area.  Therefore, you have a lot of casualties.

Chris -   And geologically Paul, what actually went on to cause this to occur?

Paul -   Well basically, we're on a plate boundary.  We're on a boundary between a San Francisco Mission District burning in the aftermath of the San Francisco Earthquake of 1906.small plate,  it's called the Caribbean plate, and the North American plate.  And if you can visualize this geographic region, this is the Caribbean - we've got Haiti and Dominican Republic sharing the island of Hispaniola.  We've got Jamaica off to the west.  We have Central America farther to the west.  So through this area runs a roughly east-west trending fault system.  We call it a 'strike-slip fault' and what that means is that the two sides of the fault are moving horizontally with respect to each other.  But this fault movement doesn't occur in a steadily slipping way.  Instead, it occurs with the sort of spasmodic jerking motions.  These faults, because they're so irregular along their surface can actually store motion for hundreds of years.

So, what's happened in Haiti is that the fault is basically a frozen surface.  It hasn't moved since, we think, about 1770.  As the plates keep moving past the fault which is frozen, the fault reaches a point where it can no longer sustain the stresses that have built up along it.  So, what happened in Haiti was that suddenly the fault ruptured in order to catch up to the plates which have been smoothly moving past each other for these hundreds of years.

Chris -   And when you say energy is being stored in the fault, in what form is the energy being stored?  Because obviously, the plates are trying to move past each other, a couple of centimetres a year, the fault isn't going anywhere.  So where is the energy actually going and how is it being stored there?

Paul -   Well, the energy is elastic energy and it's being stored in the rock beneath the fault trace that we see at the surface.  And remember the surface area of this fault is very large because it's cutting down through the upper part of the crust.  This particular earthquake, its hypocenter, or the zone of rupture at depth, was about 5 kilometres below the earth's surface, so it gives you an idea of the large surface area along these very irregular fault planes.  But it would be analogous to drawing a rubber band back and that rubber band is storing elastic energy to the point where the rubber band breaks, and that would be analogous to the earthquake.

Chris -   You made some predictions a couple of years ago, or a year and a half ago that this may be about to happen.  How did you manage to do that?

Haiti FlagPaul -   Well, in seismology, we avoid use of the term 'prediction' and really to predict something, you have to be able to precisely state many aspects of the earthquake including the epicentral area or where the earthquake occurs, the size of the earthquake, which is magnitude 7 in this case, and most importantly, when exactly that earthquake is going to occur.  For example, it's going to occur two weeks from now or two years from now.  Unfortunately in seismology, there is no success by anyone in predicting earthquakes.  What we did with this event is what we call "forecasting", much like a meteorologist might do on a weather forecast.  We stated that we had a major fault which we call the "Enriquillo-Plantain Garden fault zone." We know this fault extends about 600 kilometres between Jamaica and Southern Haiti.  We know that from our GPS studies which were done by Dr. Eric Calais at Purdue University that this fault was moving at a rate of about 7 millimetres a year, and remember the fault itself isn't moving, but the plates on either side of it are moving at that rate. And finally, from our historical records of Haiti, we know that the last fault moved, or the last large earthquake which we think was related to this fault, occurred in the 18th century. So we take the amount of time, roughly 250 years, we take the rate derived from the GPS studies, 7 millimetres a year, we calculate how much strain has accumulated which was about 2 meters.  We can convert the amount of strain accumulated to the size of the expected earthquake which we had said was about 7.2 and the event turned out to be 7.0. But I think the key element here is that we did not make any statement about "this earthquake was going to occur on January 12th".  All we said was that this was an area of high seismic risk, especially given the existence of Port-au-Prince, a city of 2 million people, very poor construction practices, and it's only 20 kilometres north of the fault.

Chris - And just to finish off very briefly, Paul.  What's the chances that this is going to happen again very, very soon? Do you think this is done for now or do you think that there's a lot more energy still sitting there and we should expect this to rumble on a bit longer?

Paul - Well, one of the interesting aspects of this type of strikes of earthquakes is that the release of strain over an area in this case of about 80 kilometres can actually cause an increase in strain on the adjacent segments of the unruptured fault.  And there are many people now at the US Geologic Survey and other universities who are working on models which are trying to predict, or to forecast, whether these adjacent of the fault will rupture and what the timeframe might be.   But again, with any studies of earthquakes, we have to be very careful about using this word prediction, just because it is a very inexact science at this point

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