Heart cells beating in a Petri dish offer new hope to heart patients


Stem cells in lab

Stem cells in a laboratory: the red areas are cells beginning to specialise as heart muscle. Photograph: Medica Research Council

Adele Johnson was 26 when she was involved in a motorway accident in 2009. She sustained only minor injuries and was able to walk away from the crash. But several weeks later she still felt stressed, tired and depressed.

Johnson’s condition initially baffled doctors, but a cardiologist provided a diagnosis: she had long QT syndrome, an incurable, potentially lethal inherited heart condition.

“It had never been spotted and it was only later, when the rest of my family was tested, that we discovered that my father and two of my three sisters also had long QT,” said Johnson, who is now training to be a youth worker.

Long QT causes serious disruptions to the heartbeat and is associated with a range of symptoms. At its most serious, the condition can set off a problem called an arrhythmia, which can result in heart failure. Some families discover they are affected by long QT only when a member, sometimes a child, dies. About 30,000 people are thought to have the condition in the UK.

Treatments can mitigate the worst effects of long QT, but these can have serious side-effects. Now, however, hopes of countering long QT’s worst effects have been boosted by scientists working on a pioneer project involving stem cell technology. They have re-created pulsating clumps of patients’ heart cells in laboratories to use as test beds for new treatments. A heartbeat has five component waves, called P, Q, R, S and T. In long QT, the gap between the Q and T waves is abormally long, which leads to heartbeat instabilities.

“At present, treatment of long QT involves prescribing beta-blockers for the rest of a patient’s life or fitting them with a small electronic defibrilator to keep their heartbeat regular,” said Professor Chris Denning of Nottingham University. “However, both have serious side-effects. Beta-blockers can induce fatigue and nausea, and some patients simply cannot tolerate them. Equally, surgically fitting devices to control a patient’s heartbeat is tricky, particularly if you are dealing with children.”

But testing drugs on heart cells is also a tricky process. “We need a supply of patients’ heart cells, so we can try different drugs on them,” said Denning. “However, we cannot keep cutting patients open to remove heart tissue samples. That is just not practical or ethical.”

Researchers at Denning’s laboratory – backed by funds from the British Heart Foundation and Heart Research UK – have devised an ingenious solution. They take samples from patients’ skin and use these to create heart cells. The skin cells are first bathed in nutrients which transforms them into stem cells, a type of cell that can be turned into any tissue. Using other techniques, the researchers are then able to turn these basic stem cells into specialist heart cells.

“The crucial point is that these heart cells can be grown in the laboratory. You put them in Petri dishes and you can see them pulse just as heart cells do in the body. And because they are taken from the skin of patients with long QT, they carry the genetic flaw that causes the condition. That means they are ideal for testing drugs on. It is an incredibly important development.”

Denning added that several candidate drugs had already been identified by researchers and these were now being tested. “I am hopeful we can make real progress towards using them in clinics in the next five years.”

For patients like Johnson, that cannot come soon enough. “I was a keen runner, skier and surfer, and have had to give all those up in case I trigger an arrhythmia. I even have to switch my phone off at night in case it goes off and the sudden shock triggers an arrhythmia. I am a very positive person, but that sort of thing does tend to get you down.”

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Diamond: Britain’s answer to the Large Hadron Collider.


At the Diamond particle accelerator in Oxfordshire, experiments using beams of light 10,000 times brighter than the sun have implications for the fight against cancer, improved air safety and energy efficiency
diamond

The huge Diamond Light Source in Oxfordshire: inside it’s ‘like something out of Star Wars’. Photograph: http://www.diamond.ac.uk

The darling of particle physics might be the Large Hadron Collider (LHC) at Cern, but as a practical tool it’s no match for the UK’s Diamond Light Source. Located at the Rutherford Appleton Laboratory campus at Harwell in Oxfordshire, Diamond is an alchemist’s dream, a place where beams of light 10,000 times brighter than the sun are deployed to probe the nature of everyday things.

Diamond is the Marmite of the physics world. Just as the sticky gunk left over from the brewing process was repurposed as a savoury spread, the light that streams from Diamond was originally the waste product of a particle accelerator.

Diamond’s 561m-diameter ring, which gives the building its distinctive circular shape, houses a synchrotron. Like the LHC, this is a particle accelerator, in Diamond’s case using synchronised pulses from powerful magnets to accelerate electrons to near the speed of light. Synchrotrons were part of the earliest particle accelerator technology, dating back to the 1940s, and were soon found to have an unwanted byproduct. Because they accelerated electrons, they generated light, known as synchrotron radiation.

When an electron accelerates it gives off energy in the form of electromagnetic radiation. Almost everyone owns an electron accelerator – the transmitters in mobile phones generate radio waves by accelerating electrons in aerials. But synchrotrons push electrons to relativistic speeds and the acceleration of electrons around the ring produces a whole spectrum of electromagnetic energy from microwaves, up through infrared, visible light, ultraviolet and x-rays.

This happens even though the electrons travel around the main storage ring at a constant speed, because acceleration is a change in velocity, which combines speed and direction. To keep the electrons in the ring they are regularly shifted through small changes of direction by steering magnets, each of which results in an acceleration and a blast of light.

In the early synchrotron light sources, such as Diamond’s predecessor at Daresbury in Cheshire, this acceleration round the ring was the sole source of light, but in a modern, so-called third generation ring, electrons are also given extra acceleration by passing them through a series of alternating magnets to force the particles into a pattern of repetitive oscillations. These devices are known as undulators if they produce a tight, narrow oscillation generating a narrow band of radiation, or wigglers if they produce a wider band.

diamond

A rare glimpse inside one of the beamline diffractometers. Photograph: http://www.diamond.ac.uk

Around the storage ring are ranged beamlines, exit beams for the radiation, where work stations known unromantically as hutches house the experiments. In Diamond’s massive 45,000 sq metre floor space (around eight times St Paul’s Cathedral) there are currently more than 20 beamlines, with space for 40 in the final configuration. “When you walk into this big hangar of a place,” says Diamond researcher David Cole, “it’s like something out of Star Wars.”

Though Diamond is a massive project, constructed between 2003 and 2007 with funding split between the Science and Technology Facility Council (86%) and the Wellcome Trust, it was relatively cheap with an initial construction cost around one-tenth of the LHC’s £2.6bn. Of course, Diamond is not on the same scale of build, but in terms of what it delivers it more than compensates.

Each year, a remarkably wide range of projects compete for time on Diamond’s beamlines, which run 24 hours a day, outside planned shutdowns. The light produced here is beyond anything that a university could deliver in a lab. Diamond’s x-ray sources, for example, are 100bn times more powerful than a conventional x-ray tube. While it is possible to produce lasers that develop as intense a blast of light as a synchrotron source, they are nowhere near as flexible because a laser is limited to a narrow range of frequencies, where Diamond produces a wide spectrum. Practically every application of Diamond requires a different frequency, fitting the sample being studied.

The sheer range of applications is remarkable. The powerful blasts of light or x-rays enable scientists to study the makeup of materials in unparalleled detail, deducing the structure of molecules far more complex than the DNA that so challenged researchers in the 1950s, establishing the exact chemical makeups and physical properties of tiny samples and finding subtle variants in the structure of manufactured items that can lead to stressing and failure.

As Professor Trevor Rayment, Diamond’s physical sciences director says: “Particle physics machines such as the LHC enable scientists to pursue inspirational goals, such as discovering the nature of dark matter, which most of the universe in made up from, and they deservedly have a high profile… [but] facilities such as Diamond are accelerating discoveries across a vast expanse of science and technology.”

He gives the example last year of a team from Oxford, Reading and the Pirbright Institute who “used Diamond’s intense x-rays to design a much safer vaccine for foot-and-mouth disease, which is endemic throughout much of the world, costs $5bn [£3bn] a year, and causes much suffering in poor countries”.

It would be a shame if particle accelerators working on particle physics were to overshadow Diamond’s remarkable work, which not only expands our scientific knowledge but makes possible the development of new drugs, new approaches in electronics and aircraft that fly more safely. The Diamond Light Source is a true national treasure.

The earthworm uncovered

Dr Mark Hodson from York University has been using Diamond in two projects based on a peculiar constituent of earthworm casts. “As a mineralogist, I was interested in rocks and hence soils, but I only gradually realised that biology is also important,” he says. “There’s plenty of work on bacteria, but I like things I can see and went to an earthworm conference, where an archaeologist was presenting on the importance of balls in worm poo to climate reconstruction.”

As well as the usual contents of faeces, earthworm casts contain small granules of calcium carbonate. This is a common mineral – the stuff of limestone, marble and chalk. These roughly spherical granules, around 2mm across, can remain in the soil for tens of thousands of years. They were already of interest for climate research, as they can be dated well from the decay rate of uranium that is incorporated into them, and the balance of oxygen isotopes in the carbonate gives a good measure of the temperature at the time the granule formed, but Hodson has more present-day concerns in his sights.

He initially used a Diamond beamline to determine how effective earthworms might be at cleaning up soil that was contaminated with heavy metals such as lead and zinc, a process known as remediation. These metals can leach out of the soil into ground water, poisoning the water supply. “We were looking for a way to give the metals something to stick to. We had already seen that earthworms can survive in contaminated soils and so began to culture worms in appropriate soils to see if they could lock up the heavy metals in the calcium carbonate, reducing their mobility.”

In these earlier experiments, Hodson was using powerful x-rays to provide a spectroscopic analysis of the calcium carbonate granules produced from the contaminated soil to find out how much of the heavy metals were being locked away. The outcome was frustrating – the metals were being held in the calcium carbonate, but not in sufficient quantities to remediate the soil. The worms would not provide an adequate solution in any sensible timescale.

Now Hodson is using an infrared beamline to examine a very different aspect of the granules that could transform our understanding of a key industrial material. Most calcium carbonate comes in one of two crystalline structures, calcite and aragonite, with a small amount of a third, vaterite. But there is a fourth form, amorphous calcium carbonate, that would be very interesting if it could be produced on a large scale, as it lacks the tendency to shear along planes that typifies the crystal structures.

The worm granules contain all four kinds of calcium carbonate, and the amorphous form can last for years. “This is remarkable,” says Hodson, “as amorphous calcium carbonate is very unstable. It usually crystallises very quickly. In the lab it might last five minutes. We are trying to find out what causes that stability in the granules.”

To perform the experiment, Hodson and his co-workers cut thin slices of the granules and map out the different forms of calcium carbonate every 5 microns (millionths of a metre) through the sample. If it is possible to discover what other substances are stabilising the amorphous form, it could have a whole range of uses, from changing the brightness of paper and other products that use calcium carbonate for whiteness, to reducing the build-up of scale in pipes or modifying the strength of building materials.

The power of Diamond’s light source makes it possible to study the detailed constituents in place. “In the laboratory we can identify the presence of various elements with granules that have been ground up. That way we can see what’s there, but not why the amorphous calcium carbonate is stabilised. Here [at Diamond] we can match up the locations.” The brighter the light, the better the resolution that can be achieved in examining the samples – and Diamond provides an unmatched intensity.

This work is still under way. Hodson estimates they are three to four years from a definitive finding. But the potential of the earthworm to transform our understanding of a substance that has been a key building material since the pyramids is impressive.

T Cell

A T-cell: potential barrier to cancer cells. Photograph: Alamy

Cancers captured

Since 1915, when the father and son team of William and Lawrence Bragg won the Nobel prize for using x-rays to analyse the structure of crystals, it has been apparent that this would be a valuable technique for understanding the way that atoms are linked to form molecules. But it is hard to imagine that the Braggs could have envisaged that their work would provide an essential tool in the search for a mechanism to cure cancers.

Pierre Rizkallah and David Cole from Cardiff University are using the Diamond Light Source’s intensely powerful x-rays to establish the modifications needed to give T-cells – a form of white blood cell – the ability to latch on to and destroy cancer cells.

T-cells have a unique ability to look into another cell and determine whether it is friendly or alien. Proteins on the surface of the T-cell called T-cell receptors can scan another cell by locking on to MHC (major histocompatibility complex) molecules, which protrude from the surface of cell. These MHC molecules reflect the internal makeup of the cell – by “reading” them, the T-cell can identify whether the cell it has approached should be ignored or destroyed.

At the moment T-cells rarely attack cancer cells. “The big problem the T-cell has is how to differentiate healthy cells from cancer cells,” Cole says. “It is difficult for the T-cells as cancer cells look similar to normal cells. We are looking at whether it’s possible to do anything to the interaction so that the T-cells can react.”

Initially the team is focusing on skin cancer, but in principle the methods they are using could be applied to any cancer cells.

The first requirement is to determine the complex shape of the receptors on the T-cells, to be able to modify them to lock on to the cancer’s MHC molecules. The traditional method, used for example in the determination of the structure of DNA, is to produce a crystal form of the substance to be studied, then blast it with x-rays. As the x-rays interact with the atoms in the repeating structure, they are diffracted, producing a pattern of dots, which is analysed from various directions to allow a painstaking build-up of the structure of the molecule.

This can be a slow process. Rizhallah explains: “It takes hundreds or thousands of exposures to build up the structure. This is where a synchrotron like Diamond is much better than a traditional x-ray source. With a traditional source the image is barely distinguishable. When I first started, using such sources, it took around eight hours to build a single image. [At Diamond] with much higher resolution, it initially took 15 minutes and now is a fraction of a second.

“It wipes out anything we could do in the laboratory. When I started one structure would take three years for a post doc to determine. Now we can analyse three in a day.”

Once the receptors are better understood the aim is to discover which parts of the molecular structures are touching each other by using crystals that combine the T-cell receptors and the MHC molecules. From this the aim is to work out how to artificially enhance T-cell receptors to attach more firmly to cancer cells, enabling them to attack and destroy the cancer. Treatment would involve taking a patient’s own T-cells, modifying them and returning them to the cancer site.

By providing unique speed and resolution, Diamond Light Source is enabling fundamental research in what could form one of the biggest medical breakthroughs of the 21st century.

Alcohol, smoking and obesity fuel ‘alarming’ global cancer surge


World Health Organisation experts issue timebomb warning and say key is prevention, possibly including tax on sugared drinks
breast cancer cells

Low and middle-income countries will be increasinly hit by cancers triggered by infections and those associated with more affluent lifestyles. Photograph: Cultura RM/Alamy

A global drive to tackle the causes of cancer linked to lifestyle, such as alcohol abuse, sugar consumption and obesity, has been urged on Monday by the World Health Organisation as it predicted the number of new cases could soar 70% to nearly 25 million a year over the next 20 years.

Half of these cases are preventable, says the UN’s public health arm in its World Cancer Report, because they are linked to lifestyle. It is implausible to think we can treat our way out of the disease, say the authors, arguing that the focus must now be on preventing new cases.

Even the richest countries will struggle to cope with the spiralling costs of treatment and care for patients, and the lower income countries, where numbers are expected to be highest, are ill-equipped for the burden to come.

The incidence of cancer globally has increased from 12.7m new cases in 2008 to 14.1m in 2012, when there were 8.2m deaths. By 2032, it is expected to hit almost 25m a year – a 70% increase.

The biggest burden will be in low- and middle-income countries, where the population is increasing and living longer. They are hit by two types of cancers – first, those triggered by infections, such as cervical cancers, which are still very prevalent in poorer countries that do not have screening, let alone the HPV vaccine.

Second, there are increasingly cancers associated with the lifestyles of more affluent countries “with increasing use of tobacco, consumption of alcohol and highly processed foods and lack of physical activity”, writes Margaret Chan, WHO director general, in an introduction to the report.

Dr Christopher Wild, director of the International Agency for Research on Cancer (IARC) and joint author of the report, said when people know his job, they asked whether a cure for cancer had been found, yet few think about preventing the disease in the first place.

“Despite exciting advances, the report shows that we cannot treat our way out of the cancer problem. More commitment to prevention and early detection is desperately needed in order to complement improved treatments and address the alarming rise in the cancer burden globally.”

His co-author, Dr Bernard Stewart from the University of New South Wales, talked of “the crucial role of prevention in combating the tidal wave of cancer” and called for discussion on how to encourage people to change their lifestyles, including a tax on sugared drinks, which could be one possible brake on cancers caused by obesity and lack of physical exercise.

The world had moved on from what Stewart called a “naive approach” to smoking, which causes lung and other cancers, and once was limited to handing out leaflets and haranguing people to give up. He cited the WHO global tobacco control treaty, which incentivises governments to pass laws banning smoking in public places.

The World Cancer Report, an 800-page volume on the state of cancer knowledge, which is the first for five years, must open up the debate, said Stewart.

“In relation to alcohol, for instance, we are all aware of the effects of being intoxicated but there is a burden of disease not talked about because it is not recognised,” he said.

The report shows that alcohol-attributable cancers were responsible for a total of 337,400 deaths worldwide in 2010, mostly among men.

The majority were liver cancer deaths, but drinking alcohol is also a risk for cancers of the mouth, oesophagus, bowel, stomach, pancreas, breast and others.

“Labelling, availability and the price of alcohol should all be on the agenda,” said Stewart.

So should taxation of sugar-sweetened drinks, he said. The report says efforts to reduce the percentage of fizzy drinks that contain substantial amounts of added sugar should become a high priority.

Stewart said that while obesity was a greater risk for diabetes than cancer, the the risk of the latter disease was likely to put more pressure on politicians to act because of the greater awareness of it in our communities.

About half of Britons do not recognise the importance of diet in protecting them against cancer, according to a poll carried out by the World Cancer Research Fund. Eating a lot of red meat – especially processed – increases the risk of bowel cancer.

Eating fruit and vegetables may protect against some forms of cancer, although the World Cancer Report says it “does not appear to be as strongly protective against cancer as initially believed”. However, IARC says it is definitely protective against diabetes and heart disease.

The survey also found that 59% of people did not know that putting on weight increased cancer risk.

Lung cancer is the most commonly diagnosed form of the disease among men (16.7% of cases) and the biggest killer (23.6% of deaths), says the IARC report. Breast cancer is the most common diagnosis in women (25.2%) and caused 14.7% of deaths, which is a drop and now only just exceeds lung cancer deaths in women (13.8%). Bowel, prostate and stomach cancer are the other most common diagnoses.

Jean King, Cancer Research UK’s director of tobacco control, said: “People can cut their risk of cancer by making healthy lifestyle choices, but it’s important to remember that the government and society are also responsible for creating an environment that supports healthy lifestyles. It’s clear that if we don’t act now to curb the number of people getting cancer, we will be at the heart of a global crisis in cancer care within the next two decades.”

TODAY IS WORLD CANCER DAY.

New bone-like material is lighter than water but as strong as steel.


Materials shape human progress – think stone age or bronze age. The 21st century has been referred to as the molecular age, a time when scientists are beginning to manipulate materials at the atomic level to create new substances with astounding properties.

Taking a step in that direction, Jens Bauer at the Karlsruher Institute of Technology (KIT) and his colleagues have developed a bone-like material that is less dense than water, but as strong as some forms of steel. “This is the first experimental proof that such materials can exist,” Bauer said.

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Material world

Since the Industrial Revolution our demand for has outstripped supply. We want these materials to do many different things, from improving the speed of computers to withstanding the heat when entering Mars’ atmosphere. However, a key feature of most new materials still remains in their strength and stiffness – that is, how much load can they carry without bending or buckling.

All known materials can be represented quite neatly in one chart (where each line means the strength or density of the material goes up ten times):

The line in the middle at 1000kg/m3 is the density of water – all materials to its left are lighter than water and those on the right are heavier. No solid material is lighter than water unless it is porous. Porous materials like wood and bone exhibit exquisite structures when observed under a microscope, and they served as inspiration for Bauer’s work.

For many years, material scientists have thought that some empty areas on the compressive strength-density chart should be filled by materials that theory predicts. Computer simulations could be used to indicate an optimum microstructure that would give a material the right properties. However, nobody had tools to build materials with defined patterns at the scale of a human hair.

With recent developments in lasers and 3D printing, however, a German company called Nanoscribe started offering lasers that could do just what Bauer wanted. Nanoscribe’s system involves the use of a polymer that reacts when exposed to light and a laser that can be neatly focused on a tiny spot with the help of lenses.

A drop of a honey-like polymer is placed on a glass slide and the laser is turned on. A computer-aided design is fed into the system and the slide carefully moves such that the laser’s stationary focus touches only those points where the material is to be made solid. Once complete, the extra liquid is washed away, leaving behind materials with intricate internal structures.

However, these materials on their own are not as strong as Bauer wanted. So he coats them with a thin layer of alumina (aluminium oxide) before subjecting them to stress tests. Based on the tests, he was able to improve the theoretical models he used to design the of the materials. Their results were just published in the Proceedings of the National Academy of Sciences.

Even though alumina layers increase the density of these materials, all of them remain lighter than water. Bauer’s strongest material has a specific honeycomb internal structure and is coated with a 50 nanometre-thick (billionth of a metre) layer of alumina. It beats all natural and man-made materials that are lighter than 1000kg/m3, being able to withstand a load of 280MPa (mega pascals is a unit of measuring pressure), which makes it as strong as some forms of steel.

There are limitations. Nanoscribe’s system can only make objects that are tens of micrometres in size. “One of their newer machines can make materials in the milimetre-range, but that’s about it for now”, Bauer added. But that is not enough for any real-life application.

However, there have been rapid improvements in all the areas this work relies on: 3D printing, new polymers and laser technology. That means we may soon have a suite of new, super lightweight for everything from skis to aircraft parts. If nothing else, Bauer’s work shows that we are definitely in the molecular age.

Diamond film possible without the pressure.


Perfect sheets of diamond a few atoms thick appear to be possible even without the big squeeze that makes natural gems.

Scientists have speculated about it and a few labs have even seen signs of what they call diamane, an extremely thin film of diamond that has all of diamond’s superior semiconducting and thermal properties.

Now researchers at Rice University and in Russia have calculated a “” for the creation of diamane. The diagram is a road map. It lays out the conditions – temperature, pressure and other factors – that would be necessary to turn stacked sheets of graphene into a flawless diamond lattice.

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In the process, the researchers determined diamane could be made completely chemically, with no pressure at all, under some circumstances.

The team led by Rice theoretical physicist Boris Yakobson and Pavel Sorokin, a former postdoctoral associate at Rice and now a senior researcher at the Technological Institute for Superhard and Novel Carbon Materials in Moscow, reported results in the American Chemical Society journal Nano Letters.

“Diamanes have a wide potential range of application,” Sorokin said. “They can be applied as very thin, dielectric hard films in nanocapacitors or mechanically stiff, nanothick elements in nanoelectronics. Also, diamanes have potential for application in nano-optics.

“The possibility of obtaining such a quasi-two-dimensional object is intriguing, but available experimental data prevents the expectation of its fabrication using traditional methods. However, the ‘bottom-up’ approach proposed by Richard Feynman allows the fabrication of diamanes from smaller objects, such as graphene.”

The researchers built computer models to simulate the forces applied by every atom involved in the process. That includes the graphene, the single-atom-thick form of carbon and one of the strongest substances in the universe, as well as the hydrogen (or, alternately, a halogen) that promotes the reaction.

Conditions, they learned, need to be just right for a short stack of graphene pancakes to collapse into a diamond matrix – or vice versa – via chemistry.

“A phase diagram shows you which phase dominates the ground state for each pressure and temperature,” Yakobson said. “In the case of diamane, the diagram is unusual because the result also depends on thickness, the number of layers of graphene. So we have a new parameter.”

Hydrogen isn’t the only possible catalyst, he said, but it’s the one they used in their calculations. “When the hydrogen attacks, it takes one electron from a carbon atom in graphene. As a result, a bond is broken and another electron is left hanging on the other side of the layer. It’s now free to connect to a carbon atom on the adjacent sheet with little or no pressure.

“If you have several layers, you get a domino effect, where hydrogen starts a reaction on top and it propagates through the bonded carbon system,” he said. “Once it zips all the way through, the phase transition is complete and the crystal structure is that of diamond.”

Yakobson said the paper doesn’t cover a possible deal-breaker. “The conversion from one phase to another starts from a small seed, a nucleation site, and in this process there’s always what is called a nucleation barrier. We don’t calculate that here.” He said carbon normally prefers to be graphite (the bulk form of carbon used as pencil lead) rather than diamond, but a high nucleation barrier prevents diamond from making the transition.

“Thermodynamically, an existing diamond should become graphite, but it doesn’t happen for exactly this reason,” Yakobson said. “So sometimes it’s a good thing. But if we want to make flat diamond, we need to find ways to circumvent this barrier.”

He said the manufacture of synthetic diamond, which was first reliably made in the 1950s, requires very high pressures of about 725,000 pounds per square inch. Manufactured are used in hardened tools for cutting, as abrasives and even as high-quality gemstones grown via techniques that simulate the temperatures and pressures found deep in Earth, where natural diamond is forged.

Diamond films are also routinely made via , “but they’re always very poor quality because they’re polycrystalline,” Yakobson said. “For mechanical purposes, like very expensive sandpaper, they’re perfect. But for electronics, you would need high quality for it to serve as a wide-band gap semiconductor.”

Solving a physics mystery: Those ‘solitons’ are really vortex rings.


The same physics that gives tornadoes their ferocious stability lies at the heart of new University of Washington research, and could lead to a better understanding of nuclear dynamics in studying fission, superconductors and the workings of neutron stars.

The work seeks to clarify what Massachusetts Institute of Technology researchers witnessed when in 2013 they named a mysterious phenomenon—an unusual long-lived wave traveling much more slowly than expected through a gas of cold atoms. They called this wave a “heavy soliton” and claimed it defied theoretical description.

But in one of the largest supercomputing calculations ever performed, UW physicists Aurel Bulgac and Michael Forbes and co-authors have found this to be a case of mistaken identity: The heavy solitons observed in the earlier experiment are likely vortex rings – a sort of quantum equivalent of smoke rings.

“The experiment interpretation did not conform with theory expectations,” said Bulgac. “We had to figure out what was really happening there. It was not obvious it was one thing or another—thus it took a bit of police work.”

A vortex ring is a doughnut-shaped phenomenon where fluids or gases knot and spin in a closed, usually circular loop. The physics of vortex rings is the same as that which gives stability to tornadoes, volcanic eruptions and mushroom clouds.

Dolphins actually create their own vortex rings in water for entertainment:

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“Using state-of-the-art computing techniques, we demonstrated with our simulation that virtually all aspects of the MIT results can be explained by vortex rings” said Forbes, an UW affiliate professor who in January became an assistant professor of physics at Washington State University.

He said the simulations they used “could revolutionize how we solve certain physics problems in the future,” such as studying nuclear reactions without having to perform nuclear tests. As for , he said the work also could lead to a better understanding of “glitches,” or rapid increases in such a star’s pulsation frequency, as this may be due to vortex interactions inside the star.

“We are now at a cusp where our computational capabilities are becoming sufficient to shed light on this longstanding problem. This is one of our current directions of research—directly applying what we have learned from the ,” Forbes said.

The computing work for the research—one of the largest direct numerical simulations ever—was performed on the supercomputer Titan, at the Oak Ridge Leadership Computing Facility in Tennessee, the nation’s most powerful computer for open science. Work was also performed on the UW’s Hyak high-performance computer cluster.

Mosquito sperm have ‘sense of smell’.


Vanderbilt biologists have discovered that mosquito sperm have a “sense of smell” and that some of same chemicals that the mosquito can smell cause the sperm to swim harder.

This unexpected discovery is reported in an article published in the online Early Edition of the Proceedings of the National Academy of Sciences for the week of Feb. 3 by a team of Vanderbilt University biologists.

The scientists report that they have detected a suite of specialized chemical sensors called (ORs) in mosquito sperm. These are the same as the sensors that play a central role in the mosquito’s olfactory system, which is found on the insect’s antennae.The researchers found that the odorant in the sperm are expressed along their tails where they drive the rapid increase in the movement (beating) of the sperm tails.

“This discovery is really ‘out of the box’ for us,” said L.J. Zwiebel, the Cornelius Vanderbilt Chair in Biological Sciences who directed the study. “It is the first time that insect ORs have been found to function in non-sensory cells or tissue. We think this could be an entirely new paradigm for how insect reproduction is regulated. If it is, it could provide a powerful new approach for controlling populations of insects of medical and/or economic importance.”

In nature, evolution often reuses successful structures after they have arisen. In this case, it is likely that the ORs evolved first in the reproductive system and then were used to form the basis of the mosquito’s complex adult olfactory system. If this is the case, then it is also likely that the use of insect odorant receptors to modulate sperm behavior is a fundamental aspect of insect biology.

Female mosquitoes, which live for about a month, only mate once. They store the male’s sperm in special organs called spermathecae. After mating, females require a blood meal to get the basic compounds they need to produce eggs. That is why they bite humans and other animals and, in so doing, act as vectors for globally important diseases such as malaria and Dengue fever. Once the eggs have developed, they are fertilized by the sperm stored within the female’s reproductive tract.

“The sperm may need a chemical signal to become ready for fertilization,” said Research Assistant Professor Jason Pitts. “There are reports that within one day after insemination, the sperm begin swimming around in the spermathecae. There must be one or more signals that activate this movement and our findings suggest that odorant receptors may be the sensor that receives these signals.”

Pitts, graduate student Chao Liu, and postdoctoral fellow Xiaofan Zhou are co-first authors of the paper.

The origin of the discovery was an observation the researchers made several years ago as part of their research into the olfaction system of the malaria mosquito Anopheles gambiae. They found unusually high expression of a group of odorant receptors in the bodies of male mosquitoes. This caught the researchers’ attention because they were receptors that females use so they didn’t expect them to be enhanced in males. It took them several years to follow up on the observation. When they did, they tracked these receptors to the males’ testes and ultimately to the sperm themselves.

The finding sparked their interest further because of controversial research that has reported finding in human sperm. “Evidence for the presence of these receptors in is very solid. What is controversial is whether they play any role in human reproduction,” Pitts said.

Because of ongoing research that the Vanderbilt researchers have been conducting aimed at discovering new and more effective mosquito repellents, they had developed the tools they needed to determine if the odorant receptors in the mosquito sperm were functional. In particular, they had identified specific chemical compounds that specifically activate insect odorant receptors as well as others that prevent them from activating.

Liu and Zhou used these compounds to design a novel video-based bioassay. They found when the mosquito sperm were exposed to odorant receptor activators as well as chemical cues like fenchone, a natural organic compound found in fennel, the started beating much more frequently. However, the sperm did not respond to the same compounds when they were simultaneously exposed to an agent that blocks the odorant receptors. The researchers also showed the ability to activate sperm beating was absent in a mutant strain of Aedes aegypti mosquitoes that are genetically altered to lack functional odorant receptors.

“This provides compelling evidence that the odorant receptors are involved in the reproduction process,” said Zwiebel. Their tests also found that cyclic-AMP, which has been shown to cause sperm beating in mammals, also increased the rate of beating in mosquito sperm. But its effect was not prevented by the OR blockers, indicating that it was linked to a different set of receptors in the sperm.

“We know there is a lot more going on. We have just scratched the surface,” said Zwiebel.

The researchers have also tested three additional insect species – the Asian Tiger mosquito Aedes albopictus, the fruit fly Drosophila melanogaster, and the jewel wasp Nasonia vitripennis – and found that their also contain odorant receptors. According to the researchers, this suggests that ORs have a general function in reproduction across most, if not all, species of insects.

https://i1.wp.com/cdn.physorg.com/newman/gfx/news/2014/mosquitosper.jpg

Undergraduate researcher Juan Malpartida has begun surveying other insect species to find out whether the reproductive role of odorant receptors is indeed universal or if it is limited to specific insect groups.

At the same time, the researchers will be exploring the possibility that their discovery can provide improved ways to control insect populations. If they can find a compound that renders males sterile, for example, it could be used for the sterile insect method of biological control. The method involves releasing overwhelming numbers of sterile males of an insect pest into the wild. The sterile males compete with the wild males to mate with females to reduce the size of the next generation. It has been successfully used to eradicate the screwworm fly from areas of North America and to control the Medfly and Mexican fruit fly. However, it is difficult to do correctly and it can be very expensive.

Black Death Left a Mark on Human Genome.


Celebrating differences. The migration of gypsies from India 1000 years ago (see map) set the stage for a telling study about how diseases can influence the genome.(Top) Corbis; (Bottom) M. Netea et al./Proceedings of the National Academy of SciencesCelebrating differences. The migration of gypsies from India 1000 years ago (see map) set the stage for a telling study about how diseases can influence the genome.

The Black Death didn’t just wipe out millions of Europeans during the 14th century. It left a mark on the human genome, favoring those who carried certain immune system genes, according to a new study. Those changes may help explain why Europeans respond differently from other people to some diseases and have different susceptibilities to autoimmune disorders.

Geneticists know that human populations evolve in the face of disease. Certain versions of our genes help us fight infections better than others, and people who carry those genes tend to have more children than those who don’t. So the beneficial genetic versions persist, while other versions tend to disappear as those carrying them die. This weeding-out of all but the best genes is called positive selection. But researchers have trouble pinpointing positively selected genes in humans, as many genes vary from one individual to the next.

Enter Mihai Netea, an immunologist at Radboud University Nijmegen Medical Centre in the Netherlands. He realized that in his home country, Romania, the existence of two very distinct ethnic groups provided an opportunity to see the hand of natural selection in the human genome. A thousand years ago, the Rroma people—commonly known as gypsies—migrated into Europe from north India. But they intermarried little with European Romanians and thus have very distinct genetic backgrounds. Yet, by living in the same place, both of these groups experienced the same conditions, including the Black Plague, which did not reach northern India. So the researchers sought genes favored by natural selection by seeking similarities in the Rroma and European Romanians that are not found in North Indians.

Netea; evolutionary biologist Jaume Bertranpetit of Pompeu Fabra University in Barcelona, Spain; and their colleagues looked for differences at more than 196,000 places in the genomes of 100 Romanians of European descent and 100 Rroma. For comparison, the researchers also cataloged these differences in 500 individuals who lived in northwestern India, where the Rroma came from. Then they analyzed which genes had changed the most to see which were most favored by selection.

Genetically, the Rroma are still quite similar to the northwestern Indians, even though they have lived side by side with the Romanians for a millennium, the team found. But there were 20 genes in the Rroma and the Romanians that had changes that were not seen in the Indians’ versions of those genes, Netea and his colleagues report online today in the Proceedings of the National Academy of Sciences. These genes “were positively selected for in the Romanians and in the gypsies but not in the Indians,” Netea explains. “It’s a very strong signal.”

Those genes included one for skin pigmentation, one involved in inflammation, and one associated with susceptibility to autoimmune diseases such as rheumatoid arthritis. But the ones Netea and Bertranpetit were most excited about were a cluster of three immune system genes found on chromosome 4. These genes code for toll-like receptors, proteins which latch on to harmful bacteria in the body and launch a defensive response. “We knew they must be important for host defense,” Netea says.

What events in history might have favored these versions of the genes in gypsies and Romanians, but not in Indians? Netea and his colleagues tested the ability of the toll-like receptors to react to Yersinia pestis, the bacterium that caused the Black Death. They found that the strength of the immune response varied depending on the exact sequence of the toll-like receptor genes.

Netea and Bertranpetit propose that the Rroma and European Romanians came to have the same versions of these immune system genes because of the evolutionary pressure exerted by Y. pestis. Other Europeans, whose ancestors also faced and survived the Black Death, carried similar changes in the toll-like receptor genes. But people from China and Africa—two other places the Black Death did not reach—did not have these changes. (There have been multiple plagues throughout history around the world, but none have been so deadly as the Black Death, which killed an estimated one in every four Europeans, and so exerted very strong selection.) The similarities in the other genes were likely caused by other conditions experienced by Rroma and Europeans, but not Indians.

“The use of two populations living in the same geographic area is very clever,” says human population geneticist Oscar Lao of Erasmus MC in Rotterdam, the Netherlands, who was not involved in the study. “This experimental evidence is very important,” he adds. It shows that the Black Death bacterium does indeed interact with the proteins coded for by the genes favored by natural selection. “That should be the goal for all those type of analyses.”

“It’s a nice hypothesis that they are putting forward,” agrees Lluis Quintana-Murci, a human population geneticist at the Pasteur Institute in Paris who was not involved in the study. The genetic changes may have modern-day effects. “The presence of these particular versions of these genes may give the evolutionary basis for why certain populations are more at risk” for certain types of diseases, says Douglas Golenbock, an immunologist at the University of Massachusetts Medical School in Worcester. “The side effect seems to be that the Europeans have a more proinflammatory immune system than those who have never experienced Black Death.”

However, Lao and Quintana-Murci wonder if the convergence in these genes might be explained another way. It’s possible that these favorable versions were introduced into the Rroma by interbreeding between the Rroma and the Romanians, they suggest. Additional sequencing of the converged genetic regions should answer this question, Quintana-Murci says. It’s also important to check how these toll-like receptors respond to other deadly bacteria to see if other diseases might have been the cause of the changes. That will likely happen, Quintana-Murci adds. “This will inspire other labs to see if other bacterial infections could also explain the [selection].”

Contraception helps lower U.S. abortion rate.


If opponents of reproductive rights are eager to see a drop in the national abortion rate, the movement should be pleased with the recent progress.

Image: US-POLITICS-ABORTION-FILES

The abortion rate and the number of abortions has fallen 13%, with just 1.1 million abortions in 2011, according to a new study by the Guttmacher Institute.
Just 16.9 per 1,000 women between the ages of 15 and 44 got an abortion in 2011.
It’s the lowest rate since the year the Supreme Court legalized abortion nationwide, 1973. Guttmacher has been periodically surveying abortion providers since the 1970s and surveyed four years for the current study, looking at abortion from 2008 to 2011.
The entirety of the 12-page Guttmacher Institute report is online here (pdf). Note that similar data for 2012 and 2013 is not yet available, so we can’t say with confidence whether or not the trend is continuing.
Because the sharp drop in the abortion rate occurred after the 2010 midterms, when conservative lawmakers at the state level launched an unprecedented campaign to restrict women’s access to abortion services, it may be tempting the plunge is directly related to new state policies. In other words, opponents of abortion rights were elected; they immediately got to work on new restrictions; and the drop in the abortion rate is proof their efforts succeeded in their intended goal.
But that’s not what the researchers found. “With abortion rates falling in almost all states, our study did not find evidence that the national decline in abortions during this period was the result of new state abortion restrictions. We also found no evidence that the decline was linked to a drop in the number of abortion providers during this period,” says Rachel Jones, lead author of the study.
In fact, in states with fewer abortion restrictions, the rate dropped just as much, if not more, than in states imposing new restrictions.
So what explains the sharp reduction?
Guttmacher Institute researchers pointed in part to the weak economic recovery, which drove the overall birth rate down, but also stressed access to contraception.
Jane Timm’s report added, “[C]ontraceptives themselves may be lowering the rate of abortion, due to the availability of highly effective long-term contraceptive, like the IUD. During the four years of the study, long-term contraceptive use rose from 4 to 11%.”
Given results like these, it’s curious that so many conservative lawmakers have been so aggressive in trying to limit access to contraception, with support for litigation and legislation intended to empower religious employers to cut off employees’ access to birth control.
If the goal is to reduce unwanted pregnancies and lower the abortion rate, it would seem the right would want more access to contraception, not less.

‘Pocket optician’ trialled in schools


Classroom

A ‘pocket optician’ made from a modified smartphone is to be used by teachers in Kenya as part of trial to catch pupils’ eye problems.

Access to eye care is a major issue in the developing world.

The same kit used on older people had promising results and led to more than 1,000 people receiving treatment.

The team behind the project, at the London School of Hygiene and Tropical Medicine, said treating children could stop them falling behind in school.

The World Health Organization says 285 million people are blind or visually impaired, but four out of every five cases can be prevented or cured.

“Start Quote

Many children under-perform at school due to undiagnosed vision problems, which if corrected gives them a greater opportunity to realise their potential”

Dr Andrew Bastawrous London School of Hygiene and Tropical Medicine

The main problem in children is poor eyesight, which means they require glasses.

But in large parts of the world there is a massive shortage of people able to perform eye tests, especially away from major towns and cities.

Basic training

Eight teachers in one of the most deprived areas of Kenya, Kitale, will be trained to use the Portable Eye Examination Kit (Peek).

The smartphone app uses a shrinking letter which appears on screen as a basic vision test and it uses the camera’s flashlight to illuminate the back of the eye, the retina, to check for disease.

A patient’s records are stored on the phone and the results can be emailed to doctors.

The mobile app in action: Scanning the back of the eye

The trial will begin in 10 schools, before expanding across neighbouring areas.

Dr Andrew Bastawrous, part of the group which designed Peek at the London School of Hygiene and Tropical Medicine, told the BBC: “Many children under-perform at school due to undiagnosed vision problems, which if corrected gives them a greater opportunity to realise their potential.

“Currently, clinicians, of which there are very few, go to schools to screen children. This takes them away from the hospital where they are needed most and puts the hospital under increased pressure.”

Children with eye problems will be referred to the Kitale Eye Unit for further evaluation and treatment.

Dr Hillary Rono, an ophthalmologist at Kitale District Hospital, said he was “extremely excited” by the project.

He commented: “Ever since the Peek team introduced their impressive adapted smartphone, we saw that it could really make a difference to the problem of screening in schools, and help increase the detection rates of children with poor vision, hopefully helping them realise their educational potential.”

The trial using Peek in adults is still taking place, but early results suggest it is effective at picking up vision problems.

The back of the eye being scanned
The phone can be used to look at the retina at the back of the eye and check the health of the optic nerve.

Operation Eyesight Universal will run the project with funding from Seeing is Believing – a collaboration of the International Agency for the Prevention (IABP) of Blindness and Standard Chartered.

Peter Ackland, the chief executive of the IAPB, said “Teachers are the gateway to testing children in many low-income countries simply because there are not enough human resources to have a more efficient way of screening.

“In people’s younger days, regular checks mean that problems with their vision can be treated as early as possible. However, in the current system, many children slip through the net and go through life with an eye condition that’s entirely avoidable.”

Richard Meddings, the chairman of Seeing is Believing at Standard Chartered, said “Developing effective methods for screening children at school is a key challenge to eliminating avoidable blindness for good.

“If this pilot test increases detection rates, it could be the difference between children spending their days seeing clearly, having blurred vision, or even going blind.”