Researchers on the trail of a treatment for cancer of the immune system

Infection with Epstein Barr means that the B cells, which are the primary memory cells of the immune system, are hi-jacked.

When the virus has penetrated, researchers observe an excess of a special bio-antenna, a receptor known as EB12, suddenly sprouting from the surface of the B cells. But why they do so remains a mystery.

The receptors are a vital component of the way cells communicate with their surroundings via hormones and other bio-molecules, for example, but in a body consisting of millions of cells and transmitters it can be hard to determine the part each molecule plays.

"It is possible that the large numbers of EB12 receptors could actually be the B cells response to the virus and an attempt to combat the infection. Another possibility is that the EB virus reprogrammes the cell for this explosive growth in the number of EB12 receptors. What we know for certain is that more EB12 receptors assist the B cell infected by the EB virus to multiply more rapidly thus spreading the infection faster," says postdoc Tau Benned-Jensen from the Faculty of Health Sciences, University of Copenhagen.

No fewer than 95 per cent of us carry the Epstein Barr Herpes virus.

We often encounter it as kids and it is normally harmless. Are we infected later in life EB virus may cause mononucleosis, and it seems to play a part in some forms of cancer, just as HPV affects the risk of cervical cancer. But we have no drugs to combat the Epstein Barr virus, and no vaccines for it.

"Under normal circumstances our immune systems can keep the EB virus infection in a latent state and a truce or stand-off may arise between the immune system and the virus," explains Mette Rosenkilde, professor of pharmacology at the Department of Neuroscience and Pharmacology, University of Copenhagen.

"We cannot dispense with the infection and we carry it all life long, but to most of us it is harmless. For people whose immune systems do not function due to disease or because they are suppressed by drugs in conjunction with organ transplants it is a very different matter. Now the Epstein Barr virus is suddenly free to reproduce so uninhibitedly and dramatically that it may lead to cancer," says Mette Rosenkilde.

While researchers know that the B cell EB12 receptors play a part when the cell visits the lymph glands, the immune system's Central Station, we have not yet explained the exact role of the receptor.

So the Danish researchers started by mapping the bio-antenna molecule by molecule and then, as the first in the world, they made a blueprint of a tiny molecule they thought could bind to the B cell EB12 receptor.

"When we know what receptors react to, it tells us more about the part they play," Mette Rosenkilde explains, "and our tiny molecule, a ligand, blocks the EB12 receptor, preventing it from doing its job."

"In time this block may be able to help transplant patients. If we can restrain EB virus reproduction when the immune system is being medically suppressed, we may well be able to avoid cancer," Tau Benned-Jensen says.

"On the other hand the EP virus also appears to play a part in other immune diseases such as autoimmune disease, where the ability to adjust the immune system would be beneficial," says Mette Rosenkilde.

And shortly after the Danish researchers published their article on their ligand, the first articles appeared about natural substances in the body, which activate the EB12 receptor and direct the B cell to specific areas in the lymph glands.

"Our molecule can inhibit the activation of the new substances, and the next step in our research will be experiments to identify even more biochemical dials to twiddle and to help us develop new drugs," Tau-Benned says.

The discovery has just been published in the Journal of Biological Chemistry.

Provided by University of Copenhagen

New theory may shed light on dynamics of large-polymer liquids

 A new physics-based theory could give researchers a deeper understanding of the unusual, slow dynamics of liquids composed of large polymers. This advance provides a better picture of how polymer molecules respond under fast-flow, high-stress processing conditions for plastics and other polymeric materials.

Kenneth S. Schweizer, the G. Ronald and Margaret H. Professor of materials science and engineering at the University of Illinois, and graduate student Daniel Sussman published their findings in the journal Physical Review Letters.

"This is the first microscopic theory of entangled polymer liquids at a fundamental force level which constructs the dynamic confinement potential that controls slow macromolecular motion," said Schweizer, who also is a professor of chemistry and of chemical and biomolecular engineering and is affiliated with the Frederick Seitz Materials Research Laboratory at the U. of I. "Our breakthrough lays the foundation for an enormous amount of future work relevant to both the synthetic polymers of plastics engineering and the biopolymers relevant to cell biology and mechanics."

Polymers are long, large molecules that are ubiquitous in biology, chemistry and materials, from the stiff filaments that give cells their structure to plastics. Linear polymers fall into two classes: rigid rods like uncooked spaghetti or flexible strands like al dente noodles.

When in a dense solution, linear polymers become entangled like spaghetti in a pot, intertwining and crowding each other. Each polymer is hemmed in by its neighbors, so that the liquid behaves like an elastic, viscous rubber. Given enough time, the liquid will eventually flow slowly as polymers crawl along like snakes, a movement called reptation. Researchers have long assumed that each polymer's reptation is confined to a tube-shaped region of space, like a snake slithering through a pipe, but have had difficulty understanding how and why the polymers behave that way.

Schweizer and Sussman's new theory, based on microscopic physics, explains the slow dynamics of rigid entangled polymers and quantitatively constructs the confining dynamic tube from the forces between molecules. The tube concept emerges as a consequence of the strong interactions of a polymer with its myriad of intertwining neighbors. The theory's mathematical approach sheds greater light on entanglement and better explains experimental data.

"Our ability to take into account these crucial physical effects allows us to predict, not assume, the confining tube concept, identify its limitations, and predict how applied forces modify motion and elasticity," Schweizer said.

Not only does the new theory predict tube confinement and reptative motion, it reveals important limitations. The researchers found that the "tubes" weaken as applied forces increase, to the point where the tube concept fails completely and the liquid loses its rubbery nature. This is particularly important in plastics processing, which exposes polymer liquids to high stress conditions.

Next, the researchers plan to continue to study how external stress or strain quantitatively determine the driven mechanical flow behavior of entangled polymer liquids. They also hope to develop a theory for how attractive forces can compete with entanglement forces to result in soft polymer gels.

The National Science Foundation supported this work.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by University of Illinois at Urbana-Champaign.

Journal Reference:

Daniel Sussman, Kenneth Schweizer. Microscopic Theory of the Tube Confinement Potential for Liquids of Topologically Entangled Rigid Macromolecules. Physical Review Letters, 2011; 107 (7) DOI: 10.1103/PhysRevLett.107.078102

New device exposes explosive vapors

Decades after the bullets have stopped flying, wars can leave behind a lingering danger: landmines that maim civilians and render land unusable for agriculture. Minefields are a humanitarian disaster throughout the world, and now researchers in Scotland have designed a new device that could more reliably sense explosives, helping workers to identify and deactivate unexploded mines.

The prototype sensor features a thin film of polymer whose many electrons jump into higher energy levels when exposed to light. If left alone, the electrons would eventually fall back down, re-emitting light. When the 'excited' polymer is exposed to the electron-deficient molecules that are common to many explosives, however, the molecules steal some of the polymer's electrons, and so quench the light emission.

Other devices have used the change in a fluorescent polymer's light-emitting power to detect explosive vapors, but the Scottish team's prototype, described in the AIP's new journal AIP Advances, is the first to use a compact silicon-based micro-system to measure the change in the length of time an electron stays in the 'excited' higher energy state. This measurement is less affected by environmental factors, such as stray light, which should make the device more reliable. It is also an example of how the complementary properties of an organic semiconductor (the polymer) and an inorganic semiconductor (the silicon) can be combined to make novel devices, the researchers write.

The team's current prototype is not yet ready for commercialization, but future work may soon see it helping to reclaim landmine-littered land.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by American Institute of Physics, via EurekAlert!, a service of AAAS.

Journal Reference:

Yue Wang, Bruce R. Rae, Robert K. Henderson, Zheng Gong, Jonathan Mckendry, Erdan Gu, Martin D. Dawson, Graham A. Turnbull, Ifor D. W. Samuel. Ultra-portable explosives sensor based on a CMOS fluorescence lifetime analysis micro-system. AIP Advances, 2011; 1 (3): 032115 DOI: 10.1063/1.3624456

Novel microscopy generates new view of fuel cells

A novel microscopy method at the Department of Energy's Oak Ridge National Laboratory is helping scientists probe the reactions that limit widespread deployment of fuel cell technologies.

ORNL researchers applied a technique called electrochemical strain microscopy that enables them to examine the dynamics of oxygen reduction/evolution reactions in fuel cell materials, which may reveal ways to redesign or cut the costs of the energy devices. The team's findings were published in Nature Chemistry.

"If we can find a way to understand the operation of the fuel cell on the basic elementary level and determine what will make it work in the most optimum fashion, it would create an entirely new window of opportunity for the development of better materials and devices," said co-author Amit Kumar, a research scientist at ORNL's Center for Nanophase Materials Sciences.

Although fuel cells have long been touted as a highly efficient way to convert chemical energy into electrical energy, their high cost -- in large part due to the use of platinum as a catalyst -- has constrained commercial production and consumption.

Large amounts of platinum are used to catalyze the fuel cell's key reaction -- -the oxygen-reduction reaction, which controls the efficiency and longevity of the cell. Yet exactly how and where the reaction takes place had not been probed because existing device-level electrochemical techniques are ill suited to study the reaction at the nanoscale. ORNL co-author Sergei Kalinin explains that certain methods like electron microscopy had failed to capture the dynamics of fuel cell operation because their resolution was effectively too high.

"When you want to understand how a fuel cell works, you are not interested in where single atoms are, you're interested in how they move in nanometer scale volumes," Kalinin said. "The mobile ions in these solids behave almost like a liquid. They don't stay in place. The faster these mobile ions move, the better the material is for a fuel cell application. Electrochemical strain microscopy is able to image this ion mobility."

Other electrochemical techniques are unable to study oxygen-reduction reactions because they are limited to resolutions of 10's of microns -- 10,000 times larger than a nanometer.

"If the reaction is controlled by microstructure features that are much finer than a micron, let's say grain boundaries or single extended defects that are affecting the reaction, then you will never be able to catch what is giving rise to reduced or enhanced functionality of the fuel cell," said ORNL's Stephen Jesse, builder of the ESM microscope. "You would like to do this probing on a scale where you can identify each of these defects and correlate the functionality of the cell with these defects."

Although this study mainly focuses on the introduction of a technique, researchers explain their approach as a much-needed bridge between a theoretical and applied understanding of fuel cells.

"There is a huge gap between fundamental science and applied science for energy-related devices like fuel cells and batteries," Kalinin said. "The semiconducting industry, for example, is developing exponentially because the link between application and basic science is very well established. This is not the case in energy systems. They are usually much more complicated than semiconductors and therefore a lot of development is driven by trial and error type of work."

Co-authors on the study are University of Heidelberg's Francesco Ciucci and Anna Morozovska from the National Academy of Science of Ukraine, whose theoretical analysis was critical in explaining the ESM measurements.

Story Source:

The above story is reprinted (with editorial adaptations) from materials provided by DOE/Oak Ridge National Laboratory.

Journal Reference:

Amit Kumar, Francesco Ciucci, Anna N. Morozovska, Sergei V. Kalinin, Stephen Jesse. Measuring oxygen reduction/evolution reactions on the nanoscale. Nature Chemistry, 2011; DOI: 10.1038/nchem.1112