DNA wires' could help physicians diagnose disease

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Scientists have found that Mother Nature uses DNA as a wire to detect the constantly occurring genetic damage and mistakes that can result in diseases like cancer. DNA wires are potentially useful in identifying people at risk for certain diseases. 

That topic ― DNA wires and their potential use in identifying people at risk for certain diseases ― is the focus of a plenary talk on August 19 during the 244th National Meeting & Exposition of the American Chemical Society in Philadelphia, Pennsylvania.

"DNA is a very fragile and special wire," said Jacqueline K. Barton, Ph.D., who delivered the talk. "You're never going to wire a house with it, and it isn't sturdy enough to use in popular electronic devices. But that fragile state is exactly what makes DNA so good as an electrical biosensor to identify DNA damage."

Barton won the U.S. National Medal of Science, the nation's highest honor for scientific achievement, for discovering that cells use the double strands of the DNA helix like a wire for signaling, which is critical to detecting and repairing genetic damage. She is a professor of chemistry and is chair of the division of chemistry and chemical engineering at the California Institute of Technology in Pasadena.

Damage is constantly occurring to DNA, Barton explained ― damage that skin cells, for instance, receive from excessive exposure to sunlight or that lung cells get hit with from carcinogens in cigarette smoke. Cells have a natural repair system in which special proteins constantly patrol the spiral-staircase architecture of DNA. They monitor the 3 billion units, or "base pairs," in DNA, looking for and mending damage from carcinogens and other sources.

Barton and other scientists noticed years ago that the DNA architecture chemically resembles the solid-state materials used in transistors and other electronic components. And DNA's bases, or units, are stacked on top of each other in an arrangement that seemed capable of conducting electricity.

"It's like a stack of copper pennies," said Barton. "And when in good condition and properly aligned, that stack of copper pennies can be conductive. But if one of the pennies is a little bit awry ― if it's not stacked so well ― then you're not going to be able to get good conductivity in it. But if those bases are mismatched or if there is any other damage to the DNA, as can happen with damage that leads to cancer, the wire is interrupted and electricity will not flow properly."

Barton's team established that the electrons that comprise a flow of electricity can move from one end of a DNA strand to the other, just as they do through an electrical wire. In one recent advance, the team was able to send electricity down a 34-nanometer-long piece of DNA. That might not sound like much -- a nanometer is one-tenth the width of a human hair. But that is just the right scale for use in medical diagnostic devices and biosensors to pick up on mutations, or changes, in DNA that could lead to cancer and other diseases.

Barton's research suggested that DNA uses its electrical properties to signal repair proteins that fix DNA damage. If the DNA is no longer conducting electricity properly, that would be a signal for repair proteins to do their thing. Barton's team is applying that knowledge in developing "DNA chips," devices that take advantage of DNA's natural electrical conductivity and its ability to bind to other strands of DNA that have a complementary sequence of base units, and thus probe that sequence for damage. Such a DNA chip would help diagnose disease risk by changes in electrical conductivity resulting from mutations or some other damage.

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The above abstract is republished from materials provided by ACS. 
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Full color images at 100,000 dots-per-inch resolution, using metal-laced nano-structures

Inspired by colorful stained-glass windows, researchers from Singapore have demonstrated an innovative method for producing sharp, full-spectrum color images at 100,000 dpi which can be applicable in reflective color displays, anti-counterfeiting, and high-density optical data recording.

This novel breakthrough allows colouring to be treated not as an inking matter but as a lithographic matter, which can potentially revolutionise the way images are printed and be further developed for use in high-resolution reflective colour displays as well as high density optical data storage.

The inspiration for the research was derived from stained glass, which is traditionally made by mixing tiny fragments of metal into the glass. It was found that nanoparticles from these metal fragments scattered light passing through the glass to give stained glass its colours. Using a similar concept with the help of modern nanotechnology tools, the researchers precisely patterned metal nanostructures, and designed the surface to reflect the light to achieve the colour images.

"The resolution of printed colour images very much depends on the size and spacing between individual 'nanodots' of colour," explained Dr Karthik Kumar, one of the key researchers involved. "The closer the dots are together and because of their small size, the higher the resolution of the image. With the ability to accurately position these extremely small colour dots, we were able to demonstrate the highest theoretical print colour resolution of 100,000 dpi."

"Instead of using different dyes for different colours, we encoded colour information into the size and position of tiny metal disks. These disks then interacted with light through the phenomenon of plasmon resonances," said Dr Joel Yang, the project leader of the research. "The team built a database of colour that corresponded to a specific nanostructure pattern, size and spacing. These nanostructures were then positioned accordingly. Similar to a child's 'colouring-by-numbers' image, the sizes and positions of these nanostructures defined the 'numbers'. But instead of sequentially colouring each area with a different ink, an ultrathin and uniform metal film was deposited across the entire image causing the 'encoded' colours to appear all at once, almost like magic!" added Dr Joel Yang.

The researchers from IMRE had also collaborated with A*STAR's Institute of High Performance Computing (IHPC) to design the pattern using computer simulation and modelling. Dr Ravi Hegde of IHPC said, "The computer simulations were vital in understanding how the structures gave rise to such rich colours. This knowledge is currently being used to predict the behaviour of more complicated nanostructure arrays."

The researchers are currently working with Exploit Technologies Pte Ltd (ETPL), A*STAR's technology transfer arm, to engage potential collaborators and to explore licensing the technology. The research was published online on August 12, 2012 in Nature Nanotechnology.

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The above abstract is republished from materials provided by ScienceDaily.
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What sets allergies in motion?

Allergies, or hypersensitivities of the immune system, are more common than ever before. According to the Asthma and Allergies Foundation of America, one in five Americans suffers from an allergy -- from milder forms like hay fever to more severe instances, like peanut allergies which can lead to anaphylactic shock.

While medications like antihistamines can treat the symptoms of an allergic reaction, the treatment is too limited, says Prof. Ronit Sagi-Eisenberg, a cell biologist at Tel Aviv University's Sackler Faculty of Medicine. Cells release dozens of molecules during an allergic reaction, and available medications address only a small subset. Now she and her fellow researchers are working to identify what triggers allergic reactions in the body, with the goal of stopping an allergic reaction before it starts.

The answer may lie within the Rab family, a group of 60 proteins that are known to regulate the distribution of proteins throughout the body. Along with her Ph.D. student Nurit Pereg-Azouz, Prof. Sagi-Eisenberg found that 30 of these proteins determined how cells react to an allergen, and two of these have been identified for further research as instruments of preventative medication. When the chain of events leading up to an allergic reaction can be understood, drugs can be developed to inhibit the initial reaction, explains Prof. Sagi-Eisenberg. This research has been published in The Journal of Immunology.

Getting to the root

Allergic reactions can appear as rashes, respiratory difficulties, or swelling, but they're all caused by the same mechanism. When exposed to an allergen, the body activates the immune system. But mast cells, located throughout the body, sense that the immune system has mistakenly been activated against something that is not bacterial or viral, and they release biologically active molecules to create an inflammatory response.

So what causes mast cells to react? Prof. Sagi-Eisenberg and her team work to identify the exact chain of events in an allergic reaction. They looked to the Rab family of proteins as a potential source for answers, screening for the proteins' involvement in initiating allergic reaction.

"We genetically manipulated mast cells so that they contained mutated versions of these proteins, which were already active without an allergen," explains Prof. Sagi-Eisenberg. If a protein was relevant, it would cause an allergic reaction. "This new methodology allowed us to screen for the functional impact of each member of this family, determining if they either inhibited or activated the allergic process."

In the end, the researchers flagged 30 proteins that were relevant to the process of creating an allergic reaction in the body, and have identified two that appear to be the most involved. Further research will use these two proteins as tools to gain more understanding of allergic reactions.

Targeted drugs could prevent allergic reaction

An allergic reaction is not only a function of two proteins interacting -- it's the result of a chain of events. By identifying crucial links in such a chain, researchers can create targeted drugs that break the chain. New medications that target tumor cells, for example, are directed at halting the tumor's ability to function and grow, starving it of crucial blood and oxygen supplies. Prof. Sagi-Eisenberg envisions similar medications for allergies, with medications that address the source of the allergic reaction instead of the symptoms.

The need for such medications is pressing. Steroids, the only available type of drug that effectively prevents mast cells from secreting biologically active agents, also cause harm to kidneys, bones, and the immune system. Patients may suffer more from the treatment than they do from the allergy itself. Alternative medications that are as effective as steroids but will be devoid of their adverse side effects are desperately needed. Prof. Sagi-Eisenberg's work will help to identify proteins that can be targeted by medications without impacting the function of other cells, she hopes.

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The above abstract is republished from materials provided by Tel Aviv University. 
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