Stopping malignancy in its tracks

 

An unusual chemical compound isolated from a mud-dwelling fungus found in a soil sample collected in Daejeon, South Korea, could lead to a new family of antitumor drugs. Discovered by teams led by Jong Seog Ahn at the Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, and  Hiroyuki Osada at the RIKEN Advanced Science Institute, Wako, the compound prevents cancerous cells from forming mobile colonies—the point at which cancers become malignant and spread through the body. The teams began collaborating after Yukihiro Asami from RIKEN joined KRIBB.

The researchers spotted the compound while searching extracts of the fungus for candidate drug compounds using a recently developed screen called a 3D epithelial culture system. To date, this kind of biological assay has rarely been used to search for natural products with novel bioactivity, says Ahn. It was during the 3D screen, which they spiked with cancerous cells, that the researchers realized that a compound produced by the fungus was inhibiting the cancer cells from clumping together to form colonies (Fig. 1). This type of screen is difficult using a conventional two-dimensional cell culture. 

The researchers isolated the bioactive compound and named it fusarisetin A. They then investigated its structure using an array of chemical characterization techniques, including nuclear magnetic resonance (NMR) and x-ray crystallography. They showed that fusarisetin A was a previously undescribed compound. Being able to grow crystals of the compound for x-ray studies was a breakthrough, says Osada. “It is very important for exact structural elucidation to get crystal analysis,” he says.

Having established that fusarisetin A is a new compound, the researchers probed its bioactivity in more detail. They showed that it simply blocks colony formation rather than killing cancer cells. They then compared the compound to others known to inhibit this process, and showed that it works differently to other compounds capable of blocking clumping. This suggests to the researchers that it could offer a new way to treat tumors.

The team is already working to discover how fusarisetin A inhibits the clumping of cancerous cells by looking for its molecular target. “We have already got candidate target proteins,” Osada adds.

Fusarisetin A itself is not bioactive enough to become a drug. However, it may be possible to fine-tune the structure to improve its activity, from which new drugs could be developed. “If we can get higher biological activity derivatives [of fusarisetin A], it may be possible,” says Ahn.

More information: Jang, J.-H., et al. Fusarisetin A, an acinar morphogenesis inhibitor from a soil fungus, Fusarium sp. FN080326. Journal of the American Chemical Society 133, 6865–6867 (2011).

Provided by RIKEN (news : web)

Stanford team devises a better solar-powered water splitter (w/ video)

The process of splitting water into pure oxygen and clean-burning hydrogen fuel has long been the Holy Grail for clean-energy advocates as a method of large-scale energy storage, but the idea faces technical challenges. Stanford researchers may have solved one of the most important ones.

Solar energy is fine when the sun is shining. But what about at night or when it is cloudy? To be truly useful, sunshine must be converted to a form of energy that can be stored for use when the sun is hiding.

The notion of using sunshine to split water into oxygen and storable hydrogen fuel has been championed by clean-energy advocates for decades, but stubborn challenges have prevented adoption of an otherwise promising technology.

A team of Stanford researchers may have solved one of the most vexing scientific details blocking us from such a clean-energy future.

The team, led by materials science engineer Paul McIntyre and chemist Christopher Chidsey, has devised a robust silicon-based solar electrode that shows remarkable endurance in the highly corrosive environment inherent in the process of splitting water.

They revealed their progress in a recent paper published in the journal Nature Materials.

Conceptually, splitting water could not be simpler. Scientists have long known that applying a voltage across two electrodes submerged in water splits the water molecules into their component elements, oxygen and hydrogen.

From an environmental standpoint, the process is a dream: an electrochemical reaction whose only requirements are water and electricity and whose only byproducts are pure oxygen and hydrogen, a clean-burning fuel applicable in a promising new class of renewable energy applications. In fact, hydrogen is the cleanest burning chemical fuel known.

Practical challenges

"In theory, water splitting is a clean and efficient energy storage mechanism. Unfortunately, solving one problem creates another," said McIntyre, associate professor of materials science and engineering. "The most abundant solar electrodes we have today are made of silicon, a material that corrodes and fails almost immediately when exposed to oxygen, one of the byproducts of the reaction."

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An interdisciplinary group of Stanford researchers from the engineering and chemistry departments have developed a new way to protect silicon semiconductors during water-splitting reactions. Scientists say the breakthrough may hold the key to storing solar energy.

This particular problem has vexed researchers since at least the 1970s. Many had given up, but McIntyre and Chidsey have devised a clever solution. They coated their silicon electrodes with a protective, ultra-thin layer of titanium dioxide.

"Titanium dioxide is perfect for this application," explained McIntyre. "It is both transparent to light and it can be efficient for transferring electricity, all while protecting the silicon from corrosion."

Sunlight travels through the protective titanium dioxide into the photosensitive silicon, which produces a flow of electrons that travels through the electrochemical cell into the water, splitting the hydrogen from the oxygen. The hydrogen gas can be stored and then, when the sun is not shining, the process can be reversed, reuniting hydrogen and oxygen back into water to produce electricity.

Decades of dead ends

Other researchers had attempted to protect the electron-producing silicon electrodes. Some tried other materials, which failed for reasons of performance or durability. Some had even tried titanium dioxide, but those efforts also fell short. Their layers were either materially flawed, allowing oxygen to seep through and corrode the semiconductor, or too thick to be electrically conductive. 

Yi Wei Chen and Jonathan Prange, the lead doctoral students on the McIntyre-Chidsey team, discovered that the key to the titanium dioxide's protectiveness is achieving a very thin, yet high quality layer of material. They found that a layer just two nanometers thick was sufficient so long as it was free of the pinholes and cracks that doomed earlier titanium dioxide experiments.

With their electrodes successfully shielded from corrosion, the researchers revealed yet one more engineering ace in the hole, adding a third layer of ultra-thin iridium, a catalyst, atop the titanium dioxide. Iridium boosts the rate of the splitting reaction and improves performance of the system.

Broader applications

In side-by-side durability experiments, the researchers put their creation to the test. Control samples without the protective layer corroded and failed in less than a half-hour, while those with the titanium dioxide lasted the full duration of the test, eight hours without apparent corrosion or loss of efficiency.

The authors pointed out that their approach is general enough to work on other semiconductor substrates and to integrate other catalysts, allowing for fine-tuning of electrodes to maximize performance. Likewise, atomic layer deposition, the technique that allowed such fine and flawless layering, is in wide application in the semiconductor industry today. It should, therefore, lend itself to application on a large scale. Lastly, the results were achieved without exploring the use of other efficiency-enhancing techniques, such as surface texturing, which could further improve performance.

"We are excited about the possibilities of this technology," said McIntyre, "as much for the electrode itself, as for the process used to create it."

Their success might just push a promising technology one step closer to practical application and the world one step closer to a clean-energy future.

Provided by Stanford University (news : web)

Branch offices: New family of gold-based nanoparticles could serve as biomedical 'testbed'

 Gold nanoparticles are becoming the … well … gold standard for medical-use nanoparticles. A new paper by researchers from the National Institute of Standards and Technology (NIST) and the National Cancer Institute's Nanotechnology Characterization Laboratory (NCL) proposes not only a sort of gold nanoparticle "testbed" to explore how the tiny particles behave in biological systems, but also a paradigm for how to characterize nanoparticle formulations to determine just what you're working with.

Prospective uses of gold nanoparticles, says NIST chemist Vince Hackley, include high-precision drug-delivery systems and diagnostic image enhancers. Gold is nontoxic and can be fashioned into particles in a range of sizes and shapes. By itself, gold doesn't do much biologically, but it can be "functionalized" by attaching, for instance, protein-based drugs along with targeting molecules that cluster preferentially around cancer cells. The nanoparticles are generally coated as well, to prevent them from clumping together and to avoid rapid clearance by the body's immune system.

NCL's Anil Patri notes that the coating composition, density and stability have a profound impact on the nanomaterial safety, biocompatibility (how well the nanoparticles distribute in the body), and efficacy of the delivery system. "Understanding these parameters through thorough characterization would enable the research community to design and develop better nanomaterials," he says.

To facilitate such studies, the NIST/NCL team set out to create a nanoparticle testbed -- a uniform, controllable core-shell nanoparticle that could be made-to-order with precise shape and size, and to which could be attached nearly any potentially useful functionality. Researchers then could study how controlled variations fared in a biological system.

Their trial system is based on regularly shaped branching molecules called dendrons, a term derived from the Greek word for "tree." Dendron chemistry is fairly new, dating from the 1980s. They're excellent for this use, says NIST researcher Tae Joon Cho, because the individual dendrons are always the same size, unlike polymers, and can readily be modified to carry "payload" molecules. At the same time, the tip of the structure -- the "tree's" trunk -- is designed to bond easily to the surface of a gold nanoparticle.

The team made an exhaustive set of measurements so they could thoroughly describe their custom-made dendron-coated nanoparticles. "There aren't a lot of protocols around for characterizing these materials -- their physical and chemical properties, stability, et cetera," Hackley says, "so, one of the things that came out of the project is a basic series of measurement protocols that we can apply to any kind of gold-based nanoparticle."

Any single measurement technique, he says, is probably inadequate to describe a batch of nanoparticles, because it likely will be insensitive to some size ranges or confused by other factors -- particularly if the particles are in a biological fluid.

The new NIST/NCL paper provides the beginnings of a catalog of analysis techniques for getting a detailed lowdown on nanoparticles. These techniques include nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry, dynamic light scattering, ultra-violet/visible spectroscopy and X-ray photoelectron spectroscopy. The dendron-coated nanoparticles also were tested for stability under "biologically relevant" conditions of temperature, acidity and some recognized forms of chemical attack that would take place in the bloodstream. In vitro biological tests are pending.

The work was funded in part by the National Cancer Institute, National Institutes of Health.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by National Institute of Standards and Technology (NIST).

Journal Reference:

Tae Joon Cho, Rebecca A. Zangmeister, Robert I. MacCuspie, Anil K. Patri, Vincent A. Hackley. Newkome-Type Dendron-Stabilized Gold Nanoparticles: Synthesis, Reactivity, and Stability. Chemistry of Materials, 2011; 23 (10): 2665 DOI: 10.1021/cm200591h

Researchers devise biomaterial that could be used in the detection of toxins and pollutants

In research recently published in the leading international journal PNAS, Trinity researchers exploit the potential of a biomaterial to reveal the activity of important fat metabolising enzymes. The findings show that the biomaterial could possibly be used in the future detection of toxins, explosives, pollutants, and medicines.

Detection devices have superior sensitivity when the sensor itself can be packaged at high density.  Certain proteins that are found in the membranes of cells can act as sensors.  However, the density with which cellular membranes can be packed in a sensor of a defined volume can limit the application.  In this study, use was made of a particular form of matter, referred to as a liquid crystal or mesophase, that behaved as a densely packed mimic for cellular membranes.

Certain naturally occurring lipids or fats, when combined with water spontaneously form liquid crystals.  One of these lipids called monoolein is a product of fat digestion.  The liquid crystalline cubic phase that monoolein forms, when wet, has the lipid arranged as a bilayer just two molecules thick that is bathed on either side by water.  This hydrated bilayer resembles the membrane that surrounds the cells in living organisms. The cubic phase is particularly notable as a liquid crystal in the extraordinary density with which it packages the membrane and the enormous surface area that it has. Thus, for example, a mere thimbleful of the cubic phase has enough surface area to cover a football field.

The research conducted by Trinity’s Professor of Membrane Structural and Functional Biology, Martin Caffrey and Research Associate Dr  Dianfan Li in the School of Medicine and School of Biochemistry & Immunology used the cubic phase; but the cubic phase made from hydrated fat alone was useless.  It needed to have a membrane protein sensor incorporated into it and the protein needed to be active.  The test sensor used in the research was a membrane protein, referred to as DgkA.  DgkA is an enzyme that interconverts the fatty components of natural cellular membranes.  The enzyme was produced in E. coli bacteria, using recombinant DNA technology, as an inactive or dead ‘scrambled egg’ type of insoluble aggregate.   ‘Life’ was breathed back into the enzyme by dissolving the aggregated protein in a soapy solution and inserting it into the membrane of the cubic phase.  In this new and quite artificial environment the researchers showed that the protein had regained its original native enzyme activity and that it could behave as a model sensor.

The research sets the stage for the exploitation of this most extraordinary of biomaterials.  These include its use in high density, high sensitivity biosensors for the detection of biological molecules such as hormones, proteins, carbohydrates, and lipids, as well as toxins, explosives, pollutants, and drugs. 

Provided by Trinity College Dublin (news : web)

Inkjet printing could change the face of solar energy industry

Inkjet printers, a low-cost technology that in recent decades has revolutionized home and small office printing, may soon offer similar benefits for the future of solar energy.

Engineers at Oregon State University have discovered a way for the first time to create successful "CIGS" solar devices with inkjet printing, in work that reduces raw material waste by 90 percent and will significantly lower the cost of producing solar energy cells with some very promising compounds.

High performing, rapidly produced, ultra-low cost, thin film solar electronics should be possible, scientists said.

The findings have been published in Solar Energy Materials and Solar Cells, a professional journal, and a patent applied for on the discovery. Further research is needed to increase the efficiency of the cell, but the work could lead to a whole new generation of solar energy technology, researchers say.

"This is very promising and could be an important new technology to add to the solar energy field," said Chih-hung Chang, an OSU professor in the School of Chemical, Biological and Environmental Engineering. "Until now no one had been able to create working CIGS solar devices with inkjet technology."

Part of the advantage of this approach, Chang said, is a dramatic reduction in wasted material. Instead of depositing chemical compounds on a substrate with a more expensive vapor phase deposition -- wasting most of the material in the process -- inkjet technology could be used to create precise patterning with very low waste.

"Some of the materials we want to work with for the most advanced solar cells, such as indium, are relatively expensive," Chang said. "If that's what you're using you can't really afford to waste it, and the inkjet approach almost eliminates the waste."

One of the most promising compounds and the focus of the current study is called chalcopyrite, or "CIGS" for the copper, indium, gallium and selenium elements of which it's composed. CIGS has extraordinary solar efficiency -- a layer of chalcopyrite one or two microns thick has the ability to capture the energy from photons about as efficiently as a 50-micron-thick layer made with silicon.

In the new findings, researchers were able to create an ink that could print chalcopyrite onto substrates with an inkjet approach, with a power conversion efficiency of about 5 percent. The OSU researchers say that with continued research they should be able to achieve an efficiency of about 12 percent, which would make a commercially viable solar cell.

In related work, being done in collaboration with Greg Herman, an OSU associate professor of chemical engineering, the engineers are studying other compounds that might also be used with inkjet technology, and cost even less.

Some approaches to producing solar cells are time consuming, or require expensive vacuum systems or toxic chemicals. OSU experts are working to eliminate some of those roadblocks and create much less costly solar technology that is also more environmentally friendly. New jobs and industries in the Pacific Northwest could evolve from such initiatives, they say.

If costs can be reduced enough and other hurdles breached, it might even be possible to create solar cells that could be built directly into roofing materials, scientists say, opening a huge new potential for solar energy.

"In summary, a simple, fast, and direct-write, solution-based deposition process is developed for the fabrication of high quality CIGS solar cells," the researchers wrote in their conclusion. "Safe, cheap, and air-stable inks can be prepared easily by controlling the composition of low-cost metal salt precursors at a molecular level."

This work was supported by the Daegu Gyeongbuk Institute of Science and Technology, the U.S. Department of Energy and OSU's University Venture Development Fund, which helps donors receive tax benefits while sponsoring projects that will bring new technology, jobs and economic growth to Oregon.

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Oregon State University.

Journal Reference:

Wei Wang, Yu-Wei Su, Chih-hung Chang. Inkjet printed chalcopyrite CuInxGa1-xSe2 thin film solar cells. Solar Energy Materials and Solar Cells, 2011; 95 (9): 2616 DOI: 10.1016/j.solmat.2011.05.011