The secret life of proteins: Researchers discover dual role of key player in immune system

That protein, STIM1, was previously known to sense a change in calcium within immune cells, a process that occurs when the body confronts a pathogen. Upon sensing this change, STIM1 opens a type of pore in the cell membrane, called a CRAC channel, to allow the flow of calcium ions — a vital step in activating the immune system.

The Feinberg team, led by Murali Prakriya, assistant professor of molecular pharmacology and biological chemistry, discovered that STIM1 not only opens these pores but is responsible for determining the exquisite selectivity for calcium ions within the CRAC channels, a critical factor in kick starting the body's immune system. These findings were recently reported in the journal Nature.

"People have generally thought that selectivity of ion channels is fixed and that selectivity and opening are separate processes; this is a fundamental shift in the way scientists believe ion channels operate," says Prakriya, referring to the 'pores' that STIM1 regulates. "CRAC channels and STIM1 are absolutely vital to activating the immune system. As is observed in some human patients, you can block key parts of the system by blocking these molecules in immune cells. These finding reveal not only a novel mechanism by which CRAC channels operate, but also new ways in which it encodes biological information. This represents exciting new possibilities to develop therapeutics to treat a broad range of conditions."

To determine that STIM1 is responsible for selectivity and opening, the researchers created a mutated CRAC channel designed to keep the pore open without the assistance of STIM1. When the channel was opened without STIM1, multiple types of ions were passed through the pore, including sodium and potassium. When STIM1 was added back in, the channel became very selective for calcium ions again, like the normal channel. Even at low doses of STIM1, the unmutated channel lost its normally high calcium selectivity, allowing the entry of multiple types of ions.

Conditions that might benefit from immune suppression are likely targets for future CRAC channel targeted therapy, including autoimmune diseases and many types of allergies. Additionally, targeting CRAC channels could provide improvements for existing immune suppression therapies such as those used during transplantation.

"The CRAC channel is emerging to be incredibly important for the immune system," says Prakriya. "But we have been solely focused on its calcium conducting mode that occurs in response to STIM1. It is certainly possible that there could be other players in the cell that open the CRAC channel pore to permit the flux of other ions to stimulate different cell functions. That's the next question."

Also in the Nature article, Prakriya's team identified the location of the barrier, or gate, within the CRAC channel that controls its opening and closing.

"The identification of the molecular and structural regions of the pore that controls opening and closing is highly valuable for facilitating drug design targeting CRAC channels for the treatment of immune disorders," he adds.

Provided by Northwestern University (news : web)

Envelope for an artificial cell

Neal Devaraj, assistant professor of chemistry at the University of California, San Diego, and Itay Budin, a graduate student at Harvard University, report their success in the Journal of the American Chemical Society.

“One of our long term, very ambitious goals is to try to make an artificial cell, a synthetic living unit from the bottom up – to make a living organism from non-living molecules that have never been through or touched a living organism,” Devaraj said. “Presumably this occurred at some point in the past. Otherwise life wouldn’t exist.”

By assembling an essential component of earthly life with no biological precursors, they hope to illuminate life’s origins.

“We don’t understand this really fundamental step in our existence, which is how non-living matter went to living matter,” Devaraj said. “So this is a really ripe area to try to understand what knowledge we lack about how that transition might have occurred. That could teach us a lot – even the basic chemical, biological principles that are necessary for life.”

Molecules that make up cell membranes have heads that mix easily with water and tails that repel it. In water, they form a double layer with heads out and tails in, a barrier that sequesters the contents of the cell.

Devaraj and Budin created similar molecules with a novel reaction that joins two chains of lipids. Nature uses complex enzymes that are themselves embedded in membranes to accomplish this, making it hard to understand how the very first membranes came to be.

“In our system, we use a sort of primitive catalyst, a very simple metal ion,” Devaraj said. “The reaction itself is completely artificial. There’s no biological equivalent of this chemical reaction. This is how you could have a de novo formation of membranes.”

They created the synthetic membranes from a watery emulsion of an oil and a detergent. Alone it’s stable. Add copper ions and sturdy vesicles and tubules begin to bud off the oil droplets. After 24 hours, the oil droplets are gone, “consumed” by the self-assembling membranes.

Although other scientists recently announced the creation of a “synthetic cell,” only its genome was artificial. The rest was a hijacked bacterial cell. Fully artificial life will require the union of both an information-carrying genome and a three-dimensional structure to house it.

The real value of this discovery might reside in its simplicity. From commercially available precursors, the scientists needed just one preparatory step to create each starting lipid chain.

“It’s trivial and can be done in a day,” Devaraj said. “New people who join the lab can make membranes from day one.”

Provided by University of California - San Diego (news : web)

Chemists to develop new materials for hydrogen storage in vehicles

The U.S. Department of Energy recently awarded Berkeley Lab a three-year, $2.1 million grant for the project, which will also include contributions by the National Institute of Standards and Technology (NIST) and General Motors (GM). The grant was part of more than $7 million awarded by DOE last month for hydrogen storage technologies in fuel cell electric vehicles.

“We’re working on materials called metal-organic frameworks to increase the capacity of hydrogen gas in a pressure cylinder, which would be the fuel tank,” said Jeffrey Long, a Berkeley Lab scientist who co-leads the project along with Berkeley Lab chemist Martin Head-Gordon. “With these materials, we’re working on storing the hydrogen without the use of very high pressures, which will be safer and also more efficient without the significant compression energy losses.”

Metal-organic frameworks (MOFs) are three-dimensional sponge-like framework structures that are composed primarily of carbon atoms and are extremely lightweight. “What’s very special about these materials is that you can use synthetic chemistry to modify the surfaces within the materials and make it attractive for hydrogen to stick on the surface,” Long explained.

Separately, Long is also using MOFs in a carbon capture project, in which the material would selectively absorb carbon dioxide over nitrogen. For the fuel cell project, the trick lies not in getting the MOF to select hydrogen out of a mixture but to store as much hydrogen as possible.

Currently, vehicles using hydrogen fuel cells can achieve a range of close to 300 miles—but only if the hydrogen is stored at extremely high pressures (600 to 700 bar), which is expensive and potentially unsafe. It is also energy intensive to pressurize the hydrogen.

So far Long has succeeded in more than doubling hydrogen capacity, but only at very low temperatures (around 77 Kelvin, or -321 Fahrenheit). “It’s still very much basic research on how to create revolutionary new materials that would boost the capacity by a factor of four or five at room temperature,” he said. “We have an idea of what kinds of frameworks we might make to do this.”

Long’s approach is to create frameworks with lightweight metal sites on the surface, making it attractive for hydrogen molecules to bind to the sites. “Our approach has been to make some of the first metal-organic frameworks that have exposed metal cations on the surface,” he said. “Now we need to figure out ways of synthesizing the materials so that instead of one hydrogen molecule we can get two or three or even four hydrogen molecules per metal site. Nobody’s done that.”

This is where Head-Gordon, a computational chemist, comes in. He will work on theoretical understanding of MOFs so that he can try to predict their hydrogen storage properties and then instruct Long’s team as to what kind of material to synthesize. “He can do calculations on a lot of different target structures and say, here’s the best one for you guys to spend time trying to make, because synthetic chemistry is very cost and labor intensive,” Long said.

The scientist at GM will aid in providing accurate high-pressure measurements. The NIST scientist is an expert in neutron diffraction and neutron spectroscopy, which will allow Long and his team to pinpoint where exactly the hydrogen is going and verify that it is binding to the metals.

Provided by University of California - Berkeley (news : web)

Portable device will quickly detect pathogens

Using synthetic DNA, Dan Luo, professor of biological and environmental engineering, has devised a method of "amplifying" very small samples of pathogen DNA, RNA or proteins. Edwin Kan, professor of electrical and computer engineering, has designed a computer chip that quickly responds to the amplified samples targeted by Luo's method. They will combine these to make a handheld device, usable under harsh field conditions, that can report in about 30 minutes what would ordinarily require transporting samples to a laboratory and waiting days for results.

The work will be supported by the Bill & Melinda Gates Foundation as part of the Grand Challenge program to develop "point-of-care diagnostics" for developing countries. The foundation has distributed $25 million to 12 teams, selected from more than 700 applicants. Various teams are working on different aspects of the technology, and eventually their work will be integrated to make a practical, low-cost testing kit, Luo said.

Luo's research group has found that DNA can be used like molecular-level Lego blocks. A single strand of DNA will lock onto another single strand that has a complementary genetic code. By synthesizing DNA strands that match over just part of their length, his team can assemble unusual shapes -- in this case, a Y. Attached to the base of the Y is a DNA strand or antibody designed to lock onto a pathogen. Attached to one of the upper arms is a molecule that will polymerize -- chain up with other similar molecules -- when exposed to ultraviolet light.

When a pathogen is added to a solution of these Y-DNA molecules, the matching receptors on the stem of the Y will lock onto pathogen molecules, but only onto part of them; the mix will contain two different Y-structures, each tagged to lock onto a different part of the pathogen molecule. The result, when the targeted pathogen is present, is the formation of many double-Ys linked together by a pathogen molecule, each assembly carrying two molecules capable of polymerizing.

When the mixture is exposed to a portable ultraviolet light, the polymer molecules at the ends of each double-Y link to those on other double-Ys, forming long chains that clump up into larger masses. This polymerization won't happen, the researchers emphasize, unless a targeted pathogen is present to link two Ys together. A single Y with only one polymer molecule attached can only link to one other single Y, and no chain will form.

Kan's new chip measures both the mass and charge of molecules that fall on it. The large clumps of Y-DNA have a much larger mass and charge than single molecules, and trigger the detector. The chip uses the popular and inexpensive CMOS technology compatible with other common electronic devices. A detector might, for example, be controlled and powered by a mobile phone, Luo suggested.

All this can be combined with nanofluidics to make a robust battery-operated testing kit, the researchers said. After further development they plan to conduct tests simulating field conditions in the developing world. Along with surviving hot or cold weather, Luo said, "It has to work in dirty water."

Provided by Cornell University (news : web)

Scorpions inspire scientists in making tougher surfaces for machinery

Zhiwu Han, Junqiu Zhang, Wen Li and colleagues explain that "solid particle erosion" is one of the important reasons for material damage or equipment failure. It causes millions of dollars of damage each year to helicopter rotors, rocket motor nozzles, turbine blades, pipes and other mechanical parts. The damage occurs when particles of dirt, grit and other hard material in the air, water or other fluids strike the surfaces of those parts. Filters can help remove the particles but must be replaced or cleaned, while harder, erosion-resistant materials cost more to develop and make. In an effort to develop better erosion-resistant surfaces, Han and Li's group sought the secrets of the yellow fattail scorpion for the first time. The scorpion evolved to survive the abrasive power of harsh sandstorms.

They studied the bumps and grooves on the scorpions' backs, scanning the creatures with a 3-D laser device and developing a computer program that modeled the flow of sand-laden air over the scorpions. The team used the model in computer simulations to develop actual patterned surfaces to test which patterns perform best. At the same time, the erosion tests were conducted in the simple erosion wind tunnel for groove surface bionic samples at various impact conditions. Their results showed that a series of small grooves at a 30-degree angle to the flowing gas or liquid give steel surfaces the best protection from erosion.

More information: Erosion Resistance of Bionic Functional Surfaces Inspired from Desert Scorpions, Langmuir, Article ASAP. DOI:10.1021/la203942r

Abstract
In this paper, a bionic method is presented to improve the erosion resistance of machine components. Desert scorpion (Androctonus australis) is a typical animal living in sandy deserts, and may face erosive action of blowing sand at a high speed. Based on the idea of bionics and biologic experimental techniques, the mechanisms of the sand erosion resistance of desert scorpion were investigated. Results showed that the desert scorpions used special microtextures such as bumps and grooves to construct the functional surfaces to achieve the erosion resistance. In order to understand the erosion resistance mechanisms of such functional surfaces, the combination of computational and experimental research were carried out in this paper. The Computational Fluid Dynamics (CFD) method was applied to predict the erosion performance of the bionic functional surfaces. The result demonstrated that the microtextured surfaces exhibited better erosion resistance than the smooth surfaces. The further erosion tests indicated that the groove surfaces exhibited better erosion performance at 30° injection angle. In order to determine the effect of the groove dimensions on the erosion resistance, regression analysis of orthogonal multinomials was also performed under a certain erosion condition, and the regression equation between the erosion rate and groove distance, width, and height was established.

Provided by American Chemical Society (news : web)

Could Alzheimer's disease be diagnosed with a simple blood test?

Alzheimer's disease is the most common form of adult onset dementia and is characterized by the degeneration of the nervous system. In particular, as the disease progresses, the amount of amyloid-ß peptide in the body rises. At present, the most reliable and sensitive diagnostic techniques are invasive, e.g. require analysis of cerebrospinal fluid (the liquid that surrounds the brain and spinal cord). However, white blood cells (or mononuclear leukocytes) are also thought to carry amyloid-ß peptide in Alzheimer patients.

The researchers used two-dimensional infrared spectroscopy to measure and compare the infrared radiation emitted or absorbed by white blood cells of healthy controls, versus those of patients with mild, moderate and severe Alzheimer's disease. A total of 50 patients with Alzheimer's and 20 healthy controls took part in the study and gave blood samples.

The authors found significant differences in the range of infrared wavelengths displayed between subjects, which were attributable to the different stages of formation of amyloid-ß structures in the blood cells. The results showed that, with this method, healthy controls could be distinguished from mild and moderate sufferers of Alzheimer's disease. The method is being explored as a tool for early diagnosis.

The authors conclude: "The method we used can potentially offer a more simple detection of alternative biomarkers of Alzheimer's disease. Mononuclear leukocytes seem to offer a stable medium to determine ß-sheet structure levels as a function of disease development. Our measurements seem to be more sensitive for earlier stages of Alzheimer's disease, namely mild and moderate."

More information: Carmona P et al (2012). Infrared spectroscopic analysis of mononuclear leukocytes in peripheral blood from Alzheimer's disease patients. Analytical and Bioanalytical Chemistry; DOI 10.1007/s00216-011-5669-9

Provided by Springer

New uses for diesel by-products

More sustainable production of sulphur-free diesel from natural gas and biomass is increasing. However the by-products, hydrocarbons like decane and other low value alkanes have little practical use.

Now a discovery by the Institute, part of the School of Chemistry, has found a potential route for upgrading these by-products into more useful chemicals.

In the past, synthetic reactions starting from alkanes like decane have been fraught with difficulty. They tend either to over-dehydrogenate or to combust, depending on whether oxygen is present in the reaction. Now a Cardiff Catalysis Institute team has reported the use of a mixed-metal catalyst to convert decane to a range of oxygenated aromatics.

The breakthrough, published in Nature Chemistry, came when the team fed a gas mixture of decane and air through an iron molybdate catalyst. At higher temperatures, the reaction formed water and decene, which is used in the production of detergents. At lower temperatures, however, the reaction took a different route to create oxygenated aromatic molecules. These included phthalic anhydride, used in the dyeing industry, and coumarin which helps in the production of anti-coagulant drugs.

Professor Stan Golunski, a member of the Institute team behind the discovery said: "This discovery breaks new ground as it implies the involvement of oxygen that has not yet made the full transition from its molecular form to its ionic form. This overturns a widely-held view that this type of oxygen was too reactive to form anything other than carbon monoxide and carbon dioxide in reactions with hydrocarbons."

"While the increased production of sulphur-free diesel has been a positive move, the glut of low value by-products will become a problem. We hope our new process will lead to less waste and the creation of more useful chemicals for a range of industries."

Provided by Cardiff University (news : web)

Researchers discover the processes leading to acute myeloid leukemia

The UCSB research team described how a certain mutation in DNA disrupts cellular function in patients with acute myeloid leukemia (AML). The researchers were prompted to study this process by another research team's discovery that AML patients have a mutation in a certain enzyme, which was reported in the New England Journal of Medicine. The enzyme is a protein called DNMT3A, which leads to changes in how the DNA of AML patients is methylated, or "tagged." Norbert Reich, professor in the Department of Chemistry and Biochemistry at UCSB, was already studying that particular enzyme with his research group, so they began to study the disease process of AML at the cellular level.

Reich explained that tagging is a way of reading DNA at the cellular level. This falls within an area of study called epigenetics, a process that occurs "on top" of genetics. Each person has approximately 200 types of cells, all with the same DNA, and these must be controlled in different ways. "There is an enzyme –– a protein –– that tags DNA and controls which of the genes in your cells, your DNA, gets turned on and off," said Reich. "So you have 20,000 genes, and you have to control them differently in your brain than in your liver."

Reich explained that there is current interest in this broader field of epigenetics as a direction for the treatment of cancer. "There's definitely the idea that this may be a new way of developing therapeutics, because you don't have to kill the cancer cell," said Reich. "Almost every cancer therapy that's out there works on the principle that a cancer cell needs to be killed."

In this artist's conception, the four-protein complex called DNMT3A is shown in its normal configuration (top left). The complex reads or "tags" the cell's DNA. In the upper right side of the image, several of these tags are shown on top of the double helix of DNA. The tags control which genes in a cell get turned on and off. In the bottom left image, the complex of four proteins is disrupted. This disruption is caused by the mutation found in patients with acute myeloid leukemia. In the right side of the bottom image, the protein leaves only one tag on the DNA and then moves on. Credit: Norbert Reich, UCSB

With epigenetics, instead of only having DNA sequence coding for certain genes, there is an epigenetic process, with another layer of information on top of the genetic process. In this case, that information is the tagging by the methyl groups.

"If you really think about it, this is part of the answer as to how your cells can be so different and yet they all have the same DNA," said Reich. "You have the same genome in every one of your cells, but you do not have the same epigenome, which is basically the methylation pattern, the tagging pattern. That is different in every type of your cells. And the way this relates back to cancer, with leukemia, in those patients, the tagging is messed up. The patterns are not correct. Our big contribution to that is we've explained how the mutations in the enzyme could lead to that disruption of the tagging pattern."

The UCSB group developed a test to demonstrate that the mutant enzymes in AML can only work on DNA for short distances. As a result, the precise methylation patterns of a healthy cell are disturbed, resulting in genes being turned on at the wrong place and time, which in turn can initiate the growth of cancerous cells.

The team found that the mutation AML patients have causes a certain complex of four proteins to be disrupted. "The surprise was that the disruption doesn't stop the enzyme from being active; it doesn't stop the enzyme from tagging the DNA," said Reich. "Instead, it stops the way it can do it. Instead of going to your DNA and tagging an entire region of chromosome, it goes there, does one thing, and leaves. That process, that change, is what we see in the AML patients. So we think we have a molecular explanation for this disease."

Reich said that the currently prescribed drug Vidaza works by affecting the same enzyme that is mutated in AML. There is interest in the pharmaceutical industry in developing other therapeutics to target the enzymes responsible for tagging the DNA. These epigenetic inhibitors would reprogram rather than kill the cell.

Traditional cancer therapies use radiation and chemotherapy to remove or kill cancer cells. "The problem with that is that cancer cells are often very subtly different from normal cells," said Reich. "So you have one of the most difficult therapeutic challenges known to man, which is to distinguish between two human cells –– one that's cancerous and one that's not. Instead of killing the cell, the notion is that if you could just reprogram the cell, then it goes back to being normal. You intercept the cancer development. This is still an aspiration; it hasn't been achieved really, but that's what attracts people to the field of epigenetic-based therapies, because of the prospect of not having to kill cells."

Provided by University of California - Santa Barbara (news : web)

Researchers model potential of toxic algae photoreceptors

Massimo Olivucci, Ph.D., a research professor of chemistry at Bowling Green State University (BGSU), is focusing on Anabaena sensory rhodopsin (ASR) bacteria, which has served as a model for studies of most cyanobacteria since its genome was fully mapped in 1999.

"An in-depth understanding of light sensing, harvesting and energy conversion in Anabaena may allow us to engineer this and related organisms to thrive in diverse illumination conditions," said Olivucci. "Such new properties would contribute to the field of alternative energy via the microbial conversion of light energy into biomasses, oxygen and hydrogen. Biophysical studies of the bacterial photoreceptor and its underlying molecular mechanisms can help us to understand its biotechnological potentials and the associated environmental implications."

Using sunlight as an energy source, a sensory protein within ASR detects light of two different colors and behaves like the "eye" of Anabaena, using its green-light sensitivity to activate a cascade of reactions. In sophisticated computer simulations Olivucci created at the Ohio Supercomputer Center (OSC), he found that a short fragment of the long retinal chromophore backbone of ASR undergoes a complete clockwise rotation powered by the energy carried by two photons of light.

"We are constructing quantum-mechanical and molecular-mechanical models on Ohio Supercomputer Center systems," Olivucci explained. "Past simulations have revealed that light induces a molecular-level rotary motion in the protein interior.

"Now, the same computer models will be used to engineer hundreds of mutants that display programmed spectroscopic, photochemical and photobiological properties and identify which mutants should be prepared in the laboratory. This new approach constitutes a unique opportunity for developing computational tools useful for understanding the molecular factors that control the spectra of proteins and their photo-responsive properties in general."

Olivucci's research is expected to lead to an unprecedented tool by which hundreds to thousands of mutant models can be screened for wanted properties, such as color, excited state lifetime or photochemical transformations. This will provide tailored genetic materials for generating organisms that, for instance, can thrive under alternative light conditions and modulate biomass production or be used in engineering applications.

"Ohio is an international player in the biosciences and energy/environmental issues, which is why OSC focuses many of its resources and services on those areas to support important research like this cyanobacteria study," said Ashok Krishnamurthy, Ph.D., interim co-executive director of OSC. "Dr. Olivucci's computational investigations into the potential uses of Anabaena are a great example of how modeling, simulation and analysis can advance research into subjects only imagined just a few short years ago."

More information: Olivucci's research project, "Computational engineering and predictions of excited state properties of bacterial photoreceptor mutants," is supported by the Ohio Board of Regents and BGSU. Initial computational work relating to the project was published in the prestigious Proceedings of the National Academy of Sciences in 2010.

Provided by Ohio Supercomputer Center

Hot attraction in bimetals: A cyano-bridged vanadium-niobium bimetal assembly with a Curie temperature of 210 K

On the basis of initial studies indicating that an increased stoichiometry of vanadium(II) led to a higher Curie temperature in vanadium hexacyanochromate systems, Ohkoshi et al. used a small amount of VIII as catalyst to convert a higher proportion of VII in a similar system. The magnetic properties of the resulting octacyano-bridged vanadium–niobium bimetal assembly were investigated. The compound, whose formula was determined to be K0.59VII1.59VIII0.41[NbIV(CN)8] ·(SO4)0.50·6.9H2O, is ferrimagnetic, and the spins on VII and VIII are antiparallel with respect to the spin on NbIV. Its Curie temperature is 210 K. This high value is a result of the enhanced superexchange interaction through the VII–NC–NbIV pathway.

This study reports a strategy to synthesize magnetic materials with high Curie temperature to enhance the suitability of their magnetic properties for applications.

More information: Shin-ichi Ohkoshi, A Cyano-Bridged Vanadium–Niobium Bimetal Assembly Exhibiting a High Curie Temperature of 210 K, European Journal of Inorganic Chemistry, http://dx.doi.org/10.1002/ejic.201101219

Provided by Wiley (news : web)

Capsules that clean: New-look laundry detergents head for supermarket shelves

C&EN Assistant Managing Editor Michael McCoy explains that the technology behind films used to package the single doses of detergent have come a long way in the five decades since their debut. Previous versions of the encapsulating films interacted poorly with the detergent and had short shelf-lives. And another type of single-dose formulation — essentially a tablet of compressed laundry powders — didn't dissolve fully, leaving partially consumed chunks among the clean clothes.

In recent years, single-dose liquids packaged in polyvinyl alcohol film have caught on in the U.K. and France. The German company Henkel now has plans to market a similar "mono-dose" in the U.S. in the coming weeks, and Procter & Gamble plan to launch "Tide Pods" within a month. The same dose is used regardless of the amount of laundry that needs to be washed. Although the main technical challenges have been solved, experts say that "the jury is still out" on whether consumers are ready for these products.

More information: Selling Detergents One Load At A Time - http://cen.acs.org/articles/90/i4/Selling-Detergents-One-Load-Time.html

Provided by American Chemical Society (news : web)

Light but stable: novel cellulose-silica gel composite aerogels

Gels are familiar to us in forms like Jell-O or hair gel. A gel is a loose molecular network that holds liquids within its cavities. Unlike a sponge, it is not possible to squeeze the liquid out of a gel. An aerogel is a gel that holds air instead of a liquid. For example, aerogels made from silicon dioxide may consist of 99.98 % air-filled pores. This type of material is nearly as light as air and is translucent like solidified smoke. In addition, it is not flammable and is a very good insulator—even at high temperatures. One prominent application for aerogels was the insulation used on space shuttles. Because of their extremely high inner surface area, aerogels are also potential supports for catalysts or pharmaceuticals. Silica-based aerogels are also nontoxic and environmentally friendly.

One drawback, however, has limited the broader application of these airy materials: silica-based aerogels are very fragile, and thus require some reinforcement. In addition to reinforcement with synthetic polymers, biocompatible materials like cellulose are also under consideration.

The researchers at Wuhan University (China) and the University of Tokyo (Japan) have now developed a special composite aerogel from cellulose and silicon dioxide. They begin by producing a cellulose gel from an alkaline urea solution. This causes the cellulose to dissolve, and to regenerate to form a nanofibrillar gel. The cellulose gel then acts as a scaffold for the silica gel prepared by a standard sol–gel process, in which a dissolved organosilicate precursor is cross-linked, gelled, and deposited onto the cellulose nanofibers. The resulting liquid-containing composite gel is then dried with supercritical carbon dioxide to make an aerogel.

The novel composite aerogel demonstrates an interesting combination of advantageous properties: mechanical stability, flexibility, very low thermal conductivity, semitransparency, and biocompatibility. If required, the cellulose part can be removed through combustion, leaving behind a silicon dioxide aerogel. The researchers are optimistic: "Our new method could be a starting point for the synthesis of many new porous materials with superior properties, because it is simple and the properties of the resulting aerogels can be varied widely."

More information: Jie Cai, Cellulose–Silica Nanocomposite Aerogels by In Situ Formation of Silica in Cellulose Gel, Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201105730

Provided by Wiley (news : web)

Protein study gives fresh impetus in fight against superbugs

Researchers have mapped the complex molecular structure of an enzyme found in many bacteria. These molecules – known as restriction enzymes – control the speed at which bacteria can acquire resistance to drugs and eventually become superbugs.

The study, carried out by an international team including scientists from the University of Edinburgh, focused on E. coli, but the results would apply to many other infectious bacteria.

After prolonged treatment with antibiotics, bacteria may evolve to become resistant to many drugs, as is the case with superbugs such as MRSA.

Bacteria become resistant by absorbing DNA – usually from other bugs or viruses – which contains genetic information enabling the bacteria to block the action of drugs. Restriction enzymes can slow or halt this absorption process. Enzymes that work in this way are believed to have evolved as a defence mechanism for bacteria.

The researchers also studied the enzyme in action by reacting it with DNA from another organism. They were able to model the mechanism by which the enzyme disables the foreign DNA, while safeguarding the bacteria's own genetic material. Restriction enzymes' ability to sever genetic material is widely applied by scientists to cut and paste strands of DNA in genetic engineering.

The study was carried out in collaboration with the Universities of Leeds and Portsmouth with partners in Poland and France. It was supported by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust and published in Genes and Development journal.

Dr David Dryden, of the University of Edinburgh's School of Chemistry, who led the study, said: "We have known for some time that these enzymes are very effective in protecting bacteria from attack by other species. Now we have painted a picture of how this occurs, which should prove to be a valuable insight in tackling the spread of antibiotic-resistant superbugs."

Provided by University of Edinburgh

Researchers discover method to unravel malaria's genetic secrets

"The malarial genome has been a black box. Our technique allows us to open that box, so that we can learn what genes in the most lethal human parasite actually do," said Dennis Voelker, PhD, Professor of Medicine at National Jewish Health and senior author on the paper that appeared in the January 2, 2012 , issue of the Journal of Biological Chemistry. "This could prove tremendously valuable in the fight against a disease that has become increasingly drug-resistant."

The genome of P. falciparum was sequenced in 2002, but the actual functions of many of the organism's genes have remained elusive. One of the primary methods for discovering gene function is to copy a specific gene, insert it into a model organism that is easy to grow, often the yeast Saccharomyces cerevisiae, then draw on the incredible knowledge base about yeast and its abundant genetic variants to discover how that inserted gene changes the organism's biology.

DNA is composed of building blocks with the shorthand designations A,T,C and G. The genome of P. falciparum is odd because it is particularly rich in A's and T's. Because of this A-T-rich nature, P. falciparum genes generally do not function when they are inserted into other organisms. As a result, scientists have been largely stymied when trying to understand the functions of P. falciparum's genes.

It turns out, however, that P. falciparum has a close cousin, P. knowlesi, which shares almost all its genes with P. falciparum, but with fewer A's and T's. As a result, P. knowlesi genes function well when inserted into yeast. Scientists can now insert P. knowlesi genes into yeast, discover their function, and then match them to corresponding genes in P. falciparum, which reveals the function of the malarial parasite's genes.

"This technique could lead to an explosion in knowledge about malaria and the parasite that causes it." said Dr. Voelker.

The researchers used the technique to discover a new gene involved in the synthesis of lipids in cell membranes of P. falciparum. The gene, phosphatidylserine decarboxylase, directs the formation of a protein unique to malarial parasites and is a potential therapeutic target. For example, selective disruption of lipid synthesis in P. falciparum, would prevent the organism from making new cell membranes, growing and reproducing in human hosts.

Provided by National Jewish Health

Researchers seek to beat 'molecular obesity'

Professor Andrew Hopkins and his team from the University's College of Life Sciences have developed a mathematical formula that they believe has the potential to more effectively identify compounds that have the best chance of being successfully developed into drugs to treat and protect against disease.

In order to succeed as a drug, a compound has to have the right balance of properties. Those compounds that are too large or too greasy - said to be molecularly obese - tend not to be well absorbed by the body when taken orally as pills and have been blamed for increasing rates of failure and rising costs in the drug development process.

This is why the most commonly used and effective orally dosed drugs that are available on the market tend to be relatively small and lean. Compounds sharing these properties are said to be "drug-like" and assessment of "drug-likeness" is a key consideration when selecting compounds for further development.

Until now this assessment has been made according to a widely used set of rules that determine whether or not compounds are suitable for further development as orally absorbed pills.

However, the evaluation of drug-likeness in black and white terms does not adequately reflect the whole spectrum of compound quality as many successful drugs apparently 'break the rules' so the Dundee team set about developing an alternative model.

They have pioneered a measure of drug-likeness based on the concept of desirability called Quantitative Estimate of Druglikeness (QED) which rates a compound between 0-1 based on its molecular properties, with 1 indicating an ideal candidate.

Once the scores have been calculated any set of compounds can be easily ranked by their relative merit. Importantly, the formula is derived entirely from historical data on the observed properties of successful drugs. This approach is more flexible than simply attributing a pass or fail to a compound, and offers several advantages to researchers looking to develop new drugs, according to Professor Hopkins.

"We think this may be a better way of appraising compounds in drug discovery," he said. "What we are trying to overcome is a problem of judging which compounds have the lowest risk of failure before synthesizing or buying them. This is important because the cost of drugs is in part driven by the high failure rate in developing new therapies.

"Compounds that don't have the correct properties or features make them particularly unsuitable, but this doesn't tell the whole story. Scientists judge them according to the rules, which might suggest a particular compound will work, but not that they will only work to a certain extent and that there are more effective alternatives available.

"Over the past two decades the compounds made by the pharmaceutical industry have tended to get larger and greasier. This trend has been called molecular obesity, and while these "obese" compounds may pass the rules they are far from the ideal.

"Some experts in the industry argue that the increasing failure rate and increasing cost in developing new drugs may be due to the rise in molecular obesity of new compounds. QED gives us a new tool to guide drug design toward leaner, fitter, more attractive compounds, with hopefully a greater overall chance of success.

"The rules which chemists use are useful, but only as far as telling us that it does or doesn't work. We are trying to get away from the concept of using hard and fast rules and looking instead at the shades of grey, which reflect the reality of the situation. What we are trying to do is increase the odds of identifying a successful compound."

The Dundee team's work is published in the most recent edition of the Nature Chemistry journal. The paper, entitled 'Quantifying the chemical beauty of drugs', is co-authored by colleagues in England and Sweden.

After attributing values to several thousand compounds, the researchers asked around 80 chemists to evaluate them based on their own knowledge and scientific methods. This showed that the Dundee method was an effective way of identifying attractive candidates which agreed very well with the chemists' intuition.

Professor Hopkins continued, "Chemists often refer to compounds as looking "good, bad or ugly" according to their suitability, and we asked the chemists who took part in this survey whether a drug was attractive or not, and found their tacit knowledge fitted well with our calculation.

"The whole idea is to use statistics, data, and underlying probability distributions which has been gathered on drugs over the years to help us more quickly and effectively identify attractive compounds in the future.

"The formula encodes the properties that seem to determine a compound's attractiveness, and reflects the knowledge required in drug discovery. What we found exciting is the idea of a mathematical formula that reflects the chemists experience and intuition of what they consider an "attractive" compound to synthesise.

"From here we can develop a more nuanced approach to identifying lower risk compounds for drug discovery."

Provided by University of Dundee

In lab, Pannexin1 restores tight binding of cells that is lost in cancer

"In healthy tissues, the recently discovered protein Pannexin1 may be playing an important role in upholding the mechanical integrity of the tissue," said first author and Brown University M.D./Ph.D. student Brian Bao. "When we develop cancer, we lose Pannexin1 and we lose this integrity."

The results appeared in advance online in the Journal of Biological Chemistry on Jan. 20.

To conduct their research, the group at Brown University and the University of British Columbia employed a "3-D Petri dish" technology that allows investigators to watch closely how cells interact with each other, without scientists having to worry about additional interactions with surrounding scaffolding or the culture plate itself. How readily the cells form large multicellular structures therefore reflects their interactions with each other, not their in vitro surroundings.

Bao's advisor, Jeffrey Morgan, associate professor of medical science, developed the 3-D Petri dish technology. Morgan is the paper's senior author.

Cancer cells converge

Starting with rat "C6" glioma (brain tumor) cells that do not express Pannexin1, the researchers left some unaltered and engineered others to express Pannexin1. After putting the different cells into the 3-D Petri dishes and watching them interact for 24 hours, they saw that the Pannexin1 cells were able to form large multicellular tissues much faster and more tightly than the unaltered cancer cells.

To confirm that Pannexin1 was indeed causing these changes, Bao and his colleagues treated their samples with the drugs Probenecid and Carbenoxolone, which are well known inhibitors of Pannexin1. They saw that sure enough, the drugs negated Pannexin1's accelerating effect.

Then the team was ready to achieve the the study's main aim, Bao said, namely to determine how Pannexin1 was able to drive these cells to clump together faster and tighter. They found that Pannexin1 sets off a chain reaction involving the energy-carrying molecule ATP and specific receptors for it.

When all experiments were done, Bao, Morgan, and their collaborators had found that as soon as the cells touched each other, Pannexin1 channels were stimulated to open and release ATP. The ATP then bound to cell surface receptors, kicking off intracellular calcium waves that ultimately remodeled the network of a structural protein called actin. This remodeling increases the forces between the cells, driving them to bind together more tightly.

Figuring out that sequence, and Pannexin1's role in it, is perhaps the study's biggest contribution to cancer research, Bao said.

"Using their single-cell systems, others have been able to carefully study individual pieces of this cascade," he said. "We came from a different perspective. Because the strength of our assay is that we can look at gross multicellular behavior in 3-D, we could ask, 'Does this actually manifest into something tangible on the multicellular level?'"

Having gained this understanding of Pannexin1's role in the mechanics of tumors, Bao is now engaged in research to answer the obvious next questions: Does Pannexin1 affect the tumor's ability to spread and invade? When cancerous cells regain Pannexin1 expression, are they less likely to spread and leave the tumor?

Provided by Brown University (news : web)

Pine transformed by modern alchemists

Pinewood made denser than ebony, textured and hard likes the pure essence of wood itself? Thanks to a process that reminds one of alchemic essays to turn lead to gold, a team led by Parviz Navi has given simple pinewood similar qualities to wood from expensive and rare tropical species. Starting on the 26th of January, EPFL+ECAL Lab is displaying several objects from daily life made out the new material. Elegant and sleek, objects such as headphones and a door handle show the promising possibilities of the new procedure.

Wood is composed of straw-like tubes filled with air—becoming much denser when compressed. This process has been known for some time now, but until very recently the wood would bounce back into its original form when in contact with humidity. By tweaking the parameters of compression, the EPFL researchers have stabilized the compacted wood without adding any resin or other substance. Suddenly, pinewood loses its working-class roots and inspires for more lofty ambitions—teck, ebony or amaranth.

EPFL+ECAL Lab has called upon Swiss and French designers to create objects out of the new material. Each new project explores a different aspect of the wood. “These first trials are meant to explore the wood’s potential,” explains Nicolas Henchoz, director of EPFL+ECAL Lab.

“We are still in the experimental phase, the procedure will be optimized in the near future in order to move to industrial production,” Henchoz added.

If the bet pays off, it could reduce the burden on tropical forests.

Provided by Ecole Polytechnique Federale de Lausanne

Scientists use silk from the tasar silkworm as a scaffold for heart tissue

Of all the body’s organs, the human heart is probably the one most primed for performance and efficiency. Decade after decade, it continues to pump blood around our bodies. However, this performance optimisation comes at a high price: over the course of evolution, almost all of the body’s own regeneration mechanisms in the heart have become deactivated. As a result, a heart attack is a very serious event for patients; dead cardiac cells are irretrievably lost. The consequence of this is a permanent deterioration in the heart’s pumping power and in the patient’s quality of life.

In their attempt to develop a treatment for the repair of cardiac tissue, scientists are pursuing the aim of growing replacement tissue in the laboratory, which could then be used to produce replacement patches for the repair of damaged cardiac muscle. The reconstruction of a three-dimensional structure poses a challenge here. Experiments have already been carried out with many different materials that could provide a scaffold substance for the loading of cardiac muscle cells.

“Whether natural or artificial in origin, all of the tested fibres had serious disadvantages,” says Felix Engel, Research Group Leader at the Max Planck Institute for Heart and Lung Research in Bad Nauheim. “They were either too brittle, were attacked by the immune system or did not enable the heart muscle cells to adhere correctly to the fibres.” However, the scientists have now found a possible solution in Kharagpur, India.

At the university there, coin-sized disks are being produced from the cocoon of the tasar silkworm (Antheraea mylitta). According to Chinmoy Patra, an Indian scientist who now works in Engel’s laboratory, the fibre produced by the tasar silkworm displays several advantages over the other substances tested. “The surface has protein structures that facilitate the adhesion of heart muscle cells. It’s also coarser than other silk fibres.” This is the reason why the muscle cells grow well on it and can form a three-dimensional tissue structure. “The communication between the cells was intact and they beat synchronously over a period of 20 days, just like real heart muscle,” says Engel.

Despite these promising results, clinical application of the fibre is not currently on the agenda. “Unlike in our study, which we carried out using rat cells, the problem of obtaining sufficient human cardiac cells as starting material has not yet been solved,” says Engel. It is thought that the patient’s own stem cells could be used as starting material to avoid triggering an immune reaction. However, exactly how the conversion of the stem cells into cardiac muscle cells works remains a mystery.

More information: Chinmoy Patra, Sarmistha Talukdar, Tatyana Novoyatleva, Siva R. Velagala, Christian Mühlfeld, Banani Kundu, Subhas C. Kundu, Felix B. Engel
Silk protein fibroin from Antheraea mylitta for cardiac tissue engineering, Biomaterials, Advance Online Publication Januar 10, 2012

Provided by Max-Planck-Gesellschaft (news : web)

Researchers develop new drug release mechanism utilizing 3-D superhydrophobic materials

The study was electronically published on January 16, 2012 in the Journal of the American Chemical Society.

Boston University (BU) graduate student Stefan Yohe, under the mentorship of Mark Grinstaff , PhD, BU professor of biomedical engineering and chemistry, and Yolonda Colson, MD, PhD, director of the Dana-Farber Cancer Institute/Brigham and Women's Hospital (BWH) Cancer Center, prepared drug-loaded superhydrophobic meshes from biocompatible polymers using an electrospinning fabrication method.

By monitoring drug release in aqueous solution and mesh performance in cytotoxicity assays, the team demonstrated that the rate of drug release correlates with the removal of the air pocket within the material, and that the rate of drug release can be maintained over an extended period.

"The ability to control drug release over a 2-3 month period is of significant clinical interest in thoracic surgery with applications in pain management and in the prevention of tumor recurrence after surgical resection," said Colson. Colson is also a thoracic surgeon at BWH with an active practice focused on the treatment of lung cancer patients.

This approach along with the design requirements for creating 3D superhydrophobic drug-loaded materials, the authors write, should facilitate further exploration and evaluation of these drug delivery materials in a variety of cancer and non-cancer applications.

Provided by Brigham and Women's Hospital

Chemists reveal how algae delete unwanted 'competitors'

Like a 'molecular toothbrush', which removes other micro-organisms thoroughly, every morning this chemical mace 'disinfects' the ground on which these diatoms grow. "Thus they can ideally grow and keep direct competitors for light and free space in check," Professor Dr. Georg Pohnert of the Friedrich Schiller University Jena (Germany) states. The director of the Institute of Inorganic and Analytical Chemistry revealed together with his team and colleagues of the University Ghent (Belgium) the chemical devastating blow of the diatoms. Their findings were published in the new edition of the well known science magazine Proceedings of the National Academy of Sciences.

Cyanogen bromide is a highly poisonous metabolic toxin and is – amongst other things – being used for the lixiviating of gold ores. During the First World War it was also used as a chemical weapon. "Until now it wasn't even known that this poison occurs in the living nature at all," says Professor Pohnert. For "Nitzschia cf pellucida" the production of cyanogen bromide seems to be easy though. As soon as the first rays of sunlight find their way into the water, the cellular 'devil's workshop' starts to work. "From two up to four hours after day break the concentration of the released cyanogen bromide is at its highest, later on it decreases," Professor Pohnert explains one of the results of his new study.

The scientists can still only speculate about the fact that the poison doesn't harm the diatoms themselves. One thing is for sure: While the 'competing' algae give up after two hours at most, subsequent to being attacked by cyanogen bromide the poison at the same time doesn't harm Nitzschia cf pellucida. To find the reasons for this is one of the next research objectives of the Jena scientists and their Belgian partners.

But according to chemist Pohnert this would be pure basic research. Cyanogen bromide is completely inapplicable to practical use – for instance as a means against unwanted algae growth. Because it is certain that in this case it is not only the algae that would be damaged.

More information: Vanelslander B et al.: Daily bursts of biogenic cyanogen bromide (BrCN) control biofilm formation around a marine benthic diatom. PNAS 2012, doi:10.1073/pnas.1108062109

Provided by Friedrich-Schiller-Universitaet Jena

MSU technology spin-out company to market portable biohazard detection

Food contamination and other biohazards present a growing public health concern, but laboratory analysis consumes precious time. The company, nanoRETE, will develop and commercialize an inexpensive test for handheld biosensors to detect a broad range of threats such as E.coli, Salmonella, anthrax and tuberculosis.

A significant leap forward in detection and diagnostic technology, it utilizes novel nanoparticles with magnetic, polymeric and electrical properties developed by Evangelyn Alocilja, MSU professor of biosystems and agricultural engineering and chief scientific officer of nanoRETE.

“Our unique preparation, extraction and detection protocol enables the entire process to be conducted in the field, without significant training,” Alocilja said. “Results are generated in about an hour from receipt of sample to final readout, quickly identifying contaminants so that proper and prompt actions can be taken.”

The mobile technology comes at only a fraction of the cost of the closest currently available competing technology, company officials said.

“Although the technology originates from research for biodefense applications, its potential reaches far beyond the initial scope,” said Fred Beyerlein, CEO of nanoRETE. “Our X-MARK platform-based technology has the ability to detect multiple pathogens or toxins at one time, in a rapid, point-of-use, cost-effective manner. Imagine the potential applications for food growers, packagers or sellers. Contaminated food or water could be quickly identified, isolated and resolved before reaching the ultimate consumer – you or me.”

nanoRETE is backed by Michigan Accelerator Fund I, a Grand Rapids, Mich., investment partnership focused on Michigan-based early stage life science and technology companies.

“Our task was to find promising technologies, identify strong management and support with investment dollars,” MAF-1 managing director Dale Grogan said. “We reviewed literally hundreds of technologies developed within MSU and determined that this particular technology best fit our investment model. We are excited about nanoRETE’s future and hope this is the first of many companies we help develop with MSU.”

“We have had great faith that Dr. Alocilja’s work in nano-scale detection would be a very successful platform on which to start a new company,” said Charles Hasemann, executive director of MSU Technologies. “MAF-1 has been a great partner in building nanoRETE. With its partnership and investment, we expect to move rapidly to a marketable product.”

Provided by Michigan State University (news : web)

Of microchemistry and molecules: Electronic microfluidic device synthesizes biocompatible probes

The research team, led by Professors R. Michael van Dam and Pei Yuin Keng in UCLA’s Crump Institute for Molecular Imaging and Professor CJ Kim in the Mechanical and Aerospace Engineering Department, faced a particularly challenging issue in developing their digital microfluidic device and applying it to microscale chemical synthesis. “When working with organic solvents at small volume scales – especially those that are volatile – evaporation is a significant problem in the relatively open configuration of EWOD chips,” van Dam tells PhysOrg.com. “Unwanted evaporation can change concentrations, dry the sample, and so on, leading to imprecise control over the chemical process and low reproducibility of the chemistry. Our main challenge was in overcoming this effect.”

Controlling liquids via electrowetting is very attractive due to the absence of moving parts, as well as the ease of integrating droplet actuation with heating and sensing. “It had been shown a few years ago that organic solvents can be manipulated on the same chips as water droplets, although not exactly by pure electrowetting,” van Dam continues. “Indeed, we didn’t have any problems moving droplets. Rather, the main operational challenges we encountered were related to on-chip mixing of liquids with solid residues, and the well-controlled evaporation of solvents at temperatures above the solvent boiling point.” This is due to the fact that under such superheated conditions, liquids can undergo bumping – the bursting of droplets and loss of reagents out of the chip.

The team explored a number of ideas to address the issue of undesired evaporation during reaction steps. “Altering the chip and droplet geometry to limit evaporation was somewhat effective, but also adversely impacted the ability to evaporate solvents during steps where evaporation was actually desired,” van Dam explains. Replenishing the solvent by loading additional droplets is a promising approach – but other technical challenges would then need to be addressed, such as how to avoid a drop in reaction temperature when a new droplet is added, and how to effectively mix the incoming droplet with the existing reaction mixture.

“The real breakthrough in the application we presented was realizing that we could alter the solvent without encountering the same difficulties associated with doing so at the macroscale. Since our reaction volume is so small, we could effectively evaporate dimethyl sulfoxide (DMSO) – a very non-volatile solvent – at a modest temperature.” At the macroscale, DMSO is typically avoided because it is very difficult to remove quickly – a concern in certain applications where synthesis time is critical, such as synthesis of positron emission tomography (PET) probes – and more volatile solvents are selected instead. However, van Dam points out, for some applications, the length of time would be less critical – for example, chemical and pharmaceutical production processes can take days, weeks or months.

Moreover, adds van Dam, the team is developing several additional innovations to enhance the current experimental design. “One area we’re working on is increasing the level of automation,” van Dam illustrates. “Once the droplets of chemicals are on-chip, they’re manipulated electronically, so sophisticated sequences of operations can readily be automated. In contrast,” he continues, “in our proof-of-concept synthesis chip, the necessary steps of adding reagents to the chip and extracting the final product are performed by pipetting or other manually-operated techniques. Increased overall automation is therefore critical to making the platform user-friendly and safe.

Another area of investigation is in situ sensing of liquid droplets. “With a very simple modification of the EWOD voltage driving circuit, it’s possible to monitor the AC current through the droplet, says van Dam. “This small current gives information about impedance, which in turn is related to droplet volume and composition. Other groups have shown how verifying that droplets have actually moved as instructed can increase the fidelity of on-chip assays and we’re planning to extend this principle to verify that the correct liquid is in the correct location and to perform real-time monitoring of chemical process variables.” This could be used, for example, to increase the reliability of on-chip microchemical production or provide an integrated readout for a chemical assay.

Van Dam also notes that microscale will eventually transition to nanoscale. “There are research efforts underway to shrink the size of electrodes and droplets handled by EWOD microfluidic devices to subnanoliter volumes. The microchemistry principles we presented could likely be scaled down to operate on these devices.”

On the other hand, van Dam points out that an in silico simulation model would be difficult to derive, given the current general lack of understanding of microscale chemistry in droplets. “For example,” he relates to PhysOrg, “one surprising result we observed was the need to use somewhat higher reagent concentrations in droplets compared to what is normally used at the macroscale to achieve comparable reaction yields. Our microchemistry platform could perhaps be used to study microscale chemistry and gather data that could lead to development of a simulation.”

One of the next steps in the group’s work is to increase the level of automation as mentioned above. “We envision a compact, benchtop system that, if loaded with the right reagents, could produce a variety of compounds on demand at the push of a button. We’re also pursuing applications of this device – in particular for the production of PET probes. Unlike most chemicals which can be produced in large batches and stored, these compounds are short-lived and require production just prior to use for medical imaging.” Currently, the production of PET probes requires expensive, complicated, and bulky equipment and infrastructure.

“Commercial networks of radiopharmacies have invested in this equipment and produce and ship the probes daily to supply hospitals, imaging centers, and research labs,” van Dam adds. “Making large batches that are divided among numerous customers provides economy of scale that makes these probes affordable, but at a cost – these radiopharmacies provide only a small number of different probes. But as we move into an era of personalized medicine, it will become increasingly important to have a diversity of diagnostic probes available so that patients can be matched to the correct drugs.” Compact, inexpensive, benchtop chemistry systems could be transformative, in that clinicians and researchers could afford to produce exactly the probes they want, when they want.

 Van Dam also points out that although these techniques have been demonstrated in the context of medical diagnostics, many different areas could also be served by performing microchemistry on EWOD. “Small scale chemistry could be useful to chemists doing natural products synthesis, where reagents and intermediates can be very costly due to the large number of reaction steps, and time, needed to produce them,” he adds. “It’s also likely that the ability to handle chemicals and organic solvents on-chip could lead to new assays in a variety of areas such as contaminant detection, environmental monitoring, and quality control in chemical production.” The techniques might also be useful for optofluidics due to the use of organic and high-index liquids in such devices.

“EWOD chips enable programmable control of liquids and thus a single chip design may be capable of supporting a wide range of reactions and assays with only software changes,” van Dam concludes. “By not having to produce a different chip for each application, cost could be substantially reduced.”

More information: Micro-chemical synthesis of molecular probes on an electronic microfluidic device. PNAS January 17, 2012 vol. 109 no. 3 690-695, doi: 10.1073/pnas.1117566109

Copyright 2012 PhysOrg.com.
All rights reserved. This material may not be published, broadcast, rewritten or redistributed in whole or part without the express written permission of PhysOrg.com.

Grafted watermelon plants take in more pesticides

Mehmet Isleyen and colleagues explain that farmers graft watermelon and other fruits onto the roots of gourd plants because it makes the fruit more resistant to diseases. In Turkey, where the group did the study, more than 95 percent of watermelons grow from grafted seedlings. Although the gourds are hardier, previous research has shown they accumulate pesticides called organochlorines. Organochlorines have been widely banned because of concerns about their effects on human health and wildlife. Despite the fact that their remnants can linger in the soil for decades, some organochlorines remain in use. While traditional watermelon plants do not take up these compounds, the researchers wanted to resolve uncertainty about watermelon grown on the roots of plants in the squash family.

The group grew common Turkish watermelon-squash graft seedlings in soil taken from a farming region there. They tested the roots, stems, leaves and fruit of the plants and found that organochlorine levels were as much as 140 times higher in the stems of squash-grafted watermelons than in intact watermelons. However, while still urging caution, the group notes that these levels are 6-12 times lower than accepted limits of the pesticides in produce in the U.S. and Turkey.

More information: Accumulation of Weathered p,p'-DDTs in Grafted Watermelon, J. Agric. Food Chem., Article ASAP. DOI:10.1021/jf204150s

Abstract
The grafting of melon plants onto cucurbit rootstocks is a common commercial practice in many parts of the world. However, certain cucurbits have been shown to accumulate large quantities of weathered persistent organic pollutants from the soil, and the potential contamination of grafted produce has not been thoroughly evaluated. Large pot and field experiments were conducted to assess the effect of grafting on accumulation of weathered DDX (the sum of p,p'-DDT, p,p'-DDD, and p,p'-DDE) from soils. Intact squash (Cucurbita maxima × moschata) and watermelon (Citrullus lanatus), their homografts, and compatible heterografts were grown in pots containing soil with weathered DDX at 1480–1760 ng/g soil or under field conditions in soil at 150–300 ng/g DDX. Movement of DDX through the soil–plant system was investigated by determining contaminant levels in the bulk soil and in the xylem sap, roots, stems, leaves, and fruit of the grafted and nongrafted plants. In all plants, the highest DDX concentrations were detected in the roots, followed by decreasing amounts in the stems, leaves, and fruit. Dry weight concentrations of DDX in the roots ranged from 7900 ng/g (intact watermelon) to 30100 ng/g (heterografted watermelon) in the pot study and from 650 ng/g (intact watermelon) to 2430 ng/g (homografted squash) in the field experiment. Grafting watermelon onto squash rootstock significantly increased contaminant uptake into the melon shoot system. In the pot and field studies, the highest stem DDX content was measured in heterografted watermelon at 1220 and 244 ng/g, respectively; these values are 140 and 19 times greater than contaminant concentrations in the intact watermelon, respectively. The xylem sap DDX concentrations of pot-grown plants were greatest in the heterografted watermelon (6.10 µg/L). The DDX contents of the leaves and fruit of watermelon heterografts were 3–12 and 0.53–8.25 ng/g, respectively, indicating that although the heterografted watermelon accumulated greater pollutant levels, the resulting contamination is not likely a food safety concern.

Provided by American Chemical Society (news : web)

How seawater could corrode nuclear fuel

But Navrotsky and others have since discovered a new way in which seawater can corrode nuclear fuel, forming uranium compounds that could potentially travel long distances, either in solution or as very small particles. The research team published its work Jan. 23 in the journal Proceedings of the National Academy of Sciences.

"This is a phenomenon that has not been considered before," said Alexandra Navrotsky, distinguished professor of ceramic, earth and environmental materials chemistry. "We don't know how much this will increase the rate of corrosion, but it is something that will have to be considered in future."

Japan used seawater to avoid a much more serious accident at the Fukushima-Daiichi plant, and Navrotsky said, to her knowledge, there is no evidence of long-distance uranium contamination from the plant.

Uranium in nuclear fuel rods is in a chemical form that is "pretty insoluble" in water, Navrotsky said, unless the uranium is oxidized to uranium-VI — a process that can be facilitated when radiation converts water into peroxide, a powerful oxidizing agent.

Peter Burns, professor of civil engineering and geological sciences at the University of Notre Dame and a co-author of the new paper, had previously made spherical uranium peroxide clusters, rather like carbon "buckyballs," that can dissolve or exist as solids.

In the new paper, the researchers show that in the presence of alkali metal ions such as sodium — for example, in seawater — these clusters are stable enough to persist in solution or as small particles even when the oxidizing agent is removed.

In other words, these clusters could form on the surface of a fuel rod exposed to seawater and then be transported away, surviving in the environment for months or years before reverting to more common forms of uranium, without peroxide, and settling to the bottom of the ocean. There is no data yet on how fast these uranium peroxide clusters will break down in the environment, Navrotsky said.

Provided by University of California - Davis

New standard for vitamin D testing to ensure accurate test results

Karen Phinney and colleagues explain that medical research suggests vitamin D deficiency or insufficiency may be even more common than previously thought and a risk factor for more than just bone diseases. An estimated 50-75 percent of people in the U.S. may not have enough vitamin D in their bodies. Low levels of vitamin D have been linked to the development of several conditions, including rickets (soft and deformed bones), osteoporosis, some cancers, multiple sclerosis and Parkinson's disease. People can make their own vitamin D simply by rolling up their shirt sleeves and exposing their skin to sunlight. But for those cooped up in offices all day long, food and dietary supplements also can provide vitamin D. With this renewed interest in vitamin D, scientists need an accurate way to measure its levels in the blood. Measuring vitamin D itself doesn't work because it is rapidly changed into another form in the liver. That's why current methods detect levels of a vitamin D metabolite called 25(OH)D. However, the test methods don't always agree and produce different results. To help laboratories come up with consistent and accurate methods, the researchers developed a Standard Reference Material called SRM 972, the first certified reference material for the determination of the metabolite in human serum (a component of blood).

The researchers developed four versions of the standard, with different levels of the vitamin D metabolites 25(OH)D2 and 25(OH)D3 in human serum. They also determined the levels of 3-epi-25(OH)D in the adult human serum samples. Surprisingly, they found that this metabolite — previously thought to only exist in the blood of infants — was present in adult serum. "This reference material provides a mechanism to ensure measurement accuracy and comparability and represents a first step toward standardization of 25(OH)D measurements," say the researchers.

More information: Development and Certification of a Standard Reference Material for Vitamin D Metabolites in Human Serum, Anal. Chem., 2012, 84 (2), pp 956–962. DOI: 10.1021/ac202047n

Abstract
The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health’s Office of Dietary Supplements (NIH-ODS), has developed a Standard Reference Material (SRM) for the determination of 25-hydroxyvitamin D [25(OH)D] in serum. SRM 972 Vitamin D in Human Serum consists of four serum pools with different levels of vitamin D metabolites and has certified and reference values for 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3. Value assignment of this SRM was accomplished using a combination of three isotope-dilution mass spectrometry approaches, with measurements performed at NIST and at the Centers for Disease Control and Prevention (CDC). Chromatographic resolution of the 3-epimer of 25(OH)D3 proved to be essential for accurate determination of the metabolites.

Provided by American Chemical Society (news : web)

From cancer research to energy storage, Berkeley Lab scientist takes on big challenges

It’s fair to say that what she does is difficult to grasp. Why she does it is easy: “I want to help solve big problems. That’s why I’m here,” she says.

In this case, the big problem is energy—or how you can drive to work without consuming fossil fuel or emitting CO2. Bardhan’s research is part of a Department of Energy goal to develop an on-board hydrogen-storage system that will enable a fuel cell powered car to go 300 miles without refueling, with water as the only by-product.

Getting there requires synthesizing new materials that can safely store a lot of hydrogen in a small package without costing too much. The work is part fundamental science and part real-world know-how. It’s also the perfect challenge for Bardhan, who recently earned a spot on Forbes’ list of 30 people under 30 who are rising stars in science.

Science seems to surround the 29-year-old chemist. Her husband, a researcher at Intel Corporation, also made the Forbes’ 30-under-30 list for work on nanotube supercapacitors for high-energy batteries. She grew up in India, where her father and several uncles are engineers. She came to the U.S. ten years ago, studied chemistry at a small liberal arts college in Missouri, and then received a PhD in chemistry from Rice University. Her graduate work focused on developing plasmonic structures for cancer therapy and diagnosis.

In 2010, she was offered a postdoctoral position in Jeff Urban’s lab at the Molecular Foundry. The research focused on clean energy, not cancer research, but she jumped at the opportunity. It was a natural transition.

“When I think of science, I think of major problems that I can help solve,” she says. “There’s human health. There’s also human sustainability, and for me, that means clean energy production and storage. We need to find renewable energy sources that have very little impact on the environment.”

Vehicles powered by hydrogen fuel cells could be one such solution, but there are significant hurdles to overcome. Chief among them is storing enough hydrogen in a car to provide a driving range that competes with a tank of gas. The most common way to store hydrogen is in a pressurized tank that contains gaseous or liquefied hydrogen. But this approach has safety issues. And the volumetric density of a tank of gaseous or liquefied hydrogen—or how much energy it holds—is very low.

Instead, Bardhan and her colleagues in Jeff Urban’s lab at the Molecular Foundry are developing storage materials composed of metal hydrides, a compound in which hydrogen is bound to a metal. Metal hydrides have the potential to store a lot of hydrogen in a small volume, and release it at low temperatures and pressures.

Recently, they designed a new composite consisting of nanoparticles of magnesium metal uniformly embedded through a matrix of a hydrogen-selective polymer, which is related to Plexiglas. Bardhan says the material is very close to the Department of Energy’s goal of six weight percent, meaning six percent by weight of the metal hydride is hydrogen. They’re now optimizing the material even more, with the goal of edging toward the material’s theoretical limit of 7.6 weight percent.

Part of this optimization involves gaining a better understanding of how a metal transitions to a metal hydride, such as how Mg becomes MgH2. To do this, Bardhan is developing optical spectroscopy techniques that will enable scientists to watch this transformation in real time as it happens.

“Without understanding these very fundamental processes, we cannot improve the properties of the materials,” says Bardhan.

Provided by Lawrence Berkeley National Laboratory (news : web)

Scientists X-ray key enzyme of common pathogen crystallized in living cells

The three-dimensional structure of a biomolecule gives biologists clues about its function, and in the case of a pathogen it also offers the perspective to block a harmful protein with a tailor-made artificial molecule. For example, if the enzyme cathepsin B of Trypanosoma brucei is blocked, the parasite will die. However, the structure analysis of biomolecules is a difficult and time-consuming process. Normally, a sufficiently large crystal of the protein in question has to be grown in the lab before it can be investigated with X-ray light of a synchrotron radiation source.

Crystal growing is complicated and often takes weeks or even months. Therefore, the team of scientists – among them scientists from the universities of Tübingen, Hamburg and Lübeck, and from Deutsches Elektronen-Synchrotron DESY in Hamburg – chose another approach. With the help of a virus, they inserted the genetic blueprint for cathepsin B into living insect cells. The infected cells started to produce the enzyme incessantly, and with the steadily increasing concentration, the enzyme eventually crystallised. After about 70 hours, the micrometre-small crystals became visible in the microscope, some of them even sticking out of the cells.

At the US accelerator centre SLAC in California, the scientists bombarded these crystals with the world’s strongest X-ray free-electron laser LCLS. Although its intensive X-ray flash completely vaporises the crystals in less than a billionth of a second, it is bright enough to previously take a detailed diffraction image of the crystal, making it possible to calculate the structure of the crystallised enzyme. However, to gain the complete structural information the experiment must be repeated very often with a large number of crystals, which was not part of the study.

But the result shows that with the new technology it is possible to generate high-quality data of the protein structure of nanocrystals. "Our experiments have shown that the promise of X-ray lasers to revolutionize structural biology is indeed becoming true," said DESY scientist Prof. Henry Chapman from the Center for Free-Electron Laser Science (CFEL). "We have shown that previous limitations to protein crystallography can be overcome by using pulses of X-rays so intense, that they transform the proteins into a dense plasma similar to the conditions inside the sun. Yet the pulses are so short that fine details are seen before destroying the sample," Dr. Anton Barty from CFEL added.

Apart from the Federal Ministry of Education and Research-funded young investigators group "Structural Infection Biology Using new Radiation Sources (SIAS)" of the universities of Hamburg and Lübeck, and the Hamburg School for Structure and Dynamics in Infection (SDI) of the State of Hamburg Excellence Initiative, the research was done with the participation of a team of scientists headed by professor Michael Duszenko from the University of Tübingen, a CFEL-group headed by professor Henry Chapman as well as other DESY scientists and international collaboraters. CFEL is a cooperation of DESY, the Max Planck Society and the University of Hamburg.

“Our result shows that the super lasers offer completely new possibilities for the structure determination of biological macromolecules, and perhaps the days will be over soon when we needed months or even years to grow crystals of certain proteins being large enough for X-ray radiation sources at synchrotrons” said SIAS leader Dr. Lars Redecke, one of the main authors of this study.

As from 2010, SIAS - an initiative of the structural research scientists professor Christian Betzel, University of Hamburg, and professor Rolf Hilgenfeld, University of Lübeck - investigates the use of innovative radiation sources for structural determination of proteins and other biological molecules.

The European X-ray laser European XFEL, currently being built in Hamburg, will open a unique opportunity for biomolecule investigation. Already today, DESY operates the free-electron laser FLASH for soft X-ray radiation.

More information: "In vivo protein crystallization opens new routes in structural biology"; Michael Duszenko et al.; "Nature Methods", Advance Online Publication; DOI: 10.1038/nmeth.1859

Provided by DESY

Scientists rediscover self-healing silicone mechanism from the 1950s

The researchers, grad student Peiwen Zheng and Professor Thomas J. McCarthy from the University of Massachusetts, have published a paper on the rediscovery of siloxane equilibration in a recent issue of the Journal of the American Chemical Society.

“We have been working on silicone materials from a couple of different perspectives,” Zheng told PhysOrg.com. “When we rediscovered the forgotten unusual properties of silicones and combined them with today’s research interests, we found that the silicone material with the siloxane equilibration was an obvious candidate for a self-healing material.”

The researchers performed several experiments to test the theoretical predictions from papers published in the early 1950s, as well as to extend some of the experiments performed at that time. In one experiment, Zheng and McCarthy prepared a siloxane-based mixture containing a cross-linking agent and a catalyst. Then they poured the solution into molds of various shapes, such as cylinders, disks, and dog bones. After heating the molds at 90 °C (194 °F) for four hours, the researchers removed clear, rubbery silicone shapes from the molds. The scientists described these silicone samples as “living polymer networks.”

“The silicone network is at a chemically anionic equilibrium,” Zheng explained of the term, “where the reactive center will cleave and reform a covalent siloxane bond.” These bonds are reversible, which enables the two sides of a crack to reconnect under the right conditions.

To demonstrate the self-healing ability, the researchers cut a 1-cm-long cylindrical sample in half using a razor blade. Then they rejoined the two pieces by wrapping them together with Teflon plumbing tape and heating them in an oven at 90 °C (194 °F) for 24 hours. When the researchers retrieved the sample and removed the tape, they found that the silicone cylinder had completely healed. Then they bent the cylinder by hand until it broke again - significantly, it broke in a different location than where it had been cut. The scientists repeated this experiment on different shaped objects with the same results.

In another experiment, the researchers molded a silicone dog bone, which they cut into multiple pieces. Then they rearranged the pieces to fit into a mold of a dog. Heating the sample resulted in a silicone dog with no visible fractures or weak spots where the pieces had been fitted together.

The researchers also quantified the strength of the healed samples in comparison with the original samples using fracture toughness measurements. The data for the two types of samples was indistinguishable, indicating exceptional self-healing.

The researchers explained that, in principle, any cross-linked dimethylsilicone elastomer (only one type was used here) can be converted into a living elastomer by the addition of basic catalysts. This possibility opens up many different routes for synthesizing a variety of self-healing silicione-based materials. While the samples used here required applied heating to self-heal, the researchers predict that samples in a sealed, high-temperature environment would self-heal “autonomically,” or automatically. Zheng explained that self-healing materials, with some improvements, could lead to a variety of applications.

“It can be developed into self-healing coatings on auto vehicles or countertops,” she said. “It is also a ‘plastic’ elastomer which can be used in molding to form desired shapes and patterns. The concept of a self-healing silicone can be used to guide the preparation of elastomers with gradient modulus, Janus elastomers, reversible surface patterns when filled with magnetic particles, and super tough materials which can chemically relax stress.”

More information: Peiwen Zheng and Thomas J. McCarthy. “A Surprise from 1954: Siloxane Equilibration Is a Simple, Robust, and Obvious Polymer Self-Healing Mechanism.” Journal of the American Chemical Society. DOI: 10.1021/ja2113257

? 2011 PhysOrg.com

Scientists probe form, function of mysterious protein

Using a combination of laboratory experiments and computer modeling, scientists from Rice University and the University of California, San Diego (UCSD) have deciphered part of mitoNEET's movements to get a better understanding of how it handles its potentially toxic payload of iron and sulfur. Their research is described this week in the Proceedings of the National Academy of Sciences.

"We scrutinize proteins with an unconventional approach," said José Onuchic, Rice's Harry C. and Olga K. Wiess Professor of Physics and Astronomy and co-director of the Center for Theoretical Biological Physics. "We use biophysics to probe biology rather than the other way around. Using computational theory, we find structures that are possible -- regardless of whether they've already been observed experimentally -- and we ask ourselves whether these structures might be biologically significant."

Study co-leader Patricia Jennings, professor of chemistry and biochemistry at UCSD, who has collaborated with Onuchic for 15 years, said they save a great deal of time by using structural biophysics to guide their experiments on a wide variety of targets. For example, Jennings' laboratory determined less than five years ago that mitoNEET contained a novel folded structure. Since then, her lab has been using insights gained from static and dynamic snapshots of the protein to guide biological and biochemical studies.

"I think people forget that proteins are machines with moving parts," said study lead author Elizabeth Baxter, a UCSD graduate student who works under the guidance of both Onuchic and Jennings. "We start with the static snapshot and model in the functional motions."

MitoNEET, which binds to the diabetes drug, Actos, immediately caught the attention of researchers when it was discovered. It has a unique ability to bind and store iron-based molecules in an iron-sulfur cluster. Iron is an essential element for all life, but it is also highly toxic, and mitoNEET is the only iron-handling protein that is known to sit on the wall of the mitochondria, one of the key structures inside a cell.

The protein's biological functions are still being unraveled. Interestingly, scientists have shown that mitoNEET sits on the outer mitochondrial wall with its potentially toxic payload of iron-sulfur molecules facing toward the cell's cytoplasm, the gel-like fluid that fills the cell. Discovery of the unique binding mode of the protein's iron-sulfur cluster led the Jennings group to show that the cluster can be delivered into the mitochondria. In addition, its sister protein interacts with proteins that participate in apoptosis -- the process cells use to kill themselves when they are no longer viable.

"I think mitoNEET is a protein that could be your best friend or your worst enemy," Jennings said. "There's some evidence that it may act as a sensor for oxidative stress and that it can lose its toxic iron-sulfur cluster under stress conditions. Depending upon where the iron ends up, that could lead to drastic problems inside the cell."

Proteins are strands of amino acids that are produced from DNA blueprints, but their shapes can provide important clues about their function. To find out how mitoNEET's control and release of its iron-sulfur payload might be related to its shape, Baxter used computer simulations to study how the protein folds, as well as the functional motions of two similar shapes that could be biologically important. In one of these shapes, there is a slight intertwining of two arms that extend away from the iron-cluster pocket. In the other, the arms also extend but are not intertwined.

Baxter found that both conformations were physically possible. She also found the protein could switch between the "strand-swapped" and "strand-unswapped" conformations without entirely unfolding. Moreover, this change in the twining of the arms was shown to alter the shape of the critical pocket that holds the iron-sulfur cluster; this makes the cluster more likely to be inserted or released in situations where the arms are untwined.

Like the magician using misdirection, the loosening of the grip on the cluster is subtle and happens in a different location than the flurry of arm motions. Jennings said it's the kind of thing that could easily be missed if the focus of the study were the cluster itself.

Onuchic said, "One of the advantages to our approach is that it allows us to look for relevant biophysical properties that control distant functional regions -- like mitoNEET's strand-swapping -- that can easily be missed with a more conventional approach."

More information: http://www.pnas.or … 109.abstract

Provided by Rice University (news : web)