Wednesday, April 6, 2011

Researchers use lobster shells to create biodegradable golf ball

Golfers on the high seas can breathe a little easier -- and so can the marine life around them -- thanks to researchers at the University of Maine. In conjunction with The Lobster Institute, UMaine Biological and Chemical Engineering Professor David Neivandt and undergraduate student Alex Caddell of Winterport, Maine, have developed a biodegradable golf ball made from lobster shells. The ball is intended for use on cruise ships.

Carin Poeschel Orr, who earned a master’s in marine bio-resources at UMaine, suggested the idea to Bob Bayer of The Lobster Institute. Bayer turned to Neivandt, who is known on campus as an innovative problem-solver.

Though biodegradable already exist, this is the first to be made with crushed lobster shells with a biodegradable binder and coating, creating value from waste material.

“We’re using a byproduct of the lobster canning industry which is currently miserably underutilized — it ends up in a landfill,” Neivandt says. “We’re employing it in a value-added consumer product which hopefully has some cachet in the market.”

And that cachet doesn’t come with a higher price tag. Biodegradable golf balls that are now on the market retail for a little under $1 per ball. The raw materials for the lobster shell balls cost as little as 19 cents per ball.

Caddell, a golfer, says the balls perform similarly to their traditional, white-dimpled counterparts. And they can be used with both drivers and irons.

“The flight properties are amazing,” Caddell says. “It doesn’t fly quite as far as a regular golf ball, but we’re actually getting a similar distance to other biodegradable golf balls.”

UMaine has filed a provisional patent for the lobster-shell mixture, which can also be used for such products as plant pots that decompose in the ground, surveying stakes and other applications.

For Caddell, a junior Biological Engineering major and Honors student, the opportunity to do research that has a real-world application has been a highlight of his UMaine experience.

“I didn’t really think it would turn out to be this fruitful,” Caddell says. “I think what really makes UMaine great is that there is a lot of funding available here, as opposed to private schools where it’s hard to get research opportunities. Here, all sorts of professors are willing to take on students. You’re not just taking classes, you can be surrounded by engineering by doing research, as well.”

Provided by University of Maine

Lighting up a protein called Spy

 James Bond frequently has to undertake spectacular feats to protect Queen and country against utter destruction under insurmountable odds. But what happens when the homeland is a bacterial cell, and the danger comes from the insurmountable odds of making large amounts of a complex molecule? You call in a sleeper agent – a protein called Spy.

That’s the discovery made by biochemist James Bardwell and his team from the University of Michigan, Howard Hughes Medical Institute, McGill University and the National Research Council of Canada’s Biotechnology Research Institute. Their findings, which included a model of the obtained from the Canadian Light Source, were published in the journal Nature Structural and Molecular Biology.

Many proteins used in pharmaceuticals, such as insulin, can be manufactured by bacteria that have had the instructions for making the desired protein inserted into their genetic code. However, the process doesn’t work well for all proteins, leading to botched batches of poorly-folded molecular clumps that are unable to function properly. Bardwell and his colleagues wanted to see if the system could be improved by making the bacteria an offer that was hard to refuse – linking protein production to their survival.

“We gave the bacteria a pretty stark choice – fold proteins or die,” explained Dr. Bardwell. “We linked making a stable target protein in strains of E. coli to their resistance to penicillin, and then grew them in a medium containing the drug. The bacteria could survive only if they could also fold the target protein really well.”

The result: surviving bacteria produced up to 700 times more of the desired target protein than they would normally, along with large amounts of a little protein called Spy (short for spheroplast protein Y). It turns out Spy is a molecular chaperone – a type of molecule that facilitates the folding of proteins. The amount of Spy normally present in cells is vanishingly small, but in response to stress it is made in huge amounts . It is particularly induced in response to threats that would cause proteins inside the bacterium to unravel or clump uselessly, such as alcohol or tannins. While Spy had been previously identified inside bacteria, its function wasn’t understood until it was implicated in these ‘fold or die’ experiments.

“A lot of people were surprised that such well-studied bacteria as E. coli had a chaperone that had remained undiscovered,” said Dr. Bardwell. “But many assay tests that look for chaperones wouldn’t find Spy; then again, no one else has tried to genetically select for protein folding like we did.”

To better understand the workings of their enigmatic chaperone, the team needed to determine Spy’s molecular structure. Dr. Bardwell turned to his collaborator, Prof. Mirek Cygler at McGill University and the NRC Biotechnology Research Institute, who in turn sent crystals of Spy to the CLS.

The molecular model obtained from the CLS data revealed that Spy had even more surprises in store. Spy is one of the thinnest chaperone ever found – a cradle-shaped molecule consisting of two parts, only nine ten-millionths of a millimetre thick (the same thickness, roughly, of nine hydrogen atoms) or about one fortieth the size of some better known chaperones. Spy’s cradle-shape may allow it to surround larger proteins, enabling them to fold properly while protecting them from harmful influences.

“It kind of acts like Teflon or a candy wrapper, covering the proteins and keeping them from clumping and sticking together,” Dr. Bardwell noted.

Now that Spy has been identified, Dr. Bardwell and his team plan to study how the protein works in detail, while also looking for similar chaperones using the same genetic selection routine. They also hope to force bacteria to produce other poorly folding, unstable proteins like HIV’s ‘tail protein,’ seen by many as the target for a potential AIDS vaccine.

“Spy is the way E. coli fights off stressful environments by protecting proteins from unfolding,” he explained. “By making Spy fold the proteins we want, there are lots of places we could go.”

More information: Quan et al. 2011. Genetic selection designed to stabilize proteins uncovers a chaperone called Spy. Nature Stuctural and Molecular Biology DOI:10.1038/nsmb.2016

Provided by Canadian Light Source

Universal detector made of DNA building blocks

A method for detecting such diverse substances as antibiotics, narcotics and explosives - a universal detector, so to speak - has been developed by German researchers at the Max Planck Institute for Polymer Research in Mainz.

The key element of this is an that can be used to subject individual molecules to a tensile test. The Mainz-based researchers are therefore focussing on aptamers, which are composed of the building blocks of the DNA. If the substance researched binds to the aptamers, the force at which they tear apart changes. In this way, the substance can not only be accurately detected at small concentrations, but can also be studied more precisely. It is therefore possible for instance to investigate how the substances researched bind to aptamers, and how great their binding strength is ( 133, pages 2025 - 2027).

Aptamers are a practically ideal means of detecting an extremely wide variety of chemicals. Typically, they consist of the building blocks from the hereditary materials DNA and RNA, and combine universality with specificity. They form, as it were, a box of bait with which to catch another kind of fish. Their versatility results from the innumerable possibilities of varying the sequence of the four bases of which DNA is composed. Their specificity, on the other hand, results from the physical structure that a strand of DNA with a certain base sequence adopts. This produces in the aptamer individually formed pockets into which only certain molecules fit - rather like a clay figure in its mould. "Aptamers with appropriate pockets can be found for most molecules, be they antibiotics, cocaine, TNT or proteins", explains Rüdiger Berger of the Max Planck Institute for Research.

Among the appropriate aptamers, the researchers in Mainz are looking for one that can be split into two parts in such a way that the target molecule bound in the pocket forms a bridge between the two halves. An aptamer such as this could be found mostly in pre-selection, explains Mark Helm of the Institute of Pharmacy at the Johannes Gutenberg University Mainz, co-author of the study. For their first trials with the universal detector, the researchers selected adenosine monophosphate (AMP) as the target molecule and an aptamer with pockets for two AMP molecules.

They then fix one half of the split aptamer to the tip of an atomic force microscope and the other to a support. When they then lower the tip and the halves come into contact, hydrogen bridge bonds form between individual bases of the two aptamer halves. If the tip is withdrawn, the joined aptamer is stretched like a spring. The force this produces can be measured: it increases with the strain until the halves tear apart at a certain force. In a second trial, before ripping apart, the researchers added a solution of the biomolecule adenosine monophosphate (AMP) to the system. In this way, two AMP molecules are placed in the free pockets; both then form hydrogen bridge bonds with the two halves of the aptamer. As a result of this bridge function, the AMP molecules reinforce the coherence between the two parts and therefore only tear apart at a much greater force. This difference enables the AMP to be detected.

To determine the rupture forces, the researchers repeated the measurements 1000 times and determined a statistical mean which was around 39 piconewtons for the AMP-loaded aptamer, around 12 piconewtons higher than without the AMP. As a control, they used a mutated aptamer with a differently formed binding pocket in which the rupture force did not change. The binding strength between the AMP and the aptamer can also be readily determined by splitting the aptamer into two. To do this, the concentration of the AMP molecules in the solution was increased stepwise until approximately half of all tensile tests showed an increase in the tear force. The greater the concentration necessary for this, the smaller the binding strength is.

The new method is suitable not only for detecting certain molecules in a solution, but also for researching individual molecules, says Rüdiger Berger. "For example, with a defined force you can pull the aptamer without tearing it and examine how the properties of the molecule-aptamer bond changes", he continues. The target molecule could also be changed so that it forms, for example, only two hydrogen bridge bonds with the pocket instead of three. "This makes is possible to understand which bonds between the target molecule and the aptamer are significant", he explains.

Knowledge of aptamers and their binding properties has great application potential. DNA fragments are already being used today for environmental analysis and in medical diagnostics; their uses as molecular tools and building blocks can be expanded even further with the new method thanks to the fresh insight, says Rüdiger Berger.

More information: Thi-Huong Nguyen, Lorenz Jan Steinbock, Hans-Jürgen Butt, Mark Helm, Rüdiger Berger, Measuring Single Small Molecule Binding via Rupture Forces of a Split Aptamer, Journal of the American Chemical Society, 2. Februar 2011, DOI:10.1021/ja1092002

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

Cancer is a p53 protein aggregation disease

Protein aggregation, generally associated with Alzheimer's and mad cow disease, turns out to play a significant role in cancer. In a paper published in Nature Chemical Biology, Frederic Rousseau and Joost Schymkowitz of VIB, K.U.Leuven and Vrije Universiteit Brussel (Belgium) describe that certain mutations of p53, an important tumor suppressor, cause the protein to misfold in a way that the proteins start to aggregate. This not only disrupts the protective function of normal p53, but of other related proteins as well.

In the study, the focus was on the which plays a key role in protecting the body against cancer. If p53 works normally, it controls cell division. If p53 control ceases - e.g. when there is a mutation in the - the cells start to divide in an uncontrolled manner and this may result in a tumor. Mutations in p53 are observed in about half of cancer cases, making the protein an important target in the development of new cancer therapies.

"We have revealed a new mechanism for the action of mutant p53," Joost Schymkowitz and Frederic Rousseau of VIB, Vrije Universiteit Brussel and K.U. Leuven say. "Mutations in p53 cause the protein to lose its protective function. The proteins change in shape, hook into each other and begin to aggregate. The active p53 disappears from the cell and can no longer carry out its control function properly." The mechanism has been encountered in about one third of .

Moreover, the mutations cause p53 to assume a completely different character. From being a protective factor, the mutated p53 changes into a substance which in fact speeds up . It seems to form aggregates with control substances (p63 and p73) in the cell, causing them to lose their function as well.

Even though the underlying principle – protein aggregation - occurs similarly in particular cancers, Alzheimer and systemic amyloidosis, the diseases are otherwise totally unconnected with each other. In , the clustering of p53 protein leads to uncontrolled cell growth. In Alzheimer, clustering of the beta-amyloid protein causes brain cells to die off.

More information: Jie Xu et al, Gain of function of mutant p53 by coaggregation with multiple tumor suppressors, Nature Chemical Biology.

Provided by Flanders Institute for Biotechnology

Household bleach can decontaminate food prep surfaces in ricin bioterrorist attack

Help for a bioterrorist attack involving ricin, one of the most likely toxic agents, may be as close at hand as the laundry shelf, according to a report presented here today at the 241st National Meeting and Exposition of the American Chemical Society (ACS). It concluded that ordinary household bleach appears to be an effective, low-cost, and widely available way to decontaminate food preparation surfaces in homes, restaurants, and processing plants that are tainted with ricin.

Ricin is a poison found naturally in castor beans, which are grown and processed throughout the world to produce castor oil. Although no longer widely used as a laxative, castor oil remains a key raw material in the manufacture of soaps, paints, dyes, inks, lubricants, hydraulic and brake fluids, and other products. Ricin occurs in the waste "mash" left behind after production of castor oil. Because it is so easy to obtain and so toxic, with no , experts regard ricin as one of the most likely bioterror agents.

"This discovery is important because it provides a practical, readily available way to inactivate ricin on food processing equipment in the event of an intentional contamination event," said Lauren Jackson, Ph.D., who reported on the research. "It is the first study to explore ricin in the presence of food, and it shows that household bleach is effective."

Jackson and colleagues prepared solutions of bleach and two other substances routinely used at food processing plants to disinfect counters, machinery and other surfaces that may contain or viruses. The other disinfectants were peroxyacetic acid (PAA) and so-called quaternary ammonium compounds. In one set of experiments, they tested the substances on discs of stainless steel smeared with milk-based infant formula, pancake mix, peanut butter and other foods that contained ricin. They also tested the three disinfectants on a "control" solution containing ricin, but without any food, to make sure it was the that inactivated ricin and not something present in the foods.

Household bleach turned out to be the most effective anti-ricin agent. Bleach significantly reduced the toxicity of ricin within five minutes, noted Jackson, a research food technologist with the U.S. Food and Drug Administration in Summit-Argo, Ill. Bleach completely eliminated ricin in the "control" samples using just a small amount of bleach. PAA also showed effectiveness, but less so than bleach.

Provided by American Chemical Society (news : web)

Shedding light on the interaction between DNA and UVA radiation

Ultraviolet A (UVA) radiation is now known to cause skin cancers. The first information on the way in which UVA radiation acts directly on DNA has been revealed by a CNRS team from the Laboratoire Francis Perrin in collaboration with a CEA-Inac laboratory in Grenoble. The interaction between UVA and DNA results from the collective behavior of the bases of the DNA double helix, which causes chemical lesions that can induce carcinogenic mutations. This work is published on-line on 18 March 2011 in the Journal of the American Chemical Society.

Ultraviolet A (UVA) radiation represents over 95% of the solar UV radiation that reaches the Earth's surface. This UVA radiation is now known to cause skin cancers due to carcinogenic brought about by chemical alterations of the four bases of DNA (adenine, cytosine, guanine and thymine). The most important chemical modification is thymine dimerization: two thymines next to each other in the DNA combine to form a new entity, known as “cyclobutane dimer”.

A CNRS team from the Laboratoire Francis Perrin (CNRS/CEA), in collaboration with researchers from the CEA Laboratoire Lésions des Acides Nucléiques, has examined the very first steps of the formation of such chemical . They are publishing the first study describing the physical and chemical effects, prior to any biological effects, of UVA radiation on model DNA. The team of physical chemists examined the behavior of a synthetic DNA (formed solely of adenine-thymine pairs) with regard to UVA photons. They then compared its behavior with that of two complementary single strands (containing only thymines or only adenines).

They found that DNA's capacity to absorb UVA photons results from the collective behavior of its bases. Studied individually, DNA bases (including thymine) are “transparent” to UVA. However, in this study, the scientists have shown that the absorption of UVA radiation substantially increases following the pairing of two single strands to form a double helix. In addition, the probability that a UVA photon absorbed leads to the formation of cyclobutanes is at least ten times higher in the case of a double strand than it is in the case of a single strand. These differences could be explained by changes induced by the UVA photons to the electronic structure of the bases. Following the absorption of a photon, the new electronic configuration adopted by the DNA, known as excited state, persists longer for a double strand than for complementary single strands. The thymines then have more time to undergo permanent alterations.

These experimental studies now need to be extended to more complex DNA sequences, similar to natural DNA. The stakes in terms of public health are high, especially since the quantity of UVA that reaches us is very high compared to UVB radiation (which represents less than 5% of the ultraviolet radiation that reaches the Earth's surface) and also because UVA is still widely used in tanning centers.

More information: Base Pairing Enhances Fluorescence and Favors Cyclobutane Dimer Formation Induced upon Absorption of UVA Radiation by DNA, Akos Banyasz, et al. – Journal of the American Chemical Society, 18 March 2011.

Provided by CNRS (news : web)

Safer, more effective skin-whitening creams from ancient Chinese herbal medicine

Scientists today reported discovery of the active ingredients in an herb used in traditional Chinese medicine for skin whitening, changing skin color to a lighter shade. The ingredients are poised for clinical trials as a safer, more effective alternative to skin whitening creams and lotions that millions of women and some men use in Asia and elsewhere, they said. The report was among more than 9,500 presentations this week at the 241st National Meeting & Exposition of the American Chemical Society (ACS).

The finding, which caps an intense search for these natural skin lightening substances, could be a boon to women in Asian countries, said study leader Hui-Min Wang, Ph.D. He explained that skin whitening products are all the rage there, but too-often accompanied by itching, redness, inflammation, and other side effects.

"Toxic skin whitening creams are a growing threat to women's health, especially in Asia," Wang said. "We hope that our product will improve lives and provide a safer, more natural way to lighten skin. A cream based on these herbal ingredients could be available on store shelves in as little as a year."

Skin-whitening is big business in countries like China, Japan, Korea, and India, where many women view whiter skin as a symbol of beauty, good health, and high social status. One study estimates that half the women in Asian countries use skin lightening creams, spending the equivalent of several billion dollars annually. People also use such products to fade unsightly age spots, freckles, and scars that have collected pigment.

Dozens of skin whitening creams, lotions, and other products are on sale throughout Asia. Some products contain toxic mercury, hydroquinone, and other potentially toxic substances that can cause redness, itching, inflammation and other skin problems. Some whitening ingredients could increase the risk of skin cancer when used frequently and at high doses, Wang said, citing the need for safer, more effective alternatives.

Wang and colleagues say that they have found a promising alternative in the form of an herbal "cure-all" used in in the form of soup or tea. The evergreen bush, Cinnamomum subavenium, is a close relative of the trees whose inner bark is the source of cinnamon. The scientists isolated two chemicals from the plant that have the ability to block tyrosinase, an enzyme that controls the synthesis of melanin, a dark pigment responsible for coloring skin, hair, and eyes. Inhibiting tyrosinase is one of the major strategies for skin-whitening, Wang said.

They tested these so-called "melanogenesis inhibitors" on the embryos of zebrafish, which are widely used as stand-ins for people and other animals in biomedical research. The embryos contain a highly visible band of black pigment. Exposure to low levels of the two chemicals reduced melanin production in the fish embryos by almost 50 percent within just four days, turning the embryos snowy white, the scientists said.

"When we saw the results, we were amazed," said Wang, who is with Kaohsiung Medical University in Taiwan. "My first thought was, well, 'If these herbal whiteners can transform zebrafish embryos from black to white, maybe they can also lighten women's skin.'"

He estimated that the chemicals are 100 times more effective in reducing melanin pigmentation than the common skin whitening agents kojic acid and arbutin, which have been used in cosmetics for more than 30 years. The substances did not appear to be toxic when tested in low doses on both cultured human skin cells and zebrafish embryos, Wang noted.

Wang is looking forward to clinical trials of a new beauty product based on the ingredients. Just a one percent solution of the chemicals could achieve dramatic skin whitening, Wang said, adding that several cosmetic companies are working with his group. Wang and his colleagues have applied for patents in the U.S., Japan, and Taiwan.

Provided by American Chemical Society (news : web)