Wednesday, November 30, 2011

Fast new test for terrible form of food poisoning

Takeshi Yasumoto and colleagues explain that 20,000-60,000 people every year come down with ciguatera poisoning from eating fish tainted with a ciguatoxin -- the most common source of from a natural toxin. Fish, such as and sea bass, get the toxin by eating smaller fish that feast on that produce the toxin in tropical and , such as the Gulf Coast of the U.S. There's no warning that a fish has the toxin -- it smells, looks and tastes fine. But within hours of ingesting the toxin, people with ciguatera have symptoms that often include vomiting, diarrhea, numbness or tingling in the arms and legs and muscle and joint aches. Debilitating symptoms may last for months. The current test for the toxin involved giving it to and watching them for symptoms. It is time-consuming, may miss the small amounts present in fish, and can't tell the difference between certain forms of the disease. That's why Yasumoto's group developed a faster, more sensitive test.

They describe development of a new test, using standard laboratory instruments, that avoids those draw backs. Yasumoto's team proved its effectiveness by identifying 16 different forms of the toxin in fish from the Pacific Ocean. Clear regional differences emerged -- for example, snappers and groupers off Okinawa shores had one type, whereas spotted knifejaw captured several miles north of Okinawa had another type. They also identified 12 types of toxin in a marine alga in French Polynesia, which could be the primary source. The researchers say that the method outperforms current detection methods and in addition to helping diagnose patients, it will also help scientists study how the toxins move through the food chain from one animal to another.

More information: Detailed LC-MS/MS Analysis of Ciguatoxins Revealing Distinct Regional and Species Characteristics in Fish and Causative Alga from the Pacific, Anal. Chem., Article ASAP. DOI: 10.1021/ac200799j

Toxin profiles of representative ciguatera species caught at different locations of Japan were investigated in fish flesh by high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Identification and quantification of 16 toxins were facilitated by the use of 14 reference toxins prepared by either synthesis or isolation from natural sources and the previous LC-MS data thereof. Sodium adduct ions [M + Na]+ were used as parent and product ions. Distinct regional differences were unveiled: ciguatoxin-1B type toxins were found in snappers and groupers from Okinawa, ciguatoxin-3C type toxins were found in a spotted knifejaw, Oplegnathus punctatus, from Miyazaki located 730 km north of Okinawa, and both types of toxins were found in a red snapper, Lutjanus bohar, from Minamitorishima (Marcus) Island. Twelve toxins were identified in a dinoflagellate, Gambierdiscus toxicus, collected as the primary toxin source in French Polynesia. Occurrence of M-seco-toxins in fish and oxidized toxins in the dinoflagellate was confirmed for the first time. The present LC-MS/MS method is rapid, specific, and accurate. It not only outperforms the currently employed mouse bioassays but also enables the study of the toxin dynamics during the food chain transmission.

Provided by American Chemical Society (news : web)

Researchers discover key aspect of process that activates breast cancer genes

Michael R. Stallcup, Ph.D., professor and chair of the Keck School's Department of Biochemistry and Molecular Biology, was the senior author, and Kwang Won Jeong, Ph.D., a postdoctoral student in Stallcup's lab, was the first author of the paper, "Recognition of enhancer element-specific histone methylation by TIP60 in transcriptional activation." It was published online in the research journal Nature Structural & Molecular Biology on Nov. 13.

Researchers at the Keck School of Medicine of the University of Southern California have discovered key processes by which , the female sex hormone, activates in breast-cancer cells. Greater understanding of how this occurs is expected to eventually lead to new treatments for the disease.

The researchers found that a protein, TIP60, recognizes when a common chemical process called methylation occurs in , the material that enfolds all genes. Methylation controls how genes are folded in the complex structure of chromatin, which determines whether the genes are active or inactive. The researchers discovered that after recognizing the methylation signal, TIP60 then binds to the signal, connecting TIP60 to the chromatin and then changing the chromatin's structure, which helps to activate the gene. The methylation that TIP60 recognizes is generated by another protein, MLL1.

"It's like when you're in your car and come to a red light," said Stallcup. "The light doesn't make you stop, but it is a signal that you have to interpret and then decide to stop. In this case, the methylation modification that TIP60 recognizes is one of those signals, and then TIP60 acts on that signal."

The findings build upon previous work of Stallcup's lab. Earlier published research revealed that the methylation of chromatin and other proteins plays many important roles in controlling the activities of genes.

While the recent findings are significant, Stallcup stressed that there is much more to be discovered.

"We want to understand more about other steps in the process of gene activation," Stallcup said. "In particular, we're interested in the function of the MLL1 protein because we think it plays a key role in controlling chromatin structure and folding, which we think is critical for activation of genes by estrogen."

Stallcup also noted that estrogen regulates just a few hundred of the tens of thousands of genes in every human cell, but that the research has broader implications.

"While the process we're studying is the regulation of gene activity by estrogen, the findings have potentially global significance,,because the methylation modification of chromatin that TIP60 recognizes is found in all active and potentially active genes in human cells," Stallcup said.

Provided by University of Southern California (news : web)

Generating ethanol from lignocellulose possible, but large cost reductions still needed

Ethanol can be blended with gasoline to reduce our dependency on fossil fuels. The last 15 years has seen a massive growth of so-called first-generation processes that use enzymes and bacteria to turn the starch and sugars in corn and sugarcane into . But corn and sugarcane are also important components of the human food web, so using them for ethanol production has the potential to affect the price and availability of these basic commodities.

On the other hand, lignocellulose materials are often hard to dispose of, but they are rich in sugars that can be fermented into ethanol following appropriate processing. "Not only is cellulose the most abundant polymer on Earth, it cannot be digested by humans, so using it for fuel production does not compete directly with food supplies," says the study's lead author Jamie Stephen, who works in the Department of Wood Science at the University of British Columbia in Vancouver, Canada. The race is on to commercialize this second generation ethanol.

Stephen's work focuses on the fact that the cost of building large scale ethanol-producing facilities will likely be higher for second generation ethanol compared to first generation technologies. One reason is that sources of lignocellulose may require significant and costly pre-treatment. "Researchers and companies are going to have to concentrate on reducing the cost of pretreatment and increasing the output of the digester in order to reduce the costs of the lignocellulose-to-ethanol process," says Stephen.

Another reason costs are higher is that lignocellulose is made of multiple kinds of sugar, while consists of pure glucose. Corn starch can be reduced to glucose with low-cost amylase enzymes, while pre-treated lignocellulose requires a cocktail of cellulase enzymes. Providing these enzymes is one of the major costs of the whole process, but you currently need 12 times more cellulase than amylase protein to generate the same amount of ethanol from woody biomass. "Despite much effort and progress over the last few years, the cost of using cellulase enzymes is still significantly higher than for amylase-based processes, and will need to be reduced substantially before lignocellulose starts to become competitive with corn and sugarcane as a feedstock," says Stephen.

Finally, while the input to sugarcane- and corn starch-based systems is fairly constant, the feedstocks that go into lignocellulose systems are much more variable. Different species of tree produce wood that has different properties, and waste paper and agricultural wastes will have many different types of material in them. To get maximum , each type of biomass needs to be processed under different conditions, which introduces another challenge for anyone wanting to make ethanol from these materials.

Overall Stephen believes we have a considerable way to go before second-generation ethanol production will be ready for commercialisation. "Production requires significant cost reductions and at least the same level of financial support that was given to the first-generation systems if second-generation ethanol is going to be fully competitive by 2020," says Stephen.

Provided by Wiley (news : web)

Scientists enumerate advances, retreats in designing new membranes for renewable energy storage

Since the vanadium redox flow battery was first invented, researchers have studied refining the Nafion membrane, a DuPont polymer containing sulfur and fluoride, or replacing the with a less-expensive option. In their paper, Schwenzer and her colleagues discuss the required features of an efficient membrane, including , water transport, and ion diffusion.

"Reviewing the membrane research, which began in the mid-1980s, is an important and ambitious undertaking," said Dr. Jun Liu, who leads the Transformational Materials Science Initiative at PNNL and is a colleague of Schwenzer's. "I'm delighted with the depth and breadth of this article."

Finding or designing an efficient membrane demands a more inclusive approach than is typically taken, notes Schwenzer. Replacements or refinements to the membranes must be examined on their own and in working batteries.

"A lot of studies provide data on the membranes ex situ, outside of the battery," said Schwenzer, an inorganic chemist. "But, there are no follow-up articles showing how the materials perform inside a battery. The studies say that some properties of the membranes are good, but they don't show you the actual battery data."

The nation relies on fossil fuels to meet its residential and industrial , with coal providing about half of the electricity consumed in the United States. The emissions from coal and other fossil fuel plants cause environmental concerns. However, replacing these power sources with wind and solar farms requires megawatt-level storage capacity to buffer the intermittent generation from these renewable sources. Vanadium redox flow batteries could fit the bill, if membrane cost and maintenance issues are resolved.

"I'm hoping that our article in ChemSusChem is a guide for researchers to see what worked and what didn't," said Schwenzer. "It could help them design the materials they need to build better batteries, showing them where the opportunities lie and where current challenges exist."

The authors of this review are part of a team of materials experts at PNNL who are putting this information to use by conducting fundamental and applied research to reduce the costs and improve the efficiency of large-scale energy storage. Currently, Schwenzer and her colleagues are building larger batteries to see how changes to the and other battery components affect the overall performance.

"We are looking at the whole system and determining why it fails -- not just if it fails," said Schwenzer.

More information: B Schwenzer, J Zhang, S Kim, L Li, J Liu, and Z Yang. 2011. "Membrane Development for Vanadium Redox Flow Batteries." ChemSusChem 4(10)1388-1406. DOI: 10.1002/cssc.201100068

Provided by Pacific Northwest National Laboratory (news : web)

Zeroing in on more powerful enzymes for degrading persistent pollutants

Certain chemical components, like , PAHs, and CFCs, are toxic biosphere pollutants that are resistant to microbial degradation. Microbial catabolic enzymes are unable to effectively metabolize them. The results obtained by Professor Sylvestre and his colleagues open up new possibilities for boosting the effectiveness of these enzymes to oxidize such compounds.

Professor Sylvestre's research team has shown that it is possible to obtain more flexible mutant enzymes by replacing some of their amino acids. Moreover, they have updated a sophisticated mechanism that helps boost the enzyme's performance not only with regard to the natural substrate, but also any other substrates it can metabolize. As such, more effective new enzymes can be developed using genetic engineering.

"From a green chemistry perspective, the results of our research could allow us to apply these enzymes to biocatalysis processes to synthesize biologically active compounds (such as flavonoids) that have strong antioxidant properties," explained Professor Michel Sylvestre, also an engineering specialist.

More information: The results were published in the following works:

Mohammadi, M., Viger, J.F., Kumar, P., Barriault, D., Bolin, J. T., Sylvestre, M. 2011. "Retuning Rieske-type oxygenase to expand substrate range." J. Biol Chem. 286, 27612-27621. … 932c85d04095

Kumar, P., Mohammadi, M., Viger, J.F., Barriault, D., Gomez-Gil, L., Eltis, L.D., Bolin, J. T., and Sylvestre, M. 2011. "Structural insight into the expanded PCB-degrading abilities of a biphenyl dioxygenase obtained by directed evolution." J. Mol. Biol. 405, 531-547. … 28361001209X

Dhindwal, S., D. N. Patil, M. Mohammadi, M. Sylvestre, S. Tomar, and P. Kumar. 2011. "Biochemical studies and ligand bound structures of biphenyl dehydrogenase from Pandoraea pnomenusa strain B-356 reveal a basis for broad specificity of the enzyme." J. Biol. Chem. 286, 37011-37022. … 932c85d04095

Provided by INRS