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Archive - Aug 2011

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August 31st

Modified Toxin from Sea Bacteria Shows Potential As Anti-Colon-Cancer Drug

University of Florida (UF) researchers have modified a toxic chemical produced by tiny marine microbes and successfully deployed it against laboratory models of colon cancer. In an article published online on August 31, 2011 in ACS Medicinal Chemistry Letters, UF medicinal chemists describe how they took a generally lethal byproduct of marine cyanobacteria and made it more specifically toxic — to cancer cells. When the scientists gave low doses of the modified compound to mice with a form of colon cancer, they found that it inhibited tumor growth without the overall poisonous effect of the natural product. Even at relatively high doses, the agent was effective and safe. "Sometimes nature needs a helping human hand to further optimize these products of evolution to treat human diseases," said the article’s senior author, Dr. Hendrik Luesch, an associate professor of medicinal chemistry at UF's College of Pharmacy. "Based on what we learned about apratoxins' mechanism of action, we knew this compound class had great potential for use in anticancer therapies; however, the natural product itself is too toxic to become a therapeutic." The researchers synthesized several apratoxin compounds that were similar to the original, except for slight differences in composition, designing one that proved to be extremely potent against the cancer cells in cultures and in mice, but without the overwhelming toxicity. The compound acts as a single agent to reduce levels of two types of proteins that are targeted by cancer research labs around the world — growth factors, and enzymes called tyrosine kinases, which act as receptors for the growth factors. Known as apratoxin S4, the compound strips colon cancer cells of their ability to both secrete and use naturally occurring factors that fuel growth — something that Dr. Luesch, postdoctoral chemist Dr.

Genetic Condition May Underlie Many Cases of Personal Bad Odor

Scientists from the Monell Center in Philadelphia report that approximately one third of patients with unexplained body malodor production test positive for the metabolic disorder trimethylaminuria (TMAU). A definitive diagnosis offers relief to these individuals, as symptoms of TMAU can hinder social and workplace interactions and cause psychological distress. But once the disease is identified, these debilitating symptoms can be ameliorated using changes in diet and other approaches. "Health care professionals must arrive at a correct diagnosis to suggest appropriate treatment," said study lead author Dr. Paul M. Wise, a sensory psychologist at Monell. "This research raises awareness of both the disease and also the proper methods of diagnosis and treatment." TMAU is a genetically-transmitted disease that inhibits the ability of an enzyme to metabolize or transform trimethylamine (TMA), a chemical compound produced naturally from many foods. TMA has a foul, fishy odor. At lower concentrations, it may be perceived as unpleasant or "garbage-like." Production of TMA is associated with foods rich in the dietary constituent, choline. Such foods include eggs, certain legumes, wheat germ, saltwater fish, and organ meats. The distressing symptoms of TMAU stem from the accumulation of excess TMA – and its associated unpleasant odor – which is then excreted from the body in urine, sweat, saliva, and breath. Importantly, TMA production and associated odor symptoms depend on what foods have been recently eaten and therefore may occur in irregular and seemingly unpredictable intervals. This makes the disease difficult to diagnose, as patients can appear to be odor-free when they consult a health professional.

August 30th

Black Death Pathogen Likely Extinct

The so-called "Black Death," a plague that ravaged Europe between the years of 1347 and 1351, was likely caused by a now-extinct version of the Yersinia pestis bacterium, according to results of a study published online on August 29, 2011 in PNAS. Dr. Hendrik Poinar, from McMaster University in Canada, and colleagues made this determination after analyzing the DNA of 109 human skeletal remains excavated at the East Smithfield mass burial site in London, England. The researchers also studied DNA from the remains of 10 humans unearthed at St. Nicholas Shambles, a site pre-dating the Black Death medieval plague. Individuals buried at East Smithfield harbored Y. pestis genes, which the authors sequenced to form among the oldest and longest genetic assemblages from an ancient pathogen. The genetic sequence differs from the sequences of other known versions of Y. pestis, the authors found, suggesting that the pathogen responsible for the Black Death is likely extinct. Because modern plague continues to affect an estimated 2,000 people per year worldwide, the authors suggest that earlier forms of the disease may yield clues about the pathogen's evolutionary history and possibly reveal how it caused such widespread devastation during the Black Death period. [Press release] [PNAS abstract]

First Kangaroo Genome Sequence Determined

Kangaroos form an important niche in the tree of life, but until now their DNA had never been sequenced. In an article published August 19, 2011 in BioMed Central's open access journal Genome Biology, an international consortium of researchers present the first kangaroo genome sequence – that of the tammar wallaby species – and find hidden in their data the gene that may well be responsible for the kangaroo's characteristic hop. "The tammar wallaby sequencing project has provided us with many possibilities for understanding how marsupials are so different to us," says Professor Marilyn Renfree of The University of Melbourne. Dr. Renfree was one of the lead researchers on the project, which was conducted by an international consortium of scientists from Australia, USA, Japan, England, and Germany. Tammar wallabies have many intriguing biological characteristics. For example, the 12-month gestation includes an 11-month period of suspended animation in the womb. At birth, the young weigh only half a gram, and spend 9 months in the mother's pouch, where the newborn babies reside for protection. Researchers hope that the genome sequence will offer clues as to how tammar wallaby genes regulate these fascinating features of kangaroo life. In addition to zeroing in on the "hop" genes, other exciting discoveries from the genome include the 1,500 smell detector genes responsible for the tammar wallaby's excellent sense of smell, and genes that make antibiotics in the mother's milk in order to protect kangaroo newborns from E. coli and other harmful bacteria. As Dr. Renfree explains, lessons to be learned from the tammar wallaby genome "may well be helpful in producing future treatments for human disease." The first kangaroo genome is a key milestone in the study of mammalian evolution.

August 18th

Vitamin C Treatment Dissolves Protein Aggregates in Alzheimer’s Disease Model

Researchers at Lund University in Sweden, and collaborating institutions, have discovered a new function for vitamin C. Treatment with vitamin C can dissolve the toxic protein aggregates that build up in the brain in an animal model of Alzheimer's disease. The research findings were presented in the August 5, 2011 issue of the Journal of Biological Chemistry. The brains of people with Alzheimer's disease contain lumps of so-called amyloid plaques which consist of misfolded protein aggregates. They cause nerve cell death in the brain and the first nerves to be attacked are the ones in the brain's memory center. "When we treated brain tissue from mice suffering from Alzheimer's disease with vitamin C, we could see that the toxic protein aggregates were dissolved. Our results show a previously unknown model for how vitamin C affects the amyloid plaques," says Dr. Katrin Mani, reader in Molecular Medicine at Lund University. "Another interesting finding is that the useful vitamin C does not need to come from fresh fruit. In our experiments, we show that the vitamin C can also be absorbed in larger quantities in the form of dehydroascorbic acid from juice that has been kept overnight in a refrigerator, for example." There is at present no treatment that cures Alzheimer's disease, but the research is aimed at treatments and methods to delay and alleviate the progression of the disease by addressing the symptoms. That antioxidants such as vitamin C have a protective effect against a number of diseases, from the common cold to heart attacks and dementia, has long been a focus of research. "The notion that vitamin C can have a positive effect on Alzheimer's disease is controversial, but our results open up new opportunities for research into Alzheimer's and the possibilities offered by vitamin C," says Dr. Mani.