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Archive - Aug 2009


August 29th

Three Genes Responsible for Coat Texture in Dogs

Researchers have found that variants in just three genes, acting in different combinations, appear to account for the wide range of coat texture seen in dogs. The study involved genome-wide SNP association analysis carried out in 1,000 individual dogs representing 80 breeds. "What's important for human health is the way we found the genes involved in dog coats and figured out how they work together, rather than the genes themselves," said senior author Dr. Elaine A. Ostrander, chief of the Cancer Genetics Branch in the National Human Genome Research Institute. "We think this approach will help pinpoint multiple genes involved in complex human conditions, such as cancer, heart disease, diabetes, and obesity." The authors noted that their work illustrates that an array of varied and seemingly complex phenotypes can be reduced to the combinatorial effects of only a few genes. Specifically, the researchers found that an alteration in the RSPO2 gene results in wiry hair that grows in a pattern that gives the dogs a mustachioed look with long details called furnishings. Examples of dogs with wiry coats are Scottish terriers, Irish terriers and schnauzers. Long hair that is silky or fluffy was linked to a variant in the FGF5 gene. Cocker spaniels, Pomeranians and long-haired Chihuahuas are examples of dogs with long coats. A variant in the KRT71 gene produces curly coated dogs, such as the Irish water spaniel. Finally, if all three variants are present, a dog has a long and curly coat with furnishings. Examples of this type of breed include poodles and Portuguese water dogs. This work was published online in Science on August 27. [Press release] [Science abstract]

August 27th

Bacterial Enzyme May Be New Antibiotic Target

Researchers have shown that inhibition of a key bacterial enzyme may be an effective approach for killing or suppressing the growth of a broad range of bacterial pathogens. The enzyme is nicotinate mononucleotide adenylyltransferase (NadD), an essential enzyme for nicotinamide adenine dinucleotide (NAD) biosynthesis. NAD has many crucial functions in nearly all important pathogens and the bacterial NadD differs significantly from the human enzyme. “It’s clear that because of bacterial resistance, we need new, wide-spectrum antibiotics,” said Dr. Andrei Osterman, senior author of the report. “This enzyme is indispensable in many pathogens, so finding ways to inhibit it could give us new options against infection.” In their work, the researchers identified small molecule compounds that efficiently inhibited target NadD enzymes from Escherichia coli (ecNadD) and Bacillus anthracis (baNadD), but had no effect on functionally equivalent human enzymes. The results of this study help validate NadD as a target for the development of antibacterial agents with potential broad-spectrum activity, the scientists said. This research was reported in the August 28 issue of Chemistry & Biology. [Press release] [C&B abstract]

August 26th

Small Peptide Blocks Human Lung Cancer Growth in Mice

Scientists have shown that a small peptide [angiotensin-(1-7)] can block the growth and shrink the size of human lung cancer xenografts in mice. The study is the first to show that a specific peptide reduces lung tumor growth by inhibiting blood vessel formation. Angiotensin-(1-7) works by inhibiting the production of signals sent out by a tumor for food. The signals prompt blood vessels to grow and invade the tumor to feed it. Over the course of the current study, the tumors treated with angiotensin-(1-7) shrank, while saline-treated tumors grew and, at the end of the study, the tumors treated with angiotensin-(1-7) weighed about 60 percent less than the tumors treated with saline. Analysis also showed that the tumors from mice treated with the peptide had significantly fewer blood vessels compared to the tumors from the saline-treated animals. The authors said the treatment likely has applications beyond lung cancer--they have collected data showing it is effective on breast, colon, and brain tumors, as well. The treatment also presents an attractive possibility for future human cancer therapy from a cost perspective, the authors said. "Because it's a peptide, it's very small and can be made very easily," Dr. Gallagher noted. "We sometimes like to say we're the aspirin of cancer therapy." The article was published in the June issue of Molecular Cancer Therapeutics. [Press release] [MCT abstract]

August 21st

Potential Non-Invasive DNA Test for Gastric and Colorectal Cancers

Preliminary testing of methylation patterns in two gene promoters in fecal DNA indicates that this might be a feasible non-invasive approach to detecting gastric and colorectal cancers. The researchers found that extensive methylation of the RASSF2 and SFRP2 gene promoters was much more likely to be found in advanced gastric tumors and colorectal tumors than in normal tissue. Methylation markers were detected in 57% of gastric cancer patients, 75% of colorectal cancer patients, and 44% of subjects with advanced colorectal adenomas, but only 10.6% of patients with none of these cancers. Because many patients are reluctant to undergo invasive tests for the detection of gastrointestinal cancers, the development of non-intrusive screening tests is desirable. Especially in cancer patients, some cells are sloughed off from the gastrointestinal tract, so small amounts of DNA from these cells present in stool samples can be examined for the presence of cancer biomarkers. "Selection of adequate biomarkers is critical to the success of any screening methodology," the authors wrote. "By identifying disease-specific methylation patterns for human fecal DNA from advanced gastric and colorectal tumors, we could more accurately identify subjects at high risk for developing, or having developed, advanced tumors." This work was published online on August 21 in the Journal of the National Cancer Institute. [Press release] [JNCI abstract]

August 20th

Aphids Spared from Parasitic Wasps by Virus-Infected Bacteria

Pea aphids harboring Hamiltonella defensa bacteria that are infected with the APSE virus tend to be spared from death due to a normally deadly parasitic wasp (Aphidius ervi), according a recent research report. Typically, the wasp lays its eggs in the aphid and the wasp larvae consume the aphid from the inside out. The APSE virus produces toxins that appear to be involved in the anti-wasp defense. The researchers first showed that pea aphids without the H. defensa bacteria were highly vulnerable to the parasitic wasp, while pea aphids with the H. defensa bacteria tended to be resistant. The scientists then showed that pea aphids carrying H. defensa bacteria that had lost the APSE virus were also vulnerable to parasitic wasp attack. On the other hand, pea aphids carrying APSE-infected H. defensa were resistant. The research is the first to demonstrate that a virus that infects bacteria can help, rather than harm, the bacteria's animal host, said first author Dr. Kerry Oliver. This work was reported in the April 21 issue of Science. The accompanying photo is credited to Dr. Oliver. [Press release] [Science abstract]

August 18th

Elevated Arginase Levels Might Contribute to Diabetic Retinopathy

Work in an animal model system has shown that elevated levels of the enzyme arginase can contribute to vascular eye damage and researchers suggested that therapies to normalize arginase levels could perhaps halt progression of potentially blinding diseases such as diabetic retinopathy. Because it is possible to measure arginase levels in the blood, the enzyme might also become a biomarker for a disease process that can work silently in the eye for months or even years, said Dr. Ruth Caldwell, the senior author of the report. This work is the first to make the connection between eye disease and arginase, an enzyme known to be a player in cardiovascular disease, the researchers said. Rather than drugs that generally suppress arginase, the researchers want to find new drugs that can restore healthy levels of arginase. "You need arginase. If you don't have it, you are in big trouble," said Dr. R. William Caldwell, also an author of the report. "We want to delineate the events that cause elevation and limit the elevation to prevent the resulting pathology." This work was reported in the August issue of the American Journal of Pathology. [Press release] [AJP abstract]

August 17th

First Protein Toxin in Amphibians Identified

The first gene-encoded protein toxin in an amphibian has been identified by researchers in China. The toxin, named anntoxin, is a 60-amino-acid neurotoxin found in the skin of a Chinese tree frog, Hyla annectans. The discovery may help shed light on the evolution of toxins. While gene-encoded protein toxins have been identified in many vertebrate animals, including fish, reptiles, and mammals, none has previously been found in amphibians or birds. In the case of poisonous amphibians, like the tropical poison dart frogs, their toxins are usually small chemicals like alkaloids that are extracted from insects and secreted onto the animal's skin. In protein sequence and structure, anntoxin is very similar to dendrotoxins (the venoms found in cobras and other mamba snakes) and cone snail toxins. Like these other toxinx, anntoxin is fast-acting and potent; the researchers found it could produce rapid convulsions, paralysis, and respiratory distress in several would-be predators such as snakes and birds. The discovery of anntoxin was reported in the August 14 issue of the Journal of Biological Chemistry. [Press release] [JBC abstract]

August 12th

Human Genome Sequenced for $50,000 Using Helicos Instrument

A Stanford University scientist, working with a team of just two others, has sequenced his own genome for a cost of under $50,000. The previous lowest-cost human genome sequencing effort was accomplished at a cost of $250,000 by a team of almost 200 people in 2008. "This is the first demonstration that you don't need a genome center to sequence a human genome," said Dr. Stephen Quake, whose genome was sequenced. "It's really democratizing the fruits of the genome revolution and saying that anybody can play in this game. This can now be done in one lab, with one machine, at a modest cost," said Dr. Quake. "It's going to unleash an enormous amount of creativity and really broaden the field." To sequence his genome, Dr. Quake and his team used a commercially available, refrigerator-sized instrument called the Helicos Biosciences SMS (Single Molecule Sequencing) HeliScope. Dr. Quake, who pioneered the underlying technology in 2003, is a co-founder of the Cambridge, Massachusetts-based company and chairs its scientific advisory board. This landmark sequencing effort was described online on August 9 in Nature Biotechnology. [Press release] [Nature Biotechnology article]

August 10th

Animal Studies Suggest Potential Oral Drug for Type 1 Diabetes

Researchers from Israel’s Tel Aviv University have shown that a modified version of an anti-Ras compound (FTS) is effective in increasing insulin production in animal models of type 1 diabetes. The compound (F-FTS) has the potential to become the first tablet-based treatment for children and adults with type 1 diabetes. In the recent study, lead author Dr. Adi Mor and colleagues treated pre-diabetic mice for six months. One group was given F-FTS; another was given no drug at all. The outcome was dramatic. Only 16% of the treated group developed diabetes, while 82% of the untreated group became diabetic. Also, insulin production from beta cells in the treated group of mice increased in comparison to insulin production in the non-treated group, Dr. Mor reported. "Our anti-Ras compound has shown very positive results in inhibiting diabetes," she said. And given the drug's history--FTS has already passed toxicity studies for other diseases and disorders--it has the potential to fast-track through FDA regulatory hurdles, skipping straight to Phase II clinical trials. A new drug for diabetes could therefore be ready in as little as five years’ time. The new research is published in the August 15 issue of the European Journal of Pharmacology. [Press release]
[EJP abstract]

August 5th

Robotic Testing of Infected Worms May Lead to New Antibiotics

In an effort to develop a new approach to screening for effective antibiotics, scientists have described the successful use of a whole-animal, high-throughput screening test --automated with a robot--to test the effects of 37,000 potential drugs on C. elegans (a type of worm) infected with E. faecalis (a type of bacteria). That bacterium causes life-threatening infections in humans. The tests identified 28 potential new drugs never before reported to have germ-fighting effects. Some of the potential new drugs worked in ways that appeared to be totally different from those in which existing antibiotics work. In their report, the scientists noted that existing methods for identifying germ-fighting drugs involve adding the potential drug to cultures of bacteria or cells and watching the results. These tests sometimes do not work well. They may give passing grades to potential drugs that are toxic, or that fight bacteria in the same ways as existing antibiotics that are losing effectiveness against drug-resistant bacteria. A much better test, the researchers maintained, would involve screening of potential new antibiotics in living animals infected with bacteria to see the effects on the entire body of the animal, which is what they did in this study. The results of this new approach, carried out by researchers at Harvard Medical School and collaborating institutions, are reported in ACS Chemical Biology. [Press release] [ACS Chemical Biology abstract]