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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]

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]

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]

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]

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]

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]

New Cilia Disease Identified

Scientists have shown that a lethal developmental disorder (hydolethalus syndrome) belongs to an emerging class of human ciliopathic disorders that includes polycystic kidney disease. "Five years ago, a human genetics study linked hydrolethalus syndrome to a mutation in a protein named HYLS1. Since this discovery, the function of HYLS1 has remained unknown. Our work solves this mystery, showing that HYLS1 is a centriolar protein required for the formation of cilia, small hair-like cellular projections that execute a variety of essential motile and sensory functions," explained Dr. Karen Oegema, an author of the study. Hydrolethalus syndrome is a rare genetic disorder characterized by severe birth defects (hydrocephalus, polydactyly, cardio/pulmonary malformations) that result in stillbirth or early neonatal death. The majority of cases affect people of Finnish ancestry, where the incidence is roughly 1 in 20,000. In the current work, Dr. Oegema and colleagues showed that the evolutionarily conserved HYLS1 protein is, in fact, a centriolar protein that is specifically required for cilia formation in both C. elegans and vertebrates. The researchers demonstrated that HYLS1 stably incorporates into centrioles during their assembly, and plays a crucial role in the early steps of the ciliogenesis pathway. Interestingly, however, HYLS1 is dispensable for centriole assembly and centrosome function during cell division. This work is reported in the September 1 issue of Genes & Development. [Press release]

Heat-Based Procedure Using Nanotubes Kills Tumor Cells

Researchers have shown that the by injecting man-made nanotubes into tumors and then heating them with a quick, 30-second burst of laser radiation, they can kill nearly 80 percent of kidney tumors in mice. The researchers said that the finding suggests a potential future cancer treatment for humans. Nanotubes are long, thin, sub-microscopic tubes made of carbon. For the study, researchers used multi-walled nanotubes (MWCNTs), which contain several nanotubes nested within each other. The tubes, when non-invasively exposed to laser-generated near-infrared radiation, respond by vibrating, creating heat. If enough heat is conducted, tumor cells near the tubes begin to shrink and die. In the mice that received the MWCNTs followed by a 30-second laser treatment, researchers found that the higher the quantity of nanotubes injected, the longer the mice lived and the less tumor regrowth was seen. In fact, in the group that received the highest dose of MWCNTs, tumors completely disappeared in 80 percent of the mice. Many of those mice continued to live tumor-free through the completion of the study, which was about nine months later. "MWCNTs are more effective at producing heat than other investigational nanomaterials," saqid Dr. Suzy Torti, lead investigator for the study. "Because this is a heat therapy rather than a biological therapy, the treatment works on all tumor types if you get them hot enough. We are hopeful that we will be able to translate this into humans." This work was published in PNAS in August. [Press release]

Health Benefits of Red Wine May Aid Treatment of Inflammatory Diseases

Scientists have unraveled the mystery of how the red wine ingredient resveratrol is able to control inflammation. In this study, researchers administered an inflammatory agent to two groups of mice. One group was pretreated with resveratrol and the other group was not. The mice that were not pretreated with resveratrol experienced a strong inflammatory response, simulating disease in humans, while the group pretreated with resveratrol was protected from the inflammation. The scientists then examined the tissues of the mice to determine exactly how resveratrol was able to protect the mice from inflammation. They found that resveratrol used a one-two punch to stop inflammation in the mice by preventing the body from creating two different molecules known to trigger inflammation, sphingosine kinase and phospholipase D. This finding suggests that resveratrol may be harnessable as a treatment for inflammatory diseases and may also lead to entirely new resveratrol-based drugs that are even more effective. This work was published in the August issue of The FASEB Journal. "The therapeutic potential of red wine has been bottled up for thousands of years," said Dr. Gerald Weissmann, Editor-in-Chief of the journal, "and now that scientists have uncorked its secrets, they find that studies of how resveratrol works can lead to new treatments for life-threatening inflammation." [Press release] [FASEB abstract]

Nanoparticles with Diphtheria Toxin Gene Target Ovarian Cancer

Nanoparticles containing the gene for a diphtheria toxin suicide protein can effectively suppress ovarian tumor growth in mice, according to a team of researchers from MIT and collaborating institutions. The findings could lead to a new treatment for ovarian cancer, which now causes more than 15,000 deaths each year in the United States. Because it is usually diagnosed at a relatively late stage, ovarian cancer is one of the deadliest forms of cancer. Currently, ovarian cancer patients undergo surgery followed by chemotherapy. In many cases, the cancer returns after treatment, and there are no good therapies for recurring and advanced-stage tumors. The new nanoparticles are made with positively charged, biodegradable polymers known as poly(beta-amino esters). When mixed together, these polymers can spontaneously assemble with DNA to form nanoparticles. The polymer-DNA nanoparticle can deliver functional DNA when injected into or near the targeted tissue. The packaged diphtheria toxin gene produces a diphtheria toxin suicide protein which kills cells by disrupting their ability to manufacture proteins. This work is reported in the August 1 issue of Cancer Research. [Press release] [Cancer Research abstract]

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