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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]

New Zealand Walking Bat Has Ancient Heritage

A bizarre New Zealand bat that is as much at home walking four-legged on the ground as winging through the air had an Australian ancestor 20 million years ago with the same rare ability, a new study has found. The discovery overturns a long-held held view that the agile walking and climbing skills of the lesser short-tailed bat--Mystacina tuberculata--evolved in the absence of any ground-dwelling mammal competitors or predators, says an international team of researchers led by Dr Suzanne Hand, a bat expert at the University of New South Wales, Sydney, Australia. Along with the American common vampire bat--Desmodus rotundus--the New Zealand bat is one of only two of 1,100 bat species worldwide that has a true four-legged walking gait when maneuvering on the ground. It uses its wings as forelegs. Its thumb and toe claws have a unique extra talon for extra grip, plus a system of adhesive, gecko-like grooves in the soft, deeply wrinkled soles of its feet. The team has found that other special muscle and bone adaptations were also present in one of its extinct rainforest-dwelling Australian ancestors, fossils of which have been found at the rich Riversleigh World Heritage Fossil Site in north-west Queensland, it says in a report published in the journal BMC Evolutionary Biology. "The lesser short-tailed bat seems to be the sole survivor of an ancient Australian lineage now found only in New Zealand," said Dr Hand. "This study shows that, contrary to existing hypotheses, bats are not overwhelmingly absent from the ground because of competition from, or predation by, other mammals. Competition with other mammals and pressure from terrestrial predators does not deter modern vampire bats from walking.

Researcher Recommend Two Genes for Barcoding of Plants

An international team of researchers has recommended using two genes for the barcoding of land plant, a step the team hopes will lead to a universal system for identifying over 400,000 species, and ultimately boost conservation efforts. Limiting the barcode to information generated from two DNA sites should help cut costs associated with sequencing and retrieving the correct information. "We've selected areas of DNA that are available in the vast majority of plants, could easily and accurately be sequenced, and when combined, provide a near-unique signature for barcoding,” said Dr. Sean Graham, an author of the study." The team selected two chloroplast genes referred to as rbcL and matK as the best candidates from which to generate barcode data. "There's no doubt this will be refined in the future, but there is a need for a core barcoding standard now," said Dr. Graham. "Particular research projects with special needs could augment the system by adding a third DNA locus to their barcode if required.” Barcodes based on portions of DNA--the taxonomical equivalent to UPC barcodes on products--have already emerged as a viable solution for uniquely identifying species in many animal groups. However, because DNA varies less between plant species, determining which portions of plant DNA to use as a unique identifier has been a thorny issue. This new work was published in PNAS the week of July 27. [Press release 1] [Press release 2] [PNAS abstract]

Androgen Receptors Are Reprogrammed in Lethal Stage of Prostate Cancer

A recent study reveals how late-stage, hormone-independent prostate tumors gain the ability to grow without the need of hormones. The onset of hormone-independent growth marks an advanced and currently incurable stage of prostate cancer, which is the most frequently diagnosed cancer in men. The study focused on androgen receptors, molecules located in the nuclei of cells of the prostate gland and other tissues. Male sex hormones—androgens--bind to these receptors to activate genes that control cell growth by regulating an early phase of the cell cycle. The researchers showed that in androgen-independent prostate cancer, androgen receptors are reprogrammed to regulate a group of genes involved in the later, mitotic phase of the cell cycle, triggering rapid cell growth. They further showed that an epigenetic modification associated with the UBE2C gene is involved in this reprogramming and that overexpression of this gene is necessary for the growth of the hormone-independent prostate cancer cells. These findings provide a better understanding of prostate cancer and could identify new therapeutic targets and lead to new treatments for the lethal, hormone-independent stage of the disease, said lead author Dr. Qianben Wang. Conducted by researchers at the Dana Farber Cancer Institute, Harvard Medical School, and collaborating institutions, this study was reported as a featured article in the July 24 issue of Cell. [Press release] [Cell article]

Gene Linked to Restless Legs Syndrome

Researchers at the Mayo Clinic, together with collaborators, have identified what is believed to be the first gene mutation linked to restless legs syndrome. The scientists identified the mutation (in the MEIS1 gene) in a family with six members. Three who had restless legs syndrome had the mutation and the other three without the disease did not. "The presence of the mutation in all affected individuals supports a pathogenic role for the MEIS1 gene, and we now need to confirm this finding with other international research groups who study restless legs syndrome," said Dr. Carles Vilariño-Güell, the lead author of the study. "The mutation we found is in a portion of the protein that is identical in species as distinct to human as frogs and fish, which tells us that this portion is very important for the proper function of the protein and that the mutation has a very high chance of causing disease," he said. The researchers doubt that a large proportion of the millions of people who suffer from the syndrome have this mutated MEIS1 gene. They point out, however, that understanding the function of both the normal gene and the abnormal gene will likely provide some insights into this mysterious disorder. Restless legs syndrome is estimated to affect between 5 and 11 percent of the population in Europe and in North America. The condition is characterized by unpleasant sensations in the legs at rest, especially in the evening, that are temporarily relieved by movement. Because restless legs syndrome often interrupts sleep, people commonly are diagnosed after they consult a sleep specialist for assistance. This research was reported in the July 21 issue of Neurology.

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