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Archive - Oct 2009

Date

October 20th

Over-Expressed Gene Produces Smarter Rat

Over-expression of a particular gene (NR2B) that lets brain cells communicate just a fraction of a second longer makes a smarter rat, according to a recent research report. The researches showed that a transgenic Long Evans rat that overexpressed NR2B was able to remember novel objects, such as a toy she played with, three times longer than the average Long Evans female rat, which is considered the smartest rat strain. The transgenic rat was also much better at more complex tasks, such as remembering which path she last traveled to find a chocolate treat. NR2B is a subunit of NMBA receptors, which are like small pores in brain cells that let in electrically-charged ions that increase the activity and communication of neurons. Dr. Joe Tsien, an author of the report, referred to NR2B as the "juvenile" form of the receptor because its levels decline after puberty and the adult counterpart, NR2A, becomes more prevalent. While the juvenile form keeps communication between brain cells open maybe just a hundred milliseconds longer, that's enough to significantly enhance learning and memory and why young people tend to do both better, Dr. Tsien said. The report was published October 19 in PLoS ONE. [Press release] [PLoS ONE article]

Potential Anti-Melanoma Compound Synthesized

Researches at the University of Alberta in Canada have synthesized a natural compound (palmerolide A) that they believe shows exceptional potential to specifically treat melanoma, a frequently fatal form of skin cancer. "The potency of palmerolide is exceptional and melanoma is a very aggressive cancer for which there is almost no chemotherapeutic recourse," said Dr. Dennis Hall, senior author of the report. "Natural substances like palmerolide offer real hope for such treatments. One of the problems with most cancer drugs is the lack of selectivity for cancer cells versus normal cells. Preliminary data for palmerolide A looks very promising in terms of solving this issue." Dr. Hall emphasized that "for commercialization, the structure needs to be made more 'drug-like;' smaller, and more water-soluble, while preserving the potency." The report was published in the October 14 issue of the Journal of the American Chemical Society. [Press release] [JACS abstract]

October 12th

RNA Repair System Discovered in Bacteria

In new papers appearing in Science and PNAS, University of Illinois biochemistry professor Dr. Raven H. Huang and colleagues describe the first RNA repair system to be discovered in bacteria. This is only the second RNA repair system discovered to date (with two proteins from T4 phage, a virus that attacks bacteria, as the first). The novelty of the newly discovered bacterial RNA repair system is that, before the damaged RNA is sealed, a methyl group is added to the two-prime hydroxyl group at the cleavage site of the damaged RNA, making it impossible to cleave the site again. Thus, the repaired RNA is "better than new." This discovery has implications for protecting cells against ribotoxins, a class of toxins that kills cells by cleaving essential RNAs involved in protein translation. Because the enzyme responsible for methylation in the newly-discovered RNA repair system is the Hen1 homolog in bacteria, the finding also has implications for the understanding of RNA interference and gene expression in plants, animals, and other eukaryotes. The eukaryotic Hen1 is one of three enzymes (along with Dicer and Argonaute) essential for the generation of small noncoding RNAs of 19-30 nucleotides in RNA interference. The new papers appear in the October 9 issue of Science and the October 12 online edition of PNAS. [Press release] [Science abstract] [PNAS abstract]

Higher Urate Levels May Slow Progression of Parkinson's

Individuals with Parkinson's disease who have higher levels of the antioxidant urate in their blood and cerebrospinal fluid appear to have a slower rate of disease progression, according to results of a new study funded, in part, by the National Institutes of Health. The results support similar findings of an earlier, 2008 study. Urate is a chemical that at very high levels is associated with gout. A clinical trial is under way to examine the safety and potential benefits of supplemental urate elevation for recently diagnosed Parkinson's patients who have low urate levels. Experts emphasize there is no proof that elevating urate levels will help against Parkinson's disease, and that it should not be attempted outside of a clinical trial, where physicians can closely monitor possible benefits and risks, such as gout and heart disease. In the new study, investigators demonstrated the link with urate by mining a repository of clinical data and tissue samples collected from Parkinson's patients more than 20 years ago as part of a pioneering study called DATATOP, funded by the NIH's National Institute of Neurological Disorders and Stroke (NINDS). The new study was funded primarily by the NINDS, with additional support from the Department of Defense and private organizations. "This study speaks to the value of saving data and biospecimens from large clinical studies, and making them available to the research community to pursue new, unanticipated ideas," said Dr. Michael Schwarzschild, of Massachusetts General Hospital in Boston, senior author of the study. "These results were critically important. Only now we can be reasonably sure that the slower rate of progression in patients with higher concentrations of urate is real and not a chance occurrence," said Dr. Alberto Ascherio of the Harvard School of Public Health and lead author of the study.

October 8th

Fractal Architecture Permits Incredibly Tight Packing of Cellular DNA

Using a new technique called Hi-C, scientists have deciphered the three-dimensional structure of the human genome, paving the way for new insights into genomic function. The researchers reported two striking findings. First, the human genome is organized into two separate compartments, keeping active genes separate and accessible while sequestering unused DNA in a denser storage compartment. Chromosomes snake in and out of the two compartments repeatedly as their DNA alternates between active, gene-rich and inactive, gene-poor stretches. Second, at a finer scale, the genome adopts an unusual organization known in mathematics as a "fractal." The specific architecture the scientists found, called a "fractal globule," enables the cell to pack DNA incredibly tightly--the information density in the nucleus is trillions of times higher than on a computer chip--while avoiding the knots and tangles that might interfere with the cell's ability to read its own genome. Moreover, the DNA can easily unfold and refold during gene activation, gene repression, and cell replication. The fractal globule architecture, while proposed as a theoretical possibility more than 20 years ago, has never previously been observed. "Nature's devised a stunningly elegant solution to storing information--a super-dense, knot-free structure," said senior author Dr. Eric Lander, director of the Broad Institute. This paper is featured on the cover of the October 9 issue of Science. [Press release]

October 7th

Bacterium May Aid Formation of Gold

Scientists in Australia, together with collaborators, have shown that a particular bacterium (Cupriavidus metallidurans) catalyzes the biomineralization of gold by transforming toxic gold compounds to their metallic form using an active cellular mechanism. “A number of years ago we discovered that the metal-resistant bacterium C. metallidurans occurred on gold grains from two sites in Australia. The sites are 3,500 km apart, in southern New South Wales and northern Queensland, so when we found the same organism on grains from both sites we thought we were onto something. It made us wonder why these organisms live in this particular environment. The results of this study point to their involvement in the active detoxification of Au complexes leading to formation of gold biominerals,” explained Dr. Frank Reith, first author of the research report. The experiments showed that C. metallidurans rapidly accumulates toxic gold complexes from a solution prepared in the lab. This process promotes gold toxicity, which pushes the bacterium to induce oxidative stress and metal resistance clusters, as well as an as yet uncharacterized Au-specific gene cluster in order to defend its cellular integrity. This leads to active biochemically-mediated reduction of gold complexes to nano-particulate, metallic gold, which may contribute to the growth of gold nuggets. This is the first direct evidence that bacteria are actively involved in the cycling of rare and precious metals, such as gold. These results open the doors to the production of biosensors that may help mineral explorers find new gold deposits. This work was published on October 7 in the online edition of PNAS.

Beta Cell Growth, Insulin Production Increased in Diabetic Mice

By “knocking out” the Lkb1 gene in the beta cells of diabetic laboratory mice, scientists have been able to increase the size and number of beta cells and also to increase the amount of insulin stored in and released by these cells. “We were surprised by the impressive accumulation of Lkb1 in beta cells of diabetic mice, which suggested that Lkb1 might contribute to their impaired function. After removal of the Lkb1 gene, the beta cells grow larger, proliferate more, and secrete more insulin. It's a one-stop shop for the much needed insulin", said Dr. Robert Screaton, senior author of the research report. Importantly, the improved beta cell function lasted for at least five months, even in mice fed a high-fat diet designed to mimic the high caloric intake associated with metabolic syndrome and type 2 diabetes in humans. "The knockout mice on a high-fat diet have lower blood glucose. If this observation is confirmed in humans, it may give us another clue into the development of type 2 diabetes, and perhaps new treatment options,” Dr. Screaton said. This work was published in the October 7 issue of Cell Metabolism. [Press release] [Cell Metabolism abstract]

October 6th

Telomere Researchers Awarded Nobel Prize

Three scientists who combined to identify the end structures of chromosomes and the enzyme that maintains these structures have been awarded the 2009 Nobel Prize in Physiology or Medicine. The prestigious award went to Dr. Elizabeth Blackburn (photo) of the University of California-San Francisoc, Dr. Carol Greider of Johns Hopkins University, and Dr. Jack Szostak of Harvard Medical School. Blackburn, Greider, and Szostak performed their groundbreaking investigations in the late 1970s and the 1980s. Blackburn showed that simple, repeated DNA sequences make up chromosome ends and, with Szostak, established that these repeated sequences stabilize chromosomes and prevent them from becoming damaged. Szostak and Blackburn predicted the existence of an enzyme that would add the sequences to chromosome ends. While a graduate student with Blackburn, who was then a member of the faculty at the University of California-Berkeley, Greider tracked down the enzyme telomerase. She later determined that each organism's telomerase contains an RNA component that serves as a template for the creature’s particular telomere DNA repeat sequence. In addition to providing insight into how chromosome ends are maintained, Blackburn, Greider, and Szostak’s work laid the foundation for studies that have linked telomerase and telomeres to human cancer and age-related conditions. Subsequent research has shown that telomerase and telomeres play key roles in cell aging and death and also play a part in the aging of the entire organism. Research has also shown that cancer cells have increased telomerase activity, protecting them from death. The award was announced on October 5.

October 5th

Small Body Size, High Mortality Rate, and Early Sexual Maturity in Pygmies

A new study suggests that high mortality rates in small-bodied people, commonly known as pygmies, may be part of the reason for their small stature. The study, by Dr. Jay Stock and Dr. Andrea Migliano, both of the University of Cambridge, may help unravel the mystery of how small-bodied people got that way. Adult males in small-bodied populations found in Africa, Asia, and Australia are less than four feet, 11 inches tall, which is about one foot shorter than the average adult male in the U.S. Why people in these populations are so small remains a mystery, but several hypotheses have been proposed. Some scientists think that small bodies provide an evolutionary advantage under certain circumstances. For example, a smaller body needs less food—a good thing in places where food supplies are inconsistent. Small bodies also may provide an advantage in getting around in thickly forested environments. Recently, however, a new hypothesis has come to the fore suggesting that reproductive consequences of high mortality rates may explain small body size. If death comes at an early age, then natural selection would favor those who are able to reproduce at an early age. But early sexual maturity comes with a cost. When the body matures early, it diverts resources to reproduction that otherwise would have gone to growth. So small body size could be essentially a side effect of early sexual maturity. Stock's and Migliano's study provides the first long-term evidence for the mortality hypothesis. The article appears in the October issue of Current Anthropology. [Press release] [Current Anthropology abstract]

October 1st

New Clue to Tuberculosis

Scientists have discovered a potential chink in the armor of the organism that causes tuberculosis in humans. They have shown that the organism (Mycobacterium tuberculosis) produces a compound (edaxadiene) that provides a defense mechanism against the killing power of macrophages that normally engulf and destroy harmful bacteria. The scientists have, in addition, identified molecules that inhibit the edaxadiene-producing enzyme and therefore have the potential to reduce the tuberculosis organism’s resistance to macrophage attack. The researchers cautioned, however, that finding an inhibitor that works outside of the test tube, and in humans, and is stable, and can be ingested safely by humans, and can help kill tuberculosis is a process that may take a decade. Nevertheless, Dr. Reuben Peters, senior author of the study, said, "This is the project where I tell my students, 'If we can make even just a 1 percent impact, we can save 15,000 - 20,000 lives a year.' That is really a significant contribution towards alleviating human suffering.” Tuberculosis is a contagious disease that is on the rise, killing 1.5 to 2 million people worldwide annually. Portions of this new work are reported in the August 28 issue of the Journal of Biological Chemistry and are slated to be the cover subject of an upcoming issue of the Journal of the American Chemical Society. [Press release] [JBC abstract]