New findings from researchers at the Stanford University School of Medicine and Lucile Packard Children’s Hospital, and colleagues, shed light on the neural basis of memory defects in Down syndrome and suggest a new strategy for treating the defects with medication. The study, which was conducted in mice, is the first to show that boosting norepinephrine signaling in the brains of mice, which have been genetically engineered to mimic Down syndrome, improves their cognition. Norepinephrine is a neurotransmitter that nerve cells use to communicate. The scientists said that their findings raise the possibility that restoring norepinephrine-mediated neurotransmission could reverse cognitive dysfunction in Down syndrome. “If you intervene early enough, you will be able to help kids with Down syndrome to collect and modulate information,” said Dr. Ahmad Salehi, the first author of the study. “Theoretically, that could lead to an improvement in cognitive functions in these kids.” The results give “a ray of hope and optimism for the Down syndrome community for the future,” said Dr. Melanie Manning, director of the Center for Down Syndrome at Lucile Packard Children’s Hospital. Dr. Manning was not a part of the research team. “It’s very exciting,” she said. “We still have a long way to go, but these are very interesting results.” This report was featured as the cover story of the November 18 issue of Science Translational Medicine. [Press release] [Science Translational Medicine abstract]
Female Mountain Goats May Be Conflicted over Mate Choice
Mountain goats are no exception to the general rule among mammals that larger males sire more and healthier offspring. But University of Alberta researcher Dr. David Coltman and colleagues have recently found a genetic quirk that might make female mountain goats think twice about their prospective mates. The larger males pass their physical attributes and mating success to their male heirs. But Dr. Coltman’s data shows the daughters of these larger males are routinely smaller and less fit than females produced by physically more modest fathers. Life on the side of a mountain favors bigger, healthier animals, both male and female. Dr. Coltman’s research shows that this anomaly could have implications for female mate choice, because a female that mates with a large, dominant male can expect to have larger sons, but smaller and less fit daughters. The research also poses the question of why female offspring sired by the dominant male would be compromised. Another question the study raises is: what if any consideration does the size of their daughters have for would-be mothers? Could this be a factor weighed by a sexually mature female when courted by males that come in a variety of sizes? This study was featured as the cover story of the November 22 issue of the Proceedings of the Royal Society B. [Press release] [PRS abstract]
Nano “Fly Paper” Captures Metastatic Cancer Cells for Testing
Just as fly paper captures insects, an innovative new device with nano-sized features developed by researchers at UCLA is able to capture cancer cells in the blood that have broken off from a tumor. These cells, known as circulating tumor cells, or CTCs, can provide critical information for examining and diagnosing cancer metastasis, determining patient prognosis, and monitoring the effectiveness of therapies. The current gold standard for examining the disease status of tumors is an analysis of metastatic solid biopsy samples, but in the early stages of metastasis, it is often difficult to identify a biopsy site. By capturing CTCs, doctors can essentially perform a “liquid” biopsy, allowing for early detection and diagnosis, as well as improved treatment monitoring. To date, several methods have been developed to track these cells, but the UCLA team’s novel “fly paper” approach may be faster and cheaper than others, and it appears to capture far more CTCs. The UCLA team developed a 1-by-2-centimeter silicon chip that is covered with densely packed nanopillars and looks like a shag carpet. To test cell-capture performance, researchers incubated the nanopillar chip in a culture medium with breast cancer cells. As a control, they performed a parallel experiment with a cell-capture method that uses a chip with a flat surface. Both structures were coated with anti-EpCAM, an antibody that can help recognize and capture tumor cells. The researchers found that the cell-capture yields for the UCLA nanopillar chip were significantly higher; the device captured 45 to 65 percent of the cancer cells in the medium, compared with only 4 to 14 percent for the flat device. The time required for CTC detection using CellSearch, a technology currently approved by the U.S.
Evolution of Highly Toxic Box Jellyfish
With thousands of stinging cells that can emit deadly venom from tentacles that can reach ten feet in length, the fifty or so species of box jellyfish have long been of interest to scientists and to the public. Yet little has been known about the evolution of this early branch in the animal tree of life. An international team of researchers has now largely unraveled the evolutionary relationships among the various species of box jellyfish, thereby providing insight into the evolution of their toxicity. “By determining the relationships among the different box jellyfish, some of which are capable of killing a healthy human, this study can help in the future development of antivenoms and treatments for their stings,” said Dr. Allen Collins, a specialist in Cnidaria, the phylum of animals that includes box jellyfish, and senior author of the report. “Researchers will now be able to make more informed choices about organisms for future venom studies, and make predictions on which species are likely to be of public health concern in addition to the known culprits.” Box jellies–also called sea wasps, stingers, or fire jellies–live primarily in warm coastal waters around the world. They are particularly well known in Australia, the Philippines and the rest of Southeast Asia, but they also occur in Hawaii and in waters off the United States Gulf and East Coasts. Their toxicity varies among species and ranges from being completely harmless to humans to causing death within minutes after a sting. Beyond their toxicity, box jellyfish have other interesting characteristics. Some species, for instance, have as many as 24 eyes, capable of sensing light and forming an image of their surroundings.
Mouse Results Suggest Possible Drug Treatment for Huntington’s Disease
Researchers have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington’s disease. In contrast, excessive extrasynaptic activity (aberrant electrical activity in the brain, usually not associated with communication between nerve cells) enhances the misfolded proteins’ deadly effects. In addition, the scientists found that the drug Memantine, which is approved to treat Alzheimer’s disease, successfully treated Huntington’s disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity. “Chronic neurodegenerative diseases like Huntington’s, Alzheimer’s, and Parkinson’s are all related to protein misfolding,” said Dr. Stuart Lipton of the Burnham Institute for Medical Research, senior author of the report. “We show here, for the first time, that electrical activity controls protein folding, and if you have a drug that can adjust the electrical activity to the correct levels, you can protect against misfolding. Also, this verifies that appropriate electrical activity is protective, supporting the ‘use it or lose it theory’ of brain activity at the molecular level. For example, this finding may explain why epidemiologists have found that ‘using’ your brain by performing crossword puzzles and other games can stave off cognitive decline in diseases like Alzheimer’s.” A small human clinical trial of Memantine for Huntington’s disease has recently shown positive effects. Larger, international clinical trials are now being planned. In addition to Dr. Lipton, the article’s authors included Dr. Michael Hayden of the University of British Columbia.
Rasberry Ants on the March
The invasion of a new species of ant (Rasberry ants) has scientists intrigued, businesses concerned, and fire ants running for the hills, said Dr. Jerry Cook, an entomologist at Sam Houston State University. Dr. Cook and other scientists are at a loss to explain the fast and furious spread of the rapacious ant, which is named after exterminator Tom Rasberry, who discovered the ant in 2002. The ant was discovered in Houston in 2002 and has quickly spread as far north as Louisiana and Mississippi within the last year. “This is a species that we do not know much about. Presumably the ant came from the Caribbean through the Port of Houston,” Dr. Cook said. “We know the ant is in the Paratrechina genus and is capable of growing a population of billions and they need to eat. They especially like other bugs, like fire ants and honey bees.” The population is growing so fast, and so large, that it is potentially an ecosystem disaster, according to Dr. Cook. “If the Rasberry ant can virtually eliminate a pain like the fire ant, what else is it capable of doing?” he asked. “If bees are eliminated, plants will not be pollinated which could result in the lack of crops producing fruits and vegetables. That in turn becomes a major problem for the agriculture community. They could become more than a nuisance, they could become a danger.” Dr. Cook emphasized the need for funding for research targeted at better understanding of the Rasberry ant. [Press release]
Absence of LKB1 Gene Increases Insulin Production
Eliminating the LKB1 gene from the beta cells of the pancreas causes the production and secretion of more insulin than from normal beta cells in a mouse model, according to researchers from the Hebrew University of Jerusalem and collaborators. This results in an enhanced response to blood glucose levels. The findings have potentially significant implications for those suffering from diabetes due to insufficient production of insulin in the pancreas. Because it was shown that LKB1 negatively regulates both insulin content and secretion, the way has now been opened to possible development of a novel therapy that would limit the presence of this gene in pancreas beta cells, thus enhancing insulin secretion. This work was reported in the October 7 issue of Cell Metabolism. [Press release] [Cell Metabolism abstract]
Preserving Ends of Chromosomes Linked to Longevity in Centenarians
Researchers at the Albert Einstein College of Medicine, and colleagues, have found a clear link between living to 100 and the inheritance of a hyperactive version of an enzyme that rebuilds telomeres. Telomeres are relatively short sections of specialized DNA that sit at the ends of all chromosomes. Telomeres have been compared to the plastic tips at the ends of shoelaces that prevent the laces from unraveling. Each time a cell divides, its telomeres erode slightly and become progressively shorter with each cell division. Eventually, telomeres become so short that their host cells stop dividing and lapse into a condition called cell senescence. As a result, vital tissues and important organs begin to fail and the classical signs of aging ensue. In investigating the role of telomeres in aging, the researchers studied Ashkenazi Jews because they are a homogeneous population that has been well studied genetically. Three groups were enrolled: 86 very old, but generally healthy, people (average age 97); 175 of their offspring; and 93 controls (offspring of parents who had lived a normal lifespan). “As we suspected, humans of exceptional longevity are better able to maintain the length of their telomeres,” said Dr. Yousin Suh, senior author of the paper. “And we found that they owe their longevity, at least in part, to advantageous variants of genes involved in telomere maintenance.” More specifically, the researchers found that participants who have lived to a very old age have inherited mutant genes that cause their telomerase-making system to be extra active and able to maintain telomere length more effectively. For the most part, these people were spared age-related diseases such as cardiovascular disease and diabetes, which cause most deaths among elderly people.
Slower Pupil Response Seen in Autistic Children
Recently, University of Missouri researchers have developed a pupil response test that is 92.5 percent accurate in separating children with autism from those with typical development. The scientists used a computerized binocular infrared device, which eye doctors normally use for vision tests, to measure how pupils react to a 100-millisecond flash of light. The results showed that pupils of children diagnosed with autism were significantly slower to respond than those of a control group. “There are several potential mechanisms currently under study,” said Dr. Gang Yao, senior author of the study. “If these results are successfully validated in a larger population, the pupils’ light response (PLR) might be developed into a biomarker that could have clinical implications in early screening for risks of autism. Studies have shown that early intervention will improve these children’s developmental outcome.” Autism is estimated to affect 1 in 150 children today, making it more common than childhood cancer, juvenile diabetes, and pediatric AIDS combined. Despite its widespread effect, autism is not well understood and there are currently no objective medical tests to diagnose it. This new report was published in the November issue of the Journal of Autism and Developmental Disorders. [Press release] [JADD article]
Genes Distinguish Rare Long Survivors of Advanced Melanoma
Although the chances of surviving advanced melanoma are not very good with current therapies, some patients can live for years with melanoma that has spread beyond the skin to other organs. Now it may be possible to identify which patients are more likely to survive by analyzing the activity of hundreds of genes involved in the immune response and gene proliferation, according New York University Langone Medical Center scientists and collaborators. In a new study, the researchers used DNA microarray technology to find 266 genes associated with shorter or longer survival among 38 patients whose melanomas had recurred after being surgically removed. Such genetic information may someday help decide the best course of treatment for patients with advanced disease. “If we could actually understand what was happening in those patients, within the tumor itself, perhaps we’d be able to help them in terms of what therapy they might go on,” said Dr. Nina Bhardwaj, the study’s senior author. The collaborative study, led by graduate student Dusan Bogunovic, provided some hints about the underlying mechanism of melanoma. “We found that patients who survived longer had gene activity consistent with an immune response,” Dr. Bhardwaj said. “Patients who didn’t survive as long didn’t have an up-regulation of those genes, but tended to have higher levels of genes associated with cell proliferation, suggesting that if your cells are growing more actively, the tumor is going to grow faster.” She cautioned, however, that the study must still be validated with a much larger, independent group of patients. The study is to be published online in PNAS during the week of November 9. [Press release]