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Duck-Tolling Retrievers Yield Genetic Clues to Autoimmune Disease

Genome-wide association studies (GWAS) of DNA from Nova Scotia duck-tolling retrievers (NSDTRs) have identified five genetic loci that predispose this breed to an autoimmune disease similar to systemic lupus erythematosis (SLE) in humans. "We know that SLE in humans is caused by many genes and were therefore not surprised to find several risk factors that contribute to the disease in dogs," said Maria Wilbe, a doctoral candidate at the Swedish University of Agricultural Sciences in Uppsala and lead author of the article. The results provide clues as to where researchers might look for corresponding SLE-related disease genes in humans. The results also demonstrate why dogs can serve as highly useful and efficient models for identifying genes for multigenic diseases and related pathways in humans. "Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases," said Dr. Hannes Lohi, of the University of Helsinki and Folkhälsan Research Center in Finland, a co-leader of the project. As the result of two genetic bottlenecks—domestication from the wolf and breed formation--the members of any particular dog breed tend to share much longer stretches of DNA with each other than do members of heterogeneous human populations or even members of relatively homogeneous human sub-populations.

Electron Tunneling-Based DNA Reader Developed

An electron tunneling-based technology for accurately reading the base sequence of DNA molecules has been developed by an Arizona State University (ASU) research team headed by Dr. Stuart Lindsay. This is the first tunneling-based DNA reader that can discriminate among DNA's four bases in one tunnel gap. If the technology can be perfected, DNA sequencing could be performed much more quickly than by current technologies, and at a fraction of the cost. The ASU work was supported, in part, by funding from the National Human Genome Research Institute’s “$1000 Genome” initiative, which is intended to make DNA genome sequencing as widespread as a routine medical checkup, thus helping to usher in the era of “personalized medicine.” The new technology relies on a scanning tunneling microscope and an atomic force microscope, to make its measurements. The microscopes have a delicate electrode tip that is held very close to the DNA sample. In its current innovation over earlier versions, Dr. Lindsay's team made two gold electrodes, one on the end of the microscope probe, and another on the surface, that had their tiny ends chemically modified to attract and catch the DNA between a gap, like a pair of chemical tweezers. The gap between these functionalized electrodes had to be adjusted to find the hydrogen-bonding sweet spot, so that when a single chemical base of DNA passed through a tiny, 2.5-nanometer opening between the two electrodes, it momentarily sticks to the electrodes and a small increase in the current is detected. Any smaller, and the molecules would be able to bind in many configurations, confusing the readout; any larger and smaller bases would not be detected. "What we did was to narrow the number of types of bound configurations to just one per DNA base," said Dr. Lindsay.

First Genes for Stuttering Discovered

Scientists have identified the first three genes ever associated with the phenomenon of stuttering. All three genes are involved in the day-to-day process by which cellular components in key regions of the brain are broken down and recycled by processing in a cell structure called the lysosome. "For hundreds of years, the cause of stuttering has remained a mystery for researchers and health care professionals alike, not to mention people who stutter and their families," said Dr. James F. Battey, Jr., director of the NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD), who was not directly involved in the research. "This is the first study to pinpoint specific gene mutations as the potential cause of stuttering, a disorder that affects three million Americans, and by doing so, might lead to a dramatic expansion in our options for treatment." Stuttering is a speech disorder in which a person repeats or prolongs sounds, syllables, or words, disrupting the normal flow of speech. It can severely hinder communication and a person's quality of life. Most children who stutter will outgrow the problem, although many do not; roughly 1 percent of adults stutter worldwide. Current therapies for adults who stutter have focused on such strategies as reducing anxiety, regulating breathing and rate of speech, and using electronic devices to help improve fluency. Former college and NBA basketball star Bill Walton (photo) suffered from a stuttering problem that he largely overcame and he has subsequently gone on to become a successful TV announcer. Stuttering tends to run in families, and researchers have long suspected a genetic component. Previous studies of stuttering in a group of families from Pakistan have been performed by Dr.

Genome of Ancient Human Is Sequenced

Using sophisticated DNA sequencing technology and powerful data analysis tools, an international team has succeeded in sequencing approximately 80 percent of the genome of a 4,000-year-old sample from a man who lived in Greenland and belonged to an extinct culture (Saqqaq) that was the first to settle in the New World Arctic. The sequencing was achieved using DNA obtained from a permafrost-preserved tuft of hair. According to the research team, led by Dr. Eske Willerslev and his graduate student Morten Rasmussen at the University of Copenhagen’s Centre of Excellence in GeoGenetics, this marks the first time that a detailed reconstructed genome of an ancient human has been published. The scientists have named the ancient human "Inuk," which means "man" or "human" in Greenlandic. The genome sequence serves as a blueprint that scientists can use to give a description of how the pre-historic Greenlander looked--including his tendency to baldness, dry earwax, brown eyes, dark skin, the blood type A+, shovel-shaped front teeth, and that he was genetically adapted to cold temperatures, and to what extent he was predisposed to certain illnesses. This is important as, aside from four small pieces of bone and hair, no human remains have been found of the first people that settled the New World Arctic. Dr. Willerslev's team was also able to determine that Inuk's ancestors crossed into the New World from north-eastern Siberia between 4,400 and 6,400 years ago in a migration wave that was independent of those of Native Americans and Inuit ancestors. Thus, Inuk and his people left no dependents behind among contemporary indigenous people of the New World. “Our findings can be of significant help to archaeologists and others as they seek to determine what happened to people from extinct cultures,” Dr. Willerslev said.

Owls Chattier on Moonlit Nights

An international team of scientists from Spain, Finland, and Portugal recently discovered that eagle owls (Bubo bubo) communicate with each other using a patch of white throat plumage that is repeatedly exposed during each call and is only visible during vocal displays. The scientists found that the owls use moonlight to increase the conspicuousness of this visual signal during their call displays. Call displays were found to be directly influenced by the amount of moonlight, with silent nights being more frequent during periods with no moonlight versus those with moonlight. Furthermore, high numbers of calling bouts were more frequent at moonlight. Finally, call posts were located on higher positions on moonlit nights. The researches said that their results support the idea that moon phase affects the visual signaling behavior of this species, and provide a starting point for examination of this method of communication by nocturnal species. This work was reported on January 20, 2010, in PLoS ONE. [PLoS ONE article]

Bees Prefer Nicotine and Caffeine in Nectar

Bees prefer nectar with small amounts of nicotine and caffeine over nectar that does not contain these substances at all, according to results of a recent study from the University of Haifa in Israel. “This could be an evolutionary development intended, as in humans, to make the bee addicted,” stated Dr. Ido Izhaki, one of the researchers who conducted the study. The researchers emphasized, however, that their study has proved a preference, not an addiction, and they are currently conducting additional studies to determine if bees do indeed become addicted to nicotine and caffeine. Flower nectar is primarily composed of sugars, which provide energy for the potential pollinators. But the floral nectar of some plant species also includes small quantities of substances known to be toxic, such as caffeine and nicotine. Nicotine is found naturally in floral nectar at a concentration of up to 2.5 milligrams per liter, primarily in various types of tobacco trees. Caffeine is found at concentration levels of 11-17.5 milligrams per liter, mostly in citrus flowers. In the nectar of grapefruit flowers, however, caffeine is present in much higher concentrations, reaching 94.2 milligrams per liter. In order to examine whether bees prefer the nectar containing caffeine and nicotine, the researchers offered artificial nectar that contained various natural sugar levels and various levels of caffeine and nicotine, alongside “clean” nectar that included sugar alone. The caffeine and nicotine concentrations ranged from the natural levels in floral nectar up to much higher concentrations than found in nature. The results showed that bees clearly prefer nectar containing nicotine and caffeine over the “clean” nectar. The preferred nicotine concentration was 1 milligram per liter, similar to that found in nature.

Experimental Drug Targets Cognitive Defects in Huntington’s Disease

The experimental drug dimebon (latrepirdine), being developed for patients with Alzheimer's disease and long used as a hay fever treatment in the former Soviet Union, appears well tolerated and may improve cognition (thinking, learning, memory skills) among individuals with Huntington's disease, according to results of an early-stage clinical trial. "This is the first clinical trial that has focused on what is perhaps the most disabling aspect of the disease," said University of Rochester Medical Center neurologist Dr. Karl Kieburtz, the lead author of the study. "While more investigation needs to be done, these results are encouraging and show, for the first time, a statistically significant benefit in terms of improved cognitive function in patients with Huntington's disease." The dominantly inherited genetic disease, which killed famous American folk singer Woody Guthrie, is a progressive neurodegenerative disorder that impacts movement, behavior, and cognition, and generally results in death within 20 years of the disease's onset. The disease steadily erodes a person's memory and his/her ability to think and learn. Over time, this cognitive impairment contributes to the loss of the ability to work and perform the activities of daily life. There are no treatments currently available that effectively alter the course of the disease or improve cognition. The only approved therapy for Huntington's disease, tetrabenazine, treats only motor symptoms and does not alter the course of the disease or prevent cognitive decline. Abnormalities in mitochondria have been implicated in the development of Huntington's disease and dimebon stabilizes and improves mitochondrial function.

Existing Drug May Be Useful in Treating 37 Million with River Blindness

Researchers at The Scripps Research Institute, together with colleagues, have reported that a drug (closantel) currently used as the standard treatment for sheep and cattle infected with liver fluke may be useful in treating river blindness, a tropical disease that is the world's second leading infectious cause of blindness for humans (the leading cause is trachoma, caused by infection with Chlamydia trachomatis). Dr. Kim Janda, an author of the new report, said that there is an urgency to fighting the infection that leads to river blindness, which is also known as onchocerciasis. Despite several eradication efforts, the disease affects more than 37 million people in Africa, Central and South America, and Yemen. "Victims of onchocerciasis suffer severe skin lesions, musculoskeletal pain, and various stages of blindness," said Dr. Janda, adding that patients also experience decreased body mass index, decreased work productivity, and social stigmatization. The new research shows that clostanel has the potential to inhibit the molting process of the parasite (Onchocerca volvulus) that causes river blindness. "We think this finding holds terrific potential for the treatment of river blindness, one of 13 recognized neglected tropical diseases," said Dr. Christian Gloeckner, the first author of the study. River blindness is caused by thread-like filarial nematode worms, O. volvulus, which are transmitted among humans through the bite of a black fly. The worms then multiply and spread throughout the body. When the worms die, they cause a strong immune system response that can destroy surrounding tissue, including that of the eye. Currently, the only drug available for mass treatment of river blindness is ivermectin, and it now appears that resistance to that drug is emerging.

First Genetic Variants Associated with Biological Aging in Humans

Scientists announced that they have identified, for the first time, definitive genetic variants associated with biological aging, as indicated by mean telomere length, in humans. An international team, led by researchers at the University of Leicester and King’s College London, analyzed more than 500,000 genetic variations across the entire human genome to identify the aging-related variants which are located near a gene called TERC, a gene that is known to play a role in telomere length. Telomeres are capping-like structures located at the tips of chromosomes. “Individuals are born with telomeres of certain length and in many cells telomeres shorten as the cells divide and age,” said Dr. Nilesh Samani, a co-leader of the project. “Telomere length is therefore considered a marker of biological aging." Dr. Samani explained that there are two forms of aging--chronological aging, i.e., how old you are in years, and biological aging whereby the cells of some individuals are older (or younger) than suggested by their chronological age. “In this study,” Dr. Samani said, “what we found was that those individuals carrying a particular genetic variant had shorter telomeres, i.e., looked biologically older. Given the association of shorter telomeres with age-associated diseases, the finding raises the question whether individuals carrying the variant are at greater risk of developing such diseases." Dr. Tim Spector, also a co-leader of the project, noted, “What our study suggests is that some people are genetically programmed to age at a faster rate. The effect was quite considerable in those with the variant, equivalent to between 3-4 years of 'biological aging’ as measured by telomere length loss.

Serotonin Inhibitor Appears to Cure Osteoporosis in Rodents

An investigational drug that inhibits serotonin synthesis in the gut effectively cured osteoporosis in mice and rats when administered orally once a day, according to a report by an international team led by researchers from the Columbia University Medical Center. "New therapies that inhibit the production of serotonin in the gut have the potential to become a novel class of drugs to be added to the therapeutic arsenal against osteoporosis," said Dr. Gerard Karsenty, Chair of the Department of Genetics and Development at the Columbia University College of Physicians and Surgeons, and a senior author of the report. "With tens of millions of people worldwide affected by this devastating and debilitating bone loss, there is an urgent need for new treatments that not only stop bone loss, but also build new bone. Using these findings, we are working hard to develop this type of treatment for human patients." The current study followed up on an earlier report, in Cell (November 28, 2008), by Dr Karsenty’s group and colleagues, showing that serotonin released by the gut inhibits bone formation, and that regulating the production of serotonin within the gut affects the formation of bone. Prior to that discovery, serotonin was primarily known as a neurotransmitter acting in the brain. Yet, 95 percent of the body's serotonin is found in the gut, where its major function is to inhibit bone formation (the remaining 5 percent is in the brain, where it regulates mood, among other critical functions). By turning off the intestine's release of serotonin, the team was able, in the new study, to cure osteoporosis in rodents that had undergone menopause. The results demonstrated that osteoporosis was prevented from developing, or when already present, could be fully cured.

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