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Archive - Aug 17, 2014

Epigenetic Breakthrough Bolsters Understanding of Alzheimer's Disease

A team led by researchers at the University of Exeter Medical School and King's College London has uncovered some of the strongest evidence yet that epigenetic changes in the brain play a role in Alzheimer's disease. Epigenetic changes affect the expression or activity of genes without changing the underlying DNA sequence and are believed to be one mechanism by which the environment can interact with the genome. Importantly, epigenetic changes are potentially reversible and may therefore provide targets for the development of new therapies. Globally, more than 26 million people are currently affected by Alzheimer's disease. As this number grows in line with an increasingly aging population, the need to identify new disease mechanisms is more important than ever. Post-mortem examinations have revealed much about how Alzheimer's damages the brain, with some regions, such as the entorhinal cortex, being particularly susceptible, while others, such as the cerebellum, remain virtually unscathed. However, little is yet known about how and why the disease develops in specific brain regions. The current study found that chemical modifications to DNA within the ANK1 gene are strongly associated with measures of neuropathology in the brain. The study, published in Nature Neuroscience, found that people with more Alzheimer's disease-related neuropathology in their brains had higher levels of DNA modifications within the ANK1 gene. The finding was particularly strong in the entorhinal cortex, and also detected in other cortical regions affected by the disease. In contrast, no significant changes were observed in less affected brain regions or blood.

8,000-Year-Old Mutation Key to Human Life at High Altitudes

In an environment where others struggle to survive, Tibetans thrive in the thin air on the Tibetan Plateau (image), with an average elevation of 14,800 feet. A study led by University of Utah scientists is the first to find a genetic cause for the adaptation – a single DNA base pair change that dates back 8,000 years – and demonstrate how it contributes to the Tibetans' ability to live in low oxygen conditions. The study appears online in the journal Nature Genetics on August 17, 2014. "These findings help us understand the unique aspects of Tibetan adaptation to high altitudes, and to better understand human evolution," said Josef Prchal, M.D., senior author of the article and University of Utah professor of internal medicine. The story behind the discovery is equally about cultural diplomacy as it is scientific advancement. Dr. Prchal traveled several times to Asia to meet with Chinese officials, and representatives of exiled Tibetans in India, to obtain permissions to recruit subjects for the study. But he quickly learned that without the trust of Tibetans, his efforts were futile. Wary of foreigners, they refused to donate blood for his research. After returning to the U.S., Dr. Prchal couldn't believe his luck upon discovering that a native Tibetan, Tsewang Tashi, M.D., had just joined the Huntsman Cancer Institute at the University of Utah as a clinical fellow. When Dr. Prchal asked for his help, Dr. Tashi quickly agreed. "I realized the implications of his work not only for science as a whole but also for understanding what it means to be Tibetan," said Dr. Tashi. In another stroke of luck, Dr. Prchal received a long-awaited letter of support from the Dalai Lama. The two factors were instrumental in engaging the Tibetans' trust: more than 90 individuals, both from the U.S. and abroad, volunteered for the study.

Stem-Cell-Based “Disease in a Dish” Studies Add to Evidence That Major Mental Illnesses Are Based on Faulty Neural Wiring

Researchers have long suspected that major mental disorders are genetically-rooted diseases of synapses – the connections between neurons. Now, investigators, supported in part by the National Institutes of Health, have demonstrated in patients' cells how a rare mutation in a suspect gene disrupts the turning on and off of dozens of other genes underlying these connections. "Our results illustrate how genetic risk, abnormal brain development, and synapse dysfunction can corrupt brain circuitry at the cellular level in complex psychiatric disorders," explained Hongjun Song, Ph.D. , of Johns Hopkins University, Baltimore, a grantee of the NIH's National Institute of Mental Health (NIMH), a funder of the study. Dr. Song and colleagues, from universities in the United States, China, and Japan, report on their discovery in Nature, August 17, 2014. "The approach used in this study serves as a model for linking genetic clues to brain development," said NIMH director Thomas R. Insel, M.D. Most major mental disorders, such as schizophrenia, are thought to be caused by a complex interplay of multiple genes and environmental factors. However, studying rare cases of a single disease-linked gene that runs in a family can provide shortcuts to discovery. Decades ago, researchers traced a high prevalence of schizophrenia and other major mental disorders – which often overlap genetically – in a Scottish clan to mutations in the gene DISC1 (Disrupted In Schizophrenia-1). But until now, most of what's known about cellular effects of such DISC1 mutations has come from studies in the rodent brain. To learn how human neurons are affected, Dr. Song's team used a disease-in-a-dish technology called induced pluripotent stem cells (iPSCs). A patient's skin cells are first induced to revert to stem cells.

FDA-Approved Drug Restores Hair in Patients with Alopecia Areata

Researchers at Columbia University Medical Center (CUMC) have identified the immune cells responsible for destroying hair follicles in people with alopecia areata, a common autoimmune disease that causes hair loss, and have tested an FDA-approved drug that eliminated these immune cells and restored hair growth in a small number of patients. The results appear online on August 17, 2014 in Nature Medicine. In the paper, the researchers report initial results from an ongoing clinical trial of the drug, which has produced complete hair regrowth in several patients with moderate-to-severe alopecia areata. Data from three participants appear in the current paper; each patient experienced total hair regrowth within five months of the start of treatment. "We've only begun testing the drug in patients, but if the drug continues to be successful and safe, it will have a dramatic positive impact on the lives of people with this disease," said Raphael Clynes, M.D., Ph.D., who led the research, along with Angela M. Christiano (image), Ph.D., professor in the Departments of Dermatology and of Genetics and Development at CUMC. Alopecia areata is a common autoimmune disease that causes disfiguring hair loss. The disease can occur at any age and affects men and women equally. Hair is often lost in patches on the scalp, but in some patients it also causes loss of facial and body hair. There are no known treatments that can completely restore hair, and patients with the disease experience significant psychological stress and emotional suffering. Scientists have known for decades that hair loss in alopecia areata occurs when cells from the immune system surround and attack the base of the hair follicle, causing the hair to fall out and enter a dormant state. Until now, the specific type of cell responsible for the attack had been a mystery.

Bone Chemistry Reveals Royal Lifestyle of Richard III; Television Coverage Sunday Evening (August 17)

A recent study by the British Geological Survey, in association with researchers at the University of Leicester, has delved into the bone and tooth chemistry of King Richard III and uncovered fascinating new details about the life and diet of Britain's last Plantagenet king. The study, published online on August 16, 2014 in an open-access article in Elsevier's Journal of Archaeological Science indicates a change in diet and location in his early childhood, and in later life, a diet filled with expensive, high status food and drink. This forensic study, the most complete to have been conducted on a medieval monarch, will feature in a documentary, Richard III: The New Evidence, airing on Channel 4 on Sunday August 17, 2014, at 9 pm. Isotope analysis of bone and tooth material from King Richard III has revealed previously unknown details of his early life and the change in his diet when he became King two years and two months before he was killed at the Battle of Bosworth. The research examines the changes in chemistry found in the teeth, the femur, and the rib; all of which develop and rebuild at different stages of life. Isotope measurements that relate to geographical location, pollution, and diet (strontium, nitrogen, oxygen, carbon, and lead) were analyzed in three locations on the skeleton of Richard III. The teeth, which form in childhood, confirmed that Richard had moved from Fotheringay castle in eastern England by the time he was seven. The data suggest that during this time he was in an area of higher rainfall, older rocks, and with a changed diet relative to his place of birth in Northamptonshire.