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Archive - Aug 2014

August 19th

New Signaling Mode ID’d for Brassinosteroid Plant Hormones

Plants can adapt extremely quickly to changes in their environment. Hormones, chemical messengers that are activated in direct response to light and temperature stimuli help them achieve this. Plant steroid hormones similar to human sex hormones play a key role here. Online on August 19, 2014 in Nature Communications, scientists describe a new signaling mode for the brassinosteroid class of hormones. Plants are superior to humans and animals in a number of ways. They have an impressive ability to regenerate, which enables them to regrow entire organs. After being struck by lightning, for example, a tree can grow back its entire crown. But there is one major downside to life as a plant: They are quite literally rooted to the habitats in which they live and therefore completely at the mercy of the elements. In response to this dilemma, plants have developed mechanisms that enable them to rapidly adapt their growth and development to changes. Plant hormones are important enablers of this flexibility. Brassinosteroids play a key role here. These hormones have an effect at the lowest concentrations; they regulate cell elongation and division and are active throughout the entire life cycle of a plant. A team of researchers from Technische Universität München (TUM) and the University of Vienna have now mapped a new signaling mode for brassinosteroids. When brassinosteroids bind to a receptor on a cell wall, they trigger a multi-level cascade of reactions that regulates the activity of the CESTA (CES) transcription factor. Transcription factors bind to the DNA in a cell's nucleus and are capable of activating genes that change the protein composition in the cell.

August 18th

Non-Coding RNA Involved in Regulating Internal Body Clocks

Researchers at the University of Teas (UT) Southwestern Medical Center have found a new way that internal body clocks are regulated by a type of molecule known as long non-coding RNA. The internal body clocks, called circadian clocks, regulate the daily "rhythms" of many bodily functions, from waking and sleeping to body temperature and hunger. They are largely "tuned" to a 24-hour cycle that is influenced by external cues such as light and temperature. "Although we know that long non-coding RNAs are abundant in many organisms, what they do in the body, and how they do it, has not been clear so far," said Dr. Yi Liu (image, courtesy of UT Southwestern Medical Center), Professor of Physiology. "Our work establishes a role for long non-coding RNAs in 'tuning' the circadian clock, but also shows how they control gene expression." Determining how circadian clocks work is crucial to understanding several human diseases, including sleep disorders and depression in which the clock malfunctions. The influence of a functional clock is evident in the reduced performance of shift workers and the jet lag felt by long-distance travelers. Dr. Liu and his team were able to learn more about the circadian rhythms by studying model systems involving the bread mold, Neurospora crassa. The researchers found that the expression of a clock gene named frequency (frq) is controlled by a long non-coding RNA named qrf (frq backwards) − an RNA molecule that is complementary, or antisense, to frq. Unlike normal RNA molecules, qrf does not encode a protein, but it can control whether and how much frq protein is produced. Specifically, qrf RNA is produced in response to light, and can then interfere with the production of the frq protein. In this way, qrf can "re-set" the circadian clock in a light-dependent way.

Breakthrough Technique Developed for Massive Parallel Genomic Analysis of Long DNA Molecules

Researchers from McGill University and the Génome Québec Innovation Centre have achieved a technical breakthrough that should result in speedier diagnosis of cancer and various pre-natal conditions. The key discovery, which was described online on August 4, 2014 in PNAS, lies in a new tool developed by Professors Sabrina Leslie and Walter Reisner of McGill’s Physics Department and their collaborator Dr. Rob Sladek of the Génome Québec Innovation Centre. The new tool allows researchers to load long strands of DNA into a tunable nanoscale imaging chamber in ways that maintain the strands’ structural identity and under conditions that are similar to those found in the human body. This newly developed “Convex Lens-Induced Confinement” (CLIC) will permit researchers to rapidly map large genomes, while at the same time clearly identifying specific gene sequences from single cells with single-molecule resolution, a process that is critical to diagnosing diseases like cancer. CLIC, the new tool, can sit on top of a standard inverted fluorescence microscope used in a university lab. The innovative aspect of CLIC lies in the fact that it allows strands of DNA to be loaded into the imaging chamber from above, a process which allows the strands of DNA to maintain their integrity. Existing tools used for genomic analysis rely on side-loading DNA under pressure into nanochannels in the imaging chamber, a practice that breaks the DNA molecules into small pieces, making it a challenge to reconstruct the genome. “It’s like squeezing many soft spaghetti noodles into long narrow tubes without breaking them,” explains Professor Leslie as she describes what it is like to use CLIC.

Zone in with Zon—Could Current Ebola Outbreak Have Been Prevented?

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, dated August 18, 2014, and published by TriLink BioTechnologies of San Diego, discusses the topic of whether the current Ebola outbreak might have been prevented. In the course of his blog, Dr. Zon provides a wealth of information on Ebola virus and the current outbreak, as well as on various efforts to develop vaccines and treatments/drugs. He concludes that inadequate advocacy and funding, rather than inadequate science is at the root of the current inability to effectively combat the disease. As background, he cited the following statements on Ebola found on the WHO website: Ebola viral disease (EVD) is a severe, often fatal illness in humans; EVD outbreaks have a case fatality rate of up to 90%; EVD outbreaks occur primarily in remote villages in Central and West Africa, near tropical rainforests; the virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission, with infection resulting from direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and indirect contact with environments contaminated with such fluids; EVD is a severe acute viral illness often characterized by the sudden onset of fever, intense weakness, muscle pain, headache, and sore throat, followed by vomiting, diarrhea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding; laboratory findings include low white blood cell and platelet counts and elevated liver enzymes; severely ill patients require intensive supportive care; and no licensed specific treatment or vaccine is available for use in people or animals. Dr.

August 17th

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.

August 16th

Science Disputes Magpie Folklore

Magpies are not attracted to shiny objects and do not routinely steal small trinkets such as jewelry, according to a new study. In European culture, it is widely accepted that magpies (Pica pica) are the pilferers of the bird kingdom, unconditionally attracted to sparkly things and prone to pinching them for their nests, almost as a compulsion. But psychologists at the Centre for Research in Animal Behaviour (CRAB) at the University of Exeter are now countering this folklore, having shown that the species is actually frightened of new and unfamiliar objects, rather than attracted to them. The researchers carried out a series of experiments with both a group of magpies that had come from a rescue center, and wild magpies from the grounds of the University. Under carefully monitored conditions, the birds were exposed to both shiny and non-shiny items, and their reactions recorded. Dr. Toni Shephard, lead author of the study, said: "We did not find evidence of an unconditional attraction to shiny objects in magpies. Instead, all objects prompted responses indicating neophobia – fear of new things – in the birds. We suggest that humans notice when magpies occasionally pick up shiny objects because they believe the birds find them attractive, while it goes unnoticed when magpies interact with less eye-catching items. It seems likely, therefore, that the folklore surrounding them is a result of cultural generalization and anecdotes rather than evidence." The field experiment was conducted at eight sites on the University of Exeter campus where magpies are accustomed to regular human activity, allowing observations to be conducted in close proximity. The test objects were shiny metal screws, small foil rings, and a small rectangular piece of aluminum foil.