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Archive - Aug 8, 2014

Uric Acid May Be New Culprit in Metabolic Syndrome

A new study suggests uric acid may play a role in causing metabolic syndrome, a cluster of risk factors that increases the risk of heart disease and type 2 diabetes. Uric acid is a normal waste product removed from the body by the kidneys and intestines and released in urine and stool. Elevated levels of uric acid are known to cause gout, an accumulation of the acid in the joints. High levels also are associated with the markers of metabolic syndrome, which is characterized by obesity, high blood pressure, elevated blood sugar, and high cholesterol. But it has been unclear whether uric acid itself is causing damage or is simply a byproduct of other processes that lead to dysfunctional metabolism. Published online on August 7, 2014 in Nature Communications, the new research at Washington University School of Medicine in St. Louis suggests excess uric acid in the blood is no innocent bystander. Rather, it apipears to be a culprit in disrupting normal metabolism. “Uric acid may play a direct, causative role in the development of metabolic syndrome,” said first author Brian J. DeBosch, M.D., Ph.D., an instructor in pediatrics. “Our work showed that the gut is an important clearance mechanism for uric acid, opening the door to new potential therapies for preventing or treating type 2 diabetes and metabolic syndrome.” Recent research by the paper’s senior author, Kelle H. Moley, M.D., the James P. Crane Professor of Obstetrics and Gynecology, and her collaborators has shown that a protein called GLUT9 is an important transporter of uric acid. Dr. DeBosch, a pediatric gastroenterologist who treats patients at St. Louis Children’s Hospital, studied mice to learn what happens when GLUT9 stops working in the gut, essentially blocking the body’s ability to remove uric acid from the intestine.

Leukemia Is Prominent in Down Syndrome

Children affected by trisomy 21 (or Down syndrome) are 50 to 500 times more likely to develop leukemia than other children. A group of geneticists working in the Faculty of Medicine at the University of Geneva (UNIGE) focused for many years on the genetic characteristics of Down syndrome. They have sequenced the exome, a specific part of our genome, in a cohort of patients affected both by Down Syndrome and Acute Lymphoblastic Leukemia (DS-ALL), a type of cancer relative to the cells of the immune system in the bone marrow. They were able to sketch an outline of the "genetic identity card" of this disease. They found that RAS, an important oncogene in many cancers, is involved in the tumorigenesis of one third of DS-ALL cases. This work was published online on August 8, 2014 in Nature Communications. The senior author was Dr. Stylianos Antonarakis. [Press release] [Nature Communications abstract]

Living Organisms Found in Oil

Miniscule water droplets in oil provide a habitat for a number of microorganisms. Scientists from the Helmholtz Zentrum München in Germany have discovered that these communities of microorganisms play a part in breaking down the oil and have published their findings online on August 8, 2014 in the renowned journal Science. Oil might not, at first sight, seem like an inhabited terrain. Within the oil, however, are tiny, suspended water droplets. “Inside them we found complex microbial communities, which play an active part in oil degradation in situ,” says first author Professor Rainer Meckenstock (image, credit: HMGU)) from the Helmholtz Zentrum München (HMGU). Previously, it was assumed that microbial oil degradation only occurred at the oil-water interface. The team headed by Professor Meckenstock from the Institute of Groundwater Ecology and the Department of Biogeochemistry at HMGU, along with international colleagues from the Technical University of Berlin, Washington State University (USA) and the University of West Indies (Trinidad and Tobago) have now been able to demonstrate that degradation processes also occur within the oil phase. “Degradation changes the chemical composition of the oil and ultimately leads to the formation of viscous bitumen, as in oil sands, “ Professor Meckenstock explains. “Our data thus supplies important information about oil quality and is therefore essential for the industry that surrounds what is still the most important energy source worldwide.” Although the breakdown of chemical compounds (hydrocarbons) damages the oil, this can be highly desirable in contaminated groundwater. The microorganisms, which have adapted to an extremely toxic habitat, could pave the way for new concepts for cleaning up pollution in groundwater.

Scientists Unravel Mystery of Brain Cell Growth

In the developing brain, special proteins that act like molecular tugboats push or pull on growing nerve cells, or neurons, helping them navigate to their assigned places amidst the brain’s wiring. How a single protein can exert both a push and a pull force to nudge a neuron in the desired direction is a longstanding mystery that has now been solved by scientists from Dana-Farber Cancer Institute and collaborators in Europe and China. Jia-huai Wang, PhD, who led the work at Dana-Farber and Peking University in Beijing, is a corresponding author of a report published in the August 7, 2014 online edition of Neuron that explains how one guidance protein, netrin-1 (see image), can either attract or repel a brain cell to steer it along its course. Dr. Wang and co-authors at the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, used X-ray crystallography to reveal the three-dimensional atomic structure of netrin-1 as it bound to a docking molecule, called DCC, on the axon of a neuron. The axon is the long, thin extension of a neuron that connects to other neurons or to muscle cells. As connections between neurons are established – in the developing brain and throughout life – axons grow out from a neuron and extend through the brain until they reach the neuron they are connecting to. To choose its path, a growing axon senses and reacts to different molecules it encounters along the way. One of these molecules, netrin-1, posed an interesting puzzle: an axon can be both attracted to and repelled from this cue. The axon’s behavior is determined by two types of receptors on its tip: DCC drives attraction, while UNC5 in combination with DCC drives repulsion. “How netrin works at the molecular level has long been a puzzle in neuroscience field,” said Dr.

Non-Standard MicroRNA Silencing Interactions Appear More Prevalent in Human Bology Than Previously Believed, Suggesting More Complex Roles for MicroRNAs

MicroRNAs (miRNAs) regulate protein-coding gene abundance levels by interacting with the 3´ end of various messenger RNAs. Each target site matches the first few nucleotides of the targeting miRNA, the so called "seed" region, and this interaction leads to the degradation of the target or prevents its translation into amino acids. This dogma has led researchers to largely look for perfect base-pair matching of the "seed" region among candidate targets. New research published today (August 8, 2014) in Nature's open-access journal Scientific Reports suggests that non-canonical binding may be much more prevalent than previously expected, revealing a much broader array of targets for miRNAs that includes both regions that code for proteins and others that do not. "The findings may help explain why the microRNA field has run into difficulty when translating these powerful molecules into therapies for diseases ranging from cancer to diabetes," says senior author Isidore Rigoutsos, Ph.D., Director of the Computational Medicine Center in the Sidney Kimmel Medical College at Thomas Jefferson University. "There is still so much we don't know about how miRNAs work in the body." The research add to previous reports by the Jefferson group and by others demonstrating that the miRNA "targetome" – the spectrum of RNAs that miRNAs attack – is much more complex than previously anticipated. "Our study shows that even conserved miRNAs that we share with animals and insects can have very different behavior across organisms and even across different tissues in our bodies," says Dr. Rigoutsos.