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Archive - Mar 2013

March 10th

Selectively Manipulating Protein Modifications

Protein activity is strictly regulated. Incorrect or poor protein regulation can lead to uncontrolled growth and thus cancer or chronic inflammation. Members of the Institute of Veterinary Biochemistry and Molecular Biology from the University of Zurich have identified enzymes that can regulate the activity of medically important proteins. Their discovery enables these proteins to be manipulated very selectively, opening up new treatment methods for inflammations and cancer. The work was published online on March 10, 2013 in Nature Structural & Molecular Biology. A related article was also published online at the same time in the same journal. For a healthy organism, it is crucial for proteins to be active or inactive at the right time. The corresponding regulation is often based on a chemical modification of the protein structure: Enzymes attach small molecules to particular sites on a protein or remove them, thereby activating or deactivating the protein. Members of the Institute of Veterinary Biochemistry and Molecular Biology from the University of Zurich, in collaboration with researches at other institutes, have now discovered how the inactivation of a protein, which is important for medicine, can be reversed. An important protein modification is ADP-ribosylation, which is involved in certain types of breast cancer, cellular stress reactions, and gene regulation. So-called ADP-ribosyltransferases attach the ADP ribose molecule to proteins, thereby altering their function. In recent years, many ADP-ribosyltransferases have been discovered that can convey single or several ADP-riboses to different proteins. Enzymes that can remove these riboses again, however, are less well known. Professor Michael Hottiger's team of researchers has now identified a new group of such ADP-ribosylhydrolases.

Telomere Length in Heart Disease Patients Can Predict Life Expectancy

Can the length of strands of DNA in patients with heart disease predict their life expectancy? Researchers from the Intermountain Heart Institute at Intermountain Medical Center in Salt Lake City, who studied the DNA of more that 3,500 patients with heart disease, say yes it can. In the new study, presented Saturday, March 9, 2013, at the American College of Cardiology's Annual Scientific Session in San Francisco, the researchers were able to predict survival rates among patients with heart disease based on the length of strands of DNA found at the ends of chromosomes known as telomeres—the longer the patient's telomeres, the greater the chance of living a longer life. The study is one of 17 studies from the Intermountain Heart Institute at Intermountain Medical Center that are being presented at the scientific session, which is being attended by thousands of cardiologists and heart experts from around the world. Previous research has shown that telomere length can be used as a measure of age, but these expanded findings suggest that telomere length may also predict the life expectancy of patients with heart disease. Telomeres protect the ends of chromosome from becoming damaged. As people get older, their telomeres get shorter until the cell is no longer able to divide. Shortened telomeres are associated with age-related diseases such as heart disease or cancer, as well as exposure to oxidative damage from stress, smoking, air pollution, or conditions that accelerate biologic aging. "Chromosomes by their nature get shorter as we get older," said John Carlquist, Ph.D., director of the Intermountain Heart Institute Genetics Lab. "Once they become too short, they no longer function properly, signaling the end of life for the cell. And when cells reach this stage, the patient's risk for age-associated diseases increases dramatically." Dr.

Maternal Care: How Mother Deer Protect Their Future Leaders

Do mothers invest more care in their sons if they believe their child is destined to be a king, president, or a high-powered leader? The answer is definitively yes – as long as those mothers and their sons happen to have hooves. New research from Brigham Young University (BYU) in Utah reports that, just like the classic tale of Bambi, females from the deer family are more likely to invest more in the survival and health of their male offspring if there is a good chance those sons will become a “Great Prince of the Forest.” “Our research demonstrates clearly that a mother’s investment in her offspring was evident during adulthood, even though offspring live independently of their mothers from a very young age,” said Dr. Brock McMillan, associate professor of wildlife ecology at BYU. The comprehensive study of deer and elk from the Intermountain West found that the most dominant males at the time of death were those who were born into the most favorable maternal conditions 5 to 15 years before. While favorable maternal conditions are largely tied to the health of the expectant mother, there are additional elements at play. A mother’s investment happens both in the womb and during the first few months of life. During those early stages of life, mothers take care to provide more excellent nourishment through lactation as well as better habitats for the baby. “Male deer and elk live independently of their mothers for several years in highly variable environments,” Dr. McMillan said. “They live through severe winters with deep snow and little to eat, dry summers with poor quality food, and years of injuries and ailments associated with everyday life.

March 9th

Genetic Defect Affecting Mechanosensitive Ion Channel Is Cause of a Hereditary Anemia

A genetic mutation that alters the kinetics of an ion channel in red blood cells has been identified as the cause of a hereditary anemia, according to a paper published online on March 4, 2013 in PNAS by University at Buffalo (UB) scientists and colleagues. The research team was led by Frederick Sachs, Ph.D., State University of New York Distinguished Professor in the UB Department of Physiology and Biophysics, who discovered in the 1980s that some ion channels are mechanosensitive, that is, they convert mechanical stress into electrical or biochemical signals. The findings of the new study are significant, Dr. Sachs says, because it is the first time that defects in a mechanosensitive ion channel have been implicated as the cause of a disease. “We found that the mutations in the gene that codes for the ion channel called PIEZO1 causes the channel to stay open too long, causing an ion leak in red cells,” explains Dr. Sachs. “Calcium and sodium enter, and potassium leaves, and that affects the ability of the red cell to regulate its volume. The cells become dehydrated and can break open, releasing their hemoglobin into the blood, and causing symptoms, such as the shortness of breath seen in anemic patients.” The anemia that results from the mutations in PIEZO1 is called familial xerocytosis, a mild to moderate form of anemia. The ion channel, PIEZO1, is about 10 nanometers across, and it increases its dimensions significantly upon opening; that change in dimensions is what is responsible for its mechanical sensitivity. Mechanosensitive ion channels are likely to play a role in many diseases, because all cells are mechanically sensitive. Dr.

Temperature-Controlled Nanopores May Enable Detailed Blood Analysis

Tiny biomolecular chambers called nanopores that can be selectively heated may help doctors diagnose disease more effectively if recent research by a team at the National Institute of Standards and Technology (NIST), Wheaton College, and Virginia Commonwealth University (VCU) proves effective. Though the findings may be years away from application in the clinic, they may one day improve doctors' ability to search the bloodstream quickly for indicators of disease—a longstanding goal of medical research. The work was published online on January 24, 2013 in the Journal of the American Chemical Society. The team has pioneered work on the use of nanopores—tiny chambers that mimic the ion channels in the membranes of cells—for the detection and identification of a wide range of molecules, including DNA. Ion channels are the gateways by which the cell admits and expels materials like proteins, ions, and nucleic acids. The typical ion channel is so small that only one molecule can fit inside at a time. Previously, team members inserted a nanopore into an artificial cell membrane, which they placed between two electrodes. With this setup, they could drive individual molecules into the nanopore and trap them there for a few milliseconds, enough to explore some of their physical characteristics. "A single molecule creates a marked change in current that flows through the pore, which allows us to measure the molecule's mass and electrical charge with high accuracy," says Dr. Joseph Reiner, a physicist at VCU who previously worked at NIST. "This enables discrimination between different molecules at high resolution.

March 8th

Hypocretin Peptide May Play Role in Human Happiness

The neurochemical changes underlying human emotions and social behavior are largely unknown. Now though, for the first time in humans, scientists at UCLA have measured the release of a specific peptide, a neurotransmitter called hypocretin, which greatly increased when subjects were happy, but decreased when they were sad. The finding suggests that boosting hypocretin could elevate both mood and alertness in humans, thus laying the foundation for possible future treatments of psychiatric disorders like depression by targeting measureable abnormalities in brain chemistry. In addition, the study measured for the first time the release of another peptide, this one called melanin concentrating hormone, or MCH. Researchers found that its release was minimal during waking periods, but greatly increased during sleep, suggesting a key role for this peptide in making humans sleepy. The study was published online on March 5, 2013 in Nature Communications. "The current findings explain the sleepiness of narcolepsy, as well as the depression that frequently accompanies this disorder," said senior author Dr. Jerome Siegel, a professor of psychiatry and director of the Center for Sleep Research at UCLA's Semel Institute for Neuroscience and Human Behavior. "The findings also suggest that hypocretin deficiency may underlie depression from other causes." In 2000, Dr. Siegel's team published findings showing that people suffering from narcolepsy, a neurological disorder characterized by uncontrollable periods of deep sleep, had 95 percent fewer hypocretin nerve cells in their brains than those without the illness. That study was the first to show a possible biological cause of the disorder. Because depression is strongly associated with narcolepsy, Dr.

Signaling Molecule May Help Stem Cells Make Bone Despite Age, Disease

A signaling molecule that helps stem cells survive in the naturally low-oxygen environment inside the bone marrow may hold clues to helping the cells survive when the going gets tougher with age and disease, researchers report. They hope their findings, reported online on March 5, 2013 in the open-access journal PLOS ONE, will result in better therapies to prevent bone loss in aging and enhance success of stem cell transplants for a wide variety of conditions from heart disease to cerebral palsy and cancer. The scientists found that inside the usual, oxygen-poor niche of mesenchymal stem cells, stromal cell-derived factor-1, or SDF-1, turns on a survival pathway called autophagy that helps the cells stay in place and focused on making bone, said Dr. William D. Hill, stem cell researcher at the Medical College of Georgia (MCG) at Georgia Regents University (GRU) and the study's corresponding author. Unfortunately, with age or disease, SDF-1 appears to change its tune, instead reducing stem cells' ability to survive and stay in the bone marrow, said Samuel Herberg, GRU graduate student and the study's first author. Additionally, cells that do stay put may be less likely to make bone and more likely to turn into fat cells in the marrow. The researchers believe it's the changes in the normal environment that come with age or illness, including diminished nutrition, that prompt SDF-1's shifting role. "You put new cells in there and, all of the sudden, you put them in a neighborhood where they are being attacked," Dr. Hill said.

Algae Tolerant of Extreme Environments Offer Wal-Mart of Genomic Material

Most organisms would die in the volcanic sulfur pools of Yellowstone and Mount Etna. Robust simple algae call these extreme environments home, and their secrets to survival could advance human medicine and bioremediation. Dr. Mike Garavito, Michigan State University (MSU) professor of biochemistry and molecular biology was part of a research team that revealed how primitive red algae use horizontal gene transfer, in essence stealing useful genes from other organisms to evolve and thrive in harsh environments. Their study, published in the March 8, 2013 issue of Science, shows that the algae’s ability to adapt to a hot and extremely acidic environment ¬lies in part in their membrane proteins. “The algae’s membrane proteins are biologically quite interesting because they’re receptors and transporters, the same classes of proteins that play key roles in energy metabolism and human immune response,” said Dr. Garavito. “This has applications in human medicine because virtually all of the important pathways that contribute to disease treatment involve membrane proteins.” What makes the algae’s membrane proteins attractive as a model for humans is their robustness. Other traditional candidates, such as yeast, insect cell cultures, and slime mold, are fragile. The hardy algae give researchers extra time to manipulate and examine their membrane proteins. Dr. Garavito was part of a team of researchers led by Dr. Andreas Weber, former MSU researcher now at Heinrich-Heine-Universitat Dusseldorf (Germany). While at MSU, Dr. Weber led a team in first sequencing the algae, one of the first major genome sequencing projects at MSU. “Dr. Weber knew that this would be a good organism from which to harvest a wide variety of genes that could be potential models for those involved in human health and disease,” said Dr.

Sequencing Study of Dust Mites Demonstrates Reversible Evolution

In evolutionary biology, there is a deeply rooted supposition that you can't go home again: Once an organism has evolved specialized traits, it can't return to the lifestyle of its ancestors. There's even a name for this pervasive idea. Dollo's law states that evolution is unidirectional and irreversible. But this "law" is not universally accepted and is the topic of heated debate among biologists. Now a research team led by two University of Michigan (U-M) biologists has used a large-scale genetic study of the lowly house dust mite to uncover an example of reversible evolution that appears to violate Dollo's law. The study shows that tiny free-living house dust mites, which thrive in the mattresses, sofas, and carpets of even the cleanest homes, evolved from parasites, which in turn evolved from free-living organisms millions of years ago. "All our analyses conclusively demonstrated that house dust mites have abandoned a parasitic lifestyle, secondarily becoming free-living, and then speciated in several habitats, including human habitations," according to Dr. Pavel Klimov and Dr. Barry O’Connor of the U-M Department of Ecology and Evolutionary Biology. Their paper is scheduled to be published online on March 8, 2013 in the journal Systematic Biology. Mites are arachnids related to spiders (both have eight legs) and are among the most diverse animals on Earth. House dust mites, members of the family Pyroglyphidae, are the most common cause of allergic symptoms in humans, affecting up to 1.2 billion people worldwide. Despite their huge impact on human health, the evolutionary relationships between these speck-sized creatures are poorly understood. According to Drs.

March 7th

Toward Unlimited Cloning: Japanese Scientists Make 25 Generations of Mouse Clones

Using the same technique that was used to create Dolly the sheep, researchers from the RIKEN Center for Developmental Biology in Kobe, Japan, have identified a way to produce healthy mouse clones that live a normal lifespan and can be sequentially cloned indefinitely. Their study was published as the cover story of the March 7, 2013 issue of Cell Stem Cell. In an experiment that started in 2005, the team led by Dr. Teruhiko Wakayama has used a technique called somatic cell nuclear transfer (SCNT) to produce 581 clones of one original “donor” mouse, through 25 consecutive rounds of cloning. SCNT is a widely used cloning technique whereby a cell nucleus containing the genetic information of the individual to be cloned is inserted into a living egg that has had its own nucleus removed. It has been used successfully in laboratory animals, as well as farm animals. However, until now, scientists had not been able to overcome the limitations of SCNT that resulted in a low success rates and restricted the number of times mammals could be recloned. Attempts at recloning cats, pigs, and mice more than two to six times had failed. “One possible explanation for this limit on the number of recloning attempts is an accumulation of genetic or epigenetic abnormalities over successive generations,” explains Dr. Wakayama. To prevent possible epigenetic changes, or modifications to DNA function that do not involve a change in the DNA itself, Dr. Wakayama and his team added trichostatin, a histone deacetylase inhibitor, to the cell culture medium. Using this technique, they increased cloning efficiency by up to 6-fold. By improving each step of the SCNT procedure, the scientists were able to clone the mice repeatedly 25 times without seeing a reduction in the success rate.