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Archive - Feb 2017

Date

February 25th

Four Variants of GLRB Gene ID’d As Risk Factors for Anxiety Disorders

Mental, social, and inherited factors all play a role in anxiety disorders. In an article published online on February 7, 2017 in Molecular Psychiatry, a research team from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, describes a hitherto unknown genetic pathway for developing such diseases: The scientists pinpointed at least four variants of the GLRB gene (glycine receptor B) as risk factors for anxiety and panic disorders. More than 5,000 voluntary participants and 500 patients afflicted by panic disorder took part in the study that delivered these results. In Germany, approximately 15 percent of adults suffer from anxiety and panic disorders. Some people may have an extreme fear of spiders or other objects while others have breathing difficulties and accelerated heart beat in small rooms or large gatherings of people. With some afflicted persons, the anxiety attacks occur for no apparent cause. Many patients suffer from the detrimental impacts on their everyday lives - they often have problems at work and withdraw from social contacts. The Molecular Psychiatry article is titled “GLRB Allelic Variation Associated with Agoraphobic Cognitions, Increased Startle Response and Fear Network Activation: A Potential Neurogenetic Pathway to Panic Disorder.” How are fear and anxiety triggered? How do anxiety disorders arise and evolve? Scientists from Münster, Hamburg, and Würzburg have looked into these questions within the scope of Collaborative Research Center (CRC) TR 58 funded by Deutsche Forschungsgemeinschaft. Their goal is to develop new therapies that are better tailored to the individual patients. Anxiety disorders can be treated with drugs and behavior therapy for instance.

New Approach Permits Revelation of Diverse Allelic Effects in Mammalian Brain That Are Not Caused by Imprinting or Genetic Variation

For over a century, scientists have thought that most of our cells express genes from both parents' chromosomes relatively equally throughout life. But the biology is more nuanced, say scientists who invented a screen to measure the activity of specific genes from both parents. In Neuron on February 23, 2017, researchers report that in rodent, monkey, and human brains, it's not unusual for individual neurons or specific types of neurons to silence genes from one parent or the other. The article is titled “Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain.” Surprisingly, the differential activation of maternal and paternal gene copies was observed most often in the developing brain, impacting about 85% of genes. Gradually, as the brain matures, neurons increasingly express both parents' genes equally. However, for at least 10% of genes, maternal and paternal copies continue to be differentially expressed in the adult brain, revealing that this imbalance exists throughout an organism's lifetime for many genes in the brain. "This story has its roots in understanding why we reproduce sexually--normally, having two copies of a gene acts as a protect buffer in case one is defective," says senior author Dr. Christopher Gregg, a neurobiologist at the University of Utah School of Medicine and a New York Stem Cell Foundation Robertson Investigator. "Our findings suggest that periods when the healthy gene copy is turned off could be critical windows during which cells are particularly vulnerable to a mutation in the other copy."

February 24th

New Tool to Map RNA-DNA Interactions Could Help Researchers Translate Gene Sequences into Functions

Bioengineers at the University of California (UC) San Diego have developed a new tool to identify interactions between RNA and DNA molecules. The tool, called MARGI (Mapping RNA Genome Interactions), is the first technology that is capable of providing a full account of all the RNA molecules that interact with a segment of DNA, as well as the locations of all these interactions -- in just a single experiment. RNA molecules can attach to particular DNA sequences to help control how much protein these particular genes produce within a given time, and within a given cell. And by knowing what genes produce these regulatory RNAs, researchers can start to identify new functions and instructions encoded in the genome. "Most of the human genome sequence is now known, but we still don't know what most of these sequences mean," said Dr. Sheng Zhong, bioengineering professor at the UC San Diego Jacobs School of Engineering and the study's lead author. "To better understand the functions of the genome, it would be useful to have the entire catalog of all the RNA molecules that interact with DNA, and what sequences they interact with. We've developed a tool that can give us that information." Dr. Zhong and his team published their findings in the February 20, 2017 issue of Current Biology. The article is titled “Systematic Mapping of RNA-Chromatin Interactions in Vivo.” Existing methods to study RNA-DNA interactions are only capable of analyzing one RNA molecule at a time, making it impossible to analyze an entire set of RNA-DNA interactions involving hundreds of RNA molecules. "It could take years to analyze all these interactions," said Tri Nguyen, a bioengineering Ph.D. student at UC San Diego and a co-first author of the study.

Diet That Mimics Fasting May Reverse Diabetes--Periodic Cycles of Fasting Reprogram Pancreatic Cells and Restore Insulin Production

A diet designed to imitate the effects of fasting appears to reverse diabetes by reprogramming cells, a new University of Southern California (USC)-led study shows. The fasting-like diet promotes the growth of new insulin-producing pancreatic cells that reduce symptoms of type 1 and type 2 diabetes in mice, according to the study on mice and human cells led by Dr. Valter Longo, Director of the Longevity Institute at the USC Leonard Davis School of Gerontology. "Cycles of a fasting-mimicking diet and a normal diet essentially reprogrammed non-insulin-producing cells into insulin-producing cells," said Dr. Longo, who is also a professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences. "By activating the regeneration of pancreatic cells, we were able to rescue mice from late-stage type 1 and type 2 diabetes. We also reactivated insulin production in human pancreatic cells from type 1 diabetes patients." The reprogrammed adult cells and organs prompted a regeneration in which damaged cells were replaced with new functional ones, he said. The study, published in the February 23, 2017 issue of Cell, is the latest in a series of studies to demonstrate promising health benefits of a brief, periodic diet that mimics the effects of a water-only fast. The Cell article is titled “Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes.” In type 1 and late-stage type 2 diabetes, the pancreas loses insulin-producing beta cells, increasing instability in blood sugar levels. The study showed a remarkable reversal of diabetes in mice placed on the fasting-mimicking diet for four days each week. They regained healthy insulin production, reduced insulin resistance and demonstrated more stable levels of blood glucose.

Focus on B-Cells Producing Autoantibodies May Point Way to More Successful Treatments for Rheumatoid Arthritis

Current treatments for rheumatoid arthritis relieve the inflammation that leads to joint destruction, but the immunologic defect that triggers the inflammation persists to cause relapses, according to research conducted at the NYU Langone Medical Center and the University of Pittsburgh. Known as autoantibodies and produced by the immune system's B cells, these defective molecules mistakenly attack the body's own proteins in an example of autoimmune disease. Now, the results of a study published online on January 24, 2017 in Arthritis & Rheumatology suggest that clinical trials for new rheumatoid arthritis (RA) drugs should shift from their sole focus on relieving inflammation to eliminating the B cells that produce these antibodies. "We have developed a test for measuring the underlying autoimmunity in rheumatoid arthritis patients that should be used to evaluate new treatment regimens," says senior author Gregg Silverman, M.D., professor in the Departments of Medicine and Pathology at NYU Langone and co-director of its Musculoskeletal Center of Excellence. "We believe this provides a road to a cure for rheumatoid arthritis." The article is titled “Disease Associated Anti-Citrullinated Protein Memory B Cells in Rheumatoid Arthritis Persist in Clinical Remission.” Rheumatoid arthritis is a chronic inflammatory autoimmune disease that affects 1.5 million people in the United States. The current standard of care begins with methotrexate, a drug that reduces inflammation. It is often followed by drugs that block a molecule called tumor necrosis factor (TNF), which promotes inflammation. Both of these classes of drugs can blunt the swelling and inflammation associated with rheumatoid arthritis and at times even allow patients to go into clinical remission that requires continued treatment.

February 23rd

“Late-Life” Genes Activated by Biological Clock May Help Protect Against Stress, Aging

Researchers at Oregon State University (OSU) have discovered that a subset of genes involved in daily circadian rhythms, or the "biological clock," only become active late in life or during periods of intense stress when they are most needed to help protect critical life functions. The findings, made in research done with fruit flies and published on February 21, 2017 in Nature Communications, reveal part of a unique stress response mechanism that was previously unknown. The open-access article is titled “Circadian Deep Sequencing Reveals Stress-Response Genes That Adopt Robust Rhythmic Expression During Aging.” These LLC genes may help to combat serious stresses associated with age, disease, or environmental challenges, and help explain why aging is often accelerated when the biological clock is disrupted. This group of genes, whose rhythmic activity late in life had not previously been understood, were named "late-life cyclers," or LLCs, by former OSU graduate student and lead author of the study, Rachael Kuintzle. At least 25 such genes become rhythmic with age, and the function of some of them remains unclear. "This class of LLC genes appears to become active and respond to some of the stresses most common in aging, such as cellular and molecular damage, oxidative stress, or even some disease states," said Dr. Jadwiga Giebultowicz, a professor in the OSU College of Science, co-senior author on the study, and international expert on the mechanisms and function of the biological clock. "Aging is associated with neural degeneration, loss of memory, and other problems, which are exacerbated if clock function is experimentally disrupted. The LLC genes are part of the natural response to that, and do what they can to help protect the nervous system."

February 21st

Scientists Explain Unique Intensity & Sheen of Buttercups

Buttercup flowers are known for their intense, shiny yellow color. For over a century, biologists have sought to understand why the buttercup stands out. University of Groningen scientists have now brought together all that was known about the buttercup and added some new information too. The results will be published by the Journal of the Royal Society Interface on February 22, 2017. The article will be titled “Functional Optics of Glossy Buttercup Flowers.” The anatomy of the buttercup's petals is the first step in discovering the secret of its color. The petals have a one-cell thick epidermis, which contains a yellow pigment. Underneath this very thin cell layer is an air chamber. During his work as a Ph.D. student at the University of Groningen, Dr. Casper van der Kooi (who now works at Lausanne University, Switzerland) measured light spectra reflecting from this epidermal layer. “We discovered that this layer acts as a thin optical film. The color-generating mechanism is similar to oil on water or a soap bubble,” says Dr. Van der Kooi. “Light is reflected on both sides of the epidermis, where the cells and air meet. As the cell layer is very smooth and thin, optical interference occurs and the reflected colors merge. This creates a white sheen, which makes the petals seem glossy.” This kind of thin pigmented film is unique in the world of plants. “Butterflies use similar structures to produce color, as do some birds, but buttercups are the only known flowers to do so,” says Dr. Van der Kooi. The structure of the epidermis has been described before, but Dr. Van der Kooi and colleagues are the first to measure light spectra and conclude that the cell layer acts as a thin film.

February 20th

Protein Once Thought Exclusive to Neurons Helps Aggressive Cancers Grow, Spread, Defy Death

How we think and fall in love are controlled by lightning-fast electrochemical signals across synapses, the dynamic spaces between nerve cells. Until now, nobody knew that cancer cells can repurpose tools of neuronal communication to fuel aggressive tumor growth and spread. University of Texas (UT) Southwestern Medical Center researchers report these findings in two recent studies, one in PNAS and the second in Developmental Cell. The PNAS article (online January 3, 2017) is titled “TRAIL-Death Receptor Endocytosis and Apoptosis Are Selectively Regulated by Dynamin-1 Activation,” and the Developmental Cell article (online February 6, 2017) is titled “Crosstalk Between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis.” “Many properties of aggressive cancer growth are driven by altered cell signaling,” said Dr. Sandra Schmid, senior author of both papers and Chair of Cell Biology at UT Southwestern. “We found that cancer cells are taking a page from the neuron’s signaling playbook to maintain certain beneficial signals and to squelch signals that would harm the cancer cells.” The two studies find that dynamin1 (Dyn1) – a protein once thought to be present only in nerve cells of the brain and spinal cord – is also found in aggressive cancer cells. In nerve cells, or neurons, Dyn1 helps sustain neural transmission by causing rapid endocytosis – the uptake of signaling molecules and receptors into the cell – and their recycling back to the cell surface. These processes ensure that the neurons keep healthy supplies at the ready to refire in rapid succession and also help to amplify or suppress important nerve signals as necessary, Dr. Schmid explained. “This role is what the cancer cells have figured out.

First Controllable Electronic Switch Within Single DNA Molecule

DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices. Much like flipping your light switch at home---only on a scale 1,000 times smaller than that of a human hair---an Arizona Statte University (ASU)-led team has now developed the first controllable DNA switch to regulate the flow of electricity within a single, atomic-sized molecule. The new study, led by ASU Biodesign Institute researcher Dr. Nongjian Tao, was published online on February 20, 2017 in Nature Communications. The open-access article is titled “Gate-Controlled Conductance Switching in DNA.” "It has been established that charge transport is possible in DNA, but for a useful device, one wants to be able to turn the charge transport on and off. We achieved this goal by chemically modifying DNA," said Dr. Tao, who directs the Biodesign Center for Bioelectronics and Biosensors and is a professor in the Fulton Schools of Engineering. "Not only that, but we can also adapt the modified DNA as a probe to measure reactions at the single-molecule level. This provides a unique way for studying important reactions implicated in disease, or photosynthesis reactions for novel renewable energy applications." Engineers often think of electricity like water, and the research team's new DNA switch acts to control the flow of electrons on and off, just like water coming out of a faucet. Previously, Dr. Tao's research group had made several discoveries to understand and manipulate DNA to more finely tune the flow of electricity through it.

February 19th

Estrogen Explains Exosome-Carried Messenger Profile in Circulation Among Postmenopausal Women

A study at the Gerontology Research Center at University of Jyväskylä in Finland has demonstrated that, in blood circulation, the exosome-carried messenger molecule profile differs between post- and premenopausal women. The differences were associated with circulating estrogen and cholesterol levels, as well as body composition and other health indicators. These findings enable using the studied molecules in the evaluation of health status. The studied messenger molecules are packed in the exosomes, which are released by the cells into the circulation. Exosomes are spherical nanoscale lipid vesicles. These small packages carry microRNA molecules, among other molecules, which are considered to be messengers between the cells regulating gene function, says Docent Eija Laakkonen. The study was the first to show that specific exosome-packed microRNAs are sensitive to the estrogen levels in the circulation, which are influenced both by age and the use of hormonal therapies. The results can be exploited in evaluating the effects of hormonal contraceptives and hormone replacement therapies on the overall physiological status of women. When the regulatory mechanisms of the microRNAs are better understood, the microRNA profile can be used for recognizing individuals with a high risk for metabolic disorders, or even lowering the risk. It seems, therefore, that the postmenopausal declining amount of circulating estrogen changes the cargo inside the exosomes. When these exosome packages are delivered to the target tissues, the contents are released to the correct recipient cell. These delivered messages change the function of the cell, explains doctoral candidate Reeta Kangas.