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Archive - Apr 2017

April 5th

Scientists ID Gene Involved in Controlling Sleep Quality in Diverse Species; Study Examines FABP2 Gene Action in Fruit Flies, Mice, and Humans

Washington State University (WSU) researchers, and colleagues, have examined how a particular gene (FABP7) is involved in the quality of sleep experienced by three different animal species--humans, mice, and fruit flies. The gene, and knowledge of its function, open a new avenue for scientists exploring how sleep works and why animals seem to need it so badly. "Sleep must be serving some important function," said Jason Gerstner, Ph.D., Assistant Research Professor in WSU's Elson S. Floyd College of Medicine and lead author of an article published in the April 5, 2017 issue of the open-access journal Science Advances. The article is titled “Normal Sleep Requires the Astrocyte Brain-Type Fatty Acid Binding Protein FABP7." “But as scientists we still don't understand what that [function] is. One way to get closer to that is by understanding how it is regulated or what processes exist that are shared across species." As a doctoral student at the University of Wisconsin-Madison, Dr. Gerstner investigated genes whose expression changes over the sleep-wake cycle and he found that expression of the gene FABP7 changed over the course of the day throughout the brain of mice. Dr. Gerstner and his colleagues observed that mice with a knocked-out FABP7 gene slept more fitfully compared to normal mice with the gene intact. This suggested the functioning gene is required for normal sleep in mammals. To determine if FABP7 is indeed required for normal sleep in humans, Dr. Gerstner and colleagues in Japan examined data from nearly 300 Japanese men who underwent a seven-day sleep study that included an analysis of their DNA. It turned out that 29 of these men had a variant of the FABP7 gene. As the mice had, these men with the variant FABP7 gene tended to sleep more fitfully.

Exosome-Based Approach to Treating Death of Neurons Wins $250,000 Top Prize in Regeneron Science Talent Search; 17-Year-Old Indrani Das Takes Home Top Honors in Nation’s Most Prestigious Science & Math Competition for High School Seniors

In Washington, D.C., on March 14, 2017, the Society for Science & the Public and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced that Indrani Das, 17, of Oradell, New Jersey, had won the top award ($250,000) in the Regeneron Science Talent Search, the nation's oldest and most prestigious science and math competition (previous sponsors of the Talent Search were Westinghouse and Intel). Forty finalists, including Indrani, were honored at the annual Regeneron Science Talent Search Awards Gala for their research projects demonstrating exceptional scientific and mathematical ability, taking home more than $1.8 million in awards provided by Regeneron. Indrani won the top award of $250,000 for her study of a possible approach to treating the death of neurons due to brain injury or neurodegenerative disease. A contributor to neuron death is astrogliosis, a condition that occurs when cells called astrocytes react to injury by growing, dividing, and reducing their uptake of glutamate, which, in excess, is toxic to neurons. In a laboratory model, she showed that exosomes isolated from astrocytes transfected with microRNA-124a both improved astrocyte uptake of glutamate and increased neuron survival. Indrani mentors younger researchers and tutors math in addition to playing the piccolo trumpet in a four-person jazz ensemble. Second place honors and $175,000 went to Aaron Yeiser, 18, of Schwenksville, Pennsylvania, for his development of a new mathematical method for solving partial differential equations on complicated geometries. Partial differential equations are ubiquitous in science and engineering and are currently solved using computers. He developed a more efficient way to do this and applied it to the challenging field of computational fluid dynamics.

April 2nd

First-Ever Global Symposium on Use of Maple Syrup to Reduce Inflammation Convened at ACS Annual Meeting in San Francisco, shared the results of their research that expands the science of maple's potential impact on several areas affected by chronic inflammation. These include metabolic syndrome, brain health, and liver disease, as well as maple's emerging link to a healthy gut microbiome. The global symposium was organized by Dr. Navindra Seeram, who currently serves as chairman of the Division of Agricultural and Food Chemistry of the ACS, and has extensive experience examining the impact of phytonutrients in foods such as berries and pomegranates. In collaboration with the Federation of Quebec Maple Syrup Producers, Dr. Seeram has been studying the unique properties of maple in his laboratory at the University of Rhode Island since 2009. The results of his research stimulated the interest of the global scientific community, which has uncovered additional health benefits of pure maple products. A new University of Rhode Island study highlighted at the symposium revealed the presence of inulin, a type of carbohydrate recently discovered for the first time in maple syrup. Inulin is a complex carbohydrate (natural dietary fiber) that acts as a prebiotic and works to encourage the growth of "good" or beneficial bacteria in the gut.

Negative Regulator (BATF2) Halts Extreme Immune Response to Trypanosome Parasite, Averting Multi-Organ Damage

Cytokines are proteins secreted by several types of immune cells in response to infection, inflammation, or injury. Interleukin-17 (IL-17) is one such cytokine that causes inflammation, by controlling the production of other cytokines and mobilizing a type of white blood cell (neutrophil) that fights infections. During some parasitic infections, host protection is achieved by an IL-17 response, but too much IL-17 causes chronic tissue damage. This response is therefore tightly regulated by other cytokines, but the precise mechanisms were previously unclear. Now, Japanese research coordinated by Osaka University has unraveled the complex network of cytokine control that prevents multi-organ damage during infection by the protozoan parasite that causes Chagas disease. Trypanosoma cruzi is an intracellular parasite that infects and destroys heart and digestive muscle, causing Chagas disease, which affects 6–7 million people worldwide, mainly in endemic areas of Central and South America. Previous work showed that T. cruzi infection in mice led to production of the cytokine IL-23 by host immune cells. This promoted the generation of CD4+ T cells that produce IL-17. Researchers built on these findings by focusing on the protein BATF2, which they found in an earlier study to be switched on by cytokine signaling in innate immune cells derived from bone marrow during T. cruzi infection. To study the role of BATF2 in this process, the team generated mice lacking the gene encoding this protein. These Batf2 knockout mice produced much more IL-17 in response to the parasite than did control mice. They also produced more IL-23, suggesting that BATF2 normally suppresses expression of the Il23a gene. However, it was not shown to be required for the killing of T. cruzi.

Identification of Protein Crucial to Development of Lymphatic System

Lymphatic vessels form a circulatory system that plays an important role in controlling the amount of fluid in tissues, and in allowing the immune system to identify and target threats. When the lymphatic system malfunctions, fluid accumulates in tissues, producing a condition known as edema. This can be fatal; for example, lung edema can cause respiratory arrest. The molecular mechanisms underlying lymphatic system development are have not been fully understood, with particular uncertainty surrounding the later stages of development, in which the primitive system is remodeled to produce a mature, functional lymphatic vasculature. Osaka University-led Japanese researchers have now identified a protein that is crucial for this lymphatic system remodeling and maturation. “Polydom” is a large protein known to interact with the receptor integrin α9β1, and is found in the extracellular matrix surrounding and supporting cells. The research team found that mice genetically engineered to lack Polydom died immediately after birth because they had lung edema, which prevented them from breathing. Further investigation revealed that a primitive lymphatic system developed in these mice, but branching vessels failed to grow and the mature vasculature did not form, leading to fluid accumulation in tissues. Genetically engineered zebrafish lacking Polydom also exhibited a failure of lymph vessel development. The team then explored the location of Polydom in mice, and found that the protein associates with lymphatic vessels throughout embryonic development. “However, we were interested to find that Polydom was not actually produced by the endothelial cells that line the vessels, but by the surrounding mesenchymal cells,” corresponding author Kiyotoshi Sekiguchi, Ph.D., says.

April 2nd

Maple Syrup Extract Boosts Antibiotic Potency

Antibiotics save lives every day, but there is a downside to their ubiquity. High doses can kill healthy cells along with infection-causing bacteria, while also spurring the creation of "superbugs" that no longer respond to known antibiotics. Now, researchers may have found a natural way to cut down on antibiotic use without sacrificing health: a maple syrup extract that dramatically increases the potency of these medicines. The researchers presented their work on April 2 at the 253rd National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding its annual meeting in San Francisco April 2-6. The meeting will feature more than 14,000 presentations on a wide range of science topics. "Native populations in Canada have long used maple syrup to fight infections," says Nathalie Tufenkji, Ph.D., of Canada’s McGill University. "I've always been interested in the science behind these folk medicines." The idea for the project really gelled when Dr. Tufenkji, who had been studying the antimicrobial effects of cranberry extracts, learned of the anti-cancer properties of a phenolic maple syrup extract. "That gave me the idea to check its antimicrobial activity," Dr. Tufenkji says. "So, I sent my postdoc to the store to buy some syrup." Using the same extraction approach as other researchers have in the past, Dr. Tufenkji's team at McGill University separated the sugar and water from the syrup's phenolic compounds, which contribute to maple syrup's signature golden hue. In an initial test, the team exposed several disease-causing bacterial strains to the extract, but they didn't see much of an effect. Rather than give up on maple syrup altogether, Dr.

Genes Newly Associated with Erdheim-Chester Disease (ECD) Also Linked to Cancer; Findings Suggest Ultra-Rare Disease Should Be Considered Form of Cancer; MAPK Blockers May Provide More Hope for Treatment & Improve 60% Mortality Rate at Three Years

NHGRI (National Human Genome Research Institute) researchers have identified new genes associated with the Erdheim-Chester disease (ECD) and some possible new therapies. Findings on this ultra-rare disease, found/discovered in approximately 600 people in the world, were published in Blood Advances. The article is titled “The Clinical Spectrum of Erdheim-Chester Disease: An Observational Cohort Study.” "The discovery of new genes associated with ECD provides hope for improving the diagnoses of a disease that affects so many parts of the body. We also hope it will help us identify new treatments," said Juvianee I. Estrada-Veras, M.D., Clinical Investigator and Staff Clinician in the NHGRI's Medical Biochemical Genetics Residency Program. "Our work on ECD builds on the Institute's goals to advance medical knowledge about rare diseases and to potentially provide insights into more common disorders." ECD is caused by the accumulation of specialized white blood cells called histiocytes in different organs. The resulting inflammation damages organs and tissues throughout the body, causing them to become thickened, dense, and scarred. Histiocytes normally function to destroy foreign substances and protect the body from infection. ECD has no standard therapy, although consensus guidelines for clinical management were published in 2014. Between 2011 and 2015, researchers examined 60 adults with ECD at the NIH Clinical Center. Of 59 samples that were available for molecular testing, half were found to have BRAF V600E gene mutations, which are sometimes seen in colon cancer, lung cancer, thyroid cancer, brain tumors, and some blood cancers. Other patients had mutations in genes of the MAPK pathway, which controls cell growth and proliferation.

New Gene-Based Blood Tests Identify More Metastatic Melanomas: Tests Based on Circulating Tumor DNA (ctDNA) May Improve Detection of Recurrence & Speed Related Treatment

Genetic testing of tumor and blood fluid samples from people with and without one of the most aggressive forms of skin cancer has shown that two new blood tests can reliably detect previously unidentifiable forms of the disease. Researchers at the New York University (NYU) Langone Medical Center and its Perlmutter Cancer Center, who led the study, say having quick and accurate monitoring tools for all types of metastatic melanoma, make it easier for physicians to detect early signs of cancer recurrence. The new blood tests, which take only 48 hours, were developed in conjunction with Bio-Rad Laboratories in Hercules, California. Currently, the tests are only available for research purposes. The new tools are the first, say the study authors, to identify melanoma DNA in the blood of patients whose cancer is spreading and who lack defects in either the BRAF or NRAS genes, already known to drive cancer growth. Together, BRAF and NRAS mutations account for over half of the 50,000 cases of melanoma diagnosed each year in the United States, and each can be found by existing tests. But the research team estimates that when the new tests become available for use in clinics, the vast majority of all melanomas will be detectable. "Our goal is to use these tests to make more informed treatment decisions and, specifically, to identify, as early as possible, when a treatment has stopped working, cancer growth has resumed, and the patient needs to switch therapy," says senior study investigator and dermatologist David Polsky, M.D., Ph.D. Dr. Polsky presented his team's latest findings at the 2017 annual meeting of the American Association for Cancer Research (AACR), on April 2 in Washington, D.C. The meeting is taking place April 1-5. Dr. Polsky is the Alfred W.

Scientists Use Modified Bee Venom to Shuttle Drugs Across Blood-Brain Barrier into Brain

Most medicines can't get through the blood-brain barrier (BBB), a highly selective membrane that separates the circulatory system from the fluid bathing the brain. Certain peptides in animal venoms, however, can navigate across the BBB to inflict damage. Now, researchers are capitalizing on such venomous sneak attacks by developing a strategy based on a bee-venom peptide, apamin, to deliver medications to the brain. The researchers are scheduled to present their work on Sunday, April 2, at the 253rd National Meeting & Exposition of the American Chemical Society (ACS) (2017). ACS, the world's largest scientific society, is holding the meeting in San Francisco Sunday through Thursday (April 2-April 6). The meeting will feature more than 14,000 presentations on a wide range of science topics. "We thought that because the venoms of some animals are able to attack the central nervous system, they should be able to go through the blood-brain barrier and possibly shuttle drugs across it," Ernest Giralt, Ph.D., says. Apamin is known to accumulate in the central nervous system of people who've been stung by bees. But the idea of using the apamin peptide itself had some drawbacks. "We knew we could not use apamin directly because it's toxic," he says. "But the good news is that the origin of the toxicity is well-known. We thought we could probably modify apamin in such a way that the toxicity would be eliminated, but it would still keep its ability to act as a transporter." Apamin's toxicity stems from its interactions with a potassium channel in neurons. A positively charged group in the apamin molecule mimics the potassium ion and blocks the potassium channel when it binds. To eliminate the toxicity, Dr.

Newly Characterized Protein Has Potential to Save U.S. Farmers $ Millions Annually

Instead of turning carbon into food, many plants accidentally make a plant-toxic compound during photosynthesis that is recycled through a process called photorespiration. University of Illinois and USDA/ARS researchers reported online on March 28, 2017 in Plant Cell the discovery of a key protein in this process, which they hope to manipulate to increase plant productivity. The open-access paper is titled “Bile Acid Sodium Symporter BASS6 Can Transport Glycolate and Is Involved in Photorespiratory Metabolism In Arabidopsis Thaliana." "Photorespiration is essential for C3 plants, such as rice and soybeans, but operates at the massive expense of fixed carbon and energy," said project lead Don Ort (at right in photo), Ph.D., USDA/ARS scientist and the Robert Emerson Professor of Plant Biology at Illinois. "We have identified photorespiration as a primary target to improve photosynthetic efficiency as a strategy to improve crop yield. Successfully re-engineering photorespiration requires deep knowledge of the process, for which understanding of transport steps is most lacking." Related to a family of transport proteins that move bile around in animals, the newly discovered role of the plant protein bile acid sodium symporter 6 (BASS6) is to transport the toxic product glycolate out of the chloroplast where it is recycled into a useful sugar molecule (glycerate) through a series of chemical reactions, which release carbon dioxide and harmful ammonia while sacrificing energy. Since the 1960s, researchers have known that plant chloroplasts export two molecules of glycolate to recover one molecule of glycerate.