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Archive - Mar 2017

March 24th

NAD+ “Booster” Could Have Significant Anti-Aging Effects

Researchers at the University of New South Wales (UNSW) in Australia have made a discovery that could lead to a revolutionary drug that actually reverses aging, improves DNA repair, and could even help NASA get its astronauts to Mars. In a paper published in Science on March 23, 2017, the team identifies a critical step in the molecular process that allows cells to repair damaged DNA. The article is titled “A Conserved NAD+ Binding Pocket That Regulates Protein-Protein Interactions During Aging.” The scientists’ experiments in mice suggest a treatment is possible for DNA damage from aging and radiation. It is so promising it has attracted the attention of NASA, which believes the treatment can help its Mars mission. While our cells have an innate capability to repair DNA damage - which happens every time we go out into the sun, for example - their ability to do this declines as we age. The scientists determined that the metabolite NAD+, which is naturally present in every cell of our body, has a key role as a regulator in protein-to-protein interactions that control DNA repair. Treating mice with a NAD+ precursor, or "booster," called NMN improved their cells' ability to repair DNA damage caused by radiation exposure or old age. "The cells of the old mice were indistinguishable from the young mice, after just one week of treatment," said lead author Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School. Human trials of NMN therapy will begin within six months. "This is the closest we are to a safe and effective anti-aging drug that's perhaps only three to five years away from being on the market if the trials go well," says Dr. Sinclair, who maintains a lab at UNSW in Sydney.

March 21st

Genetic Assessment Developed to Determine Age-Specific Risk for Developing Alzheimer's Disease

An international team of scientists, led by researchers at University of California San Diego School of Medicine and University of California San Francisco (UCSF), has developed a novel genetic score that allows individuals to calculate their age-specific risk of developing Alzheimer's disease (AD), based upon genetic information. A description of the polygenic hazard scoring (PHS) system and its validation was published on March 21, 2017 in PLOS Medicine. The open-access article is titled “Genetic Assessment of Age-Associated Alzheimer Disease Risk: Development and Validation of a Polygenic Hazard Score.” "We combined genetic data from large, independent cohorts of patients with AD with epidemiological estimates to create the scoring, then replicated our findings on an independent sample and validated them with known biomarkers of Alzheimer's pathology," said co-first author Rahul S. Desikan, M.D., Ph.D., Clinical Instructor in the UCSF Department of Radiology & Biomedical Imaging. Specifically, the researchers combined genotype-derived polygenic information with known AD incidence rates from the U.S. population to derive instantaneous risk estimates for developing AD. "For any given individual, for a given age and genetic information, we can calculate your 'personalized' annualized risk for developing AD," said Dr. Desikan. "That is, if you don't already have dementia, what is your yearly risk for AD onset, based on your age and genetic information.

March 20th

Parsley, Orchids, and Other Plants Lend Form to Human Stem Cell Scaffolds

Borrowing from nature is an age-old theme in science. Form and function go hand-in-hand in the natural world and the structures created by plants and animals are only rarely improved on by humans. Taking that lesson to heart, scientists at the University of Wisconsin-Madison are using the decellularized husks of plants such as parsley, vanilla, and orchids to form three-dimensional scaffolds that can then be primed and seeded with human stem cells to optimize their growth in the lab dish and, ultimately, create novel biomedical implants. In an article published online on March 20, 2017 in Advanced Healthcare Materials, a team led by William Murphy, Ph.D., a professor of biomedical engineering and co-director of the UW-Madison Stem Cell and Regenerative Medicine Center, describes the use of a variety of plants to create an efficient, inexpensive, and scalable technology for making tiny structures that could one day be used to repair muscle, organs, and bone using stem cells. The article is titled “Biofunctionalized Plants as Diverse Biomaterials for Human Cell Culture.” "Nature provides us with a tremendous reservoir of structures in plants," explains Dr. Gianluca Fontana, the lead author of the new study and a UW-Madison postdoctoral fellow. "You can pick the structure you want." The new technology capitalizes on the elegant, efficient structural qualities of plants: strength, rigidity, porosity, low mass and, importantly, surface area. It may help overcome the limitations of current methods such as 3-D printing and injection molding to create feedstock structures for biomedical applications. "Plants are really special materials as they have a very high surface area to volume ratio, and their pore structure is uniquely well-designed for fluid transport," says Dr. Murphy.

Approach Based on Extracellular Vesicles (EVs) May Enable Earlier Diagnosis of Pancreatic Cancer

Pancreatic cancer, one of the nation’s deadliest diseases, kills 80 percent of those diagnosed within one year, but an Arizona State University researcher has devised an early detection technique that could help improve those odds, according to a new study. Biomedical Engineering professor Tony Hu, Ph.D., of the Biodesign Virginia G. Piper Center for Personalized Diagnostics, and colleagues, in research published online on February 8, 2016 in Nature: Biomedical Engineering, describe a method for finding tiny bubbles of material called extracellular vesicles (EVs), which can identify pancreatic cancer in its initial stages. “Pancreatic cancer is one type of cancer we desperately need an early blood biomarker for,” Dr. Hu said. Typically, pancreatic cancer, which kills about 40,000 people a year, has few symptoms, spreads quickly, and isn’t diagnosed until it’s in an advanced stage. Approximately 95 percent of patients die within five years of diagnosis. “Other technology has been used for detection, but it doesn’t work very well because of the nature of this cancer,” Dr. Hu said. “It’s really hard to capture an early diagnostic signal when there are no symptoms. It’s not like breast cancer, where you may feel pain and you can easily check for an abnormal growth.” Dr. Hu’s research, a pilot study involving nearly 160 people, showed the ability to differentiate patients with pancreatic cancer, pancreatitis, and healthy subjects. If proven effective on a larger scale, it could lead to a screening exam that could save lives. Further, the technique may ultimately be used to detect a range of diseases based on their unique EV signatures. (Dr.

March 16th

Atlantic Cancer Research Institute Signs Non-Exclusive License Agreement with BioVendor for Liquid Biopsy Enabling Technology Based on Vn96 Capture of Extracellular Vesicles (EVs)

On March 15, 2017, the Atlantic Cancer Research Institute (ACRI) announced an agreement with BioVendor – Laboratorní medicína a.s. to license its patented intellectual property for the use of the Vn96 synthetic peptide in liquid biopsy applications. The agreement gives BioVendor non-exclusive rights to use the Vn96 peptide for the isolation of extracellular vesicles (EVs) for the diagnosis of diseases, such as cancer. EVs, which include exosomes, are small, cell-derived particles that are present within body fluids such as plasma and urine. EVs can contain a sample of the DNA, RNA, protein, lipids, and metabolites found within the cells from which they are derived and therefore are a valuable source of biomarkers that reflect the real-time state of both healthy and diseased cells. The Vn96 synthetic peptide, developed by ACRI and New England Peptide Inc. (Gardner, Massachusetts), is recognized as one of the leading technologies that enables EV capture from body fluids. Liquid biopsy is a precision medicine technology that offers physicians and health professionals the ability to test a patient in real time to obtain multi-parametric biomarker information and guide therapeutic choices. The Vn96 peptide enables liquid biopsy by providing a fast and reproducible method for the isolation of EVs, and the information that they contain, which is clinically amenable and requires minimal specialized equipment. BioVendor - Laboratorni medicina a.s. was established in the Czech Republic in 1992 as a distributor of clinical chemistry and life science laboratory products. The BioVendor Research and Diagnostic Products Division is an innovative biotechnology company focused on the development and manufacture of in vitro diagnostics and for-research-use immunoassays, recombinant proteins, and antibodies.

Deficiency of SPRED2 Protein May Be a Cause of Obsessive-Compulsive Disorder

Some people have an extreme fear of dirt or bacteria. As a result, they may develop a habit of compulsive washing and repeatedly cleaning their hands or body. They are trapped in a vicious circle, as the fear of new contamination returns quickly after washing. Sufferers see no way out. They are even incapable of changing their behavior when the excessive washing has led to skin irritation or damage. Approximately two percent of the general population suffer from some kind of obsessive-compulsive disorder (OCD) at least once in their life. The disorder is characterized by persistent intrusive thoughts which the sufferers try to compensate for by repetitive ritualized behavior. Like depression, eating disorders, and other mental diseases, OCD is treated with antidepressants. However, the drugs are non-specific, that is they are not tailored to the respective disease. Therefore, scientists have been looking for new and better targeted therapies that have fewer side-effects. Professor Kai Schuh from the Institute of Physiology at the Julius-Maximilians-Universität (JMU) Würzburg (Germany) and his team have explored the underlying causes of obsessive-compulsive disorder in collaboration with the JMU's Departments of Psychiatry and Neurology. "We were able to show in mouse models that the absence of the protein SPRED2 alone can trigger an excessive grooming behavior," Dr. Schuh says. He believes that this finding is crucial as no clear trigger for this type of disorder has been identified until now. Previous research pointed to multiple factors being responsible for developing OCD. Occurring in all cells of the body, the protein SPRED2 is found in particularly high concentrations in regions of the brain, namely in the basal ganglia and the amygdala.

New Plant Research Solves Colorful Mystery

Research led by scientists at the John Innes Centre has solved a long-standing mystery by deducing how and why strange yet colorful structures called “anthocyanic vacuolar inclusions” (AVIs) occur in some plants. Pansy petals, blueberries, and autumn leaves all have something in common - their characteristic purple, blue, and orange-red colors are all caused by the accumulation of pigment molecules called anthocyanins. As well as contributing to a wide range of plant colors, the patterns and shading caused by anthocyanins can help to guide pollinators towards flowers, or animals towards fruits for seed dispersal. Anthocyanins also help to protect plants against the destructive photo-oxidative damage that can be caused by various stresses including high levels of ultraviolet light. It has been known for some time that anthocyanins accumulate in the vacuoles of plant cells and, being soluble, they are usually uniformly distributed throughout the vacuole. However, previous research has also noted that, in some plants, distinct, densely colored clusters of anthocyanins can form within vacuoles. Until now, it was not known how these unusual AVIs formed - or indeed why. However, a study led by the John Innes Centre's Professor Cathie Martin and published online on March 16, 2017 in the journal Current Biology, reveals new understanding of the molecular mechanisms underpinning the formation of AVIs. The open-access article is titled “'Aromatic Decoration Determines the Formation of Anthocyanic Vacuolar Inclusions.” Several other John Innes Centre researchers were also involved in the research, along with international collaborators from China, New Zealand, and Norway.

Anti-Wolbachia Drug Regimen Using Rifampicin Could Reduce Treatment Times for Elephantiasis & River Blindness to 1-2 Weeks

On March 16, 2017, scientists from the A·WOL Consortium based at the Liverpool School of Tropical Medicine published online an open-access paper entitled “Short-Course, High-Dose Rifampicin Achieves Wolbachia Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic Filariasis and Onchocerciasis” in Scientific Reports. The study explored the development of a shorter treatment regimen, resulting in adult filarial worm death (macrofilaricidal), by using the antibiotic drug rifampicin to target Wolbachia. Unlike doxycycline, this regimen could be safely administered to pregnant women and children. Professor Mark Taylor, corresponding author on the paper, said: "The anti-Wolbachia strategy has proved to be a paradigm-changing therapeutic approach to the treatment of onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis). The data in this paper shows that a clinically safe dose of rifampicin can elicit the same result as the standard 4-6-week doxycycline therapy when administered over just 1-2 weeks. What's more, the fact that it is also safe for children and during pregnancy means that interventions are more likely to benefit the community as a whole, taking us one step closer to the WHO's ambition to control and eliminate these terrible diseases." Previously published findings by the authors have shown that a 4-week course of the tetracycline antibiotic, doxycycline, depletes Wolbachia populations in onchocerciasis and leads to long-term sterilization and a macrofilaricidal effect, whereas a 3-week course of doxycycline delivers sub-optimal effects. This treatment regimen would be compatible for use in children and during pregnancy and, because of the shortened duration of administration required, would be more readily deliverable by health care systems in resource-poor community settings.

How Do Ebola Virus Proteins Released in Exosomes Affect the Immune System?

Cells infected by the deadly Ebola virus may release viral proteins such as VP40 packaged in exosomes, which, as new research indicates, can affect immune cells throughout the body impairing their ability to combat the infection and to seek out and destroy hidden virus. The potential for exosomal VP40 to have a substantial impact on Ebola virus disease is examined in a review article published online on February 6, 2017 in DNA and Cell Biology, a peer-reviewed journal from Mary Ann Liebert, Inc., Publishers. The article is available free on the DNA and Cell Biology website until April 13, 2017 (http://online.liebertpub.com/doi/full/10.1089/dna.2017.3639). In the article, entitled "The Role of Exosomal VP40 in Ebola Virus Disease," Michelle Pleet, Catherine DeMarino, and Fatha Kashanchi, of George Mason University, Benjamin Lepene, of Ceres Nanosciences, Manassas, Virginia, and M. Javad Aman, Integrated BioTherapeutics, Gaithersburg, Maryland, discuss the latest research on the effects of the Ebola VP40 matrix protein on the immune system. The authors suggest that in addition to VP40, additional viral proteins may also be packaged in the membrane-bound exosomal vesicles, intensifying the damaging effects on immune cells. "Starting in December 2013, Ebola re-emerged in Western Africa and devastated the population of three countries, prompting an international response of physicians and of basic and translational scientists. This epidemic led to the development of new vaccines, therapeutics, and insights into disease pathogenesis and epidemiology," says Carol Shoshkes Reiss, Ph.D., Editor-in-Chief of DNA and Cell Biology and Professor, Departments of Biology and Neural Science, and Global Public Health at New York University, NY.

March 15th

UNC Researchers Make Discovery That Could Increase Plant Yield in Wake of Looming Phosphate Shortage

Scientists at the University of North Carolina at Chapel Hill have pinpointed a key genetic switch that helps soil bacteria living on and inside a plant's roots harvest a vital nutrient with limited global supply. The nutrient, phosphate, makes it to the plant's roots, helping the plant increase its yield. The work, published online on March 15, 2017in Nature, raises the possibility of probiotic, microbe treatments for plants to increase their efficient use of phosphate. The open-access article is titled “Root Microbiota Drive Direct Integration of Phosphate Stress and Immunity.” The form of phosphate plants can use is in danger of reaching its peak - when supply fails to keep up with demand - in just 30 years, potentially decreasing the rate of crop yield as the world population continues to climb and global warming stresses crop yields, which could have damaging effects on the global food supply. "We show precisely how a key 'switch protein,’ PHR1, controls the response to low levels of phosphate, a big stress for the plant, and also controls the plant immune system," said Jeff Dangl, Ph.D., John N. Couch Distinguished Professor at UNC-Chapel Hill and Howard Hughes Medical Institute Investigator. "When the plant is stressed for this important nutrient, it turns down its immune system so it can focus on harvesting phosphate from the soil. Essentially, the plant sets its priorities on the cellular level." Dr. Dangl, who worked with lead authors, postdoctoral researchers Dr. Gabriel Castrillo and Dr. Paulo José Pereira Lima Teixeira, graduate student Sur Herrera Paredes, and research analyst Theresa F. Law, found evidence that soil bacteria can make use of this tradeoff between nutrient-seeking and immune defense, potentially to help establish symbiotic relationships with plants.