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Archive - 2018 - Story

February 8th

Researchers Test Antibiotics Produced by Ants

Ants, like humans, deal with disease. To deal with the bacteria that cause some of these diseases, some ants produce their own antibiotics. A new comparative study identified some ant species that make use of powerful antimicrobial agents - but found that 40 percent of ant species tested didn't appear to produce antibiotics. The study has applications regarding the search for new antibiotics that can be used in humans. The paper, "External Immunity in Ant Societies: Sociality and Colony Size Do Not Predict Investment in Antimicrobials," was published online on February 7, 2018 in the journal Royal Society Open Science. "These findings suggest that ants could be a future source of new antibiotics to help fight human diseases," says Clint Penick, PhD, an Assistant Research Professor at Arizona State University and former postdoctoral researcher at North Carolina State University, who is lead author of the study. "One species we looked at, the thief ant (Solenopsis molesta) (photo), had the most powerful antibiotic effect of any species we tested - and until now, no one had even shown that they made use of antimicrobials," says Adrian Smith, PhD, co-author of the paper, an Assistant Research Professor of Biological Sciences at NC State and head of the NC Museum of Natural Sciences' Evolutionary Biology & Behavior Research Lab. "But the fact that so many ant species appear to have little or no chemical defense against microbial pathogens is also important,” Dr. Penick said. That's because the conventional wisdom has long been that most, if not all, ant species carry antimicrobial agents. But this work indicates that the conventional wisdom is wrong. "We thought every ant species would produce at least some type of antimicrobial," Dr. Penick says.

February 7th

Celltex Therapeutics and Texas A&M Institute for Regenerative Medicine Announce Research Agreement Focused on Use of MSC-Derived Exosomes to Treat Alzheimer’s Disease

On February 6, 2018, Houston-based biotechnology company, Celltex Therapeutics Corporation, and Texas A&M University Health Science Center College of Medicine Institute for Regenerative Medicine announced an intellectual property license acquisition and research agreement. The announcement signals the first year of a multi-year research study investigating potential therapies for Alzheimer’s disease using autologous mesenchymal stem cell (MSC)-derived exosomes. Celltex, a pioneer in autologous stem cell technology, is known for its proprietary stem cell process, which yields adult MSCs in quantities never before possible for use in therapy for vascular, autoimmune, and degenerative diseases, as well as injuries. Celltex’s acquisition of the exclusive license adds to its portfolio of cellular and exosomes intellectual property. As part of the research agreement, Darwin J. Prockop, MD, PhD, the Stearman Chair in Genomic Medicine, Director of the Texas A&M Institute for Regenerative Medicine, and Professor at the Texas A&M College of Medicine, and his lab will prepare adult MSCs and use them to derive anti-inflammatory exosomes, which are tiny vesicles that can deliver anti-inflammatory agents to the brain. Ashok K. Shetty, PhD, a Professor at the Department of Molecular and Cellular Medicine at the Texas A&M College of Medicine, Associate Director of the Institute for Regenerative Medicine and Research Career Scientist at the Olin E. Teague Veterans’ Medical Center, and his team will test the efficiency of these exosomes to reduce brain inflammation and assist in repair of neuronal damage related to Alzheimer’s disease.

Small Molecule Prevents Cartilage Damage and Promotes Cartilage Repair; Scientists Will Pursue Further Investigation of Possible Treatment for Arthritis

Will there come a time when a patient with arthritis can forgo joint replacement surgery in favor of a shot? Keck School of Medicine of USC scientist Denis Evseenko, MD, PhD, has reason to be optimistic. In an article published online on February 7, 2018 in the Annals of Rheumatic Diseases, Dr. Evseenko's team describes the promise of a new molecule named "Regulator of Cartilage Growth and Differentiation," or RCGD 423 for short. The article is titled “Drug-Induced Modulation of Gp130 Signaling Prevents Articular Cartilage Degeneration and Promotes Repair.” The RCGD 423 molecule was identified in high-throughput screening of 170,000 small molecule compounds. As its name implies, RCGD 423 enhances regeneration while curbing inflammation. When RCGD 423 was applied to joint cartilage cells in the laboratory, the cells proliferated more and died less, and when injected into the knees of rats with damaged cartilage, the animals could more effectively heal their injuries. RCGD 423 exerts its effects by communicating with a specific molecule in the body. This molecule, called the glycoprotein 130 (Gp130) receptor, receives two very different types of signals: those that promote cartilage development in the embryo, and those that trigger chronic inflammation in the adult. RCGD 423 amplifies the Gp130 receptor's ability to receive the developmental signals that can stimulate cartilage regeneration, while blocking the inflammatory signals that can lead to cartilage degeneration over the long term. Given these auspicious early results, the team is already laying the groundwork for a clinical trial to test RCGD 423 or a similar molecule as a treatment for osteoarthritis or juvenile arthritis.

Two-Step Process of Enzyme Inhibition and Drug Treatment Inhibits Liver Cancer Cell Growth in Lab Tests

Scientists at the University of Delaware (UD) and the University of Illinois at Chicago (UIC) have found a new way to kill liver cancer cells and inhibit tumor growth. First, they silence a key cellular enzyme, and then they add a powerful drug. They describe their methods in an open-access article published online on January 31, 2018 in Nature Communications. The article is titled “Hexokinase-2 Depletion Inhibits Glycolysis and Induces Oxidative Phosphorylation in Hepatocellular Carcinoma and Sensitizes to Metformin.” This research could accelerate the development of new treatments for liver cancer, which is currently difficult to cure. Often surgery is not an option for liver cancer, and the available drugs are only modestly effective. More than 82 percent of liver cancer patients die within five years of diagnosis, according to the National Institutes of Health. This project originated in labs at the UIC, where researchers grew liver cancer cells and manipulated their expression of an enzyme called hexokinase-2. Then, the cells were treated with metformin, a diabetes drug that decreases glucose production in the liver. The research group of Maciek R. Antoniewicz, PhD, Centennial Professor of Chemical and Biomolecular Engineering at the University of Delaware (UD), designed a set of experiments to measure how cancer cells respond to the loss of hexokinase-2, an enzyme that helps cells metabolize glucose, their food source. Dr. Antoniewicz is an expert in metabolic flux analysis, a technique for studying metabolism in biological systems. His research group is one of only a few in the world with expertise in a technique called 13C metabolic flux analysis of cancer cells, and he recently published a paper in Experimental & Molecular Medicine describing his methods.

Venus Fly Traps Rarely Consume Insects That Pollinate Them

While most people are familiar with Venus flytraps and their snapping jaws, there is still much that scientists don't know about the biology of these carnivorous plants. Researchers have for the first time discovered which insects pollinate the rare plants in their native habitat - and discovered that the flytraps don't eat these pollinator species. Venus flytraps (Dionaea muscipula) are in a genus all their own, and are native to a relatively small area, restricted to within a 100-mile radius of Wilmington, North Carolina. "These findings answer basic questions about the ecology of Venus flytraps, which is important for understanding how to preserve a plant that is native to such a small, threatened ecosystem," says Elsa Youngsteadt, a research associate at North Carolina State University and lead author of a paper on the work. "It also illustrates the fascinating suite of traits that help this plant interact with insects as both pollinators and prey." The paper, "Venus Flytrap Rarely Traps Its Pollinators," was published online on February 5, 2018 in the journal American Naturalist. "Everybody's heard of Venus flytraps, but nobody knew what pollinated them - so we decided to find out," says Clyde Sorenson, PhD, co-author of the paper describing the work and Alumni Distinguished Undergraduate Professor of Entomology at NC State. To that end, researchers captured insects found on Venus flytrap flowers at several sites during the plant's five-week flowering season. The researchers identified each insect and checked to see if they were carrying Venus flytrap pollen - and, if they were carrying pollen, how much.

Scientists Identify Secretion-Mediated Pathway Essential for Survival of Glioma Stem Cells

Glioblastoma multiforme is the most common and aggressive primary brain tumor and has one of the worst survival rates of all cancers. Despite surgery, radiation, and chemotherapy, these tumors virtually always become resistant to therapy and eventually recur. The cancer stem cells within these tumors are thought to be important drivers of resistance and recurrence. Researchers at Dartmouth's Norris Cotton Cancer Center, led by Damian A. Almiron Bonnin, MD-PhD candidate of the Mark Israel laboratory, are devising strategies to target glioma stem cells which could significantly improve patient survival. "The presence of glioma stem cells within high-grade gliomas is one of the reasons they are so difficult to treat," says Almiron Bonnin. "In this study, we have successfully identified a secretion-mediated pathway that is essential for the survival of glioma stem cells within aggressive brain tumors." Multiple studies suggest that these cancer stem cells resist therapy and give rise to recurrences. "To put it simply, if you eliminate most of the tumor with standard treatments, but leave even one cancer stem cell behind, that cell could, in theory, give rise to an entire new tumor," says Almiron Bonnin. "Therefore, making sure these cells are being effectively targeted is an important goal of cancer research." The team is using its understanding of the mechanism by which these cells are maintained within brain tumors to develop new and potentially more effective approaches to treating high-grade brain tumors. The team’s strategy of utilizing drugs that target glioma stem cells may increase the effectiveness of chemotherapy agents in brain tumors and ultimately prolong the survival of patients with this type of tumor.

February 6th

More Structured Senescence May Be Another Clue to Long Life Span and Cancer Resistance of Naked Mole Rat

With their large buck teeth and wrinkled, hairless bodies, naked mole rats won't be winning any awards for cutest rodent. But their long life span--they can live up to 30 years, the longest of any rodent--and remarkable resistance to age-related diseases, offer scientists key clues to the mysteries of aging and cancer. That's why University of Rochester biology professors Vera Gorbunova, PhD, and Andrei Seluanov, PhD, and postdoctoral associate Yang Zhao, PhD, studied naked mole rats to see if the rodents exhibit an anticancer mechanism called cellular senescence--and, if so, "how the mechanism might work differently than in short-lived animals, like mice," says Dr. Zhao, the lead author of the study, published online on February 5, 2018 in PNAS. The article is titled “Naked Mole Rats Can Undergo Developmental, Oncogene-Induced and DNA Damage-Induced Cellular Senescence.” Cellular senescence is an evolutionary adaptation that prevents damaged cells from dividing out of control and developing into full-blown cancer. However, senescence has a negative side too: by stopping cell division in order to prevent potential tumors, it also accelerates aging. Previous studies indicated that when cells that had undergone senescence were removed from mice, the mice were less frail in advanced age as compared to mice that aged naturally with senescent cells intact. Researchers therefore believed senescence held the key to the proverbial fountain of youth; removing senescent cells rejuvenated mice, so perhaps it could work with human beings. Companies began investigating drugs--known as senolytic agents--that would kill senescent cells and translate the anti-aging effects to humans.

Structure of Full-Length Serotonin Receptor Imaged for First Time by Cryo-EM; Results May Drive “Targeted Drug Design and Better Therapeutic Strategies”

A team of researchers from Case Western Reserve University School of Medicine has used Nobel-prize-winning electron microscope technology (cryo-EM) to image full-length serotonin receptors for the first time. The tiny proteins--approximately a billionth of a meter long--are common drug targets, despite limited available information about their structure. Now, new images published online on February 6, 2018 in Nature Communications provide snapshots of the receptors, including details about molecular binding sites that could lead to more precise drug design. The open-access article is titled “Cryo-EM Structure of 5-HT3A Receptor in Its Resting Conformation.” Serotonin receptors sit in cell membranes throughout the body, including membranes in the brain, stomach, and nerves. These receptors are highly dynamic with many moving parts, making them difficult subjects to capture in images. Researchers commonly break the receptor into pieces to study it. But by studying full-length serotonin receptors, researchers in the new study showed how its different portions interact. The researchers describe "a finely-tuned orchestration of three domain movements" that allows the receptors to elegantly control passageways across cell membranes. The study reveals how serotonin receptors work, says study first author Sandip Basak, PhD, a postdoctoral fellow in the Department of Physiology and Biophysics at Case Western Reserve University School of Medicine. "The serotonin receptor acts as a gateway, or channel, from outside the cell to inside," he says. "When serotonin binds onto the receptor, the channel switches conformation from closed to open. It eventually twists into a 'desensitized' state, where the channel closes but serotonin remains attached.

New CRISPR/Cas9 Gene-Editing Technique Abolishes Splice Sites for Frequently Mutated Exons in Duchenne Muscular Dystrophy (DMD) Heart Muscle Cells

Scientists have developed a CRISPR/Cas9 gene-editing technique that can potentially correct a majority of the 3,000 mutations that cause Duchenne muscular dystrophy (DMD) by making a single cut at strategic points along the patient’s DNA, according to a study from the University of Texas (UT) Southwestern Medical Center. The method, successfully tested in heart muscle cells from patients, offers an efficient alternative to the daunting task of developing an individualized molecular treatment for each gene mutation that causes DMD. It also opens up possible new treatment approaches for other diseases that have thus far required more intrusive methods to correct single-gene mutations. Scientists say the new strategy enhances the accuracy for surgical-like editing of the human genome, correcting mistakes in the DNA sequence that cause devastating diseases like DMD, a deadly condition caused by defects in the dystrophin gene. Normally, the dystrophin protein helps strengthen muscle fibers. “This is a significant step,” said Dr. Eric Olson, Director of UT Southwestern’s Hamon Center for Regenerative Science and Medicine. “We’re hopeful this technique will eventually alleviate pain and suffering, perhaps even save the lives, of DMD patients who have a wide range of mutations and, unfortunately, have had no other treatment options to eliminate the underlying cause of the disease.” A study published online on January 31, 2018 in Science Advances documents the success of the new CRISPR/Cas9 gene-editing technique designed to treat DMD. The open-access article is titled “Correction of Diverse Muscular Dystrophy Mutations in Human Engineered Heart Muscle by Single-Site Genome Editing.” In the article abstract, the authors, including Dr. Olson, state the following.

Arginine May Have Played Key Role in Origin of Life; Finding Would Put Constraints on Types of Scenarios That Could Have Given Rise to the Genetic Code

Life as we know it originated roughly 3.5 to 4 billion years ago in the form of a prebiotic soup of organic molecules that somehow began to replicate themselves and pass along a genetic formula--or so goes the thinking behind the RNA World, one of the most robust hypotheses on the origin of life. Researchers at the University of California-Santa Barbara (UCSB) have now found evidence that the amino acid arginine (or its prebiotic world equivalent) may have been a more important ingredient in this soup than previously thought. "People tend to think of arginine as not being prebiotic," said Irene Chen, MD, PhD, a biophysicist whose research focuses on the chemical origins of life. "They tend to think of the simpler amino acids as being plausible, such as glycine and alanine." Arginine, by contrast, is relatively more complex, and was therefore thought to have entered the game at a later stage. Primordial Earth, according to the RNA World theory, had the conditions to host several types of biomolecules, including nucleic acids (which become genetic material), amino acids (which eventually link to form the proteins that are responsible for structure and function of cells), and lipids (which store energy and protect cells). Under what circumstances and how these biomolecules worked together is a source of ongoing investigation for researchers of the origins of life. For their investigation, the UCSB scientists analyzed a dataset of in vitro evolved complexes of proteins and aptamers (short RNA and DNA molecules that bind to specific target proteins).