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Antibodies As a Potential Fix to HIV/AIDS—Interview with Adrian McDermott, Acting Chief of the Immunology Core in the NIH’s Vaccine Research Center

by Sara Malmanger, University of Wisconsin-Madison, Science Writing Intern with BioQuick News

HIV researchers have found that giving the human body’s immune system a boost of specific antibodies may be a potential fix to HIV/AIDS as we seek a cure or vaccine. Our world could be free of this deadly virus sooner than we ever thought possible. Researchers are hopeful that they have found a way to turn our own immune systems against the disease. In an interview, Adrian McDermott (photo), PhD, from the NIH’s Vaccine Research Center, said, “We are hoping to use HIV-specific antibodies that target vulnerable parts of the HIV envelope to prevent and treat HIV.” The Vaccine Research Center is within the NIH’s National Institute of Allergy and Infectious Diseases, and Dr. McDermott is presently Acting Chief, Immunology Core, within the Vaccine Research Center. He is a former Director of Immunobiology and Vaccine Design at the International AIDS Vaccine Initiative (IAVI) in New York. The antibody studies are important because more than 35 million people have HIV worldwide, and around one million people have HIV in the United States. Despite the common feeling that AIDS (acquired immunodeficiency syndrome) is a disease of the past, it is still harming and destroying many lives. HIV (human immunodeficiency virus) essentially erodes and ultimately destroys the immune system over time. HIV, without appropriate health care and treatment, can develop into AIDS. Once a person reaches the AIDS stage of the infection, the immune system can’t fight off pathogens that cause common illnesses, where a healthy immune system could knock these bugs out with ease.

Autoimmune Disease Discovery Could Spark New Treatments; Scientists Synthesize Small Molecule Inhibitor of Toll-Like Receptor 8 (TLR8)

University of Colorado (UC) Boulder researchers have discovered a potent, drug-like compound that could someday revolutionize treatment of rheumatoid arthritis and other autoimmune diseases by inhibiting a protein instrumental in prompting the body to start attacking its own tissue. "We have discovered a key to lock this protein in a resting state," said Dr. Hang Hubert Yin, a biochemistry professor at the BioFrontiers Institute and lead author of a paper, published on November 20, 2017 in Nature Chemical Biology, describing the discovery. "This could be paradigm shifting." The article is titled “Small-Molecule Inhibition of TLR8 Through Stabilization of Its Resting State.” More than 23.5 million Americans suffer from autoimmune diseases like rheumatoid arthritis, scleroderma, and lupus, in which an excessive immune response leads to pain, inflammation, skin disorders, and other chronic health problems. Three of the top five selling drugs in the United States aim to ease autoimmune disease symptoms. But no cure exists, and treatments are expensive and come with side effects. "Given the prevalence of these diseases, there is a big push for alternatives," Dr. Yin said. For years, scientists have suspected that a protein called Toll-like receptor 8 (TLR8) plays a key role in the innate immune response. When TLR8 senses the presence of a virus or bacterium, it goes through a series of steps to transform from its passive to active state, triggering a cascade of inflammatory signals to fight off the foreign invader. But, as Dr. Yin explained, "it can be a double-edged sword" leading to disease when that response is excessive.

Dog Ownership Linked to Lower Mortality, Especially in Persons Living Alone

A team of Swedish scientists have used national registries of more than 3.4 million Swedes aged 40 to 80 to study the association between dog ownership and cardiovascular health. Their study shows that dog owners had a lower risk of death due to cardiovascular disease or to other causes during the 12-year follow-up. A total of more than 3.4 million individuals without any prior cardiovascular disease in 2001 were included in the researchers' study linking together seven different national data sources, including two dog ownership registers. The results were published for the first time on November 17, 2017 in Scientific Reports. The goal was to determine whether dog owners had a different risk of cardiovascular disease and death than non-dog owners. The open-access Scientific Reports article is titled “Dog Ownership and the Risk of Cardiovascular Disease and Death – A Nationwide Cohort Study.” "A very interesting finding in our study was that dog ownership was especially prominent as a protective factor in persons living alone, which is a group reported previously to be at higher risk of cardiovascular disease and death than those living in a multi-person household. Perhaps a dog may stand in as an important family member in the single households. The results showed that single dog owners had a 33% reduction in risk of death and 11% reduction in risk of myocardial infarction during follow-up compared to single non-owners. Another interesting finding was that owners of dogs from breed groups originally bred for hunting were most protected," says Mwenya Mubanga, lead junior author of the study and a PhD student at the Department of Medical Sciences and the Science for Life Laboratory, Uppsala University. In Sweden, every person carries a unique personal identity number.

Ancient RNA-Detecting Enzyme (TGIRT) Could Boost Power of Liquid Biopsies to Detect and Profile Cancers

Scientists are developing a set of medical tests called liquid biopsies that can rapidly detect the presence of cancers, infectious diseases, and other conditions from only a small blood sample. Researchers at The University of Texas at Austin are developing a new tool for liquid biopsy that could soon provide doctors with a more complete picture of an individual's disease, improving their chances of finding the best treatment, while also sparing patients the pain, inconvenience, and long wait times associated with surgical biopsies. Dr. Alan Lambowitz, a Professor in the Institute for Cellular and Molecular Biology and the Department of Molecular Biosciences, and his team are studying an ancient enzyme in bacteria that can be used to detect bits of genetic material shed by cancer or other diseased cells into a patient's bloodstream. Many current liquid biopsies can detect DNA in blood; others can detect RNA, although they tend to miss many key RNA biomarkers and misinterpret others. But this ancient enzyme, described in a paper published online on November 16, 2017 in Molecular Cell, detects the full range of RNAs with much higher accuracy, which is helpful for understanding both the general profile of a disease such as cancer and specific information about its activity in a particular patient. This improved method could provide a key tool for doctors pursuing the dream of precision medicine, or treatments tailored to individuals based on their genetics and life histories, as well as the unique aspects of their diseases. In this new study, postdoctoral researcher Dr. Jennifer Stamos uncovered for the first time the molecular structure of this RNA-detecting enzyme in action, offering clues about how it works and how it can be improved for use in medical tests.

How Bacteria in the Gut May Influence Neurodegenerative Disorders

Humans have roughly as many bacterial cells in their bodies as human cells, and most of those bacteria live in the gut. New research released on November 13, 2017 reveals links between the gut microbiome -- the population of microorganisms living in the gastrointestinal tract -- and brain diseases such as Parkinson's and Alzheimer's, including potential new ways to track and treat these diseases. The studies were presented at Neuroscience 2017, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health. Neuroscience 2017 took place in Washington, DC, November 11-15. Almost 100 trillion microbes -- some beneficial and some harmful -- live in the human gastrointestinal tract at any time, helping to regulate immune function and inflammation, two factors hypothesized to play a role in neurodegenerative diseases like Parkinson's and Alzheimer's. As brain-focused cures for such diseases remain elusive, scientists are looking to the microbiome for new insight and novel strategies. New findings presented at the meeting include the following: Metabolites derived from the microbiome block protein misfolding in test tubes and prevent neurodegeneration in a fly model of a disease related to Parkinson's, hinting that gut-derived metabolites may hold therapeutic promise (Lap Ho, abstract 573.23). A rat model of Parkinson's disease displays increased levels of an inflammatory protein in the colon, identifying a possible new biomarker for the disease (Doris J. M. Doudet, abstract 133.13). Nonhuman primates that received stomach injections of a protein associated with Parkinson's disease show signs of the disease in their brains, revealing that pathology can spread from the gut to the brain (Erwan Bezard, abstract 131.02).

Why Hot Water Can Freeze Faster Than Cold Water; Possible Explanation from Computer Simulation of Mpemba Effect in Granular Fluids

Researchers in Spain have discovered that hot granular fluids can freeze faster than cold granular fluids, opening the door to the theoretical understanding of the so-called Mpemba effect. The researchers, who published the findings on October 4, 2017 in Physical Review Letters, have confirmed how this phenomenon occurs in granular fluids, that is, those composed of particles that are very small and interact among those that lose part of their kinetic energy. The article is titled “When the Hotter Cools More Quickly: Mpemba Effect in Granular Fluids.” Thanks to this theoretical characterization, "we can simulate on a computer and make analytical calculations to know how and when the Mpemba effect will occur," said Dr. Antonio Lasanta. Dr. Lasanta is from the UC3M Gregorio Millán Barbany University Institute for Modeling and Simulation on Fluid Dynamics, Nanoscience and Industrial Mathematics. "In fact," he said, "we find not only that the hottest can cool faster but also the opposite effect: the coldest can heat faster, which would be called the inverse Mpemba effect." The fact that preheated liquids freeze faster than those that are already cold was observed for the first time by Aristotle in the 4th century AD. Francis Bacon, the father of scientific empiricism, and René Descartes, the French philosopher, were also interested in the phenomenon, which became a theory when, in 1960, a Tanzanian student named Erasto Mpemba explained to his teacher in a class that the hottest mixture of ice cream froze faster than the cold one. This anecdote inspired a technical document about the subject, and the effect began to be analyzed in educational and science magazines. However, its causes and effects have hardly been studied until now.

Cornell Study Reveals Why Testicular Cancer Is So Responsive to Chemotherapy

Cornell researchers have taken a major step toward answering a key question in cancer research: Why is testicular cancer so responsive to chemotherapy, even after it metastasizes? Professional cyclist Lance Armstrong, for example, had testicular cancer that spread to his lung and brain, yet he made a full recovery after conventional chemotherapy. The key to such success appears to lie in the cancer's stem cells, which are more sensitive to chemotherapy than stem cells found in other types of cancer. Defining why testicular cancers are so susceptible to chemotherapy could eventually provide insights for treating other, more resistant cancers. The group's study, published today (November 14, 2017) in Cell Reports, also helped confirm that risk for testicular cancer is determined in utero. The open-access article is titled “Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.” The research offers some evidence to support a hypothesis that, in humans, testicular cancers are initiated during embryonic development and lie dormant for 18 to 35 years. "The study provides new insights into the basis for the responsiveness of testicular cancer to chemotherapy, which has always been an intriguing observation, but the basis for it was not clear," said Dr. Robert Weiss, Professor of Biomedical Sciences at Cornell's College of Veterinary Medicine and senior author of the study. Timothy Pierpont, a graduate student in Dr. Weiss' lab, is the paper's first author. Most types of tumors contain distinct populations of cells. A small fraction of these are stem cells, which have the ability to grow new tumors from a single cell and - in most cancers - are extremely resistant to therapy.

Distinct Molecular Signatures (miRNAs) Identified in Spinal Fluid of Patients with Gulf War Illness and Chronic Fatigue Syndrome

Researchers at Georgetown University Medical Center (GUMC) have found distinct molecular signatures in two brain disorders long thought to be psychological in origin -- chronic fatigue syndrome (CFS) and Gulf War Illness (GWI). In addition, the work supports a previous observation by GUMC investigators of two variants of GWI. The disorders share commonalities, such as pain, fatigue, cognitive dysfunction, and exhaustion after exercise. The study, published online on November 10, 2017 in Scientific Reports, lays groundwork needed to understand these disorders in order to diagnose and treat them effectively, says senior investigator James N. Baraniuk, MD, Professor of Medicine at Georgetown University School of Medicine. Narayan Shivapurkar, PhD, Assistant Professor of Oncology at the medical school worked with Dr. Baraniuk on the research. Their open-access article is titled “Exercise-Induced Changes in Cerebrospinal Fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and Sedentary Control Subjects.” The changes in brain chemistry -- observed in levels of miRNAs that turn protein production on or off -- were seen 24 hours after subjects rode a stationary bike for 25 minutes. "We clearly see three different patterns in the brain's production of these molecules in the CFS group and the two GWI phenotypes," says Dr. Baraniuk. "This news will be well received by patients who suffer from these disorders who are misdiagnosed and instead may be treated for depression or other mental disorders." Chronic fatigue syndrome (also called myalgic encephalomyelitis, ME/CFS) affects between 836,000 and 2.5 million Americans, according to a National Academy of Medicine report.

How “Flipped” Gene Helped Butterflies Evolve Mimicry: Rare Genetic Inversion 2 Million Years Ago Helped Asian Swallowtail Butterflies Develop Different Wing Patterns to Disguise Themselves from Predators

Female swallowtail butterflies do something a lot of butterflies do to survive: they mimic wing patterns, shapes and colors of other species that are toxic to predators. Some - but not all - swallowtail species have evolved several different forms of this trait. But what kind of genetic changes led to these various disguises, and why would some species maintain an undisguised form when mimicry provides an obvious evolutionary advantage? In a new study published online on November 7, 2017 in Nature Communications, scientists from the University of Chicago analyzed genetic data from a group of swallowtail species to find out when and how mimicry first evolved, and what has been driving those changes since then. The open-access article is titled “Tracing the Origin and Evolution of Supergene Mimicry in Butterflies.” It's a story that started around two million years ago, but instead of steady, progressive changes, one chance genetic switch helped create the first swallowtail mimics. And it has stuck around ever since. "In butterflies with one color pattern, we have a gene in a normal orientation on the chromosome. In the butterflies with the unusual, alternate color pattern, that gene was spliced out, flipped, and then spliced back into the chromosome at some point," said Marcus Kronforst, PhD, Associate Professor of Ecology and Evolution at U Chicago and the senior author of the study. "That flip, or inversion, keeps the two genes from recombining if those two different kinds of butterflies mate, so they've kept both copies of the gene over evolutionary time, because they split from their common ancestor two million years ago," Dr. Kronforst said. For a long time, scientists thought that butterfly mimicry was controlled by "supergenes," groups of several tightly linked genes that were always inherited as a group.

Former NFL Football Players Twice As Likely to Have Enlarged Aortas; Health Risk Currently Unknown

Former NFL players were more likely to have enlarged aortas, but further study is needed to determine whether that puts them at greater risk for life-threatening aneurysms, researchers found. The former National Football League players were twice as likely to have enlarged aortas as those in a control group, even after adjusting for their typically larger size and other factors, said researchers with the Dallas Heart Study at UT Southwestern Medical Center, from which the control group was drawn. “Whether that translates to the same risk for these former elite athletes as a dilated, or enlarged, aorta does for the general population is unclear,” said cardiologist Dr. Parag Joshi, Assistant Professor of Internal Medicine and one of the study’s authors. “Is this a normal adaptation from having trained at the elite level throughout their youth, or is this a bad adaptation that puts them more at risk for problems?” Former linemen – players who tend to be larger and engage in more strength training than non-linemen – were more likely to cross the threshold into the enlarged aorta range, suggesting that increased aortic diameter is an adaptation to the demands placed on a player’s heart during his career, said co-author and fellow cardiologist Dr. James de Lemos, Professor of Internal Medicine and Medical Director for the Dallas Heart Study. Nearly 30 percent of the former NFL players studied had enlarged aortas compared with less than 9 percent in the comparison group from the Dallas Heart Study, a one-of-a-kind population-based study to identify new genetic, protein, and imaging biomarkers that can detect cardiovascular disease at its earliest stages, when prevention is most effective.

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