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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.

Transplant of Skin Derived from Genetically Modified Stem Cells Saves Life of Child with Life-Threatening Congenital Skin Disease (Epidermolysis Bullosa); 80% of Body Surface Transplanted in World-First Success

A medical team at the Ruhr-Universität Bochum’s burn unit (Germany) and the Center for Regenerative Medicine at the University of Modena (Italy) is the first ever to successfully treat a child suffering from extensive skin damage using transplants derived from genetically modified stem cells. The boy is a so-called butterfly child: he suffers from epidermolysis bullosa, a genetic skin disease that had destroyed approximately 80 percent of his epidermis. After all established therapies had failed, the medical team from Bochum decided to try an experimental approach: the doctors transplanted skin derived from genetically modified stem cells onto the wound surfaces. Thanks to the successful therapy, the boy is now – two years after the treatment – able to participate in his family’s life and social life. The scientists published their report online on November 8, 2017 in Nature. The article is titled “Regeneration of the Entire Human Epidermis by Transgenic Stem Cells.” Epidermolysis bullosa is the scientific name of a congenital skin disease that is currently considered to be incurable. Its underlying mechanism is a defect in protein-forming genes that are essential for skin regeneration. Even minor stress can result in blisters, wounds, and skin loss with scar formation. Depending on disease severity, internal organs may likewise be affected, leading to critical dysfunctions. The disease significantly reduces the patients’ quality of life; often it is also life-threatening, as in the case of Hassan, the seven-year-old: by the time he was admitted to the pediatric intensive care unit at Katholisches Klinikum Bochum in June 2015, 60 percent of his epidermis had been lost.

Sheep Can Recognize Human Faces from Two-Dimensional Images

Sheep can be trained to recognize human faces from photographic portraits - and can even identify the picture of their handler without prior training - according to new research from scientists at the University of Cambridge (UK). The study, published online on November 8, 2017 in Royal Society: Open Science, is part a series of tests given to the sheep to monitor their cognitive abilities. The open-access article is titled “Sheep Recognize Familiar and Unfamiliar Human Faces from Two-Dimensional Images.” Because of the relatively large size of their brains and their longevity, sheep are a good animal model for studying neurodegenerative disorders such as Huntington's disease. The ability to recognize faces is one of the most important human social skills. We recognize familiar faces easily, and can identify unfamiliar faces from repeatedly presented images. As with some other animals such as dogs and monkeys, sheep are social animals that can recognize other sheep as well as familiar humans. Little is known, however, about their overall ability to process faces. Researchers from the University of Cambridge's Department of Physiology, Development, and Neuroscience trained eight sheep to recognize the faces of four celebrities from photographic portraits displayed on computer screens. The celebrities were Fiona Bruce, Jake Gyllenhaal, Barack Obama, and Emma Watson. Training involved the sheep making decisions as they moved around a specially-designed pen. At one end of the pen, they would see two photographs displayed on two computer screens and would receive a reward of food for choosing the photograph of the celebrity (by breaking an infrared beam near the screen); if they chose the wrong photograph, a buzzer would sound and they would receive no reward. Over time, they learn to associate a reward with the celebrity's photograph.

Three-Step, Pre-Targeted Radioimmunotherapy Approach to Treating Colorectal Cancer Leads to Complete Cure in Mouse Model

Researchers at Memorial Sloan Kettering Cancer Center in New York City and Massachusetts Institute of Technology in Boston have developed a new, three-step system that uses nuclear medicine to target and eliminate colorectal cancer. In this study in a mouse model, researchers achieved a 100-percent cure rate--without any treatment-related toxic effects. The study is reported in the November 2017 featured article (image) in The Journal of Nuclear Medicine. The article is titled “Curative Multicycle Radioimmunotherapy Monitored by Quantitative SPECT/CT-Based Theranostics, Using Bispecific Antibody Pretargeting Strategy In Colorectal Cancer." Until now, radioimmunotherapy (targeted therapy) of solid tumors using antibody-targeted radionuclides has had limited therapeutic success. "This research is novel because of the benchmarks reached by the treatment regimen, in terms of curative tumor doses, with non-toxic secondary radiation to the body's normal tissues," explains Steven M. Larson, MD, and Sarah Cheal, PhD, both of Memorial Sloan Kettering Cancer Center. "The success in murine tumor models comes from the unique quality of the reagents developed by our group, and the reduction to practice methodology, including a theranostic approach that can be readily transferred, we believe, to patients." Theranostics, a term derived from therapy and diagnostics, is the use of a single agent to both diagnose and treat disease. The theranostic agent first finds the cancer cells, then destroys them, leaving healthy cells unharmed--minimizing side effects and improving quality of life for patients.

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