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Supercomputer Analysis Supports Darwin’s Theory on the Eastern Pacific’s “Impassable” Barrier

An international team of scientists used a state-of-the-art computer model, a high-powered supercomputer, and five billion “virtual” coral larvae to test Charles Darwin's 1880 hypothesis that marine species cannot cross the Eastern Pacific's "impassable" marine barrier. The research team, which included University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science Associate Professor Claire Paris, found that Darwin's theory still holds true today even under extreme El Niño conditions known to speed up ocean currents. To trace the journey of coral larvae transported by ocean currents in the Eastern Pacific Barrier, a 4,000-mile stretch of ocean that separates the central from the eastern Pacific Ocean, researchers from the University of Bristol and Penn State University used Paris's biophysical model on Bristol University's BlueCrystal supercomputer to simulate five billion model “larvae” from 636 remote reefs traveling on ocean currents over a 14-and-a-half year period. "This work wouldn't have been possible until recently because of the computer power, the climate data, and the probabilistic biophysical model necessary to find some robust modeling results," said Dr. Paris, a coauthor of the study. Dr. Paris's open-source software, called the Connectivity Modeling System, simulates the movement of larvae in the ocean by currents and incorporates aspects of their biology, such as development and death. The simulations showed that, even in extreme environmental events such as the 1997-1998 El Niño that speed ocean currents, coral larvae could not survive long enough to make the trip from coral reefs in the western and central Pacific to help corals in the east recover from recent environmental damage.

Perilipin 5 Protein Found to Break Down Fat and Stimulate Production of New, More Efficient Mitochondria; May Explain Above-Normal Levels of Perilipin 5 in Endurance Athletes, While Offering New Clues to Treating Diabetes

Researchers at the UT (University of Texas) Southwestern Medical Center have found that a protein often located on the surface of fat droplets within cells – and especially abundant in the muscles of endurance athletes – can kick-start the more efficient and healthful breakdown of fat. The findings could have significant implications for development of new ways to treat obesity and type 2 diabetes, said Dr. Perry Bickel, Associate Professor of Internal Medicine at UT Southwestern and senior author of the study published online on September 24, 2016 in Nature Communications. The open-access article is titled “Nuclear Perilipin 5 Integrates Lipid Droplet Lipolysis with PGC-1α/SIRT1-Dependent Transcriptional Regulation of Mitochondrial Function.” More than 29 million Americans have diabetes, and it is the seventh leading cause of death in the U.S., according to the American Diabetes Association. Almost 26 percent of Americans age 65 and older have diabetes. The study reports a new role for the protein, Perilipin 5, in the cell nucleus as a regulator of fat metabolism. The finding that it was in the nucleus “was a complete surprise to us,” said Dr. Bickel, who is also Chief of the Division of Endocrinology and holds the Daniel W. Foster, M.D. Distinguished Chair in Internal Medicine at UT Southwestern. In obese people and rodents, excess fat can accumulate in tissues not specialized for fat storage, such as skeletal muscle, the heart, and liver. This buildup can lead to dysfunction of those tissues, Dr. Bickel said. Trying to break down large amounts of fat can overload the body’s metabolic system, swamping the tiny cellular mitochondria whose jobs are to turn fat into fuel for work or heat, he explained.

Insulin Pill Could Make Diabetes Treatment “Ouchless”

Every day, millions of Americans with diabetes have to inject themselves with insulin to manage their blood-sugar levels. But less painful alternatives are emerging. Scientists are developing a new way of administering the medicine orally with tiny vesicles that can deliver insulin where it needs to go without a shot. On August 24, the developing scientists share their in vivo testing results. The researchers are presenting their work at the 252nd National Meeting & Exposition of the American Chemical Society (ACS) in Philadelphia. The ACS is the world's largest scientific society and this year’s meeting features more than 9,000 presentations on a wide range of science topics The meeting runs from August 21 through August 25. "We have developed a new technology called a CholestosomeTM," says Mary McCourt, Ph.D., a leader of the research team. "A CholestosomeTM is a neutral, lipid-based particle that is capable of doing some very interesting things." The biggest obstacle to delivering insulin orally is ushering it through the stomach intact. Proteins such as insulin are no match for the harsh, highly acidic environment of the stomach. The proteins are degraded before they get a chance to move into the intestines and then the bloodstream where they're needed. Some efforts have been made to overcome or sidestep this barrier. One approach packages insulin inside a protective polymer coating to shield the protein from stomach acids and is being tested in clinical trials. Another company developed and marketed inhalable insulin, but despite rave reviews from some patients, sales have not been good. No, its future is uncertain.

New Insights into Killing Pathogenicic Mycobacteria

Bacteria that cause tuberculosis, leprosy, and other diseases, survive by switching between two different types of metabolism. EPFL(Ecole Polytechnique Fédérale de Lausanne) scientists have now discovered that this switch is controlled by a mechanism that constantly adapts to meet the bacterium's survival needs, like a home's thermostat reacting to changes in temperature. Mycobacteria are a category of pathogenic bacteria that causes tuberculosis, leprosy, and various infections that harm people with compromised immune systems, e.g., AIDS patients. When in the human body, mycobacteria produce energy by metabolizing fats through a "cycle" of biochemical reactions. Along the way, the cycle also produces a molecule that the bacterium can take away to use elsewhere, thus stopping the energy-producing cycle. EPFL scientists have now found that mycobacteria can switch between these two routes by using a "volume control" mechanism that improves their survival. The findings, published online on August 24, 2016 in Nature Communications, could prove critical for developing new treatments. The open-access article is titled” A Rheostat Mechanism Governs the Bifurcation of Carbon Flux in Mycobacteria.” The molecule in question is called isocitrate, which, once produced, can go in two directions: continue the energy production cycle or be taken away to synthesize other parts of the bacterium. But if isocitrate goes the biosynthesis route, it must be replenished or else the energy-producing cycle will stop. Devastating though it sounds, this does present an excellent target for killing off an infecting mycobacterium.

MicroRNA-Containing Vesicles Released from Primary Melanoma Lay the Groundwork for Metastasis; Landmark Discovery May Point the Way to Treatment and Even Cure for This Deadly Cancer

In a landmark discovery, researchers at Tel Aviv University have unraveled the metastatic mechanism of melanoma, the most aggressive of all skin cancers. According to a paper published online on August 22, 2016 in Nature Cell Biology, the scientists discovered that before spreading to other organs, a melanoma tumor sends out tiny vesicles containing molecules of microRNA. These induce morphological changes in the dermis in preparation for receiving and transporting the cancer cells. The researchers also found chemical substances that can stop the process and are therefore promising drug candidates. "The threat of melanoma is not in the initial tumor that appears on the skin, but rather in its metastasis -- in the tumor cells sent off to colonize in vital organs like the brain, lungs, liver, and bones," said research leader Dr. Carmit Levy of the Department of Human Molecular Genetics and Biochemistry at TAU's Sackler School of Medicine. "We have discovered how the cancer spreads to distant organs and found ways to stop the process before the metastatic stage." The TAU group worked in close collaboration with Professor Jörg D. Hoheisel and Laureen Sander at the German Cancer Research Center (DKFZ) in Heidelberg, Dr. Shoshi Greenberger at the Sheba Medical Center at Tel HaShomer, Israel and Dr. Ronen Brenner at the Wolfson Medical Center in Holon, Israel. Lab research was led by Dr. Shani Dror of Dr. Levy's research group. Melanoma, the most aggressive and lethal type of skin cancer, causes the death of one person every 52 minutes according to data from the Skin Cancer Foundation, and the number of diagnosed cases has been on the rise for the past three decades. Despite a range of therapies developed over the years, there is still no full remedy for this life-threatening disease.

New Optogenetics Work Enables Spatially Restricted ChR Expression; Allows Unmasking of Synaptic Connections from Neurons Whose Cell Bodies Lie Close to the Dendrites of the Postsynaptic Cell

>Optogenetics is a technique that combines genetics and optics to control neuronal activity, which is based on the discovery of light-sensitive membrane channels within pond algae that control movement in response to light. When genes that produce one such light-sensitive membrane channel, called channelrhodopsin (ChR), are inserted into neurons and subsequently exposed to light, they regulate the flow of ions across cell membranes, increasing the neuron's activity. This allows scientists to discretely control neuronal activity by using p ulses of light to activate specific populations of neurons. Optogenetics is leveraged for mapping connections in the brain by stimulating individual neurons with light and recording the responses of nearby neurons with an electrode. In this manner, scientists ask whether stimulation of a putative presynaptic neuron causes a response in the putative postsynaptic neuron being monitored by the electrode. When ChRs are inserted into neurons using genetic techniques, however, their expression occurs throughout the entire surface of the neuron, from dendrites, the parts of the neuron that receive information, to the axon, the part of the neuron that sends information. The fact that ChR expression is not restricted to one particular domain of the neuron limits the information researchers can collect and interpret about synaptic connectivity, because it can be difficult to determine whether ChR stimulation was generated in a protein located in that neuron's cell body, or in the axon terminal or in the dendrites of other cells that happen to be passing through the light-stimulated area. In their article published online on August 15, 2016 in eLIFE, Max Planck Florida Institute (MPFI) researchers, Christopher A. Baker, Ph.D.

Exosomes Derived from Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

The medical world may be one step closer to an affordable, effective therapeutic vaccine for hepatitis C virus (HCV), according to a new study appearing in the latest issue of Stem Cells Translational Medicine. According to a release issued on August 5, 2016, the study, by scientists at Second Military Medical University in Shanghai, China, showed how exosomes secreted from umbilical mesenchymal stem cells (uMSC) efficiently suppressed HCV infection. Chronic hepatitis C is a serious disease that can result in long-term health problems. Worldwide, 700,000 people die each year from HCV-related liver diseases, according to the World Health Organization. While newly developed antiviral medicines could cure approximately 90 percent of those with HCV infection, access to diagnosis and treatment is limited and there is currently no vaccine to prevent it. There are other issues, also, according to Zhongtian Qi, Ph.D., M.D., the SCTM study’s lead investigator. “Though the development of these antivirals has improved the response rate in HCV patients, new more effective anti-HCV agents that also have better tolerance and cheaper production costs are still urgently needed,” he said. His research team wanted to see if a cell-based therapy might provide the answer. “Cell-based therapy is of great interest to us because of exosomes, miniscule fluid-filled sacs that can transfer information and thereby affect immune responses to specific antigens,” Dr. Qi explained. Research into exosomes roles in pathogen infection is still in the early stages, but reports have shown that exosomes, among other desirable properties, can shuttle protective host molecules between cells. Mesenchymal stem cells (MSCs) produce high amounts of exosomes. Collecting MSCs from umbilical cord is a relatively low-cost, non-invasive procedure – the uMSCs that Dr.

Novel MRI Technique Distinguishes Healthy Prostate Tissue from Cancerous Using Zinc

A novel MRI method that detects low levels of zinc ion can help distinguish healthy prostate tissue from cancer, University of Texas (UT) Southwestern Medical Center radiologists have determined. Typical MRIs don’t reliably distinguish between zinc levels in healthy, malignant, and benign hyperplastic prostate (BHP) tissue, so discovery of the technique could eventually prove useful as a biomarker to track the progression of prostate cancer, according to researchers at the Advanced Imaging Research Center, part of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center. “This research provides the basis for differentiating healthy prostate from prostate cancer by use of a novel Zn(II) ion sensing molecule and MRI,” said senior author Dr. A. Dean Sherry, Director of the Advanced Imaging Research Center and Professor of Radiology at UT Southwestern. The findings were published recently in the Proceedings of the National Academy of Sciences. “The potential for translating this method to human clinical imaging is very good, and will be useful for diagnostic purposes. The method may prove useful for monitoring therapies used to treat prostate cancer,” said Dr. Sherry, who is also Professor of Chemistry at UT Dallas, where he holds the Cecil and Ida Green Distinguished Chair in Systems Biology. The majority of prostate cancers are classified as adenocarcinomas and originate in epithelial cells. The UTSW researchers initially determined that glucose stimulates release of the zinc ions from inside epithelial cells, which they could then track on MRIs. The prostate cancer tissue secreted lower levels of zinc ions, offering an opportunity to distinguish between malignant and healthy tissue.

Exosome-Based Studies May Improve Understanding of Signals Triggering Labor and Delivery Process

In a normal full-term pregnancy, signals from the mature organs of the fetus and the aging placental membranes and placenta prompt the uterus' muscular walls to begin the labor and delivery process. It's still unclear how these signals accomplish this goal or how they reach from the fetal side to the maternal side. A team from The University of Texas Medical Branch (UTMB) at Galveston has unlocked key clues in understanding what triggers the birthing process, according to research findings recently published in the open-access journal PLOS ONE. The article is titled “Amnion-Epithelial-Cell-Derived Exosomes Demonstrate Physiologic State of Cell under Oxidative Stress.” "It's important that we gain a better understanding of how these signals interact and work in normal full-term pregnancies because it can provide insights into how and why these signals activate too early and trigger the labor and delivery process prematurely," said lead author and UTMB Assistant Professor in the Department of Obstetrics and Gynecology, Ramkumar Menon, Ph.D. According to the World Health Organization, an estimated 15 million babies are born preterm, or before 37 weeks of pregnancy, each year. Complications from preterm birth are the chief cause of death among children under five. UTMB researchers studied the production and movement of exosomes, which are a specific type of molecular container that transports chemical signals between cells. The exosomes in question for this study came from amnion epithelial cells (AECs), which come from the inner lining of the placenta that forms the uterine cavity and is close to the growing fetus. This tissue protects the fetus during its uterine growth.

Rheumatoid Arthritis Patients Taking Interleukin-1Beta Inhibitors Are at Much Increased Risk of Group A Strep Infections

Rheumatoid arthritis (RA) patients taking medications that inhibit interleukin-1beta (IL-1beta), a molecule that stimulates the immune system, are 300 times more likely to experience invasive Group A Streptococcal infections than patients not on the drug, according to University of California San Diego School of Medicine researchers. Their study, published August 19, 2016 in Science Immunology, also uncovers a critical new role for IL-1beta as the body's independent early warning system for bacterial infections. The article is titled “IL-1β Is an Innate Immune Sensor of Microbial Proteolysis.” "The more we know about each step in the body's immune response to bacterial infections, the better equipped we are to design more personalized, targeted therapies for autoimmune diseases -- therapies that are effective, but minimize risk of infection," said senior author Victor Nizet, M.D., Professor of Pediatrics and Pharmacy at UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. IL-1beta is a molecule that stimulates an immune response, calling white blood cells (WBCs) to the site of an infection so theWBCs can engulf and clear away invading pathogens. The body first produces the molecule in a longer, inactive form that must be cleaved to be activated. The scientific community long believed that only the body itself could cleave and activate IL-1beta, by employing a cellular structure known as the inflammasome. But, in experiments employing cell cultures and mouse models of infection, Dr. Nizet and his team found that SpeB, an enzyme secreted by strep bacteria, also cleaves and activates IL-1beta, triggering a protective immune response.

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