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Archive - Aug 2017

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August 16th

How Genome Sets Its Functional Micro-Architecture

The genes that are involved in the development of the fetus are activated in different tissues and at different times. Their expression is carefully regulated by so-called "enhancer sequences,” which are often located far from their target genes, and this expression requires the DNA molecule to loop around and bring the enhancer sequences in close proximity to their target genes. Such 3D changes of the DNA are in turn controlled by other sequences called topologically associating domains (TADs). École Polytechnique Fédérale de Lausanne (EPFL) scientists have now studied the TADs involved in digit development in the fetus and have gained insights regarding some of the important questions surrounding them. The work was published online on August 7, 2017 in Genome Biology. The open-access article is titled “Large Scale Genomic Reorganization of Topological Domains at The Hoxd Locus.” TADs are portions of the DNA molecule that divide the entire genome of an organism into manageable chunks, like districts in a city. Inside the cell, the vast amount of DNA is packaged into chromatin and chromatin is packaged into the familiar chromosomes. Inside every TAD, there exist genes as well as the elements that regulate them, all packaged together and insulated from genes and regulators in neighboring TADs, like channels or walls that separate city districts. Breaking down the boundaries set by TADs leads to a number of disorders such as colon, esophagus, brain, and blood cancers. But despite their importance, we know little about these boundaries, which confer to a TAD its structure. This raises the question: Is the information coming from the inner parts of a TAD or due to boundaries.

August 16th

Study of Exosome miRNA in Canine Mitral Valve Disease & Congestive Heart Failure Provides Clues to Target Therapies in Dogs and Human Mitral Valve Prolapse

esearchers at the Cummings School of Veterinary Medicine at Tufts University have discovered important biomarkers in extracellular vesicles in dogs with myxomatous mitral valve disease and congestive heart failure. This is the first biomarker discovery based on extracellular vesicles in a veterinary disease. The genomic material (microRNA, or miRNA) was isolated from small extracellular vesicles called exosomes, which are released from cells and can circulate in blood. These findings could provide important insight into the molecular basis, diagnosis, and therapies for myxomatous mitral valve disease in dogs, as well as mitral valve prolapse, a similar disease in humans. The results were published online on July 12, 2017 in the Journal of Extracellular Vesicles. The open-access article is titled “Circulating Exosome MicroRNA Associated With Heart Failure Secondary to Myxomatous Mitral Valve Disease in a Naturally Occurring Canine Model.” In their analysis of circulating exosome miRNA (Ex-miRNA), researchers found that the expressions not only change with disease progression and development of heart failure in dogs with myxomatous mitral valve disease but also exhibit changes solely on the basis of aging in dogs. Additionally, they found that Ex-miRNA expression level changes appear to be more specific to disease states than the measure of miRNA from plasma without attention to the isolation of Ex-miRNA. This suggests that Ex-miRNA may offer a novel approach that improves upon current established methods of monitoring patients with heart disease and other diseases, yet relies on readily available samples such as blood and urine.

Scientists Develop Blood Test That Spots Tumor-Derived DNA in People with Early-Stage Cancers; Hopkins-Developed Test Targets 58 Cancer-Associated Genes Using Deep Sequencing Technology

In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center, and colleagues, report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early-stage colorectal, breast, lung, and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumors and other altered DNA that can be mistaken for cancer biomarkers. A report on the research, performed on blood and tumor tissue samples from 200 people with all stages of cancer in the U.S., Denmark, and the Netherlands, appears in the August 16, 2017 issue of Science Translational Medicine. The open-access article is titled “Direct Detection of Early-Stage Cancers Using Circulating Tumor DNA.” "This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high-accuracy sequencing method is a promising approach to achieve this goal," says Victor Velculescu (photo), MD, PhD, Professor of Oncology at the Johns Hopkins Kimmel Cancer Center. Blood tests for cancer are a growing part of clinical oncology, but they remain in the early stages of development. To find small bits of cancer-derived DNA in the blood of cancer patients, scientists have frequently relied on DNA alterations found in patients' biopsied tumor samples as guideposts for the genetic mistakes they should be looking for among the masses of DNA circulating in those patients' blood samples. To develop a cancer screening test that could be used to screen seemingly healthy people, scientists had to find novel ways to spot DNA alterations that could be lurking in a person's blood but had not been previously identified.

Micromotors Deliver Drugs to Treat Bacterial Infection in Stomach; New Results in Animals Open Door to Use of Synthetic Motors As Active Delivery Platforms for In Vivo Treatment of Diseases

Nanoengineers at the University of California San Diego have demonstrated, for the first time, the use of micromotors to treat a bacterial infection in the stomach. These tiny vehicles, each about half the width of a human hair, move rapidly throughout the stomach while neutralizing gastric acid, and then release their cargo of antibiotics at the desired pH. The researchers published their findings on August 16, 2017 in Nature Communications. The open-access article is titled “Micromotor-Enabled Active Drug Delivery for In Vivo Treatment of Stomach Infection.” This micromotor-enabled delivery approach is a promising new method for treating stomach and gastrointestinal tract diseases with acid-sensitive drugs, researchers said. The effort is a collaboration between the research groups of nanoengineering professors Joseph Wang (photo) and Liangfang Zhang at the UC San Diego Jacobs School of Engineering. Dr. Wang and Dr. Zhang pioneered research on the in vivo operation of micromotors and this study represents the first example of drug-delivering micromotors for treating bacterial infection. Gastric acid can be destructive to orally administered drugs such as antibiotics and protein-based pharmaceuticals. Drugs used to treat bacterial infections, ulcers, and other diseases in the stomach are normally taken with additional substances, called proton pump inhibitors, to suppress gastric acid production. But when taken over longer periods or in high doses, proton pump inhibitors can cause adverse side effects including headaches, diarrhea, and fatigue. In more serious cases, they can cause anxiety or depression.

Compounds in Desert Creosote Bush Could Be Used to Treat Giardia and “Brain-Eating” Amoeba Infections

Researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego and the University of Colorado Anschutz Medical Campus have found that compounds produced by the creosote bush, a desert plant common to the southwestern United States, exhibit potent anti-parasitic activity against the protozoa responsible for giardia infections and an amoeba that causes an often-lethal form of encephalitis. The findings, published online on August 9, 2017 in PLOS Neglected Tropical Diseases, offer a starting point for widening the arsenal of antimicrobial agents, effective against deadly parasitic infections, scientists said. The open-access article is titled “Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.” The World Health Organization estimates that giardiasis, a diarrheal illness, is linked to approximately 846,000 deaths around the world each year. Infection usually occurs through ingestion of contaminated water or food. Though rarely lethal in the U.S., it's estimated there are more than 1 million cases of giardiasis in the country annually. Standard treatment usually involves antibiotics and anti-parasitic drugs. "The significance and intrigue of our study is that it shows the value of prospecting for new medicines from plants traditionally used by indigenous people as medicine," said co-principal investigator Anjan Debnath, PhD, an Assistant Adjunct Professor at Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego. The creosote bush (Larrea tridentata), also known as greasewood, or gobernadora in Spanish, is a tough evergreen bush with small waxy leaves, yellow flowers, and a distinctive turpentine-like scent. Native Americans in both the U.S.

August 15th

Artificial Intelligence and Blockchain Companies Partner to Advance Healthcare Research

On August 15, 2017, Insilico Medicine, Inc, a Baltimore-based next-generation artificial intelligence (AI) company today announced a research collaboration with The Bitfury Group, the world's leading full-service blockchain technology conglomerate, to develop novel solutions for healthcare applications. The companies signed a memorandum of understanding (MOU) to collaborate in the academic and commercial settings to develop AI on blockchain solutions for the healthcare industry. "Blockchain can secure and streamline our medical systems, while AI has the potential to revitalize data management and machine learning to help identify trends and diseases," said Valery Vavilov, Founder and CEO of The Bitfury Group. "By partnering with Insilico, we will be able to combine their expertise in deep learning and bioinformatics with our blockchain proficiency and real-time solutions to create bespoke and innovative new products for the healthcare sector." "The Bitfury Group is one of the most reputable companies in blockchain, developing their own semiconductors and end-to-end blockchain solutions trusted by the major corporations and governments worldwide. We are happy to enter into a research collaboration with Bitfury to develop innovative solutions that may save lives and extend human healthspan,” said Alex Zhavoroknov, PhD, Founder and CEO of Insilico Medicine, Inc. [Editor’s Note. The following excerpt from an article (http://mitsloan.mit.edu/newsroom/articles/blockchain-explained/) from the MIT Sloan School of Management provides some insight into blockchain technology: Blockchain is a term widely used to represent an entire new suite of technologies. There is substantial confusion around its definition because the technology is early-stage, and can be implemented in many ways depending on the objective.

Therapeutic Fusion Protein (ApoM-Fc) Could Mitigate Blood Vessel Damage from Cardiovascular Disease

Scientists from Boston Children's Hospital Vascular Biology Program have revealed an engineered fusion protein that could recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack, and other cardiovascular diseases. The findings were published on August 14, 2017 in Science Signaling. The article is titled “An Engineered S1P Chaperone Attenuates Hypertension and Ischemic Injury.” On average, each person has 60,000 miles of blood vessels coursing through his or her body. There are a number of mechanisms that the body uses to keep its vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role. S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body's blood cells. Together, these so-called endothelial cells form a barrier between the body's circulating blood and surrounding tissue. When S1P molecules activate their receptors, that suppresses endothelial inflammation and generally helps regulate cardiovascular health. Now, researchers led by Timothy Hla, PhD, from the Boston Children's Vascular Biology Program, have designed a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of a range of cardiovascular diseases. As crucial as S1P is to our health, it cannot do its job alone. Instead, S1P relies on another set of the body's molecules to ferry it through the bloodstream so that it can find and bind with its cell receptors on the endothelium. "High density cholesterol (HDL) -- also known as good cholesterol -- carries a protein called ApoM, which in turn attracts and binds S1P in its cargo," says Dr. Hla, an investigator in the Vascular Biology Program, Patricia K.

Possible Metabolic Treatment for Pancreatic Cancer Would Target an Enzyme (Arginase 2) That Helps Dispose of Excess Nitrogen

Pancreatic cancer is now the third leading cause of cancer mortality. Its incidence is increasing in parallel with the population increase in obesity, and its five-year survival rate still hovers at just 8 to 9 percent. Research led by Nada Kalaany, PhD, at Boston Children's Hospital and the Broad Institute of MIT and Harvard, now suggests a novel approach to treating this deadly cancer: targeting an enzyme that tumors use to get rid of nitrogen. The study, published online on August 14, 2017 in Nature Communications, provides evidence that targeting the enzyme arginase 2 (ARG2) (image) can curb the growth of pancreatic tumors, especially in people who are obese. The open-access article is titled “Critical Role for Arginase 2 in Obesity-Associated Pancreatic Cancer." The researchers began by introducing human pancreatic tumors into obese and lean mice. They then analyzed what genes the tumors turned on and what metabolic products they were producing. They found that tumors in obese mice had enhanced expression of many genes involved in metabolizing nitrogen, a natural byproduct of cells when proteins are broken down. Until now, how nitrogen excess affects tumor growth has been largely unknown. "We found that highly malignant pancreatic tumors are very dependent on the nitrogen metabolism pathway," says Dr. Kalaany, a researcher in Boston Children's Division of Endocrinology and an Assistant Professor at Harvard Medical School. Pancreatic tumors grew faster in obese mice than in lean mice and produced increased amounts of ARG2, an enzyme that helps dispose of excess nitrogen by breaking down ammonia, as part of the urea cycle. Dr.

Scientists Identify Weight-Gain Receptor Linked to Atypical Antipsychotic Drugs (Olanzapine)

Many schizophrenic and depressed patients experience weight gain and type 2 diabetes in their quests for the life-changing benefits of a major class of antipsychotic drugs. University of Texas (UT) Southwestern Medical Center researchers identified a cellular receptor central to these undesirable effects. They then eliminated most of these metabolic changes in mice co-treated with a weight-loss drug that targets the serotonin 2c receptor. "Atypical antipsychotics are essential medications for millions of schizophrenia patients worldwide and they are increasingly being prescribed for bipolar disorder, major depressive disorder, and autism," said Dr. Chen Liu, an Assistant Professor of Internal Medicine and Neuroscience and co-corresponding author of an August 14, 2017 Journal of Clinical Investigation study along with Dr. Joel Elmquist, Director of the Division of Hypothalamic Research and a Professor of Internal Medicine, Pharmacology, and Psychiatry. The open-access article is titled “The Atypical Antipsychotic Olanzapine Causes Weight Gain by Targeting Serotonin Receptor 2C.” "Most members of this class of antipsychotics are linked to a drug-induced metabolic syndrome characterized by excessive weight gain, blood fat abnormalities, and type 2 diabetes. Obesity and diabetes often develop shortly after treatment begins," added Dr. Liu, who is also in the Division of Hypothalamic Research. The researchers found that six weeks of exposure to the antipsychotic drug olanzapine caused weight gain - particularly in female mice - due to increased fat rather than muscle. "Similar to treatment in humans, mice given olanzapine showed significant weight gain, higher food intake, and metabolic changes associated with insulin resistance and diabetes," said Dr.

August 14th

UCLA Scientists Identify New Way to Activate Stem Cells to Make Hair Grow; Increasing Lactate Dehydrogenase Activity Is Key

UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Dr. Heather Christofk and Dr. William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment. The research was published online on August 14, 2017 in Nature Cell Biology. The article is titled “Lactate Dehydrogenase Activity Drives Hair Follicle Stem Cell Activation.” Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a person's lifetime. They are "quiescent," meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases, they fail to activate, which is what causes hair loss. In this study, Dr. Christofk and Dr. Lowry, of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from that of other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy, and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce "metabolites." As hair follicle stem cells consume the nutrient glucose from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria -- the part of the cell that creates energy -- or can convert pyruvate into another metabolite called lactate.