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Archive - May 2017


May 9th

Scientists Gain Insights into How Fragile X Syndrome Disrupts Perception

A collaboration among scientists in Belgium, the United States, Norway, France, and the UK has resulted in a study that sheds light on the neural mechanisms of fragile X syndrome. This genetic disorder, which affects males twice as often as females due to males’ single X chromosome, causes disruptions in the way neurons transmit information to each other. Led by one current and two former VIB scientists during their tenure at VIB, the multidisciplinary team used fruit fly models to demonstrate that the Fragile X mutation causes signals between neurons to be more widely spread, possibly leading to confusion in the perception and discrimination of information from the environment. The work was published online on March 30, 2017 in Current Biology. The open-access article is titled “Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome.” In normal brains, 20% of neurons are inhibitory, meaning that they send signals that limit communication between other neurons to make sure that signals exchanged within the brain are finely tuned and confined to specific areas, depending on what the person or animal is doing or perceiving. Fragile X syndrome, which is caused by a fault on the X chromosome, leads to defects in how brain neurons communicate with each other. In this study, scientists observed that fruit flies that lack the fragile X protein have much less inhibition among their brain neurons, possibly leading to “noise” during information processing. Even though the research was performed on fruit flies, there are many analogues between flies and humans that lead to insights into human brain diseases.

Scientists Assess Impact of Cytosine Methylation on Binding Specificities of Human Transcription Factors

A new study published online on May 4, 2017 in Science from Karolinska Institutet and collaborating institutions maps out how different DNA-binding proteins in human cells react to certain biochemical modifications of the DNA molecule. The article is titled “'Impact of Cytosine Methylation on DNA Binding Specificities of Human Transcription Factors.” The scientists report that some “master”' regulatory proteins can activate regions of the genome that are normally inactive due to epigenetic changes. Their findings contribute to a better understanding of gene regulation, embryonic development, and the processes leading to diseases such as cancer. The DNA molecule carries information in the form of a sequence of four nucleotide bases, adenine (A), cytosine (C), guanine (G) and thymine (T), which can be thought of as the letters of the genomic language. Short sequences of the letters form “DNA words” that determine when and where proteins are made in the body. Almost all of the cells in the human body contain the letters in precisely the same order. Different genes are however active (expressed) in different cell types, allowing the cells to function in their specialized roles, for example as a brain cell or a muscle cell. The key to this gene regulation lies in specialized DNA-binding proteins -- transcription factors -- that bind to the sequences and activate or repress gene activity. The DNA letter C exists in two forms, cytosine and methylcytosine, which can be thought of as the same letter with and without an accent (C and Ç). Methylation of DNA bases is a type of epigenetic modification, a biochemical change in the genome that does not alter the DNA sequence. The two variants of C have no effect on the kind of proteins that can be made, but they can have a major influence on when and where the proteins are produced.

Genetic Findings in “Type 1.5” Diabetes May Shed Light on Better Diagnosis, Treatment

Researchers investigating a form of adult-onset diabetes that shares features with the two better-known types of diabetes have discovered genetic influences that may offer clues to more accurate diagnosis and treatment. Latent autoimmune diabetes in adults (LADA) is informally called "type 1.5 diabetes" because like type 1 diabetes (T1D), LADA is marked by circulating autoantibodies, an indicator that an overactive immune system is damaging the body's insulin-producing beta cells. But LADA also shares clinical features with type 2 diabetes (T2D), which tends to appear in adulthood. Also, as in T2D, LADA patients do not require insulin treatments when first diagnosed. A study published on April 25, 2017 in BMC Medicine used genetic analysis to show that LADA is closer to T1D than to T2D. The open-access article is titled “Relative Contribution of Type 1 And Type 2 Diabetes Loci to the Genetic Etiology of Adult-Onset, Non-Insulin-Requiring Autoimmune Diabetes.” "Correctly diagnosing subtypes of diabetes is important, because it affects how physicians manage a patient's disease," said co-study leader Struan F.A. Grant, PhD, a genomics researcher at Children's Hospital of Philadelphia (CHOP). "If patients are misdiagnosed with the wrong type of diabetes, they may not receive the most effective medication." Dr. Grant collaborated with European scientists, led by Richard David Leslie of the University of London, U.K.; and Bernhard O. Boehm, of Ulm University Medical Center, Germany and the Lee Kong Chian School of Medicine, a joint medical school of Imperial College London and Nanyang Technological University, Singapore. Occurring when patients cannot produce their own insulin or are unable to properly process the insulin they do produce, diabetes is usually classified into two major types.

New Evidence Indicates Traffic Jams in Nuclear Pores Cause Brain Cell Death in Huntington’s Disease

Working with mouse, fly, and human cells and tissue, Johns Hopkins researchers and collaborators report new evidence that disruptions in the movement of cellular materials in and out of a cell's control center -- the nucleus -- appear to be a direct cause of brain cell death in Huntington's disease, an inherited adult neurodegenerative disorder. Moreover, they suggest, laboratory experiments with drugs designed to clear up these cellular "traffic jams" restored normal transport in and out of the nucleus and saved the cells. In the featured article published in the April 5, 2017 issue of Neuron, the researchers also conclude that potential treatments targeting the transport disruptions they identified in Huntington's disease neurons may also work for other neurodegenerative diseases, such as ALS and forms of dementia. The Neuron article is titled “Mutant Huntingtin Disrupts the Nuclear Pore Complex.” Huntington's disease is a relatively rare fatal inherited condition that gradually kills off healthy nerve cells in the brain, leading to loss of language, thinking and reasoning abilities, memory, coordination, and movement. Its course and effects are often described as Alzheimer's disease, Parkinson's disease, and ALS rolled into one, making Huntington's disease a rich focus of scientific investigation. "We're trying to get at the heart of the mechanism behind neurodegenerative diseases and with this research believe we've found one that seems to be commonly disrupted in many of them, suggesting that similar drugs may work for some or all of these disorders," says Jeffrey Rothstein, M.D., Ph.D., a Professor of Neurology and Neuroscience, and Director of the Brain Science Institute and the Robert Packard Center for ALS Research at the Johns Hopkins University School of Medicine.

May 2nd

Dr. Zon Alerts to National ALS Advocacy Day May 16; Notes Promising Stem Cell Work

In his latest “Zone in with Zon” blog post, dated May 2, 2017, and published by TriLink BioTechnologies of San Diego, Gerald “Jerry” Zon, PhD, gives advance notice of National ALS Advocacy Day that will take place on Tuesday, May 16, 2017. He notes that ALS (amyotrophic lateral sclerosis) is commonly called “Lou Gehrig’s disease” in the United States after the famous New York Yankee baseball player Lou Gehrig who was struck by the disease and died two years after the dread disease forced him to leave the game in 1939. In his popular blog, Dr. Zon outlines the grim features of this fatal disease for which there is still no cure, but he also highlights promising stem cell work that has taken place recently in Israel. He reported that a company named BrainStorm Cell Therapeutics, Inc. (BCLI) has developed a patented stem cell-based technology that delivers a growth factor that can help neurons live longer at or near the site of injury or damage. More specifically, Dr. Zon noted, “a mesenchymal stem cell isolated from an ALS patient is grown in a cell culture under certain conditions to produce a differentiated phenotype that secretes brain-derived neurotrophic factor (BDNF) at a level at least five-times greater than normal.”….“After these ‘super secreting’ cells are obtained ex vivo, they are reintroduced into the same ALS patient (i.e., an autologous transplant), wherein BDNF acts on neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses.” Dr.

Chemical Compound Promotes Running Endurance in Sedentary Mice

Every week, there seems to be another story about the health benefits of running. That's great--but what if you can't run? For the elderly, obese, or otherwise mobility-limited, the rewards of aerobic exercise have long been out of reach. Salk Institute scientists, building on earlier work that identified a gene pathway triggered by running, have discovered how to fully activate that pathway in sedentary mice with a chemical compound, mimicking the beneficial effects of exercise, including increased fat burning and stamina. The study, which appears in Cell Metabolism on May 2, 2017, not only deepens our understanding of aerobic endurance, but also offers people with heart conditions, pulmonary disease, type 2 diabetes, or other health limitations the hope of achieving those benefits pharmacologically. The open-access article is titled “PPARδ Promotes Running Endurance by Preserving Glucose.” "It's well known that people can improve their aerobic endurance through training," says senior author Ronald Evans, Howard Hughes Medical Institute investigator and holder of Salk's March of Dimes Chair in Molecular and Developmental Biology. "The question for us was: how does endurance work? And if we really understand the science, can we replace training with a drug?" Developing endurance means being able to sustain an aerobic activity for longer periods of time. As people become more fit, their muscles shift from burning carbohydrates (glucose) to burning fat. So researchers assumed that endurance is a function of the body's increasing ability to burn fat, though details of the process have been murky.

Scientists Develop Fruit Fly Model of Kidney Cyst Formation; May Be Applicable to Study of Polycystic Kidney Disease (PKD)

According to PKD International, 12.5 million people worldwide are affected by polycystic kidney disease (PKD). There is no known cure. But that may one day change, thanks in part to new research by a Concordia University (Montreal, Canada) biology researcher. In a study, published online on April 13, 2017 in PLOS Genetics, Chiara Gamberi, PhD, and her coauthors developed an innovative fruit-fly-based model of the types of harmful cysts that can form on kidneys. The model has enormous potential for assisting the study of how cells proliferate in PKD and cancer. But what do fruit flies have to do with it? "The human and fly genomes show a surprising level of similarity. In fact, gene relationships, or genetic pathways, are virtually identical between human beings and fruit flies," explains Dr. Gamberi, who is affiliate assistant professor of biology in Concordia's Faculty of Arts and Science. "Most human organs have fly counterparts. That's a great advantage we can leverage to study the functions of disease-associated genes, and also to identify possible methods of combating those diseases." The PLOS Genetics article is titled “Bicaudal C Mutation Causes myc and TOR Pathway Up-Regulation and Polycystic Kidney Disease-Like Phenotypes in Drosophila.” Kidneys are particularly challenging to investigate because of the difficulties of isolating the nephrons -- tiny tubes in the kidney that filter substances from body fluids. The fruit fly equivalent, small though it is, acts as an effective stand-in, with the added advantage of allowing researchers to rapidly assess genetic and chemical influences because of the fruit fly's short lifespan. Dr. Gamberi and her coauthors reported the first example of renal cysts in the fruit fly species Drosophila melanogaster.

Annual ISEV Meeting on Extracellular Vesicles (Including Exosomes) in Toronto May 18-21

The annual meeting of the International Society for Extracellular Vesicles (ISEV 2017) (, will take place from May 18-21 (plus the May 17 Education Day) in Toronto, Canada, and will offer an unparalleled opportunity to network with, and learn from, the preeminent leaders in extracellular vesicle (EV) research. To register for this meeting, please click here ( The scope and quality of the anticipated scientific exchange make ISEV 2017 the largest and the premier meeting in EV research in the world. This event features four days of the best in vesicle science covering all aspects of basic, clinical, and translational research. The research theme includes diverse areas of science encompassing rare and neglected diseases, infectious disease, coagulation, cancer, neuroscience, cardiovascular studies, immunology, regenerative medicine, virology, parasitology, and more. The overall theme of ISEV 2017 is “Diversity of EV Composition and Function in Disease Diagnosis and Therapeutics.” Amidst growing interest in the promise of EVs in disease detection and treatment, ISEV 2017 will bring scientists and clinicians in medical and biotechnology communities together to translate their research. No other meeting in the world offers the scope, participation level, and thematic focus of ISEV 2017 concentrating and cross-pollinating scientific investigations in the field of disease biomarkers and therapeutic tools by disseminating cutting-edge developments in EV research. Among the plenary speakers scheduled to address the meeting are Clotilde Thery, Ph.D. (Research Director, Institut Curie), Philip Stahl, Ph.D. (Professor Emeritus of Cell Biology and Physiology, Washington University School of Medicine), Thomas Thum M.D., Ph.D.

Stereotactic Radiation Highly Effective for Metastatic Kidney Cancer, Study Indicates

Kidney cancer patients may soon have more treatment choices that provide a higher quality of life, thanks to research completed by physician scientists at the University of Texas (UT) Southwestern Medical Center. Their recent study showed that treating metastatic kidney cancer with an advanced and focused form of radiation called stereotactic ablative radiation therapy achieves more than 90 percent control of local tumors, and offers the possibility of safely delaying systemic therapy. “This study shows that stereotactic radiation provides a good noninvasive alternative to conventional treatment such as surgery, and that it effectively controls the disease,” said Raquibul Hannan (photo), MD, PhD, Assistant Professor of Radiation Oncology and Co-Leader of the Kidney Cancer Program of the Harold C. Simmons Comprehensive Cancer Center and senior author of the study. “It may also offer an alternative to patients who are not candidates for surgery. Often due to the number and location of the metastases and sometimes due to other conditions, patients are not candidates for surgery.” The standard of care for metastatic renal cell carcinoma is systemic therapy, which can be associated with significant side effects like tiredness, fatigue, high blood pressure, and rash. These side effects can be significant and debilitating. According to Dr. Hannan, the new study shows that patients with metastatic kidney cancer can be treated with stereotactic radiation therapy with the goal of being cured, or to delay systemic therapy allowing patients to enjoy a better quality of life without the side effects of the drugs.

Study Opens New Line of Attack on Spinal Muscular Atrophy

Though spinal muscular atrophy (SMA) in its most severe form remains incurable and fatal in early childhood, researchers are sustaining a multipronged counterattack for patients and their families. The first treatment for the disease gained U.S. market approval in December. Now a new discovery led by Brown University scientists deepens the basic understanding of how the genetic mutation that causes SMA appears to undermine the communication between motor neurons and the muscles they control. "We are making progress," said Anne Hart (photo), PhD, Professor of Neuroscience at Brown and senior author of the new study published online on May 2, 2017 in eLife. The open-access article is titled “Decreased MicroRNA Levels Lead to Deleterious Increases in Neuronal M2 Muscarinic Receptors in Spinal Muscular Atrophy Models.” About one in 8,000 children is born with some form of SMA in which mutations in both copies of the gene that code for the survival motor neuron (SMN) protein cripple its production. The end result, which the new study helps to explain, is dysfunction of motor neurons that control muscle along with muscle atrophy and weakness. In the most acute form, Type I, children die by age two as even functions as fundamental as breathing become compromised. With other SMA types, patients can live much longer, but they still suffer significant muscle weakness. It's a positive sign that spinal cord injections of nusinersen, the newly approved drug, restore some motor function and prolong survival by improving SMN production, Dr. Hart said, but researchers can make further and perhaps more lasting headway by understanding how the lack of SMN ultimately undermines muscle function.