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October 28th, 2018

The Scents of Action—GABAergic Circuitry of Olfactory Bulb Acts As Gatekeeper of Hard-Wired Neural Pathway Connecing Olfactory & Motor Centers of the Brain

In all animals, including humans, smell - the oldest of the five senses - plays a predominant role in many behaviors essential for survival and reproduction. It has been known since ancient times that animals react to odours. Yet researchers are just beginning to elucidate the neural pathways and mechanisms responsible for odour-induced behavior. A first step has recently beenm made by showing the existence of a neural pathway connecting the olfactory and motor centers of the brain in invertebrates with the worm C. elegans and in vertebrates with the lamprey (photo), a primitive, eel-like fish native to the Atlantic Ocean. In a new study published online on October 4, 2018 in PLoS Biology, scientists at Université de Montréal (UdeM), in Quebec, and the University of Windsor, in Ontario, show that an inhibitory circuit that releases the neurotransmitter GABA into the olfactory bulb strongly modulates behaviouralresponses to odors in lampreys. The study of these modulatory mechanisms allowed the researchers to discover a new pathway linking together olfactory and motor centers in the brain. This discovery demonstrates that odourscan activate locomotor centers via two distinct brain pathways," said lead author Gheylen Daghfous, PhD, a researcher in the laboratory of UdeM Neuroscience Associate Professor Réjean Dubuc, PhD, also a Professor at Université du Québec à Montréal. "This work sheds new light on the evolution of the olfactory systems in vertebrates." He added: "It is well-known that animals are attracted to odors, whether it be a dog tracking its prey or a shark attracted to blood. On the other hand, we are only beginning to understand how the brain uses odors to produce behavior. Our study revealed a new brain highway dedicated to transmitting smell information to the regions controlling movements."

October 28th

American Society for Exosomes and Microvesicles (ASEMV) Holds 2018 Annual Meeting in Baltimore

The 2018 annual meeting of the American Society for Exosomes and Microvesicles was held October 20-24 in Baltimore, hard by the water’s edge in the Baltimore Marriott Waterfront Conference Center. ASEMV president, Stephen Gould, PhD, Professor of Biological Chemistry & Co-Director, Graduate Program in Biological Chemistry, Johns Hopkins, reported a record attendance of 250 scientists from the United States and around the world (Korea, Norway, Sweden, Canada, Australia, Japan, UK, Italy, Portugal, The Netherlands) at this historically intimate and highly interactive meeting that benefits greatly from having communal meals and no overlapping sessions. The five-day meeting featured over 100 podium presentations and myriad posters. The daily consecutive sessions typically ran from 8.30 in the morning to 9.30 in the evening, and were followed by two hours of poster viewing and interaction among researchers and with sponsors. The communal meals and poster sessions offered excellent opportunities for significant interaction amongst conference participants and also for interaction between attendees and the over 20 companies (see below) that were sponsors of the meeting. Dr. Gould highlighted the key role of these sponsors in enabling this very special meeting, and noted that this year featured record sponsorship, with almost triple the number of sponsors relative to the number for last year’s meeting at Asilomar in California. This impressive increase in sponsorship is a reflection of the recent explosion of research and interest in exosomes from many quarters of medicine and science.

October 24th

Institute of Human Virology (IHV) & Director Robert Gallo Honor Renowned Clinical Researchers Henry Masur and Kiyoshi Takatsuki with Lifetime Achievement Awards; Ceremony Held During IVH’s 20th Annual International Meeting in Baltimore

The 20th Annual International Meeting of the Institute of Human Virology (IHV) at the University of Maryland School of Medicine is being held from October 21-25, 2018 at the Four Seasons Hotel in Baltimore, Maryland. This year, among other viral and cancer-related topics, the meeting is holding special sessions on the 40th anniversary of discovery of the first human retrovirus, Human T cell Leukemia Virus (HTLV), and the 15th anniversary of the President’s Emergency Plan for AIDS Relief (PEPFAR). The IHV’s Annual International Meeting attracts hundreds of elite scientists who descend upon Baltimore to share ideas and inspire medical virus research collaborations. “Our meeting is designed to highlight cutting-edge science and provide a platform for provocative discussion,” said Robert C. Gallo (photo), MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-founder and Director of the Institute of Human Virology at the University of Maryland School of Medicine, and Co-founder and Director of the Global Virus Network (GVN). “It is clear from yesterday’s session that there is still much research needed forty years since announcing our discovery of HTLV-1 at a Cold Spring Harbor meeting. It is my hope that governments far and wide will recognize this need and provide the resources needed. I am looking forward to hearing about the enormous success of PEPFAR during our special sessions tomorrow, and about the lessons learned which could potentially be applicable to the HTLV pandemic today.” The meeting program’s organization was led by Man Charurat, PhD, Professor of Medicine and the Director of the Division of Epidemiology and Prevention of the IHV at the University of Maryland School of Medicine.

October 19th

“We Are All Africans”--Presidential Symposium on Origin of Human Species Electrifies Record 9,000 Attendees at ASHG Annual Meeting

(BY MICHAEL A. GOLDMAN, PhD, Professor, Former Chairman of Biology, San Francisco State University). The American Society of Human Genetics (ASHG) Presidential Symposium, titled “Origins of Our Species: Advances in Our Understanding of Ancient Humans in Africa,” began in late afternoon Thursday October 18, and was open to all of the meeting’s ~9,000 attendees (an ASHG meeting attendance record). This symposium featured stimulating presentations by three prominent evolutionary geneticists, followed by a brief panel discussion amongst the three speakers, which was moderated by Dr. Charles N. Rotimi, of the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, and Dr. Sarah Tishkoff, of the University of Pennsylvania in Philadelphia, Pennsylvania. Dr. Rotimi is a Senior Investigator at NIH, and Dr. Tishkoff is David and Lyn Silfen University Professor, Departments of Genetics and Biology, Perelman School of Medicine and School of Arts and Sciences, University of Pennsylvania. The essence of being human, according to first presenter paleoanthropologist Dr. John D. Hawks of the University of Wisconsin-Madison, is a process, rather than a specific thing. We share a common heritage, and we will make a common future, he said. We are all part of that process whether we share particular traits that are thought to be characteristic of humans, such as speech and walking upright, or not. This simple observation belies the extraordinarily complex and controversial story of human origins featured in the President's Symposium. In a field where each new fossil discovery seems to add yet another gap to the record, Dr. Hawks admits that we still have much to learn, and that we will be continuously surprised, as now is as exciting as any time in the study of human evolution. Dr.

October 18th

Environmental Associations with Genes May Yield Opportunities for Precision Medicine; Findings Reported at ASHG 2018 Annual Meeting

A new approach to genetic analysis finds associations between environmental factors and pharmacogenes – genes associated with a person’s response to drugs – sparking ideas for new research at the interface of population genetics and medicine. Findings were presented Thursday, October 18, at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). “Humans have developed and used pharmaceutical drugs for a few centuries, but their genes have been functioning on their own and interacting with other environmental factors for long before that,” explained presenting author Chris Gignoux (photo), PhD, of the University of Colorado Anschutz Medical Campus. Like changes in the physical environment, drugs affect the micro- environment within the body, which alters the way its cells and genes function. This suggests that genes with pharmacogenomic relevance may also be useful in studying broader correlations between genetics and environment. To explore a variety of environmental factors, Dr. Gignoux collaborated with Elena Sorokin, PhD, of Stanford University, who created a geocoded resource of over 20 climate, geographic, and ecological variables, using data from NASA, the World Wildlife Fund, and other sources. With collaborators from across the United States, they examined samples from the Population Architecture using Genomics and Epidemiology (PAGE) Study, a large initiative to highlight the utility of studying clinically and epidemiologically relevant variation in 51,698 individuals from 99 global populations. In a new type of analysis they termed an Enviro-WAS (environment-wide association study), the researchers examined 19,690 pharmacogenomically-relevant variants to identify associations between genotypes and the 20 environmental variables.

Docs May Be Overly Conservative in Use of New Drug Combinations for Cancer, UCSD Speaker Suggests; Over 4 Million Three-Drug Combinations of Existing Drugs Possible, Too Many for Clinical Trials; Biomarker Use to Target Treatment Is Recommended

(BY MICHAEL A. GOLDMAN, PhD, Professor, Former Chairman of Biology, San Francisco State University). Speaking at this week's 2018 annual meeting of the American Society for Human Genetics (ASHG) in San Diego (October 16-20), Razelle Kurzrock (photo),MD, Director of the UC San Diego (UCSD) Center for Personalized Cancer Therapy, told a very large audience that oncologists have been conservative about using new drug combination therapies. Yet, with nearly 300 drugs on the market, there are more than 4 million 3-drug combinations, far too many to test in controlled trials. She uses a patient-centric, rather than a drug-centric, treatment plan, employing a consistent strategy, but with different drugs or, when appropriate, immunotherapy. Addressing more than 600 scientists and clinicians in a two-day symposium sponsored by the Pharmacogenomics Research Network (PGRN), Dr. Kurzrock said cancers are like malignant snowflakes, each different and magnificently complex. Profiling more than 12,000 tumors using genomic markers, her group uses biomarkers to target treatment in a "tissue-agnostic" manner. For example, PIK3CA mutations are found in 10% of patients with advanced cancers, and can be seen in a subset of most cancer types. Elevated HER2 expression occurs across a wide variety of tumors, and the same HER2 antagonists seem to work. Dr. Kurzrock calls her approach PREDICT (Profile-Related Evidence Determining Individual Cancer Therapy), which reflects a family of master protocols at UCSD. These protocols for trial combinations of drugs have limited exclusion criteria; almost every patient in need is eligible. Dr. Kurzrock stressed the need for genomics education for medical professionals, which she finds to be inadequate today. "In five years," she says, "it will be routine practice to do these [genomic] tests."

EXOSOME NEWS: Fat Cells & Extracellular Vesicles (EVs) They Release May Hold Solutions for Diabetes; “Findings Represent a New Way of Thinking for Researchers Who Study Diabetes, Obesity, and Metabolism”

Researchers have long known that cells in the human body communicate with one another. Now a team of scientists at the University of Texas (UT) Southwestern Medical Center is hacking into this communication network to learn how fat cells talk with other cells and tissues in the body. Dr. Philipp Scherer, a metabolism expert and Director of the Touchstone Center for Diabetes Research at UT Southwestern, is excited about the new findings because they will allow researchers to test new ideas and re-examine old ones. The study, published online on October 4, 2018 in Cell, shows that fat cells communicate with endothelial cells of the blood vessels that course through fat tissue, and potentially with other organs, by secreted packages of information (extracellular vesicles or EVs, often called exosomes). This communication between cells was demonstrated in a number of new mouse models that researchers created. The title of the new article is “An Endothelial-to-Adipocyte Extracellular Vesicle Axis Governed by Metabolic State.” These findings represent a new way of thinking for researchers who study diabetes, obesity, and metabolism. They open an entirely new door to our understanding of how tissues communicate,” said Dr. Clair Crewe, a postdoctoral researcher in the Touchstone Diabetes Center and first author of the study. “Once we understand the communication process, we can potentially shape it to either enhance or reduce the signaling effect.” The study identified a type of vesicle, a membrane-enclosed sphere, released by fat and other cells. Dr. Scherer compares them to the chocolate surrounding a bonbon. The “filling” includes lipids, signaling molecules, and proteins. The timing of their release is regulated by cycles of fasting and feeding. These vesicles travel throughout the body.

Ancient Andean Genomes Show Distinct Adaptations to Farming and Altitude; Findings Presented at ASHG 2018 Annual Meeting

Ancient populations in the Andes mountains of Peru adapted to their high-altitude environment and the introduction of agriculture in ways distinct from other global populations that faced similar circumstances, according to findings presented on October 17 at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). The ASHG has reported a record attendance of 8,500 at this year’s meeting. John Lindo, PhD, JD, Assistant Professor of Anthropology at Emory University, and a group of international collaborators headed by Anna Di Rienzo, PhD, at the University of Chicago and Mark Aldenderfer, PhD, at the University of California, Merced, set out to use newly available samples of 7,000-year-old DNA from seven whole genomes to study how ancient people in the Andes adapted to their environment. The scientists compared these genomes with 64 modern-day genomes from both highland Andean populations and lowland populations in Chile, in order to identify the genetic adaptations that took place before the arrival of Europeans in the 1500’s. “Contact with Europeans had a devastating impact on South American populations, such as the introduction of disease, war, and social disruption,” explained Dr. Lindo. “By focusing on the period before that, we were able to distinguish environmental adaptations from adaptations that stemmed from historical events.” The scientists found that Andean populations’ genomes adapted to the introduction of agriculture and resulting increase in starch consumption differently from other populations. For example, the genomes of European farming populations show an increased number of copies of the gene coding for amylase, an enzyme in saliva that helps break down starch.

October 17th

Genome Sequencing Found Feasible & Informative for Pediatric Cancer Treatment; Recommendations Reported at ASHG 2018 Annual Meeting; Work Is Part of St. Jude’s “Genomes for Kids” Study

Comprehensive genetic testing of tumors and non-cancerous tissue from pediatric cancer patients is a feasible and clinically useful approach that can guide patient care, according to findings presented on October 17 at the American Society of Human Genetics (ASHG) 2018 Annual Meeting in San Diego, California (October 16-20). The ASHG reports a record attendance of 8,500 for this year's meeting. Presenting author Scott Newman, PhD; Jinghui Zhang, PhD; and Kim Nichols (photo), MD, along with an interdisciplinary team at St. Jude Children’s Research Hospital, studied 253 pediatric oncology patients with a variety of cancers. In 79 percent of cases, there was at least one finding that could help guide care by providing a diagnosis, revealing patient-specific risks, or identifying drug targets. The researchers conducted whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing of the patients’ tumors, as well as WGS and WES of non-cancerous tissue from the same patient. WGS involves sequencing the patient’s complete genome, while WES involves sequencing those portions that are transcribed into mRNA, most of which codes for proteins. This work was part of the “Genomes for Kids” study (G4K), a large effort to understand how best to use genetic data for pediatric cancer diagnosis and treatment. Differing from other studies that require a specific diagnosis to participate, this study had no prerequisite beyond the presence of adequate tumor tissue for testing. “To my knowledge, this is the first study to offer comprehensive sequencing prospectively for all new patients with adequate samples," said Dr. Nichols. She also noted that the diversity of cancers that were tested helped to verify the relationships between genetic variants and disease. Dr.

October 14th

RNA Key (Non-Coding 886) That Unlocks Innate Immunity

RNA has long been the neglected middle child of biomolecules, the go-between from DNA, which encodes the cell's instructions, to proteins, which carry them out. Increasingly, though, researchers are recognizing RNA as a versatile molecule with, possibly, as many functions as proteins have. New research from Emory University, published in the October 12, 2018 issue of the Journal of Biological Chemistry, shows that one such versatile RNA molecule may be a key player in human cells' frontline defenses against viruses. The title of the article is “A Human Cellular Noncoding RNA Activates the Antiviral Protein 2′–5′-Oligoadenylate Synthetase 1,” Dr. Graeme Conn, the biochemistry professor who oversaw the work, studies how RNA is involved in the body's responses to infections. When a human cell senses a virus, it activates a signaling pathway: a protein called OAS (oligoadenylate synthetase) gets turned on and produces a signaling molecule, which in turn activates another protein that both directly defends against the virus as well as activating other parts of the cell's innate immune system. As it turns out, human RNA might play an important role in this pathway, specifically a human RNA molecule called nc886. The "nc" stands for "noncoding," which means this RNA molecule is not carrying instructions for building a protein. It's doing something all on its own. What it's doing, the new JBC paper shows, is turning on OAS, thus setting off the chain of events that destroys viruses. "We saw that (nc886) wasn't just an activator of this pathway, but a very potent activator," said Brenda Calderon, who carried out the research as a graduate student in Dr. Conn's lab. The nc886 molecule can adopt two different shapes, and one of them is much better at activating OAS than the other.