Syndicate content

Archive - Oct 2018

Date

October 31st

STUNNER: Appendix Identified As Potential Starting Point for Parkinson's Disease

Removing the appendix early in life reduces the risk of developing Parkinson's disease by 19 to 25 percent, according to the largest and most comprehensive study of its kind, published in the October 31, 2018 issue of Science Translational Medicine. The open-access article is titled “The Vermiform Appendix Impacts the Risk of Developing Parkinson’s Disease.” The findings also solidify the role of the gut and immune system in the genesis of the disease, and reveal that the appendix acts as a major reservoir for abnormally folded alpha-synuclein proteins, which are closely linked to Parkinson's onset and progression. "Our results point to the appendix as a site of origin for Parkinson's and provide a path forward for devising new treatment strategies that leverage the gastrointestinal tract's role in the development of the disease," said Viviane Labrie, PhD, an Assistant Professor at Van Andel Research Institute (VARI) and senior author of the study. "Despite having a reputation as largely unnecessary, the appendix actually plays a major part in our immune systems, in regulating the makeup of our gut bacteria and now, as shown by our work, in Parkinson's disease." The reduced risk for Parkinson's was only apparent when the appendix and the alpha-synuclein contained within it were removed early in life, years before the onset of Parkinson's, suggesting that the appendix may be involved in disease initiation. Removal of the appendix after the disease process starts, however, had no effect on disease progression. In a general population, people who had an appendectomy were 19 percent less likely to develop Parkinson's. This effect was magnified in people who live in rural areas, with appendectomies resulting in a 25 percent reduction in disease risk.

Barn Owls Help Hopkins Scientists Unlock Secret of How Brain Pays Attention; Cover Article Provides “Beautiful Answer” to How Brain Determines Where to Focus

By studying barn owls, scientists at Johns Hopkins University believe they've taken an important step toward solving the long-standing mystery of how the brain chooses what most deserves attention. The finding, which is the subject of the cover article of the October 30, 2018 issue of the journal Cell Reports, likely applies to all animals, including humans, and offers new insight into what goes wrong in the brain with diseases like attention-deficit disorder (ADD). The open-acces article is titled “Combinatorial Neural Inhibition for Stimulation Across Space.” "There are a million things out there in the world bombarding our eyes, our ears, our skin, and other sensory organs. Of all of those things, what particular piece of information do we most need to pay attention to at any instant to drive our behavior?" said co-author Shreesh Mysore, PhD, a Johns Hopkins University neuroscientist. "Our work provides a really beautiful answer to how the brain solves a key component of that problem." Despite studying the forebrain of animals for decades, scientists haven't found a good answer to the question of how the brain decides what to pay attention to. The researchers decided instead to look at the midbrain, an evolutionarily older part of the brain found in everything from fish and mammals to birds and humans. "All animals have a need to pay attention to the thing that might impact our survival, but we don't all have a highly developed forebrain," said Dr. Mysore, who is also an Assistant Professor of Psychological and Brain Sciences.

October 30th

GangSTR—New Algorithm Applied to Genome-Wide Genotyping of Short Tandem Repeat (STR) Expansions, Such As Those Implicated in Huntington’s Disease, Fragile X Syndrome, & Myotonic Dystrophy

(BY SALLY G. PASION, PhD, Associate Professor of Biology, San Francisco State University). On October 18, at the 2018 American Society for Human Genetics (ASHG) Annual Meeting in San Diego, California (http://www.ashg.org/2018meeting/) (October 16-20), software engineer Nima Mousavi, PhD (@nmmsv), in the Electrical and Computer Engineering Department, University of California San Diego (UCSD), in the laboratory of Dr. Melissa Gymrek (https://gymreklab.github.io/), highlighted GangSTR, a novel algorithm for genome-wide profiling of both normal and expanded tandem repeats (TRs). GangSTR provides a new way to identify short tandem repeats (STRs) from next-generation sequencing (NGS) data. STRs are 1-6 base-pair (bp) sequences, repeated in tandem in the genome. Dr. Mousavi’s presentation was one of six that were delivered in a late-morning meeting session (#51) titled ““What Are We Missing? Identification of Previously Underappreciated Mendelian Variants.” The session is described at the following link: http://www.ashg.org/2018meeting/listing/NumberedSessions.shtml#sess51. Dr. Mousavi’s presentation (#188) was titled “GangSTR: Genome-Wide Genotyping Short Tandem Repeat Expansions” (https://eventpilot.us/web/page.php?page=IntHtml&project=ASHG18&id=180122313). STRs exhibit a higher mutation rate compared to insertion-deletions (indels) or single nucleotide polymorphisms (SNPs). Three percent of the human genome contains STRs, and the presence of the repeats may affect the coding region and thus the protein sequence, or it may occur in the non-coding region and affect gene expression. There are STRs that are implicated in trinucleotide repeat diseases such as Huntington’s disease (HD), fragile X syndrome, Friedreich ataxia, spinocerebellar ataxia, and myotonic dystrophy.

From Pond Hockey to Top of Scientific World--U Minnesota Honors Distinguished Alumnus, World-Class Immunologist Dr. Ronald Faanes

On October 11, 2018, the University of Minnesota College of Biological Sciences (CBS) honored one of its own—eminent immunologist Ronald Faanes, PhD—at the College’s annual Recognition and Appreciation Dinner at Memorial Hall in the McNamara Alumni Center. Dr. Faanes, who received his BS (chemistry) and PhD (microbiology) from U Minnesota, was the keynote speaker at this year’s dinner, which drew a crowd of 300 donors, faculty, and student scholarship winners. Ron was introduced by CBS Dean Dr. Valery Forbes (https://cbs.umn.edu/contacts/valery-forbes), who noted that as a pupil and mentee of longtime CBS faculty member Dr. Palmer Rogers, “Ron brings a wealth of insight, and some really great stories, about the revered scientist and teacher for whom the Palmer Rogers Microbiology Scholar ship is named.” Some of Dr. Rogers family were in the audience and they could not help being moved by the poignant memories of Palmer that Ron would recount in his address. Ron, who had also played hockey for the Gophers, had moved on from U Minnesota to work first as a tumor immunologist at the Sloan-Kettering Institute, the research arm of the renowned Memorial Sloan Kettering Cancer Center, in New York. Legendary U Minnesota physician/scientist Dr. Robert Good, who had led the team that performed the world’s first successful human bone marrow transplant between persons who were not identical twins and is regarded as a founder of modern immunology, had just been named Director of Sloan-Kettering and he brought many of his best scientists, including Ron, along with him to New York.

October 28th

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."