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Archive - Oct 2020

October 16th

Study Suggests Higher Dopamine Levels May Be Associated with Better Mobility in Frail & Elderly Adults

Variations in a gene that regulates dopamine levels in the brain may influence, positively or negatively, the mobility of elderly and frail adults, according to new research from the University of Pittsburgh (Pitt) Graduate School of Public Health. These results, published online on October 12, 2020 in the Journal of The American Geriatrics Society, add to a growing body of evidence hinting that lower dopamine levels can contribute to the slower, often disabling walking patterns seen in some elderly populations. The article is titled “Catechol‐O‐Methyltransferase Genotype, Frailty, and Gait Speed in a Biracial Cohort of Older Adults.” "Most people think about dopamine's role in mobility in the context of Parkinson's disease, but not in normal aging," said senior author Caterina Rosano, MD, MPH, Professor of Epidemiology at Pitt Public Health. "We were curious to see if a genetic predisposition to produce more or less dopamine was related to mobility in individuals who had some level of frailty, yet did not have dementia, parkinsonism or any other neurological condition." While several genetic elements control dopamine signaling, Dr. Rosano and her team focused on a gene called COMT (catechol-O-methyltransferase), which breaks down dopamine to control its levels within the brain. They also considered the frailty status of participants, which is a common consequence of aging marked by a decline in physiological function, poor adjustment to stressors and a susceptibility toward adverse health outcomes. The researchers suspected that frail participants could be particularly vulnerable to COMT-driven differences in dopamine levels. Dr.

How Deadly Parasites “Glide” Along and Into Human Cells

In biological terms, gliding refers to the type of movement during which a cell moves along a surface without changing its shape. This form of movement is unique to parasites from the phylum Apicomplexa, such as Plasmodium and Toxoplasma. Both parasites, which are transmitted by mosquitoes and cats, have an enormous impact on global heath. Plasmodium causes 228 million malaria infections and approximately 400,000 deaths per year. Toxoplasma, which infects an estimated one third of the human population, can cause severe symptoms in some people, and is particularly dangerous during pregnancy. Gliding enables the Apicomplexa parasites to enter and move between host cells. For example, upon entering the human body through a mosquito bite, Plasmodium glides through human skin before crossing into human blood vessels. This type of motion relies on actin and myosin, which are the same proteins that enable muscle movement in humans and other vertebrates. Myosin has a form of molecular 'legs' that 'march' along actin filaments and thereby create movement. In Apicomplexa, myosin interacts with several other proteins, which together form a complex called the “glideosome.” The exact mechanism by which the glideosome works is not well understood, among other reasons because the molecular structure of most glideosome proteins are unknown. Yet understanding this mechanism could aid the development of drugs that prevent the assembly of the glideosome and thereby stop the progression of diseases such as malaria and toxoplasmosis. Scientists at European Molecular Biology Laboratory (EMBL) Hamburg analyzed the molecular structure of essential light chains (ELCs), which are glideosome proteins that bind directly to myosin.

Scientists Develop “Unprecedented” 3-D Model of Molecular Machine (BAF Complex) That Regulates Expression of Genes by Modifying Chromatin; Model Has Enabled Investigators to Map Many Cancer-Related Mutations to Locations in BAF Complex

Scientists have created an unprecedented 3-dimensional structural model of a key molecular “machine” known as the BAF complex (mammalian SWI/SNF complex) (https://en.wikipedia.org/wiki/SWI/SNF), which modifies DNA architecture and is frequently mutated in cancer and some other diseases. The researchers, led by Cigall Kadoch (photo), PhD, (http://www.kadochlab.org/ of Dana-Farber Cancer Institute, have reported the first 3-D structural “picture” of BAF complexes purified directly from human cells in their native states--rather than artificially synthesized in the laboratory--providing an opportunity to spatially map thousands of cancer-associated mutations to specific locations within the complex. “A 3-D structural model, or ‘picture,’ of how this complex actually looks inside the nucleus of our cells has remained elusive--until now,” says Dr. Kadoch. The newly obtained model represents “the most complete picture of the human BAF complex achieved to date,” said the investigators, reporting in the journal Cell. The article is titled “A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms.” Dr. Kadoch is Associate Professor of Pediatric Oncology, Dana-Farber Cancer Institute; Affiliated Faculty, Biological Chemistry and Molecular Pharmacology, Harvard Medical School; and Institute Member and Epigenomics Program Co-Director, Broad Institute of MIT and Harvard. The new findings “provide a critical foundation for understanding human disease-associated mutations in components of the BAF complex, which are present in over 20% of human cancers and in several intellectual disability and neurodevelopomental disorders,” the authors said.

October 15th

Codiak BioSciences, Specializing in Exosome-Based Therapeutics, Announces Pricing ($15/Share) of Initial Public Offering

On October 13, 2020, Codiak BioSciences, Inc., a clinical-stage company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, announced the pricing of its initial public offering (IPO) of 5,500,000 shares of its common stock at a public offering price of $15.00 per share, for gross proceeds of approximately $82.5 million, before deducting underwriting discounts and commissions and offering expenses. [Editor’s Note: CDAK price at end of day October 15 was $12.09/share.] All of the shares are being offered by Codiak. In addition, Codiak has granted the underwriters a 30-day option to purchase up to 825,000 additional shares of common stock at the initial public offering price, less underwriting discounts and commissions. The shares are scheduled to begin trading on the Nasdaq Global Market on October 14, 2020 under the ticker symbol “CDAK,” and the offering is expected to close on October 16, 2020, subject to customary closing conditions. Goldman Sachs & Co. LLC, Evercore ISI, and William Blair are acting as joint book-running managers for the offering and as representatives of the underwriters. Wedbush PacGrow is acting as lead manager for the offering. A registration statement relating to these securities has been filed with the Securities and Exchange Commission and became effective on October 13, 2020. This offering is being made only by means of a prospectus. Copies of the final prospectus, when available, may be obtained from: Goldman Sachs & Co.

Researchers ID Mechanism Underlying Bone Marrow Failure in Fanconi Anemia

Researchers at the University of Helsinki in Finland and the Dana-Farber Cancer Institute in the USA have identified the mechanism behind bone marrow failure developing in children that suffer from Fanconi anemia. The findings may help to develop new therapies for the disorder. Fanconi anemia (FA) is a genetic disease affecting small children and characterized by bone marrow failure, developmental abnormalities, and predisposition to multiple forms of cancer. The molecular mechanisms behind FA are inherited mutations in genes encoding DNA repair proteins, leading to irreversible bone marrow failure. The exact mechanisms of how these genetic mutations lead to the exhaustion of stem cells from the bone marrow have been unknown. Now, the researchers have identified a cause for this failure. The findings were published online on September 29, 2020 in Cell Stem Cell. The article is titled “MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia.” “The results open new paths for developing novel therapies for the disease, for which the only curative treatment currently available is stem cell transplantation. Understanding the mechanism of bone marrow failure better can help to plan stem cell transplantations and to develop new therapies for milder forms of Fanconi anemia,” says Anniina Färkkilä (photo), MD, PhD, Docent and Clinical Researcher at the University of Helsinki, and Specialist in Obstetrics and Gynecology at Helsinki University Hospital. In the study, researchers at the University of Helsinki analyzed the gene expression of individual cells, and found, to their surprise, overexpression of the MYC gene in the bone marrow stem cells of patients with Fanconi anaemia. MYC is one of the best-known genes regulating the formation of malignant tumors.

New Study Suggests Crucial Role for T-Cells in Asymptomatic COVID-19 Infection

COVID-19 remains stubbornly inconsistent. More than a million people have died and 35 million have been diagnosed, but a large fraction of people infected with the coronavirus--about 45%, according to recent estimates--show no symptoms at all. A retrospective study of 52 COVID-19 patients, published online on October 7, 2020 in mSphere, an open-access journal of the American Society for Microbiology, may help researchers better understand why not everyone show symptoms of the disease. The article is titled “Descriptive, Retrospective Study of the Clinical Characteristics of Asymptomatic COVID-19 Patients.” The study's authors found that asymptomatic patients hosted viral loads comparable to those of symptomatic patients, but asymptomatic patients showed higher levels of lymphocytes (a type of white blood cell responsible for immune responses), cleared the viral particles faster, and had lower risks of long-term complications. Further analyses suggested the interaction between the virus and the immune system likely played a role in that process. "Our findings suggested an important role for lymphocytes, especially T-cells, in controlling virus shedding," said virologist Yuchen Xia, PhD, at Wuhan University's School of Basic Medical Sciences in China, senior author of the new study. The wide range of COVID-19 symptoms is well documented. Asymptomatic carriers, on the other hand, often go undiagnosed, but can still shed the virus and spread it to others. Understanding why some patients get sick and others don't is one of the most important challenges in curbing the pandemic, Dr. Xia said. "They may cause a greater risk of virus transmission than symptomatic patients, posing a major challenge to infection control." Dr.

October 14th

ASHG Honors Janina Jeff, PhD, with Its $10,000 Advocacy Award for Producing Hip-Hop Inspired Podcast That Uses Genetics to Uncover Lost Identities of African-Descended Americans Through Lens of Black Culture

The American Society of Human Genetics (ASHG) has named Janina Jeff, PhD, MS, as the 2020 recipient of the Society’s Advocacy Award (https://www.ashg.org/membership/awards/advocacy/). Dr. Jeff is the host and executive producer of “In Those Genes,” described as “a hip-hop inspired podcast that uses genetics to uncover the lost identities of African descended Americans through the lens of Black Culture.” See sample podcast at https://www.youtube.com/watch?v=BldybNBDqv0. Dr. Jeff is a Senior Scientist at Illumina, a company at the intersection of biology and technology. This award, which includes a plaque with a $10,000 prize, honors individuals or groups who have exhibited excellence and achievement in applications of human genetics for the common good, in areas such as facilitating public awareness of genetics issues, promoting funding for biomedical research, and integrating genetics into health systems. “Dr. Janina Jeff’s groundbreaking podcast ‘In Those Genes’ has provided fundamental insight into genetics and the exploration of the lost identities of African-descended Americans through the lens of Black culture,” said ASHG President Anthony Wynshaw-Boris, MD, PhD. “She is also an inspiring leader with a deep commitment to educating others and is a very important spokesperson in human genetics for a wider audience beyond scientists.” “In the wake of COVID-19, the podcast has quickly evolved as a forum dispensing scientific and medical truths and dispelling rumors and conspiracy theories circulating in the Black community on social media,” said Dana Crawford, PhD, Associate Professor, Department of Population and Quantitative Health Services, Case Western University, in her nomination letter. Dr.

Two UTSW Studies in Science Focus on Elucidating Molecular Underpinnings of Schistosiomiasis

Two studies led by University of Texas (UT) Southwestern (UTSW) researchers have shed light on the biology and potential vulnerabilities of schistosomes – parasitic flatworms that cause the little-known tropical disease schistosomiasis. The findings, published in the Septembr 25, 2020 issue of Science, could change the course of this disease that kills up to 250,000 people a year. About 240 million people around the world have schistosomiasis – mostly children in Africa, Asia, and South America in populations that represent “the poorest of the poor,” says study leader James J. Collins (photo) (https://profiles.utsouthwestern.edu/profile/154775/james-collins.html), PhD, Associate Professor in UTSW’s Department of Pharmacology. Most of those infected survive, but those who die often suffer organ failure or parasite-induced cancer. Symptoms can be serious enough to keep people from living productive lives, Dr. Collins says. The parasite that causes this disease has a complicated life cycle that involves stages in both freshwater snails and mammals. Dwelling in mammalian hosts’ circulatory systems, schistosomes feed on blood and lay copious numbers of eggs, all while causing an array of symptoms including abdominal pain, diarrhea, bloody stool, or blood in the urine. Larval worms are released from snails into water, where the flatworms then may infect humans by penetrating the skin. Schistosomiasis may become a chronic disease that affects the person for years. Only one drug, praziquantel, is available to treat this condition. However, Dr. Collins explains, it is of limited use – it doesn’t kill all intramammalian stages of the schistosome life cycle, and it has a variable cure rate in some endemic settings. There’s been little interest by pharmaceutical companies in developing new drugs for this disease, he adds, because there is no monetary incentive to do so.

Fighting Intestinal Infections with Body's Own Endocannabinoids: Native Chemicals Similar to Those Found in Cannabis Can Inhibit Bacterial Virulence, UTSW-Led Study Suggests

Endocannabinoids, signaling molecules produced in the body that share features with chemicals found in marijuana, can shut down genes needed for some pathogenic intestinal bacteria to colonize, multiply, and cause disease, new research led by University of Texas (UT) Southwestern (UTSW) scientists shows. The findings, published online on October 7, 2020 in Cell, could help explain why the cannabis plant--the most potent part of which is marijuana--can lessen the symptoms of various bowel conditions and may eventually lead to new ways to fight gastrointestinal infections. The Cell article is titled” Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens.” Discovered in 1992, endocannabinoids are lipid-based neurotransmitters that play a variety of roles in the body, including regulating immunity, appetite, and mood. Cannabis and its derivatives have long been used to relieve chronic gastrointestinal conditions, including irritable bowel syndrome and inflammatory bowel disease. Studies have shown that dysregulation of the body’s endocannabinoid system can lead to intestinal inflammation and affect the makeup of gut microbiota, the population of different bacterial species that inhabit the digestive tract. However, study leader Vanessa Sperandio (photo), PhD, Professor of Microbiology and Biochemistry at UTSW, says it’s been unknown whether endocannabinoids affect susceptibility to pathogenic gastrointestinal infections.

October 13th

ASHG 2020 Virtual Annual Meeting to Showcase Innovative Research in Human Genetics (October 27-30)

The American Society of Human Genetics (ASHG) 2020 Virtual Annual Meeting taking place October 27-30 will showcase global advances in human genetics and genomics research that are transforming the scientific landscape and leading to new advances in the treatment of devastating diseases. The ASHG 2020 Virtual Meeting (https://www.ashg.org/meetings/2020meeting/) will feature more than 200 oral presentations, nearly 2,000 scientific poster presentations, 80+ exhibit booths, networking and professional development opportunities, and more, making it the digital epicenter of human genetics. As always, it will be among the world’s largest events for genetic and genomic discovery, with thousands of scientists, clinicians, advocates, and others participating from more than 50 countries.“As a global showcase of the latest developments in human genetics, the ASHG 2020 Virtual Meeting will provide an online venue for researchers who conduct human genetics and genomics research around the world to exchange scientific knowledge,” said Anthony Wynshaw-Boris, MD, PhD, ASHG President. “I am excited about the fantastic talks, posters, and special sessions, that will be presented at the Virtual Meeting.” The meeting will host chat sessions throughout the program to continue scientific conversations and exchanges around the latest scientific updates and breakthroughs. The Society will also recognize the outstanding scientific achievements of its members in the human genetics and genomics community with special awards and lectures throughout the meeting. Not only will the ASHG 2020 Virtual Meeting host exceptional plenaries, but also concurrent programming sessions covering critical areas of the field.