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Archive - 2019

October 31st

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 3, Tuesday October 8

Tuesday’s sessions of the annual ASEMV 2019 meeting at Asilomar, California, featured many exciting presentations. Among the 16 talks of the day, five were of particular interest. The first was by Ryan McNamara, PhD, of University of North Carolina-Chapel Hill, whose presentation was titled “EVs from Kaposi Sarcoma-Associated Herpes Lymphoma Induce Long-Term Endothelial Cell Reprogramming.” Dr. McNamara noted that extracellular communication is critical for organismal homeostasis, and thus presents as a major network for viruses to usurp for viral pathogenesis. EVs package contents from a donor cell to communicate with its surroundings, and evolutionarily diverse viruses have been shown to hijack this communication axis to promote pathogenesis. Previously, Dr. McNamara and colleagues had showd that the oncovirus Kaposi’s Sarcoma-Associated Herpes Virus (KSHV) incorporates viral miRNA into EVs secreted from infected cells during the “latency stage” of the viral life cycle. They hypothesized that these modified EVs, termed KSHV-EVs, aid in the establishment of a more favorable niche for disease/tumor progression. Their current results demonstrate that KSHV can modify the local environment using EVs. The group currently proposes that oncoviruses such as KSHV utilize the extracellular communications network through EVs to establish a niche favorable for disease progression and tissue transformation. This allows for the virus to reshape the local environment with minimal spread of the infectious agent, and without tripping immune alarms. In a following presentation, Jeffrey Savas, PhD, from Northwestern University, spoke on how “Viral Scission Factor Alix Tunes Neuronal Communication Through EVs.” Dr. Savas began by noting that synaptic plasticity is a dynamic process facilitating adaptable and flexible communication.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 2, Monday October 7

Monday’s sessions of the annual ASEMV 2019 meeting at Asilomar, in Pacific Grove, California, featured many exciting presentations. Among the 16 talks of the day, five were of particular interest. The first, “Methamphetamine Use Disorder Alters Plasma EV MicroRNA Expression,” was presented by Ursula Sandau, PhD, of Oregon Health & Science University (OHSU) in Portland, Oregon. Dr. Sandau noted that methamphetamine has deleterious effects to both peripheral organs and the central nervous system. The rewarding properties and addictive potential of methamphetamine are correlated with increased synaptic dopamine availability following alterations in dopamine and vesicular monamine transporter function. She reported results demonstrating that EV miRNA expression in subjects with methamphetamine use disorder was significantly different than in control participants, suggesting that methamphetamine may affect EV communication among cells. Dr. Sandau further noted that the differential miRNA expression also implicates a role for EVs in behavioral and physiological effects specific to methamphetamine and suggests that there may be changes in expression of miRNAs that are relevant to specific drugs of addiction, as well as to a spectrum of drug-mediated addiction disorders. In another compelling presentation, Franklin Monzon, PhD, of Spectradyne Particle Analysis (https://nanoparticleanalyzer.com/), spoke on “The Importance of Orthogonal Techniques in Quantifying Extracellular Vesicles.” Dr. Monson noted that, as EV research matures, so must the relevant measurement technologies.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles Opened Sunday Evening, October 6, at Asilomar in Pacific Grove, California

The 2019 annual meeting of the American Society for Exosomes and Microvesicles (ASEMV) was held October 6-10 at the gorgeous Asilomar Conference Grounds in Pacific Grove, California, home of migrating monarch butterflies, steps from the Pacific Ocean, and just 120 miles south of San Francisco. The glorious natural setting was almost matched perhaps by the broad range of 60 scintillating presentations delivered by scientists from around the country and world, during the five intense days of meetings focused on one of the most exciting aspects of biology and mediicine. This year’s meeting, organized as always by Stephen Gould, PhD, of Johns Hopkins, began on Sunday evening with a brief introduction on the history of the ASEMV annual meetings by Michael Graner, PhD, University of Colorado-Denver, and this was followed by the keynote presentation, sponsored by Caris Life Sciences, and delivered by Dr. Travis Thomson of the University of Massachusetts (Worcester, MA). Dr. Thomson’s address was titled “Arc and Copia in Exosome-Mediated Information Exchange.” Dr. Thomson described Arc as a “master regulator of neuronal plasticity and as a remnant of a transposon gag region of a virus. In a 2018 article in Cell (https://www.ncbi.nlm.nih.gov/pubmed/29328915), Dr. Thomson and colleagues noted that Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. In the Cell article, Dr.

October 29th

Scientists Discover Involvement of Known Protein (Clathrin) in Liver Cancer: Finding Has Clear Clinical Relevance, As It Will Facilitate Patient Selection for More Specific Therapy

Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona, Spain, have just described, for the first time, the crucial involvement of a cell membrane protein in the development and progression of liver cancer, according to an article published online on September 25, 2019 in the Journal of Hepatology. The open-access article is titled “Clathrin Switches Transforming Growth Factor-β role to Pro-Tumorigenic in Liver Cancer.” This protein, called clathrin, is known for its key role in the process of internalization of molecules from the extracellular space into the cell, called endocytosis. In this process, the cell membrane folds, creating vesicles with a cladded structure. Thanks to the new results, analyzing the levels of clathrin expression in biopsies of hepatocellular carcinoma patients will help select those patients who will benefit from a much more targeted and personalized therapy. The research team, led by Dr. Isabel Fabregat, who is a professor at the Faculty of Medicine and Health Sciences of the University of Barcelona and a researcher at the CIBER of Hepatic and Digestive Diseases, has shown that liver cells with invasive features have high levels of clathrin, a protein whose involvement in liver cancer was unknown until now. Specifically, researchers showed that high expression levels of clathrin correlate with the activation of the pro-tumorigenic pathway of a known hepatic carcinogenesis actor: TGF-β. In this sense, the work provides completely new and clinically valuable knowledge when it comes to understanding the complex and controversial role of TGF-β in this type of cancer.

October 25th

Lupus Study Illustrates Importance of Considering Diversity In Genetic Research

Scientists at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, have pinpointed epigenetic differences in the way lupus affects black women compared to other lupus patients, revealing important mechanics of the puzzling disease. Epidemiologists have identified that lupus impacts black women with greater frequency and severity than other populations. Scientists in Dr. Devin Absher's Lab (https://hudsonalpha.org/faculty/devin-absher/) at HudsonAlpha published findings on August 20, 2019, in an open-access article in Arthritis & Rheumatology, showing that increased risk and harm to lupus patients can be linked to epigenetic differences--essentially, the degree to which certain genes are functioning. The finding helps create a more complete understanding of an often misunderstood disease, revealing some of the mechanisms that contribute to it. The article is titled “Epigenetic Defects in the B cell lineage of Systemic Lupus Erythematosus Patients Display Population‐Specific Patterns.” The study also reveals a gap in genetic research, highlighting the lack of information scientists have regarding racial differences on the genetic level. Lupus is an autoimmune disorder, meaning that the immune system attacks healthy cells in the body. It causes symptoms that are often difficult to quantify, including fatigue and extreme joint pain. Lupus is one of the most historically chronicled diseases, having first been documented by Socrates in 400 BC. The disease gets its name from a common rash that forms on the face which is said to resemble the markings of wolves, hence the latin name "lupus" meaning wolf. There are more than 200,000 cases of lupus in the US every year, yet there is no universally accepted cause or cure. The disease is chronic, meaning it can last for years or even an entire lifetime.

October 25th

Mutation Discovery in Monkeys Could Lead to Treatment for Blindness-Causing Syndrome (Bardet-Biedl Syndrome or BBS), and Other Forms of Retinitis Pigmentosa in Humans; OHSU Scientists Report First-Ever Non-Human Primate Model for BBS

A genetic mutation that leads to a rare, but devastating blindness-causing syndrome has been discovered in monkeys for the first time. The finding offers a promising way to develop gene and cell therapies that could treat the condition in people. Three rhesus macaques with a mutated gene that's associated with Bardet-Biedl syndrome (BBS) have been discovered, according to a study published in the December 2019 issue of Experimental Eye Research. The article is titled “Bardet-Biedel Syndrome in Rhesus Macaques: A Nonhuman Primate Model of Retinitis Pigmentosa.” It is the first known naturally occurring non-human primate model of the syndrome. BBS leads to vision loss, kidney disfunction, extra fingers or toes, and other symptoms. It occurs in 1 of 140,000 to 160,000 North American births. "There is no cure for Bardet-Biedel Syndrome today, but having a naturally occurring animal model for the condition could help us find one in the future," said the paper's corresponding author, Martha Neuringer, PhD, a Professor of Neuroscience at the Oregon National Primate Research Center at Oregon Health & Science University (OHSU), and a research associate Professor of Ophthalmology in the OHSU School of Medicine and OHSU Casey Eye Institute. Rhesus macaques with this disease could help more than just BBS patients. BBS is part of a larger family of diseases called retinitis pigmentosa, in which all of the diseases affect the retina, or the back part of the eye. A naturally occurring animal model for BBS might help researchers find treatments for a variety of retinitis pigmentosa diseases.

October 23rd

New Alpha-Gel; An Environment-Friendly and Easily Producible Surfactant Used to Prepare Effective Water-Retaining Mixture That Can Be Used in Skincare

A layer of lipids covers our skin, and with its help our skin retains moisture and remains healthy. In the lipid layer, a compound called ceramide forms a "lamellar gel" with cholesterol, fatty acids, and water. Lamellar gels are mixtures that are thick, do not flow easily, and can hold large amounts of water. Natural ceramide is therefore an important factor for water retention in our skin. A type of lamellar gel, called the "α-gel," can be formulated by mixing compounds called surfactants with a fatty alcohol and water. As you may have guessed by this explanation, α-gels are widely used in skincare products such as skin creams. In a new study published in Colloids and Surfaces A (https://www.sciencedirect.com/journal/colloids-and-surfaces), scientists from Tokyo University of Science and Miyoshi Oil and Fat Co. Ltd., Japan, led by Dr Kenichi Sakai, synthesized an α-gel using an oleic acid-based surfactant, which can potentially be used in skincare products. This is a surfactant they had previously developed and is structurally similar to natural ceramide (both are amphiphiles with two tails). "I was interested in whether α-gels could be prepared using gemini surfactants (two-tailed and two-headed surfactants), and in what their structural and physical properties would be," Dr Sakai says. Once the α-gel was ready, Dr Sakai and his team used a technique called small- and wide-angle X-ray scattering (SWAXS), another technique called nuclear magnetic resonance (NMR) spectroscopy, and an optical microscope to confirm its characteristics. For this, they prepared several mixtures containing different molar ratios of the oleic acid-based surfactant, water, and 1-tetradecanol (a fatty alcohol). The findings were, indeed, satisfactory.

Breakthrough in Genetic Skin Disease; Epigenetic Modifers DNMT3A and BCOR Are Recurrently Mutated in CYLD Cutaneous Syndrome (CCS)

A breakthrough has been made in understanding a rare genetic skin disease that causes progressively enlarging skin tumors over the scalp, face, and body. For the first time, scientists at Newcastle University, UK, have identified changes in the DNA of the tumor cells in those with CYLD (CYLD lysine 63 deubiquitinase) (image) cutaneous syndrome (CCS) that may help them grow. A study published online on October 17, 2019 in Nature Communications suggest that the tumor cells gain a “survival advantage” when the changes occur - an important step in understanding ways to develop treatments. The open-access article is titled “Epigenetic Modifiers DNMT3A and BCOR Are Recurrently Mutated in CYLD Cutaneous Syndrome.” CCS is a hereditary condition that affects areas of the body where there are hair follicles and leads to skin tumors called "cylindromas" forming and continually growing. The alterations discovered by the experts were in two genes (DNMT3A and BCOR) that are found in the skin tumors. One of the changes highlights a mechanism that the skin tumor cells use to survive and it is hoped that these could be targeted with a new class of drug to inhibit their growth. The change to the second gene is novel for skin tumors and warrants further investigation to establish the significance it has on the growth of the tumors. Dr. Neil Rajan, Senior Lecturer and Honorary Consultant Dermatologist at Newcastle University's Faculty of Medical Sciences, led the research, which was done in collaboration with Dr Serena Nik-Zainal's team at the University of Cambridge.Dr. Rajan said: "This research is an important step in the ongoing work to develop treatments for patients with CCS, which is a central goal of my research group.

Scientists Reveal Novel Oncogenic Driver Gene (DEPDC5) on Chromosome 22q in Human Gastrointestinal Stromal Tumors (GISTs); Intriguing Connection with Focal Epilepsy; DEPCD5 Agonists May Serve As Anti-Cancer Drugs

Sarcomas - cancers that arise from transformed mesenchymal cells (a type of connective tissue) - are quite deadly. Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma and are initiated by activating mutations in the KIT receptor tyrosine kinase. Micro-GISTs are a smaller variation of clinical GISTs and are found in one-third of the general population without clinical symptoms. Although the micro-GISTs and clinical GISTs share the same KIT mutations, micro-GISTs have limited growth potential and do not exceed a centimeter. This size limitation suggests that additional genetic alterations contribute to the progression of clinical GISTs. Chromosome 22q deletions are frequent chromosomal abnormalities in human GISTs, occurring in ~50% of GISTs, and are thought to contribute to the pathogenesis of this disease. However, the crucial gene in 22q was unknown for decades. In a study published online on October 21, 2019 in PNAS, a team led by Professor Yuexiang Wang of the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences, together with Professor Jonathan Fletcher from Brigham and Women's Hospital and Harvard Medical School, described a novel druggable driver gene in GISTs. The PNAS article is titled “Mutational Inactivation of mTORC1 Repressor Gene DEPDC5 in Human Gastrointestinal Stromal Tumors.” The researchers performed whole exome sequencing and reported recurrent genomic inactivated DEPDC5 gene mutations in GISTs. DEPDC5 was shown to be a chromosome 22q-targeting tumor suppressor, silenced by mutations in GIST specifically. The scientists further provided evidence that inactivation of DEPDC5 promotes GIST cell proliferation by activating the mTORC1 signaling pathway and subsequently inhibiting cell cycle arrest.

October 23rd

In Nine-Year Effort, Scientists Sequence Transcriptomes of Over 1,100 Plants, Illuminating 1 Billion Years of Evolution

Plants are evolutionary champions, dominating Earth's ecosystems for more than a billion years and making the planet habitable for countless other life forms, including us. Now, scientists have completed a nine-year genetic quest to shine a light on the long, complex history of land plants and green algae, revealing the plot twists and furious pace of the rise of this super group of organisms. The project, known as the “One Thousand Plant Transcriptomes Initiative” (1KP), brought together nearly 200 plant biologists to sequence and analyze genes from more than 1,100 plant species spanning the green tree of life. A summary of the team’s findings was published online on October 23, 2019 in Nature. The open-access article is tited “One Thousand Plant Transcriptomes and the Phylogenomics of Green Plants.” "In the tree of life, everything is interrelated," said Gane Ka-Shu Wong, PhD, lead investigator of 1KP and Professor in the University of Alberta's Department of Biological Sciences. "And if we want to understand how the tree of life works, we need to examine the relationships between species. That's where genetic sequencing comes in." Much of plant research has focused on crops and a few model species, obscuring the evolutionary backstory of a clade that is nearly half a million species strong. To get a bird's-eye view of plant evolution, the 1KP team sequenced transcriptomes - the set of genes that is actively expressed to produce proteins - to illuminate the genetic underpinnings of green algae, mosses, ferns, conifers, flowering plants, and all other lineages of green plants.