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International Study Led by Harvard Scientists Reveals Surprising Amount of Gene Flow Among Butterfly Species, Even Between Some That Are Distantly Related

An international team of researchers analyzed the genomes of 20 butterfly species and discovered a surprisingly high amount of gene flow among them - even between species that are distantly related. The findings, published in the November1, 2019 issue Science, challenge conventional views about species and point to hybridization as a key process in the emergence of biological diversity. The article, which serves as the cover story of this issue of Science, is titled “Genomic Architecture and Introgression Shape A Butterfly Radiation.” Different species of passion vine butterflies (Heliconius) have similar color patterns that serve as warnings to predators. Scientists have previously found that one reason for their similarity is that they actually share parts of their DNA, thanks to hybridization that occurred at some point in their ancestry. The new findings suggest that this process of DNA sharing is far more common than previously thought. To understand how butterflies pass genes to other species by hybridizing, a process known as introgression, the researchers analyzed new genome assemblies of 20 Heliconius butterfly species. "DNA sharing had been shown in closely related species, but we wanted to probe deeper into the phylogenetic tree," said senior author James Mallet, Professor of Organismic and Evolutionary Biology in Residence and Associate of Population Genetics in the Museum of Comparative Zoology. "What we found is really astonishing: introgression even among species that are distantly related. "Species" are simply not what we thought they were, and now we have the data to show it.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Final Day (Day 5), Thursday, October 10

Thursday was the last day of the 2019 ASEMV meeting and a number of interesting topics were presented. Two are reported on here. Louis Laurent, MD, PhD, of the University of California-San Diego (UCSD), spoke on the “Discovery and Verfication of Extracelular miRNA Biomarkers for Non-Invasive Prediction of Preeclampsia in Asymptomatic Women.” Dr. Laurent said that she and colleagues performed small RNA-seq of maternal serum exRNAs to discover and verify miRNAs differentially expressed in patients who later developed preeclammpsia. Serum collected from 73 preeclampsia cases and 139 controls between 17-28 weeks gestational age, divided into separate Discovery and Verification cohorts, was analyzed by small RNA seq. Discovery and verification of univariate and bivariate miRNA biomarkers revealed that bivariate biomarkers verified at a markedly higher rate than univariate markers. The majority of verified biomarkers contained miR-155-5p, which has been reported to mediate the preeclampsia-associated repression of eNOS by TNF-alpha. Deconvolution analysis revealed that several verified miRNA biomarkers came from the placenta and were likely carried by placenta-specific EVs. Norman Haughey, PhD, Johns Hopkins University School of Medicine, presented a talk entitled “Astrocyte-Derived EVs Shed in Response to IL-1 Promote Stabilization of APP Translation Through Ligand-Independent Activation of the Wnt Pathway in Neurons.” In his introduction, Dr. Haughey noted that chronic inflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD) by upregulating amyloidogenic processing of APP. Based on previous findings that inflammatory stimuli modify the cargo of astrocyte-derived EVs (ADEV), Dr.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 4, Wednesday, October 9

Wednesday’s sessions of the annual ASEMV 2019 meeting at Asilomar,in Pacific Grove, California, featured multiple exciting presentations. Among the 19 talks of the day, we will focus on five of particular interest. Luis Rodriguez-Borlado, PhD, of Capricor Therapeutics, delivered as presentation titled “Extracellular Vesicles from Cardiosphere-Derived Cells (CDCs) Are Taken Up by Muscle Stem Cells and Increase Exercise Capability in a Duchenne Muscular Dystrophy Model.” Dr. Rodriguez-Borlada introduced his discussion by stating that Duchenne muscular dystrophy (DMD) patients infused with CDCs showed an improvement in PUL (pullulanase) activity, skeletal muscle activity, and a reduction in myocardial scarring when compared to placebo-treated patients. He noted that there is wide acceptance that most of the therapeutic effects observed in cell therapies using non-engrafting cells are caused by paracrine factors secreted by the delivered cells. In the current work, Dr. Rodriguez-Borlado said his group observed significant improvement in exercise capability in mdx mice (DMD model mice) treated wit CDC-EVs when compared with control-treated mice. EVs from immortal CDCs also showed immunomodulatory capabilities on macrophages and improved exercise capability in mdx mice, opening the possibility of developing consistent, robust, and affordable manufacturing process for producing clinical-grade EVs. Julia Saugstad, PhD, Oregon Health & Science University, presented work by a collaborative group and the presentation was titled “Establishing the Contributions of Extracellular miRNAs to Alzheimer’s Disease.” As background, Dr. Saugstad said that Alzheimer’s disease (AD) is the most common form of dementia, the sixth leading cause of death in the United States, and fifth-leading cause of death in those age 65 and older.

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.

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.

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.

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.

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.

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