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July 9th, 2020

Study of Giant Ant Heads Using Simple Models May Aid Bio-Inspired Designs

[This article was written by Ananya Sen, a graduate student in Microbiology at the University of Illinois at Urbana-Champaign. Ms. Sen is also a science writer and her articles can be found at http://ananyasen.web.illinois.edu/. This article was originally published as a Research News article by the University of Illinois News Bureau (https://news.illinois.edu/view/6367). Permission to reprint this article in BioQuick News has also been granted by Ms. Sen.] Researchers use a variety of modelling approaches to study form and function. By using a basic biomechanical model for studying body form and center of mass stability in ants, new research by scientists at the University of Illinois at Urbana-Champaign identifies the benefits of “simple models” and hope that it can be used for bio-inspired designs. “Most organisms are constrained in their shape and size because they are juggling different needs such as the ability to fly, forage for food, and reproduce,” said Andrew Suarez, PhD, a Professor of Entomology and Head of the Department of Evolution, Ecology, and Behavior at the University of Illinois at Urbana-Champaign. “Ants are unique because they live in colonies and divide their responsibilities. Therefore, they don’t have the body constraints that other insects do.” “Ants have a wide range of head sizes relative to their body,” said Philip Anderson, PhD, an Assistant Professor of Evolution, Ecology, and Behavior at the University of Illinois at Urbana-Champaign. “Some ants have such extremely large heads that even though they look like their heads should pitch forward, they don’t.

Cancer-Derived Extracellular Vesicles (EVs) May Carry Cancer-Associated Signatures of Palmitoylated Proteins, New Study Shows; Findings Support Further Study to Assess Possible Utility As Liquid Biopsy for Cancer Diagnosis & Monitoring

A new study sheds light on proteins in particles called extracellular vesicles (EVs), which are released by tumor cells into the bloodstream and promote the spread of cancer. The findings suggest how a blood test involving these vesicles might be used to diagnose cancer in the future, avoiding the need for invasive surgical biopsies. The research is a large-scale analysis of what are known as palmitoylated proteins inside EVs, according to Dolores Di Vizio (photo) (https://bio.cedars-sinai.org/diviziod/index.html), MD, PhD, Professor of Surgery, Biomedical Sciences and Pathology and Laboratory Medicine at Cedars-Sinai. Dr. Di Vizio is co-corresponding author of the study, published online on June 10, 2020 in the Journal of Extracellular Vesicles. The open-access article is titled “Comprehensive Palmitoyl-Proteomic Analysis Identifies Distinct Protein Signatures for Large and Small Cancer-Derived Extracellular Vesicles.” EVs have gained significant attention in the last decade because they can contain proteins and other biologically important molecules whose information can be transferred from cell to cell. EVs are known to help cancer metastasize to distant sites in the body, but exactly how this happens is not clear. To learn more about this process, Dr. Di Vizio and the research team looked into a process called palmitoylation, in which enzymes transfer lipid molecules onto proteins. Palmitoylation can affect where proteins are located within cells, what their activities are, and how they might contribute to cancer progression. The investigators examined two types of EVs, small and large, in samples of human prostate cancer cells. Using centrifuges, they separated the EVs from the other cell materials and analyzed the levels of palmitoylation and the types of proteins present.

Italy’s Rigenerand Launches 3D Bioreactor Development for cGMP Production of Extracellular Vesicles Exosomes

On June 8, 2020, Rigenerand SRL (https://rigenerand-biotech.com/), a biotech company in Italy that both develops and manufactures medicinal products for cell therapy applications, primarily for regenerative medicine and oncology, announced it has commenced development of a novel 3D bioreactor and pipeline, specifically designed for the incremental production of extracellular vesicles including exosomes (collectively termed EVs) in a cGMP (current Good Manufacturing Practice) environment. Rigenerand’s project development will be supported with part of a grant of EUR 4.4 million (almost $5 million) from Horizon 2020 for the H2020-EU.1.2.2.-FET Proactive program, awarded to the Biogenic Organotropic Wetsuits project (https://cordis.europa.eu/project/id/952183). This project comprises a consortium of companies involving Rigenerand. The Biogenic Organotropic Wetsuits (Grant Agreement ID: 952183) project involves eleven organizations across seven countries in Europe. Rigenerand will contribute to the consortium its combination of expertise, technology, and innovation focused on biomaterials, prototypes production, and industrialization of cell culture devices and 3D cell cultures. Rigenerand will start developing novel ways of improving current EV cGMP production technologies. These technologies ultimately aim to produce EV clinical batches to be used as drug substances for cell-free therapy medicinal products.

Forkhead Box Protein 01 (Fox01) Is Key Transcription Factor Regulating Abnormal Heart Growth; Fox01 Binds Widely Throughout Genome in Mouse Model of Cardiac Hypertrophy, Activating Broad Array of Genes in Heart Cells & Stimulating Growth Signaling

The human heart is like a sponge, able to expand and grow, increasing its capacity to take up blood. In theory, an enlarged heart can also squeeze out more blood, with more power, than an average-sized heart. But in reality, for most people, this growth--known as cardiac hypertrophy--is abnormal and signals trouble. Cardiac hypertrophy is brought on by various factors, high blood pressure in particular. Existing treatments only delay the inevitable--that the spongy heart muscle becomes thicker and stiffer over time, culminating in heart failure, in which the heart can no longer contract strongly enough to pump blood through the body. A greater understanding of the molecular mechanisms driving abnormal heart growth promises to turn this around, however, and in new work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) cast fresh light on a key molecular regulator in the heart known as FoxO1 (forkhead bozx protein 01). In an article published online on July 9, 2020 in Circulation, the Temple scientists are the first to show that the transcription factor FoxO1 attaches to and activates a wide array of genes in heart cells, leading to widespread increases in growth signaling, specifically within the heart. The article is titled “Genomic Binding Patterns of Forkhead Box Protein O1 Reveal Its Unique Role in Cardiac Hypertrophy.” "FoxO1 is a major transcription factor that regulates genes involved in metabolism and growth," said Jessica Pfleger (photo), PhD, Instructor in the Center for Translational Medicine at LKSOM and lead author of the new study.

Gall Fly Outmaneuvers Goldenrod Host Plant in Ongoing Competition for Survival

Over time, goldenrod plants and the gall flies that feed on them have been one-upping each other in an ongoing competition for survival. Now, a team of researchers has discovered that by detecting the plants' chemical defenses, the insects may have taken the lead. According to John Tooker, PhD, Professor of Entomology in the Department of Entomology at Penn State, this complex scenario begins when a female gall fly (Eurosta solidaginis) lays its eggs in the leaf bud of a goldenrod plant (Solidago altissima). This action forces the plant to produce a tumor-like growth, called a gall. This gall, he said, provides the fly larvae with a source of nutrition and safety from predators and the environment, but decreases the plants' ability to reproduce. "Our previous research showed that goldenrod plants have evolved to 'eavesdrop' on the sexual communications of their gall fly herbivores -- specifically, the sex pheromones used by males to attract females," he said. "Our new research, suggests that the plants respond to this 'intelligence' by strengthening, also known as 'priming,' chemical defenses to prevent females from laying eggs and inducing gall formation." Eric Yip, PhD, postdoctoral scholar in the Department of Entomology, Penn State, explained that this plant-insect dynamic is similar to the reversals of fortune that occur in the "Spy vs. Spy" comic strip, only the characters are a plant and an insect rather than a pair of cartoon drawings. To investigate the effects of priming, the researchers, in their new study, exposed almost 300 goldenrod plants comprising 11 genetic types--or genotypes--to male gall flies that varied in age, from one to four weeks old, as well as a control in which the plants were not exposed to flies.

PANEL SESSIONS--International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting, Including Exosomes, July 20-22: Plenary Speakers, Panel Sessions, Oral Abstract Talks, Poster Chats, & Educational Sessions

The International Society for ExtracellularVesicles (ISEV) AnnualMeeting (ISEV2020), Including #Exosomes, Is Now VIRTUAL (July 20-22); and will feature over 600 Discussions (Plenary Addresses, Panel Sessions, Oral Abstract Talks, Poster Chats, & Educational Sessions). The program can viewed here (https://www.isev.org/mpage/2020Program) and registration can be done here (https://www.isev.org/mpage/2020Registration). As eminent Yale professor Philip Askenase, MD, has said, “Exosomes are a sensational biological discovery and they seem to be involved in nearly all biological and clinical processes.” Please attend the virtual ISEV 2020 meeting to learn more about these fascinating and immensely important tiny particles. The 2020 virtual meeting will feature four live panel sessions which will offer presentations by experts in the field, followed by moderated half-hour Q&A/panel discussions. The topics of the four panel discussions are “EV Heterogeneity,” “EVs in Liquid Biopsy (Diagnostics/Biomarkers),” “Extracellular RNA,” and “In Vivo Approaches to Understanding EV Function.” Details on these four panel discussion sessions and the speakers who will be presenting are given below.

PANEL 1--EV HETEROGENEITY

July 8th

Dark Matter of Genome Is Focus of Enlightening Presentation During AACR 2020 Virtual Meeting June 22-24

[This article was written for BioQuick News by Michael A. Goldman, PhD, Professor & Former Chair, Biology, San Francisco State University (SFSU) (https://faculty.sfsu.edu/~goldman/). Dr. Goldman has written Op-Ed pieces or letters for the Los Angeles Times, the Wall Street Journal, the Sacramento Bee, the San Francisco Chronicle and the New York Times, as well as a variety of technical articles, including ones appearing in Science and Nature Genetics. He has been Associate Editor for Chromosome Research and a contributing editor to Bio-IT World. Dr. Goldman believes that the public learns much about science and bioethics from fiction, and he reviews novels addressing various aspects of genetic science and its implications, in publications such as Nature, Science, Nature Genetics, and the San Francisco Chronicle. Dr. Goldman can be contacted at goldman@sfsu.edu. This article is copyrighted by Michael A. Goldman. BioQuick News is grateful to Dr, Goldman for this excellent contribution.] ARTICLE BY DR. MICHAEL A. GOLDMAN: Genome projects just seem to nucleate around Washington University in St. Louis. If it isn't the genome, it's the Pangenome or the Epigenome. Dr. Ting Wang (https://www.genome.wustl.edu/people/ting-wang/), of the Department of Genetics and McDonnel Genome Institute at Washington University, has been involved in all of them. He currently directs the NIH 4D Nucleome Network Data Coordination Integration Center (http://dcic.4dnucleome.org/) and the NIEHS Environmental Epigenomics Data Center, and his laboratory hosts the WashU Epigenome Browser (https://epigenomegateway.wustl.edu/). Dr. Wang's own research isn't as pedestrian as you might think.

RNA Is Key in Helping Stem Cells Know What to Become; Polycomb Repressive Complex 2 (PRC2) Requires RNA Binding for Chromatin Localization in Human Pluripotent Stem Cells and for Defining Cellular State, Paper from Nobelist Cech & Rinn Labs Asserts

Look deep inside our cells, and you'll find that each has an identical genome--a complete set of genes that provides the instructions for our cells' form and function. But if each blueprint is identical, why does an eye cell look and act differently than a skin cell or a brain cell? How does a stem cell--the raw material with which our organ and tissue cells are made--know what to become? In a study published online on July 6, 2020 in Nature Genetics (https://www.nature.com/articles/s41588-020-0662-x), University of Colorado-Boulder (CU Boulder) researchers come one step closer to answering that fundamental question, concluding that the molecular messenger RNA (ribonucleic acid) plays an indispensable role in cell differentiation, serving as a bridge between our genes and the so-called "epigenetic" machinery that turns them on and off. When that bridge is missing or flawed, the researchers report in their article, a stem cell on the path to becoming a heart cell never learns how to beat. The article is titled “RNA Is Essential for PRC2 Chromatin Occupancy and Function in Human Pluripotent Stem Cells.” The paper comes at a time when pharmaceutical companies are taking unprecedented interest in RNA. And, while the research is young, it could ultimately inform development of new RNA-targeted therapies, from cancer treatments to therapies for cardiac abnormalities. "All genes are not expressed all the time in all cells. Instead, each tissue type has its own epigenetic program that determines which genes get turned on or off at any moment," said co-senior author Thomas Cech (photo) (https://en.wikipedia.org/wiki/Thomas_Cech), PhD, a Nobel laureate and Distinguished Professor of Biochemistry. "We determined in great detail that RNA is a master regulator of this epigenetic silencing and that in the absence of RNA, this system cannot work. It is critical for life."

Experimental Drug (Tofersen from Biogen) Shows Early Promise Against Rare Inherited Form of ALS Caused by Mutations in Superoxide Dismutase 1 (SOD1)

An experimental drug for a rare, inherited form of amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s disease) has shown promise in a phase 1/phase 2 clinical trial conducted at Washington University School of Medicine in St. Louis, Massachusetts General Hospital in Boston, and other sites around the world and sponsored by the pharmaceutical company Biogen Inc. The trial indicated that the experimental drug, known as tofersen, shows evidence of safety that warrants further investigation and lowers levels of a disease-causing protein in people with a type of amyotrophic lateral sclerosis, or ALS, caused by mutations in the gene SOD1 (superoxide dismutase 1). The results of the study, published on July 9, 2020 in the New England Journal of Medicine (https://www.nejm.org/doi/full/10.1056/NEJMoa2003715), have led to the launch of a phase 3 clinical trial to further evaluate the safety and efficacy of tofersen, The NEJM article is titled "Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS." "ALS is a devastating, incurable illness," said principal investigator Timothy M. Miller (Photo, Credit: Huy Mach), MD, PhD, the David Clayson Professor of Neurology at Washington University and Director of the ALS Center at the School of Medicine. "While this investigational drug is aimed at only a small percentage of people with ALS, the same approach--blocking the production of specific proteins at the root of the illness--may help people with other forms of the illness. "This trial indicated that tofersen shows evidence of safety that warrants further investigation and that the dose we used lowers clinical markers of disease. There are even some signs that it slowed clinical progression of ALS, although the study was not designed to evaluate effectiveness at treating the disease, so we can't say anything definitive.

Hormone (GDF15) Being Studied As Possible Treatment for Obesity Is Risk Factor for Sepsis, New Study Shows; Inhibitor of GDF15 May Be Useful As Complementary Treatment for Sepsis

A group of scientists from the Instituto Gulbenkian de Ciência (IGC) (https://gulbenkian.pt/ciencia/) in Portugal, led by Luís Moita, PhD, discovered that a hormone that is being studied as a treatment for obesity reduces the resistance to infection caused by bacteria and is a risk factor for sepsis. The work, developed in collaboration among researchers from Portugal, France, Germany, and South Korea, was published online on June 2, 2020 in PNAS. The open-access article is titled “CXCL5-Mediated Recruitment of Neutrophils into the Peritoneal Cavity of Gdf15-Deficient Mice Protects Against Abdominal Sepsis” (https://www.pnas.org/content/117/22/12281). Sepsis is a potentially fatal illness, that derives from a deregulated response of the organism to an infection, leading to organ malfunction. A study recently published in the scientific journal The Lancet (https://www.sciencedirect.com/science/article/abs/pii/S0140673618306962), estimated that, in 2017, sepsis affected 49 million people and 11 million people worldwide have died. With the aim of expanding knowledge about this disease, Dr. Moita’s team at IGC investigated whether the hormone known as GDF15 (growth and differentiation factor 15) could play a role in sepsis. This hormone is currently being widely studied by several laboratories and pharmaceutical companies as a treatment for obesity. “We’ve discovered a critical effect of GDF15 on infection, which is relevant because this hormone increases in many common diseases, like obesity, [and] pulmonary and cardiovascular diseases”, explains Dr. Moita.