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February 24th, 2021

Whale Sharks Show Remarkable Capacity to Recover from Injuries

A new study has, for the first time, explored the rate at which the world's largest fish, the endangered whale shark, can recover from its injuries. The findings reveal that lacerations and abrasions, increasingly caused through collisions with boats, can heal in a matter of weeks and researchers found evidence of partially removed dorsal fins re-growing. This work, published online on February 4, 2021 in Conservation Physiology, comes at a critical time for these large sharks, that can reach lengths of up to 18 meters (~59 feet). The open-access article is titled “Wound-Healing Capabilities of Whale Sharks (Rhincodon typus) and Implications for Conservation Management” (https://academic.oup.com/conphys/article/9/1/coaa120/6102284). Other recent studies have shown that, as their popularity within the wildlife tourism sector increases, so do interactions with humans and boat traffic. As a result, these sharks face an additional source of injury on top of natural threats, and some of these ocean giants exhibit scars caused by boat collisions. Until now, very little was known about the impact from such injuries and how they can recover. "These baseline findings provide us with a preliminary understanding of wound healing in this species" says lead author Freya Womersley, a PhD student with University of Southampton based at the Marine Biological Association, UK. "We wanted to determine if there was a way of quantifying what many researchers were anecdotally witnessing in the field, and so we came up with a technique of monitoring and analyzing injuries over time.”

Lou Gehrig’s Disease (ALS) Neuron Damage Reversed with New Compound In Mouse Model

Northwestern University scientists have identified the first compound that eliminates the ongoing degeneration of upper motor neurons that become diseased and are a key contributor to ALS (amyotrophic lateral sclerosis) (also known as Lou Gehrig’s disease), a swift and fatal neurodegenerative disease that paralyzes its victims. In addition to ALS, upper motor neuron degeneration also results in other motor neuron diseases, such as hereditary spastic paraplegia (HSP) and primary lateral sclerosis (PLS). In ALS, movement-initiating nerve cells in the brain (upper motor neurons) and muscle-controlling nerve cells in the spinal cord (lower motor neurons) die. The disease results in rapidly progressing paralysis and death. So far, there has been no drug or treatment for the brain component of ALS, and no drug for HSP or PLS patients. "Even though the upper motor neurons are responsible for the initiation and modulation of movement, and their degeneration is an early event in ALS, so far there has been no treatment option to improve their health," said senior author Hande Ozdinler, PhD, Associate Professor of Neurology at Northwestern University Feinberg School of Medicine. "We have identified the first compound that improves the health of upper motor neurons that become diseased." The study was published online on February 23, 2021 in Clinical and Translational Medicine. The open-access article is titled “Improving Mitochondria and ER Stability Helps Eliminate Upper Motor Neuron Degeneration That Occurs Due to mSOD1 toxicity and TDP‐43 Pathology (https://onlinelibrary.wiley.com/doi/10.1002/ctm2.336). Dr. Ozdinler collaborated on the research with study author Richard B. Silverman, PhD, the Patrick G. Ryan/Aon Professor of Chemistry at Northwestern.

Seeing Schizophrenia: X-Rays Shed Light on Neural Differences

Schizophrenia, a chronic, neurological brain disorder, affects millions of people around the world. It causes a fracture between a person's thoughts, feelings and behavior. Symptoms include delusions, hallucinations, difficulty processing thoughts and an overall lack of motivation. Schizophrenia patients have a higher suicide rate and more health problems than the general population, and a shorter life expectancy. There is no cure for schizophrenia, but a key to treating it more effectively is to better understand how it arises. And that, according to Ryuta Mizutani, PhD, Professor of Applied Biochemistry at Tokai University in Japan, means studying the structure of brain tissue. Specifically, it means comparing the brain tissues of schizophrenia patients with those of people in good mental health, to see the differences as clearly as possible. "The current treatment for schizophrenia is based on many hypotheses we don't know how to confirm," Dr. Mizutani said. "The first step is to analyze the brain and see how it is constituted differently." To do that, Dr. Mizutani and his colleagues from several international institutions collected eight small samples of brain tissue -- four from healthy brains and four from those of schizophrenia patients, all collected post-mortem--and brought them to beamline 32-ID of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE's Argonne National Laboratory. At the APS, the team used powerful X-rays and high-resolution optics to capture three-dimensional images of those tissues.

February 23rd

Kittens Could Hold Key to Understanding Deadly Diarrheal Disease in Children

Kittens could be the model for understanding infectious, sometimes deadly, diarrheal disease in both animals and children, according to new research from North Carolina (NC) State University. Diarrheagenic Escherichia coli (DEC) bacteria cause lethal diarrheal disease in children worldwide, killing up to 120,000 children under the age of five annually. Atypical enteropathic Escherichia coli (aEPEC) are a form of DEC increasingly associated with diarrheal disease in humans and in kittens. "We were looking for causes of infectious diarrhea in kittens, which has a high mortality rate, and came across this pathogen," says Jody Gookin, DVM, PhD, FluoroScience Distinguished Professor in Veterinary Scholars Research Education at NC State and corresponding author of the research. "The interesting thing about aEPEC is that you can find it in both healthy and sick individuals. Having it in your intestinal tract doesn't mean you're sick, but those that are sick have a higher burden, or amount of the bacteria, in their bodies." Dr. Gookin and Victoria Watson, DVM, PhD, a former PhD student at NC State, lead author of the study, and now a veterinary pathologist at Michigan State University, performed a genomic analysis of aEPEC isolates from both healthy kittens that were colonized by the bacteria and kittens with lethal infections to try to determine why aEPEC causes illness in some kittens but remains dormant in others. With collaborators at the University of Maryland, Dr. Gookin and Dr. Watson then compared the genomic data from both groups of kittens to human aEPEC isolates. However, there were no specific genetic markers that allowed the researchers to distinguish between the groups of isolates.

New Therapeutic Approach May Help Treat Age-Related Macular Degeneration (AMD) Effectively--Inhibiting Gene (RUNX1) Involved in Abnormal Growth of Blood Vessels in Certain Ocular Disorders May Reduce Retinal Neovascularization

Runt-related transcription factor 1 (RUNX1) has been linked to retinal neovascularization and the development of abnormal blood vessels, which result in vision loss in diabetic retinopathy. Now, scientists have found that RUNX1 inhibition presents a new therapeutic approach in the treatment of age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly worldwide. The results were first reported online on December 23, 2020 are published in the March 1, 2021 issue of The American Journal of Pathology, published by Elsevier (https://ajp.amjpathol.org/article/S0002-9440(20)30560-5/fulltext). The open-access article is titled “Treatment of Experimental Choroidal Neovascularization via RUNX1 Inhibition.” Abnormal growth of blood vessels, or aberrant angiogenesis, arises from the choroid, a part of the eye located behind the retina. This condition, known as choroidal neovascularization (CNV), is present in several ocular diseases that lead to blindness such as AMD. This study is the first to implicate RUNX1 in CNV and to test RUNX1 inhibition therapy for treating CNV. Researchers found that application of a RUNX1 inhibitor, alone or in combination with a standard treatment for AMD, may represent an important therapeutic advance. “Incomplete response to anti–vascular endothelial growth factor (VEGF) drugs is a critical problem that hinders visual outcomes in CNV. RUNX1 represents a promising therapeutic target that may help address current limitations of anti-VEGF therapy,” explains first author Lucia Gonzalez-Buendia, MD, a retina specialist at Puerta de Hierro-Majadahonda University Hospital (Spain), and former postdoctoral fellow at the Schepens Eye Research Institute of Mass Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.

February 22nd

Malaria Parasites Secrete EVs Containing Proteasome 20S Complex and Kinases to Target Specific Cytoskeleton Proteins and Weaken RBC Membrane to Greatly Enhance Infectivity; Possible Treatment Approaches Suggested; Wider Applications Envisioned

Red blood cells (RBCs) are the body's lifeline, but they also serve as the perfect hosts for one of the deadliest infectious organisms: the malaria parasite. About two weeks after infecting the body, the deadliest malaria parasite, Plasmodium falciparum (Pf), launches its invasion, rapidly taking over masses of red blood cells so as to grow within them. That's when the disease can turn life-threatening, ultimately killing approximately a thousand children around the world every day. Two research teams at the Weizmann Institute of Science in Israel have joined forces to reveal what enables the malaria parasite to mount such an effective takeover. Neta Regev-Rudzki (photo) (http://www.weizmann.ac.il/Biomolecular_Sciences/Regev/home), PhD, Senior Scientist, and her team in the Weizmann’s Biomolecular Sciences Department discovered that tiny sac-like "packages" called extracellular vesicles (EVs), released by Pf, contain peculiar cargo: including a cellular protein-degrading machine called a proteasome (https://en.wikipedia.org/wiki/Proteasome), which normally breaks down misfolded or unneeded proteins. Departmental colleague Professor Michal Sharon (phote below) (http://www.weizmann.ac.il/Biomolecular_Sciences/MichalSharon/), PhD, Principal Investigator, whose team specializes in studying proteasomes, suggested that the two labs combine their expertise to figure out what, if anything, those proteasomes are doing in the malaria EVs. The joint study--led by PhD student Elya Dekel from Dr. Regev-Rudzki's lab and postdoctoral fellow Dr. Dana Yaffe from Professor Sharon's lab--uncovered an extraordinary strategy by which the malaria parasite harnesses the proteasome for its own purpose: priming naïve RBCs for the coming invasion. Their results were published online on February 19, 2021 in Nature Communications (https://www.nature.com/articles/s41467-021-21344-8).

February 21st

Evox Therapeutics Completes $95.4 Million Series C Financing to Support Advancement of Company’s Exosome-Based Therapeutics Pipeline and Its World-Leading Exosome Platform

On February 18, 2021, Evox Therapeutics Ltd, a leading exosome therapeutics company, announced that it has raised $95.4 million in a Series C financing round. The financing was significantly oversubscribed with high demand from both existing and new investors. The Series C financing was led by Redmile Group, which was joined by new investors OrbiMed and Invus. In addition to Redmile, all existing Series B investors reinvested, including major investors Oxford Sciences Innovation (OSI), GV (formerly Google Ventures), and Cowen Healthcare Investments. Eli Lilly, also converted a $10 million convertible note, that formed part of Evox’s 2020 collaboration agreement with them, into equity as part of this round. Proceeds from this financing will support the advancement of Evox’s exosome-based therapeutics pipeline, including progression of several rare disease assets into the clinic, and continued development of its world-leading DeliverEXTM exosome drug platform. In connection with the financing, Evox will appoint Chau Khuong, partner at OrbiMed, to its Board of Directors. Antonin de Fougerolles, PhD, Chief Executive Officer of Evox, commented: “We are delighted with the support received in this Series C financing from both our existing investors and our new investors. The level of interest in this financing round is testament to the progress we have made over the last few years. Since our Series B round in 2018, we have continued to develop our DeliverEXTM platform, advance our pipeline of exosome therapeutics, expand our intellectual property portfolio, build our R&D capabilities, and bolster our management team. We have also signed significant partnership deals with Eli Lilly and Takeda, two of the world’s leading pharma companies.

February 19th

Stress Response Protein (HSF1) Links Inflammatory Disease to Colon Cancer; Findings Might Help Identify Those at Extra Risk for This Cancer and Develop Means of Prevention

Inflammation promotes some of the deadliest cancers. In the colon, inflammatory bowel disease is well known to be associated with higher-than-average rates of malignancy. Nevertheless, the developing tumor is commonly diagnosed only when it has already advanced or even metastasized, possibly because the early symptoms of malignancy are often mistakenly ascribed to a flare-up of intestinal inflammation. Weizmann Institute of Science researchers have now revealed a molecular missing link between chronic gut inflammation and cancer. This revelation may help develop ways of preventing colon cancers in people with inflammatory diseases of the intestines. The results were published online on December 7, 2020 in Nature Communications (https://www.nature.com/articles/s41467-020-20054-x). The open-access article is titled “Heat Shock Factor 1-Dependent Extracellular Matrix Remodeling Mediates the Transition from Chronic Intestinal Inflammation to Colon Cancer." Ruth Scherz-Shouval (photo) (http://www.weizmann.ac.il/Biomolecular_Sciences/Shouval/), PhD, of the Biomolecular Sciences Department hypothesized that the path from chronic bowel disease to cancer winds through the stress response to inflammation within the intestinal cells. She focused on heat shock factor 1 (HSF1), a protein that triggers cellular changes in just such instances of stress and strain on the cells. In earlier work, Dr. Scherz-Shouval had found that HSF1 causes supporting cells called fibroblasts to start assisting the progression of cancer in their vicinity. In the new research, Dr. Scherz-Shouval and her team asked whether this process begins even before cancer is seen—i.e., in colon inflammation that eventually leads to colon cancer.

In “Technical Tour de Force,” Scientists Develop Explainable AI for Decoding Genome Regulatory Code

Researchers at the Stowers Institute for Medical Research, in Kansas City, Missouri, in collaboration with colleagues at Stanford University and Technical University of Munich, have developed advanced explainable artificial intelligence (AI) in a technical tour de force to decipher regulatory instructions encoded in DNA. In a report published online on February 18, 2021, in Nature Genetics, the team found that a neural network trained on high-resolution maps of protein-DNA interactions can uncover subtle DNA sequence patterns throughout the genome and provide a deeper understanding of how these sequences are organized to regulate genes. The article is titled “Base-Resolution Models of Transcription-Factor Binding Reveal Soft Motif Syntax.” Neural networks are powerful AI models that can learn complex patterns from diverse types of data such as images, speech signals, or text to predict associated properties with impressive high accuracy. However, many see these models as uninterpretable because the learned predictive patterns are hard to extract from the model. This black-box nature has hindered the wide application of neural networks to biology, where interpretation of predictive patterns is of paramount importance. One of the big unsolved problems in biology is the genome's second code--its regulatory code. DNA bases (commonly represented by letters A, C, G, and T) encode not only the instructions for how to build proteins, but also when and where to make these proteins in an organism. The regulatory code is read by proteins called transcription factors that bind to short stretches of DNA called motifs. However, how particular combinations and arrangements of motifs specify regulatory activity is an extremely complex problem that has been hard to pin down.

Termite Gut Microbes Could Aid Biofuel Production

Wheat straw, the dried stalks left over from grain production, is a potential source of biofuels and commodity chemicals. But before straw can be converted to useful products by biorefineries, the polymers that make it up must be broken down into their building blocks. Now, researchers reporting in an article published online on January 25, 2021 in ACS Sustainable Chemistry & Engineering (https://pubs.acs.org/doi/abs/10.1021/acssuschemeng.0c07817) have found that microbes from the guts of certain termite species can help break down lignin, a particularly tough polymer in straw. The article is titled “Termite Gut Microbiota Contribution to Wheat Straw Delignification in Anaerobic Bioreactors.” In straw and other dried plant material, the three main polymers--cellulose, hemicelluloses, and lignin--are interwoven into a complex 3D structure. The first two polymers are polysaccharides, which can be broken down into sugars and then converted to fuel in bioreactors. Lignin, on the other hand, is an aromatic polymer that can be converted to useful industrial chemicals. Enzymes from fungi can degrade lignin, which is the toughest of the three polymers to break down, but scientists are searching for bacterial enzymes that are easier to produce. In previous research, Guillermina Hernandez-Raquet, PhD, Toulouse Biotechnology Institute, and colleagues had shown that gut microbes from four termite species could degrade lignin in anaerobic bioreactors. Now, in a collaboration with Yuki Tobimatsu, PhD, Kyoto University, and Mirjam Kabel, PhD, Wageningen University & Research, the researchers wanted to take a closer look at the process by which microbes from the wood-eating insects degrade lignin in wheat straw, and identify the modifications they make to this material.