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Archive - 2021

Date

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.

February 18th

Dingoes Are Different, Expert Says

Dogs are generally considered the first domesticated animal, while its ancestor is generally considered to be the wolf, but where the Australian dingo fits into this framework is still debated, according to a retired Penn State anthropologist. "Indigenous Australians understood that there was something different about the dingoes and the colonial dogs," said Pat Shipman, PhD, retired Adjunct Professor of Anthropology, Penn State. "They really are, I think, different animals. They react differently to humans. A lot of genetic and behavioral work has been done with wolves, dogs, and dingoes. Dingoes come out somewhere in between." Wolves, dogs, and dingoes are all species of the canidae family and are called canids. In most animals, hybridization between closely related species does not happen, or like female horses and male donkeys, produce mules--usually non-fertile offspring. However, many canid species, including wolves, dingoes, and dogs, can interbreed and produce fertile offspring. Consequently, defining species boundaries in canids becomes more difficult. Domestic dogs came to the Australian continent in 1788 with the first 11 ships of convicts, but dingoes were already there, as were aboriginal Australians who arrived on the continent about 65,000 years ago. A large portion of dingoes in Australia today have domestic dog in their ancestry, but dingoes came to Australia at least 4,000 years ago according to fossil evidence. Shipman believes that date may be even earlier, but no fossils have yet been found. "Part of the reason I'm so fascinated with dingoes is that if you see a dingo through American eyes you say, 'that's a dog,'" said Dr. Shipman. "In evolutionary terms, dingoes give us a glimpse of what started the domestication process." Dr.

Parse Biosciences Launches Whole Transcriptome Kit to Dramatically Scale Single-Cell Sequencing

On February 18, 2021, Parse Biosciences (https://www.parsebiosciences.com/), a company providing researchers with scalable and flexible single-cell sequencing solutions, announced the launch of its Single Cell Whole Transcriptome Kit. The kit, which was previously available only through Parse’s early-access program, is now generally available to all researchers in North America. The Whole Transcriptome Kit from Parse Biosciences contains everything needed to run a single-cell experiment with 100,000 cells across 48 samples, the company states. Previously, according to Parse, single-cell sequencing solutions demanded that researchers invest in expensive lab equipment to get started. Now, with the launch of Parse Bioscience’s Whole Transcriptome Kit, researchers have a reliable and scalable, end-to-end single cell sequencing technology that utilizes only basic lab equipment, the company states. “For too long, labs have been held back by technologies that not only compromise on data quality, but which also don’t scale to match researchers’ ambitions,” said Alex Rosenberg, PhD, Co-Founder and CEO of Parse. “Through our Whole Transcriptome Kit, we support researchers who are taking on some of the most challenging problems in biology--spanning neuroscience, immunology, and beyond. We provide them with a technology that is more scalable and offers higher resolution than anything else on the market, including droplet-based solutions.” Since the company’s pioneering paper on SPLiT-seq published in Science in 2018 (https://science.sciencemag.org/content/360/6385/176), Parse Biosciences has continued to refine its technology.

Capuchin Monkey Genome Reveals Clues to Its Long Life and Large Brain

An international team of scientists has sequenced the genome of a capuchin monkey for the first time, uncovering new genetic clues about the evolution of the long lifespan and large brains of these animals. Published online on February 16, 2021 in PNAS, the work was led by researchers at the University of Calgary in Canada and also involved scientists at the University of Liverpool. The open-access article is titled “The Genomics of Ecological Flexibility, Large Brains, and Long Lives in Capuchin Monkeys Revealed with fecalFACS.” "Capuchins have the largest relative brain size of any monkey and can live past the age of 50, despite their small size, but their genetic underpinnings had remained unexplored until now," explains co-author Professor Joao Pedro De Magalhaes, PhD, who researches aging at the University of Liverpool. The researchers developed and annotated a reference genome assembly for white-faced capuchin monkeys (Cebus imitator) to explore the evolution of these traits. Through a comparative genomics approach spanning a wide diversity of mammals, the scientists identified genes under evolutionary selection associated with longevity and brain development. "We found signatures of positive selection on genes underlying both traits, which helps us to better understand how such traits evolve. In addition, we found evidence of genetic adaptation to drought and seasonal environments by looking at populations of capuchins from a rainforest and a seasonal dry forest," said senior author Amanda Melin, PhD, University of Calgary, who has studied capuchin monkey behaviour and genetics for almost 20 years. The researchers identified genes associated with DNA damage response, metabolism, cell cycle, and insulin signaling.