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December 18th, 2019

Study Reveals Domestic Horse Breed (Cleveland Bay) Has Third-Lowest Genetic Diversity, Just Higher Than Friesian & Clydesdale Breeds

A new study by Dr. Gus Cothran, Professor Emeritus at the Texas A&M School of Veterinary Medicine & Biomedical Sciences (CVM), has found that the Cleveland Bay (CB) horse breed has the third-lowest genetic variation level of domestic horses, ranking above only the notoriously inbred Friesian and Clydesdale breeds. This lack of genetic diversity puts the breed at risk for a variety of health conditions. Genetic variation refers to the differences between different individuals' DNA codes. Populations where there is high genetic diversity will have a wider range of different traits and will be more stable, in part because disease traits will be more diluted. In populations with low genetic variation, many individuals will have the same traits and will be more vulnerable to disease. The CB is the United Kingdom's oldest established horse breed and the only native warm-blood horse in the region. Used for recreational riding, driving, and equestrian competition, the CB is considered a critically endangered breed by the Livestock Conservancy. Because maintaining genetic diversity within the breed is important to securing the horses' future, Dr. Cothran and his team worked to gain comprehensive genetic information about the breed to develop more effective conservation and breeding strategies. In this study, published online on Septembr 20, 2019 in Diversity, researchers genotyped hair from 90 different CB horses and analyzed their data for certain genetic markers. These samples were then compared to each other, as well as to samples from other horse breeds to establish the genetic diversity within the breed and between other breeds.

MicroRNA-1 Alleviates Protein Accumulation by Controlling Autophagy; Finding May Be Key to New Therapeutic Approaches in Huntington’s Disease and Parkinson’s Disease

Research led by a Monash University (Australia) scientist has identified a highly conserved mechanism in worms and humans that controls the removal of toxic protein aggregates – hallmarks of neurodegenerative diseases. Insights from their study may provide a novel therapeutic approach for diseases such as Huntington's and Parkinson's. Associate Professor Roger Pocock, from the Monash Biomedicine Discovery Institute (BDI), and colleagues from the University of Cambridge led by Professor David Rubinsztein, found that microRNAs are important in controlling protein aggregates, proteins that have amassed due to a malfunction in the process of ‘folding’ that determines their shape. The scientists’ findings were published online on December 9, 2019 in eLIFE. The open-access article is titled “Interferon-β-Induced miR-1 Alleviates Toxic Protein Accumulation by Controlling Autophagy.” MicroRNAs, short strands of genetic material, are tiny but powerful molecules that regulate many different genes simultaneously. The scientists sought to identify particular microRNAs that are important for regulating protein aggregates and homed in on miR-1, which is found in low levels in patients with neurodegenerative diseases such as Parkinson’s disease. “The sequence of miR-1 is 100 per cent conserved; it’s the same sequence in the Caenorhabditis elegans worm as in humans even though they are separated by 600 million years of evolution,” Associate Professor Pocock said. “We deleted miR-1 in the worm and looked at the effect in a preclinical model of Huntington’s and found that when you don’t have this microRNA there’s more aggregation,” he said. “This suggested miR-1 was important to remove Huntington’s aggregates.”

Scientists Find Way to Supercharge Protein Production; Discovery Promises to Aid Production of Protein-Based Drugs, Vaccines, Other Biomaterials

Medicines such as insulin for diabetes and clotting factors for hemophilia are hard to synthesize in the lab. Such drugs are based on therapeutic proteins, so scientists have engineered bacteria into tiny protein-making factories. But even with the help of bacteria or other cells, the process of producing proteins for medical or commercial applications is laborious and costly. Now, researchers at the Washington University School of Medicine in St. Louis have discovered a way to supercharge protein production up to a thousand-fold. The findings, published online on December 18, 2019 in Nature Communications, could help increase production and drive down costs of making certain protein-based drugs, vaccines, and diagnostics, as well as proteins used in the food, agriculture, biomaterials, bioenergy, and chemical industries. The open-access article is titled “A Short Translational Ramp Determines the Efficiency of Protein Synthesis.” “The process of producing proteins for medical or commercial applications can be complex, expensive, and time-consuming,” said Sergej Djuranovic, PhD, an Associate Professor of Cell Biology and Physiology and the study’s senior author. “If you can make each bacterium produce 10 times as much protein, you only need one-tenth the volume of bacteria to get the job done, which would cut costs tremendously. This technique works with all kinds of proteins because it’s a basic feature of the universal protein-synthesizing machinery.” Proteins are built from chains of amino acids hundreds of links long. Dr. Djuranovic and first author Manasvi Verma, an undergraduate researcher in Dr. Djuranovic’s lab, stumbled on the importance of the first few amino acids when an experiment for a different study failed to work as expected.

Scientists Discover New Mechanism in Childhood Kidney Cancer (Wilms’ Tumor); Findings on Possible Role of ENL Chromatin Reader Protein May Point to New Treatment Approaches

As an embryo develops, its cells must learn what to do with the thousands of genes they've been equipped with. That's why each cell comes with a detailed gene-expression manual outlining exactly which genes should be switched on, to what extent, and when. To execute their respective manuals, the cells employ so-called chromatin reader proteins that identify which gene is up for expression. Now, a new study has found that a problem in this gene-regulatory process may cause normal cells to turn malignant and produce Wilms’ tumor, the most common kidney cancer in children. The findings, which were published online on December 18, 2019, in Nature, open up new treatment possibilities for the disease, which is currently treated by surgery and chemotherapy. The article is titled “Impaired Cell Fate Through Gain-of-Function Mutations in a Chromatin Reader.” The findings also raise intriguing questions about other cancer types. The researchers found that the implicated reader protein causes problems by acquiring a new property and being too active. "We have never seen this type of mechanism before," says Liling Wan, PhD, a former postdoctoral associate in the Rockefeller Univeersity lab of Dr. C. David Allis, and now an Assistant Professor at the University of Pennsylvania. "It raises the question whether this type of molecular mechanism is also hijacked in other cancer types." A few years ago, Dr. Wan discovered that a reader protein called ENL is involved in blood cancer leukemia by activating the cancer-causing genes. Her attention was turned to Wilms' tumor recently, when it was discovered that some people with Wilms' tumor carry mutations in the gene that codes for ENL.

Bio-Techne's Exosome Diagnostics Lab Receives Accreditation from College of American Pathologists (CAP); Recognition Builds on Recent Achievements of Company’s ExoDx™ Prostate (IntelliScore) (EPI) Exosome-Based Liquid Biopsy Test

In a December17, 2019 press release, Bio-Techne Corporation (NASDAQ:TECH) announced that the Accreditation Committee of the College of American Pathologists (CAP) has awarded accreditation to its Exosome Diagnostics (ExosomeDx) laboratory based on results of a recent on-site inspection as part of the CAP's Accreditation Program. ExosomeDx was advised of this national recognition and congratulated for the excellence of services being provided. ExosomeDx is now one of more than 8,000 CAP-accredited facilities worldwide. "Receipt of CAP Accreditation represents another milestone in a banner year for our ExosomeDx platform and team," commented Chuck Kummeth, President and Chief Executive Officer of Bio-Techne. "This accreditation, combined with the CLIA, ISO 13485 and New York certifications already awarded to our laboratory, serve as a testament to the high-quality standards at our Waltham, Massachusetts facility. This recognition builds on the recent achievements of our ExoDx™ Prostate (IntelliScore) (EPI) test, including NCCN guideline inclusion, attaining FDA Breakthrough Device Designation, as well as the recently effective Medicare reimbursement determination issued by Medicare Administrative Contractor (MAC) National Government Services, Inc. All of these achievements position Bio-Techne to scale our EPI test and enable men to make more informed decisions on whether to proceed with an initial prostate biopsy.” Johan Skog (https://www.pmwcintl.com/speaker/johan-skog_exosome-diagnostics_2020sv/), PhD, CSO of Exosome Diagnostics, willbe giving a presentation at the upcoming Precision Medicine World Conference (PMWC 2020) in Santa Clara, California (January 21-January 24) (https://www.pmwcintl.com/2020sv/).

December 17th

Brain Protein (CD33) Regulates Microglia Cells and May Protect Against Alzheimer’s

Research shows that white blood cells in the human brain are regulated by a protein called CD33 (image)--a finding with important implications in the fight against Alzheimer's disease, according to a new study by University of Alberta chemists. "Immune cells in the brain, called microglia, play a critical role in Alzheimer's disease," explained Matthew Macauley, PhD, Assistant Professor in the Department of Chemistry and co-author on the paper. "They can be harmful or protective. Swaying microglia from a harmful to protective state could be the key to treating the disease." Scientists have identified the CD33 protein as a factor that may decrease a person's likelihood of Alzheimer's disease. Less than 10 percent of the population have a version of CD33 that makes them less likely to get Alzheimer's disease. "The fact that CD33 is found on microglia suggests that immune cells can protect the brain from Alzheimer's disease under the right circumstances," said Abhishek Bhattacherjee, PhD, first author and postdoctoral fellow in the Macauley lab. Now, Dr. Macauley's research shows that the most common type of CD33 protein plays a crucial role in modulating the function of microglia."These findings set the stage for future testing of a causal relationship between CD33 and Alzheimer's Disease, as well as testing therapeutic strategies to sway microglia from harmful to protecting against the disease--by targeting CD33," said Dr. Macauley.

Extrachomosomal Circular DNA Drives Oncogenic Remodeling in Childhood Cancer; First Detailed Map of Circular DNA in Neuroblastoma Yields Unanticipated Insights

Cancer development is associated with the gradual accumulation of DNA defects over time. Thus, cancer is considered an age-related disease. But why do children develop cancer? An international team of researchers, led by scientists at Charité-Universitätsmedizin Berlin and the Memorial Sloan Kettering Cancer Center in New York, now reveal that mysterious rings of DNA known as extrachromosomal circular DNA can contribute to cancer development in children. Producing the first detailed map of circular DNA, the scientists have shed new unanticipated insights on long-standing questions in the field of cancer genetics. The work was published online on December 16, 2019 in Nature Genetics. The article is titled “Extrachromosomal Circular DNA Drives Oncogenic Genome Remodeling.” Every year, nearly half a million people in Germany develop cancer. Approximately 2,100 cancer patients are children under the age of 18. The fact that the majority of cancers develop in old adults is due to the mechanisms contributing to cancer development. A range of exogenous factors, including tobacco smoke and radiation, can cause damage to cellular DNA. If this type of DNA damage is left to accumulate over many years, affected cells may lose control over cell division and growth. This results in cancer development. Children, however, are not old enough to be affected by this mechanism of cancer development. What, then, is the reason for childhood cancers? A team of researchers, led by Dr. Anton Henssen of Charité's Department of Pediatrics, Division of Oncology and Hematology and the Experimental and Clinical Research Center (ECRC,) an institution jointly operated by Charité and the Max Delbrück Center for Molecular Medicine (MDC), is now a significant step closer to finding an answer.

December 15th

LAM’s Liquid Biopsy Test of cfDNA Methylation Panel Enables Highly Sensitive and Specific Detection of the Most Common Liver Cancer (Hepatocellular Carcinoma)

Today we discuss the dissemination of DNA-methylation-based tests for non-invasive detection of cancer. BioQuick News recently sat down with Dhruvajyoti Roy (photo), PhD, who is the Director of Technology at the Laboratory for Advanced Medicine Inc. (LAM), an AI-driven healthcare company focused on commercializing early cancer detection tests from a simple blood draw, to learn about the company’s technology and recent advances in the field of DNA methylation analysis. LAM developed a blood-based Liver Cancer Test, which can be used for early detection of liver cancer, as well as for monitoring disease recurrence. Dr. Roy had presented data from a validation study conducted by LAM on the ability of the assay to detect hepatocellular carcinoma (HCC), the most common form of liver cancer (more than 75% of all liver cancers, at The Liver Meeting® 2019 hosted by the American Association for the Study of Liver Diseases (AASLD), which was held in Boston from November 8-12, 2019. AASLD selected LAM's data for its poster presentation as a "Poster of Distinction." Posters of Distinction are classified as being in the top 10% of scored poster abstracts. (Dr. Roy was interviewed by BioQuick News editor Michael D. O'Neill and the text of the interview is provided below). QUESTION: Why did your group decide to focus on methylation status of cfDNA for your test? DR. ROY: Both genetic and epigenetic changes are known to be associated with the development of tumors. Over the last decade, analysis of cell-free DNA (cfDNA) from liquid biopsy samples, has emerged as a promising and potentially transformative, non-invasive diagnostic approach in oncology. cfDNA is composed of fragmented DNA released by cells into the circulation, typically as a result of cell death.

December 13th

DNA Stress Sensed by Mitochondria Can Cause Them to Activate Innate Immune System, Including Interferon-Stimulated Genes (ISGs) That Act to Protect Nuclear DNA and This May Support Development of Resistance to DNA-Damaging Chemotherapy

Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery. Now, Salk researchers have discovered a new function of mitochondria: they set off molecular alarms when cells are exposed to stress or chemicals that can damage DNA, such as chemotherapy. The results, published online in Nature Metabolism on December 9, 2019, could lead to new cancer treatments that prevent tumors from becoming resistant to chemotherapy. The article is titled “Mitochondrial DNA Stress Signalling Protects the Nuclear Genome.” "Mitochondria are acting as a first line of defense in sensing DNA stress. The mitochondria tell the rest of the cell, 'Hey, I'm under attack, you better protect yourself,'" says Gerald Shadel, PhD, a Professor in Salk's Molecular and Cell Biology Laboratory and the Audrey Geisel Chair in Biomedical Science. Most of the DNA that a cell needs to function is found inside the cell's nucleus, packaged in chromosomes and inherited from both parents. But mitochondria each contain their own small circles of DNA (called mitochondrial DNA or mtDNA), passed only from a mother to her offspring. And most cells contain hundreds--or even thousands--of mitochondria. Dr. Shadel's lab group previously showed (in “Mitochondrial DNA Stress Primes the Antiviral Innate Immune Response” at https://www.nature.com/articles/nature14156) that cells respond to improperly packaged mtDNA similarly to how they would react to an invading virus--by releasing it from mitochondria and launching an immune response that beefs up the cell's defenses.

Why Giant Pandas Are Born So Tiny; Short Gestation Period May Be Cause

Born pink, blind, and helpless, giant pandas typically weigh about 100 grams at birth -- the equivalent of a stick of butter. Their mothers are 900 times more massive than that. This unusual size difference has left researchers puzzled for years. With a few exceptions among animals such as echidnas and kangaroos, no other mammal newborns are so tiny relative to their mothers. No one knows why, but a Duke University study of bones across 10 species of bears and other animals finds that some of the current theories don't hold up. Duke biology professor Kathleen Smith, PhD, and her former student Peishu Li published their findings this month in the Journal of Anatomy. The article was published online on December 2, 2019 and is titled "Comparative Skeletal Anatomy of Neonatal Ursids and the Extreme Altriciality of the Giant Panda.” Baby panda skeletons are hard to come by, but the researchers were able to study the preserved remains of baby pandas born at the Smithsonian's National Zoo in Washington, D.C. The National Zoo's first panda couple, Ling-Ling and Hsing-Hsing, had five full-term cubs in the 1980s, but none of them survived long after birth. The researchers took micro-CT scans of two of those cubs, along with newborn grizzlies, sloth bears, polar bears, dogs, a fox, and other closely related animals from the Smithsonian National Museum of Natural History and the North Carolina State College of Veterinary Medicine. They used the scans to create 3-D digital models of each baby's bony interior at birth. As a baby animal grows and develops inside the womb, its bones and teeth do also. The researchers examined the degree of ossification, or how much the skeleton has formed by the time of birth.