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Archive - Mar 2020

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March 13th

Newly Discovered Family of Flexible, Heat-Resistant, Non-Chaperone Proteins Protect Against Protein Instability and Aggregation; The Newly Identified “Hero” Proteins May Find Application in Neurodegenerative Diseases

Protein aggregation and misfolding underpin several neurodegenerative diseases such as Huntington’s and Alzheimer’s. Proteins can also become aggregated or denatured under conditions of stress, such as extreme heat. A new study, published online on March 12, 2020 in the open-access journal PLOS Biology by Dr. Kotaro Tsuboyama and Dr. Yukihide Tomari (photo) of The University of Tokyo, Japan, and colleagues, reveals a newly discovered family of proteins in both humans and flies which protect vulnerable proteins from becoming aggregated or denatured in extreme heat and other stresses – a function previously only known in “extremophile” organisms such as heat-loving bacteria. The PLOS Biology article is titled “A Widespread Family of Heat-Resistant Obscure (Hero) Proteins Protect Against Protein Instability and Aggregation.” The proteins, discovered through a serendipitous observation, may find applications in biotechnology and protection from neurodegenerative disease. Proteins are molecules held in their active folded shape by weak attractions between and among amino acids. Heat can disrupt these attractions, changing protein shape and causing them to clump together. This also stops the proteins from functioning. An entire class of already known proteins—the “molecular chaperones”—use cellular energy in the form of ATP to either refold or dispose of misfolded proteins. But for proteins in most organisms, temperatures close to the boiling point of water irreversibly destroy their structure. In the course of their research on an entirely different question, while trying to purify a structurally unstable fly protein called Ago2, the authors of the PLOS Biology article found that liquid extracted by breaking open fly cells contained some factor that stabilized this Ago2 protein.

March 11th

New Study Sheds Light on “Dark Region” of Drosophila Genome

Just as there is a mysterious dark matter that accounts for 85 percent of our universe, there is a "dark" portion of the human genome that has perplexed scientists for decades. A study published online on March 6, 2020, in Genome Research identifies new portions of the fruit fly genome that, until now, have been hidden in these dark, silent areas. The collaborative open-access paper, titled "Gene Expression Networks in the Drosophila Genetic Reference Panel," is the culmination of years of research by Clemson University geneticists Trudy Mackay, PhD, and Robert Anholt, PhD. Their ground-breaking findings could significantly advance science's understanding of a number of genetic disorders. The "dark" portion refers to the approximate 98 percent of the genome that doesn't appear to have any obvious function. Only 2 percent of the human genome codes for proteins, the building blocks of our bodies and the catalysts of the chemical reactions that allow us to thrive. Scientists have been puzzled by this since the 1970s when gene sequencing technologies were first developed, revealing the proportion of coding to noncoding regions of the genome. Genes are traditionally thought to be transcribed into RNAs, which are subsequently translated into proteins, as dictated by the central dogma of molecular biology. However, the entire assemblage of RNA transcripts in the genome, called the “transcriptome,” contains RNA species that appear to have some other function, apart from coding for proteins. Some scientists have proposed that noncoding regions might contain regulatory regions that control gene expression and the structure of chromosomes, yet these hypotheses were difficult to study in past years as diagnostic technology was developing.

March 11th

Microbial DNA in Patient Blood May Be Tell-Tale Sign of Cancer--From Simple Blood Draw, Microbial DNA May Reveal Who Has Cancer and Which Type, Even at Early Stages, Nature Study Suggests

When Gregory Poore was a freshman in college, his otherwise healthy grandmother was shocked to learn that she had late-stage pancreatic cancer. The condition was diagnosed in late December. She died in January. "She had virtually no warning signs or symptoms," Poore said. "No one could say why her cancer wasn't detected earlier or why it was resistant to the treatment they tried." As Poore came to learn through his college studies, cancer has traditionally been considered a disease of the human genome -- mutations in our genes allow cells to avoid death, proliferate, and form tumors. But when Poore saw a 2017 study in Science that showed how microbes invaded a majority of pancreatic cancers and were able to break down the main chemotherapy drug given to these patients, he was intrigued by the idea that bacteria and viruses might play a bigger role in cancer than anyone had previously considered. Poore is currently an MD/PhD student at University of California (UC) San Diego School of Medicine, where he's conducting his graduate thesis work in the lab of Rob Knight, PhD, Professor and Director of the Center for Microbiome Innovation. Together with an interdisciplinary group of collaborators, Poore and Dr. Knight have developed a novel method to identify who has cancer, and often which type, by simply analyzing patterns of microbial DNA -- bacterial and viral -- present in their blood. The study, published online on March 11, 2020 in Nature, may change how cancer is viewed, and diagnosed.

Primitive One-Cell Organism Reveals Amazing Clues to Structure of the Universe; Slime Mold Simulations Used to Map Dark Matter Holding Universe Together; Art Initially Prompts Incredible Connection Between Slime Mold and Dark Matter

The behavior of one of nature's humblest creatures is helping astronomers probe the largest structures in the universe. The single-cell organism, known as slime mold (Physarum polycephalum), builds complex filamentary networks in search of food, finding near-optimal pathways to connect different locations. In shaping the universe, gravity builds a vast cobweb structure of filaments tying galaxies and clusters of galaxies together along faint bridges hundreds of millions of light-years long. There is an uncanny resemblance between the two networks: one crafted by biological evolution, and the other by the primordial force of gravity. The cosmic web is the large-scale backbone of the cosmos, consisting primarily of the mysterious substance known as dark matter and laced with gas, upon which galaxies are built. Dark matter cannot be seen, but it makes up the bulk of the universe's material. The existence of a web-like structure to the universe was first hinted at in the 1985 Redshift Survey conducted at the Harvard-Smithsonian Center for Astrophysics. Since those studies, the grand scale of this filamentary structure has grown in subsequent sky surveys. The filaments form the boundaries between large voids in the universe. But astronomers have had a difficult time finding these elusive strands, because the gas is so dim it is hard to detect. Now a team of researchers has turned to slime mold to help them build a map of the filaments in the local universe (within 500 million light-years from Earth) and find the gas within them.

March 9th

Human Protein (LY6E) Can Potently Inhibit Corona Virus in Animal Model, UTSW Med Center Researchers & International Collaborators Report in Non-Peer-Reviewed Publication

A protein produced by the human immune system can potently inhibit several coronaviruses, including the one behind the current COVID-19 outbreak, an international team of investigators reported in a non-peer-reviewed article on March 8, 2020. The research reveals that the interferon-inducible lymphocyte antigen 6 complex, locus E protein (LY6E) impairs the coronavirus’ ability to initiate infection, which could lead to treatments for the illness. Mechanistic studies revealed that LY6E inhibits CoV entry into cells by interfering with spike protein-mediated membrane fusion. Strikingly, mice lacking Ly6e (the mouse version of the gene) were highly susceptible to a usually nonlethal mouse coronavirus, the researchers reported on March 8, 2020 in bioRxiv, an online preprint server that posts articles prior to peer review. The bioRxiv open-access article is titled “LY6E Impairs Coronavirus Fusion and Confers Immune Control of Viral Disease.” (Editor’s note: It should be emphasized that bioRxiv is receiving many new papers on coronavirus 2019-nCoV. A reminder: these are preliminary reports that have not been peer-reviewed. bioRxiv emphasizes that these articles should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information). “Remarkably, this potent inhibitory effect carried over to all the coronaviruses we tested, including those responsible for the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2003, the Middle East respiratory syndrome (MERS) coronavirus in 2012, and the recently emerged causative agent of COVID-19, known as SARS-CoV-2,” says John Schoggins, PhD, an Associate Professor of Microbiology at UT Southwestern Medical Center and one of three corresponding authors on the report.

“Primitive” Stem Cells Shown to Regenerate Blood Vessels in the Eye; Johns Hopkins Advance Offers Hope of Ultimately Reversing Diabetic Retinopathy

Scientists at Johns Hopkins Medicine say they have successfully turned back the biological hands of time, coaxing adult human cells in the laboratory to revert to a primitive state, and unlocking their potential to replace and repair damage to blood vessels in the retina caused by diabetes. The findings from this experimental study, they say, advance regenerative medicine techniques aimed at reversing the course of diabetic retinopathy and other blinding eye diseases. "Our study results bring us a step closer to using stem cells more widely in regenerative medicine, without the historical problems our field has encountered in getting such cells to differentiate and avoid becoming cancerous," says Elias Zambidis, MD, PhD, Associate Professor of Oncology at the Johns Hopkins Kimmel Cancer Center and a member of Johns Hopkins' Institute for Cell Engineering. Results of experiments using human cells and mice were published online on March 5, 2020 in Nature Communications. The open-access article is titled “Vascular Progenitors Generated from Tankyrase Inhibitor-Regulated Naïve Diabetic Human iPSC Potentiate Efficient Revascularization of Ischemic Retina.” According to the National Eye Institute, diabetic retinopathy is a leading cause of blindness in U.S. adults. By 2050, researchers estimate that some 14.6 million Americans will have the condition, which results in abnormal blood vessel growth in the retina, where light is processed into vision. For the study, the scientists began their experiments with a fibroblast -- a connective tissue cell -- taken from a person with type 1 diabetes. Reprogrammed fibroblasts function as "stem" cells, with the potential to give rise to all tissues in the body, including blood vessels.

March 4th

High-Tech Contact Lenses Correct Form of Color Blindness; Researchers Apply Ultra-Thin Metasurfaces to Standard Contact Lenses for Customizable Color Correction

Researchers have incorporated ultra-thin optical devices known as metasurfaces into off-the-shelf contact lenses to correct deuteranomaly, a form of red-green color blindness. The new customizable contact lens could offer a convenient and comfortable way to help people who experience various forms of color blindness. "Problems with distinguishing red from green interrupt simple daily routines such as deciding whether a banana is ripe," said Sharon Karepov from Tel Aviv University in Israel, a member of the research team. "Our contact lenses use metasurfaces based on nano-metric size gold ellipses to create a customized, compact and durable way to address these deficiencies." In a recent issue (Volume 46, Issue 6, 2020) of The Optical Society (OSA) journal Optics Letters, Karepov and a colleague (Tal Ellenbogen) report that, based on simulations of color vision deficiency, their new metasurface-based contact lens can restore lost color contrast and improve color perception by up to a factor of 10. The article is titled “Metasurface Based Contact Lenses for Color Vision Deficiency.” The approach used to introduce new and tailor-designed functionalities to contact lenses could be expanded to help other forms of color vision deficiency and even other eye disorders, according to the researchers. Deuteranomaly, which occurs mostly in men, is a condition in which the photoreceptor responsible for detecting green light responds to light associated with redder colors. Scientists have known for more than 100 years that this vision problem can be improved by reducing detection of the excessively perceived color, but achieving this correction in a comfortable and compact device is challenging.