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March 11th, 2020

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.

February 27th

Researchers Discover Second Type of Schizophrenia; In a Study of More Than 300 Patients from Three Continents, Over One Third Had Brains That Looked Similar to Those in Healthy People

Penn Medicine researchers are the first to discover two distinct neuroanatomical subtypes of schizophrenia after analyzing the brain scans of over 300 patients. The first type showed lower widespread volumes of gray matter when compare to healthy controls, while the second type had volumes largely similar to those in normal brains. The findings, published online on February 27, 2020 in Brain, suggest that, in the future, accounting for these differences could inform more personalized treatment options. "Numerous other studies have shown that people with schizophrenia have significantly smaller volumes of brain tissue than healthy controls. However, for at least a third of patients we looked at, this was not the case at all -- their brains were almost completely normal," said principal investigator Christos Davatzikos, PhD, the Wallace T. Miller Professor of Radiology in the Perelman School of Medicine at the University of Pennsylvania. "In the future, we're not going to be saying, 'This patient has schizophrenia,' We're going to be saying, 'This patient has this subtype' or 'this abnormal pattern,' rather than having a wide umbrella under which everyone is categorized." Schizophrenia is a poorly understood mental disorder that typically presents with hallucinations, delusions, and other cognitive issues -- though symptoms and responses to treatment vary widely from patient to patient. Up until now, attempts to study the disease, by comparing healthy to diseased brains, has neglected to account for this heterogeneity, which Dr. Davatzikos says has muddled research findings and undermined clinical care. To better characterize the distinct brain differences within the schizophrenia patient population, Dr.

Huntington's Disease-Causing DNA Repeat Mutations Reversed in the Lab; International Team Identifies Compound That Could Slow Huntington's Disease Onset and Progression In Humans

Neurodegenerative diseases, like Huntington's disease and myotonic dystrophy, are often referred to as DNA repeat diseases, named because of long repeated sequences in the DNA of patients. Increasing repeat expansion length in the affected tissues contribute to earlier age of disease onset and worsen the progression and severity of the disease over time. In an international study published online on February 14, 2020 Nature Genetics, scientists from The Hospital for Sick Children (SickKids), Canada, along with research teams from Osaka University, Japan, reveal the ability to reverse this repeat mutation length in the brains of a mouse model with Huntington's disease. The article is titled “"A Slipped-CAG DNA-Binding Small Molecule Induces Trinucleotide-Repeat Contractions in Vivo.” The team discovered a compound that targets the unusual DNA structure and was shown to reverse repeat expansions with undetectable off-target effects. Huntington's disease is one of more than 40 neurodegenerative diseases caused by DNA repeat expansion mutations in specific genes. The unusual DNA structures, called slipped-DNAs, are formed by the repeats, and levels of slipped-DNAs are greater in affected tissues that have longer repeat expansions, causing more severe mutations. The study found evidence that the molecule compound called naphthyridine-azaquinolone (NA) can recognize slipped-DNAs and reverse the mutation -- essentially causing a contraction of the expansion. In the lab, the research team was able to successfully reduce the repeat expansions in the brain of a Huntington's disease mouse model, as well as in cells extracted from tissues of individuals affected by Huntington's disease.

February 26th

Hong Kong Scientists Shed Light On COVID-19 Coronavirus (SARS-CoV-2) Vaccine Development

A team of scientists at the Hong Kong University of Science and Technology (HKUST) has recently made an important discovery in identifying a set of potential vaccine targets for the SARS-CoV-2 coronavirus, providing crucial leads for guiding experimental efforts towards the vaccine development against the novel pneumonia (COVID-19) caused by the virus. Like SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003, SARS-CoV-2 belongs to the same Betacoronavirus genus. By considering the genetic similarity between SARS-CoV-2 and SARS-CoV, the team leveraged experimentally-determined immunological data to identify a set of SARS-CoV- derived B cell and T cell epitopes that exactly match to SARS-CoV-2. Epitopes are biomarkers recognized by the immune system to trigger actions against the virus. As no mutation has been observed in the identified epitopes among the available SARS-CoV-2 genetic sequences, immune targeting of these epitopes may potentially offer protection against the novel pneumonia COVID-19. The team, led by data scientists Professor Matthew McKay and Dr. Ahmed Abdul Quadeer, expected that their work can assist in guiding experimental research towards the development of effective vaccines against SARS- CoV-2. Professor McKay highlighted that "Despite similarities between SARS-CoV and SARS-CoV-2, there is genetic variation between the two, and it is not obvious if epitopes that elicit an immune response against SARS-CoV will likely be effective against SARS-CoV-2. We found that only roughly 20% of the SARS-CoV epitopes map identically to SARS-CoV-2, and believe these are promising candidates." "For the identified T cell epitopes, we also performed a population coverage analysis and determined a set of epitopes that is estimated to provide broad coverage globally, as well as in China" said Dr.

February 24th

Artificial Intelligence Yields New Antibiotic (“Hlicin”), “Arguably One of the More Powerful Antibiotics That Has Been Discovered”

A deep-learning model identifies a powerful new drug that can kill many species of antibiotic-resistant bacteria. Using a machine-learning algorithm, MIT researchers have identified a powerful new antibiotic compound. In laboratory tests, the drug killed many of the world’s most problematic disease-causing bacteria, including some strains that are resistant to all known antibiotics. It also cleared infections in two different mouse models. The computer model, which can screen more than a hundred million chemical compounds in a matter of days, is designed to pick out potential antibiotics that kill bacteria using different mechanisms than those of existing drugs.“ We wanted to develop a platform that would allow us to harness the power of artificial intelligence to usher in a new age of antibiotic drug discovery,” says James Collins, PhD, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “Our approach revealed this amazing molecule which is arguably one of the more powerful antibiotics that has been discovered.” In their new study, the researchers also identified several other promising antibiotic candidates, which they plan to test further. They believe the model could also be used to design new drugs, based on what it has learned about chemical structures that enable drugs to kill bacteria. “The machine learning model can explore, in silico, large chemical spaces that can be prohibitively expensive for traditional experimental approaches,” says Regina Barzilay, PhD, the Delta Electronics Professor of Electrical Engineering and Computer Science in MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL). Dr. Barzilay and Dr.

February 23rd

Model for X-Linked Adrenoleukodystrophy (X-ALD) Identified in C. elegans Worm

The IDIBELL Neurometabolic Diseases group, with international collaboration, has identified a model of chromosome X-linked adrenoleukodystrophy (x-ALD) in the earthworm C. elegans. X-ALD is a rare disorder of the nervous system with no treatment available. The model should permit the acceleration of research and a reduction in the price of that research, which is studying the mechanisms and the possible pharmacological targets for the neuronal alterations of this disease. The earliest results of studies with this organism point to glial cells as responsible for the neurological damage caused by the disease. X-ALD is a rare genetic disease in which long-chain fatty acids accumulate in the blood and the nervous tissue, and where the myelin in the neurons is damaged. People who suffer from X-ALD (1 in 14,700 newborns) may have, among other things, brain and mobility problems, as well as hormonal disorders. The cause is a deficiency in the ABCD1 gene, which encodes the adrenoleukodystrophy protein (ALDP), which transports long-chain fatty acids to peroxisomes. These organelles play a very important role in lipid degradation and their subsequent cell use. This work has identified and characterized the worm C. elegans as a model of the disease, this model is deficient for the human analog protein (homologous) ALDP. The research team, co-led by Dr. Aurora Pujol and Esther Dalfó, analyzed the consequences of this deficit on a cellular level and found that, as in human and in existing mouse models, exist an accumulation of long-chain fatty acids, changes in lipid metabolism, oxidative imbalances in the mitochondria, and neuronal disorders. The model will allow accelerating the study of this disease, for which there is currently no treatment.