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Archive - Jun 4, 2019

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Dogma-Shattering Work Shows That One Cell Type Can Change into Another Cell Type After Development; Key Incisive Observation Comes in Long-Studied Zebrafish (“Secret Hiding in Plain Sight”); Finding May Have Major Implications for Regenerative Medicine

A new study by researchers at the University of Virginia (UVA) and other institutions has revealed the existence of a type of pigment cell in zebrafish that can transform after development into another cell type. The work was reported online on May 28, 2019 in PNAS in an open-access article titled “Fate Plasticity and Reprogramming in Genetically Distinct Populations of Danio leucophores.” David Parichy, PhD, the Pratt-Ivy Foundation Distinguished Professor of Morphogenesis in UVA's Department of Biology, said that researchers in his lab noticed that some black pigment cells on zebrafish became gray and then eventually white. When they looked more closely, they found dramatic changes in gene expression and pigment chemistry. "We realized that the cells have a secret history hiding in plain sight," he said. "Zebrafish have been studied closely for more than 30 years - we know a lot about them - but this is the first time this transformation has been noticed. It's a very surprising discovery." The unique cell population sheds the pigment melanin, changing in color from black to white during the life cycle of an individual fish. These special cells are found at the edges of the fins, where they seem to act as a signal to other zebrafish. The ability of a developed cell to differentiate directly into another type of cell is exceptionally rare. Normally such a change requires experimental intervention, returning the cell to a stem-cell state in a dish, before it can differentiate, or transform, as something else. The new finding suggests that some developed cells might be more amenable to change than generally believed.

Gum Disease May Help Cause/Accelerate Loss of Memory & Alzheimer’s Disease; Small Molecule Inhibitors Designed to Block Neurotoxic Enzymes (Gingipains) Produced by Gum Disease Bacteria May Prove Helpful

Researchers have determined that gum disease (gingivitis) may play a decisive role in whether a person develops Alzheimer´s disease (AD) or not. "We discovered DNA-based proof that the bacteria causing gingivitis can move from the mouth to the brain," says researcher Piotr Mydel, PhD, at Broegelmanns Research Laboratory, Department of Clinical Science, University of Bergen (UiB) in Norway. The bacteria produce enzymes (gingipains) that destroy nerve cells in the brain, which in turn leads to loss of memory and, ultimately, Alzheimer´s. The research results of Dr. Mydel and his team were published in the January 23, 2019 issue of Science Advances. The open-access article is titled “Porphyromonas gingivalis in Alzheimer’s Disease Brains: Evidence for Disease Causation and Treatment with Small-Molecule Inhibitors.” Dr. Mydel points out that the bacteria is not causing Alzheimer´s alone, but the presence of these bacteria substantially raises the risk for developing the disease and the bacteria are also implicated in a more rapid progression of the disease. However, the good news is that this study shows that there are some things you can do yourself to slow down Alzheimer´s. First--"Brush your teeth and use floss.” Dr. Mydel adds that it is important, if you have established gingivitis and have Alzheimer´s in your family, to go to your dentist regularly and clean your teeth properly. Researchers have previously discovered that the bacteria causing gingivitis can move from the mouth to the brain where the harmful enzymes they excrete can destroy the nerve cells in the brain. Now, for the first time, Dr. Mydel has DNA-evidence for this process from human brains. Dr.

New Chemical Process Should Be “Important First Step Toward Establishing New Technology Platform to Greatly Facilitate Drug Discovery Across Diverse Landscape of Therapeutic Indications”—Glioblastoma & Estrogen Receptor β Are Early Targets

A research team at Dartmouth College has developed a new strategy for drug discovery and development that can be used to produce targeted therapies against diseases such as cancer and neurodegeneration, according to a study published online on June 4, 2019 in Nature Communications. The open-access article is titled “A Synthesis Strategy for Tetracyclic Terpenoids Leads to Agonists of ERβ.” It is hoped that the process will also be useful in the large-scale production of new pharmaceuticals. The team has already used the new approach to develop a molecule that is selectively effective against glioblastoma, without little effects on non-cancerous human neural stem cells and human astrocytes, and to the development of a potent inhibitor of the the nuclear hormone receptor estrogen receptor beta. The new technique uses a novel synthesis approach for a class of organic compounds known as tetracyclic terpenoids. Tetracyclic terpenoids are responsible for more than 100 FDA-approved drugs and are considered the most successful class of natural product-inspired pharmaceuticals. "Until now, there was nothing like this available for drug discovery and development," said Glenn Micalizio (photo), PhD, the New Hampshire Professor of Chemistry at Dartmouth. "While additional development is expected to enhance the power of this new technology, I believe that we are at the beginning of establishing a truly enabling and potentially transformative technology for the pharmaceutical industry." The process combines two new chemical reactions that establish bonds between carbon atoms with a unique metal-centered ring-forming reaction, also developed by Dr. Micalizio. The new technique allows for uniting molecular building blocks en route to developing a terpenoid skeleton in just a few chemical transformations.