Exosome-Based Blood Test Distinguishes Between Parkinson’s Disease and Multiple System Atrophy (MSA); Ratio of Alpha-Synuclein in Neuron-Derived Exosomes Versus Alpha-Synuclein in Oligodendrocyte-Derived Exosomes Is Key

Researchers at UCLA Health have developed a blood test that can distinguish between two very similar movement disorders, Parkinson’s disease and multiple system atrophy (MSA). The test, which is currently for research use only, identifies the disease by analyzing the contents of tiny sub-cellular vesicles called “exosomes” that are sent out by brain cells and wind up in the blood. The researchers reported their findings online on May 15, 2021 in Acta Neuropathologica. Their open-access article is titled “α-Synuclein in Blood Exosomes Immunoprecipitated Using Neuronal and Oligodendroglial Markers Distinguishes Parkinson’s Disease From Multiple System Atrophy.” Parkinson’s disease can be difficult to distinguish from other neurodegenerative diseases, including MSA, due to similar symptoms such as muscle rigidity and tremors. Patients who have been incorrectly diagnosed with one or the other disease may feel anxiety when unexpected symptoms occur, or, in the case of a Parkinson’s misdiagnosis, the disease progresses faster than predicted.

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Multicellular Arctic Rotifer Lives After 24,000 Years in Frozen State

Bdelloid rotifers are multicellular animals so small you need a microscope to see them. Despite their small size, they’re known for being tough, capable of surviving through drying, freezing, starvation, and low oxygen. Now, researchers reporting in the June 7, 2021 issue of Current Biology, have found that not only can they withstand being frozen, but they can also persist for at least 24,000 years in the Siberian permafrost and survive. The article is titled “”A Living Bdelloid Rotifer Recovered from 20,000 Year Old Arctic Permafrost.” “Our report is the hardest proof, as of today, that multicellular animals could withstand tens of thousands of years in cryptobiosis, the state of almost completely arrested metabolism,” says Stas Malavin, PhD, of the Soil Cryology Laboratory at the Institute of Physicochemical and Biological Problems in Soil Science in Pushchino, Russia.

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Nature Communications Publishes Study Showing CytoDyn’s Monoclonal Antibody (Leronlimab) Prevents SHIV Infection in Non-Human Primates; Results Termed “Potentially Ground-Breaking”

On June 7, 2021, CytoDyn Inc. (OTC.QB: CYDY), a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced the publication in Nature Communications of a study showing that the company’s monoclonal antibody drug leronlimab prevented non-human primates from being infected with simian human immunodeficiency virus (SHIV), a monkey-human chimeric form of HIV. The results will inform a future human clinical trial evaluating leronlimab as a potential pre-exposure prophylaxis (PrEP), therapy to prevent human infection from the virus that causes AIDs. The open-access Nature Communications article is titled “Antibody-Based CCR5 Blockade Protects Macaques from Mucosal SHIV Transmission.”

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Scientists Confirm That Certain Insect Larvae Host Bacteria That Help Shut Down Plant Defense Mechanisms

The oral secretions of herbivorous insects can activate plant defense mechanisms that protect plant cells from being digested. However, scientists at the Tokyo University of Science have discovered that some larvae “partner up” with bacteria that help interrupt these plant defense mechanisms. This disrupts the plant’s defenses before the digestive proteins that the larvae smear on them. These findings may help agricultural scientists devise countermeasures that protect important agricultural species from the larvae. Although insect larvae may seem harmless to humans, they can be extremely dangerous to the plant species that many of them feed on, and some of those plant species are important as agricultural crops. Although plants cannot simply flee from danger as animals typically would, many have nonetheless evolved ingenious strategies to defend themselves from herbivores. Herbivorous insect larvae will commonly use their mouths to smear various digestive proteins onto plants that they want to eat, and when plants detect chemicals commonly found in these oral secretions, they can respond to the injury by producing defensive molecules, including proteins and specialized metabolites, of their own that inactivate the insect’s digestive proteins and thus prevent the insect from obtaining nutrients from the plant.

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Preclinical Experiments Show That Combination of Cepharanthine and Nelfinavir May Be Effective Treatment for COVID-19

COVID-19 continues to claim lives across the world and is infecting millions more. Although several vaccines have recently become available, making significant strides towards preventing COVID-19, what about the treatment of those who already have the infection? Vaccines aren’t 100% effective, highlighting the need–now more than ever–for effective antiviral therapeutics. Moreover, some people can’t receive vaccines due to health issues, and new variants of SARS-CoV-2, the virus that causes COVID-19, that can penetrate vaccine-conferred immunity, are being reported, indicating that we need to think beyond prevention. Given this need, a team of researchers based in Japan, the US, and the UK launched a project to develop effective therapeutics. This team included several researchers based at Tokyo University of Science: Visiting Professor Koichi Watashi, Dr. Hirofumi Ohashi, Professor Shin Aoki, Professor Kouji Kuramochi, and Assistant Professor Tomohiro Tanaka. Their goal was clear and simple: finding a cure for COVID-19. The first results of their study were published online on April 23, 2021 in iScience. The open-access article is titled “Potential Anti-COVID-19 Agents, Cepharanthine and Nelfinavir, and Their Usage for Combination Treatment.”

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Increased Perilipin 5 in Brown Fat Linked to Healthy White Fat Remodeling and Systemic Glucose Tolerance; Findings May Lead to New Solutions for Type 2 Diabetes and Related Conditions

Increasing a protein concentrated in brown fat appears to lower blood sugar, promote insulin sensitivity, and protect against fatty liver disease by remodeling white fat to a healthier state, a new study led by University of Texas Southwestern (UTSW) scientists suggests. The finding, published online on June 3, 2021 in Nature Communications, could eventually lead to new solutions for patients with diabetes and related conditions. The open-access article is titled “Perilipin 5 Links Mitochondrial Uncoupled Respiration in Brown Fat to Healthy White Fat Remodeling and Systemic Glucose Tolerance.” “By taking advantage of this natural system, we may be able to help make fat depots more metabolically healthy and potentially prevent or treat obesity-associated diabetes,” says study leader Perry E. Bickel, MD, Associate Professor of Internal Medicine at UTSW.

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An Epigenetic Signature for Susceptibility to Severe COVID-19

by Michael A. Goldman,* PhD, Professor & Former Chair, Biology, San Francisco State University (SFSU).

Although COVID-19 is an infectious disease, caused by exposure to the now not-so-novel coronavirus, SARS-CoV-2, the degree to which an individual person is affected by COVID-19, if at all, is in part due to host genetic factors. One of the hallmarks of COVID-19 is the way in which some individuals experience no, or very mild, symptoms, while others end up on respirators, dying, or having long-term effects (called long-COVID). Potential host genetic factors have been identified by genome-wide association studies (GWAS), in regions 3p21.31, 12q24.13, the ABO blood group system, and a type I interferon immunity defect. While the current pandemic is yielding to public health measures and highly successful vaccines, produced in record time, a fundamental understanding of the host factors that influence disease risk can be of tremendous value in preparing for future epidemics and in rapidly putting an end to COVID-19. New studies show that, in addition to host genetics, which involves heritable variation at the DNA sequence level, changes at the epigenetic level, such as DNA methylation, may also be involved. The most common form of DNA methylation in mammals involves the conversion and subsequent propagation of a cytosine in a CpG dinucleotide into a 5-methyl-cytosine. Occurring in critical regulatory regions of the genome, CpG methylation often silences gene expression. In vitro drug treatment of rodent-human hybrid cells with 5-aza-cytidine can reverse methylation and re-activate previously silent genes, such as those on the inactive X chromosome in human females.

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Extensive Study Identifies Over Dozen Existing Drugs As Potential COVID-19 Therapies; FDA-Approved Drugs or Experimental Drugs with Ample Health Data Could Be Rapidly Tested in Humans for Treatment of COVID-19

Mining the world’s most comprehensive drug repurposing collection for COVID-19 therapies, scientists have identified 90 existing drugs or drug candidates with antiviral activity against the coronavirus that’s driving the ongoing global pandemic. Among those compounds, the Scripps Research study identified four clinically approved drugs and nine compounds in other stages of development with strong potential to be repurposed as oral drugs for COVID-19, according to results published online on June 3, 2021 in Nature Communications. The open-access article is titled “Drug Repurposing Screens Identify Chemical Entities for the Development of COVID-19 Interventions.” Of the drugs that prevented the coronavirus from replicating in human cells, 19 were found to work in concert with or boost the activity of remdesivir, an antiviral therapy approved for treatment of COVID-19. “While we now have effective vaccines against COVID-19, we still lack highly effective antiviral drugs that can prevent COVID-19 infections or stop them from worsening,” says Peter Schultz, PhD, President and CEO of Scripps Research and a co-author of the published article. “Our results raise the possibility of a number of promising avenues for repurposing existing oral medications with efficacy against SARS-CoV-2,” he adds. “We have identified promising existing drugs and are also leveraging our findings to develop optimized antivirals that will be more effective against SARS-CoV-2, including variants and drug-resistant strains, as well as against other coronaviruses that currently exist or might emerge in future.”

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How an Elephant’s Trunk Manipulates Air to Eat and Drink; Findings Could Have Applications to Robotics; Elephant Trunks Can Suck Up Water at 330 MPH

New research from the Georgia Institute of Technology (Georgia Tech) finds that elephants dilate their two nostrils in order to create more space in their trunks, allowing them to store up to nine liters of water. They can also suck up water at three liters per second–a speed 30 times faster than a human sneeze (elephant’s sucking speed is estimated at 150 meters per second/330 mph). The Georgia Tech College of Engineering study sought to better understand the physics of how elephants use their trunks to move and manipulate air, water, food, and other objects. The scientists also sought to learn if the mechanics could inspire the creation of more efficient robots that use air motion to hold and move things. While octopus use jets of water to move and archer fish shoot water above the surface to catch insects, the Georgia Tech researchers found that elephants are the only animals able to use suction on land and underwater. The open-access paper, “Suction Feeding by Elephants,” was published online on June 2, 2021 in the Journal of the Royal Society Interface.

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Modulating Rapamycin Target Protein FKBP51 with Small Molecule SAFit2 Promotes Autophagy, Lowering Toxic Huntingtin Protein

Researchers world-wide are focused on clearing the toxic mutant Huntingtin (HTT) protein that leads to neuronal cell death and systemic dysfunction in Huntington’s disease (HD), a devastating, incurable, progressive neurodegenerative genetic disorder. Scientists in the lab of Buck Institute Professor Linda Ellerby, PhD, lab have found that the targeting the protein called FK506-binding protein 51 (FKBP51) promotes the clearing of those toxic proteins via autophagy, a natural process whereby cells recycle damaged proteins and mitochondria and use them for nutrition. In an article published online on May 24, 2021 in Autophagy, researchers showed that FKBP51 promotes autophagy through a new mechanism that could avoid worrisome side effects associated with rapamycin, an immune-suppressing drug which also extends lifespan in mice. They show that both rapamycin and the small pharmacological inhibitor of FKBP51, SAFit2, protect HD neurons but that the mechanisms of the two drugs are distinct. The open-access Autophagy article is titled “Modulating FKBP5/FKBP51 and Autophagy Lowers HTT (Huntingtin) Levels.”

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