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COVID-19 Mouse CRISPR Engineered to Recapitulate Human COVID-19

In addition, the mice developed interstitial pneumonia, which affects the tissue and space around the air sacs of the lungs, causing the infiltration of inflammatory cells, the thickening of the structure that separates air sacs, and blood vessel damage. Compared with young mice, older mice showed more severe lung damage and increased production of signaling molecules called cytokines. Taken together, these features recapitulate those observed in COVID-19 patients.

When the researchers administered SARS-CoV-2 into the stomach, two of the three mice showed high levels of viral RNA in the trachea and lung. The S protein was also present in lung tissue, which showed signs of inflammation. According to the authors, these findings are consistent with the observation that patients with COVID-19 sometimes experience gastrointestinal symptoms such as diarrhea, abdominal pain, and vomiting. But 10 times the dose of SARS-CoV-2 was required to establish infection through the stomach than through the nose.

Future studies using this mouse model may shed light on how SARS-CoV-2 invades the brain and how the virus survives the gastrointestinal environment and invades the respiratory tract. “The hACE2 mice described in our manuscript provide a small animal model for understanding unexpected clinical manifestations of SARS-CoV-2 infection in humans,” concluded co-senior study author Chang-Fa Fan of NIFDC. “This model will also be valuable for testing vaccines and therapeutics to combat SARS-CoV-2.”

‘Knowing how’ is in your brain

Although we often think of knowledge as “knowing that” (for example, knowing that Paris is the capital of France), each of us also knows many procedures consisting of “knowing how,” such as knowing how to tie a knot or start a car. Now, a new study has found the brain programs that code the sequence of steps in performing a complex procedure.

In a just published paper in Psychological Science, researchers at Carnegie Mellon University have found a way to find decode the procedural information required to tie various knots with enough precision to identify which knot is being planned or performed. To reach this conclusion, Drs. Robert Mason and Marcel Just first trained a group of participants to tie seven types of knots, and then scanned their brains while they imagined tying, or actually tied the knots while they were in an MRI scanner. The main findings were that each knot had a distinctive neural signature, so the researchers could tell which knot was being tied from the sequence of brain images collected. Furthermore, the neural signatures were very similar for imagining tying a particular knot and planning to tie it.

Dr. Just said, “Tying a knot is an ancient and frequently performed that is the epitome of everyday procedural knowledge, making it an excellent target for investigation.”

Algorithm tracks down buried treasure among existing compounds

A machine-learning algorithm has been developed by scientists in Japan to breathe new life into old molecules. Called BoundLess Objective-free eXploration, or Blox, it allows researchers to search chemical databases for molecules with the right properties to see them repurposed. The team demonstrated the power of their technique by finding molecules that could work in solar cells from a database designed for drug discovery.

Chemical repurposing involves taking a molecule or material and finding an entirely new use for it. Suitable molecules for chemical repurposing tend to stand apart from the larger group when considering one property against another. These materials are said to be out-of-trend and can display previously undiscovered yet exceptional characteristics.

‘In public databases there are a lot of molecules, but each molecule’s properties are mostly unknown. These molecules have been synthesised for a particular purpose, for example drug development, so unrelated properties were not measured,’ explains Koji Tsuda of the Riken Centre for Advanced Intelligence and who led the development of Blox. ‘There are a lot of hidden treasures in databases.’

Letting off electrons to cope with metabolic stress

Whereas textbooks depict metabolism in perfect homeostasis, disturbances occur in real life. One particularly relevant disturbance, caused by excess food and alcohol consumption and exacerbated by genetics, is reductive stress. New work by Goodman et al. identifies a biomarker of reductive stress and uses a gene therapy solution in mice. This work suggests how exercise and an accessible nutritional technology can synergistically increase catabolism and relieve reductive stress.

BRIAN KENNEDY — Reversing Human Aging (#0004)

Sirtuins, telomeres, A.I. experiment with vitamin A and personalized medicine, a bit of everything here.


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