The Rhyothemis princeps Brain Externalization Project

Last notes were about intracellular pH and senescent cell clearance, cancer and neurodegeneration. Just a few days later, an article on Nrf2 appeared in my news feed: https://medicalxpress.com/news/2021-01-nrf2-magic-molecule-eternal-youth.html "At the risk of overstating the obvious, if a little extra NRF2 is good for every cell in your body, and every cell in your body is good, then NRF2 must be good for your body. The weak link in that argument, however, is that all cells are not good. Nobody wants harmful bacterial cells to flourish, and nobody wants cancer cells to flourish. A paper recently published in Nature now suggests that inhibiting NRF2 can block the migration and invasion of non-small-cell lung cancer cells through the body. If anyone is going to derive benefit from NRF2, they may need to be smart about it. The main reason NRF2, or Nuclear factor-erythroid 2-related factor 2, is so highly sought, is because it is a key transcriptional regulator of several an

New article on kidney type glutaminase and senescent cell clearance: https://science.sciencemag.org/content/371/6526/265   related:   Simultaneously Targeting Tissue Transglutaminase and Kidney Type Glutaminase Sensitizes Cancer Cells to Acid Toxicity and Offers New Opportunities for Therapeutic Intervention https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291776/   It's interesting that this all hinges on intracellular pH; there was a good talk on intracellular pH and neurodegeneration a while back: https://youtu.be/OUmFkfTFm_o

The topic of low dose doxycycline (DOX) for Parkinson's came up on a forum. Rationale for its use in PD is typically based inhibition of a-syn aggregation , however DOX is a matrix metalloproteinase inhibitor (2 and 9). Matrix metalloproteinases are a group of enzymes that break down collagen and some other extracellular matrix proteins. White tea is supposed to be good for preventing skin aging since it contains a substance that inhibits one or two matrix metalloproteinases (can't remember which ones). The extracellular matrix is the stuff in between cells and it is mostly collagen. A lot of TGF-beta, a signalling molecule involved in the immune system, is localized in the ECM and engages in 'solid state' signalling - it is not dissolved in fluid, it stays put and interacts with cells as they come in contact when the tissue is deformed by mechanical pressure or cells migrate . People with connective tissue disorders often have immune system problems because

Got into a discussion about the U-shaped or J-shaped mortality curve for serum urate. U or J, there's an inflection point, and the lowest mortality is not at the extreme lower end. Could this be due to impaired kidney function causing both high mortality and low serum urate levels? Or is it because very low levels are harmful? People with mutations in the urate transporter (URAT1) gene SLC22A12 have low levels of serum urate due to low resorption rate and have endothelial dysfunction, likely due to oxidative stress. - Extremely Low Levels of Serum Uric Acid Are Associated With Endothelial Dysfunction in Humans https://www.jstage.jst.go.jp/article/circj/79/5/79_CJ-15-0232/_pdf/-char/en Primates have evolved higher serum urate levels as the result of positive selection pressure through loss of the uricase gene and also increase in efficiency of the urate transporter.  - Coevolution of URAT1 and Uricase during Primate Evolution:Implications for Serum Urate Homeostasis and Gout https

This morning brought me a rather disturbing story about squirrels aggressively attacking residents of a Queens, New York neighborhood. The attacks were unprovoked. The story is reported in detail here: https://patch.com/new-york/ foresthills/vicious-squirrel- attacks-rattle-rego-park- residents   What could cause the squirrels to behave this way? It could be due to food scarcity; there have been a lot of restaurant closures due the pandemic - so fewer scraps around and less garbage to raid. There have been cases of people feeding meth (methamphetamine) to squirrels in order to make them more aggressive: https://www.newsweek.com/man- accused-feeding-squirrel-meth- 1485460 The other thought that comes to mind is that the behavior change could be due to SARS-CoV-2 infection. It is at least theoretically possible for squirrels to become infected and there is some preliminary evidence linking covid with onset of mental illness in humans. https://www.medscape.com/viewarticle/940922 The m