The Rhyothemis princeps Brain Externalization Project

https://www.justintimemedicine.com/CurriculumContent/p/4954 "This basolateral secretion of HCO 3 − into the bloodstream is sometimes called the “alkaline tide” which normally accompanies gastric acid secretion with eating. The metabolic alkalosis of vomiting is essentially an exaggeration of this response; HCl is lost from the stomach so more is made to replace it, causing even more bicarb to be secreted "out the back end" of the parietal cell and into the bloodstream."   from Wikipedia: "Alkaline tide refers to a condition, normally encountered after eating a meal, where during the production of hydrochloric acid by parietal cells in the stomach, the parietal cells secrete bicarbonate ions across their basolateral membranes and into the blood, causing a temporary increase in pH . [1] "   ~ PPIs can cause metabolic acidosis; can be prescribed to prevent metabolic alkalosis from vomiting.

Lemon balm ( Melissa officinalis ) methanolic extract was shown to have antiviral activity in vitro against enterovirus 71 - attributed to the antioxidant constituent rosmarinic acid. https://www.nature.com/articles/s41598-017-12388-2 "Several lines of evidence support the notion that the redox status of host affects viral pathogenesis 26 . We have previously shown that EV71 infection induces oxidative stress, which in turn promotes viral replication 27 , 28 . Treatment with antioxidants, such as N-acetylcysteine (NAC) or mito-Tempo, suppresses EV71 replication 27 , 28 , 29 . Natural antioxidants, epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), in green tea have antiviral activity, which correlates well with their antioxidant capacity 30 . It is probable that the antiviral activities of natural products may be partly attributed to their antioxidative activities." Review article on redox biology of respiratory viral infections: https://pubmed.ncbi.nlm.nih....

Videos on methemoglobinemia: https://youtu.be/2RFcH_nlR84 Regular pulse oximeter will read normal in cases of methemoglobinemia. Signs include central cyanosis - blue lips, tongue (as opposed to perhipheral). Deficiencies in glucose-6-phosphate dehydrogenase or NADH cytochrome b5 reductase (CYB5R ; aka methemoglobin reductase) are risk factors. Excessive nitrite or nitrate consumption can cause MetHb; infants are at higher risk since they produce less CYB5R. Methemoglobinemia can be a side effect of dopamine antagonists such as metocloparmide (Reglan). Methemoglobinemia from metoclopramide more often occurs in infants, cases in adults are rare but can occur: https://europepmc.org/article/med/10870338 Elevated methemoglobin is among the plasma biomarkers of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) - as is elevated alpha ketoglutarate: https://pubmed.ncbi.nlm.nih.gov/30563204/ Interesting abstract: https://2018.febscongress.org/abstract_preview.aspx?idAbstractEnc=442...

    Another in a great series of webinars by NUS Medicine. 5:10 Start of 1st presentation - Berenice A. Benayoun - Why we need age-relevant mouse models of menopause Ovariectomized mice are not good models of menopause.  10:43 Slide - comparison of post-reproductive lifespan among mammalian species 18:46 VCD injection; VCD is 4-vinylcyclohexene diepoxide, an environmental toxicant that causes ovarian failure 20:31 Genetic models - Foxl2 +/- ; Fshr +/- 25:00 Start of 2nd presentation - Ingrid Fetter Pruneda - The molecular and cellular basis of high fertility in social insects Queen ants manage to have extremely high fertility at the same time as longer lifespan relative to worker ants. 35:20 ant reproductive mode can be flexible; some species have cyclic castes - switching from queen to worker and back 51:54 Apart from sex organs,  liver is most sexually dimorphic organ - important implications for drug metabolism { Does this have implications for liver transplantati...

Mutations in the gene that codes for LRRK2, a kinase, are a risk factor for Parkinson's disease . Increase in the kinase activity of LRRK2 caused by these mutations leads to increased apoptosis and neuronal loss in PD.   Vitamin B12 inhibits LRRK2 kinase activity: https://pubmed.ncbi.nlm.nih.gov/21198553/   "Herein we identify 5'-deoxyadenosylcobalamin (AdoCbl), a physiological form of the essential micronutrient vitamin B 12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity. Multiple assays show that AdoCbl directly binds LRRK2, leading to the alterations of protein conformation and ATP binding in LRRK2. ... Our study uncovers vitamin B 12 as a novel class of LRRK2 kinase modulator with a distinct mechanism, which can be harnessed to develop new LRRK2-based PD therapeutics in the future. "   High B12 status has been found to be associated with increased  risk of lung cancer: "Circulating concentrations of vitamin B12, based on pre-diagno...

Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages   https://www.nature.com/articles/s41467-021-21617-2   " ‘M1-like’ inflammatory macrophages utilize aerobic glycolysis for the generation of ATP. This is accompanied with a downregulation of mitochondrial oxidative phosphorylation (OxPhos) and an accumulation of certain metabolites in the tricarboxylic acid (TCA) cycle, such as citrate and succinate 2 , 3 . IL-10 increases arginase expression to limit the availability of arginine for NO production 13 , 17 . In fact, IL-10 was shown to regulate macrophage glycolytic commitment by preserving OxPhos through its suppression of NO 18 or via suppression of mammalian target of rapamycin (mTOR) 19 . It has also been shown that IL-10, via STAT3, inhibits the pro-inflammatory microRNA miR-155 20 . IL-10 was shown to modulate miR-155 target genes suggesting a distinct mechanism that IL-10 uses to maintain an anti-inflammatory s...

  Making Reproductive Longevity a Reality | Episode 3 - March 5, 2021 4:26 Start of Dr Ivana Celic on LINE1 retrotransposons in reproductive aging   11:12 Impact of LINE1 on genome structure { holy moly }   12:55 LINE1 mRNA can induce interferon response - inflammatory diseases and aging   14:55 LINE1 and Germ Cells ; spermatogenesis   17:31 LINE1 and fetal follicular atresia   18:59 Aging and LINE1in somatic tissue - upregulation of LINE1 due to changes in chromatin and methylation status 29:09 Start of Dr Carlos Ribeiro on nutrients, neuronal circuits and microbiome ...   38:31 Sodium (salt) is needed for reproduction   43:24 gut bacteria in Drosophila can produce essential amino acids needed for reproduction   https://www.nature.com/articles/s41467-020-18049-9   Comment: 50:32 re: salt consumption and preeclampsia   One way to get around the problem might be miso, which contains sodium, but its consumption has b...

Stomach acid suppression can result in deficiencies of B12, calcium and other important nutrients. B12 is needed for tetrahydrobiopterin production which is in turn a cofactor for nitric oxide [NO] synthesis by nitric oxide synthase [NOS]. Also, nitrite is converted in the presence of stomach acid to nitrous acid, which then forms NO. So it seems plausible that the association of cardiovascular disease with long-term proton pump inhibitor [PPI] use could be due to lowered production of NO as the result of acid reduction. However, other mechanisms may be at work, and may be more significant -  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864131/   "The evidence obtained in the aforementioned studies suggest that the underlying mechanism for cardiovascular effects of PPIs are not directly related to acid suppression, since H2-receptor antagonists are not associated with the cardiovascular risk [45, 46]. " Another explanation for the association is that PPIs inhibit PON1 ( in...

Stuff I wrote on YT comments in response to a question of mosaicism and aging: "Interesting question, especially with respect to neurodegeneration (may partly explain the phenomenon of selective vulnerability as well as some sporadic cases of neurodegenerative diseases). There is a related article I would like to link to, but YT does not seem to allow that anymore. The article can be found by googling "Brain discovery explains a great mystery of Alzheimer's, Parkinson's" (February 15, 2019) about research conducted by Michael McConnell of UVA." { But I can link to it here (stupid YT) } https://www.sciencedaily.com/releases/2019/02/190215135835.htm Then found some YT videos on the topic ... "This one is technical - https://youtu.be/y-XWoEjsg5Y   The main takeaways for me were that there are distinct signatures for somatic mutations acquired during development and for those accrued during aging, and that chromothr...

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...