The Rhyothemis princeps Brain Externalization Project

  Dr. Crystal Ripplinger 5:40 nerve:myocyte ratio similar to capillary myocyte ratio; all myocytes in ventricular myocardium are in contact with at least one neuronal process     6:27 more nerves at base of heart than apex, more sympathetic in epicardium, more parasympathetic in endocardium   11:15 how sympathetic nerve loss contributes to arrhythmia post-myocardial infarction (heart attack) 12:52 heterogeneity in innervation can be arrhythmogenic   13:02 nerve loss, lack of norepinephrine can lead to beta adrenergic receptor hypersenstitivity & supersensitive response to neurotransmitters     14:03 Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic regeneration after infarction, also prevent spinal cord regeneration   20:22 localized lesioning with anti-DBH-saporin; anti-dopamine beta hydroxylase antibody conjugated to toxin that gets into cell via synaptic vesicle   28:30 differences between larger animals (rabbits) and mice in how sympathetic stimulation

The eat 'five a day' (referring to servings of fruits and vegetables) recommendation of the World Health Organization and many national health agencies has new support based on findings by Wang et al. (2021) from the Nurses' Health Study and the Health Professionals Follow-up Study.   - link to open access article: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.048996 The study found a reduction in all-cause mortality as well as reductions in mortality due to respiratory diseases, cardiovascular disease and cancer. The thresholds for reductions in mortality were achieved at two servings of fruit and three servings of vegetables per day. No additional benefit was seen for over five servings. Sadly, there was no significant reduction found for neurodegenerative diseases (but see the Michley et al. (2017, open access) study on Parkinson disease re: fresh vs. canned/frozen). Wang et al. (2021) Above is Figure 1 from Wang et al. (2021); it is quite small and th

 Another reason why infants are prone to methemoglobinemia is that fetal hemoglobin is more easily oxidized.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071541/ "Methemoglobinemia has been reported in young infants (<6 months) in whom severe metabolic acidosis develops from diarrhea and dehydration. 7 Young infants may be particularly susceptible to this complication because of their low stomach acid production, large number of nitrite-reducing bacteria, and the relatively easy oxidation of fetal hemoglobin. Small infants have lower erythrocyte levels of cytochrome b reductase. 8 Higher intestinal pH of infants may promote the growth of gram-negative organisms that convert dietary nitrates to nitrites." ~ I was reminded of  fetal hemoglobin when I watched a video recently where persistence of fetal hemoglobin as a rescue mutation for thalassemia was discussed; here's my comment on it: https://youtu.be/ml1svbRo7Lg?t=990  Great interview. I'm sure this wi

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 transplantation? }

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-diagnos

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 state in

  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 been shown to not increase blood pressure generally (th

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