The Rhyothemis princeps Brain Externalization Project

Dr Ruslan Medzhitov presented 'What is a disease' at the inaugural meeting of the International Society for Evolution, Medicine and Public Health held March 19-21, 2015. Interesting perspective on the causes of type 2 diabetes and diseases of aging. 9:13 Robustness, resilience and vulnerability   15:45 Anna Karenina Principle in Life History Theory - only one way an environment can be perfect and many ways it can be hostile   16:00 Homeostasis - Maintenance - Defense 17:58 taking out the garbage is not part of homeostasis, it's a function of maintenance   20:24 Extrinsic and Intrinsic Mortality - investment in maintenance programs is dictated by extrinsic mortality rates   32:00 systems that have adjustable set points are vulnerable to dysregulation example: insulin signalling pathway - change in glucose allocation to fetus in pregnancy or to immune system in infection "That built-in property to change the set point of the insulin system also makes it vulnerab

While most proteins are degraded during digestion, some fibrinolytic enzymes and prions can be resistant to digestion and there is evidence for their intestinal absorption. Nattokinase has been reported to be orally bioavailable [1], though some have told me they discount the study by Ero et al. (2013), citing that it was  funded by a supplement maker that sells nattokinase (I can't verify the sponsorship of the study since the article is paywalled). Of course, clinical trials for most new prescription drugs sold in the United States are funded by the pharmaceutical companies that make them. Gastrointestinal absorption of lumbrokinase was also demonstrated by Yan et al. (2010) [2]; the authors propose some possible mechanisms: "Gastrointestinal absorption of macromolecules, such as, proteins can be explained by three mechanisms as follows [16,17]. First, proteins are absorbed via receptor mediated endocytosis are as some growth factors. Second, proteins are absorbed by

"Aquaporin water channels - from transfusion medicine to malaria" by Dr. Peter Agre Sept. 9, 2015 22:22 Rarity of AQP1 null mutants despite apparently limited effect on phenotype - at birth lung goes from being secretory organ to being absorptive, may be a critical point 25:46 AQP4 and blood brain barrier { not mentioned in lecture: Evidence that pericytes regulate aquaporin-4 polarization in mouse cortical astrocytes https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223569/ }   26:54 AQP4 - accelerated brain damage   27:49 in many cases or stroke the individual succumbs not to the infarct, but to brain edema 30:04 Aquaporins, stress response , decline in function with aging   41:34 AQP7 and AQP9 - Glycerol Metabolism AQP7 - present in fat; water & glycerol permeation; suppressed by insulin; releases glycerol from fat catabolism during starvation AQP9 - present in liver; water, glycerol & urea permeation; facilitates hepatic glycerol uptake for gluconeogen

[2020-7-13] Someone posted about nocturia on HealthUnlocked's Parkinson's Movement forum and I replied with the  following (I don't think I can keep up with doing the reference properly, perhaps if it starts to really bother me I will edit): Apart from prostate and autonomic nervous system problems, one issue in aging related to nocturia might be loss of function of aquaporins. Aquaporins are membrane channels for water; though water can diffuse across cell membranes AQPs move water faster and are particularly important under stress conditions. AQP function declines with age and could contribute to many age-related health issues including reduction in blood brain barrier function. hindawi.com/journals/omcl/2... ncbi.nlm.nih.gov/pmc/articl... Oxytocin has some vassopressin-like activity and helps move AQP from inside the cell to the membrane surface when needed. jasn.asnjournals.org/conten... Oxytocin levels decline with age: ncbi.nlm.nih.gov/pmc/articl... The probiot

The Biochemical Society posted a recording of a fascinating webinar titled ACE2: Friend or Foe. I have indexed the third portion, a talk by Prof Michael Bader on the non-enzymatic functions of ACE2. I hope to index the other portions soon. Highlights:  - ACE2 enzymatic function is not affected by SARS-CoV-2 binding. Dr Roger Seheult, a pulmonologist, and others have proposed what I thought to be a quite plausible hypothesis that loss of ACE2 function due to SARS-CoV-2 binding results in high levels of oxidative stress which in turn causes hypercoagulability and attendant pathologies. Loss of ACE2 activity may be occurring due to reduced ACE2 transcription, however [ see previous post on this ]. - Vascular pericytes are potential targets of infection (very interesting, IMHO) - AT2 pneumocytes are targets of infection in lung tissue - loss of ACE2 results in reduced tryptophan uptake due to loss of amino acid transport function > reduction in serotonin production > loss of exercis

[2020-07-07] Fadason et al. (2020)           A preprint  by Fadason et al. [1] discusses a mechanism by which SARS-CoV-2 could alter gene expression of ACE2 and associated genes and produce a host environment that favors its replication. In doing so, it looks like the virus not only 'takes out' ACE2 by binding with its catalytic domain (see update below), it may also decrease ACE2 expression. I am not familiar with this type of alteration of chromatin structure and I don't know how long lasting the changes could be. Some epigenetic alterations can be quite long lasting, even multi-generational.         S everal genes in the network that are also affected impact lipid metabolism and gluconeogenesis. Gluconeogenesis can also be a response to hypoxia [2] and is a common feature of the acute phase response in both infection and injury [5].                      The article does not discuss changes in collectrin expression. The collectrin and ACE2 genes are located on the X chro

[2020-07-03] Presentation by Ruslan Medzhitov from 2018 titled "Inflammation and Disease Tolerance: Surviving Acute Illness" 1:25 cost of inflammation and cost vs. benefit trade-off 4:01 sickness behaviors, includes loss of appetite - observed in all animals including insects   5:10 Decreased Food Intake After Listeria Infection - disease induced anorexia   6:32 Anorexia Protects Against Listeria Infection (survival rate)   7:43 Glucose is Sufficient for Lethality in Listeria Infection - even at only 2% of normal caloric intake 8:26 2DG (inhibits metabolism of glucose) increased survivorship (100% survival vs. 50% without 2DG)   9:06 Effects of Feeding on Sepsis Survival - sepsis model using lipopolysaccharide (LPS) injection - same results found for feeding, glucose and 2DG experiments   11:10 Effects of Glucose in LPS Sepsis is Independent of Magnitude of Inflammation   11:48 Mechanism for Glucose-mediated Death in Bacterial Inflammation - review of fasting metab

[2020-07-01] Procalcitonin in Emergency Department Patients With Suspected COVID-19 Presentation  by Dr. Charles Cairns On using biomarkers (classifiers) to distinguish between causes of acute inflammation (infectious vs non infectious, bacterial vs viral, co-infections) with emphasis on procalcitonin. Procalcitonin is elevated in severe covid, but not in non-severe (95% of cases)   5:37 inflammatory response over the time course of infection / injury recovery   12:15 sepsis survivors vs. sepsis non-survivors gene expression profile shows marked difference   16:54 procalcitonin (PCT) is a prohormone of calcitonin ; elevated PCT levels indicate bacterial infection accompanied by systemic inflammatory reaction   24:28 nice diagram of events in SARS-CoV-2 infection   25:09 another really nice diagram { seems to indicate that antibody dependent enhancement can occur in the course of a single infection, rather than during a re-infection }   29:11 laboratory parameters in covid-19 pat

[2020-06-30] Interesting finding reported by Prostiv et al. earlier this year [1] - human body temperature has decreased in the US since the Industrial Revolution. The authors suggest the change is due to a reduction in chronic inflammation: "Although there are many factors that influence resting metabolic rate, change in the population-level of inflammation seems the most plausible explanation for the observed decrease in temperature over time. Economic development, improved standards of living and sanitation, decreased chronic infections from war injuries, improved dental hygiene, the waning of tuberculosis and malaria infections, and the dawn of the antibiotic age together are likely to have decreased chronic inflammation since the 19 th century. ... Reduction in inflammation may also explain the continued drop in temperature observed between the two more modern cohorts: NHANES and STRIDE. Although many chronic infections had been conquered before the NHANES study, s

There's this book I want to get, Hochachka and Somero's Biochemical Adaptation (or the latest edition, which is  by Somero et al.); of course since it is a science book it is ridiculously expensive and there's no ILL in a pandemic. The book has some interesting passages (p. 402) on Na/K ATPase that are visible on Google Books preview. I took a snip since there's no cut and paste: Main points: - futile cycling of ions may play a vital role in thermogenesis - Na/K ATPase may account for 5-10% of BMR - there are differences in Na/K ATPase activity between ectotherms and endotherms - 7x higher activity in mammals - "Correlated with this difference in estimated costs of sodium pump activity were differences in in the rates if passive efflux of K+ and passive influx of Na+ in liver cells. The costs of maintaining transmembrane gradients in concentrations of Na+ and K+ are reflected in differences in sodium pump-dependent oxygen consumption." - the degree of differen

In the post on osteocalcin that I can never quite finish I paraphrased a review on the topic that suggested that undercarboxylated osteocalcin may be one of the anti-aging factors present in 'young blood'.  Heterochronic parabioss experiments - wherein the circulatory systems of an old and a young mouse are joined - have shown rejuvenating effects for the old mouse and some age-promotion in the young. This has lead to speculation that there are youth-promoting factors in the blood of the younger mouse that provide benefit to the older mouse.  However the Conboys and their research team, who pioneered heterochronic parabiosis experiments, have proposed that it is actually dilution of pro-aging factors that provides the age-reversing effects. They recently published an article [Mehdipour et al. 2020] showing dilution of the blood of an old mouse is sufficient for rejuvenation.  From the article: "The above concept fits well with the age-imposed increase in systemic TGF-beta

[2020-06-13] Talk by Kelvin J.A. Davies on Lon protease from 2013(?) 12:56 Degradation of oxidized proteins by proteasome is mostly ATP independent; degradation by Lon is ATP dependent   20:08 the most decreased mRNA in skeletal muscle in mice in aging is Lon 20:36 the main one that comes up is aconitase, but there are many, many others   20:17 Lon inducibility is diminished in senescent cells & they have more carbonylated proteins   22:20 slide - Aging Decreases Lon Induction and Stress Protection 26:28 Lon attaches to mtDNA and allows for biogenesis; under stress it detaches and degrades oxidized proteins and at that point proliferation stops   28:59 Lon is inducible by H2O2, heat stress, starvation, cold stress, mechanical shear stress, peroxynitrite Also, loss of frataxin upregulates Lon and ClpP proteases and results in too much degradation of Fe-S proteins [1]. 1 - Guillon, Blanche, Anne-Laure Bulteau, Marie Wattenhofer-Donzé, Stéphane Schmucker, Bertrand Friguet,