The Rhyothemis princeps Brain Externalization Project

Read a bit about lipid metabolism in PD https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099649/ "Since oligomers seem to be the toxic species rather than fibrils, we believe that the increasing DHA concentration in the cell could worsen toxicity rather than having a protective role." oh dear Eating fish is associated with reduced risk of PD - but maybe the benefit is from beta parvalbumin?? ~ A clinical trial published in 2019 found omega-3 from flax plus vitamin E to be beneficial in PD - though of course flax does not contain DHA, but ALA which may be converted to DHA - but not very efficiently & there are sex differences (reproductive age women do so more efficiently than others) https://www.sciencedirect.com/science/article/abs/pii/S0303846718304633 ~ Seems like fibrates would be helpful, but one study in a rat models says no https://pubmed.ncbi.nlm.nih.gov/28403913/ but brilliant blue G, a P2X7R anatgonist, was beneficial ~ Cereblon - "Our study reveals a novel ...

These notes are to keep track of things I am reading up on and thinking about and perhaps may write a post on in future. I making them public because - why not? Also, I may never get a chance to write a full post on them. ~~~ MSA, glycine & EPO    Related references are tagged MSA-EPO-Gly on my zotero account and listed below. Lithium trial for multiple system atrophy (MSA) had to be stopped as it caused harm - quite severe harm. One proposed MOA for lithium for biopolar and other disorders where it has been found to be therapeutic is that it increases glycine levels in the brain. However, this hypothesis appears to have been abandoned in recent years and does not have much empirical support - though nothing in the way of  disconfirming findings has turned up so far in literature searches, either. Elevated levels of glycine in cerebrospinal fluid (CSF) have been found in DLB, ALS and MS. Results of studies on PD patients has been conflicting, but the bulk of evidence ...

Is it possible that machine learning-assisted anthropometric analysis could provide better risk assessment than genetic screening for cancer or other conditions (e.g., connective tissue disorders, heart failure, etc.)?  Relative proportions are reflective of relative growth rates of organs and tissues which in turn are the product of both genes and environment and are dependent on factors such as the balance of growth hormones and nutrient intakes. It seems that if a large number of individuals were scanned photographically - or much better with MRI (since more interesting measurements could be taken, e.g. width of the aorta) and the scans were provided as input, along with data from their health records, to an appropriately designed  machine learning algorithm, it may be possible to  predict risk of various diseases based on anthropometric parameters alone. This occurred to me just prior to learning that a new company, Ezra, is offering whole body MRI scans for ...

Since March, I have been hoping someone would study whether covid-19 patients with type 2 diabetes (T2D) on metformin fare better than those on other types of anti-diabetes medications. Many of the risk factors associated with severe covid-19 (e.g., obesity, diabetes, hypertension, older age) relate to AMPK signalling and metformin, a drug that improves AMPK signalling, has been found to benefit these conditions.  My question has finally been answered  - T2D patients on metformin have a 70% reduced  risk of death as compared with those on other anti-diabetic medications [1,2]. Unfortunately the study did not control for other important factors such as age, degree of blood sugar control, BMI, and time since diagnosis; a future study designed specifically to examine metformin in covid-19 should be conducted that controls for these factors. The study authors discuss the potential role of AMPK signalling in covid-19, delineating a number of possible mechanisms by which it cou...

In trying to find information on the effect of radiation on aquaporins, a paper came up on a treatment for radiation-induced salivary hypofunction: Baum, Bruce J., Changyu Zheng, Ana P. Cotrim, Linda McCullagh, Corinne M. Goldsmith, Jaime S. Brahim, Jane C. Atkinson, et al. “Aquaporin-1 Gene Transfer to Correct Radiation-Induced Salivary Hypofunction.” Handbook of Experimental Pharmacology , no. 190 (2009): 403–18. https://doi.org/10.1007/978-3-540-79885-9_20 .           " Indeed, IR leads to a dramatic loss of the fluid secreting salivary acinar cells, resulting in severe glandular hypofunction (a diminished production of saliva) in most patients ( Vissink et al. 2003 ; Nagler and Baum 2003 ). The reason for this damage remains enigmatic, as salivary acinar cells are well differentiated and very slowly dividing, the opposite of the classical target cell for IR sensitivity [emphasis added] . If patients have sufficient functional acinar tissue p...

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 vulner...

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 glucone...

[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 exe...

[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 ar...