Measuring pH links what is known about nutritional epigenetics from the innate immune system to healthy longevity via everything known about autophagy. The measurements can be compared in the context of what is known about virus-driven energy theft, which links stress from the replication of viruses to all pathology via critical care testing of other blood gas analytes such as pCO2, pO2, Sodium, Potassium, Chloride, Calcium, Glucose, Lactic Acid, and Hematocrit.
For example in a mammal, see: Epistasis Among Adaptive Mutations in Deer Mouse Hemoglobin (June 14, 2013)
See Fig. 2 Difference in the network of hydrogen bonds between high- and low-altitude Hb variants, HH-H and LL-L, respectively.
My comment to the Science site (submitted 6/14/13 published 6/20/13):
In my model species-specific epistasis is nutrient-dependent and pheromone-controlled. An additional example of this showed up earlier this week in the context of the epigenetically-effected microRNA/messenger RNA balance: “miR-124 controls male reproductive success in Drosophila”
miR-14 acts in neurosecretory cells in the adult brain to control metabolism and miR-124 acts in the context of brain-directed neuroendocrine control of sexual differentiation and male pheromone production, which is controlled in mammals by gonadotropin-releasing hormone (GnRH) neurosecretory cells of the hypothalamus.
We can anticipate extension to mammals of the Drosophila model from the abstract of a forthcoming Science article: “MiR-200b and miR-429 Function in Mouse Ovulation and Are Essential for Female Fertility.” Given our earlier work in the context of molecular epigenetics and the concept of alternative splicings and sexual differentiation in Drosophila and C. elegans, I suspect we will see evidence for nutrient-dependent adaptive evolution of GnRH pulse frequency-controlled LH secretion and pheromone-controlled female fertility in mice.
If I’m correct, this evidence will link glucose and pheromones to feedback loops that control reproduction in invertebrates and vertebrates. (See Nutrient–dependent / pheromone–controlled adaptive evolution: a model). Model organisms exemplify these feedback loops in microbes, nematodes, insects, and other mammals. The mouse to human example that Kamberov et al., and Grossman et al., detailed is the most telling.
A single amino acid substitution appears to result in what seem to be nutrient-dependent changes in the thermodynamics of intracellular signaling, intranuclear interactions, stochastic gene expression, and selection for phenotype via organism-level thermoregulation in a human population that arose in what is now central China during the past ~30K years.
Using a model that integrates what is known about the common molecular mechanisms may help establish whether adaptive mutations lead to thermodynamic effects on organism-level thermoregulation and epistasis, or whether epigenetic effects of nutrients and their metabolism to species-specific pheromones that control reproduction via changes in the microRNA/messenger RNA balance are the driving force behind adaptive evolution in species from microbes to man.
See: Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys
Reported as: Estrogen discovery could shed new light on fertility problems December 12, 2017
Estradiol builds in the bloodstream until it reaches a concentration that causes a surge of the hypothalamic and pituitary hormones, including one called luteinizing hormone, which in turn trigger an ovary to release an egg.
“It’s a feedback loop…
The feedback loop is food energy-dependent and pheromone-controlled.
See: Feedback loops link odor and pheromone signaling with reproduction
Energy-dependent autophagy is the link from feedback loops to ecological adaptation. Science Magazine now has the opportunity to challenge the pseudoscientific nonsense of published works from the Nature Publishing Group. There is no need to consider mutations and evolution outside the context of virus-driven energy theft, which links the degradation of messenger RNA from mutations to all pathology.
See also: Combating Evolution to Fight Disease
Darwin probably anticipated the insemination of population genetics that led to the bastardization of his detailed observations in the “Modern Synthesis.” He politely insisted that ‘conditions of life’ be considered before natural selection.
There are two ‘conditions of life.’ It is nutrient-dependent and pheromone-controlled. Rosenberg and Queitsch now note the work with Dobzhansky’s rarely acknowledged claim: “I am a creationist and an evolutionist.” They also declare the need for “Deep understanding of the mechanisms that generate variation at the molecular level…”
Deep understanding of the ‘conditions of life’ does not come from theory.
Problems with the “modern synthesis” now lead us back to the facts about biologically-based cause and effect that Darwin and Dobzhansky approached with humility, which are the same biological facts that evolutionists approached with ignorance about behavioral affects and the arrogance that accompanies that ignorance. Rosenberg and Queitsch echo the sentiments of those who have been subjected to academic suppression.
Clearly, however, “nothing in evolution makes sense except in the light of biology” is not an exaggeration. It is a common sense statement about the biologically plausible genesis of functional cell types. Population genetics and evolutionary theories abandoned the biophysical constraints of ecological variation and the physiology of reproduction, which enable epigenetically-effected nutrient-dependent pheromone-controlled receptor-mediated ecological adaptations and species diversity via the complexities of protein folding and niche construction.
It’s time for biophysicists to tell theorists and pathologists how to differentiate between theories about the genesis of different cell types and the biological facts about the nutrient-dependent pheromone-controlled ecological adaptations that enable the genesis of different cell types in individuals of different species. Simply put, it’s time to stop trying to explain ecological adaptations in the context of mutations and evolution.
The retraction of Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication attests to the amount of pseudoscientific nonsense published by the “Nature Publications Group” during the past few decades.
See: Retraction Watch
In retrospect, we were totally blinded by our belief [in our findings]…we were not as careful or rigorous as we should have been (and as Tivoli was) in interpreting these experiments.
How many others who published via the Nature Publishing Group were blinded by their belief in pseudoscientific nonsense that failed to link the food energy-dependent creation of enzymes and the creation of RNA from blood gas analyses to patient outcomes?
See for comparison: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)
The synthesis of RNA in isolated thymus nuclei is ATP dependent.
Who did not know that? How did non-enzymatic RNA replication become a non-energy-dependent consideration for anyone associated with the Nature Publishing Group?
See for comparison: Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40
Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB–mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis.
The global conformational change that allosterically realigns active-site residues (i.e., amino acids), accelerating catalysis, is an energy-dependent change.
Reported as: Scientists unlock structure of mTOR, a key cancer cell signaling protein
1) Like many proteins, mTOR is an enzyme, which binds to target molecules called substrates in a precise way to hasten chemical reactions. Specifically, it is a type of kinase, which removes phosphates (P) from ATP, the cell’s energy currency, and places them on other molecules.
The creation of the enzymatic activity of mTOR is quantized energy-dependent and it links the pheromone-controlled physiology of reproduction to biophysically constrained viral latency via autophagy. The retractions of Jack Szostak’s nonsense about the magical creation of enzymes after the energy of life emerged and organisms subsequently evolved in the context of differences in H2 to all biodiversity on Earth, can be placed into the context works by serious scientists.
2) …mTOR is an enzyme, which binds to target molecules called substrates in a precise way to hasten chemical reactions. Specifically, it is a type of kinase, which removes phosphates (P) from ATP, the cell’s energy currency, and places them on other molecules. From that 2013 study, which took more than five years to complete, the team learned some key things about the protein, such as what the ATP-binding site looks like…