MicroRNA-mediated enhancer-promoter chemistry

Summary: The claim that loop extrusion and homotypic attraction are two antagonistic fundamental forces that are linked to what enhancer-promoter contacts and chromatin domains physically represent exemplifies human idiocy.

Regulatory Landscaping: How Enhancer-Promoter Communication Is Sculpted in 3D (6/20/19)

We focus on emerging views of what enhancer-promoter contacts and chromatin domains physically represent and how two antagonistic fundamental forces—loop extrusion and homotypic attraction—likely form them.

They refuse to focus on what is known to all serious scientists about the energy-dependent link from endogenous substrates to biophysically constrained viral latency and healthy longevity.

Substrate:

In chemistry, a substrate is typically the chemical species being observed in a chemical reaction, which reacts with a reagent to generate a product. In synthetic and organic chemistry, the substrate is the chemical of interest that is being modified.

Endogenous substances… originate from within a system such as an organism, tissue, or cell. The term is chiefly used in biology but also in other fields. Endogenous substances and processes contrast with exogenous ones, such as drugs, which originate from outside of the organism.

Vaccines are like drugs and genetically modified organisms (GMOs). They are exogenous sources of virus-driven pathology because they come from outside of the organism. Endogenous retroviruses are also sources of pathology when nutrient-stress and/or social stress reactivate them.

Chemists know that energy is required to modify the substrates of interest to biologists.  See Chemists Know. Theorists know nothing of importance for comparison.

Serious scientists detailed the importance of feedback loops that biophysically constrain viral latency via light-activated endogenous substrates. The substrates exemplify the eternal significance of microRNAs, which are the endogenous substrates. Simply put, endogenous substrates are the Alpha (Α or α) and omega (Ω or ω) of biologically-based cause and effect.

I didn’t know why in 1992, but Bruce McEwen told me that my model could not be validated unless I started with gene activation in gonadotropin releasing hormone neurosecretory neurons.  Since then, I learned that microRNAs are the endogenous substrates that link food odors and pheromones to the representations of biologically-based cause and effect in the model that he patiently discussed with me.

Others who have followed the extant literature will find evidence of confusion in claims of others about models. See: Ecological and evolutionary consequences of viral plasticity (2019)

For bacteriophages, this link between host and viral performance has been characterized empirically and with intracellular theories. Such theories are too detailed to be included in models that study host-phage interactions in the long term, which hinders our understanding of systems that range from pathogens infecting gut bacteria to marine phage shaping the oceans.

The theories are not well-detailed because they are based on other theories. Facts led to this model of host-phage interactions across kingdoms for comparison to their ridiculous claim that

…plasticity on the offspring number drives the phage ecological and evolutionary dynamics by reinforcing feedbacks between host, virus, and environment.

No offspring exist outside the context of Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems (4/11/18)

This angstroms to ecosystems model of ecological adaptation links nutrient energy-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA/messenger RNA balance and chromosomal rearrangements via the physiology of reproduction in species from microbes to humans. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experiencedependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity. Species-specific pheromones link quorum-sensing in microbes from chemical ecology to the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection for codon optimality links nutritional epigenetics to the behaviors that enable ecological adaptations. All biodiversity is an ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. Simply put, olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of supercoiled DNA in the organized genomes of species from microbes to man during their development.

See for validation: Exosome-delivered microRNAs modulate the inflammatory response to endotoxin (6/18/15)

…endogenous microRNAs undergo a functional transfer between immune cells and constitute a mechanism of regulating the inflammatory response.

See also: Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns (7/27/18)

MicroRNAs in milk exosomes are the substrates that exemplify how the eternal significance of microRNAs, which are the endogenous substrates, must be linked to all biodiversity across kingdoms to mammals via food odors and pheromones.

See: Unexpected Potential of Iso-oligosaccharides in the Generation of Important Food Odorants

The generation of selected Maillard-derived odorants from iso-oligosaccharides (IOSs), namely, from isomaltose, isomaltotriose, isomaltulose, and melibiose, was studied and… newly obtained data brought for the first time evidence about the extraordinary potential of IOSs in the formation of several potent food odorants.

The binary mixtures of sugar and the amino acids glycine, proline, and cysteine could have led them to proclaim the the fixation of achiral glycine in positon 6 of the GnRH decapeptide was the key to biophysically contrained viral latency and all diversity among all vertebrates with jaws.

But they missed the obvious connection to amino acid substitution-dependent biophysically constrained viral latency in invertebrates.

See: Pathway of 5-hydroxymethyl-2-furaldehyde formation in honey

…different content of proline, the most abundant amino acid in honey (a substance in Maillard reaction), had no effect on 5-HMF formation. Free acids in honey can catalyze fructose and glucose to form 5-HMF. These results suggest that dehydration of glucose or fructose, instead of the Maillard reaction, is the main pathway of 5-HMF formation in honey. This study gives new insights for the mechanisms of 5-HMF formation and provides method for reducing 5-HMF formation during honey processing.

Dehydration of glucose or fructose link the creation of the amino acid proline to the potential of hydrogen (pH). The energy of hydrogen comes from the sun. The effect of sunlight can be linked to all downstream effects on cell type differentiation by anyone who starts with the creation of sunlight and links it to pH and the creation of different amino acids, which change food odors, flavors, and colors across kingdoms.

See: The effect of pH and amino acids on the formation of methylglyoxal in a glucose-amino acid model system

Amino reactivity and pH were two important factors affecting the formation of MGO in the Maillard reaction.

The energy-dependent pH-dependent creation of amino acids and fixation of amino acid substitutions in the organized genomes of species from microbes to humans biophysically contrain viral latency. That fact makes the claims about enhancers and promoters appear to be among the claims made by biologically uninformed science idiots who know nothing about healthy longevity.

See also: Dietary Maillard reaction products and their fermented products reduce cardiovascular risk in an animal model

This study examined the effects of Maillard reaction products (MRP) and MRP fermented by lactic acid bacteria on antioxidants and their enhancement of cardiovascular health in ICR mouse and rat models. In previous in vitro studies, the selected lactic acid bacteria were shown to significantly affect the activity of MRP. The expression of genes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) related to antioxidant activity was upregulated by Maillard-reacted sodium caseinate (cMRP), and cMRP fermented by Lactobacillus fermentum H9 (F-cMRP) synergistically increased the expression of catalase and superoxide dismutase when compared with the high-cholesterol-diet group. Bleeding time, the assay for determination of antithrombotic activity, was significantly prolonged by Maillard-reacted whey protein concentration (wMRP) and wMRP fermented by Lactobacillus gasseri H10 (F-wMRP), similar to the bleeding time of the aspirin group (positive control). In addition, the acute pulmonary thromboembolism?induced mice overcame severe body paralysis or death in both the wMRP and the F-wMRP groups. In the serum-level experiment, cMRP and F-cMRP significantly reduced the serum total and low-density lipoprotein cholesterol levels and triglycerides but had only a slight effect on high-density lipoprotein cholesterol. The levels of aspartate transaminase and alanine transaminase also declined in the cMRP and F-cMRP intake groups compared with the high-cholesterol-diet group. In particular, F-cMRP showed the highest reducing effects on triglycerides, aspartate transaminase, and alanine transaminase. Moreover, the expression of cholesterol-related genes in the F-cMRP group demonstrated greater effects than for the cMRP group in the level of cholesterol 7 α-hydroxylase (CYP7A1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and low-density lipoprotein receptors compared with the high-cholesterol-diet group. The protective role of cMRP and F-cMRP in the high-cholesterol group may have been the result of an antioxidative defense mechanism that regulated cholesterol synthesis and metabolism. Therefore, F-cMRP and cMRP have the potential to play preventive and therapeutic roles in the management of cardiovascular disease.

See for comparison: microRNA “cardiovascular disease” Items: 1- 1156 and enhancer promoter “cardiovascular disease”Items: 1 to 57 and enhancer promoter “cardiovascular disease” microRNA 

Fibrinogen gene regulation (2012)

…we discuss regulation of the fibrinogen genes from proximal promoters and enhancers, the influence of acute-phase stimulation, post-transcriptional regulation by miRNAs and functional regulatory variants identified in genetic studies.

Non-coding RNAs as regulators of gene expression and epigenetics (2011)

Genome-wide studies have revealed that mammalian genomes are pervasively transcribed. This has led to the identification and isolation of novel classes of non-coding RNAs (ncRNAs) that influence gene expression by a variety of mechanisms. Here we review the characteristics and functions of regulatory ncRNAs in chromatin remodelling and at multiple levels of transcriptional and post-transcriptional regulation. We also describe the potential roles of ncRNAs in vascular biology and in mediating epigenetic modifications that might play roles in cardiovascular disease susceptibility. The emerging recognition of the diverse functions of ncRNAs in regulation of gene expression suggests that they may represent new targets for therapeutic intervention.

What has anyone who ever mentioned enhancers and promoters done to link microRNA-mediated enhancer-promoter chemistry to healthy longevity via what is known to all serious scientists about cardiovascular disease susceptibility or susceptibility to any other form of virus-driven pathology.

For comparison, see: microRNA Items: 1 to 88068

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Author: James Kohl

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