79,000 reasons to believe in biophysical constraints

See also: 10,000 reasons to believe in biophysical constraints

There once was a time when nobody knew how to do it. Now, anyone who fails to place their research results into the context of a model that must link energy-dependent changes from angstroms to ecosystems and biophysically constrained viral latency in species from microbes to man will not fare well among the serious scientists with their academic pursuits.

Reason #1 The synthesis of RNA in isolated thymus nuclei is ATP dependent. (McEwen et al., 1964)

That fact was represented for ages 10+ in Subatomic and Cytosis.

Taken together, the creation of subatomic particles is linked to biophysically constrained viral latency by light-activated microRNA biogenesis in plants.

See also: The Influence of MicroRNAs on Mitochondrial Calcium

The potential for miRNA therapeutics is limitless, and could be applied to any disease, including Alzheimers, Parkinson’s, cancer, and heart failure, which are characterized by alterations in their MitomiR profiles.

Most serious scientists know this fact is like a death blow to “Big Pharma” as it is known for side effects that may do more harm than their medications and vaccines do good. MicroRNA therapeutics link naturally occurring RNA-mediated DNA repair to healthy longevity. What naturally occurs, typically constrains virus-driven pathology.

Reasons # 1-79,000+ See: microRNA

Add the most recent entry from researchers in Beijing, China:  Dissection of RNAi-based antiviral immunity in plants

RNA interference (RNAi)-based antiviral defense is a small RNA-dependent repression mechanism of plants to against viruses. Although the core components of antiviral RNAi are well known, it is unclear whether additional factors exist that regulate RNAi. Recently, a forward genetic screen identified two novel components of antiviral RNAi, providing important insights into the antiviral RNAi mechanism. Meanwhile, it was discovered that microRNAs make important contributions to host antiviral RNAi. On the other hand, to counteract host antiviral RNAi, most viruses encode viral suppressors of RNA silencing (VSRs). Recent studies have revealed the multiple functions of VSRs and the intricate interactions between plant hosts and viruses. These findings add to our knowledge of the sophisticated host antiviral defense mechanism in plants. Ongoing molecular functional studies will improve our understanding of the co-evolutionary arms race between viruses and plants, and thereby provide key information for the development of plant antiviral strategies.

There is no co-evolutionary arms race between viruses and plants. The anti-viral RNAi mechanism is light-activated. Viral suppressors of RNA silencing (VSRs) are energy-dependent and the antiviral defense mechanism in plants has been linked via the physiology of reproduction to changes in angstroms to ecosystems in all living genera.

See: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems

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 nutrientdependent 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 also: Get Well in the RNAi Way-RNAi, A Billion Dollar Baby in Therapy

RNAi has targeted exogenous genes in models of viral infection…

See for support of the claims in my 2018 monograph:

A recent entry from a researcher in South Korea who collaborated with researchers from Argentina:  A Quick HYL1-Dependent Reactivation of MicroRNA Production Is Required for a Proper Developmental Response after Extended Periods of Light Deprivation (July 16, 2018)

…plants alter microRNA (miRNA) biogenesis in response to light transition.

The creation of the sun’s anti-entropic virudal energy has been linked from the light transitions in plants to ecological adaptations in the context of the Seneca Valley Virus. See Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus.

Our refined atomic model of the SVV-ANTXR1 complex suggests that hydrogen-bonding (H-bond) interactions are exclusive to the VP1-ANTXR1 and VP2-ANTXR1 interfaces, whereas a variety of amino acid interactions are shared among all three interfaces.

Interestingly, these residues were found to be among the key amino acids governing the striking difference in PA-binding affinities between ANTXR1 and ANTXR2 in previous studies (29).

The so-called “residues” from the so-called “atomic model” link energy-dependent changes in base pairs in my model  to the fixation of amino acid substitutions in the bacterium, Bacillus anthracis. No other model links energy-dependent changes from angstroms to ecosystems via nutrient-dependent pheromone-controlled biophysically constrained viral latency in bacteria and ecological adaptations to viruses in species from microbes to humans.

For example, Seneca Valley Virus (SVV) is not a human pathogen. Anthrax is a pathogen that has ecologically adapted to SVV.

From a historical perspective, anthrax can now be linked from pheromone-controlled ecological adaptations in bacrteria to problems with viruses in the context of Homeland Security.

Sci-fi author Greg Bear tells Jon about the not-so-distant future of technology and helping Homeland Security. (video)

Serious scientists have linked the ecological adaptations to SVV to the pathogenicity of anthrax and other viruses and the pathogenicity if soil bacteria via the sun’s anti-entropic virucidal energy. See: What is Life?

Indeed, in the case of higher animals we know the kind of orderliness they feed upon well enough, viz. the extremely well-ordered state of matter in more or less complicated organic compounds, which serve them as foodstuffs. After utilizing it they return it in a very much degraded form -not entirely degraded, however, for plants can still make use of it. (These, of course, have their most power supply of ‘negative entropy’ the sunlight.) (pp. 73 and 74)

Plants make use of the bacteria in soil to link light and water to thermodynamic cycles of growth. The combination links everything known about biophysically constrained viral latency to healthy longevity.

See: What is life when it is not protected from virus driven entropy

The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair. In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans. Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry. Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.

In the early 1990s, Bruce McEwen told me I would need to start with gene activation or my model could not be validated. See also the most recent reports from: B.S. Mcewen and others who have linked energy-dependent changes in base pairs from epigenetic effects on biophysically constrained fixation of amino acid substitutions to morphological and behavioral traits in animal models.

314.12 / RR2 – Chronic immobilization stress primes the hippocampal opioid system for oxycodone associated learning in female but not male rats

…oxycodone conditioned place preference (CPP) induces sex-dependent changes in the redistribution of the hippocampal opioid receptors in a manner that promotes excitation and drug-related learning processes…

317.18. Rapid behavioral responses to treatment with ketamine or acetyl-L-carnitine in males and females

Our work suggests that LAC is superior to ketamine in ameliorating depressive-like symptoms in experimental rodent models. Further research should focus on elucidating the mechanisms of LAC action, including the suggested role of mGlu2 receptors in the vHip.

315.15. Sex-specific behavioral endocrinology of BDNF Val66Met mice maintained on chronic oral corticosterone

…we demonstrated that CORT significantly decreased z-score in Het-Met females but had an opposite effect in WT and Het-Met males. These findings indicate that the chronic oral CORT model highlights sex-specific sensitivity to CORT overexposure that intersects the Met genotype.

315.16. Cross-species epigenetic signature of stress-related psychiatric disorders

…the BDNF Met allele induces an epigenetic signature that recapitulates that of subjects who are vulnerable for major psychiatric disorders. Animal models of stress-related disorders can help shed light on epigenetic markers conserved across species relevant for novel diagnostic and therapeutic interventions.

317.16. Role for mGlu2 receptors in a circuit signaling mechanism underlying rapid behavioral responses to LAC

Re: acetyl-L-carnitine (LAC)

This data shows that the action of LAC involves key synaptic plasticity markers that are known targets for the rapid antidepressant action of ketamine. Therefore, this data suggests that regulation a yet-to-be-determined common pathway in a circuit between the vHip and mPFC may be required for rapid antidepressant action.

See also: Effects of Carnitine on Fatty-Acid Oxidation by Muscle (1959) It may help you to learn how to ask Bruce McEwen or others relevant questions about how serum fatty acids are transported via blood vessels through the interstitial space to the active sites for oxidation in muscle cells. For example, “Is all transport via the food energy-dependent creation of microRNAs in the blood of mammals?”

317.17. Acetyl-L-carnitine deficiency in patients with major depressive disorder: Implications for treatment resistant depression

…decrease in LAC was larger and was associated with history of childhood trauma, and specifically emotional neglect. Supported by an initial validation in two independent cohorts, these findings suggest that the LAC deficiency may aid with the diagnosis of a clinical phenotype of depression. Further studies of LAC as a therapeutic target may help to define individualized treatments in biologically-based depression subtype consistent with the spirit of precision medicine.

592.04. Individual difference of aggression and interleukin 1 beta in the dorsal raphe nucleus

…our results indicate that IL-1R mediated pathways in the DRN have an inhibitory role on aggressive behavior.

593.09. Effects of dorsal hippocampal inhibition of actin polymerization or protein synthesis on rapid estrogen-facilitated social recognition, dendritic spines, and Arc protein expression in ovariectomized female mice

…actin polymerization and protein synthesis were found to be necessary for E2 to rapidly facilitate social recognition. Brains from these animals were collected and either stained with Golgi-Cox solution to evaluate dendritic spine density and length in the dorsal CA1 or were used to determine the effects of treatment on Activity-regulated cytoskeleton-associated protein (Arc) expression, as a potential target of estrogen action. These studies provide a mechanism through which estrogens rapidly facilitate social recognition.

698.03. Exploring differences in hippocampal gene expression across three different animal models of mood disorder: Prototyping a meta-analysis pipeline

These differentially expressed genes are enriched within particular biological pathways: down-regulated genes are enriched within pathways related to synaptic function, and upregulated genes are enriched within pathways related to cell adhesion, vascular development, extracellular matrix, methylation, and inflammation. We conclude that it is beneficial to integrate results from various different models in order to understand the neurobiology of mood disorder.

762.15. The monocytic inflammatory response to head trauma is contained by Apobec1-mediated RNA editing

This data suggests lack of Apobec1-mediated RNA-editing may exacerbate the secondary injury response and alter mTBI-induced neurogenesis.

Loss of APOBEC1 RNA-editing function in microglia exacerbates age-related CNS pathophysiology (2017)

These data provide powerful evidence supporting the critical role of APOBEC1-mediated RNA editing in maintaining the balance between the homeostatic and activated immune functions of MG.

See also: Redefining neuroendocrinology: Epigenetics of brain-body communication over the life course (2017)

See also: Human APOBEC3G prevents emergence of infectious endogenous retrovirus in mice (2018)

Anyone who thinks they can start from anything except the energy-dependent creation of RNA may be living in a world of their own, or one that is shared only with biologically uninformed science idiots. Most of the idiots have failed to link anything to the prevention of the “emergence” of infectious ERVs because they did not know how to link sunlight to the creation of microRNAs in the context of more than 79,000 published works and Feynman’s claims about food energy-dependent units of energy.

Author: James Kohl

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