Constraints on microRNAs: Buried in patents

Theme: MicroRNAs are the pre-mRNAs from the past. That fact has since been buried in the patent on RNA-interference (aka RNA-guided human genome engineering).

Pheromones constrain gene regulation and systems complexity

[Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)] 8/1/1994

…results obtained during last 10-15 years are discussed. The adaptive role of cytogenetic and other observed pheromonal effects is considered. The possible existence of interorganism systems of genetic regulation is discussed, the search for and study of which may help in more complete understanding of the regularities of functioning of genetic material.

See also: Olfaction regulates organismal proteostasis and longevity via microRNA-dependent signalling 2/18/19 and: MicroRNA-dependent Items: 1 to 20 of 124

Although the article about how olfaction regulates microRNA-dependent signalling, organismal proteostasis, and longevity does not currently appear among 124 other published works linked to microRNA-mediated systems complexity, anyone who has followed the extant literature during the past few decades could have predicted the facts that have since been established.

Simply put, the metabolism of food by enzymes produces species-specific pheromones that biophysically constrain virus-driven pathology in all living genera. If others realized that pheromones regulate food energy-dependent genetic processes but failed to report it,  they have contributed to unnecessary suffering and premature death. That claim can be examined in the context of the extant literature.

Therein lies the problem. For example, see: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems 4/18/18

See also: Main constraints for RNAi induced by expressed long dsRNA in mouse cells 2/26/19

Although optimized endogenous Dicer substrates mimicking miRNA features could evolve for endogenous regulations, the same principles would make antiviral RNAi inefficient as viruses would adapt to avoid efficacy.

The problem with the adaptations of viruses was buried in this 2015 patent application RNA-Guided Human Genome Engineering

5. Repetitive elements or endogenous viral elements can be targeted with engineered Cas+gRNA systems in microbes, plants, animals, or human cells to reduce deleterious transposition or to aid in sequencing or other analytic genomic/transcriptomic/proteomic/diagnostic tools (in which nearly identical copies can be problematic).

Get it? The gene-editing technology cannot stop the viruses from adapting. It has been clear to many serious scientists for ~75 years that something, such as human endogenous retroviruses, causes the creation of nearly identical problematic copies. Thus, it became clear that the problematic copies caused by the endogenous viral elements must be biophysically constrained in the context of naturally occurring RNA interference, or life would not exist on Earth. That’s why money-making capitalists patented naturally occurring RNA interference as other less intelligent capitalists fought for patents on relatively useless technology.

See also: What is Life? (1944)

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.)

Schrodinger (1944) inadvertently or intentionally suggested that the creation of sunlight was the source of ‘negative entropy.’ He was not specific about the details, but was obviously many decades ahead of his time. Neo-Darwinian theorists and Big Bang cosmologists, for comparison, continued to fall further behind.

See: 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… 3/30/16

For comparison, listen to the discussion with George Church and the a16z bio general partner who also founded a company with Church.

a16z Podcast: What’s in the Water at the George Church Lab?

at 5:51

…it’s vandalism in the sense that it can add or delete a small number of base pairs, typically in the range of one to hundreds.

At 15:10 in the Edge video and audio, George establishes a link to Schrodinger (1944) with this claim:

…the cyanobacteria turn out that they fix light ah as well or better than land plants…

He subsequently claims

We found the enzymes that occur in nature, which was not obvious…

In the context of what is known about the energy-dependent creation of enzymes, this question arose more than a year ago:

Who thinks that light-activated carbon fixation is not obviously required to link the light-activated assembly of the microRNA-RNA-peptide nanocomplex from the creation of enzymes to naturally occurring RNA interference and the prevention/cure for all cancer?

It may be time to ask George Church and others to specify what they did not think was obvious about the need for anti-entropic energy in the context of the creation of enzymes, or to be more specific about the creation of how enzymes would be created outside the context of Schrodinger (1944).

See for instance:  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.

McEwen et al., (1964) made the facts about the energy-dependent link from the creation of Adenosine TriPosphate (ATP) and the ATPase enzymes to the synthesis of RNA perfectly clear. ATPases are enzymes that break down ATP into ADP and free phosphate ions, releasing energy. Without the creation of the ATPases and ATP, cell type differentiation could only occur outside the context of an anti-entropic virucidal source of energy. 

Indeed, that was recently suggested again. Genetic dissection of assortative mating behavior 2/7/19

Ecologically relevant mating cues (sometimes known as “magic traits” [2,6]) are now predicted to be widespread in nature [6,7],

All serious scientists know that cell type differentiation is energy-dependent and biophysically constrained by the epigenetic effects of food and pheromones in species from microbes to humans.

See also: Genetic and epigenetic engines of diversity in pathogenic microbes

Fig 1

Multiple pathways to phenotypic diversity lead to virulence.

Evolution can take any of multiple routes to enhance fitness and, in the case of pathogens, virulence. Here, we depict the 5 mechanisms of adaptation that we discuss in this review, which are only some of the myriad pathways available to microbes.

No experimental evidence suggests that evolution takes any route to enhanced fitness. More than 83,500 published works on microRNAs attest to the fact that link ecological variation to ecological adaptations in all living genera via the energy-dependent physiology of reproduction.

See for instance (in plants): The interaction between miR160 and miR165/166 in the control of leaf development and drought tolerance in Arabidopsis 2/16/19

If other pathways could be taken towards enhanced evolutionary fitness, the molecular mechanisms of energy-dependent biophysically constrained microRNA-mediated cell type differentiation might not have been clear at the time we included a section on molecular epigenetics in our 1996 review of RNA-mediated cell type differentiation.

From Fertilization to Adult Sexual Behavior

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988).

See: Buried in patents: constraints on RNA

Author: James Kohl

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