See also: Molecular Diagnostics: What is unprotected life?

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

Published on 30 Mar 2016. Presentated at Molecular Diagnostics on April 6 and 7, 2016 The poster also is available at Figshare

POSTER (abstract)

“The anti-entropic force of virucidal ultraviolet (UV) 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.”

Narrative:

Hi, my name is James Kohl. I am a medical laboratory scientist. The diagram represents what I learned about molecular diagnostics during the past 40 years.

First,  Life is nutrient-dependent.

Also, there is no defined boundary between epigenetics and genetics.

That fact is the basis for the Precision Medicine Initiative.

Nutrient-dependent metabolic networks must be linked to genetic networks via the energy-dependent physiology of reproduction in all living genera.

You probably already know that the RNA-mediated innate immune system links nutrient energy-dependent physics and chemistry. That’s how the immune system links nutritional epigenetics to the conserved molecular mechanisms of RNA-mediated cell type differentiation. Simply put, the immune system links energy from physics and chemistry to biologically-based cause and effect.

In the early years of my career, I used information provided by flame photometers and spectrophotometers to link physics from chemistry to biologically-based cause and effect. Now,  quantum physics links epigenetics to the biophysically constrained chemistry of cell type differentiation, which is the basis for molecular diagnostics. If cell type differentiation was not biophysically constrained, no one could test for what goes wrong.

Fortunately, the complexity of analysis at different levels of examination has been linked from the sun’s anti-entropic virucidal energy to hydrogen-atom transfer in DNA base pairs in solution. The speed of light on contact with water has been linked to the biophysically constrained chemistry of RNA-mediated protein folding.

Molecular biologists are not surprised to find that energy-dependent amino acid substitutions are the obvious link from the epigenetic landscape to the immune system and the physical landscape of supercoiled DNA.

In this diagram, RNA-mediated amino acid substitutions are linked to supercoiled DNA, which protects organized genomes from virus-driven entropy. I’ve integrated claims from Darwin, Einstein, Schrodinger and Dobzhansky. Simply put, Darwin’s nutrient-dependent “conditions of life” come before natural selection. That’s how Einstein’s math and physics link Schrodinger’s claims in “What is Life?” to Dobzhansky’s claims about amino acid substitutions and biodiversity in all living genera.

I included citations to support the representations in the diagram. Taken together, the citations show that nutrient-dependent microRNA flanking sequences link the life history transitions of all marine invertebrates to all vertebrates via the RNA-mediated physiology of energy-dependent reproduction.

Schrodinger’s claims about the anti-entropic energy of the sun predicted everything included in this diagram. But, like many others, Schrodinger knew little or nothing about  virus-driven energy theft.  Neo-Darwinian theorists, for example, have only recently started to consider virus-driven energy theft. And the likelihood that theft of energy links viruses from mutations to all pathology requires all theorists to revise all their theories.

For comparison, anyone who assumes the energy-dependent physiology of reproduction is not the link to biophysically constrained RNA-mediated transgenerational epigenetic inheritance probably never worked as a medical laboratory scientist. They may not know how to trouble-shoot the theories that led to their assumptions. This diagram may help theorists tether their claims to facts about energy-dependent RNA-mediated cell type differentiation.

The diagram is based on scientific experiments, which are tests that attempt to produce accurate results.  Medical laboratory scientists are trained to eliminate sources of error before testing.  For example, I learned that theories are sources of error. Theories do not link top-down causation from chemotaxis to phototaxis by what is known about the innate immune system, metabolic networks, and genetic networks. Theories about mutations and evolution are dead ends. That’s why the dead ends are represented in RED color in the diagram.

Everything in RED is linked from virus-driven energy theft to pathology. It would be appropriate to think of everything in red in the context of blood loss in humans. Without the nutrient energy-dependent RNA-mediated DNA repair that protects organized genomes from virus-driven entropy, molecular diagnostics would exist only in theory.

Content: Part 1

Energy-dependent nutritional epigenetics

Everything currently known to physicists, chemists, and molecular biologists attests to the following representations.

The speed of light on contact with water [1] links the energy-dependent de novo creation of nucleic acids and photosynthesis from metabolic networks to genetic networks. [2]

Conserved molecular mechanisms link hydrogen-atom transfer in DNA base pairs in solution from microRNA flanking sequences to base pair substitutions. [3]

The base pair substitutions link RNA-mediated amino acid substitutions to adhesion proteins. For example, the ribosome links heat shock proteins to biophysically constrained nutrient energy-dependent RNA-mediated protein folding chemistry and cell type differentiation via supercoiled DNA  in the context of the physiology of reproduction. [4]

Distinct nutrient energy-dependent pathways link microRNA biogenesis from RNAs to biological functions, but the distinct pathways are typically examined collectively. [5] The collective examination of nutrient-dependent RNA-mediated de novo gene creation and chemotaxis is not always phylogenetically linked to coordinated phototaxis and responses to other sensory input throughout life history transitions in all living genera.

Chemosensory input is the first phylogenetically conserved link from the epigenetic landscape to the physical landscape of supercoiled DNA, which appears to protect all organized genomes from virus-driven entropy in the context of the nutrient-dependent innate immune system. [6]

For example, metabolic energy links guanine nucleotide binding proteins (G proteins) to the experience-dependent de novo creation of monoallelic G protein-coupled receptors (GPCRs). Ligand-receptor binding links the de novo creation of olfactory receptor genes, which are GPCRs, to the creation of other receptors such as photoreceptors. [7-9]

[1] Single-residue insertion switches the quaternary structure and exciton states of cryptophyte light-harvesting proteins

[2] Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism

[3] The phylogenetic utility and functional constraint of microRNA flanking sequences

[4] Structural diversity of supercoiled DNA

[5] Single-molecule fluorescence measurements reveal the reaction mechanisms of the core-RISC, composed of human Argonaute 2 and a guide RNA

[6] Regulatory evolution of innate immunity through co-option of endogenous retroviruses

[7] UV-Induced Charge Transfer States in DNA Promote Sequence Selective Self-Repair

[8] An Epigenetic Signature for Monoallelic Olfactory Receptor Expression

[9] Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications

Content: Part 2

Virus-driven energy theft and pathology.

Retroviral integrase catalyses the integration of viral DNA into host target DNA.[10]  Viruses enter cells and they steal metabolic energy to replicate.[11]

The energy that is stolen is required to link nutrient-dependent RNA-mediated amino acid substitutions to the de novo creation of receptors that allow more nutrients or different nutrients to enter different cell types. The accumulation of viruses prevents nutrient-dependent cell type differentiation. The viruses link perturbed protein folding from mutations to pathology via metabolic networks and genetic networks in the context of the Precision Medicine Initiative. [12-13]

Unfortunately, claims about new ways to build molecules are not tethered to what is known about the need for an anti-entropic force that prevents dissipation of energy via amino acid substitutions that stabilize the organized genomes of all living genera. [14-15]. For example, achiral glycine in position 6 of the GnRH decapeptide is linked to the stability of all organized genome in all vertebrates.[16]

Prevention of increased virulence appears to be nutrient-dependent and controlled by the physiology of reproduction. Transgenerational epigenetic effects of food odors and pheromones link supercoiled DNA to protection from virus-driven entropy.

For example, the quality of foraging in crustaceans and insects links microRNA flanking sequences from sunlight to energy metabolism and genetic networks via amino acids and transgenerational epigenetic inheritance of sex differences in morphological and behavioral phenotypes in bulls, cows and humans. [17-18]

Conserved molecular mechanisms link nutrient energy-dependent changes in microRNAs to cell type differentiation and morphological and behavioral phenotypes of humans. [19]

Every aspect of cell type differentiation has been linked to energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solution from bacteria [20] to nematodes [21] and all mammals.[22] via RNA mediated events, which are perturbed by viruses, which have been linked from energy theft to all pathology by as little as a single base pair change and single amino acid substitution during life history transitions.[23-24]

[10] Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function

[11] Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

[12] RNA-Mediated Regulation of HMGA1 Function

[13] An expanded sequence context model broadly explains variability in polymorphism levels across the human genome

[14] Ligand-Controlled C(sp3)–H Arylation and Olefination in Synthesis of Unnatural Chiral α–Amino Acids

[15] Dissipation Bounds All Steady-State Current Fluctuations

[16] Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity

[17] The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression

[18]  Systematic microRNAome profiling reveals the roles of microRNAs in milk protein metabolism and quality: insights on low-quality forage utilization

[19] Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

20] Design and synthesis of a minimal bacterial genome

[21] A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions

[22] Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos

[23] Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity

[24] Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

See also:

Neuroscience of Early-Life Learning in C. elegans

Differential Odour Coding of Isotopomers in the Honeybee Brain

Breast Milk Sugars Support Infant Gut Health

C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins

Ancient virus found hibernating in the human genome—and it might wake up

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