Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications

ON 11/14/16 The co-author Mohamed Samir wrote: 

Because our article is among the top 25% most viewed and downloaded articles in the third quarter of 2016 in “Frontiers in Veterinary Science”, The editor of the journal has invited me to host and moderate a new research topic in his journal about miRNAs in veterinary filed. Thanks God.

The topic is virtually guaranteed to bring out the best in researchers who have already linked energy-dependent changes from angstroms to ecosystems in all genera via animal models that make it clear that virus-driven energy theft causes all pathology.

See also: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The bias between codons or amino acids, and mRNA expression levels has been previously recognized across species and is thought to result from selection for efficient, accurate translation, and folding of highly expressed genes (Ikemura, 1982; Akashi, 1994; Akashi & Gojobori, 2002; Drummond & Wilke, 2008; Kudla et al, 2009; Novoa & Ribas de Pouplana, 2012). The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

See also: RNA Structural Modules Control the Rate and Pathway of RNA Folding and Assembly

Natural selection for codon optimality is an energy-dependent biophysically constrained RNA-mediated sexually differentiated biological function that has been linked to RNA folding and the assembly of functional protein structures in species from yeasts to mammals.

See: Yeast and cancer cells – common principles in lipid metabolism

See also: Signaling from the Cell Surface to the Genome: Pheromone Response in the Sexually Aroused
Yeast Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21 Evolution: A View from the 21st Century

Excerpt:

The two-stage replication proofreading system in E. coli and other bacteria has more complex analogues in nucleated eukaryotic organisms, from yeast to plants and animals.2

Excerpt:

There are two particularly significant facts about the S. cerevisiae mating pheromone response:

• It provides a concrete example of how one cell can communicate through well-defined molecular events with the genome of another cell. This example shows that we cannot consider the genome in any way isolated from the outside world; it is a fully informed cell organelle that works dynamically in response to a wide range of organic and inorganic inputs.

• The yeast pheromone response system utilizes sophisticated and complex sensory and signaling components (such as a G protein-coupled receptor) that researchers have encountered repeatedly in many quite distant organisms [160].

Proof-reading is nutrient energy-dependent and pheromone-controlled in species from microbes to humans. The ab initio creation of energy is linked from the de novo creation of G protein-coupled receptors and cell type differentiation via energy-depnedent chemotaxis and phototaxis. Both are required to find food and to remember where to find it. Nutrient selection is the link to energy-dependent translation of codon identify from the paternal lineage, which involves different cell types. Cell type differentiation is nutrient-dependent and pheromone-controlled in species from microbes to humans.

See also: Learning from Bacteria about Natural Information Processing

See for contrast: 7/25/13

Jay R. Feierman:

Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding [of] Darwinian biological evolution.

In some species that sexually reproduce, one of the sexually-differentiated cell types is called a spermatozoa. The other is called the ovum. In both energy-dependent sexually-differentiated cell types RNA interference is essential for cellular quiescence. The quiescence links autophagy to the transgenerational epigenetically-effected stability of organized genomes in all cell types.

In our 1996 Hormones and Behavior review, we put RNA-mediated interference (RNAi) into the context of sexual differentiation of cell types via the pheromone-controlled energy-dependent physiology of sexual reproduction.

See: From Fertilization to Adult Sexual Behavior

Abstract excerpt: 

The general sense of the word “environment” as something exterior to the person is retained, even if that something influences intraperson processes. In addition, we focus directly on molecular events themselves. Here the “environment” involved can be that within a DNA segment. We also expand the notion of “biologically based sex differences.”

Unlike Jay R. Feierman, others have since recently decided to continue Addressing sex as a biological variable, which is probably what all serious scientists have always done. It is difficult to imagine why anyone who is not a serious scientist would link mutations and/or natural selection to the evolution of sex differences in cell types.

See:

This themed issue of the Journal of Neuroscience Research highlights sex differences of the brain at all scales, from the genetic and epigenetic, to the synaptic, cellular, and systems differences—differences known to be present throughout the life span.

My comment: Epigenetically-effected sex differences in the brain that develop during the lifespan have been linked from nutrient energy-dependent biophysically constrained RNA-mediated protein folding chemistry to fixation of amino acid substitutions such as VAl158Met, which links energy-dependent behavioral transitions from adolescence to adulthood in humans.

See for example: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

The function of the amino acid substitution is altered by a single nucleotide polymorphism (SNP) in COMT (G-to-A base-pair substitution) leading to a methionine (Met) valine (Val) substitution at codons 108/158 (COMT Val158Met). Carriers of the Met allele display a fourfold decrease in enzymatic activity compared to Val allele carriers. The decrease is accompanied by an increase of prefrontal DA activity. (Lachman et al. 1996; Lotta et al. 1995).

See also: Amino acids and virus penetration

Conclusion:

Theorists have ignored what serious scientists have detailed in the context of energy-dependent RNA methylation and cell type differentiation that must link learning and memory from ecological variation to ecological adaptation via the conserved molecular mechanisms of protein folding biochemistry that link metabolic networks to genetic networks.  The amount of ignorance is overwhelming, and the theorists are not attempting to inform themselves.

Even Tim Bredy’s group seems to have fallen behind after publication of Experience-Dependent Accumulation of N6-Methyladenosine in the Prefrontal Cortex Is Associated with Memory Processes in Mice

They clearly linked energy-dependent RNA-methylation from learning and memory to RNA-mediated cell type quiescence and to sex differences in cell types in species from yeasts to mammals. With publication of Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain, they appear to ignore their prior claims, which link learning and memory in spermatozoa to the ability to find the ovum, which is another biophysically constrained sexually differentiated cell type. That energy-dependent ability of a sperm cell to find an ovum becomes increasingly important in the context of other published works such as this one. Mitochondrial genome and epigenome: two sides of the same coin

That claim made me more interested in seeing what I could find by scanning the table of contents in the Journal of Neuroscience Research :An Issue Whose Time Has Come: Sex/Gender Influences on Nervous System Function

From what initially saw, no one is addressing the facts about how energy-dependent biophysically constrained protein folding chemistry links RNA-mediated amino acid substitutions to supercoiled DNA via the physiology of pheromone-controlled reproduction in species from marine microbes to humans. Perhaps the special issue only claims to be Addressing Sex as a Biological Variable — 20 years after we did that.

See for comparison: From Fertilization to Adult Sexual Behavior (1996)

Excerpt:

The general sense of the word “environment” as something exterior to the person is retained, even if that something influences intraperson processes. In addition, we focus directly on molecular events themselves. Here the “environment” involved can be that within a DNA segment. We also expand the notion of “biologically based sex differences.”

See also: Misunderstanding cancer

The fact that detection of accumulated mutations does not provide diagnostic clarity should eliminate theories about accumulated mutations and evolution. How could mutations not be linked to physiopathology, but somehow lead to the evolution of biodiversity. For example, see the conclusion from Mutation-Driven Evolution: “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements” (p. 199).

I cited several different works from Tim Bredy’s group and am grateful to him for helping to inform me after I asked him about microRNAs in November 2012. All works from Tim Bredy’s group and the works of others can now be placed into the context of this one: Single-nucleotide polymorphism rs948854 in human galanin gene and multiple sclerosis: a gender-specific risk factor

These data demonstrate for the first time an association between rs948854 polymorphism and multiple sclerosis and, further, that this association is sex specific.

Why isn’t someone else linking the energy-dependent change in the base pair to changes in hydrogen-atom tranfer in DNA base pairs in solution in all living genera and linking the changes in base pairs to amino acid substitutions that determine thei differences in all cell types? It’s not just about sex differences and never has been. All cell type differentiation is energy-dependent and all biodiversity is controlled by the physiology of reproduction.

Before you read anything else from the special issue Journal of Neuroscience Research: An Issue Whose Time Has Come: Sex/Gender Influences on Nervous System Function, I recommend that you read Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain

How else are they going to link cell type differentiation in species from microbes to humans via sex differences without including what was known about genetics and molecular epigenetics 20 years ago? No matter how hard they try to ignore the facts we presented in the molecular epigenetics section of our 1996 review and all other facts about energy-dependent cell type differentiation, they cannot escape the fact cell type differentiation is energy-dependent and controlled by the physiology of reproduction.

I’ll let you know more about what I find in other articles from the same special issue when I have time to unravel any attempts to obfuscate facts that serious scientists have always know, like this one: Feedback loops link odor and pheromone signaling with reproduction

See Energy-dependent maternal-to-zygotic transition (in prep)

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