5th-6th Sept 2018 Dublin, Ireland

The eternal significance of microRNAs (8)

Use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation and aging has been replaced by the use of model systems of biological processes.  Biological processes can be compared to so-called “evolutionary processes” to show that only biological processes need to be considered in the context of Darwin’s “conditions of life” or answers to the the question  What is Life? Schrödinger (1944).
K. L. Mettinger et al. (eds.), Exosomes, Stem Cells and MicroRNA, Advances in Experimental Medicine and Biology 1056, https://doi.org/10.1007/978-3-319-74470-4_6

This volume provides insight into the pivotal roles of stem cells, exosomes and other microvesicles in biofunction and molecular mechanisms and their therapeutic potential in translational nanomedicine. It further highlights evidence from recent studies as to how stem cell derived exosomes and microRNAs may restore and maintain tissue homeostasis, enable cells to recover critical cellular functions and begin repair regeneration.

Chapter 2 The Emerging Roles of microRNAs in Stem Cell Aging

involved in many biological processes such as developmental timing, differentiation, cell death, stem cell proliferation and differentiation, immune response, aging and cancer. Accumulating studies in recent years suggest that miRNAs play crucial roles in stem cell division and differentiation. In the present chapter, we present a brief overview of these studies and discuss their contributions toward our understanding of the importance of miRNAs in normal and aged stem cell function in various model systems.

Chapter 6  MicroRNAs, Regulatory Messengers Inside and Outside Cancer Cells

…like hormones, miRNAs can be secreted and regulate gene expression in recipient cells. Altered expression levels of miRNAs in cancer cells determine the acquisition of fundamental biological capabilities (hallmarks of cancer) responsible for the development and progression of the disease.

Model systems link the energy-dependent creation of microRNAs from microRNA biogenesis to the regulation of all cancer hallmarks. The virus-driven degradation of messenger RNA has been linked to all cancers and all other pathology in species from microbes to humans. Natural selection for energy-dependent codon optimality has been linked to healthy longevity.
See: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition
See for comparison:  The Neutral Theory in Light of Natural Selection May 2, 2018

…50 years after its introduction by Kimura. We argue that the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality. The ubiquity of adaptive variation both within and between species means that a more comprehensive theory of molecular evolution must be sought.

The ubiquity of adaptive variation attests to the facts about how the creation of quantized energy is linked to biophysically constrained viral latency. Adaptive variation links energy-dependent changes from angstroms to ecosystems in all living genera  via the physiology of their food energy-dependent pheromone-controlled reproduction.

For comparison to mRNA stability during the maternal-to-zygotic transition, see: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

The energy-dependent molecular mechanisms of recombination clearly link microRNA biogenesis to the stability of organized genomes during the life histories of all genera. Serious scientists object to the use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

…it is tiresome to raise the same objections repeatedly, wondering why researchers have not fulfilled some of the basic requirements for establishing the occurrence of an autophagic process.

 

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Viruses in pathogenic variants disrupt alternative splicings (3)

See: Viruses in pathogenic variants disrupt alternative splicings (2)
See also: What is life without sunshine?

Exosomes—small, membrane-derived extracellular vesicles capable of carrying diverse biological cargo including proteins and microRNAs—have been found in a broad range of biological fluids and appear to be predominantly involved in cell-to-cell communication. Their natural characteristics make them uniquely suited for research and clinical applications, including as biomarkers both for diseases and for intrinsic biological activity.
 
The naturally occurring intrinsic biological activity of cell-to-cell communication is energy-dependent and RNA mediated. Virus-driven energy theft links the degradation of messenger RNA to all pathology in all living genera.
 
This is the first of two free webinars tooday, in which theorists and pseudoscientists will make attempts to place what is known to serious scientists about biophysically constrained RNA-mediated protein folding chemistry back into the context of drug development.
 
Why? Because that’s where the money is.
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Experimental evidence vs evolutionary theory

Kara C. Hoover: Smell with inspiration: The evolutionary significance of olfaction
Excerpt from 2010:

Human pheromones, a controversial subject, seem to be a natural phenomenon, with a small number identified in clinical studies.

Researchers show how our sense of smell evolved, including in cave men

Excerpt:

People with different DNA sequences in the gene producing the OR7D4 receptor respond differently to this smell…. People’s responses to androstenone can be predicted by their OR7D4 DNA sequence, and vice versa.

Journal article excerpt:

The underlying adaptive context of possible selective pressures acting on olfactory receptor genes is not known but may be linked to food… and health….

My comment: DNA sequences do not evolve. The epigenetic landscape is linked to the physical landscape of DNA via nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions. The substitutions are fixed in organized genomes via the physiology of nutrient-dependent reproduction in all genera. No experimental evidence of biologically-based cause and effect suggests there is any way to link mutations, which perturb protein folding, to the evolution of increasingly complex biodiversity.

Anyone who looks at the comments linked to the articles below will see that no amount of experimental evidence that links the physics and the chemistry of nutrient-dependent RNA-mediated amino acid substitutions to protein folding will convince theorists that mutation-driven evolution cannot occur in the context of what is known to serious scientists. Thus, Hoover et al., (2015) have restated the obvious in the context of mutations and evolution: “The underlying adaptive context of possible selective pressures acting on olfactory receptor genes is not known…”
Theorists who attribute evolution to mutations ignore the obvious link from ecological variation to ecological adaptations via olfaction and pheromones. That means they must also ignore all evidence that links food odor and pheromones to receptor-mediated changes in the morphological phenotypes and behavioral phenotypes of species from microbes to man via their RNA-mediated metabolic networks and genetic networks.

Thus, the high frequency of variants that impair receptor function, high fixation values for deleterious alleles, and selection test results all suggest the interpretation of the Ka/Ks ratio as maintenance of the ancestral state via purifying selection is not likely.

My comment: Fixation of the deleterious alleles eliminates the associated olfactory receptor genes in the context of selection for the de novo creation of nutrient-dependent olfactory receptor genes, which are fixed in organized genomes via links from nutrient uptake to the physiology of reproduction.

Conclusion: (excerpt)

Olfaction is a primary sense involved in the detection of environmental and conspecific cues…. Mutations often accumulate on redundant genes, including olfactory receptor genes, rendering them nonfunctional over time. This pattern is evident in humans but we also see new functional variants emerge (Mainland et al. 2014). An example… exhibits geographically patterned variation linked to adaptation.

They try to place their study results into the context of how our olfactory genome evolved, but acknowledge the fact that “a range of anthropological, genetic, and neurobiological skills will be necessary…”
My comments on the following articles attest to that fact.

Brain folding related to surface area and thickness, not number of neurons

My comment: From a purely physical perspective they link the probable mechanisms involved “…that control the rate of neurogenesis and increases in cell size relative to the rate of progenitor and intermediate progenitor cell proliferation in early cortical development.”
From any perspective that involves the biophysically constrained nutrient-dependent RNA-mediated cell type differentiation of all genera via their physiology of reproduction, they inadvertently link the nutrient-energy dependent fixation of amino acid substitutions to cortical development in different mammals via their nutrient-dependent pheromone-controlled physiology of reproduction.
These researchers appear to be like the serious scientists who reported that “Feedback loops link odor and pheromone signaling with reproduction
They do not appear to be like evolutionary theorists who do not understand biologically-based cause and effect.

Heaven scent: Finding may help restore fragrance to roses

Excerpt: This gene, which produces an enzyme, revealed the odor-producing process.
My comment: This exemplifies how quickly traits are removed that are linked from nutrient-uptake to metabolic networks and genetic networks via RNA-mediated amino acid substitutions and scent production in plants.

‘Map of life’ predicts ET. (So where is he?)

Excerpt:

The book claims that evolution is therefore far from random, but a predictable process that operates according to a fairly rigid set of rules.

My comment: No one seems willing to place the difference in the bacteria that re-evolved their flagella in 4 days and the difference in the roses (3 generations) into the context of mutations and evolution.

The book by Simon Conway-Morris about a predictable process and rigid set of rules can be compare to the conclusion in the 2013 book by Masatoshi Nei: Mutation-Driven Evolution
Excerpt:

…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.

My comment: Nei’s claims have been the subject of a month-long discussion at Evolution is unpredictable and irreversible, biologists show.
The claims by Conway-Morris have been exemplified in the context of nutrient-dependent RNA-mediated amino acid substitutions that determine the cell types of all genera via fixation of the substitutions in the context of their physiology of reproduction. The rules that Conway-Morris may be referring to may be strict, but they also seem to predict that likelihood that ecological variation in the food supply leads to ecological adaptations via the physiology of nutrient-dependent reproduction in all genera.  The rules probably fit Darwin’s claims about the need to place “conditions of life” before natural selection. If the rules are that all organisms must eat and reproduce for biodiversity to arise, the rules also make more sense than claims about contraint-breaking mutations, since mutations perturb protein folding. RNA-mediated amino acid substitutions, for comparison, stabilize the organized genomes of all genera.

See also:

Discovery of nanotubes offers new clues about cell-to-cell communication

Single-celled predator evolves tiny, human-like ‘eye’

Sniff tests used to create olfactory fingerprint

Can autism be measured in a sniff?  

Epigenetic Mechanism Tunes Brain Cells