Mathematical model: microRNA and epigenetic regulation

Hypothesis & Theory ARTICLE

Front. Genet. | doi: 10.3389/fgene.2014.00345

Excerpt: “…a detailed model of the epigenetic interaction and its relations with the cellular environment would be required, and this is still an open issue (24).”
My comment: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
Conclusion:  “Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.”
The model starts with nutrient-uptake and odor-induced de novo creation of receptors that allow nutrients to enter the cell. It links nutrient-dependent changes in the microRNA/messenger RNA balance to the production of species-specific pheromones that control the physiology of reproduction in species from microbes to man.
The conserved molecular mechanisms of amino acid substitutions that stabilize DNA in organized genomes have since been linked to chromosomal rearrangements common in the context of ecological variation that leads to nutrient-dependent pheromone-controlled ecological adaptations all cells of all individuals of all organisms.
If there is a model of evolutionary events linked to biologically-based increasing organismal complexity, it has not been mentioned so that it could be compared to this model of RNA-mediated events. If someone is concealing their model of biologically-based events and evolution, it may never be compared to the conserved molecular mechanisms that appear to result in ecological speciation, outside the context of mutations, natural selection, and the evolution of biodiversity.
Summary: The issue of a detailed model may remain open if only due to the fear my model has instilled among evolutionary theorists who appear to have realized they have not modeled evolution in the context of nutrient-dependent evolutionary events. Kudos to those who have provided a mathematical model that also challenges the approach of population geneticist who invented neo-Darwinism and defined it in terms of DNA-mediated events associated with the pathology of perturbed protein folding, not biodiversity.


Nutrient-dependent pheromone-controlled exercise-induced physiques

How to explain exercise-induced phenotype from molecular data: rethink and reconstruction based on AMPK and mTOR signaling
Excerpt: “…cellular and molecular phenotype for exercise capacity is always acquired from regular exercise or muscle contraction; it is absurd to use drug and gene modification…”
My comment: What is known about RNA-mediated events shows that the slightest deficit in nutrient uptake will be manifested in your exercise-induced physique, which is also epigenetically-effected by the pheromones of others via the same pathway.
Meanwhile, even some serious scientists claim that our morphological and behavioral phenotypes ‘evolved’ via mutations and natural selection, because they have no understanding of epigenetically-effected RNA-mediated events and how amino acid substitutions differentiate all cell types in all individuals of all species by stabilizing the DNA in organized genomes of species from microbes to man.

Amir Siddiqui  (Symmetry Gym) is the only trainer/owner I know who understands enough about molecular biology to include what is known in his approach to helping others develop their potential.

If others are also beginning to understand the difference between those who think supplements will help ensure their success and biological facts that explain morphological and behavioral phenotypes, their comments are welcome here.


Evolutionary heritage or ecological adaptation? Racism versus reality

Jewish Heritage Written in DNA

Fully sequenced genomes of more than 100 Ashkenazi people clarify the group’s history and provide a reference for researchers and physicians trying to pinpoint disease-associated genes.

By Kate Yandell | September 9, 2014

Excerpt: These results are compatible with those of prior work on mitochondrial DNA (mtDNA), which is passed on maternally. This prior work suggested that Ashkenazi men from the Middle East intermarried with local European women. The Ashkenazi population “hasn’t been likely as isolated as at least some researchers considered,” said Keinan.
Finally, the newly sequenced genomes shed light on the deeper history of Europe, showing that the European and Middle Eastern portions of Ashkenazi ancestry diverged just around 20,000 years ago.

My comment: In flies, “Mitochondrial replication, transcription, translation and respiration depend upon interactions between RNAs and proteins encoded in both genomes, and epistatic interactions between mitochondrial and nuclear polymorphisms are known to contribute to phenotypic and fitness variation within species [1]–[6].” That suggests ecological variation and nutrient-dependent ecological adaptations in all species are manifested in different human populations via pheromone-controlled RNA-mediated events.
I mentioned that likelihood in the following context of a 2013 review: “In flies, ecological and social niche construction can be linked to molecular-level cause and effect at the cellular and organismal levels via nutrient-dependent changes in mitochondrial tRNA and a nuclear-encoded tRNA synthetase. The enzyme enables attachment of an appropriate amino acid, which facilitates the reaction required for efficient and accurate protein synthesis (Meiklejohn et al., 2013).”
I also provided examples from other model organisms that show amino acid substitutions may link cell type differentiation in all cells of all individuals of all genera. Thus, claims by evolutionary theorists about mutations, natural selection, and the evolution of biodiversity are antithetical to what is currently known about transgenerational epigenetic effects.
I’m not claiming that evolutionary theorists think mutations can explain Jewish and European origins via natural selection associated with any last universal common ancestor. However, I think any claims that involve undisclosed evolutionary events, which appear to begin with light-induced amino acid substitutions in plants, should be compared with what is currently known about RNA-mediated events — if only to stop to the pseudoscientific nonsense of ridiculous claims based on population genetics.
I apologize for being adamant about this. But already I can see — from the first comment on this news — that racism may enter the picture because theorists never realized skin color is a nutrient-dependent morphological trait, not the result of any mutation. That links other morphological and behavioral phenotypes in other species to nutrient-dependent RNA-mediated events and ecological adaptions, not to the mutations discussed in Nicholas Wade’s “A Troublesome Inheritance.”
Transgenerational epigenetic inheritance is only troublesome when it’s attributed to mutations. Let’s stop doing that, shall we?
Excerpt 2: “This is, I think, the first evidence from whole human genomes that the most important wave of settlement from the Near East was most likely shortly after the Last Glacial Maximum  . . . and, notably, before the Neolithic transition—which is what researchers working on mitochondrial DNA have been arguing for some years,” Martin Richards, an archeogeneticist at the University of Huddersfield in the U.K., told The Scientist in an e-mail.
My comment: Who has been arguing that? The first evidence “…that the most important wave of settlement from the Near East was most likely shortly after the Last Glacial Maximum…” was published in January 2013, and companion papers linked a single base pair and one nutrient-dependent amino acid substitution from the mouse-to-human model of RNA-mediated receptor-mediated changes in morphology to differences in skin, teeth, hair, and mammary tissue. Anyone who argues against that fact may encounter opposition from serious scientists who understand what is currently known about RNA-mediated ecological adaptations.
Are others about to be attacked by researchers in Israel who understand how ecological variation leads to ecological adaptations without the pseudoscientific nonsense touted by evolutionary theorists? See for example: Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans and the claim that: “Our principle aim in the lab is to attack scientific dogmas. Mainly, we aim to use powerful genetic tools to discover novel biological principles by which RNA affects formation and inheritance of complex traits.” That claim went missing in September 2014. Perhaps it drew unwanted attention to the lab. No matter, the short perspective: RNA and dynamic nuclear organization helped to clarify the fact that “…the interactions between pre-mRNA and proteins fine-tune alternative splicing in a manner that can gradually create new protein functionalities without the need to create additional genes and without affecting existing proteins [4-6].” Clearly, the focus on RNA-mediated events and amino acid substitutions that stabilize DNA in organized genomes will lead to a future in which no serious scientist reports results in terms of mutations, natural selection, and the evolution of biodiversity.
What’s next? Are they going to force the evolutionary theorists to explain how Fragile X syndrome (FXS), which arises from interactive relationships among a single-nucleotide polymorphism (SNP) variant and the systems biology of neurogenic niche construction, can be linked to mutations and natural selection for intelligence in other modern human populations? If so, as I’ve already predicted several times in past blog posts, I think we will see the end of evolutionary theory by the end of this year. Too many people will be offended by those who continue to tout pseudoscientific nonsense as biological facts about RNA-mediated events become well-known.

Biophysically constrained beginnings of RNA and DNA

Any anonymous participant in the discussion of: DNA may have had humble beginnings as nutrient carrier (Sep 01, 2014 by Adam Hadhazy) asks:
“when are you going to keep quiet?”
In a series of responses, I have explained the problem I have with honoring his request.
The following excerpts from Wikipedia and other sources are loosely strung together because there is no point to providing more extensive details of biologically-based cause and effect until others accept the fact that mutations and natural selection cannot lead to the evolution of biodiversity. Even without accepting the fact that nutrient-dependent amino acid substitutions differentiate the cell types of all individuals in all species, it should be clear that mutations do not. Until that fact becomes clear, nothing known about physics, chemistry, and molecular biology can be used to refute ridiculous theories. Here are examples of what cannot be used.
1) In mammals, phosphatidylserine is produced by base-exchange reactions with phosphatidylcholine and phosphatidylethanolamine. The products of this reaction are novel dinucleotides. Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells. (The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups.)
The flipping of one base pair appears to result in Fragile X Syndrome, which is the most common form of mental retardation. It may represent what happens when an atomic-level change in nutrient-dependent energy perturbs protein folding.
For comparison, the nutrient-dependent flipping of a base pair associated with vitamin C uptake in mammals links frugivory in bats via morphological and behavioral phenotypes to their adaptive radiations. Their phenotypes link nutrient-dependent pheromone-controlled reproduction in all vertebrates and invertebrates to morphological and behavioral changes during the development of human preferences for food odors and pheromones.
2) Rather than be quieted by the pseudoscientific nonsense of evolutionary theorists who want others to believe that mutations and natural selection lead to the evolution of biodiversity, ecologists and other serious scientists continue to link biologically-based cause and effect from atoms to ecosystems via the conserved molecular mechanisms of amino acid substitutions that I detailed in my model.
Serious scientists know that models will lead to atomic level (nutrient-dependent) cures for diseases and disorders that evolutionary theorists claim are due to the same molecular mechanisms they think must link mutations to increasing organismal complexity manifested in morphological and behavioral phenotypes of species from microbes to man.
The difference between a serious scientist and a theorist (or any other idiot) is recognized by differences in their beliefs about biologically-based cause and effect. Theorists have no understanding of links between atoms and ecosystems; serious scientists attempt to understand the experimental evidence.
3) In metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another.
Most organisms synthesize NAD+ from simple components.[2] The specific set of reactions differs among organisms, but a common feature is the generation of quinolinic acid (QA) from an amino acid—either tryptophan (Trp) in animals and some bacteria, or aspartic acid in some bacteria and plants.[21][22] Besides assembling NAD+ de novo from simple amino acid precursors, cells also salvage preformed compounds containing nicotinamide. Despite the presence of the de novo pathway, the salvage reactions are essential in humans; a lack of niacin in the diet causes the vitamin deficiency disease pellagra.[28] This high requirement for NAD+ results from the constant consumption of the coenzyme in reactions such as posttranslational modifications, since the cycling of NAD+ between oxidized and reduced forms in redox reactions does not change the overall levels…
4) Rather than continue to examine facts that link the thermodynamic cycles of protein biosynthesis and degradation from atoms to ecosystems via organism-level thermoregulation, others may want to consider the alternative.
In “Mutation-Driven Evolution” for example, the claim is made that “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.”
That claim is not supported by any experimental evidence of biologically-based cause and effect, but many evolutionary theorists are convinced that the differences in morphology and behavior they can see are due to mutations that perturb protein folding at the level detailed in the Laws of Physics, which lead to everything known about chemistry and Kohl’s Laws of Biology, which are linked to the de novo Creation of olfactory receptor genes via the de novo Creation of RNA and DNA.
Addendum: Anyone willing to accept the fact that RNA and DNA somehow ‘evolved’ or that what’s known about the biophysical constraints that link ecological variation to ecological adaptations via conserved molecular mechanisms in species from microbes to man is not likely to lead to cures for diseases and disorders associated with mutations should participate in discussions on blog sites run by atheistic biology teachers like PZ Myers. For example see: One crank dies, another rises to take his place. Anyone willing to accept the fact that RNA and DNA were Created should examine the content of articles that represent what is known about the Laws of Physics; what is known about chemistry; and what is known about molecular biology. See for example: Darwin vs. Genetics: Surprises and Snags in the Science of Common Ancestry
In the context of biophysically-contrained ecological adaptations it may interest others to learn what is obviously missing from what’s being billed as the Theory of Everything. A theory of everything should have some explanatory power in the context of biologically-based cause and effect that does not link perturbed protein and nutrient-dependent ecological variation to pheromone-controlled ecological adaptations via the same molecular mechanisms. What if Hawkings’ disabled body could be linked from epigenetically-effected RNA and DNA to his highly functional mind? Would others be more interested in biological facts about the de novo Creation of proteins that can be compared to his theory of everything?
What if a nutrient-dependent flip in a single base pair led to amino acid substitutions that differentiate all the cell types of all individuals of all species via conserved molecular mechanisms? Could the link from Fragile X Syndrome and mental retardation be the same as the link to hemoglobin S and nutrient-dependent brain development in someone like you, or like Hawkings? If so, the link is likely to be nutrient-dependent amino acid substitutions that differentiate all cell types in all tissues of all organs in all organ systems of invertebrates and vertebrates via conserved molecular mechanisms of pheromone-controlled reproduction.
We can see the origins of that perspective on autophagy, which was the basis for my works in these two published works.
Effects of Carnitine on Fatty-Acid Oxidation by Muscle (1959)
My comment: Both were co-authored by Bruce McEwen. He told me in 1991 that I would need to start with energy-dependent gene activation before my model of cell type differentiation could be completely validated. I did that in the following year with the help of Robert L. Moss and his co-authors in a series of published works that linked pheromones to gene activation in GnRH neurosecretory neurons of the mammalian hypothalamus.


Genes and Race: Human History?

Roundup of Book Reviews of Nicholas Wade’s A Troublesome Inheritance

My comment: Many reviewers of Wade’s book on genes and race appear to think he has accurately represented issues of differences in cell types that evolutionary theorists associate with mutations, natural selection, and the evolution of human biodiversity. This may be cause for concern among those who are interested in accurate representations of biologically-based cause and effect.

In this century, it has become clear that ecological variation results in biodiversity, which is manifested in morphological and behavioral phenotypes that exemplify ecological adaptations in species from microbes to man. Therefore, most people might want to escape the criticisms associated with evolutionary theories based on population genetics that have received no support from experimental evidence of biologically based cause and effect. Yet, Wade sticks with mutations and natural selection as the cause of differences that somehow evolved. Reviewers claim no knowledge of biological facts that refute Wade’s outdated assertions. That’s scary, but no one says, BOO!

Indeed, he even discusses the modern human population that arose in what is now central China as if mutations and natural selection enabled the changes that occurred in hair, teeth, sweat glands, and mammary tissue — supposedly during the past ~30K years. The changes followed the climate change associated with disappearance of Neanderthals. That climate change and the associated dietary change can clearly be linked to reproductive success via a change in a single base pair linked to the substitution of a single amino acid in the organized genome of what may be the most successful human population on this planet.

If humans were frugivorous bats that ecologically adapted due to the availability of dietary ascorbic acid via the de novo creation of olfactory receptor genes, the human population would represent another population of mammals, albeit without wings, that successfully radiated to different regions of the planet via the conserved molecular mechanisms that enable adaptive radiation. If humans were mice, the amino acid substitution would be manifested in the same changes in cell types. Humans are not mice, but the same changes in cell types occur due to the same amino acid substitution. Amino acid substitutions also differentiate the cell types of other human populations.
The question arises, do serious scientists still think that mutations and natural selection enable adaptive radiation? Is there a model for that? If so, the model could be compared to what is known about the conserved molecular mechanisms of biolophysically constrained cause and effect. See for example: Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. The article links genes to differences in morphology and behavior without resorting to claims made by neo-Darwinists.
Indeed, the focus is more on the fact that Darwin set forth when he repeatedly urged consideration of  the ‘conditions of life’ that must be met before natural selection could occur. His conditions of life require selection for food, which is manifested in changes in the microRNA/messenger RNA balance and cell type differentiation in bats and humans — if not all species, or some that might have mutated into existence. The report on the article mentions the fact that “With the recent discovery that non-coding microRNA’s in food are capable of directly altering gene expression within human physiology,[1] this new study further concretizes the notion that the age old aphorism ‘you are what you eat’ is now consistent with cutting edge molecular biology.”
Nicholas Wade’s book includes nothing known about the molecular biology of cause and effect. Reviewers seem to know about nothing but evolutionary theory.


Darwinian theories vs Darwin's facts

Darwin’s Theories, submitted by Celia Secades of the Elesapiens website was the runner-up in the Third Annual NESCent Evolution Video Contest. (unfortunately, the video has been removed — perhaps for good reasons. For example:

My comment: No experimental evidence supports the representations of mutation-initiated natural selection in the video.
For comparison, tenOever on microRNA and Vaccines  addresses what is currently known about glucose-dependent RNA-mediated amino acid substitutions and self vs non-self identification in viruses to living species with varying degrees of nutrient-dependent pheromone-controlled ecologically-adapted organismal complexity.

Professor tenOever’s award-winning works cannot be placed into the context of Celia Secades “Darwinian facts” about evolution.
Darwin’s facts placed Darwin’s ‘conditions of life’ before natural selection. In the following four articles, we see that even in a virus (a non-living organism), glucose enables adaptations without mutation-initiated natural selection.
1) Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution (1) First, the amino acid substitutions are falsely attributed to mutations.
2) Stability-mediated epistasis constrains the evolution of an influenza protein 2) Next an article asked “How does epistasis arise from an evolutionary process that is conceived as proceeding through the incremental accumulation of mutations?’ Obviously, epistasis does not arise via mutations. The article places the evolutionary process into the context of biophysical constraints via an analogy to words. “WORD→WORE→GORE→GONE→GENE. Implicit in this analogy is the idea that there are biophysically constraints on evolution—for example, the original parent sequence does not tolerate three of the four eventual changes, as GORD, WERD and WOND are not words.” The fact that those words are nonsense words attests to the fact that mutation-driven evolution is a nonsensical theory.
3) Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection 3) This article links glycolysis and influenza virus infection. The amino acid substitution in the human influenza virus that enables new antigenic properties is obviously nutrient-dependent, even when the nutrient (i.e., glucose) must come from an infected cell.
Aerobic Glycolysis in the Human Brain Is Associated with Development and Neotenous Gene Expression 4) Aerobic glycolysis in the human brain links amino acid substitutions from the epigenetic landscape of  the influenza virus to the physical landscape of DNA in the organized genomes of living cells in different organisms via the conserved molecular mechanisms that enable nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction during the ecological adaptations that are manifested in increased organismal complexity of species from microbes to man.
Evolutionary theorists may object to the idea of crossing species barriers via what is known by molecular biologists about conserved molecular mechanisms, but that’s because evolutionary theorists don’t know enough about biology to reject the theory of mutation-driven evolution. Even though no experimental evidence supports it, theorists cling to their ridiculous theory because it’s all they have. There is no “fall-back” position. Either ecological adaptations are responsible for species divergence or mutation-initiated natural selection somehow enables increasing organismal complexity.
The video about how natural selection somehow enables increasing organismal complexity is only appropriate for an audience of children who are not expected to ask any questions about how mutations could be fixed in the genome so that they could be naturally selected. It is horribly inappropriate for use as a teaching tool for students age 5 or older, who are more likely to ask: “Is there a model for that?”
Since it has been removed, others may want to see those that remain, and attempt to determine whether anything they claim makes sense in the context of what is known about physics, chemistry, and molecular biology.
Also see the links to viral microRNAs from this blog site.