terrarium-eco-system

Dobzhansky 1973 and precision medicine

MicroRNA-34 directly targets pair-rule genes and cytoskeleton component in the honey bee

Our findings point to miR-34-5p as novel regulatory component in the complex molecular cascade that governs insect segmentation and to a broader role of miRNAs in the early development due to the detection of mature transcripts from both 5p and 3p arms for several precursor miRNAs. Thus, this work encourages further investigation to pinpoint miRNAs as fine tuners of insect early development.

Anna Di Cosmo‘s group took the lead and already linked all invertebrates to all vertebrates via the conserved molecular mechanisms that link microRNA flanking sequences to all energy-dependent  biophysically constrained biodiversity.

See for example: Role of olfaction in Octopus vulgaris reproduction (January 1, 2015)

For a perspective, see: The phylogenetic utility and functional constraint of microRNA flanking sequences (February 18, 2015)

The majority of flanking sequences used in our analyses are composed of non-coding intergenic DNA, suggesting that conservation of these hairpin-loop flanking sequences is independent of either the presence of exonic sequence or protein-coding gene regions.

For the extension to humans, see:

Practical Approaches for Whole-Genome Sequence Analysis of Heart- and Blood-Related Traits

 …all amino acid substitutions or all promotor variants are not equal, and one can predict the impact based on knowledge of the location and type of substitution.

All cell type specific and tissue type specific amino acid substitutions in all individuals of all living genera are energy-dependent and biophysically constrained by the physiology of pheromone-controlled reproduction. A long-time antagonist echoed that fact in the human ethology yahoo group, but he took facts about complex traits out of context. See: Practical application of whole-genome sequencing

The complex traits used here are heart and blood related ones, but the concepts are applicable to all complex genetically-sourced traits, including behavioral ones. — Clarence A. ‘Sonny’ Williams

Complex traits are not genetically sourced. The physiology of pheromone-controlled reproduction is clearly the link to the complexity of all nutrient energy-dependent morphological and behavioral traits.
See: No Genetics without Epigenetics? No Biology without Systems Biology?

…a unified understanding of life requires: (1) a view on its component parts, the cells, (2) a view on the life cycles of all cells—their formation, growth, development, and reproduction—as based in chemical reactions among similar sorts of molecules, (3) a view on the way in which amino acids are put together to form proteins, as specified by DNA and RNA according to a nearly universal and precise scheme.

That fact makes it perfectly clear that behavioral traits are not genetically sourced. All traits arise only in the context of systems biology, which links the epigenetic landscape to the physical landscape of supercoiled DNA in all living genera. For comparison, Clarence A ‘Sonny Williams wrote:

mutations in gene regulatory regions are the “driving force” behind human brain complexity. 

and

I do not reply to creationists or anyone who does not believe that humans evolved via Darwinian natural selection.

The facts about systems biology were stated clearly in Dobzhansky’s Nothing in Biology Makes Any Sense Except in the Light of Evolution (1973)

Cytochrome C is an enzyme that plays an important role in the metabolism of aerobic cells. It is found in the most diverse organisms, from man to molds. E. Margoliash, W. M. Fitch, and others have compared the amino acid sequences in cytochrome C in different branches of the living world. Most significant similarities as well as differences have been brought to light. The cytochrome C of different orders of mammals and birds differ in 2 to 17 amino acids, classes of vertebrates in 7 to 38, and vertebrates and insects in 23 to 41; and animals differ from yeasts and molds in 56 to 72 amino acids. Fitch and Margoliash prefer to express their findings in what are called “minimal mutational distances.” It has been mentioned above that different amino acids are coded by different triplets of nucleotides in DNA of the genes; this code is now known.

See also:

For example, the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.

The de novo creation of amino acids has since been linked from chirality to autophagy and healthy longevity via chromosomal rearrangements.
See:
Light-Induced Opening and Closing of the Intramolecular Hydrogen Bond in Glyoxylic Acid
Single-residue insertion switches the quaternary structure and exciton states of cryptophyte light-harvesting proteins
Dynamic control of chirality and self-assembly of double-stranded helicates with light
The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes

The cycle of interconversion of assemblies and helicities shown here holds promise to design other dynamic systems driven out of equilibrium by light energy.

See also: ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons
The de novo creation of amino acids has since been linked from the energy-dependent creation of helicase to the structure of functional DNA. Theories about minimal mutational distances have been replaced by facts that link angstroms to ecosystems in all living genera via biophysically constrained RNA-mediated protein folding chemistry.

See: Structural diversity of supercoiled DNA

Our data provide relative comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes.

They linked energy-dependent metabolic networks to genetic networks by recapitulating Dobzhansky’s claims and in this parody they add: “every angstrom is dynamic from the 5 prime to the three”

See also: Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation

…definitive conclusions about the exact role of the N-tier in helicase mechanism will require higher resolution to identify candidate-specific amino acid residues, followed by direct mutagenesis and biochemical characterization.
 

Although the candidate-specific amino acid residues have not been identified, the energy-dependent creation of RNA-mediated amino acid “residues” links the anti-entropic virucidal energy of sunlight from angstroms to ecosystems in all living genera via chirality and autophagy, which protect all organized genomes from virus-driven entropy in the context of the transgenerational epigenetic inheritance of all morphological and behavioral phenotypes.

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

The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

See also: Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes

The ZAL2 and ZAL2m alleles code for 597 amino acids, with two fixed differences driving a Val73Ile and Ala552Thr polymorphism in ZAL2m. valine to alanine substitution

How social learning adds up to a culture: from birdsong to human public opinion
Conclusion:

For human online cultures, we suggest that it may be useful to consider features of birdsong learning, which have been optimized over millions of generations to give rise to stable polymorphic cultures. Experimenting with implementation of similar features in online communication systems could potentially facilitate the design of more stable and balanced information systems, which can potentially promote distributed self-governance.

Public opinion (above) is based on bird-brained representations of pseudoscientific nonsense about “…balanced information systems, which can potentially promote distributed self-governance.” The information systems are not linked from energy-dependent changes in the microRNA/messenger RNA balance to all biodiversity via the physiology of pheromone-controlled reproduction. Instead the information systems automagically may promote “distributed self-governance” across all species in the context of millions of years of evolution.

In my model of biologically-based cause and effect, top-down causation is linked from natural selection for energy-dependent codon optimality to the physiology of reproduction and all biodiversity via supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy.

For an example of medication-induced genomic entropy, see: Some Antibiotics Linked to Serious Nerve Damage

The FDA is strengthening its warning that a popular class of antibiotics, called fluoroquinolones, may cause sudden, serious, and potentially permanent nerve damage called peripheral neuropathy.

See also: There is nothing inevitable or natural about chronic disease

Causation at the molecular level, deep inside the body, appears to be beyond our current reach

See for comparison: Understanding and accounting for relational context is critical for social neuroscience

George Ellis:

This is absolutely correct and forms part of the larger concept that top-down causation is a key factor not just in the way the brain works but in broader contexts in biology and even physics. This is explored here: http://rsfs.royalsocietypublishing.org/content/2/1.toc

I wrote:

New data on how genetic predispositions are epigenetically linked to phenotypically distinct neuroanatomy and behaviors is provided in the honeybee model. Across-species comparisons from insects to vertebrates clearly show that the epigenetic influence of food odors and pheromones continues throughout the life of organisms that collectively survive whereas individuals do not. These comparisons also attest to the relative salience of sensory input from the rearing environment. For example, when viewed from the consistency of animal models and conditioned behaviors, food odors are obviously more important to food selection than is our visual perception of food. Animal models affirm that food odor makes food either appealing or unappealing. Animal models reaffirm that it is the pheromones of other animals that makes them either appealing or unappealing.

Socioaffective neuroscience and psychology may progress more quickly by keeping these apparent facts in mind: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).” — Kohl, JV (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors
See also: Methylation Maestro

So are many others who do not understand how energy-dependent changes in chirality must be linked from autophagy to supercoiled DNA in the context of the physiology of reproduction and fixation of RNA-mediated amino acid substitutions.

They have failed to link the National Microbiome Initiative to the Precision Medicine Initiative via RNA-mediated protein folding chemistry and are trapped in theories with no explanatory power.

If you ask one of them about the virus-driven energy theft of quantized energy, which is linked to all pathology, they will run away. They cannot stand to think about how the potential of hydrogen (pH) must be linked from sunlight to all biodiversity via the claims of Schrodinger in What is Life? (1944)

Alternative splicing of pre-mRNA

Explorers who do not know what is known (2)

See: Explorers who do not know what is known
See also: Energy-dependent polycombic ecological adaptation

Now see: The B/Z reaction, and the problem with peer review December 9. 2016 by John Leonard

  1. … oscillating chemical reactions predictable by mathematical formula are partially responsible for organizing cells to form organs, bone, and tissue.
  2. Alan Turing didn’t live to see the publication of evidence that would have validated his theory almost immediately.
  3. …when Belousov attempted to have his research published in 1951, the leading scientific journals flatly rejected his work, based on the assumption that the experiment results were “impossible.”
  4. Only a single paragraph from Belousov’s analysis was finally published four years later, in 1955. Alan Turing was already dead. And so was the career of Boris Belousov,  so disgusted the editors of the leading journals had flatly rejected his work without even trying to replicate the results that he stopped performing scientific research.
  5. A horribly flawed peer review process utterly failed Boris Belousov. The editors of science journals successfully asserted themselves as the arbiters of what may be considered acceptable science, and their power remains largely unchecked even today.
  6. Rather than simply assuming that some process or claim  is “impossible,” perhaps we should seriously consider at minimum a cursory investigation of the alleged evidence.
  7. Peer review is a horribly flawed system, but unfortunately, it remains the best system we have.
Peer-review fuels plagiarism. Plagiarism fuels ignorance when what is known about physics, chemistry, and conserved molecular mechanisms is placed back into the context of ridiculous theories. People and plagiarists like John L. Leonard fuel ignorance when they refer to me as an ill-mannered idiot.
October 24, 2016 at 1:15 pm he wrote:

And I don’t like ill-mannered idiots.

Less than two months later, John L. Leonard plagiarizes my detailed model and referenced claims about energy-dependent cell type differentiation. He put them into the context of failed peer review, Turing’s suicide, and the reason why Boris Belousov stopped his research.  I think that if Facebook groups had been available so that people like John L.Leonard could criticize his works, Boris Belousov might also have committed suicide.
Clearly, the amount of overwhelming ignorance displayed in the context of peer review now extends across many more forms of communication in which the opinions of the biologically uninformed prevail. See for example my invited review of nutritional epigenetics, which was returned without review. Then see the subsequent publications from two guest editors of the journal “Nutrients” who requested my review: Lynnette Ferguson and Justin O’Sullivan.
Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition
Insights from Space: Potential Role of Diet in the Spatial Organization of Chromosomes

See for comparison: A protein conjugation system essential for autophagy (1998)

This process is crucial for survival during starvation and cell differentiation.

See also: A Harvard scientist just won $3 million for discovering the hidden ‘intelligence’ that defends our cells (2016)
He discovered nutrient energy-dependent autophagy, again.
See for instance: How autophagy both activates and inhibits cellular senescence (2016)

Although autophagy was originally recognized as a nonspecific lysosomal degradation pathway (general autophagy), increasing evidence supports a selective form of autophagy that mediates the degradation of specific targets (selective autophagy).

Yoshinori Ohsumi won the 2016 Nobel Prize in Physiology or Medicine for experimental evidence that links selective autophagy to supercoiled DNA, which protects all organized genomes from virus-driven energy theft.
See: Structural Basis for Receptor-Mediated Selective Autophagy of Aminopeptidase I Aggregates (2016)

Selective autophagy mediates the degradation of various cargoes, including protein aggregates and organelles, thereby contributing to cellular homeostasis.

Others have helped to establish the fact that energy-dependent receptor-mediated selective autophagy is RNA-mediated.
Schrodinger (1944)  What is life?

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.) (pp. 73 and 74)

Diamond et al. (1996) 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). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

Ben-Jacob et al. (2006) Seeking the foundations of cognition in bacteria: From Schrödinger’s negative entropy to latent information

We proposed that, besides “negative entropy,” organisms sense the environment to extract latent embedded information.13 By latent information we refer to data embedded in the environment that, once processed cognitively, initiates change in the organism’s function or behavior. Information induces changes; hence it can be used to generate an internal condensed description (model or usable information) of the environment, which guides the organism’s functioning.

Ben Jacob (2009) Learning from Bacteria about Natural Information Processing

It seems that bacteria have some sort of collective memory by which they keep track of how they handled their previous encounters with antibiotics. They know how to collectively glean information from the environment, “talk” with each other, distribute tasks, generate collective memory, and turn their colony into a “cybernetic system”—a massive “brain” that can perform natural distributed information processing, learn from past experience, and possibly alter the genome organization or even create new genes to better cope with novel challenges.8–13,17,18

Fortunately, serious scientists are now limiting attempt by pseudoscientists and opinionated laypeople to present more pseudoscientific nonsense about mutations, natural selection, and evolution. Those attempts may stop here.
See: The complex evolutionary history of aminoacyl-tRNA synthetases November 29, 2016
This article includes ongoing misrepresentations of how biophysically constrained protein folding chemistry is linked from RNA-mediated amino acid substitutions to the nutrient-dependent pheromone-controlled weekend resurrection of the bacterial flagellum.
Everything known to serious scientists is again placed back into the context of theories and “complex evolutionary histories.”
But the resurrection of the flagellum occurred within 96 hours in an organism (P. fluorescens) that fluoresces with exposure to ultraviolet light.
The failure to link the anti-entropic virucidal energy of sunlight to healthy longevity is the reason some researchers still frame their results in the context of ridiculous theories. In this article, they could refute the theories by the mere mention of the energy source that powers all cell type differentiation in all cell types of all individuals of all living genera.
Instead of the explanatory power of energy as information, an “evolutionary history” approach is used, which ignores the weekend evolution of the irreducibly complex bacterial flagellum.
The journal article was reported as: Ancient enzyme morphed shape to carry out new functions in humans

 Schimmel compared it to reshaping an airplane’s wing to serve as the airplane’s tail instead. “Nature has provided ways for reshaping objects, like C-Ala, and when that happens, new functions occur,” he said.

Selective autophagy is akin to the complete destruction of the airplane, which is rebuilt in its entirety via energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solution in all living genera. All the reassembled parts must be linked from energy transfer to functional structures at every level of examination. In the context of biologically-based cause and effect, angstroms must be linked to ecosystems in all living genera via conserved molecular mechanisms.
Attributing all that to “Nature” is an example of the pervasive ignorance that is common among theorists. That ignorance should probably never be displayed by creationists, especially if they attempt to argue with theorists.
Instead, all creationists can stay silent or they can learn about the experimental evidence that has linked selective autophagy to chromosomal rearrangements since the time of the 1933 Nobel Prizes for Physiology or Medicine (Thomas Morgan Hunt) and for Physics (Schrodinger/Dirac).
See also: “aminoacyl-tRNA synthetase” microRNA
miR-15a and miR-16-1 down-regulation in pituitary adenomas (2005)
Feedback loops link odor and pheromone signaling with reproduction (2005)

From Fertilization to Adult Sexual Behavior December 1996

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). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

The alternative splicings are energy-dependent. Virus-driven energy theft causes all pathology by using the energy to stabilize the genomes of viruses. If not for the atheists, plagiarists, and other creationists who would rather steal the information or fight against its dissemination, the neo-Darwinists would never have stood a chance.Watch for more reports that link energy-dependent RNA-mediated amino acid substitutions to supercoiled DNA, which protects all organized genomes from virus-driven entropy.

Someone else will also soon expose the fact that what theorists are calling ancient aminoacyl tRNA synthetases are the enzymes in bacteria that decode genetic information to help produce amino acids in all living genera. The nutrient energy-dependent fixation of the RNA-mediated amino acid substitutions links selective autophagy from nutritional epigenetics to healthy longevity via the physiology of reproduction in all genera.

terrarium-eco-system

Explorers who do not know what is known

Can genetic testing determine antimicrobial susceptibility? EUCAST experts say not yet… (link opens pdf)

Reported as:  Whole genome sequencing cannot yet be used to determine antimicrobial susceptibility

For most bacterial species there is currently insufficient evidence to support the use of WGS-inferred AST to guide clinical decision making. WGS-AST should be a funding priority if it is to become a rival to phenotypic AST.

My comment:

JVKohl said…

Perhaps the focus should be on what can be done with WGS. It can be used to link energy-dependent bioluminescence from bacteria in the light organ of bobtail squid to the nutrient energy-dependent pheromone controlled weekend resurrection of the bacterial flagellum in Pseudomonas fluorescens via the conserved molecular mechanisms of cell type differentiation in all living genera.
Examining that fact in the context of what is currently known about autophagy (Yoshinori Ohsumi)links everything known about biophysically constrained protein folding chemistry (Ben Feringa) to energy-dependent fixation of RNA-mediated amino acid substitutions in supercoiled DNA, which protect all organized genomes from virus-driven energy theft and genomic entropy (Gunter Witzany). December 9, 2016 at 4:34 PM

——————————-
Addendum:
Pleas for funding should be required to include information on what is already known.
Perhaps the focus should be on what can be done with WGS. It can be used to link energy-dependent bioluminescence from bacteria in the light organ of bobtail squid to the nutrient energy-dependent pheromone controlled weekend resurrection of the bacterial flagellum in Pseudomonas fluorescens via the conserved molecular mechanisms of cell type differentiation in all living genera.
Examining that fact in the context of what is currently known about autophagy (Yoshinori Ohsumi)links everything known about biophysically constrained protein folding chemistry (Ben Feringa) to energy-dependent fixation of RNA-mediated amino acid substitutions in supercoiled DNA, which protect all organized genomes from virus-driven energy theft and genomic entropy (Gunter Witzany).
See also: CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling

…improving the resolution of our cryoET data to better than 8Å using the novel lipid-monolayer system described above would allow generation of an atomic homology model of the E. coli chemosensory array, greatly facilitating the use of the wealth of existing biochemical and biophysical data and providing directly transferrable structural and dynamical predictions.

Reported as: Researchers resolve structure of a key component of bacterial decision-making
Excerpt 1)

A new study offers atomic-level details of the molecular machinery that allows swimming bacteria to sense their environment and change direction when needed.

My comment (from last year):

The nutrient-dependent pheromone-controlled links from atoms to ecosystems were established in the context of the report on re-evolution of the bacterial flagellum that occurred in 4 days.

Conclusion: “To know how this mechanical system works, we need to know the structure,” he said. “Once we open the clock, see how the gears fit together, then we can start thinking about how the clock actually works. The gears of the bacterial brain are now in place.”

The “gears” of the “brain” are linked to the “gears” of the bacterial flagellum in 4 days by 2 nutrient-dependent amino acid substitutions in another microbial species. That suggests that the molecular mechanisms may be the same in all individuals of all living genera, unless there is a different model that links ecological variation from atoms to ecosystems and ecological speciation and all morphological and behavioral biodiversity.

The terms they use link the evolution of irreducibly complex structures and functions to life history transitions in morphological and behavioral phenotypes in 4 days.

Serious scientists would probably place this example of atoms to ecosystems adaptations into the context of links from physics and chemistry to the conserved molecular mechanisms that link biophysically constrained nutrient-dependent RNA-mediated cell type differentiation in all living genera via the physiology of reproduction and fixation of the amino acid substitutions in organized genomes that protects all organisms from DNA damage and virus-driven genomic entropy.

Repeated attempts to link conserved molecular mechanisms of energy-dependent protein folding chemistry from species of microbes to humans have failed. Neo-Darwinian theorists are not like molecular biologists because theorists prefer theories to facts.
See also (from last year) Dinosaurs Evolved Rapidly For No Reason

Excerpt: “…apparently that thought falls into a black hole in their evolved brains.”

Again?

Without a thought, another recent report of an evolved microbial “brain” in E.coli linked the “Blind Watchmaker” metaphor to the over-the-weekend re-evolution of the bacterial flagellum in another species.

See: Researchers resolve structure of a key component of bacterial decision-making

Excerpt: “He compares the process of discovery to that of someone encountering a mechanical clock for the first time.

“To know how this mechanical system works, we need to know the structure,” he said. “Once we open the clock, see how the gears fit together, then we can start thinking about how the clock actually works. The gears of the bacterial brain are now in place.”

See also: Evolutionary Rewiring

If you are interested in how serious scientists rather gleefully place these two reports into the context of the creation of functional structures across species via what is known about atoms to ecosystems links to biophysically constrained nutrient energy-dependent base pair changes and cell type differentiation in all living genera, see this parody. The gears of the bacterial brain and the gears of the bacterial flagellum appear to have co-evolved in 4 days, or must be considered in the context of what is known about their creation.


 

Alternative splicing of pre-mRNA

Energy-dependent de novo creation and neurogenesis

See also: Tasting light links energy from creation to adaptation

Developmentally defined forebrain circuits regulate appetitive and aversive olfactory learning

reported as: When neurons are ‘born’ impacts olfactory behavior in mice

My summary:

The de novo creation of different cell types is placed into the context of their energy-dependent birth and the transgenerational epigenetic inheritance of molecular mechanisms that link virus-driven energy theft to all pathology via olfaction, food odors, and human pheromones.

See for comparison: Metabolism and neurogenesis

…it seems quite obvious that cellular metabolism determining for example the cell’s energy status will be linked to NSPC activity and neuronal differentiation processes, as cell division and differentiation are associated with an increase in cell volume and biomass production and require substantial amounts of energy for DNA replication and organelle synthesis [7].

See also: Extensive variability in olfactory receptors influences human odor perception

…the underlying amino acid sequence can vary slightly for each of the 400 receptor proteins, resulting in one or more variants for each of the receptors.

See my comments:

1) The truth revealed in the context of amino acid substitutions is that the theory of mutation-driven evolution does not make sense and it never did.

See for example: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

“…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution.”

One reason you may not know this yet is that you were taught to believe in a theory that was never supported by experimental evidence from any species.
See for review: An experimental test on the probability of extinction of new genetic variants.

2) For contrast, note the insistence by the moderator of the International Society for Human Ethology’s yahoo group. He thinks that random mutations are the substrates on which directional natural selection acts. This is what happened when I told him that natural selection is for food:

https://groups.yahoo.com/neo/groups/human-ethology/conversations/topics/48182

Jay R. Feierman, best known to me for his ridiculous question: “What about birds?” wrote:

“It is very sad for me to see that when several different people on this group, all with doctorate degrees, tell you that you are not correct, you don’t consider that they might be telling you something helpful. Instead, you respond with arrogance and ignorance. I’ll add my voice to the other people on this group who have told you that you are not correct in terms of your understanding of what “variation” means in Darwinian biological evolution and what is doing the selecting. Variation is not nutrient availability…”

All experimental evidence of biologically-based energy-dependent cause and effect has proved that Jay R. Feierman and others like him are biologically uninformed and that they choose to remain that way. This evidence from December 2012 shows that nutrient availability is the only variant that can be directly linked from the energy-dependent physiology of reproduction in bacteria to neurogenesis in the human brain!

See also: No two people smell the same

A difference at the smallest level of DNA—one amino acid on one gene—can determine whether you find a given smell pleasant.

See also: Human-specific genomic signatures of neocortical expansion

 My unedited comment:

The genomic signatures are energy-dependent and biophysically constrained by the availability of nutrients. Supercoiled DNA links what is known about nutritional epigenetics to all cell type differentiation in all living genera.

See: Metabolism and neurogenesis

  “…it seems quite obvious that cellular metabolism determining for example the cell’s energy status will be linked to NSPC activity and neuronal differentiation processes, as cell division and differentiation are associated with an increase in cell volume and biomass production and require substantial amounts of energy for DNA replication and organelle synthesis [7].”

I have access to this excellent review on the subject.

See for comparison: [MODERATOR NOTE: Edited for publishing. jrf]

RNA-mediated.com

Now that Clarence Williams is back and jrf is again editing the responses he allows me to post, I hope everyone will see more than 800 examples of what they have missed.

The examples link energy-dependent epigenetically effected alternative RNA splicing from amino acid substitutions such as BDNF Val66Met and COMT Val158Met to cell type differentiation in all cell types of all living genera via what is known about biophysically constrained biologically-based cause and effect.

In the context of what is known about animal models, Samir et al (2016) published: MicroRNAs in the Host Response to Viral Infections of Veterinary Importance MicroRNAs in the Host Response to Viral Infections of Veterinary Importance

 Many people are now aware of the role that virus-driven energy theft plays in all pathology . . ..

Feierman’s passive/aggressive ignorance and his editing of my comments has reached peak efficiency. I do not expect any attempt to contribute to discussion to appear without his editorial omissions of my content.

He exemplifies academic suppression at its finest, and has done that for more than a decade. His legacy of ignorance may be historically significant. His question “What about birds?” was answered by researchers who linked epigenetic effects of nutrients and pheromones to chromosomal rearrangements in white-throated sparrows, which led others to look for, and to find, evidence of chromosomal rearrangement and biodiversity in other species.

See: Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes

…our results illustrate a detailed chain of events linking a chromosomal rearrangement to changes in overt social behavior.

Their results were perfectly predictable, and so were the Nobel Prize winning results of these two researchers.

  1. Ben Feringa (2016 Chemistry)
  2. Yoshinori Ohsumi (2016 Physiology or Medicine)

1) Dynamic control of chirality and self-assembly of double-stranded helicates with light Feringa with co-authors (2016)

2) Structural Basis for Receptor-Mediated Selective Autophagy of Aminopeptidase I Aggregates Ohsumi with co-authors (2016)

The works, cited above, predictably linked the works of these two 1933 Nobel Prize-winner to everything currently known about biophysically constrained energy-dependent RNA-mediated protein folding chemistry

  1. Thomas Hunt Morgan (Physiology or Medicine 1933)
  2. Erwin Schrodinger (Physics 1933)

1) Thomas Hunt Morgan (September 25, 1866 – December 4, 1945)[1] was an American evolutionary biologist, geneticist, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries elucidating the role that the chromosome plays in heredity.[2]

2) Schrodinger monograph (1944) What is Life?

Thermodynamic cycles of protein biosynthesis and degradation link Schrodinger’s claims about higher temperatures from autophagy to nutrient energy-dependent fixation of RNA-mediated amino acid substitutions and all cell type differentiation in humans via transgenerational epigenetic inheritance.  Everything known to all serious scientists about all cell type differentiation suggests that our immune system typically functions at it best when the supply of nutrients is linked from natural selection for codon optimality to ecological adaptation via the nutrient energy-dependent pheromone-controlled physiology of reproduction.

See also: When neurons are ‘born’ impacts olfactory behavior in mice
My summary: The de novo creation of different cell types is placed into the context of their energy-dependent birth and transgenerational epigenetic inheritance of the molecular mechanisms that link virus-driven energy theft to all pathology via olfaction, food odors, and human pheromones.
See also: TET proteins drive early neurogenesis
All neurogenesis is energy-dependent and biophysically constrained by RNA-mediated protein folding chemistry. Energy drives neurogenesis.
Proteins do not evolve. If they did, biologically uniformed theorists could claim that virus-driven energy theft linked mutated proteins to the evolution of the human brain without linking the physiology of reproduction to behavior. Simply put, as others have learned sex is a biological variable.

Addressing sex as a biological variable

Each new misrepresentation of biophysically constrained cell type differentiation outside the context of energy-dependent differences or sex as a biological variable must be viewed in the context of how theorists must continue to try to deceive those who might otherwise become serious scientists.
In this case, the journal article about the TET proteins, Tet proteins influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling, claims: “…Wnt3 was shown to activate Nodal expression directly through its proximal epiblast enhancer at the gastrulation stage (58, 59).
58. Blaschke, K., Ebata, K. T., Karimi, M. M., Zepeda-Martinez, J. A., Goyal, P., Mahapatra, S., et al. (2013). Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature, 500(7461), 222-226.
59. Hashimoto, H., Pais, J. E., Zhang, X., Saleh, L., Fu, Z.-Q., Dai, N., et al. (2013). Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA. [Letter]. Nature.
If you are not told that the epiblast enhancers must first link nutrient energy-dependent changes in base pairs to cell type differentiation via RNA-mediated amino acid substitutions before the structure of functional proteins can be linked to anything else, you are less likely to learn that fixation of the substitutions in organized genomes only occurs via the physiology of reproduction. The pheromone-controlled physiology of reproduction links the metabolism of nutrients to all morphological and behavioral diversity in species from microbes to humans via the conserved molecular mechanisms of transgenerational epigenetic inheritance.
There is no question that transgenerational epigenetic inheritance is nutrient-dependent and pheromone-controlled is species from microbes to humans. That fact is now appearing in articles co-authored by the guest editors of a special issue of “Nutrients” who invited me to submit this review of nutritional epigenetics.

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.

My invited review was returned without review. Since then, one of the guest editors incorporated my claims into this: Insights from Space: Potential Role of Diet in the Spatial Organization of Chromosomes Published: 10 December 2014

The other guest editor incorporated my claims into this: The Interaction between Epigenetics, Nutrition and the Development of Cancer  Published: 30 January 2015

Many academics clearly cannot be trusted with accurate representations of biophysically constrained biologically-based cause and effect. Unless they have a record of accurate representations they are forced to try to establish a record after-the-fact. For example, see: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. This is the 2013 published review that led Justin O’Sullivan and Lynnette Ferguson to request the invited review of nutritional epigenetics, which they returned without review.

My model was cited in Role of olfaction in Octopus vulgaris reproduction

Future work on O. vulgaris olfaction must also consider how animals acquire the odours detected by the olfactory organ and what kind of odour the olfactory organ perceives. The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000).

It was also cited in Two fatty acyl reductases involved in moth pheromone biosynthesis (see #10)

Studies over the last two decades have pinpointed that the epigenetic effect of pheromone-driven adaptive evolution is one of the major factors driving the successful diversification of Lepidopteran insects10. In moths, a few substitutions in critical amino acids in the key pheromone biosynthetic enzymes are sufficient to create a novel pheromone component11,12.

If others had not cited my model, which is a refutation of neo-Darwinian pseudoscientific nonsense, there would be no record of experimentally established facts that link energy-dependent changes in the microRNA/messenger RNA balance to all cell type differentiation via RNA-mediated amino acid substitutions in all invertebrates and vertebrates.

fruit-dove

Theories vs facts about polycombic adaptation

See: Demoncrats fight polycombic ecological adaptation

Exosomes as miRNA Carriers: Formation–Function–Future

Important aspects will be highlighted as a take-home message (THM) at the end of each paragraph.

THM: Extracellular vesicles transport miRNA in a paracrine and endocrine manner. Questions regarding the cellular options of producing either microvesicles or exosomes and their difference in miRNA composition and number are still unknown.

In my 2014 invited review, the four F’s, Formation–Function–Future and Copulation were included in details about how the nutrient energy-dependent de novo creation of microRNAs must be linked to nutritional epigenetics. My invited review was returned without review by the guest editors of a special issue of “Nutrients.”
I realized the guest editors had “baited me” into providing them with all the available current information and published my submission to Figshare. That’s how I show the level of deception that biologically uninformed theorists still use to obfuscate what is known to serious scientists about biologically-based cause and effect.

See for example: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (April 10, 2014)

Abstract: “This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.”

Lynnette Ferguson, was one of two guest editors that invited my review.
 
She is the co-author of The Interaction between Epigenetics, Nutrition and the Development of Cancer This article belongs to the Special Issue NutritionalEpigenetics
 

Conclusion:

…it is imperative to understand the implications of diet on epigenetic modifications, and the effect of those modifications on the development of cancer today and in future generations. Such an understanding and an appropriate resultant response would help decrease the level of risk in future generations.

There would be no future generations if diet could not be epigenetically linked from metabolism to the pheromones that control the physiology of reproduction in species from microbes to human via energy-dependent changes in the microRNA/messenger RNA balance. The microRNA/messenger RNA balance biophysically contrains RNA-mediated protein folding chemistry.

Protein folding chemistry links energy-dependent changes from angstroms to ecosystems in all living genera via the innate immune system and fixation of RNA-mediated amino acid substitutions in supercoiled DNA. Supercoiled DNA exemplifies natural section for energy-dependent codon optimality, but theorists will not accept that fact. They would rather believe that the mutations in DNA are naturally selected and that mutation-driven evolution automagically occurs outside the context of energy or the virus-driven energy theft that causes all mutations and all pathology.

See also: The developmental basis for the recurrent evolution of deuterostomy and protostomy

This scenario challenges the assumed value of extant blastoporal behaviours for explaining the evolutionary origin and diversification of Bilateria that has been presumed for over 100 years4,5,6,7,9,10,11. Freeing the constraint that the mouth and anus have a necessary association with the embryonic blastopore will help in understanding the developmental events underlying the evolution of an alimentary canal5,20,21,50, and ultimately the appearance and diversification of bilaterian body plans.

All scenarios that failed to link energy-dependent behavior to the physiology of reproduction and also failed to link virus-driven energy theft to all pathology have always been based on questionable assumptions. The assumptions fall outside the context of Darwin’s “conditions of life,” which require links from what organisms eat to signaling and sensing and the behavior of other organisms.

For example, Schrodinger (1944) linked excretion from mammals to sunlight as the source of anti-entropic virucidal energy used to support all ecosystems. All serious scientists have done that since Thomas Hunt Morgan won the 1933 Nobel Prize in Physiology or Medicine for linking chromosomes to transgenerational epigenetic inheritance long before most people understood what the term autophagy means.

Alternative splicing of pre-mRNA

Metabolic Phenotyping Research

Global Consortium to Conduct Metabolic Phenotyping Research

Consortium members in six countries will use chromatography, mass spectrometry, and other technologies to conduct metabolic phenotyping research that examines the dynamic interactions between genes, environments, microbiomes, diets, and lifestyles, and their collective impact on disease.

My Predictions.
1. They will link energy as information to healthy longevity.
2. They will report their findings as if they discovered new molecular mechanisms.
3. The mechanisms will link the anti-entropic virucidal energy of ultraviolet light to all biophysically constrained RNA-mediated cell type differentiation in all living genera via the innate immune system and supercoiled DNA, which protects all organized genome from virus-driven entropy.
4. They will not link virus-driven energy theft to all pathology.
5. They will claim that the energy emerged and that all biodiversity on Earth evolved.
6. They will continue to be funded by the evolution industry and big bang cosmology industry, which ignore the obvious link from food energy to the physiology of reproduction and ecological adaptation.
SARCASM ALERT
7. They will claim that the Extended Evolutionary Synthesis will have explanatory power when it automagically evolves into a model of top-down causation that links physics and chemistry to the conserved molecular mechanisms of biologically-based cause and effect, which serious scientists have detailed during the past century.
See for comparison:

Diagram with abstract
Full text with references
See also: Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion

… these dual screens further the understanding of the role of host-derived small noncoding RNAs in the infection cycle of henipaviruses, and provide a miRNA-based resource for the study of viruses from the order mononegavirales, including members of both the filovirus and paramyxovirus families, which presents significant threats to human and animal health. This study implicates miR-181 and certain class A Eph receptors as critical modulators of henipavirus membrane fusion, and highlights how the natural innate immune response of the host can be exploited by a RNA virus to promote cell-to-cell spread.

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.

Alternative splicing of pre-mRNA

De novo gene creation: Ignoring the experimental evidence

Regularly Whiffing Essential Oils Can Retrain Lost Sense of Smell

It’s not entirely clear how olfactory training works on a neurological level.

Olfactory training links the experience-dependent de novo creation of G protein-coupled receptors to supercoiled DNA. Conserved molecular mechanisms link food odors and pheromones from the innate immune system to the physiology of reproduction. Simply put, autophagy protects all organized genomes from virus-driven entropy and all pathology via the de novo creation of odor receptor genes.
See for proof: Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo

The 3D segmentation of high-resolution images provided by SXT reveals an unappreciated interconnectivity between distinct forms of chromatin. The continuous nature of like-chromatin, which is evident even in the nucleolus, supports the existence of non-stereotypic but extensive interactions between different chromosomes, which might have significant regulatory roles in transcription and other nuclear processes.

Natural selection for energy-dependent codon optimality is the obvious link to experience-dependent chromatin remodeling and the de novo creation of species-specific G protein-coupled receptors, which link chemotaxis and phototaxis from the innate immune system to the physiology of reproduction in all living genera. It is obvious to all serious scientists that energy-dependent receptor-mediated biophysically constrained cell type differentiation is the link from angstroms to ecosystems in all living genera. But, in the next sentence, these authors claim (with my emphasis):

Although sequence-specific association of co-regulated genomic loci is appealing, random interactions between loci with shared chromatin properties might be an equally effective way of modulating transcription levels.

No experimental evidence of biologically-based cause and effect supports that ridiculous claim about random interactions. No experimental evidence of biologically-based cause and effect has ever supported similar claims that link anything except the energy-dependent de novo creation of functional protein structures via the modulation of transcription.

Transcription is energy-dependent and biophysically constrained. It links the innate immune system to supercoiled DNA, which protects all organized genomes from virus-driven energy theft and protects all organisms from all pathology via autophagy.

Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo was reported as

Imaging Technique Reveals Movement of Genetic Material Within Nucleus

Chromatin functions to package DNA so that it can fit inside of a cell, and forms chromosomes. In the video above, take a trip through the nucleus of a cell; in the video below, DNA reorganization in the nucleus a mouse cell is illustrated.

…it had been thought that chromatin existed as a group of disconnected islands, but the latest report indicated that chromatin is compartmentalized into two areas of “crowding” that comprise a continuous network throughout the nucleus.

The continuous network of chromatin distributes energy as information in the context of hydrogen-atom transfer in DNA base pairs.  Energy-dependent changes in base pairs link quantized energy from angstroms to ecosystems in all living genera via changes in the microRNA/messenger RNA balance. The ability to image the changes has not been linked from chromatin remodeling to RNA-mediated amino acid substitutions and chromosomal rearrangements, because the detailed sequence of biologically-based cause and effect refutes all neo-Darwinian theories. Natural selection for codon optimality comes first, not natural selection for benefical mutations. There is no such thing as a beneficial mutation.

Reported also as: 3-D Imaging Technique Maps Migration of DNA-carrying Material at the Center of Cells
Excerpt:

Detailed 3-D visualizations show an unexpected connectivity in the genetic material in a cell’s nucleus, and provide a new understanding of a cell’s evolving architecture.

What architecture evolves? Does it evolve via mutation-driven evolution? How is that possible?

These unique 3-D reconstructions of mouse olfactory cells, which govern the sense of smell, were obtained using X-ray imaging tools at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab). The results could help us understand how patterning and reorganization of DNA-containing material called chromatin in a cell’s nucleus relate to a cell’s specialized function as specific genes are activated or silenced.

The 3-D reconstructions govern the sense of smell via the de novo creation of G protein-coupled receptors in the mouse olfactory cells. The cells do not create or recreate themselves. Organization and reorganization of chromatin is energy-dependent.

“We’re trying to understand how the reorganization of chromatin affects gene expression,” Larabell said.

No you are not. You’re trying to avoid admitting that you got caught with your pants down after having missed all the experimental evidence of biologically-based cause and effect that refutes neo-Darwinian nonsense.

“No one’s been able to study this at the human level yet.” This research will hopefully lead to new insights about diseases and disorders that relate to gene expression. Already, the study’s results are being incorporated into models of cell development.

There is only one model of cell energy-dependent cell type differentiation during the development of all morphological and behavioral phenotypes in species from microbes to humans.
See for example: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

One of the precursors to Alzheimer’s disease, which attacks the brain’s nerve cells, is a loss of smell, so understanding this connection to olfactory nerve cells could perhaps serve as a diagnostic tool and perhaps unlock a deeper understanding of the degenerative disorder.

Who is claiming that this energy-dependent connection to the de novo creation of genes in olfactory nerve cells is not already understood by all serious scientists? Why are they lying about what is already known?

“This work highlights the power of multidisciplinary research,” said Mark Le Gros, associate director of the NCXT and a physicist who was responsible for the design and construction of the X-ray microscope. Le Gros, the lead author in this research, added, “This is an example of work that required a combination of molecular biologists and cell biologists with physicists and computer scientists.”

It highlights the ignorance of theorists. See for example: Search Results for “alzheimer”
For a historical perspective on the ignorance of theorists who are among the molecular biologists and cell biologists with physicists and computer scientists who published a paper that ignored all the accumulated experimental evidence of biologically-based cause and effect, see: Learning from Bacteria about Natural Information Processing

We proposed that, besides “negative entropy,” organisms sense the environment to extract latent embedded information.13 By latent information we refer to data embedded in the environment that, once processed cognitively, initiates change in the organism’s function or behavior. Information induces changes; hence it can be used to generate an internal condensed description (model or usable information) of the environment, which guides the organism’s functioning.

See also: From Fertilization to Adult Sexual Behavior
We included a section on molecular epigenetics, and nothing about the facts that we detailed has changed at any level of examination that links energy-dependent changes from angstroms to ecosystems in all living genera.

The Genome, positioning, timings. There are major structural differences between the X and Y chromosomes; e.g., centromeric aiphoid repeats sequences and distribution of heterochromatin (Graves, 1995; Wolfe et al., 1985). These structural differences correlate with sexually dimorphic chromosomal positioning within the nucleus and with male/female differences in replication timing of the active X, the inactive X, and the Y chromosomes, e.g., Boggs and Chinault (1994), Clemson and Lawrence (1996); Hansen, Canfield, and Gartler (1995). Increasingly the structure and timings within the nucleus are realized as contributing to gene expression regulation (Manders, Stap, Strackee, van Driel, and Aten, 1996; Stein, Stein, Lian, van Wijnen, and Montecino, 1996).

See also The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity Published September 30, 2015
Their cited works link energy-dependent chromatin interactions from the determinants of nucleosome organization to G+C content and intrinsic nucleosome occupancy, which is linked to biophysically constrained cell type differentiation via chromosomal inheritance in primary human cells. The terms “promoter elements” and “self-renewal” are used to obfuscate the fact that energy-dependent RNA-mediated amino acid substitutions differentiate all cell types in all living genera in the context of autophagy and polycombic ecological adaptations. The nutrient energy-dependent fixation of the RNA-mediated amino acid substitutions in supercoiled DNA is not mentioned in the context of autophagy, which must be linked to physiology of reproduction. The game of hide the facts about virus-driven energy theft and all pathology continues to be played by experts who do not want anyone to know what they missed when they invented their theories and taught others to believe in them.
Reported Nov 22, 2016  as: Researchers uncover a survival mechanism in cancer cells

The results showed an inverse relation between H1.0 and the division of cancer cells: “As the H1.0 levels fall, the greater the potential of uncontrolled division of cells. In contrast, high levels of the protein prevent this process. We found that the disappearance of protein H1.0 is characteristic of cancer stem cells and it is necessary to maintain the ability of partition and the potential for growth creation.”

Virus-driven energy theft is clearly linked to the disappearance of H1.0 via everything known to serious scientists about autophagy. Energy-dependent RNA-directed DNA methylation stops the proliferation of undifferentiated cell types is all living genera and it links amino acid substitutions from biophysically constrained protein folding chemistry to supercoiled DNA and all biodiversity. Reports of negative supercoiling in bacteria link virus-driven energy theft from the creation of archaea to the transgenerational epigenetic inheritance of Zika virus-damaged DNA via the conserved molecular mechanisms of epigenetic top-down causation that links food odors from pheromones to the physiology of reproduction.
See also: How keeping active pays off in the olfactory system
open access with comments at Neuroscience: How keeping active pays off in the olfactory system

Is what’s being elucidated the bottom-up epigenetic effects on stochastic gene expression via chromatin remodeling, which is controlled by the top-down epigenetic effects of pheromones on reproduction in species from microbes to man?
Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors. Socioaffective Neuroscience & Psychology, 2: 17338. DOI: 10.3402/snp.v2i0.17338.

The article elucidates how the environment can broadly influence gene expression through an epigenetic effect chromatin – the way DNA is package and organized. This allows the environment to influence sensory function, to tune the olfactory sense to better suit the surrounding environment, because these environmentally regulated chromatin changes are coupled to cell longevity. This results in a change in the distribution of cells in the tissue that have made particular stochastic choices, where the stochastic choice is which olfactory receptor to express, without affecting the mechanism of stochastic gene expression.

I have since modeled nutrient-dependent pheromone-controlled adaptive evolution and uploaded the text and diagram, which are available here: http://dx.doi.org/10.6084/m9.f… I was advised I should have previously declared ownership of the domain Pheromones.com and my commercial involvement in marketing products based on animal models of common molecular mechanisms in species from microbes to man.

I have since published “Nutrient-dependent/pheromone-controlled adaptive evolution: a model” http://www.socioaffectiveneuro…

Model organisms exemplify the fact that the epigenetic effects of olfactory/pheromonal input result in nutrient-dependent amino acid substitutions and changes in phenotype associated with the pheromone-controlled physiology of nutrient-dependent reproduction. Included are example in microbes, nematodes, insects, other mammals, and a human population that adaptively evolved in what is now central China during the past ~30,000 years.

rp_levels-of-organization.jpg

Energy-dependent maternal-to-zygotic transition

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)

Filtering light through a prism to identify tissue type

Epigenetics and autophagy vs mutations and evolution (5)

Excerpt:

Yuste says he’s proud of what he and Denk accomplished. “But now I go to meetings where everyone is presenting two-photon calcium imaging, and no one knows, or remembers, or cites our work,” he says, laughing.

My comment: What else can be done but laugh? Most researchers still have not linked the anti-entropic energy of virucidal ultraviolet light from the biophysically constrained RNA-mediated chemistry of protein folding to all biodiversity in all genera despited the advances that link biophotonics and femotosecond blasts of UV light to DNA repair and to supercoiled DNA via the physiology of reproduction.

Many still seem to be largely unaware that supercoiled DNA protects all organized genomes from virus-driven entropy because they cannot see the femtosecond blasts. They decide to link mutations to the evolution of all biodiversity, instead.

See for comparison the molecular epigenetics section of our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior

I stopped attending meetings where everyone is presenting on molecular epigenetics and no one knows, or remembers, or cites our work. Neo-Darwinian theorists have continued to present findings in the context of pseudoscientific nonsense and the are now trying to link the molecular mechanisms of energy-dependent polycombic ecological adaptation to a new ridiculous theory of evolution, which they refer to as adaptation.

Unified theory of evolution 

Introduction:

The unifying theme for much of modern biology is based on Charles Darwin’s theory of evolution, the process of natural selection by which nature selects the fittest, best-adapted organisms to reproduce, multiply and survive. The process is also called adaptation, and traits most likely to help an individual survive are considered adaptive.

My comment: The process of evolution was not called adaptation until people like Michael Skinner realized there is no such thing as mutation-driven evolution. They know it is obvious that nutrient energy-dependent pheromone-controlled biophysically constrained protein folding chemistry controls cell type differentiation because otherwise life could not exist on Earth.

See also: Why do some cancers suddenly disappear?

See also: Scientists analyze repeats in proteins implicated in neurological diseases

Glutamine is the amino acid coded for by the genomic trinucleotide CAG. Repeating glutamines, called polyglutamines, are normal in huntingtin proteins, but when the DNA is copied incorrectly, the repeating sequence of glutamines can become too long. The result can be diseases like Huntington’s or spinocerebellar ataxia.
The number of repeats of glutamine can grow as the genetic code information is passed down through generations. That means a healthy parent whose huntingtin gene encodes proteins with 35 repeats may produce a child with 36 repeats. A person having the longer repeat is likely to develop Huntington’s disease.

My comment: The number of repeats is nutrient energy-dependent and longer repeats link virus-driven energy theft to all pathology.

Alternative splicing of pre-mRNA

Polycombic ecological adaptation as a science, not a theory (2)

Evolutionary Constraints in the β-Globin Cluster: The Signature of Purifying Selection at the δ-Globin (HBD) Locus and Its Role in Developmental Gene Regulation

Conclusion:

… the results here presented indicate that purifying selection is driving not only HBD evolution but also its neighbor pseudogene, HBBP1. In the light of recent advances in the characterization of the β-globin cluster, we propose that the complex patterns of diversity observed in this genomic region arose from distinct functional constraints related with the intricate process of chromatin and protein interactions coordinating the differential expression of genes at the β-globin cluster during development.

My comment: No experimental evidence of biologically-based cause and effect suggests that any locus of genes or any pseudogene has ever evolved. Purifying selection cannot drive evolution. Only energy-dependent variations can can be linked to polycombic ecological adaptation, and only virus-driven energy theft has been linked to the creation of pseudogenes in the context of biophysical constraints on viral latency.

See for comparison: microRNA Function Is Limited to Cytokine Control in the Acute Response to Virus Infection

Excerpt:

miRNA function is generally limited to cytokine levels in response to RNA viruses

Reported as: Mount Sinai Researchers Use Cellular miRNA-Elimination Tool to Study Viral Infection Dynamics

Excerpt:

…while the loss of miRNAs had a negligible impact on the cell’s immediate reaction to a virus or the short-term biology of the cell, sustained depletion had dramatic results on gene expression that was coupled to a burst of cytokines. The researchers concluded in the paper that miRNA function is limited to modulating the biology of the cell over long periods of time.

My comment: In my model, energy-dependent changes in the microRNA/messenger RNA balance link nutrient energy-dependent changes to all healthy longevity and virus-driven energy theft is linked to all pathology. Over long periods of time, autophagy is the link to polycombic ecological adaptation or virus-driven hecatombic evolution of pathology via energy-dependent biophysically constrained RNA-mediated protein folding chemistry. For example, fixation of amino acid substitutions differentiates all cell types in all individuals of all living genera in the context of the physiology of reproduction. For comparison, virus-driven hecatombic pathology is linked from mutations to all pathology.

Simply put, in my model of polycombic ecological adaptation, differential gene expression is nutrient-dependent and controlled by the physiology of reproduction.

See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Conclusion: 

…the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

My comment: Claims about RNA-mediated polycombic ecological adaptation were first placed into the context epigenetic imprinting in our 1996 review.

See: From Fertilization to Adult Sexual Behavior

Excerpt:

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). 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). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

My comment: Polycombic ecological adaptation appears to link energy-dependent epigenetic effects on hormones (i.e., proteins) to chromatin structure in telomeric regions, which links the effect on transcription and silencing of various genes to hormone-organized and hormone-activated affects on behavior. The hormone-organized and hormone-activated behaviors link the epigenetic landscape of yeasts to the physical landscape of supercoiled DNA in species from bacteria to invertebrates and all vertebrates via the de novo creation of G protein-coupled receptors, which link chemotaxis and phototaxis to all biodiversity.

For comparison, see: Mutation-Driven Evolution

Excerpt:

Mutation… includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc.

My comment: The definition above links mutations to any change in any genome.

See for comparison: Updates of the HbVar database of human hemoglobin variants and thalassemia mutations

Excerpt:

Single nucleotide substitutions or indels [insertions/deletions] can lead to several hemoglobin variants owing to amino acid replacements, while molecular defects [mutations] in either regulatory or coding regions of the human HBA2, HBA1, HBB or HBD genes can minimally or drastically reduce their expression, leading to α-, β- or δ-thalassemia, respectively.

My comment: The facts about nutrient energy-dependent amino acid substitutions link hemoglobin variants from ecological adaptation to healthy longevity and the facts also link molecular defects from mutations to the pathology of α-, β- or δ-thalassemia, respectively. It would be difficult to include facts about biophysically constrained energy dependent cell type differentiation in the context of any other model that links amino acid substitutions to healthy longevity and links mutations to all pathology in all living genera.

See for example:  Criticisms of the nutrient-dependent pheromone-controlled evolutionary model 

Excerpt:

…James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others’ research.

My comment: The claims of a biologically uninformed undergraduate student reviewer were placed into the context of modern evolutionary theory, which involves Masatoshi Nei’s simple-minded revision of neo-Darwinian pseudoscientific nonsense. Nei does not compare his theory of mutations to the facts about nutrient energy-dependent fixation of amino acid substitutions in supercoiled DNA. The problem appears to be the use of the term “mutation” in the textbook published on the same day as my 2013 review was published.

I linked the energy-dependent fixation of amino acid substitutions to all healthy longevity. Nei’s textbook misrepresentations did not link anything to healthy longevity, but linked mutations to what I claimed are nutrient-dependent pheromone-controlled polycombic ecological adaptations.

I failed to include what is known about energy-dependent codon optimality in the context of polycombic ecological adaptations because there was no experimental evidence of biologically-based cause and effect to support those claims at the time of our 1996 review or my 2013 review. For comparison, there has never been any experimental evidence of biologically-based cause and effect to support claims about mutation-driven evolution. Simply put, nothing known to serious scientists about cell type differentiation suggest that mutation-driven evolution can occur.

For comparison, see: New analysis of big data sheds light on cell functions
Excerpt:

With today’s technology, scientists are able to generate data about a cell’s or organism’s complete set of genes, proteins, RNA profiles, metabolites and much more—known as omic data. Using omic data, scientists can model complex biological interactions and gain a more holistic view of different cellular processes.

See also: Research Topic Multi-omic Data Integration

Excerpt:

Stable, predictive biomarkers and interpretable disease signatures are seen as a significant step towards personalized medicine. In this perspective, integration of multi-omic data coming from genomics, transcriptomics, glycomics, proteomics, metabolomics is a powerful strategy to reconstruct and analyse complex multi-dimensional interactions, enabling deeper mechanistic and medical insight.

My comment: Glycomics, transcriptomics, proteomics, metabolomics and genomics have established fact about the biological basis of complex multi-dimensional interactions that link the nutrient-dependent pheromone-controlled physiology of reproduction in bacteria from quorum sensing to the molecular mechanisms that enable deeper mechanistic and medical insight in the context of the National Microbiome Initiative and Precision Medicine Initiative.

See for example: ‘Oming in on RNA–protein interactions

Excerpt:

…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].

See for comparison: From Fertilization to Adult Sexual Behavior

Excerpt:

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…. That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

My comment: Detailed examples of how the interactions between pre-mRNA and alternative splicings create new genes in the fine-tuned energy-dependent functional structure of supercoiled DNA explain how all cell types of all individuals of all living genera are protected from virus-driven energy theft. Energy-dependent RNA-mediated amino acid substitutions are fixed in organized genomes via the physiology of reproduction, which helps to prevent the transgenerational epigenetic inheritance of nearly all pathology by linking innate immune system to supercoiled DNA.

For comparison, viruses steal the energy that is required for cell type differentiation, which is how mutations are linked to all pathology. All differences between healthy longevity and virus-driven human pathology can be explained in the context of how nutrient energy-dependent microRNAs. The nutrient energy-dependent microRNAs are carried by erythrocytes in species with circulating blood.

See: Pitfalls of analysis of circulating miRNA: role of hematocrit

MicroRNAs are are delivered to the cell types on an as needed basis. When too few nutrient energy-dependent microRNAs are available, viruses use the existing energy they steal from cells to replicate. Eventually, the replication of the viruses causes the mutations, which are linked to all pathology. That’s why it is important to revisit the facts presented in the context of this article, which was published on 10/26/16

See: Multi-omic data integration enables discovery of hidden biological regularities
I reported this here as: Polycombic ecological adaptation as a science, not a theory for comparison to Biological evolution as a philosophy, not a science.
Despite several attempts to discuss the difference between science and philosophy, no progress was made.
See for example: Evolutionary assumptions (revisited)
See also the impasse that was reached in this attempt to discuss the anti-entropic virucidal energy of the sun.
It is worth joining The Battlefield FB group to see that others would rather hold on to their theories and opinions despite the overwhelming amount of experimental evidence that I have used to support my claims. For me, it is time to move forward and focus on the rediscovery of hidden biological regularities.
Finally, others have discovered that small intranuclear proteins generate alternative splicing techniques of pre-mRNA, which is how microRNAs link hydrogen-atom transfer in DNA base pairs in solution to the conserved molecular mechanisms of energy-dependent cell type differentiation, and to all cell type differences in all individuals of all living genera.
For comparison, this is an example of how virus-driven energy theft is linked viral replication and to virulence:
Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.

For an example of how nutrient energy-dependent RNA-mediated amino acid substitutions are linked to healthy longevity via the physiology of reproduction, see:

…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla (p. 127).”

My comment: The facts stated above have forced theorists to invent evolutionary cell biology.
See Evolutionary cell biology: Two origins, one objective
Reported as: Why some junk DNA is selfish, but selfish genes are junk
Excerpt:

“A commonly held but incorrect stance is that essentially all of evolution is a simple consequence of natural selection.” They point out, for example, that many pathways to greater complexity of both genomes and cells don’t confer any selective fitness.

My comment: Greater complexity requires a link from ecological variation to polycombic ecological adaptation, which links supercoiled DNA to protection from the virus-driven hecatombic evolution of all pathology.
My comment: New theories are worthless if they do not include information on the role of energy in cell type differentiation or the role of virus-driven energy theft in all pathology.
See for comparison the facts about: Detection of hemoglobinopathies and thalassemias using automated separation systems
See also: In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery
Excerpt: 

The combination of nanoparticle delivery, next generation γPNAs and SCF treatment may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration.

My comment: That fact suggests all suffering and death caused by hemoglobin variants is caused by neo-Darwinian theorists who do not know how the variants link ecological variation to polycombic ecological adaptation.

Reported as: Scientists edit gene mutations in inherited form of anemia
Excerpt:

The researchers found that the technique corrected the mutation to such a degree that the mice no longer had symptoms of thalassemia. After 140 days, they tested hemoglobin levels in the animals and found them to be normal.
“The fundamental result here is that with nanoparticles containing PNAs, along with template DNA, and simple IV infusion of molecules, we achieved enough gene editing to effectively cure the anemia in mice that had thalassemia,” Glazer said.

My comment: The ability to correct the mutation requires a link from energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solutions such as blood. That’s how their IV therapy works. It changes the microRNA/messenger RNA balance and that forces the innate immune system to repair the damaged DNA.
See also:  Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans
Excerpt:

Two SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability.

Reported as: Study Identifies Two New Genes Responsible for Alzheimer’s in African Americans
Excerpt:

In 2013, a genome-wide association study of AD in more than 5,500 African Americans identified two genetic risk factors for AD. This study looked at genetic variants across subjects’ entire genome and compared their frequency in cases versus controls.
By doing so they were able to identify two new genes (COBL and SLC10A2) associated with risk of AD in African Americans.

My comment: The author’s study results link hydrogen-atom transfer in DNA base pairs in solution to energy-dependent changes in the microRNA/messenger RNA balance. The neuroscience news report claims they identified two new genes. The neuroscience news report then links the genes — instead of the energy-dependent changes — to the disease in a human population. Many African Americans are examples of how ecological variation has been linked to polycombic ecological adaptation via hemoglobin variants. The adaptations include amino acid substitutions linked to the stability of organized genomes in populations where malaria is endemic. Failed adaptations are included in examples of virus-driven energy theft linked to mutations and the pathology of Alzheimer’s disease.

My comment: The ability to edit out gene mutations clearly links RNA-mediated amino acid substitutions to supercoiled DNA and all biodiversity.
See also: Inventing neo-Darwinism
See also: Pioneering Geneticist Explains Ambitious Plan to “Write” the Human Genome

Excerpt:

…he notes that with an editing tool like CRISPR, one base out of many can be altered, but with a synthesis approach, a hundred edits could be made. This sort of change, he tells JAMA, could make a cell resistant to multiple viruses.

My comments: All the changes in base pairs may already have been linked from natural selection for codon optimality and energy-dependent changes in RNA-mediated cell type differentiation to supercoiled DNA, which links the physiology of reproduction from the innate immune system to fixation of the amino acid substitutions that differentiate the cell types of all living genera. If so, what might happen to an organized genome when a hundred edits are made?

Will anyone be able to stop the hecatombic evolution of pathology via the polycombic ecological adaptation, which links autophagy to healthy longevity via protection of organized genomes from virus-driven entropy?

See also: Yale scientists edit gene mutations in inherited form of anemia Genetics & Genomics

A new gene therapy is being tested for its ability to treat thalassemia, a form of anemia caused by genetic mutations. So far, scientists have successfully corrected gene mutations causing the disease in mice, and now researchers are interested in seeing if the same approach will work effectively in humans.
“The fundamental result here is that with nanoparticles containing PNAs, along with template DNA, and simple IV infusion of molecules, we achieved enough gene editing to effectively cure the anemia in mice that had thalassemia. We demonstrated we have extremely low off-target effects.”

See for comparison:

Product Development Pipeline

Excerpt:

Each microRNA mimic in our pipeline is designed to replicate the activity of a single tumor suppressor miRNA and regulate the expression of key oncogenes across multiple oncogenic pathways which can prevent proliferation and induce apoptosis in cancer cells.

See also: VACRC Projects

Excerpt: Future Projects

 The Influence of Carbon Dioxide Enhancement on Plant Growth
 Thermoregulation in Honey Bees
 Biochemistry and Taxonomy in Pine Trees
 The Formation of Multiple Tree Rings in Bristlecone Pine Trees

The VACRC suddenly seems willing to take everything I have claimed about RNA-mediated cell type differentiation during the past twenty years and begin to investigate the claims. This would have been a desirable outcome 20 years ago, but now it might prevent progress via use of my model. The model links energy-dependent changes from angstroms to ecosystems in all living genera, it and links virus-driven energy theft to all pathology.

The Pacific Yew Tree and production of taxol is an example of how the physi0logy of reproduction in soil bacteria can be linked from plant growth to the honeybee model organism of thermoregulation and behavior, which must be linked to the biochemistry and taxonomy of all species. That becomes meaningful via the explanatory power of a model that links RNA-mediated amino acid substitutions to all energy-dependent biodiversity via the conserved molecular mechanisms of polycombic ecological adaptation we detailed in our 1996 review.

However, when others wait too long to accept a model that may already have led to a paradigm shift, they may also realize it. That fact was addressed by Kaveli Kull in the context of next week’s meeting of the Royal Society.

See: Kalevi Kull: Censorship & Royal Society Evo Event

Excerpt:

Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge.

My comment: Some work by young earth creationists has been at the cutting edge since 1996, as indicated here: Where do viruses come from?

Excerpt:

‘Viruses tend to keep nutrients away from the big stuff and keep them going around in the little stuff,’ says Fuhrman. If so, viruses have shaped the entire structure of the ecosystem.”9

My comment: 9 is Holmes, B. (1996) Who Rules the Waves? New Scientist 152(2054):8-9, supp I have not read it in its entirety but the claim fits into the context of everything else I have learned about physics, chemistry, and conserved molecular mechanisms of RNA-mediated cell type differentiation, which appears to be biophysically constrained in all living genera via their nutrient-dependent pheromone-controlled physiology of energy-dependent reproduction.