Redox sensing controls DNA replication!

Schrodinger's answer to Schrodinger's question

There is no such thing as de novo control of electrons or self-assembly.

Answering Schrödinger’s question: A free-energy formulation

The free-energy principle (FEP) is a formal model of neuronal processes that is widely recognised in neuroscience as a unifying theory of the brain and biobehaviour. More recently, however, it has been extended beyond the brain to explain the dynamics of living systems, and their unique capacity to avoid decay.

They don’t understand the question that Schrodinger answered. He linked the anti-entropic virucidal energy of sunlight to the physiology of pheromone-controlled reproduction via what organisms eat. What they eat protects them from the virus-driven degradation of their messenger RNA. What they eat links food energy-dependent changes in base pairs from microRNA editing to RNA editing and fixation of RNA-mediated amino acid substitutions in organized genomes of all individuals of all living genera.

Schrodinger answered this question: What is life when it is not protected from virus driven entropy? (video 6:37) Published on 30 Mar 2016

Abstract:

The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair. In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans. Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry. Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.

Life that is not protected from the virus-driven degradation of messenger RNA links the reduced number of food energy-dependent microRNAs to activation of the death gene. See for example:

Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene 

The natural contribution of food energy is linked to the endogenous level of microRNA expression seen in neuronal cells in the context of limited cell death compared control glioblastoma cells. That fact was linked to the treatment of brain cancers.

For a review of how food energy-dependent microRNAs protect the organized genomes of all living genera from the virus-driven degradation of messenger RNA that links mutations to all pathology, see:

A Concise Review of MicroRNA Exploring the Insights of MicroRNA Regulations in Bacterial, Viral and Metabolic Diseases

For a example of how human idiocy has prevented the effective treatment of all pathology, see also:

Neuropathological and transcriptomic characteristics of the aged brain

Reported as: Researchers reveal new details on aged brain, Alzheimer’s and dementia

One factor that is not always taken into account when studying gene expression in the aged brain is the quality of the genetic material itself,” says Miller. “This variable is not necessarily related to any specific pathology or disease, but these results highlight the importance of properly controlling for RNA quality when studying the aged brain and indicate that degradation of genetic material may be an underappreciated feature of neurodegeneration or dementia.

 Re: degradation of genetic material may be an underappreciated feature of neurodegeneration or dementia.

See: Cytosis

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

Alternative splicing of pre-mRNA

From base editing to RNA editing (4)

Summary: To claim evolution, Koonin must link food energy from the pheromone-controlled physiology of reproduction to fixation of a beneficial mutation in the organized genome of one species that evolved into another species.
Search Results for “base editing” = 82 blog posts starting with Cell-type differentiation on February 7, 2014
Search Results for “RNA editing” = 95 blog posts starting with In theory, or supported by experimental evidence? October 22, 2014
See for comparison PubMed: “base editing” (33 citations) and “RNA editing” (4222 citations)
The failure to link energy-dependent base editing to RNA editing and RNA-mediated cell type differentiation in all publications about healthy longevity compared to pathology can be attributed to the pseudoscientific nonsense touted by theorists. In their ridiculous mathematical models, they claimed the emergence of energy could be linked to the evolution of all biodiversity. Their lack of experimental evidence, which is required to link biologically-based cause and effect to biodiversity, was placed into the context of “human idiocy” by Richard P. Feynman.

See Richard P. Feynman’s lecture on: Food energy. See for comparison see: Energy as information and constrained endogenous RNA interference.

Feedback loops link quantized energy as information to biophysically constrained RNA-mediated protein folding chemistry. Light induced energy-dependent changes link angstroms to ecosystems from classical physics to chemistry/chirality and to molecular epigenetics/autophagy.

The National Microbiome Initiative links microbial quorum sensing to the physiology of reproduction via endogenous RNA interference and chromosomal rearrangements. The rearrangements link energy-dependent fixed amino acid substitutions to the Precision Medicine Initiative via genome wide inferences of natural selection.

This detailed representation of energy-dependent natural selection for codon optimality links biologically- based cause and effect from G protein-coupled receptors to RNA-mediated amino acid substitutions and the functional structure of supercoiled DNA. Energy-dependent polycombic ecological adaptations are manifested in supercoiled DNA. Chromosomal inheritance links the adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes. For contrast, virus-driven energy theft is the link from messenger RNA degradation to negative supercoiling, constraint breaking mutations, and hecatombic evolution. The viral hecatomb links transgenerational epigenetic inheritance from archaea to Zika virus-damaged DNA, which typically is repaired by endogenous RNA interference and fixation of RNA-mediated amino acid substitutions in organized genomes.

The failure to link energy-dependent base editing and energy-dependent RNA editing to healthy longevity predicted the failure to link the virus-driven degradation of messenger RNA to all pathology. See for instance: The Science of Personalized Nutrition

A single nucleotide polymorphism (SNP) or change occurs in nearly 1 in 1,000 base pairs and accounts for much of an individual’s uniqueness. Research on SNPs and other genetic variations like deletions, inversions, duplications and copy number variations (CNV), which represent up to 9.5 percent of the human genome, have changed the face of human nutrition and validated the concept that nutrition could and should be personalized. (Mullally, 2007)

A single nucleotide polymorphism (SNP) is a single base-pair difference in the DNA sequence of individual members of a species. SNPs in genes may lead to variations in the amino acid sequence, but SNPs can also occur in noncoding regions of DNA. Base editing of A•T to G•C in genomic DNA was linked from RNA editing to the physiology of pheromone-controlled reproduction and fixation of amino acid substitutions in organized genomes. The amino acid substitutions differentiate all cell types in all individuals of all living genera.
See: Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage
Reported as: Base Editing Now Able to Convert Adenine-Thymine to Guanine-Cytosine

Bioengineer Feng Zhang of MIT’S Broad Institute notes in an email that the team employed “a comprehensive and creative approach” to achieve such precision. “As a field, we have been looking for ways to precisely rewrite parts of the genetic code,” writes Feng, whose own, CRISPR-based method to edit single bases in RNA was published today in Science. “Base editors move us closer to this goal.”

The CRISPR-based editing of single base pairs in RNA links the energy-dependent function of the innate immune system to all biophysically constrained biodiversity via the pheromone-controlled physiology of reproduction, which biophysically constrains viral latency. Natural selection for energy-dependent codon optimality, links the editing of single base pairs in RNA to every aspect of healthy longevity via RNA editing.
See: RNA editing with CRISPR-Cas13
Reported as: RNA Editing Possible with CRISPR-Cas13

“This work is an impressive study from a highly productive research group that suggests the possibility of editing RNA transcripts to alter their coding potential in a programmable manner,” David Liu…[who] has a report out today in Nature describing specific nucleotide editing of DNA by a similar method.

Feng Zhang (base editing) gives a pat on the back to David Liu (RNA editing), and Liu reciprocated, or vice versa. Taken together, they are making face-saving attempts that ignore everything known to serious scientists about biophysically constrained viral latency.

The tool itself could be further developed, adds computational biologist Eugene Koonin of the National Center for Biotechnology Information who also was not involved in the study. “This paper is not the end of the road,” he says. It’s possible that Cas13b could be fused to a variety of editing enzymes that would allow a range of different sequence changes. The possibilities are numerous, Koonin says, and “the best is still to come.”

Koonin is a biologically uninformed science idiot who has followed in the footsteps of others like him. Their computations link mutations to evolution across millions of years. The computational biologists are evolutionary biologists who have failed to link food energy from the creation of enzymes and the the RNA-mediated editing of the enzymes, which is required to link differences in sequence changes from fixation of RNA-mediated amino acid substitutions in organized genomes to the prevention of virus-driven messenger RNA degradation. All serious scientists have linked the virus-driven degradation of messenger RNA from mutations to all pathology. Koonin’s claim that “the best is still to come” is moronic.
Every link to energy-dependent RNA-mediated cell type differentiation via the pheromone-controlled fixation of amino acid substitutions has been detailed in the context of experimental evidence. But, Koonin (2016) made this ridiculous claim:

The proper question is: how has this sequence evolved? And the proper null hypothesis posits that it is a result of neutral evolution: that is, it survives by sheer chance provided that it is not deleterious enough to be efficiently purged by purifying selection. To claim adaptation, the neutral null has to be falsified.

To claim evolution, Koonin must link food energy from the pheromone-controlled physiology of reproduction to fixation of a beneficial mutation in the organized genome of one species that evolved into another species.
If Koonin and others like him cannot provide an example of how biologically-based evolution occurs, there is only the pseudoscientific nonsense of their mathematical models for comparison to facts about: How flu shot manufacturing forces influenza to mutate

“Now we can explain — at an atomic level — why egg-based vaccine production is causing problems,” said TSRI Research Associate Nicholas Wu, Ph.D., first author of the study, published recently in the journal PLOS Pathogens.

Clearly, an explanation — at the atomic level — of how viruses adapt to the cell types of one species during the production of an egg-based vaccine must be linked from atoms to ecosystems in all living genera via adaptations in the host.
See for example: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (2014)

The genesis of variation is manifested in ecological variation, which confers the ability to adapt via nutrient-dependent epigenetically-effected pheromone-controlled ecological, social, neurogenic, and socio-cognitive niche construction. Niche construction is manifested in organismal complexity. Everything about ecological adaptation appears to make sense in the light of what is currently known about molecular biology. What is currently known about the conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA can now be compared to any forthcoming explanations that attempt to make sense of how mutation-driven evolution might occur.

"Evolution of Man. - Undoubtedly there once lived upon the earth races of men who were much lower in their mental organization than the present inhabitants.

Science vs Secularism: Molecular Mechanisms or Math?

Summary: An example from ancient knowledge of trigonometry links pattern recognition as the basis for the science of creationism, and pattern recognition also is the basis for molecular biology.
What form of virus-driven pathology would you most like to see eliminated from future consideration by serious scientists who know how energy-dependent RNA-mediated cell type differentiation occurs? In any case, a PubMed search for microRNA and your disease of choice will be enlightening. See for example: microRNA + Alzheimer’s or microRNA + fragile X syndrome; Parkinson’s disease; diabetes; cancer; malaria; and/or other human diseases
See:  Are scientists who speak out against religion hurting science? for discussion of Why religion is not going away and science will not destroy it

…science needs all the friends it can get. Its advocates would be well advised to stop fabricating an enemy out of religion, or insisting that the only path to a secure future lies in a marriage of science and secularism.

Serious scientists have met the enemies of science. One of them is the author of Quantum common sense

We don’t need a conscious mind to measure or look. With or without us, the Universe is always looking

More than 64,000 indexed publications on the PubMed site attest to the fact that the energy-dependent de novo creation of plant microRNAs is linked to all healthy longevity via the food energy-dependent pheromone-controlled physiology of reproduction in species from microbes to humans. Experimentally established facts about the virus-driven degradation of messenger RNA are linked to all pathology via changes in the microRNA/messenger RNA balance.

See: Cytosis: A Cell Biology Board Game

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

What form of virus-driven pathology would you most like to see eliminated from future consideration by serious scientists who know how energy-dependent RNA-mediated cell type differentiation occurs? In any case, a PubMed search for microRNA and your disease of choice will be enlightening. See for example: microRNA + Alzheimer’s or microRNA + fragile X syndrome; Parkinson’s disease; diabetes; cancer; malaria; and/or other human diseases
Role of miRNAs in development and disease: Lessons learnt from small organisms

MicroRNAs (miRNAs) constitute a class of small (18-22 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation. The miRNAs associated with fragile X syndrome, Parkinson’s disease, Alzheimer’s disease, diabetes, cancer, malaria, infectious diseases and several other human diseases have been identified from small organisms. These organisms have been used as platforms in deciphering the functions of miRNAs in the pathogenesis of human diseases and to study miRNA biogenesis. Small organisms have also been used in the development of miRNA-based diagnostic, prognostic and therapeutic strategies. The molecular techniques such as genome sequencing, northern blot analysis, and quantitative RT-PCR, have been used in deciphering the functions of miRNAs in small organisms. How miRNAs from small organisms especially those from Drosophila and C. elegans regulate development and disease pathogenesis is the focus of this review. The outstanding questions raised by our current understanding are discussed.

See for comparison: Quantum Theory Rebuilt From Simple Physical Principles by Philip Ball

“What is needed is new mathematics that will render these notions scientific,” he said. Then, perhaps, we’ll understand what we’ve been arguing about for so long.”

I do not believe that new mathematics will end the arguments, and I do not believe anything Philip Ball claims. Does any intelligent person on Earth believe this claim? “We don’t need a conscious mind to measure or look. With or without us, the Universe is always looking”

For a historical perspective on the nonsense touted by theorists and so-called science journalists, like Philip Ball, see:

Secularism: This ancient Babylonian tablet may contain the first evidence of trigonometry

He and Wildberger concluded that the Babylonians expressed trigonometry in terms of exact ratios of the lengths of the sides of right triangles, rather than by angles, using their base 60 form of mathematics, they report today in Historia Mathematica. “This is a whole different way of looking at trigonometry,” Mansfield says. “We prefer sines and cosines … but we have to really get outside our own culture to see from their perspective to be able to understand it.”

When have serious scientists not gone outside our own culture to understand how the history of human behavioral development has been misrepresented by so-called experts.

See: Past 5,000 years prolific for changes to human genome

The findings confirm their earlier work suggesting that the majority of variants, including potentially harmful ones, were picked up during the past 5,000–10,000 years.

Simply put, the harmful variants probably contribute to our relative lack of intelligence compared to the intelligence of our ancestors, unless you think that a single-celled organism is one of your ancestors. Obviously, however, even if that is the case, you are somewhat more intelligent that pond scum. But, let me apologize in advance for referring to you as a “biologically uninformed science idiot” — in the context of the definition of “idiot” as someone with no professional expertise. Apologists might use the term “fool” in the context of this passage from the Holy Bible:

Thou fool, that which thou sowest is not quickened, except it die:”

Feynman used the term “human idiocy” in the context of representations made by theoretical physicists:

Prepare yourself to experience more insults from experts who have, during the past 5-10,000 years confirmed the links from energy to physics, chemistry, and molecular biology in the context of food energy and the biophysically constrained pheromone-controlled physiology of reproduction.

Apologetics:Indiana Banks and the Tablet of Trig

This story attracted my attention because it is yet more evidence against the Darwinian narrative of human history, which holds that we evolved from apes and have been steadily gaining in technology and science ever since. The reality is very different. The evidence often points to initial brilliance followed by decline, the pattern that creationists would expect. In this instance, extremely ancient people pioneered a form of trigonometry that is more exact than the form used by later Mesopotamian nations and by the Greeks, Romans, and later Western Civilization.

Pattern recognition is the basis for the science of creationism and pattern recognition is the basis for molecular biology.

See also: Olfaction Warps Visual Time Perception

In their concluding paragraph, the authors link irreverent representations of the space-time continuum (Hawking, 1988) to our visual perception of mass and energy. With no vague representations of untested theories, they suggest that neural energy represents multisensory input at subsecond scales.

If what they suggest is true, their published work is an unprecedented refutation of neo-Darwinian pseudoscientific nonsense and an unparalleled refutation of “Big Bang” cosmology. Simply put, they concurrently link the creation of energy to the energy-dependent creation of the sense of smell in bacteria. The sense of smell is linked to the pheromone-controlled physiology of reproduction in all living genera via representations that link neural energy from the epigenetic landscape to the physical landscape of supercoiled DNA.

For example, the sense of smell in bacteria is linked to the weekend resurrection of the bacterial flagellum.

See:Evolutionary Rewiring

Strong selective pressure can lead to rapid and reproducible evolution in bacteria.

Natural selection for food energy-dependent codon optimality was linked to the ability of P. fluorescens to find food, which was linked to their pheromone-controlled physiology of reproduction by everything known about quorum sensing. But wait, that fact defies attempts to put the refutation of all theories into the context of something as simple-minded as this claim:

We don’t need a conscious mind to measure or look. With or without us, the Universe is always looking

For more information on the mutation-driven “dumbing down” of you and your ancestors play the game “Cytosis” when it becomes available later this month and watch for more information on the game “Subatomic.” It is less difficult now than it ever has been to link energy-dependent changes from atoms to ecosystems by what is known to serious scientists. But first, you may need to dismiss the pseudoscientific nonsense touted by theorists.

See also: 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.

See also: Protecting 4 billion people from virus-driven entropy September 8, 2016
See also: Recurrence-Based Information Processing in Gene Regulatory Networks

We also show that the readout layer can learn to decode the information stored in the reservoir via standard evolutionary strategies. Our work thus suggests that recurrent dynamics is a key element for the processing of complex time-dependent information by cells.

What evolutionary strategies led to the recurrent dynamics of time-dependent information processing and the use of trigonometry ~5000 years ago?
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

Physiology is rocking the foundations of evolutionary biology

Perhaps the elegant mathematics and the extraordinary reputation of the scientists involved blinded us to what now seems obvious: the organism should never have been relegated to the role of mere carrier of its genes.

 
 
 

God's shrinking role in salvation (2)

Conclusion: There is no such thing as a blind dance of atoms. Quantized energy-dependent changes link angstroms to ecosystems in all living genera via the physiology of reproduction. Serious scientists do not link “high-level cause and purposes” to anything that does not link what organisms eat from food energy to the physiology of reproduction. Only pseudoscientists claim that ideas about “emergence” are “…a remarkable synthesis across fields and levels.”
See: God’s shrinking role in salvation

These 6 Common Vegetables Are Actually All The Same Plant Species
The morphological traits are quantized energy-dependent, They link the de novo creation of plant microRNAs from the anti-entropic virucidal energy of sunlight to the physiology of reproduction in all living genera via the energy-dependent creation of microRNAs in animals.
See: Viral MicroRNAs, Host MicroRNAs Regulating Viruses, and Bacterial MicroRNA-Like RNAs

The interactions of these small noncoding RNAs in such primitive species have wide-reaching effects, from increasing viral and bacterial proliferation, better responses to stress, increased virulence, to manipulation of host immune responses to provide a more ideal environment for these pathogens to thrive. Here, we explore those roles to obtain a better grasp of just how complicated disease truly is.

Disease is much more complicated when it cannot be linked from top-down causation via physics, chemistry, and molecular biology. See for comparison; ‘Liquid Light’ Can Bend Around Objects in a Frictionless Flow
Thanks to Fiona Myrglwitz for calling attention to this claim that they can:

…conceive and design future photonic superfluid-based devices where losses are completely suppressed.

That suggests they may link the metabolism of bacteria from the creation of uranium isotopes to the errors made in mathematical models of evolved traits. The errors in mathematical models fail to link quantized energy-dependent changes in the microRNA/messenger RNA balance to the biophysically constrained by the physiology of reproduction.The errors are magnified by the fact that they fail to link incompletely suppressed energy losses to all pathology via the virus-driven degradation of messenger RNA.

For comparison, the physiology of reproduction links the solar analemma to the biophysically constrained energy in uranium, which is the reason that radiation therapy is used to treat cancer. Everything known about the link from sunlight to radiation therapy can be placed into context via use of the Mobius strip.
It is an example of how nutrient energy-dependent pheromone-controlled choices made by all living genera must link feedback loops to the biophysically constrained virucidal energy of sunlight. Any loss of energy can potentially be linked to the proliferation of viruses via a slight drop in the potential of hydrogen (pH).

That fact makes it more be obvious that God’s shrinking role in salvation can be viewed in the context of medical practices that appear to make physicians and/or other medical professionals your savior(s). They will warn you to avoid too much sun exposure and treat your cancer with radiation because you did not get enough sun exposure to protect you via the increased production of Vitamin D.
They will tell you to use a chemical “sun-screen” and treat your cancer with chemotherapy that was caused by the chemical imbalance your body could no longer cope with.
See also: Electrolytes induce long-range orientational order and free energy changes in the H-bond network of bulk water
This was reported as: A single ion impacts a million water molecules
So far as I know there has been no discussion of the link from free energy changes in the H-bond network to the hydrophobicity of supercoiled DNA, which links quantum physics to the protection of all organized genomes from the virus-driven degradation of messenger RNA and genomic entropy.
Could the lack of discussion be attributed to the claim that no one understands quantum mechanics in an age where the speed of light on contact with water has been linked to all biodiversity via energy-dependent changes in angstroms to ecosystems in all living genera?
From last year: How Can Physics Underlie the Mind? Top-Down Causation in the Human Context

My review on Amazon (6/12/16)

Others linked the sun’s anti-entropic virucidal energy from energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy.

Ellis comments on at least one of Schrodinger’s claims from “What is Life?” but he largely ignores the energy-dependent links from ecological variation to ecological adaptation that also were reported in two recent publications. See: “Structural diversity of supercoiled DNA” and “Epigenetics and Genetics of Viral Latency.”

Ellis cannot be held accountable for not knowing the most recent work (May 11, 2016) reported that “…viral latency is responsible for life-long pathogenesis and mortality risk…”

However, it seems inappropriate for anyone whose opinions are held in high regard to ignore everything else that is known about energy-dependent RNA methylation and the biophysically constrained morphological and behavioral diversity of all living genera. Experimental evidence has established facts that are being used to link the Precision Medicine Initiative to the National Microbiome Initiative via attempts to crack the olfactory code.

When researchers report the direct link from energy-dependent RNA methylation to differences in behavior, this book will be compared to Masatoshi Nei’s “Mutation-driven evolution.” The biggest difference between the two seems to be that Ellis tries to link emergence to evolution via Darwin’s “conditions of life.”

But he now bears the burden of the report in “Science” of nutrient energy-dependent pheromone-controlled weekend evolution of the bacterial flagellum: “Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system.”

The “resurrection” is obviously energy-dependent and it also links the innate immune system to biophysically constrained biologically-based cause and effect in species from microbes to humans via RNA-mediated amino acid substitutions. Resurrecting Darwin’s “conditions of life” after they were ignored by neo-Darwinists for many decades should not be attempted by physicists, cosmologists, or biologically uninformed theorists from any other discipline without first learning more about what is known about the RNA-mediated links from physics and chemistry to molecular epigenetics.

See for comparison, this review by

An admirable, systematic approach to the issue of emergence from physics to sociology, of great originality, broad scope, and deep understanding. George Ellis argues with admirable clarity of thought that much of the world we live in is governed not by the blind dance of atoms, but by high-level causes and purposes. This is a much needed book and a remarkable synthesis across fields and levels. I know of no other book where the evidence for emergence is presented so thoroughly and with as much insight.

There is no such thing as a blind dance of atoms. Quantized energy-dependent changes link angstroms to ecosystems in all living genera via the physiology of reproduction. Serious scientists do not link “high-level cause and purposes” to anything that does not link what organisms eat from food energy to the physiology of reproduction. Only pseudoscientists claim that ideas about “emergence” are “…a remarkable synthesis across fields and levels.”

See: God’s shrinking role in salvation (3)
Cytosis

CRISPR Cas9 technology refutes theistic evolution

Summary: RNA-guided human genome engineering presents a direct conflict to claims made in the context of CRISPR–Cas9 editing, which creates more mutations. The repair of mutations is nutrient energy-dependent and virus-driven energy theft is biophysically constrained by the physiology of pheromone-controlled reproduction. The unexpected mutations are examples of ignorance expressed by theorists in the claims about evolution. The theorists seem reluctant to admit to the facts about RNA-mediated cell type differentiation because it is energy-dependent, and most of them don’t seem to know that the quantized energy comes from sunlight.

See: From E. coli to monkeys and mankind: Theories vs models (5)

This article became available during the last hour: Unexpected mutations after CRISPR–Cas9 editing in vivo [subscription required]

CRISPR–Cas9 editing shows promise for correcting disease-causing mutations. For example, in a recent study we used CRISPR-Cas9 for sight restoration in blind rd1 mice by correcting a mutation in the Pde6b gene1. However, concerns persist regarding secondary mutations in regions not targeted by the single guide RNA (sgRNA)2.…

It was reported as: Crack in CRISPR Façade after Unanticipated In Vivo Mutations Arise

“Researchers… may be missing potentially important mutations,” Dr. Tsang remarked. “Even a single nucleotide change can have a huge impact.”

That fact is not just a “Crack in the CRISPR Facade.” It dismisses all claims about mutation-driven evolution. Those ridiculous claims have been replaced by what is known to serious scientists about how viral latency must be biophysically constrained. It must be constrained by a light-activated endogenous substrate in all cell types of all living genera. The light comes from the sun. For example, the anti-entropic energy of ultraviolet light kills viruses.

See also: A promoter-proximal transcript targeted by genetic polymorphism controls E-cadherin silencing in human cancers 5/30/17

The so called promoter-associated noncoding RNA (paRNA), microRNAs, and epigenetic regulators control transcription of the tumour suppressor E-cadherin in epithelial cancers. E-cadherin silencing is energy-dependent and RNA-mediated. The energy must link the innate immune system to an endogenous substrate, which links endogenous RNA interference to biophysically constrained protein folding chemistry via the physiology of reproduction in all living genera. These researchers report…

“…formation of a complex between the paRNA and microRNA-guided Argonaute 1 that, together, recruit SUV39H1 and induce repressive chromatin modifications in the gene promoter. A single nucleotide polymorphism (rs16260) linked to increased cancer risk alters the secondary structure of the paRNA, with the risk allele facilitating the assembly of the microRNA-guided Argonaute 1 complex and gene silencing. Collectively, these data demonstrate the role of a paRNA in E-cadherin regulation and the impact of a noncoding genetic variant on its function. Deregulation of paRNA-based epigenetic networks may contribute to cancer and other diseases making them promising targets for drug discovery.

Collectively, these researchers appear to be making a desperate attempt to keep others from leanring that everything they link to the single nucleotide polymorphism and cancer risk has already been linked by serious scientists to energy-dependent cell type differentiation and healthy longevity in all living genera via the physiology of reproduction. If they dropped their attempts to obfuscate what is known about energy-dependent biophysically constrained RNA-mediated protein folding, they would report on how virus-driven energy theft links changes in the microRNA/messenger RNA balance to all pathology.

See for instance: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity 8/24/15

…our data untangle the complicated roles of E-cadherin and p120 in the context of distinct junctional complexes, spatially separating their functions and providing an explanation for their conflicting behaviour in cell growth. In addition, they identify PLEKHA7 as a specific marker of ZA that mediates suppression of growth-related signalling. Finally, they reveal an interaction of the ZA with the microprocessor complex, and uncover a mechanism whereby the ZA regulates a set of miRNAs to suppress cellular transformation and maintain the epithelial phenotype.

The difference between data-based representations of biophysically constrained biologically-based cause and effect and  theoretical representations that link promoter–proximal transcripts can be compared. Simply put, the theories ignore food energy as the information that sustains all RNA-mediated life on Earth. The theories invented in the published work from today substitutes what they refer to as promoter-associated RNAs, (paRNAs).

Outside the context of food energy as information, pseudoscientists claim that they do not understand how cis-acting elements in transcriptional regulation of neighbouring genes are linked to the functional structure of supercoiled DNA, which protects all orgnanized genomes from the virus-driven energy theft that links the degradation of messenger RNA from mutations to all pathology in all living genera.

See also: Discovery of extremely halophilic, methyl-reducing euryarchaea provides insights into the evolutionary origin of methanogenesis 5/30/17 by senior author Eugene Koonin

Within the phylum Euryarchaeota, these isolates form a separate, class-level lineage ‘Methanonatronarchaeia’ that is most closely related to the class Halobacteria. Similar to the Halobacteria, ‘Methanonatronarchaeia’ are extremely halophilic and do not accumulate organic osmoprotectants. The high intracellular concentration of potassium implies that ‘Methanonatronarchaeia’ employ the ‘salt-in’ osmoprotection strategy. These methanogens are heterotrophic methyl-reducers that use C1-methylated compounds as electron acceptors and formate or hydrogen as electron donors. The genomes contain an incomplete and apparently inactivated set of genes encoding the upper branch of methyl group oxidation to CO2 as well as membrane-bound heterodisulfide reductase and cytochromes. These features differentiate ‘Methanonatronarchaeia’ from all known methyl-reducing methanogens. The discovery of extremely halophilic, methyl-reducing methanogens related to haloarchaea provides insights into the origin of methanogenesis and shows that the strategies employed by methanogens to thrive in salt-saturating conditions are not limited to the classical methylotrophic pathway.

The classical methyltrophic pathway links energy-dependent changes in base pairs to RNA-directed DNA methylation and biophysically constrained changes in amino acid substitutions that are required to create the functional structure of supercoiled DNA. All the energy-dependent changes have been linked from angstroms to ecosystems in all living genera via the sense of smell in bacteria and nutrient-dependent pheromone-controlled ecological adaptations.

Eugene Koonin may have been one of the first to admit that the role of virus-driven energy theft had not been considered in the context of ridiculous claims made by neo-Darwinian theorists.

See: Riding the Evolution Paradigm Shift With Eugene Koonin

The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis…

It may be fun for serious scientists to watch as he and others try to recover from their mistakes in the past by inventing new terms for use in new theories that still fail to link what serious scientists know about food energy to the physiology of reproduction and that also link virus-driven energy theft to all pathology. For example, here they do what Carl Woese did when he invented a third domain of life to fit the ridiculous theories of mutation-driven evolution. The discovery of a fourth domain, is not reported as a fourth domain. Instead moderately thermophilic and extremely halo(natrono)philic methanogens that thrive in the hypersalinity of lakes is reported to forms a class-level lineage, called ‘Methanonatronarchaeia.’ The lineage is automagically linked to the deep euryarchaeal lineage because the Methanonatronarchaeia posess a form of methlyation.

A methyl-reducing type of methanogenesis links C1-methylated compounds from their role as acceptors from formate or H2, which serve as external electron donor. This fits into the context of Darwin’s energy-dependent “conditions of life” via the transfer of quantized energy from the sun as an external electron donor to the deep euryarchaeal lineage. The difference in  the electron transport mechanism supposedly also supports the claim that metabolism evolved to link their discovery to an impact on what is understood about biogeochemical cycles of protein biosynthesis and degradation, ecology and the evolution of microbial methanogenesis.

Figure 6 from this published work attests to the complexity of the “evolution of microbial methanogenesis” by placing everything into the context of energy-dependent thermodynamic cycles of RNA-mediated protein folding chemistry, which are biophysically constrained by the physiology of reproduction in species from microbes to humans.

Two complete CRISPR-Cas systems in HMET1 compared to none in AMET1 help to explain why an excess number of genes for anti-parasitic defense appear to have been created in the context of food energy-dependent lifestyle differences that indicate HMET1 is subject to much more nutrient stress and social stress due to virus-driven energy theft in the context of stronger pressure from mobile elements than AMET1.

Nothing explains why these researcher think that their ongoing obfuscation of facts about virus-driven energy theft and all pathology will continue to be acceptable to anyone who acquires and plays this cell biology game.

Cytosis: A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

Light-induced-conformer-intercoversion-of-hydrogen-bond

Energy-dependent pheromone-controlled entropy (2)

See also: Energy-dependent pheromone-controlled entropy (1)
Let’s make peer review scientific

…peer review is often biased and inefficient. It is occasionally corrupt, sometimes a charade, an open temptation to plagiarists. Even with the best of intentions, how and whether peer review identifies high-quality science is unknown. It is, in short, unscientific.


The androgynous baby-faced boy or girl pictured among those wearing pink “crotch” hats appears to representing others at the March for Women. The sign may also be representing the intent of one of the organizers whose support for terrorists became better known after this March.
Next comes the March for Science, where anyone whose photo appears can be asked what area of scientific expertise most interested them. Attempts will be made to learn more about what they did to link energy-dependent changes in angstroms from sunlight to ecosystems in all living genera via hydrogen-atom transfer in DNA base pairs in solution.

See for example: Quantifying Intracellular Rates of Glycolytic and Oxidative ATP Production and Consumption Using Extracellular Flux Measurements

Abstract excerpt:

Measurement of ATP use revealed no significant preference for glycolytic or oxidative ATP by specific ATP consumers. Overall, we demonstrate how extracellular fluxes quantitatively reflect intracellular ATP turnover and cellular bioenergetics.

The energy-dependent extracellular fluxes link pheromone-controlled entropy from cellular bioenergetics to the physiology of reproduction. Virus-driven energy theft compromises the conserved molecular mechanisms of cellular bioenergetics.
See for example: Endothelial cell tropism is a determinant of H5N1 pathogenesis in mammalian species

…our study demonstrates that endothelial cell tropism is a determinant of the high virulence associated with HPAI H5N1 infection in mammalian hosts. By utilizing endogenous miRNA mediated restriction of viral tropism, we demonstrate that H5N1 infection of endothelial cells results in increased cytokine production in the lungs and loss of endothelial barrier function, which culminates in vascular leakage in the lungs. In addition, extrapulmonary spread of H5N1 virus likely occurs via the hematogenous route by infection of endothelial cells.

They link virus-driven energy theft from microRNAs in bacteria to messenger RNA degradation in archaea and L-forms (cells without walls). They fail to link energy theft to the substitution of nutrient energy-dependent amino acid substitutions in viruses, which links viruses to pathology in all living genera.
See for example: Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses

In conclusion, substitutions in or near the RBS can influence the antigenic properties of A(H1N1)pdm09 viruses. Based on the current and previous studies of antigenic change of influenza A viruses (11, 12), it is probable that emerging antigenic variants of A(H1N1)pdm09 viruses will escape from population immunity because of substitutions in or near the RBS. However, our results also suggest that the presence of antibodies directed to epitopes on seasonal A(H1N1) and A(H1N1)pdm09 viruses in much of the population limits the number of antigenic variants that can emerge to cause new epidemics.

Antigenic variants that are biophysically constrained cannot “emerge.” Nutrient stress or social stress must first break the biophysical constraints or there would be no new epidemics. That fact means that nutrient-dependent pheromone-controlled neurogenesis links the physiology of reproduction to ecological adaptations in all cell types of all individuals of all living genera, including organisms with no brain. If you start from neurogenesis in the human brain without realizing that it is pheromone-controlled, you may never learn how food odors and pheromones link the physiology of reproduction to the transgenerational epigenetic inheritance of all morphological and behavioral diversity via conserved molecular mechanisms of endogenous RNA interference.
See also from 6 years ago: Reproduction: A New Venue for Studying Function of Adult Neurogenesis?

Recent studies disclose that SVZ neurogenesis is under regulation of reproductive cues like pheromones.

Some recent debate about this fact was published to the Discover Magazine blog site in the context of accurate claims that Ben Carson made about learning and memory. A anonymous character with the screen name “Neuroskeptic” caused me to voice some concerns about the intelligence of people who accused Ben Carson, a pediatric neurosurgeon, of being wrong about anything.
See: Ben Carson and the Power of the Hippocampus 3/10/17

See also: Social phobia: Indication of a genetic cause — reported on “medicalxpress”
Excerpt: The cause of genetic illnesses often lies in the SNPs.
My comment: The energy-dependent differences in the SNPs is RNA-mediated. In this case, the differences link RNA methylation from endogenous RNA interference to learning and memory via experience-dependent cell type differentiation during life history transitions.
For example, one amino acid substitution (COMT Val158Met) was already linked to differences in the behavior of adolescents and adults. When will Neuroskeptic and others admit that they need to learn more about biologically-based cause and effect before they attack people like Ben Carson.

My comment from 3/11/17
See also:Reproduction: A New Venue for Studying Function of Adult Neurogenesis?” (2011) Cell Transplant

Excerpt: …the number of dividing neurons in the hippocampus of female sheep increased robustly (43), which is accompanied with a sharp increase in circulating luteinizing hormone. Additionally, luteinizing hormone level and hippocampal neurogenesis were also upregulated by the soiled bedding. With the use of prolactin and leutinizing hormone receptor knock-out mice, it was confirmed that the hippocampal neurogenesis is due to the increase of the luteinizing hormone but not prolactin; in contrast, prolactin is the regulatory factor of SVZ neurogenesis (69).

Neuroskeptic displayed the ignorance of all theorists and left them with no excuse to say anything more about Ben Carson, or anyone else who intends to help the President of the United States “Make America Great Again.” Only biologically uniformed liberals will continue their attempts to stop President Trump. The anti-entropic effect of pheromones on GnRH and luteinizing hormone links food odors and pheromones from feedback loops to the physiology of reproduction in all vertebrates via the substitution of the achiral amino acid glycine in position 6 of the GnRH decapeptide.

With co-authors, Donald Pfaff did this in the context of autism. For example, substitution of the achiral amino acid glycine in position 6 of the GnRH decapeptide also links food odors and pheromones from stress-linked changes and feedback loops to sex-specific gene–environment interactions via the hypothalamic-pituitary-gonadal axis.
See: Sex-specific gene–environment interactions underlying ASD-like behaviors

…we found a significant three-way interaction on corticotropin-releasing hormone receptor-1 (Crhr1) gene expression, in the left hippocampus specifically, which co-occurred with epigenetic alterations in histone H3 N-terminal lysine 4 trimethylation (H3K4me3) over the Crhr1 promoter. Although it is highly likely that multiple (synergistic) interactions may be at work, change in the expression of genes in the hypothalamic–pituitary–adrenal/stress system (e.g., Crhr1) is one of them. The data provide proof-of-principle that genetic and environmental factors interact to cause sex-specific effects that may help explain the male bias in ASD incidence.

This was reported as: Study tests the ‘three-hit’ theory of autism

…the researchers looked for molecular changes within these rodents’ brains that might help to explain the differences in behavior. They found an increase in the expression of a gene that helps to kick off stress responses, in a brain region called the left hippocampus. With help from C. David Allis’s lab, they looked for chemical alterations in the packaging of DNA that might explain this uptick in gene activity. This effort revealed one particular chemical change in the nerve cell nucleus that encourages the expression of this stress-relevant gene.

The chemical alterations are energy-dependent and RNA-mediated via methylation, which alters gene activation to help ensure that all organisms of all living genera have the best opportunity to ecologically adapt. If they fail to adapt, they die. They do not mutate and become another species.
See: Every amino acid matters: essential contributions of histone variants to mammalian development and disease  (2014) by senior author C. David Allis.
Conclusion:

…numerous histone variants seem to be restricted to specific cell lineages or tissue types, yet it remains unclear how such expression patterns are maintained and what the consequences are of increasing or reducing combinatorial variant deposition across cell types. Aberrations in these processes result in detrimental phenotypic outcomes across numerous mammalian systems, including humans. Although we are clearly still in the infancy of this ever-expanding and diverse field, we imagine that future endeavours related to histone variant biology will hold great promise for human health and disease.

The tag-team of Pfaff and Allis will continue to prevent others from what is known to all serious scientists about epigenetically-effected gene-environment interactions among all living genera. The interactions are nutrient-energy-dependent and pheromone controlled by the physiology of reproduction.
I posted this question to the CRISPR Cas 9 FB group and to the miRNA & siRNA FB group

Does any experimental evidence of biologically-based cause and effect suggest that microRNA-mediated host-induced gene silencing is not linked from biophysically constrained viral latency to energy-dependent RNA-mediated cell type differentiation via amino acid substitutions in the cell types of all living genera?

For example, could host-induced gene silencing occur outside the context of natural selection for energy-dependent codon optimality and endogenous RNA interference and the physiology of reproduction?

See also: What’s Next for Diagnostic Patents After Ariosa v. Sequenom

…we should use language that highlights the inventive piece of the invention rather than the natural law underlying it.
 
The natural law underlying all links from ecological variation to ecological adaptation could be applied to the patent for RNA-Guided Human Genome Engineering. If so, the examiners will find that host-induced gene silencing is the obvious link from nutrient energy-dependent RNA methylation to the pheromone-controlled physiology of reproduction in all living genera via Kohl’s Laws of Biology.
 
Simply put, Kohl’s Laws includes two facts:
 
1) all organisms must eat or they die.
2) all species must reproduce or they become extinct.
 

Can you imagine what the value of future patents on drugs will be if researchers continue to deny what is known about those two natural laws?

Alternative splicing of pre-mRNA

Autophagy: from pre-mRNAs to microRNAs, enhancers, QTLs et al.

Nothing known to serious scientists links anything except energy-dependent changes in chirality to autophagy and biodiversity via RNA-mediated amino acid substitutions that differentiate all cell types in all living genera. That fact forces pseudoscientists to invent new terms to confuse the biologically uninformed masses who were taught to believe in the neo-Darwinian pseudoscientific nonsense of mutation-driven evolution.
Autophagy in the liver: functions in health and disease 
See the section: Regulation of autophagy by amino acids

See for comparison: From Fertilization to Adult Sexual Behavior

Excerpt from our section on molecular epigenetics.

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 family members and friends of Robin Williams might be appalled to learn that death from Parkinson’s and death from Lewy Body Disease both include instances of suicide that is caused by untreated virus-driven energy theft. The virus-driven energy theft also is the cause of all pathology in species from archaea to humans. It is manifested as energy-dependent changes in alternative splicings of otherwise identical genes.

The prevention of unnecessary suffering and death could be as simple as restoring the balance of amino acids and sugar to prevent all pathology via RNA-mediated cell type differentiation.

That’s not going to happen without some discussion of what is known to serious scientists about the links from angstroms to ecosystems. All of them are energy-dependent. So, “go ahead,  make my day!”

Ask your professors where the energy came from and how it is linked to the changes in pH that predict when difference in healthy longevity become differences in the types of pathology via links from autophagy to supercoiled DNA or to negative supercoiling.

See also: Processing and transcriptome expansion at the mRNA 3′ end in health and disease: finding the right end

This review suggests the term “pre-mRNA” changed to “microRNA” as serious scientists learned more about how energy-dependent cell type differentiation was biophysically constrained.

We illustrate the medical importance by presenting examples that are associated with perturbations of this process and indicate resulting implications for molecular diagnostics as well as potentially arising novel therapeutic strategies.

This was ~20 years after we linked alternative splicings of pre-mRNA to all cell type diversity via the pheromone-controlled physiology of reproduction in yeasts at the advent of energy-dependent sexual reproduction.

See also: Implications of polyadenylation in health and disease

This review addresses the key steps of polyadenylation and alternative polyadenylation in different cellular conditions and diseases focusing on the molecular effectors that ensure a faultless pre-mRNA 3′ end formation.

Watch as researchers continue to invent new names for the molecular effectors in attempts to obfuscated the facts about biophysically-contrained protein folding chemistry that have been known to all serious scientists since Schrodinger (1944) linked the anti-entropic energy of the sun to all biodiversity.

Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus

Abstract excerpt:

Eusocial insects organize themselves into behavioral castes whose regulation has been proposed to involve epigenetic processes…

Research article summary excerpt:

…behavioral plasticity can be manipulated in the ant C. floridanus by pharmacological and genetic tools that target chromatin regulatory enzymes to stimulate, inhibit, and reprogram behavior. These findings reveal the epigenome as a likely substrate  underlying caste-based division of labor in eusocial insects.

Conclusion:

…our ability to alter a canonical altruistic behavior in a truly social organism by experimental perturbation of a single gene suggests that the application of increasingly versatile reverse genetic approaches in eusocial insects will allow us to expose the general organizational principles underlying complex social systems (10).

See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
All general organizational principles underlying complex social systems are nutrient-dependent and pheromone-controlled in the context of the regulation of gene expression that enables the transgenerational epigenetic inheritance of all morphological and behavioral phenotypes.

‘Mysterious’ non-protein-coding RNAs play important roles in gene expression

Berger and Daniel Bose, PhD, a postdoctoral fellow in her lab, study the regulation of gene expression from enhancers, non-coding regions of the genome more distant from protein-coding regions.

The only mystery should focus on why they thought they could continue to suppress the facts by referring to natural selection for energy-dependent codon optimality in terms like “enhancers.” Since 2013, everything known to serious scientists about nutrient-dependent microRNAs has been linked to all healthy longevity and virus-driven energy theft has been linked to to all pathology. Serious scientists are not using the term “enhancer.” See for example any of the 56,000 published works that use the term “MicroRNA

Ask why Phys.org / Medical Xpress must report old news from 2013 in the context of unpublished research by two people who cannot be found on the PubMed indexed list of research that links sunlight from chirality to autophagy and chromosomal rearrangements to all biodiversity via energy-dependent changes in the microRNA/messenger balance, which link supercoiled DNA to the protection of all organized genomes from virus-driven entropy.

See: Enhancer RNAs alter gene expression: New class of molecules may be key emerging ‘enhancer therapy’

Enhancers are sequences in the genome that act to boost or “enhance” the activity or expression of nearby genes. They “often behave in a cell-specific manner and play an important role in establishing a cell’s identity and functional potential,” said Christopher Glass, MD, PhD, a professor in the department of Medicine and Cellular and Molecular Medicine at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of RNA on a broad scale in neurons and macrophages, a type of immune system cell. Dubbed eRNAs…

I do not know any serious scientists who accepts the term invented to replace pre-mRNAs after the term microRNAs was introduced at the turn of this century and more than 56,000 published papers now use the term microRNA in the context of links from metabolic networks to genetic networks in all living genera via non-coding RNAs..

SnapShot: Non-coding RNAs and Metabolism

In recent years, understanding the crucial role played by cellular homeostasis in disease initiation and progression became the focus of scientists and clinicians. This SnapShot sketches the involvement of both short microRNAs and long ncRNAs in the major metabolic pathways altered in diseases.

Functional Importance of eRNAs for Estrogen-dependent Transcriptional Activation Events

Who do they think does not know that the functional importance of microRNAs and the functional difference of eRNAs is the same. eRNAs are the term theorists use for microRNAs.

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.

See also: SPECIAL ISSUE—THE ZIKA VIRUS GLOBAL PANDEMIC: THE LATEST EMERGING INFECTION
Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia

It is still not well understood what role(s) the Hofbauer cell has in facilitating or inhibiting transplacental transmission of infectious agents such as the Zika virus. However, based on the demonstration in this communication of proliferation and prominent hyperplasia of Hofbauer cells in the placenta from a microcephalic fetus infected early in gestation, the identification of residual Zika virus in villous stromal cells, using an RNA probe, and the previously published results of in vitro infection and replication of Zika virus in human Hofbauer cells, it appears highly probable that the Hofbauer cell has an important, or even primary, role in those cases where transplacental transmission of the Zika virus does occur. The unexpected absence in placental tissues of any necrosis or leukocytic response by the mother or fetus to transplacental Zika virus infection is also interesting and of unknown significance.

The absence of a response in the organized genomes of the host clearly indicates ecological adaptation to the virus has already occurred and the supercoiled DNA of the host helps to protect a host from DNA damage. The infants are comparatively unprotected. If they survive to reproduce, and their bones turn up in what a future paleontologist thinks is a fossil record that spans hundreds of thousands of years, the paleontologist would almost undoubtedly claim to have found a new species of non-human primate.
For comparison, all serious scientists known that energy-dependent autophagy is the link to supercoiled DNA, which protects all organized genome from virus-driven energy theft and genomic entropy.
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.

IMG_3010

Base pairs, amino acids and phenotypes

Holliday junction trap shows how cells use recombination and a junction-guardian role of RecQ helicase

DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution.

Autophagy is the established link from energy-dependent changes in base pairs and RNA-mediated amino acid substitutions to DNA repair in the context of polycombic ecological adaptations that prevent the hecatombic evolution of virus-driven pathology. Inventing new detailed models of DNA repair serves only to confuse those who have already linked energy-dependent changes from angstroms to ecosystems via the physiology of reproduction, which links the innate immune system to supercoiled DNA and all biodiversity in all living genera.
See for comparison. This is another confusing attempt to link energy-dependent autophagy via the physiology of pheromone-controlled reproduction from changes is base pairs to RNA-mediated amino acid substitutions, which differentiate all cell types in all living genera in the context of polycombic ecological adaptations.
Very few published works use the term RNA regulons for comparison to energy-dependent changes in microRNAs in the context of hydrogen-atom transfer in DNA base pairs in solution. The changes in base pairs must be linked to the post-transcriptional events via biophysically constrained RNA-mediated protein folding chemistry, which links metabolic networks to genetic networks in all living genera.
RNA regulons: coordination of post-transcriptional events (2007)

Here I describe several recently discovered examples of RNA operons in budding yeast, fruitfly and mammalian cells, and their potential importance in processes such as immune response, oxidative metabolism, stress response, circadian rhythms and disease. I close by considering the evolutionary wiring and rewiring of these combinatorial post-transcriptional gene-expression networks.

The claims about RNA regulons in the context of the innate immune system and claims about a model of biologically-based cause and effect were included in this model.
See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. My model is a refutation of the neo-Darwinian nonsense about beneficial mutations, natural selection and evolution. Natural selection for energy-dependent codon optimaility links the pheromone-controlled physiology of nutrient-dependent reproduction to all biodiversity in all living genera via polycombic ecological adaptations.
The refutation of neo-Darwinian nonsense is supported by experimental evidence from many different published works that link energy-dependent changes in base pairs to fixation of RNA-mediated amino acid substitutions in organized genomes. The ~55,000 indexed published works on nutrient energy-dependent microRNAs and virus-driven energy theft can now be place into these claims about the hecatombic evolution of all virus-driven pathology
See:Freeze-frame’ proteins show how cancer evolves: Researchers capture elusive clues about cells’ path to cancer.

“The intermediate molecules are the most important parts of biochemical reactions,” said Rosenberg… “They define what the reaction is and how it will proceed. But because they are transient and elusive, it’s really difficult to study them, especially in living cells.

The “intermediate molecules” are energy-dependent microRNAs. They link hydrogen-atom transfer in DNA base pairs in solution to all cell type differentiation in all genera via microRNA flanking sequences.
See: The phylogenetic utility and functional constraint of microRNA flanking sequences

Both miRNAs and their flanking sequences provide phylogenetic signals suitable for the inference of phylogeny with high levels of accuracy, when sufficient numbers of this type are concatenated. As detailed here, the clear identity and easy alignment of these sequences makes them good candidates for estimating phylogeny, and they can reliably be found and identified across all members of a clade of interest. Their relatively slow evolution [3] also means that they can easily be identified in de novo assemblies of genomes.

There is no such thing as the de novo assemblies of genomes or relatively fast or slow evolution. Cell type differentiation is energy-dependent and biophysically constrained. Energy-dependent changes in the microRNA/messenger RNA balance are required to link the epigenetic landscape to the physical landscape of supercoiled DNA.
Everything known about energy-dependent biophysically constrained RNA-mediated protein folding chemistry was placed into the context of Combating Evolution to Fight Disease.  Simply put, the innate immune system defends all cell types against the virus-driven evolution of cancer and all other pathology.

As predicted in “The Darwin Code,” That fact has forced A radical revision of human genetics

“…geneticists don’t have an accurate understanding of how mutations behave in people who are not obviously sick. “This is a fascinating flashpoint in the field right now,” says Robert Green, a geneticist at Brigham and Women’s Hospital in Boston, Massachusetts. “Many people are deeply concerned that widespread screening of ostensibly healthy people could actually lead to harm.”

The harm comes from not knowing how nutrient energy-dependent RNA-mediated cell type differentiation occurs. The availabiity of nutrients varied in the ancestors of people from Asian, African, Latino and other non-European ancestries. That is why…

…failing to include people from Asian, African, Latino and other non-European ancestries is holding back understanding of how genes influence disease by limiting the view of human genetic diversity.

Natural selection of food for energy-dependent codon optimality links base pairs and amino acid substitutions to sex specific cell type differences and all other RNA-mediated cell type differences.

See for example: Gender-Specific Association of Galanin Polymorphisms with HPA-Axis Dysregulation, Symptom Severity, and Antidepressant Treatment Response (2010)

Human galanin (GAL) is a 30 amino-acid neuropeptide, proteolytically processed from preprogalanin (PPGAL) (Evans and Shine, 1991; Schmidt et al, 1991). PPGAL is a single-copy gene located on chromosome 11q13.3–13.5, spanning over 6 kb of genomic DNA and organized into six exons (Rokaeus and Brownstein, 1986; Vrontakis et al, 1987).

Single-nucleotide polymorphism rs948854 in human galanin gene and multiple sclerosis: a gender-specific risk factor (2017)

Although it remains to be demonstrated whether A-to-G substitution in rs948854 leads to an increased or decreased transcriptional activity of the GAL gene, functional studies suggest a decrease of galanin level in the minor G allele carriers. It has been shown that reduction in galanin level leads to or exacerbates neurodegeneration, whereas an increased galanin level has neuroprotective effects (Hobson et al., 2008; Elliott-Hunt et al., 2011; Liu et al., 2013). Furthermore, galanin may exhibit anti-inflammatory effects, possibly via inhibition of excitatory neurotransmitter release and/or regulation of cytokine production by activated microglia (Hokfelt et al., 1987; Su et al., 2003; Elliott-Hunt et al., 2004). The associations between rs948854 variants and MS demonstrated in the current study support our hypothesis that polymorphism in the promoter region that are likely to change expression level of the GAL gene affect the cause and the outcome of MS, shifting the balance in favor of either neuroprotection or neurodegeneration.

Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant (2013)

Alternatively, it could be precisely the pleiotropic nature of 370A that allowed multiple distinct selective forces to act on this variant over its long history, when many of the postulated selective pressures such as temperature and humidity changed dramatically. The fact that EDAR acts mostly on ectodermal appendages and that the phenotypic effects of the 370A allele are not extreme reduces the costs of pleiotropy and would facilitate this process. Thus, what were initially neutral changes in some appendages driven by 370A would gain adaptive significance in the face of new selective pressures. It is worth noting that largely invisible structural changes resulting from the 370A allele that might confer functional advantage, such as increased eccrine gland number, are directly linked to visually obvious traits such as hair phenotypes and breast size. This creates conditions in which biases in mate preference could rapidly evolve and reinforce more direct competitive advantages. Consequently, the cumulative selective force acting over time on diverse traits caused by a single pleiotropic mutation could have driven the rise and spread of 370A.

My comment: 370 A exemplifies an energy-dependent change in rs3827760, which is also known as 1540T/C, 370A or Val370Ala. It is a single nucleotide polymorphism (SNP) linked from a base pair change to an amino acid substitution in the ectodysplasin A receptor EDAR gene on chromosome 2.
A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence (2015)

One SNP rs4713668 (P=4.62 × 10−4) identified in our study, was in LD (r2=0.65) with rs3227, which is one of the three variants recently reported with genome-wide significant evidence of association with educational attainment.46

A genetic basis of variation in eccrine sweat gland and hair follicle density (2015)
rs3827760 appears to have become En1 [Engrailed-1), and modulation of En1 levels became a driver of natural differences in eccrine gland and hair follicle density between mouse strains. Previously, those differences were linked to a single energy-dependent base pair change and one amino acid substitution.

This finding not only provides insight into a distinct molecular program that promotes increased eccrine gland density, but also reveals that this effect on eccrine development occurs at the expense of hair follicles in a tissue where the two appendage types are naturally interspersed.

The link to behavior via visually obvious traits such as hair phenotypes and breast size is missing. That means there is no link to sex differences and biases in mate preference via rs948854. That means everything known to serious scientists about biophysically constrained RNA-mediated amino acid substitutions and cell type differentiation in all individuals in all living genera may continue to be ignored.
See for instance: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Two additional recent reports link substitution of the amino acid alanine for the amino acid valine (Grossman et al., 2013) to nutrient-dependent pheromone-controlled adaptive evolution. The alanine substitution for valine does not appear to be under any selection pressure in mice. The cause-and-effect relationship was established in mice by comparing the effects of the alanine, which is under selection pressure in humans, via its substitution for valine in mice (Kamberov et al., 2013).

These two reports (Grossman et al., 2013; Kamberov et al., 2013) tell a new short story of adaptive evolution. The story begins with what was probably a nutrient-dependent variant allele that arose in central China approximately 30,000 years ago. The effect of the allele is adaptive and it is manifested in the context of an effect on sweat, skin, hair, and teeth. In other mammals, like the mouse, the effect on sweat, skin, hair, and teeth is due to an epigenetic effect of nutrients on hormones responsible for the tweaking of immense gene networks that metabolize nutrients to pheromones. The pheromones control the nutrient-dependent hormone-dependent organization and activation of reproductive sexual behavior in mammals such as mice and humans, but also in invertebrates as previously indicated. That means the adaptive evolution of the human population, which is detailed in these two reports, is also likely to be nutrient-dependent and pheromone-controlled, since there is no other model for that.

The fact that there is no other model of energy-dependent biophysically constrained cell type differentiation that also links virus-driven energy theft to all pathology has not escaped the attention of those who might wish they had a model. Because they don’t, all they can do is claim that no model refutes their ridiculous theories about evolution.

For a failed discussion attempt of everything known to serious scientists about energy-dependent base pair changes, RNA-mediated amino acid substitutions and cell type differentiation, see Creationism May 22, 2016

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This open access article may be too technical for most people to discuss, but Creationism is difficult to discuss outside the context of energy-dependent creation compared to energy theft and pathology.

A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

My summary of the excerpt: They linked an energy-dependent changes in rs3827760 from the base pair to the same amino acid substitution, which had already been linked to cell type differentiation across populations of modern humans. Fixation of the energy-dependent base pair change in the amino acid substitution that differentiates the morphological and behavioral phenotypes of modern humans links supercoiled DNA to protection from virus-driven energy theft and genomic entropy in species from archaea to all primates.
In the same study they linked virus-driven energy theft to loss of function mutations and transgenerational epigenetic inheritance of healthy longevity for comparison to mutation-driven pathology via the mouse model. The mouse to human model was already used to link the EDAR variant to similar morphological differences in humans. The morphological differences appear to link the Zika virus pathology to craniofacial changes and differences in brain development via what is known about the bull sperm microRNAome and presence of microRNAs in human breast milk that protect infants from virus-driven energy theft during the first few years of development.
Excerpt:

The derived G allele at the index SNP in this region (rs3827760) encodes a functional substitution in the intracellular death domain of EDAR (370A) and is associated with reduced chin protrusion (Table 2). EDAR is part of the EDA signalling pathway (comprising EDA, EDAR and EDARADD (the EDAR-binding death domain adaptor protein)) which specifies prenatally the location, size and shape of ectodermal appendages (such as hair follicles, teeth and glands)23. The death domain has been shown to be involved in the interaction of EDAR with EDARADD, the 370A form having higher activity than the ancestral variant24. The G allele at rs3827760 is not present in Europeans and Africans but is seen at high frequency in East Asians and is essentially fixed in Native Americans (Table 3). This SNP has been associated in East Asians with characteristic tooth morphologies, hair type and sweat gland density25, 26, 27. Recently, we showed, in the same study sample examined here, that rs3827760 impacts on aspects of pinna morphology, including: lobe size and attachment, ear protrusion and helix rolling12. Mutations in the EDA pathway cause hypohidrotic ectodermal dysplasia28. This disorder is characterized by a reduced number of sweat glands, oligodontia, decrease in the amount of hair and facial dysmorphia, including a markedly protrusive chin29.”

Energy-dependent base pair changes are the only known link from RNA-mediated amino acid substitutions to cell type differentiation via supercoiled DNA and protection from virus-driven energy theft. The energy-dependent base pair changes prevent the entropy of organized genomes.
The focus of my 2013 model was on the RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all living genera. The focus of theorists has been to obfuscate what is known about the links from energy-dependent base pair changes to RNA-mediated amino acid substitutions and cell type differentiation, which is the only way to explain biologically-based cause and effect. It also explains why some species survived and others became extinct during the past ~6000 years.
See for example:
Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants
Genome divergence and diversification within a geographic mosaic of coevolution
Difference in Plumage Color Used in Species Recognition between Incipient Species Is Linked to a Single Amino Acid Substitution in the Melanocortin-1 Receptor
Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution
Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses.
The fact that all divergence and diversification in all living genera must be energy-dependent and the fact that virus-driven energy theft causes all pathology must be ignored by those whose financial support for their research comes from the evolution industry or the big bang cosmology industry. We cannot expect much scientific progress until the financial constraints are broken and the biophysical constraints on energy-dependent RNA-mediated cell type differentiation are addressed at every level from angstroms top ecosystems after starting from quantized energy-dependent changes in base pairs.
See for comparison: Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters
Re: “…the interactomes of 31,253 annotated promoters in 17 human primary blood cell types.”
Excerpt:

Here, we link thousands of GWAS SNPs to their putative target genes and prioritize more than 2,500 potential disease-associated genes, three-quarters of which were not previously implicated.

Reported as: Researchers identify missing links that connect human DNA variation with disease
All “missing links” are nutrient energy-dependent and biophysically constrained by the physiology of reproduction. They link RNA-mediated amino acid substitutions to cell type differentiation in all cell types of all living genera via the innate immune system and supercoiled DNA. Mathematical models are useless in that context. They are based on inferences and assumptions.
It’s time to finish this blog post. I linked energy-dependent changes in SNPs from amino acid substitutions to cell type differentiation via a model of biologically-based cause and effect, and the “science” news is still reporting biologically-based cause and effect in the context of their pseudoscientific nonsense about mathematical models of inferences and assumptions.

Alternative splicing of pre-mRNA

The human virome (revisited)

From October 2013: Describing the Silent Human Virome with an Emphasis on Giant Viruses

“…viruses infect all domains of life, including bacteria, archaea and eukaryotes, and are found in all ecological niches [2]. This pleiotropic distribution on our planet allows viruses to play the role of ‘natural motors’ that drive global energy and nutrient cycling [3,4].”

My comment: The portrayal of viruses as ‘natural motors’ is made outside the context of the fact that the energy-dependent changes attributed to the ‘natural motors’ is not possible in the context of virus-driven energy theft, which is linked to all pathology — not to the evolution of anything.

See also: (Air date: April 22, 2015) Thanks to Teresa Binstock for calling attention to this: The mammalian virome in genetic analysis of health and disease pathogenesis

Teresa Binstock wrote: This NIH lecture titled, “The mammalian virome in genetic analysis of health and disease pathogenesis,” radically refutes conventional assumptions about the inherent pathogenicity of viruses, illuminating how many latent viruses within the human body (e.g. Herpesviruses) are indispensable to prevent infection by mediating the genotype-phenotype relationship within the host.

As the indispensable role of the human virome in proper immune function comes to light it will be increasingly difficult to maintain the ideologically myopic, if not imbecilic view that “viruses are bad,” must be vaccinated against, and eventually “eradicated” from the face of the earth.

See also: Creating and maintaining the human virome June 5, 2015

Excerpt:

Epistasis is perturbed by viruses, which is why the viruses are linked to pathology. They are not linked to beneficial mutations because there is no such thing as a pathological benefit.

See also: What is life when it is not protected from virus driven entropy Mar 30, 2016

See for comparison: The Human Virome Oct 21, 2016   |   Posted by: Carmen Leitch
My comment: Carmen Leitch and other science journalists have repeatedly ignored my Labroots presentations, published works, and my comments on their misrepresentations of what is known to all serious scientists about biologically-based cause and effect. With this post, Leitch sinks to a new low. She is helping others to tout the pseudoscientific nonsense of neo-Darwinian evolution by ignoring this fact:

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

Description:

In this talk by Frederic Bushman, PhD, William Maul Measey Professor in Microbiology, Perelman School of Medicine, presented by the American Society for Microbiology, an overview of the human virome – the viruses present in a human body – is presented.

There are many viruses on Earth, with estimates as high as billions. Human harbor many viruses, with some infection most of the population; Herpes simplex, for example, is estimated to infect as much as 80% of people or more if you count both types of the virus. Viruses can also confer benefits, such as in some vaccines.

Improvements in genetic technology have allowed researchers to learn more about viruses and nature. Researchers would like to delve deeper into the study of viruses and questions that surround them such as why the viruses in the human gut are so variable from person to person. Bushman’s lab is working in this area, and he shares some of his results with us.


 
He claims that “viruses mutate themselves,” and that much of his work is funded by the Human Microbiome Project, which might be another source of funding akin to the more recent National Microbiome Initiative (link opens pdf), which was announced on May 13, 2016.
See for comparison to what is known to serious scientists about energy-dependent polycombic ecological adaptation via nutrient-dependent fixation of RNA-mediated amino acid substitutions for comparison to hecatombic evolution of all virus-driven pathology. Both polycombic ecological adaptation and the hecatombic evolution of all virus-driven pathology can be placed into the context of the Precision Medicine Initiative via links from quantised energy to amino acid substitutions of from the theft of quantised energy to mutations and all pathology.
Until people like Professor Bushman are willing to admit that they have misrepresented the differences between a mutation and an amino acid substitution, scientific progress will be stalled by reporters like Carmen Leitch. She cannot be expected to know anything more about biophysically constrained energy-dependent RNA-mediated protein folding chemistry than what she was taught to believe by professors like Professor Bushman, who have taught her to believe in pseudoscientific nonsense.
See for comparison: What is life when it is not protected from virus driven entropy
Published on 30 Mar 2016
Poster: The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair. In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans. Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry. Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.
See also: The Microbiome Initiative
How much would it cost to fund a Nutrient-dependent Pheromone-controlled “Polycombic Adaptation Inititative”
See also: Beyond the gut bacterial microbiota: The gut virome

Excerpt:

The creation of a “human virome project” just like the human genome project could lay the basis in understanding not only diseases pathophysiology but also to know how viral populations that inhabits the human body could interfere with therapies and vice versa how therapies could change the viral ecosystem.

Big Bang

Nutrient-dependent autophagy

Autophagy: cellular and molecular mechanisms

Excerpt:

Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Autophagy also plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, such as mitochondria, endoplasmic reticulum and peroxisomes, as well as eliminating intracellular pathogens.

My comment: Autophagy is energy-dependent

See for example: Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms

Conclusion:

 …TET may represent a conduit through which alterations in this ion are signaled to the genome. Moreover, the observation that RA signaling enhances TET2 expression could be relevant for the treatment of certain cancers. TET2 is a well-described tumor suppressor that is regularly mutated in a number of hematopoietic malignancies (46). Acute promyelocytic leukemia (APL) is a form of myeloid malignancy characterized by PML-RARα translocation and sensitivity to RA treatment, such that RA used in combination with arsenic trioxide can provide a 5-year event-free survival rate of >90% (47, 48), a dramatic improvement for what was once considered the deadliest form of acute leukemia. Nevertheless, a significant number of patients are resistant to RA treatment. A recent analysis found that 4.5% of patients with APL have mutations in TET2, and that a mutation in this and other epigenetic modifiers is a significant indicator of poor disease outcome (49). Our work provides a potential mechanistic explanation for RA insensitivity in patients with APL with TET2 mutations, and if proven in further experimentation, could affect the management of this disease.

Reported as: Vitamins A and C help erase cell memory

Excerpt:

The family of enzymes responsible for active removal of the methyl tags are called TET. The researchers looked at the molecular signals that control TET activity to understand more about how the activity of the TET enzymes can be manipulated during cellular programming to achieve pluripotency.
They found that vitamin A enhances epigenetic memory erasure in naïve ESC by increasing the amount of TET enzymes in the cell, meaning greater removal of methyl tags from the C letters of the DNA sequence. In contrast, they found that vitamin C boosted the activity of the TET enzymes by regenerating a co-factor required for effective action.

My comment: Enzymes do not automagically create themselves for use in links from metabolic networks to genetic networks. The de novo creation of enzymes is energy-dependent and it must link energy-dependent changes from angstroms to ecosystems via biophysically constrained RNA-mediated protein folding chemistry in the context of autophagy.

See for instance: Kohl, James V. (2014): Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.

Excerpt:

…the conserved molecular mechanisms of nutrient-dependent organizing base pair changes are attributed to the epigenetic effects of food odors and the pheromone-controlled physiology of reproduction (J. V. Kohl, 2012). Indeed, methylation of the carbon-5 position of cytosine, which results in differences in 5hmCs, may be the most commonly studied type of nutrient-dependent pheromone-controlled structural and functional eukaryotic modification that results from organizing base pair changes.

Because vitamin C and other vitamins appear to epigenetically effect nutrient-dependent methylation at the level of single-base resolution in mammals, it has become more important to determine how base-pair changes alter intracellular interactions in embryonic stem cells or intercellular interactions in other cells that result in cascades of downstream intracellular and intercellular organizing interactions throughout life. Other vitamins, such as vitamin D, and metal ions such as calcium, iron, lead and manganese also appear to epigenetically alter these organizing interactions. Therefore, a biophysically constrained, nutrient-dependent, epigenetically-effected, receptor-mediated recognizable organized pattern of emergence can be viewed in the context of ecological variations and ecological adaptations.

My comment: For example, lead and manganese containing leaves were linked to the changes in peppered moths that were reported in the context of mutation-driven evolution and selection against predation. Serious scientists know that all organized patterns of emergence must also be viewed in the context of virus-driven energy theft that prevents recognition of any pattern of biophysically constrained cell type differentiation.

Virus-driven energy theft is linked only to patterns of mutations, which are linked to all pathology by the failure of cells to differentiate. Only differentiated cells can be linked to biodiversity in all living genera via the physiology of energy-dependent reproduction. In the peppered moth and all other invertebrates and vertebrates the nutrient-dependent pheromone-controlled physiology of reproduction is linked from autophagy to supercoiled DNA, which protects all organized genomes from virus-driven energy theft.

See also: Pheromone-controlled autophagy