Caption: Contemporary analyses of cell metabolism have called out three metabolites: ATP, NADH, and acetyl-CoA, as sentinel molecules whose accumulation represent much of the purpose of the catabolic arms of metabolism and then drive many anabolic pathways. Such analyses largely leave out how and why ATP, NADH, and acetyl-CoA (Figure 1) at the molecular level play such central roles. Yet, without those insights into why cells accumulate them and how the enabling properties of these key metabolites power much of cell metabolism, the underlying molecular logic remains mysterious. Four other metabolites, S-adenosylmethionine, carbamoyl phosphate, UDP-glucose, and Δ2-isopentenyl-PP play similar roles in using group transfer chemistry to drive otherwise unfavorable biosynthetic equilibria. This review provides the underlying chemical logic to remind how these seven key molecules function as mobile packets of cellular currencies for phosphoryl transfers (ATP), acyl transfers (acetyl-CoA, carbamoyl-P), methyl transfers (SAM), prenyl transfers (IPP), glucosyl transfers (UDP-glucose), and electron and ADP-ribosyl transfers (NAD(P)H/NAD(P)+) to drive metabolic transformations in and across most primary pathways. The eighth key metabolite is molecular oxygen (O2), thermodynamically activated for reduction by one electron path, leaving it kinetically stable to the vast majority of organic cellular metabolites

Odor activation of ATP (2)

Metabolic Regulation of Cytoplasmic DNA Synthesis (1974)

The curve that results when the rate of DNA synthesis is plotted as a function of ATP concentration is sigmoidal, suggesting that more than one site on the enzyme interacts with ATP and that these sites are acting cooperatively.

Odor activation of ATP is the obvious link to RNA-mediated feedback loops that control the food energy-dependent pheromone-controlled physiology of reproduction via the rate of DNA repair in species from microbes to humans.
See: “ATP activation
See for comparison: Feedback loops link odor and pheromone signaling with reproduction (2005)
See also: “ATP activation” microRNA
See also: Mapping malaria by combining parasite genomic and epidemiologic data

Here, we discuss the spatial epidemiology of malaria in the context of transmission-reduction interventions, and the challenges and promising directions for the development of integrated mapping, modeling, and genomic approaches that leverage disparate data sets to measure both connectivity and transmission.

The sun’s anti-entropic virucidal energy has been linked to protective food energy-dependent hemoglobin variants via 1700+ examples. The variants link interethnic similarities and differences to all extant human populations.
HbVar: A Database of Human Hemoglobin Variants and Thalassemias
SNPs or indels [insertions/deletions] link amino acid substitutions to hemoglobin variants. Molecular defects [mutations] in regulatory or coding regions of the human genes can minimally or drastically reduce their expression, leading to α-, β- or δ-thalassemia, respectively.
What can be said about so-called scientists and so-called science journalists who do not know the difference between how a food energy-dependent amino acid substitution is linked to ecological adaptations and how a mutation is linked to diseases?
Who was the first to say it?

Who will be the next to disagree:
7/25/13
Jay R. Feierman:

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

Darwin repeatedly asserted that “conditions of life” must be placed before natural selection. Without the sun’s anti-entropic energy, no species on Earth can adapt to ecological variation.

A rendering of how changes in an electron's motion (bottom view) alter the scattering of light (top view), as measured in a new experiment that scattered more than 500 photons of light from a single electron. Previous experiments had managed to scatter no more than a few photons at a time. Credit: Extreme Light Laboratory|University of Nebraska-Lincoln

From base editing to RNA editing

Base Editing Now Able to Convert Adenine-Thymine to Guanine-Cytosine

“Nature conveniently provides us with cytosine deaminase enzymes that operate on DNA,” Liu tells The Scientist.

The creation of quantized energy in sunlight links energy as information from electrons to ecosystems via the physiology of reproduction in all living genera. The claim that “Nature” provides us with cytosine deaminase enzymes makes it seem that the enzymes emerged and automagically evolved to become purposeful and meaningful in the context of ridiculous theories about mutation-driven evolution.
See for comparison: All about that base (video parody)
See also: RNA Editing Possible with CRISPR-Cas13

Introducing specific sequence changes into RNA molecules could allow researchers to answer questions about alternative splicing mechanisms, translation, and even editing, he says. “There’s a lot of scope.”

The entirety of that scope was addressed in the context of energy-dependent RNA-mediated cell type differentiation in our section on molecular epigenetics from this 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior
Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.
All biophysically constrained RNA-mediated energy-dependent cell type differentiation has since been linked from the pheromone-controlled physiology of reproduction to supercoiled DNA via the fixation of amino acid substitutions and chromosomal rearrangements.
The facts about the amino acid substitutions in the context of transgenerational epigenetic inheritance link electrons to ecosystems via the cryo-EM technology that won the 2017 Nobel Prize in Chemistry.
See: Chemists know (video parody)
See also:

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

Lethal virus kills 5 billion people?

Predicting who wins the 2017 Nobel Prizes (2)

Summary: Endogenous RNA interference is the energy-dependent epigenetic link from the physiology of pheromone-controlled reproduction to biophysically constrained viral latency. The stress-linked virus-driven degradation of messenger RNA has been linked to all pathology.
Three Americans win Nobel medicine prize for body rhythm work [But they failed to link Americanism to Creationism]
I predicted that Wen Zhou would win for linking the energy-dependent creation of G protein-coupled receptors to all biodiversity via olfaction and the space-time continuum in the context of RNA-mediated cell type differentiation via the physiology of pheromone-controlled reproduction. See: Olfaction Warps Visual Time Perception. 
She returned to China after training in the United States of America, but is a good example of someone who appears to practice Americanism, which is an ideology that appears to be integrated into her research. I do not know what people in China refer to in the context of this ideology.

In the words of Theodore Roosevelt, “Americanism is a question of spirit, conviction, and purpose, not of creed or birthplace.”[3]

After Ben Feringa (Chemistry/chirality) and Yoshinora Ohsumi (Physiology or Medicine/autophagy) won last year, I thought that all gene-centric nonsense would be eliminated. It became perfectly clear that energy-dependent changes in chirality must be linked to autophagy, which protects all organized genomes from the virus-driven degradation of messenger RNA.
Instead, see:

Excerpt 1) The awardees’ work stems back to 1984, when Rosbash and Hall, who was then also at Brandeis, along with Young isolated the “period gene” in fruit flies. Hall and Rosbash found that a protein encoded by the gene accumulated during the night and degraded during daytime. A decade later, Young discovered another “clock gene.”

Excerpt 2) “The paradigm-shifting discoveries by the laureates established key mechanisms for the biological clock,” the Nobel Assembly said in its prize statement.

See for comparison: The Nobel Prize in Physiology or Medicine 1973 Karl von Frisch, Konrad Lorenz and Nikolaas Tinbergen

for their discoveries concerning organization and elicitation of individual and social behaviour patterns.

The organization and elicitation of individual social patterns of behavior is energy-dependent and it links what organisms eat to the metabolism that links the energy to the physiology of pheromone-controlled reproduction in species from microbes to humans.
Since 1973,  and especially during the past 13 years, there has not been a gene-centric theory that has successful been linked to a paradigm shift. For example, all paradigm-shifting Nobel Prizes in Physiology or Medicine during the past 13 years have linked the energy-dependent creation of ATP and the creation of messenger RNA to protection from the virus-driven energy theft that serious scientists have linked from the degradation of messenger RNA to all pathology.
See for examples:
2016: Yoshinori Ohsumi of Japan for his work on autophagy—a process whereby cells “eat themselves”—which when disrupted can cause Parkinson’s and diabetes.
2015: William Campbell (US citizen born in Ireland) and Satoshi Omura (Japan), Tu Youyou (China) for unlocking treatments for malaria and roundworm.
2014: John O’Keefe (Britain, US), Edvard I. Moser and May-Britt Moser (Norway) for discovering how the brain navigates with an “inner GPS”.
2013: Thomas C. Suedhof (US citizen born in Germany), James E. Rothman and Randy W. Schekman (US) for work on how the cell organises its transport system.
2012: Shinya Yamanaka (Japan) and John B. Gurdon (Britain) for discoveries showing how adult cells can be transformed back into stem cells.
2011: Bruce Beutler (US), Jules Hoffmann (French citizen born in Luxembourg) and Ralph Steinman (Canada) for work on the body’s immune system.
2010: Robert G. Edwards (Britain) for the development of in-vitro fertilisation.
2009: Elizabeth Blackburn (Australia-US), Carol Greider and Jack Szostak (US) for discovering how chromosomes are protected by telomeres, a key factor in the ageing process.
2008: Harald zur Hausen (Germany), Francoise Barre-Sinoussi and Luc Montagnier (France) for work on the viruses causing cervical cancer and AIDS.
2007 Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells.
2006 Andrew Z. Fire and Craig C. Mello for their discovery of RNA interference – gene silencing by double-stranded RNA.
2005 Barry J. Marshall and J. Robin Warren for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.
2004 Richard Axel (US) and Linda Buck (US) for their discoveries of “odorant receptors and the organization of the olfactory system.
Endogenous RNA interference is the energy-dependent epigenetic link from the physiology of pheromone-controlled reproduction to biophysically constrained viral latency. The stress-linked virus-driven degradation of messenger RNA has been linked to all pathology.
Addendum 1)
This morning I spoke with a 10-year veteran who had served in Iraq. He was not happy with the treatment for PTSD that he was receiving from the VA because he and his wife know he is getting worse (e.g., hyper-vigilance and more nightmares).

He has a 20% disability and my antagonists are causing it to get worse with their claims that my life’s works are “bullspit” and/or that “nobody cares.”
 
How can anyone convince a veteran that people care at a time when most will not take the time to watch a short video like this one?  Superbugs, Bacteriophages and Phage Therapy: An Interview with James Kohl Published on 17 May 2017
 
See for comparison:3/09/17 Jay Feierman: One can’t have Darwinian evolution by natural selection without either “random” mutations or directional selection. They are both necessary, proximate, contributing causes for genes and the proteins they code for changing in frequency over time in a population and by which the population becomes adaptively configured to the current environment.
 
Adaptations are food energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction in species from microbes to humans.The claim that populations are adaptively configured are nothing more than pseudoscientific nonsense.
 

If you let our veterans, as individuals, continue to think they are less than human because a mutation or something else causes their failure to adapt to the challenges of life after returning from military service overseas, how will you convince yourself that you are not contributing to the death rate by suicide?

Addendum 2) Las Vegas Shooting: Live Updates (with video)

Other lawmakers woke up to the news and offered thoughts and prayers. Governor Brian Sandoval of Nevada called the shooting a “heinous act of violence.”

All heinous acts of violence are caused by the virus-driven degradation of messenger RNA, not by the natural selection for mutations as claimed in Mutation-Driven Evolution

(2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation.

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

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

Alternative splicing of pre-mRNA

Evolutionary theories of epigenetic drift (2)

Summary: For another refutation of neo-Darwinian pseudoscientific nonsense, see: Conformational landscape of isolated capped amino acids: on the nature of non-covalent interactions
reported as:  Folding biomolecule model shows how form dictates function

Mapping Human Genetic Ancestry (2007)

…the sorting of such ancestral phenotypic polymorphisms in subsequent speciation events provides a parsimonious explanation why evolutionary derived characteristics are shared among species that are not each other’s closest relatives.

The claims about evolutionary derived characteristics require acceptance of the belief that one species can evolve into another. For comparison to ridiculous neo-Darwinian theories of mutation-driven evolution, which are now being framed in the context of epigenetic drift see: Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease

…a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation…”

See also: MicroRNA: Basic concepts and implications for regeneration and repair of neurodegenerative diseases

The relationship between miRNA, neurodegeneration and neurogenesis will be highlighted. Moreover, the benefits, outcomes and limitations of therapies using miRNA technology for neurodegenerative disorders will also be discussed.

See also: A ventral glomerular deficit in Parkinson’s disease revealed by whole olfactory bulb reconstruction
Reported as: Researchers find the key to loss of smell with Parkinson’s disease

This reduction is consistent with the hypothesis that Parkinson’s disease begins with bacteria, viruses or environmental toxins entering the brain via the nose and affecting first the olfactory bulb, where the neurodegenerative disease is triggered and gradually spreads through other parts of the brain.

The link from quantized energy as information to the virus-driven degradation of messenger RNA and the loss of olfactory acuity/specificity was detailed in molecular epigenetics section of of our 1996 Hormones and Behavior review: “From fertilization to adult sexual behavior.”
 
At that time, microRNAs were called pre-mRNAs. Since the turn of the 21st century, the pre-mRNAs have been called microRNAs in attempts to obfuscate what has been known to serious scientists about the ATP-dependent creation of RNA. The creation of the sun’s anti-entropic virucidal energy links the creation of microRNAs to all morphological and behavioral diversity on Earth via the sense of smell and physiology of reproduction in bacteria.
 

See: microRNA

See also: Olfaction Warps Visual Time Perception

Reported as:  Odors Alter Subjective Time Experience

The sense of smell is like a time machine that links our experiences from the past to our behaviors throughout life.

All pseudoscientists use changes in words and definitions to prevent anyone who intends to become a serious scientist from learning how energy as information must be linked from the physiology of pheromone-controlled reproduction by feedback loops.

See: Feedback loops link odor and pheromone signaling with reproduction

All serious scientists are Combating Evolution to Fight Disease

See my comment to Science from March 7, 2014

Darwin probably anticipated the insemination of population genetics that led to the bastardization of his detailed observations in the “Modern Synthesis.” He politely insisted that ‘conditions of life’ be considered before natural selection.

There are two ‘conditions of life.’ It is nutrient-dependent and pheromone-controlled. Rosenberg and Queitsch now note the work with Dobzhansky’s rarely acknowledged claim: “I am a creationist and an evolutionist.” They also declare the need for “Deep understanding of the mechanisms that generate variation at the molecular level…”

Deep understanding of the ‘conditions of life’ does not come from theory.

Problems with the “modern synthesis” now lead us back to the facts about biologically-based cause and effect that Darwin and Dobzhansky approached with humility, which are the same biological facts that evolutionists approached with ignorance about behavioral affects and the arrogance that accompanies that ignorance. Rosenberg and Queitsch echo the sentiments of those who have been subjected to academic suppression.

Clearly, however, “nothing in evolution makes sense except in the light of biology” is not an exaggeration. It is a common sense statement about the biologically plausible genesis of functional cell types. Population genetics and evolutionary theories abandoned the biophysical constraints of ecological variation and the physiology of reproduction, which enable epigenetically-effected nutrient-dependent pheromone-controlled receptor-mediated ecological adaptations and species diversity via the complexities of protein folding and niche construction.

It’s time for biophysicists to tell theorists and pathologists how to differentiate between theories about the genesis of different cell types and the biological facts about the nutrient-dependent pheromone-controlled ecological adaptations that enable the genesis of different cell types in individuals of different species. Simply put, it’s time to stop trying to explain ecological adaptations in the context of mutations and evolution.

See also: A new paradigm for treating transcription factor-driven cancers

Figuring out how EWS interacts with other EWS portions, and with FLI, could result in a clinical revolution for transcription factor-driven cancers. “If you can disrupt the function of the EWS component, you can stop cancer in its tracks. New cancer would be prevented, and the cancer that exists will die,” says Dr. Lessnick. “Another target would be to block the binding of FLI to the microsatellites. Without this binding, Ewing sarcoma can’t manifest.”

All pathology is caused by virus-driven energy theft, which links changes in the microRNA/messenger RNA balance from the degradation of messenger RNA to changes in transcription factors via autophagy.
See: Conformational landscape of isolated capped amino acids: on the nature of non-covalent interactions
reported as:  Folding biomolecule model shows how form dictates function
Outside the context of the obvious fact that form dictates function, there are theories that our ancestors evolved in caves. The theories make no sense to creationists who recognize that the fossil record includes examples of humans with virus-driven degradation of their messenger RNA.
See for example: Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria
This was reported as: New Genetic Cause Discovered for Photosensitive Blood Disorder
Without realizing it, they report that virus-driven energy theft links a dominant mutation and the ATPase active site of human CLPX. Specifically, p.Gly298Asp results in pathological accumulation of the heme biosynthesis intermediate protoporphyrin IX (PPIX).
Tthe virus-driven degradation of messenger RNA links the Gly298Asp amino acid substitution to the photosensitive blood disorder, erythropoietic protoporphyria (EPP). They place that fact into the context of a mutation in CLPX that inactivates its ATPase activity, which supposedly alters the coassembly of mutant and Wild Type “protomers” to form an enzyme with reduced activity.
Conclusion: Use of the terms mutation, coassembly, and protomer obfuscate fact about energy-dependent RNA-mediated cell type differentiation. Instead, they claim that “The presence of low-activity CLPX increases the posttranslational stability of ALAS, causing increased ALAS protein and ALA levels, leading to abnormal accumulation of PPIX.”
My summary: Biologically uninformed science idiots must still try to avoid any direct link between the anti-entropic virucidal of sunlight and healthy longevity. No matter how obvious the direct link becomes, the word games of pseudoscientists must continue for a few more weeks. Then the release of the cell biology game “Cytosis” means it is “game over” for all theorists. It will become clearer that the remains of cave-dwelling primates and their paintings on the wall are evidence that they suffered from virus-driven low-activity CLPX, which increased the posttranslational stability of ALAS. The fact that altered posttranslatkional stability caused increased ALAS protein and ALA levels, which lead to abnormal accumulation of PPIX suggests that they were driven back into the caves by the lack of nutrients that led to their virus-driven pathology and ultimately to their extinction. Claims that they evolved into modern humans are ridiculous at every level of examination that clearly links energy-dependent changes from angstroms to ecosystems in all living genera.
See also: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems and the complaints about the facts in Uproar in Turkey over removing evolution from biology class
 
 
 
 

rp_levels-of-organization.jpg

Pseudoscientists fail to refute theistic evolution

Darwinism for the Genomic Age: Connecting Mutation to Diversification

…the chief cause of our natural unwillingness to admit that one species has given birth to other and distinct species, is that we are always slow in admitting any great change of which we do not see the intermediate steps. (Darwin, 1859)

Darwin put energy-dependent “conditions of life” before what is now known about natural selection for codon optimality. That is the chief cause for ignoring anything that neo-Darwinists claim about mutations and diversification.
Energy-dependent codon optimality links the epigenetic landscape to the physical landscape of supercoiled DNA in all living genera via endogenous RNA interference and fixation of amino acid substitutions. The energy-dependent fixation of amino acid substitutions differentiates all cell types in all living genera in the context of the pheromone-controlled physiology of reproduction and supercoiled DNA
For comparison: Virus-driven energy theft has been linked from mutations to all pathology.

See also: Circulating Plasma and Exosomal microRNAs as Indicators of Drug-Induced Organ Injury in Rodent Models

…circulating plasma and exosomal miRNAs can be used as potential biomarkers specific for drug-induced liver, kidney or muscle injury.

The circulating microRNAs typically link nutrient energy-dependent changes in the microRNA/messenger RNA balance from endogenous RNA interference to supercoiled DNA via RNA-mediated DNA repair.

For comparison, see: DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification

Reported as: Study shows higher than expected sequencing errors in public databases

…the accuracy of public databases has been called into question by work done by the team at NEB, which in turn calls into question the accuracy of the cancer datasets.

The link to specimen processing to the number of errors helps to explain why only serious scientists have refuted theistic evolution. Pseudoscientists incorporated the specimen processing errors into their ridiculous mathematical models. Their mathematical models failed to link energy dependent changes in base pairs to single nucleotide polymorphisms and endogenous RNA interference. That fact destroyed any chance that natural selection for energy-dependent codon optimality would be linked from supercoiled DNA to protection from virus-driven energy theft and genomic entropy in all living genera.

See for example: 2007 Using genomic data to unravel the root of the placental mammal phylogeny

A revised molecular timescale based on these phylogenetic inferences suggests Afrotheria and Xenarthra diverged from other placental mammals ∼103 (95–114) million years ago.

Then this: 2013  Making the impossible possible: rooting the tree of placental mammals

…two groups of researchers have scrutinized the largest available genomic data sets bearing on the question and have come to opposite conclusions, as reported in this issue of Molecular Biology and Evolution.

Then this: 2016  Rooting the family tree of placental mammals

“The molecular clock analysis uses a combination of fossils and genomic data to estimate when these lineages diverged from each other,” said author Dr Mario Dos-Reis of Queen Mary London, UK. “The results show that the afrotherians and xenarthrens diverged from one another around 90 million years ago.”

“You don’t always need to overturn the status quo to make a big impact,” said Dr Tarver. “All of the competing hypotheses had some evidence to support them — that’s precisely why it was the source of such controversy. Proving the roots of the placental family tree with hard empirical evidence is a massive accomplishment.”

Nothing about the roots of any family tree has ever been proved in the context of the fossil record and genomic data. The organization of genomes is nutrient-dependent and pheromone-controlled in the context of energy-dependent links from chirality to autophagy and supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy, which is clearly the only link to pathology that consistently shows up in the pathology of dead things.

It’s time to admit that many researchers do not know how RNA-mediated cell type differentiation is biophysically constrained in the context of energy-dependent endogenous RNA interference. The magnitude of the problem increases every day for students in the USA who are taught to believe in mutation-driven evolution.

See for comparison: Endogenous RNAi Pathways Are Required in Neurons for Dauer Formation in Caenorhabditis elegans

Conclusion:

Our data presented here suggest the intriguing possibility that RNAi pathways may mediate distinct effects on gene expression in postdauer animals that experienced different environmental stresses. Since other animals, such as pea aphids, form polyphenisms due to crowding or starvation as well, we predict that this work may have broader implications for the RNAi-mediated regulation phenotypic plasticity.

My goodness, what an “intriguing possiblity.” It might be possible to link energy-dependent RNAi from chirality to autophagy and all biodiversity on Earth by starting from the anti-entropic virucidal energy of sunlight and linking it to the differences between bacteria and virus-infected archaea in the ocean via the physiology of their pheromone-controlled reproduction.

See also: Dobzhansky 1973 and precision medicine (5)

See also: RNA-Guided Human Genome Engineering

5. Repetitive elements or endogenous viral elements can be targeted with engineered Cas+gRNA systems in microbes, plants, animals, or human cells to reduce deleterious transposition or to aid in sequencing or other analytic genomic/transcriptomic/proteomic/diagnostic tools (in which nearly identical copies can be problematic).

Targeting viral elements with energy-dependent Cas+gRNA systems in microbes, plants, animals, or human cells links energy-dependent RNA-mediated amino acid substitutions to viral latency in all living genera. That fact links these three refutations of theist evolution to the examples of the refutations in this model. Nutrient-dependent/pheromone-controlled adaptive evolution: a model
One George Church refutes theistic evolution (3-part series)
Two Francis S. Collins refutes theistic evolution
Three Stuart Kauffman refutes theistic evolution
See also: Scientific Seeker Stuart Kauffman on Free Will, God, ESP and Other Mysteries

He proposed that our scientific understanding of reality is radically incomplete, and that some sort of anti-entropy, order-generating force remains to be discovered.

Let me make this perfectly clear:

The anti-entropic order-generating force is sunlight.

 

Amino acid modification FA_Epigenetics_Table1

Francis S. Collins refutes theistic evolution

Criticisms of the nutrient-dependent pheromone-controlled evolutionary model

Based on his writings, both published and unpublished, James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others’ research. — Andrew Jones, BA

Editor’s note

The 2013 review article by James Vaughn Kohl published in Socioaffective Neuroscience & Psychology and criticized in the above Letter to the Editor was subjected to standard peer review and the revised version was accepted by me after it had been accepted by both reviewers.

See for comparison: The Language of God: A Scientist Presents Evidence for Belief, by Francis S. Collins. The current director of the NIH also is a co-author of Genetic regulatory signatures underlying islet gene expression and type 2 diabetes

…T2D risk alleles that overlap with RFX footprints uniformly disrupt the RFX motifs at high-information content positions. Together, these results suggest that common regulatory variations have shaped islet TF footprints and the transcriptome and that a confluent RFX regulatory grammar plays a significant role in the genetic component of T2D predisposition.

No experimental evidence of biologically-based cause and effect suggest that any common regulatory variations has ever evolved. Let me make that fact perfectly clear in the words of the co-authors:

“Individuals who are heterozygous for a frameshift mutation in RFX6 have increased 2-h glucose levels (33). Importantly, rare autosomal recessive mutations that alter DNA-contacting amino acids in the DNA binding domain of RFX6 result in Mitchell–Riley syndrome, which is characterized by neonatal diabetes (29).

The frameshift mutation and rare autosomal recessive mutations occur outside the context of energy-dependent endogenous RNA interference (RNAi). For comparison RNA-directed DNA methylation (aka endogenous RNAi) typically links DNA-contacting amino acids to healthy longevity via the transgenerational epigenetic inheritance of morphological and behavioral phentoypes in species from microbes to humans. It is difficult to describe all the links, but it is clear that RNAi links RNA-directed DNA methylation from energy-dependent changes in chirallity to base pairs, single nucleotide polymorphisms (SNPs) and autophagy via the innate immune system.
Without any mention of how virus-driven energy theft links mutations from SNPs to pathology, Francis S. Collins and his co-authors link the rare autosomal recessive mutations to altered DNA-contacting amino acids. Apparently, they do not want to mention anything about the fact that natural selection for energy-dependent codon optimality is the link from RNA-mediated protein folding chemistry to all biophysically constrained healthy longevity. Instead, they seem willing to ignore the facts about energy-dependent fixation of RNA-mediated amino acid substitutions in cell types.
Indeed, they seem to put everything known to serious scientists into the context of the theistic evolution of pathology. Serious scientists know that nutrient energy-dependent pheromone-controlled cell type differentiation is the link from atoms to ecosystems in models of ecological adaptation.
Clearly, anyone who does not want to expose the pseudoscientific nonsense touted by neo-Darwinian theorists and theistic evolutionists should not mention “amino acid” and “mutation” in the same context. Using only the definitions of both terms in the same sentence (above) alerts all serious scientists to the fact that nutrient energy-dependent amino acid substitutions are not the same as mutations, which are caused by virus-driven energy theft.
Reported as: Diabetes in your DNA? Scientists zero in on the genetic signature of risk

…for now, it’s the first demonstration that many Type 2 diabetes-linked DNA changes have to do with the same DNA-reading molecule. Called Regulatory Factor X, or RFX, it’s a master regulator for a number of genes.

The regulation of genes is energy dependent.

“RFX is probably unable to read the misspelled words, and this disruption of regulatory grammar plays a significant role in the genetic risk of Type 2 diabetes.”

The concept of “misspelled words” is appropriate for use only in the context of pseudoscientific nonsense that fails to address facts about natural selection for energy-dependent codon optimality. Codon optimality links the speed of light on contact with water to biophysically constrained RNA-medidated cell type differentiation in all living genera.

They characterized differences not just in DNA sequences, but also in the way DNA was packaged and modified by epigenetic factors, and the levels of gene expression products that indicated how often the genes had been read and transcribed.

Epigenetically-effected reading and transcription is energy dependent and biophysically constrained via the speed of light and hydrogen-atom transfer in DNA base pairs in solution such as seawater and blood. Serious scientists noticed that pattern and linked virus-driven energy theft from pathology in bacteria to archaea and from the transgenerational epigenetic inheritance of Zika-virus damaged DNA in human infants. The craniofacial morphology and brain development of infected human infants clearly links energy-dependent fixation of amino acids to the morphological and behavioral phenotypes of all living genera.
See: Nothing in Biology Makes Any Sense Except in the Light of Evolution

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

Facts about nutrient energy-dependent codon optimality also are known to be refutations of neo-Darwinian pseudoscientific nonsense because codon optimality links Darwin’s “conditions of life” to the physiology of reproduction in all living genera.
See: Codon optimality controls differential mRNA translation during amino acid starvation and Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition
See for comparison: Epigenetic Editing of Ascl1 Gene in Neural Stem Cells by Optogenetics

Each DNA change might alter this binding in a different way, leading to a slightly different effect on Type 2 diabetes risk or blood sugar regulation. But the common factor for many of these changes was its effect on the area where RFX is predicted to bind, in the cells of pancreatic islets.

So, says Parker, this shows how the genome – the actual sequence of DNA—can influence the epigenome, or the factors that influence gene expression.

The sequence of DNA cannot influence the epigenome before the energy-dependent sequence has been created via natural selection for codon optimality. That is why epigenetically-effected nutrient-dependent pheromone-controlled energy-dependent changes in supercoiled DNA were linked from the weekend resurrection of the bacterial flagellum in Pseudomonas fluorescens to all biodiversity in all living genera via the conserved molecular mechanisms that link light energy-induced changes in microRNAs to all biodiversity.
See also: Optokinetically encoded nanoprobe-based multiplexing strategy for microRNA profiling
Programmable artificial phototactic microswimmer

For active drug delivery, the nanomotor should be able to orient towards specific chemical signals, such as those demonstrated in chemotaxis21–25 and pH taxis26.

See also: pH-Taxis of Biohybrid Microsystems

…assuming that it is possible to tune the preferred pH of bioactuators by genetic engineering, these biohybrid microsystems could potentially be applied to sense the pH gradient induced by cancerous cells in stagnant fluids inside human body and realize targeted drug delivery.

If naturally occurring chemotaxis could not readily be linked from pH-taxis and phototaxis to natural selection for codon optimaility and supercoiled DNA, light energy as information could not be linked to communication between the microscopic and the macroscopic world.
Light Could Propel Nanorobots on a “Fantastic Voyage” Through the Human Body

“Light is a more effective option to communicate between the microscopic world and the macroscopic world,” said Tang.

The fact that the energy-dependent virucidal effects of sunlight have been linked to the weekend resurrection of the bacterial flagellum in an organism that fluoresces on exposure to UV light was placed into the context of claims about two amino acid substitutions that were reported as if they were mutations.
Summary: Francis S. Collins, current NIH director, is a theistic evolutionist. He should not use his position to tout the pseudoscientific nonsense of evolution. He is supposed to link experimental evidence of biologically-based facts to healthy longevity or to pathology.
See also: United states health care reform: Progress to date and next steps

All of the individuals who assisted with the preparation of the manuscript are employed by the Executive Office of the President.

Former President Barrack Obama should not have used his position or his employees to mislead the voters in the United States of America. He correctly stated that “…partisanship and special interest opposition remain…,” which ensured that “…experience with the Affordable Care Act…” would demonstrate “…that positive change is achievable on some of the nation’s most complex challenges.” That claim was placed into the context of misrepresentations made by ~50% of people who are biologically uninformed theorists and/or those who are atheists. Clearly there is overlap among those groups of people. Hopefully, others will see why. They’ve been taught to believe in theistic evolution or nothing.
Experimental evidence of biologically-based cause and effect refutes theistic evolution by linking virus-driven energy theft to all pathology in all living genera. In the context of  Genetic regulatory signatures underlying islet gene expression and type 2 diabetes, Francis S. Collins revealed either his ignorance or his treachery.
The article links the nutrient energy-dependent pheromone-controlled physiology of reproduction to the weekend resurrection of the bacterial flagellum in P. fluorescens via RNA synthesis, not mutations.
Virus-driven energy theft influences energy-dependent RNA-mediated gene expression, and the energy theft is clearly linked to mutations. See for example: DEPENDENCE OF RNA SYNTHESIS IN ISOLATED THYMUS NUCLEI ON GLYCOLYSIS, OXIDATIVE CARBOHYDRATE CATABOLISM AND A TYPE OF “OXIDATIVE PHOSPHORYLATION”

The synthesis of RNA in isolated thymus nuclei is ATP dependent.

See also: microRNA “Regulatory Factor X” 
 

IMG_3010

Bio-functional information

Peter Berean‘s attack on my model of energy as information led him to invent or re-introduce the term “Bio-Functional Information.” The comment from Greg Thurston (below) can be placed into the context of Schrodinger’s claims from “What is Life?”
For instance, Schrodinger challenged de Vries definition of the term mutation with this entry:

“Indeed, in the case of higher animals we know the kind of orderliness they feed upon well enough, viz. the extremely well-ordered state of matter in more or less complicated organic compounds, which serve them as foodstuffs. After utilizing it they return it in a very much degraded form -not entirely degraded, however, for plants can still make use of it. (These, of course, have their most power supply of ‘negative entropy’ the sunlight.) (pp. 73 and 74)”

Watch as Greg launches another personal attack against me because I refuse to allow Peter Berean‘s comments on my representations of energy as information to go unchallenged. In my model, for comparison,  the anti-entropic energy of sunlight is linked to all biodiversity,
See: What is life when it is not protected from virus driven entropy?
Greg makes it appear that I am the only person who knows Peter Berean is trying to introduce a term that must be defined before others realize it is synonymous with de Vries 1902 definition of mutation. Peter Berean’s treachery could conceivably delay scientific progress for at least one more generation if students are taught that “Bio-Functional Information” is different that energy as information.
The success of all threats to scientific progress depends on the misrepresentations of theorists, and definitions are one way to eliminate energy as information from biologically-based cause and effect. De Vries definition of mutation did that and his definition has served biologically uninformed theorists very well during the past 114 years.
Sudden energy jumps were used to link the assumptions of theorists to claims about mutation-driven evolution, which supposedly occurred via natural selection. All serious scientists have since realized that natural selection for energy as information must be linked from codon usage to energy-dependent changes, which link the physiology of reproduction to supercoiled DNA in all living genera.
Theorists are not likely to ever accept that fact. The levels of complexity are too difficult for pseudoscientists to integrate, which helps to explain why many of them are also atheists or agnostics. When creationists tout the same pseudoscientific nonsense, it shows why we have come so close to the virus-driven apocalypse.
———————————–
Greg Thurston wrote:
December 17 at 10:59am
James Kohl – it was nice to see your name in the comments on this thread when it first appeared. Then it was quite a surprise to see the nature of your comments. It’s been a while since we connected. I believe you are onto something, but somehow you are unable to convey it in a way that anyone (or at least most) can assimilate. As you may recall, I even thought for a while that I could help unpack it enough to make it clear (to me and then others), but the more I waded into it, the denser the thicket seemed to get, and I was overwhelmed. I don’t have the time. I am so disappointed to see the tone of your comment [to] Peter Berean. I thought you were above ad hominem et al. I hope you can take this as not an insult, but a caution from one who would like to be considered a friend, that it seems perhaps ego has clouded your ability to be gracious and have courteous discourse with others who see things differently. It is amazing to me how much ego commandeers intellect in so many instances. It is a threat to us all, of which we must be exceedingly diligent to resist.
———————–
See also: What is Life?
“How often do we still hear that quantum effects can have little relevance in the study of biology, or even that we eat food in order to gain energy?” — Roger Penrose (8 August 1991)
I get the impression that Greg Thurston might think Roger Penrose is an ego-maniacal threat to Peter Berean‘s intellect.
Perhaps, someone like Greg Thurston will first ask Peter Berean to tell others the difference between a “mutation” and “bio-functional information.” For contrast, in the context of my model, the fixation of energy-dependent RNA-mediated amino acid substitutions links biophysically constrained cell type differentiation to the physiology of reproduction in all living genera.
Theorists do not have a model for how that occurs in the context of biophysical constraints. They have theories, which helps to explain why Peter Berean is tweaking the theories via his usage of words. He knows nothing about natural selection for energy-dependent codon optimality. That requires the invention and/or reuse of the term “bio-functional information.” It is a great way for pseudoscientists to dismiss everything known to serious scientists via a vague term.
Alternative splicing of pre-mRNA

Energy-dependent purifying selection / autophagy (6)

See: Energy-dependent purifying selection / autophagy (5)

Simply put all aspects of biophysically constrained energy-dependent cell type differentiation must first be linked from the physiology of reproduction to ecological adaptations, or they must be linked from energy theft to the evolution of pathology.

See for contrast and comparsion: Finding your diagnosis in the brave new world of genetics-based medicine by John Hewitt

Excerpts:

  1. Typically all they have is a stack of diffuse paper reports and xeroxed publications from the primary medical literature with no clear explanation to tie everything together.
  2. This current state of affairs is not the direct fault of anybody in particular, but rather a side effect of an incomplete and evolving body of knowledge that necessarily contains significant ambiguity in its presentation.
  3. Having a ‘genomic sequencing’ reference (g.) would be a little more informative here for many reasons, namely, the presence of multiple transcription initiation sites (promoters), alternative splicing, the use of different poly-A addition signals, multiple translation initiation sites (ATG-codons), and the occurrence of length variations. Potentially, if exome sequencing draws on mRNAs after they are edited, (either in nucleus-specific or cytosol-specific editing), this would be an issue too, although RNA editing (post-transcriptional modification of bases, mostly A to G or A to I substitutions in humans) is quite rare.
  4. An important related question here is what tissue source got sequenced in the exome analysis—was it blood, skin, or epithelium? Because the same gene is typically spliced differently in different tissues it would also give different cDNAs in exome analysis of different tissues.
  5. Isoleucine is a hydrophobic amino acid and serine is a polar and uncharged amino acid. These are fairly different animals altogether and it is normally assumed that this kind substitution should have some significant effect on protein structure or function. The question is what effect?
  6. I will not delve much further into the other variants found in the genetic testing other than to note that the one for PGAP1 has a slightly different notation from the others, given as c.2525+4C>T. This annotation c.2525+4C>T appears to suggest that this variant is located +4 nucleotides apart from the last exonic nucleotide. This variant is predicted to be a “splice donor” which means that can alter the length of the resulting protein, a different transcript. PGAP1 has 22 exons and at least 11 splice variants. This variant has a mutation in the intron downstream of nucleotide position 2525. This creates a splice junction failure where the intron will not be spliced out and thus the variant will include protein sequence corresponding to the intron.

Thanks to John Hewitt for calling attention to this at a time when others are beginning to realize there is no such thing as “genetics-based” medicine. Personalized species-specific treatments across different human populations must link nutrient energy-dependent changes from angstroms to ecosystems.
All serious scientists will continue to attest to that fact. Even the best science journalists may not be able to cross disciplines and report on what is already known. For example, John Hewitt comes up short.
Excerpt (I paraphrase to reiterate):

I will not delve much further into the other variants found in the genetic testing other than to note that … [one variant] …. is predicted to be a “splice donor” which means that can alter the length of the resulting protein, a different transcript. PGAP1 has 22 exons and at least 11 splice variants. This variant has a mutation in the intron downstream of nucleotide position 2525. This creates a splice junction failure where the intron will not be spliced out and thus the variant will include protein sequence corresponding to the intron.

My comment: There is no need to delve any further into the differences in the splice variants. The differences link natural selection for energy-dependent codon optimality to the RNA-mediated fixation of amino acid substitutions in supercoiled DNA. Supercoiled DNA links chromosomal rearrangements to the physiology of reproduction, which prevents most of the transgenerational epigenetic inheritance of virus-driven energy theft. Virus-driven energy theft links negative supercoiling in DNA to all pathology in all living genera.
Until more people understand that fact, even the best science journalists are not likely to escape from the pseudoscientific nonsense touted by theorists who fail to link energy to healthy longevity and/or fail to link virus-driven energy theft to all pathology.
No one gets out of this alive who cannot understand that the splice variants are energy-dependent, which is why no one lives for ever. Eventually, the viruses steal too much energy and use it for their genomic stability.
Not only does that fact limit the life expectancy of all humans but the limits are predictably linked from nutrient stress and/or social stress to everything known about energy-dependent amino acid substitutions in the context of life history transitions, which link the energy-dependent differences in archaea to humans via differences in base pairs and amino acid substitutions.

Alternative splicing of pre-mRNA

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

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

Conclusion:

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

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

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

Excerpt:

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

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

Excerpt:

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

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

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

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

Conclusion: 

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

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

See: From Fertilization to Adult Sexual Behavior

Excerpt:

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

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

For comparison, see: Mutation-Driven Evolution

Excerpt:

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

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

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

Excerpt:

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

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

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

Excerpt:

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

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

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

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

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

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

See also: Research Topic Multi-omic Data Integration

Excerpt:

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

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

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

Excerpt:

…the interactions between pre-mRNA and proteins fine-tune alternative splicing in a manner that can gradually create new protein functionalities without the need to create additional genes and without affecting existing proteins [4-6].

See for comparison: From Fertilization to Adult Sexual Behavior

Excerpt:

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans…. That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Excerpt:

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

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

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

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

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

See for comparison:

Product Development Pipeline

Excerpt:

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

See also: VACRC Projects

Excerpt: Future Projects

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

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

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

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

See: Kalevi Kull: Censorship & Royal Society Evo Event

Excerpt:

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

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

Excerpt:

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

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

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.