terrarium-eco-system

Epigenetics Skeptism

Thanks to Joost G. Wouters for the alert to this nonsense:
1) Michael White in Pacific Standard magazine flatly states that “Epigenetics Is Not Revolutionizing Biology.”
2) Adrian Bird points out in the journal Cell that many of the field’s assumptions and promises remain unproven and are perhaps excessive.
1) White’s article sketches the field’s promise and hype, from questionable epigenetic‬ diets and wild claims about controlling genes with your thoughts. He follows with a summary of epigenetics, then runs through a list of his ridiculous qualms about the field. White paraphrases, “the hype has outrun the science” at a time when serious scientists are Combating Evolution to Fight Disease by integrating everything known about epigenetic links between metabolic networks and genetic networks.
“…scientists have long been aware that our genes aren’t chiseled in stone—they are in a constant dialogue with our environment,” White says. Obviously, he means “gene expression” is not chiseled in stone because the epigenetic landscape is linked to the physical landscape of DNA in all organized genomes by RNA-mediated events. But that point gets glossed over in his excited attack on everything he thinks is not supported by what is currently known about physics, chemistry, and molecular epigenetics.
He doesn’t like the fact that many of the field’s supposed findings for humans — say, that you can inherit specific fears — are based entirely on animal studies, although that is the basis for nearly everything incorporated into today’s medical practice. And of course, pseudoscientists make an issue of whether epigenetic marks are truly a cause or an effect of changes wrought on gene expression by other factors. They have no concept of how the epigenetic landscape is linked via sensory input to the physical landscape of DNA.
White says, “There is no reason to believe that drugs, treatments, or health advice that target these DNA markings will be unusually effective compared to therapies that aren’t specifically epigenetic.” He concludes that it’s overall a good development, but perhaps we need to mind the hype. But see: Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing. It links what is also known about nutritional epigenetics to biologically-based cause and effect in species from microbes to man.
2) Edinburgh University’s Adrian Bird writes in the journal Cell about the overblown idea that biology is undergoing some sort of revolutionary turmoil, only part of which is due to epigenetics.
“So that’s not *junk* DNA?”, “What’s the definition of a gene?”, and “What how much effect does long, non-coding RNA actually have?” These issues consume the article’s first half, but he really gets rolling later. We have good evidence of transgenerational epigenetic inheritance in precious few places, which include C. elegans inheritance of RNA-based viral resistance. That Swedish “hunger winter” stuff is interesting, but hardly rigorous just yet.
And anyway, says Bird, why would passing along diabetes or obesity — as with the hunger winter — be some sort of adaptive mechanism? After all, perhaps the apparently inherited traits just result from malfunctions in the slate-wiping that every animal seems to do early in development.’
My comment: Viral resistance is nutrient-dependent and in animals it is controlled by the metabolism of nutrients to species-specific pheromones that control the physiology of reproduction. Thanks to Joost for permission to use pars of his original introduction, with alterations. He wrote: “No permission required on my part…”
Most links are in the PSMAG article itself. Check out those articles here! See also: Serving epigenetics before its time and Scrutinizing the epigenetics revolution

Epigenetics Is Not Revolutionizing Biology

[if you are a social scientist]

human-evolution

Is DNA-directed transcription RNA-mediated?

Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles.
Concluding sentence excerpt: “…rather than a rigid deterministic mechanism, transcription is not hardwired and able to select against potentially adverse changes in the DNA template. Such transcription avoidance may be yet another layer of protection against the detrimental consequences of mutations and provide further clues to understanding its possible consequences, including reduced penetrance and variable expressivity.”
Reported as:

Rather than being a one-way street, DNA-directed RNA transcription may have profound adaptability

Excerpt: “…allowed the authors, for the first time, to prove the tendency of the transcriptional machinery in the cell to avoid transcribing DNA strands harboring a newly induced mutation. This is likely to be a novel cellular defense mechanism to prevent genetic mutations from being expressed.”
My comment: I detailed this cause and effect relationship in the context of the anti-entropic epigenetic effects of light-induced amino acid substitutions in plants and animals, and nutrient-dependent amino acid substitutions that control the physiology of reproduction via their fixation in the organized genomes of all genera. If I had not already done that, I would be scrambling to present accurate representations of top-down causation by detailing the links between viral microRNAs and nutrient-dependent microRNAs that lead from entropic elasticity to epistasis in all genera. I would not be waiting for someone else to do it.
Why should anyone else get to enjoy all the negative feedback from evolutionary theorists and theoretical physicists who support the evolution industry and “big bang” cosmology industry?  Now, after the laughter about their ridiculous theories dies down, everyone can join other serious scientists who are Combating Evolution to Fight Disease.
Welcome to the real world of biologically-based top-down causation that links physics, chemistry, and the conserved molecular mechanisms of cell type differentiation from atoms to ecosystems. Wave goodbye to people like Masotoshi Nei who claim “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.” (p. 199) Mutation-Driven Evolution
See for comparison: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

human-evolution

RNA directed DNA methylation and cell types

Cell type differentiation is included in all topics in biology, which is why it is important to understand what is currently known about top-down causation in the context of physics and chemistry. Taken together, physics, chemistry, and the conserved molecular mechanisms of biology link Drosophila to Octopuses and all other species on this planet via RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate cell types. See for examples: Let there be anti-entropic light (1)
An antagonist led me to ask: “How can anyone who has worked with squid not link light-induced amino acid substitutions in plants and animals to the nutrient-dependent pheromone-controlled physiology of reproduction in bobtail squid via what is currently known about quantum physics, quantum biology, and quantum smell linked to quantum consciousness?”
The ever more antagonistic Ricardo Lara Ramírez responded: “I´ll put it simply: that sentence is at least worth 10 PhD projects together…”

He was berating me for claiming  what George F.R. Ellis claimed about top-down causation and what Stuart A. Kauffman claimed about anti-entropy. It’s as if the thought never occurred to him and to several other theoretical physicists that “Life is physics and chemistry and communication” Having no thoughts of their own about top-down causation might explain their attitude towards me. I’ve provided examples of how the anti-entropic epigenetic effects of light and food link physics, chemistry, and communication, to biodiversity.

For another example of how light-induced amino acid substitutions are linked from what organisms eat to their morphological and behavioral phenotypes via the physiology of their nutrient-dependent reproduction see: Honey, I shrunk the ants: How environment controls size and Researchers nearly double the size of worker ants .

These reports address the most recent work that links RNA-directed DNA methylation to RNA-mediated amino acid substitutions and cell type differentiation, which links the physiology of reproduction to the morphological and behavioral phenotypes of species from microbes to man.

Epigenetic variation in the ​Egfr gene generates quantitative variation in a complex trait in ants

Excerpt:

The evolution of quantitative traits is therefore thought to occur through random mutations across these loci3,56.
However, the empirical search for QTLs has revealed that trait variation often maps to specific genetic regions of small or large effect, and with specific functions4,57. The apparent gap between the assumptions of the infinitesimal model and the results of QTL analyses is further exacerbated by the fact that countless studies have demonstrated that QTLs cannot in themselves explain all heritable variation underlying quantitative traits5, such as growth or size in humans58, Arabidopsis59 and yeast60. 

My comment: We continue to see cell type differentiation accurately portrayed in the context of nutrient-dependent pheromone-controlled fixation of amino acid substitutions in species from yeasts to humans. That links cell type differentiation to light-induced amino acid substitutions in plants. The extension from plants and other animals to modern human populations also has become clear.
See: New genetic evidence resolves origins of modern Japanese
Excerpt: The results from a genome-wide, single nucleotide polymorphism (SNP) data strongly support the hybridization model as the best fit for Japanese population history.
My comment: Hybridation is not mutation-driven evolution. Also, in 2014, others reported what appears to be an RNA-mediated UV light-induced amino acid substitution that may be linked from nutrient uptake to RNA-directed DNA methylation and ecological adaptation in a modern human population.
See: Sunlight adaptation region of Neanderthal genome found in up to 65 percent of modern East Asian population
My comment: Nutrient-dependent pheromone-controlled fixation of the replacement of leucine with isoleucine at the 418th amino acid of HYAL2 and suppression of the oncogenic virus Jaagsiekte sheep retrovirus appears to link the viral microRNA / nutrient-dependent microRNA balance and the survival of a modern human population via the physiology of their pheromone-controlled reproduction. There also are similarities in the mouse-to-human model that links EDAR to cell type differentiation from top-down causation to cell type differentiation in the modern Chinese. For example, a single base pair and single amino acid substitution link the mouse model to adaptations in a modern human population in China.
See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
Excerpt: “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.”
My comment: The story is about ecological variation and ecological adaptation that, as usual is told as one about mutations and evolution. But, as we can see in the reports on Epigenetic variation in the ​Egfr gene generates quantitative variation in a complex trait in ants, it is RNA-directed DNA methylation and RNA-mediated amino acid substitutions that appear to link the epigenetic landscape to the physical landscape of DNA in the organized genomes of all genera.
I will continue to address the fact that their innate ability to respond to viruses and viral microRNAs with nutrient-dependent defenses links metabolic networks and genetic networks to survival and biodiversity, and hope that someone will offer another model of biologically-based cause and effect for comparison — if there is another model.

terrarium-eco-system

Rejecting what is known about viral microRNAs and nutrient-dependent microRNAs

Of Cells and Limits

Leonard Hayflick has been unafraid to speak his mind, whether it is to upend a well-entrenched dogma or to challenge the federal government. At 86, he’s nowhere near retirement.

By Anna Azvolinsky | March 1, 2015

Excerpt:

The rejection letter came from Francis Peyton Rous who received the Nobel Prize a few years later for his discovery of chicken tumor viruses.

My comment:
My 2014 invited review of nutritional epigenetics detailed how differences in the microRNA/messenger RNA balance link viral microRNAs from ecological variation to ecological adaptations via the RNA-mediated differentiation of all cell types in all individuals of all species. It was returned without review.
The problem appears to be the clear link from viruses to RNA-mediated cell type differentiation via amino acid substitutions that stabilize DNA in the organized genomes of all species. That clear link led to the invitation to submit the review.
The invitation came after publication of  Nutrient-dependent/pheromone-controlled adaptive evolution: a model and a series of other previously published works that detail the molecular epigenetics of biophysically constrained RNA-mediated protein folding.
Many of my “peers” still seem to think that mutations lead to the evolution of biodiversity. They won’t consider the fact that viral microRNAS cause entropy or that nutrient-dependent microRNAs link entropic elasticity from DNA repair to the physiology of reproduction.
That anti-entropic fact links the metabolism of nutrients to species-specific pheromones that control the physiology of reproduction. The pheromones link RNA-mediated fixation of nutrient-dependent amino acid substitutions from metabolic networks to genetic networks in species from microbes to humans. See for examples in humans: Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing.
Examples from more than 14,000 patients now show what serious scientists have learned during the past two decades. What they have learned is exemplified in the honeybee model organism and many other model organisms.
In 2013, I wrote: “The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012).”
In his 2003 presentation to the American Philosophical Society, Greg Bear told others about ancient viruses in the human genome that link sexual recombination and pheromonal interaction in multicellular organisms. The organisms communicate with each other, which links what is currently known about physics, chemistry, and molecular epigenetics to species-wide epigenesis and to the obvious anti-entropic examples of epistasis via metabolic and genetic networks.
Unfortunately, more than a decade after Greg Bear presented the facts about biodiversity in two of his science fiction novels, the accuracy of his claims about viruses goes largely unnoticed. Honeybee colony collapse is noticed. But, despite the fact that facts are facts and the fact that facts about viral microRNAs and nutrient-dependent microRNAs have replaced theories, theorists prefer their ridiculous theories.
Perhaps honeybee colony collapse has nothing to do with their nutrient-dependent pheromone-controlled reproduction. Perhaps Greg Bear was wrong when he claimed that “Networks from beehives to brains solve problems through the exchange and the selective cancellation and modification of signals. Species and organisms in ecosystems live and die like signals in a network.”
Perhaps evolutionary theorists like Masatoshi Nei are correct and “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.” Mutation-Driven Evolution (p. 199).
Is there a model for that?

human-evolution

Reverse phosphorylation

See for review: Let there be anti-entropic light (1)

 

Squid are hyper-editors when it comes to RNA

This is a great summary of what is currently known about anti-entropic light and nutrient-dependent RNA-mediated pheromone-controlled cell type differentiation.
Excerpt: “During RNA editing, specific enzymes alter nucleotides in mRNA transcripts so that the resulting protein differs in amino acid sequence from what was encoded by the original DNA. Such RNA editing is a means to generate greater protein diversity…”
The RNA-editing links specific enzymes to differences in the amino acid sequences of the bioluminescent bacteria in the light organ of the bobtail squid to its successful foraging and pheromone-controlled physiology of nutrient-dependent reproduction. An example of how quickly specific enzymes can cause reversible changes in phosphorylation linked to across-species changes in amino acid substitutions in the organized genomes of species from microbes to man was published as:
Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system
Excerpt: Table 1 Mutational trajectory toward slow- and fast-spreading phenotypes.

Mutations confirmed in slow-spreading motility variants are predicted to result in hyperphosphorylation of NtrC; mutations in fast-spreading variants lead to predicted switched specificity of NtrC-P toward FleQ targets. Slow- and fast-spreading variants share the same ancestry.”

My comment: Nutrient-dependent phosphorylation and the pheromone-controlled fixation of amino acid substitutions appears to be the most obvious difference between bacteria that “re-evolved” their functional flagella over-the-weekend and those that did not. However, the nutrient-dependent phosphorylation was reported in the context of mutations in the slow-spreading and in the fast-spreading variants that shared the same ancestry. Results were reported in the context of mutations and evolution in Bacteria ‘hotwire their genes’ to fix a faulty motor.
Excerpt: “Amazingly, we found that just a single tiny change to one of these genetic switches was enough to convert it from being a switch that would normally turn on the genes for using nitrogen into a switch that now turns on the genes to build the flagella. The result is that the bacterium had, in effect, evolved a way to hotwire its motor practically overnight.”
My comment: This does not seem to me to exemplify mutation-driven evolution of microbial flagella or their re-evolution, which occurs “practically overnight.” Instead, it places both outcomes into the same process of what must involve the biophysically constrained chemistry of protein folding and RNA-directed DNA methylation that appears to leads to the RNA-mediated amino acid substitutions via reversible phosphorylation.
If flagella are required to find food, the mutations that caused their loss and loss of function can be repaired if the right nutrients are within their reach.
“Nutrients within reach” is one of the basic principles of DNA repair. In the context of viral microRNAs and genetic entropy, nutrients lead to anti-entropic epigenetic effects on the pheromone-controlled physiology of reproduction. If they did not, organisms could not ecologically adapt. They would be forced to mutate and become another species, which is only possible in the context of ridiculous theories about evolution and some science fiction novels.
The tractable model of fixed amino acid substitutions that they presented was extended across species to primates brain development in 1973, when Dobzhansky wrote: “…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.” Links from nutrient-dependent energy to cell type differentiation via amino acid substitutions were addressed, in theory, in Metabolic theory predicts whole-ecosystem properties. However, the intimate relationships among carbon and energy budgets are not just theoretical.
Excerpt: Carbon dioxide, water, and solar energy are incorporated into the high-energy bonds of organic compounds of plant producers during photosynthesis. When the organic bonds are broken during respiration, plants, animal consumers, and microbial decomposers obtain usable energy in the form of ATP.
My comment: If the authors had simply explained that all biological energy comes from the sun, the link from light-induced amino acid substitutions and photosynthesis to nutrient-dependent pheromone-controlled fixation of amino acid substitutions liked to expansion of the human neocortex compared to other primates might have been clearer. The link is clear in Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion.
Journal Excerpt: “This indicates that the C-terminal 47 amino-acids of ARHGAP11B (after lysine-220) constitute not only a unique sequence, resulting from a frameshifting deletion (fig. S10), but also are functionally distinct from their counterpart in ARHGAP11A.”
My comment: The unique sequence of amino-acids that differentiate the cell types in primate brains was reported as A gene for brain size only found in humans.
Excerpt: “ARHGAP11B is the first human-specific gene where we could show that it contributes to the pool of basal brain stem cells and can trigger a folding of the neocortex. In that way, we managed to take the next step in tracing evolution”, summarizes Wieland Huttner.
My comment: The article about mutations and the evolution of the flagellum and its re-evolution over the weekend, can now be placed into the context of an evolved human-specific gene that might otherwise link mutations to developmental difference in primate brains. However, mutations perturb protein folding, which means they cannot possibly lead to increasing organismal complexity manifested in the structure and function of the flagellum or the structure and function of cell types in primate brains. Simply put, despite the claims of theorists, there is no such thing as a beneficial mutation that could lead to the creation or evolution of a new structure or function.
Note, however, that the co-author of the article on the human-specific gene and neocortex is Svante Paabo, who is considered one of the world’s foremost experts on the evolution of different species. He is frequently involved in reporting on the fossil record and many other aspects of evolution. Most researchers have recently quit reporting evolution as if it occurred via natural selection. See for example: The Surprising Origins of Evolutionary Complexity.
Excerpt:  “Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed “the blind watchmaker.” To some extent, it just happens.
My comment: Evolution also seems to “just happen” in the context of constraint-breaking mutation. See for example: Mutation-Driven Evolution.
Conclusion: “In other words, genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements.” (p. 199)
The problem with reporting evolution in the context of mutations and natural selection is tractable to the senior author, Svante Paabo, of  Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees
Conclusion (2003):  “We find evidence for natural selection acting on OR genes in both human and chimpanzee. The data are consistent with purifying selection acting on intact OR genes in chimpanzee and positive selection acting on at least some of the intact OR genes in humans. We suggest that, whereas most human OR genes are under no or little evolutionary constraint, others have important functions shared with the apes and that a subset have evolved under positive selection in humans. Further studies of specific OR gene clusters in humans may identify the selected changes and shed light on what olfactory stimuli have exercised selective pressures on the human OR gene repertoire.”
My comment: The de novo creation of olfactory receptor genes is biophysically constrained by the nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation. The protein biosynthesis and degradation is perturbed by mutations, for example in the female mosquitoes of some species. See: orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET. The protein biosynthesis and degradation is nutrient-dependent and pheromone-controlled, which enables fixation of the amino acid substitutions linked to the de novo creation of olfactory receptor genes in species from insects to humans. See: Evolution of mosquito preference for humans linked to an odorant receptor and also see: Amino Acid Residues Contributing to Function of the Heteromeric Insect Olfactory Receptor Complex. (March 5, 2012)
I don’t think the link from the epigenetic landscape to the physical landscape of DNA in the organized genome of species from microbes to man will become much clearer, which is why I wrote this:
My March 15, 2012 conclusion: “Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000). — Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors.
My 2013 conclusion: “Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.” — Nutrient-dependent/pheromone-controlled adaptive evolution: a model
My comment: Experts still make claims about mutations that lead to the re-evolution of the flagellum in microbes within days and they make claims about evolution of the human brain that supposedly somehow occurred during millions of years linked to natural selection on olfactory receptor genes. Serious scientists have realized that mutations perturb protein folding, which is stabilized by nutrient-dependent amino acid substitutions. Unfortunately, some scientists appear to be unable to coordinate the reporting of their results. On February 27, 2015 in “Science” ‘Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system‘ was linked to mutations and Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion was reported as if it “just happens.”
Excerpt: “ARHGAP11B arose on the human evolutionary lineage after the divergence from the chimpanzee lineage by partial duplication of ARHGAP11A (25, 26), which is found throughout the animal kingdom…”
My comment: The flagellum did not automagically arise in the microbial lineage. It arose in the context of nutrient uptake and pheromone-controlled fixation of amino-substitutions that differentiated the cell types of the same lineage, virtually overnight. The expansion of the human neocortex did not occur virtually overnight, but it clearly was nutrient-dependent and clearly involves RNA-directed DNA methylation and the RNA-mediated amino acid substitutions that link the de novo creation of structures and functions to difference in morphological and behavioral phenotypes in species from microbes to man via the biophysically constrained chemistry of protein folding. Clearly, serious scientists must view biologically-based cause and effect in the context of physical constraints and chemical constraints. For example, see:  Intronic Non-CG DNA hydroxymethylation and alternative mRNA splicing in honey bees
Excerpt: “…alternative splicing is used to alter protein phosphorylation, which can alter protein stability, subcellular localization, activity, and other properties [45].
My comment: Without alternative splicings, nutrient-dependent pheromone-controlled cell type differentiation could not be linked from RNA-directed DNA methylation to RNA-mediated amino acid substitutions that stabilize the DNA in the organized genomes of species from microbes to man.

diseases-disorders

Let there be anti-entropic light (1)

Summary: Light-induced amino acid substitutions link cell type differentiation in plants to nutrient-dependent pheromone-controlled reproduction in animals via the biophysically constrained chemistry of protein folding. Protein folding is perturbed by mutations that limit the ability of organisms to adapt to ecological variation. Viruses contribute to mutations. The sun’s biological energy appears to supply the anti-entropic force that links entropic elasticity to the development of successful morphological and behavioral phenotypes that are exemplified in extant versus extinct biodiversity. The importance of the anti-entropic force seems to have gone virtually unnoticed by theoretical physicists and evolutionary theorists who argue for “Big Bang” cosmology and mutation-driven evolution in the context of the evo-devo debate.

Arguments in the evo-devo debate: say it with flowers!

Abstract excerpt: “The widely accepted view was that morphological changes resulted from differences in number and/or type of transcription factors, or even from small changes in the amino acid sequence of similar proteins.
Excerpt: “Fig. 1. Schematic representation of a gene with its cis-regulatory elements (CREs) and the potential mutations that can affect transcriptional processes.

My comment: The “widely accepted view” of cell type differentiation confuses the effects of mutations, which perturb protein folding, and RNA-mediated amino acid substitutions that stabilize it. Serious scientists now realize the need for links from epigenesis to epistasis. Many are slow to realize that no link from ecological variation to ecological adaptation has been suggested in discussion about evolutionary theories. See for instance:
Epigenomics: Roadmap for regulation

Excerpt 1) “Future work should try to address the changing relationship between the epigenome and genome over the lifespan of the cell, in different phases of the cell cycle and across cellular generations. Other factors that modulate chromatin organization also remain to be investigated — the proteins responsible for chromatin remodelling, for example, and the chaperone proteins associated with histone variants that control assembly and disassembly of chromatin14.”
Excerpt 2) ” “A case in point is modification of the amino-acid residue lysine 27 (K27) on histone H3 in chromatin. Addition of an acetyl group (a modification known as H3K27ac) correlates with transcription of the corresponding region of DNA, whereas trimethylation (H3K27me3) is linked to transcriptional repression.”
My comment: The proteins responsible for chromatin remodelling are nutrient dependent and the chaperones help to buffer the nutrient stress, which is typically accompanied by social stress, during changes in ecology that lead to successful ecological adaptation of individuals and some species.
See also: Cas9 specifies functional viral targets during CRISPR–Cas adaptation. It was published (in advance) in the same issue of “Nature” that contains the articles about Epigenomics: Roadmap for regulation.
CRISPR–Cas adaptation was reported here Virus-cutting enzyme helps bacteria remember a threat.
Excerpt: “…memories are embedded in the bacterial equivalent of an adaptive immune system capable of discerning helpful from harmful viruses called a CRISPR (clustered regularly interspaced short palindromic repeats) system. It works by altering the bacterium’s genome, adding short viral sequences called spacers in between the repeating DNA sequences. These spacers form the memories of past invaders. They serve as guides for enzymes encoded by CRISPR-associated genes (Cas), which seek out and destroy those same viruses should they attempt to infect the bacterium again.”
My comment: There is no mention of the fact that the enzymes do not automagically appear with their ability to enable the destruction of harmful viruses. In the representation above, there is a missing link between the epigenetic landscape and the physical landscape of DNA in the organized genomes of species from microbes to man. That missing link is the sun’s biological energy, which is the source of all nutrition. Nutrient-uptake links the biological energy from the sun to metabolic networks and to genetic networks that might otherwise be perturbed by harmful viruses that cause mutations.
The importance of nutritional epigenetics must be considered in any attempt to explain evolutionary theory, or to accurately represent how ecological variation leads to ecological adaptations via the anti-entropic epigenetic effect of the sun’s biological energy on cell type differentiation. Too much sun exposure, for example, can lead to mutations and skin cancer. But why just skin cancer? And why does some sun exposure seem to lead to vitamin-D production that stabilizes the organized genome of human populations in areas where malaria is endemic. Those were among the questions I answered in an invited review of nutritional epigenetics. Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems. Others have since become interested in answering those questions.

‘DNA spellchecker’ means that our genes aren’t all equally likely to mutate

Excerpt: “… liver, colorectal and lymphocyte malignancies present more mutations in some parts of our chromosomes, while breast, ovarian and lung cancers accumulate more mutations in other places.”
My comments: That is the basis for the claims I made in the context of nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all species.
Amino acid substitutions stabilize DNA in organized genomes. Mutations perturb the biophysically constrained chemistry of protein folding that leads from entropic elasticity to anti-entropic epistasis and to the phenotypes exemplified in morphological and behavioral diversity of species from microbes to man.See for examples: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. It led to the invitation to submit the invited review on nutritional epigenetics.
See for criticisms of the model by someone who believes in beneficial mutations:Criticisms of the nutrient-dependent pheromone-controlled evolutionary model.
See also: Fruit flies remember a good meal, Blood growth factor activates neural stem cells
In my model of ecological adaptations, the obvious links from food odors to thermodynamic cycles of protein biosynthesis and degradation are typically controlled by nutrient uptake, which links ecological variation to ecological adaptation via species-specific pheromones. Adaptations across a continuum of increasing organismal complexity link epigenetically-effected brain development in insects to humans during their life history transitions. S. cerevisiae is the model organism linked to stem cell activation, and in my model it also sets the stage for explanations of the nutrient-dependent pheromone-controlled RNA-mediated events. See: Predicting phenotypic variation in yeast from individual genome sequences and  From Fertilization to Adult Sexual Behavior and Organizational and activational effects of hormones on insect behavior.
The aspects of organization and activation of behavior do not address the origins of life, which typically have been linked to mutations across billions of years. See for instance:
Initiation of translation in bacteria by a structured eukaryotic IRES RNA
Abstract excerpt: “…bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.
Reported as: Researchers find link in how cells start process necessary for life
Excerpt: “…the CU scientists and their colleagues “have shown for the first time that a bona fide signal in an RNA structure promotes protein synthesis in the two domains of life.”
My comment: What they’ve shown includes the anti-entropic epigenetic effect of light-induced amino acid substitutions in all domains and on all cell types of all individuals of all species of all kingdoms. Their report can be placed into the context of A universal trend of amino acid gain and loss in protein evolution.
Excerpt: “We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.”
My comment: That universal, intrinsic, anti-entropic trend is RNA-mediated by light-induced amino acid substitutions that stabilize DNA in the organized genomes of species from microbes to man. Indeed, the journal article suggests: “That a compact IRES RNA can use this primitive mechanism suggests that RNA structure-driven or structure-assisted initiation may be used in potentially all domains of life, driven by diverse RNAs…”
The obvious link across all domains of life is not mutations and evolution across billions of years. It is nutrient-dependent amino acid substitutions. RNA-mediated cell type differentiation incorporates what is currently known about physics, chemistry, and information. Without that transfer of information across all three domains and all kingdoms, ecological variation cannot be linked from atoms to ecosystems via epigenesis and epistasis.
See also: FISH Labeling Reveals a Horizontally Transferred Algal (Vaucheria litorea) Nuclear Gene on a Sea Slug (Elysia chlorotica) Chromosome, which was reported as: Sea slug has taken genes from algae it eats, allowing it to photosynthesize like a plant
Light-induced amino acid substitutions in plants, algae, and sea slugs link the stability of DNA in the context of biologically-based top-down causation and anti-entropic epigenetic effects linked to increasing organismal complexity via horizontal gene transfer and the physiology of reproduction, which enables the fixation of the amino acid substitutions.
The manifestations of anti-entropic light and the RNA-mediated fixed amino acid substitutions in the morphological and behavioral phenotypes and in the biodiversity of species from microbes to man may be somewhat unnerving to those who think they have discovered the biological basis for life in all domains. That may explain why these authors did not include any speculation about the across-kingdom link via the microRNA/messenger RNA balance. That across-kingdom link must be addressed, if serious scientists ever intend to make scientific progress based on experimental evidence of biologically-based cause and effect. See for example:

Combined agonist–antagonist genome-wide functional screening identifies broadly active antiviral microRNAs

Excerpt: “Since the discovery of the first microRNA (miRNA) in Caenorhabditis elegans, research in diverse organisms has illuminated the role of this class of small RNA in a wide range of cellular processes (reviewed in ref. 1). MicroRNAs modulate the expression of specific genes by guiding the RNA-induced silencing complex (RISC) to complementary sites within messenger RNAs (mRNAs) (2). This generally serves to down-regulate target genes at specific times, in concert with other regulatory mechanisms in the cell (reviewed in ref. 3).”
My comment: The miRNA/mRNA balance appears to be perturbed by viral miRNAs — unless it is well-maintained by nutrient uptake and RNA-directed DNA methylation. In my invited review of nutritional epigenetics, I wrote:
“Experimental evidence continues to add support for the role of ecological variation and nutrient-dependent epigenetically-effected ecological adaptations that occur via amino acid substitutions, which determine the cell types of individuals in all species. More substantial support for epigenetic effects on cell type differentiation comes from what has been learned during the past decade about the role of small non-coding RNA molecules. The small non-coding RNA molecules are called microRNAs (miRNAs). MiRNAs alter intercellular signaling by changing the balance between miRNAs and messenger RNA (mRNA) . The changes are linked to health and to pathology (Mori et al., 2014).”
In this video, cell density-dependent miRNAs are linked to cancer. Note, however, miRNA biogenesis does not appear to occur outside the biphysically constrained context of viruses and nutrient uptake. This suggests a balance between nutrient stress and viral microRNA damage must be achieved for healthy organism-level themoregulation to lead from entropic elasticity to epistasis.

See also: Phosphorylation-Mediated Regulation of Alternative Splicing in Cancer
Abstract: Alternative splicing (AS) is one of the key processes involved in the regulation of gene expression in eukaryotic cells. AS catalyzes the removal of intronic sequences and the joining of selected exons, thus ensuring the correct processing of the primary transcript into the mature mRNA. The combinatorial nature of AS allows a great expansion of the genome coding potential, as multiple splice-variants encoding for different proteins may arise from a single gene. Splicing is mediated by a large macromolecular complex, the spliceosome, whose activity needs a fine regulation exerted by cis-acting RNA sequence elements and trans-acting RNA binding proteins (RBP). The activity of both core spliceosomal components and accessory splicing factors is modulated by their reversible phosphorylation. The kinases and phosphatases involved in these posttranslational modifications significantly contribute to AS regulation and to its integration in the complex regulative network that controls gene expression in eukaryotic cells. Herein, we will review the major canonical and noncanonical splicing factor kinases and phosphatases, focusing on those whose activity has been implicated in the aberrant splicing events that characterize neoplastic transformation.
My comment: The complexity of epigenetically-effected alternative splicing of exons that leads from enzymes and reversible phosphorylation to gene expression has led biologically uninformed theorists to claim that cell type differentiation occurs in the context of  mutations. For example, in the abstract above, mutations are clearly linked to “…the aberrant splicing events that characterize neoplastic transformation.”
By placing everything known about cell type differentiation in all cells of all individuals of all species into the context of mutations and evolution, theorists have caused the stagnation of genetic and evolutionary research. Mutations cannot be linked via perturbed protein folding and physiopathology to the physiology of health and reproduction.
Attempts to explain how evolution via mutations occurs have led to the surprising claim that “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.” Mutation-Driven Evolution (p. 199)
The idea of constraint-breaking mutation fails to link ecological variation leads to ecological adaptations via RNA-mediated amino acid substitutions. The amino acid substitutions differentiate cell type in species from microbes to man, but evolutionary theorists claim that physiopathology and ecological adaptations somehow arise via the same unexplained mechanisms. Until recently, theorists claimed that natural selection was somehow involved but even that pseudoscientific nonsense has begun to fall out of favor.
See:  The Surprising Origins of Evolutionary Complexity
Excerpt: “Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed “the blind watchmaker.” To some extent, it just happens.”
My comment: Until now, theorists only needed to claim that beneficial mutations were the key to species-wide success. Serious scientists have been required to use experimental evidence of biologically-based cause and effect that links the biological energy from the sun to the physics, chemistry, and molecular biology of life.
Fortunately, in the context of yet another report that links the epigenetic effects of light from ecological variation to ecological adaptations across species, a new model organism has emerged. See: The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing
Conclusion: “Our results open the possibility that extensive recoding is common in many organisms, rivaling alternative splicing as a means of creating functional diversity.”
Reported as:Squid recode their genetic make-up on-the-fly to adjust to their surroundings
Excerpt: “Does the squid have some mechanism we can learn from?”
My comment: Some people have already learned that the conserved molecular mechanisms of alternative splicing link the extensive recoding that occurs in the squid and all other species during the development of their behaviors. The squid model organism tells us is more about how quickly this extensive recoding can occur. The squid model organism of ecological adaptation does not tell us about anything that suggests extensive recoding occurs outside the context of alternative splicing. It reaffirms that fact that “…alternative splicing may be the critical source of evolutionary changes differentiating primates and humans from other creatures such as worms and flies with a similar number of genes.” — Jon Lieff (2012)
For example, in my model of ecological adaptations I’ve placed alternative splicing into the context of feedback loops and chromatin loops that link RNA-mediated amino acid substitutions to cell type differentiation of all cell types in all individuals of all species. I reiterate. See, for instance: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.
In the squid model organism, deamination of adenosine to inosine (A-to-I) appears to link the epigenetic landscape to the physical landscape of DNA by chemically modifying the structure of mRNAs. The link from adenosine-to-inosine RNA editing to the diversity of neuronal proteomes probably integrates the changes in morphology and behavior that I attribute to changes in the miRNA/mRNA balance.
A-to-I RNA editing appears to be included in the process that alters genetic information that I detailed in my invited review of nutritional epigenetics. The unpublished review also links what is now known about viral miRNAs and nutrient-dependent miRNAs. The influence of both types of miRNAs extends across species from microbes to man via a finely-tuned atoms to ecosystems model of cell type differentiation. For example fixation of RNA-mediated amino acid substitutions occurs in the context of nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation that are epigenetically-effected by viral miRNAs.

Fixation of amino acid substitutions that differentiate cell types is perturbed by the accumulation of viral miRNAs. If, for example, viral microRNAs perturb the light-induced amino acid substitutions of luminescent bacteria in the bobtail squid, fixation of the squid’s nutrient-dependent pheromone-controlled amino acid substitutions would also be perturbed. Instead, ingestion of the luminescent bacteria is linked to more efficient foraging in the squid. The success of the squid ensures the survival of the bacteria and the survival of the squid species. See for example: A single natural nucleotide mutation alters bacterial pathogen host tropism
Excerpt 1) “For bacterial host adaptation, horizontal acquisition of a single gene regulator in the bacterial squid symbiont Vibrio fischeri was demonstrated to be an essential step in adaptation to its host28.”
Excerpt 2)  “In summary, our results reporting a single naturally occurring mutation associated with a bacterial host-switching event represent a paradigm shift in the understanding of the minimal adaptations required for a bacterium to overcome species barriers and establish itself in new host populations.”
It is not a “single naturally occurring mutation.” In my model, it’s an ecological adaptation that links bioluminescent microbes from their nutrient-dependent pheromone-controlled physiology of reproduction to bioluminescence in squid and their nutrient-dependent pheromone-controlled physiology of reproduction via the biophysically constrained chemistry of protein folding that links amino acid substitutions to biodiversity in species from microbes to human.
Nutrient-stress and social stress contribute to the accumulation of viral miRNAs that would typically be prevented by nutrient-dependent pheromone-controlled feeback loops that link food odors and social odors to the nutrient-dependent physiology of reproduction via controlled changes in the miRNA/mRNA balance. The changes are manifested in transgenerational epigenetic inheritance of some physiopathology that is not always manifested in the context of metabolic networks linked to genetic networks by offspring who understand more about molecular epigenetics than their parents.
If your offspring are taught to believe in the pseudoscientific nonsense about mutations and evolution, they probably will not understand anything more than what you do about biologically-based cause and effect.That places the responsibility for “Combating Evolution to Fight Disease” on others who were not taught to believe in ridiculous theories.
 

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Imagining that data historically supports evolutionary theory

1) Arguments in the evo-devo debate: say it with flowers!
Abstract excerpt: A key question in evolutionary developmental biology is how DNA sequence changes have directed the evolution of morphological diversity. The widely accepted view was that morphological changes resulted from differences in number and/or type of transcription factors, or even from small changes in the amino acid sequence of similar proteins.
My comment: This is the first time I have seen anyone claim that the “…small changes in the amino acid sequence of similar proteins…” is a widely accepted view of how the number and/or type of transcription factors lead to morphological changes. See for comparison: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.
In my model, RNA-mediated amino acid substitutions link atoms to ecosystems. Their claim is linked to an “…increasing amount of data, especially from the plant field…” They claim that data “…implies that changes in cis-regulatory sequences in fact played a major role in evolution.” I claim that the same data links the epigenetic landscape to the physical landscape of DNA in the organized genomes of all genera via conserved molecular mechanisms of cell type differentiation. In my model, the honeybee model organism links species from microbes to man via the conserved molecular mechanisms that link light-induced amino acid substitutions to cell type differentiation in plants and other animals. I intend to learn more about their claim. Perhaps it is based on confusion caused by definitions that appear to make mutations, which perturb protein folding, and amino acid substitutions, which stabilize protein folding, the same thing.
2) Evolution of transcription factor function as a mechanism for changing metazoan developmental gene regulatory networks
Abstract excerpt: Most studies of GRN evolution focus on changes to cis-regulatory DNA, and it was historically theorized that changes to the transcription factors that bind to these cis-regulatory modules (CRMs) contribute to this process only rarely. A growing body of evidence suggests that changes to the coding regions of transcription factors play a much larger role in the evolution of developmental gene regulatory networks than originally imagined.
My comment: Their claim is that documentation of mutation-driven evolution was based on the imaginations of evolutionary theorists.
3) Modular Evolution of DNA-Binding Preference of a Tbrain Transcription Factor Provides a Mechanism for Modifying Gene Regulatory Networks
Abstract except: Gene regulatory networks (GRNs) describe the progression of transcriptional states that take a single-celled zygote to a multicellular organism. It is well documented that GRNs can evolve extensively through mutations to cis-regulatory modules (CRMs).
My comment: Their claim is that mutation-driven evolution of gene regulatory networks has been well documented.
Three questions arise:
1) What data suggests that mutations played a major role in the evolution of plants?
2) What data links mutations in plants to mutations in cis-regulatory modules and gene regulatory networks during the development of a single-celled zygote to a multicellular organism?
3) Does experimental evidence that links light-induced amino acid substitutions in plants and animals to cis-regulatory modules and gene regulatory networks during the development of gene regulatory networks link the nutrient-dependent pheromone-controlled development of morphological and behavioral phenotypes in the honeybee model organism, link entropic plasticity to examples of anti-entropic epigenesis and epistasis via RNA-mediated amino acids substitutions in the DNA or organized genome of species from microbes to man?
The only thing that can be said with flowers about the evo-devo debate is that the honeybee model organism ends the debate. Morphological and behavioral development in animals is nutrient-dependent and pheromone-controlled. The morphological and behavioral phenotypes of birds are linked to the biodiversity of plants via the nutrient-dependent pheromone-controlled behavior of bees.
See also: Epigenomics and the concept of degeneracy in biological systems
Excerpt: Selection began to operate not simply on genes for ascorbic acid synthesis but also across a distributed network of sensory biases, behavioural inclinations and digestive-metabolic mechanisms that increased the probability of obtaining ascorbic acid from the environment. In this way, within certain degrees of freedom, if there is degeneracy between environmental and genomic factors, then selection can result in an offloading of function from the genome to the environment, or a potential divergence of the environmental and genomic elements leading to the random exploration of adjacent function space.
My comment: Exploration that increases the probability of finding specific nutrients is based on the ability of food odors to cause the de novo creation of olfactory receptor genes via amino acid substitutions in the DNA of organized genomes of iinsects and other organisms. The physiology of nutrient-dependent reproduction is controlled by the metabolism of nutrients to species-specific pheromones that enable fixation of the amino acid substitutions that leads to nutrient-dependent biodiversity in all genera.
The link from entropic plasticity to anti-entropic epigenesis and epistasis can also be viewed from a creationist perspective in: Honey Bee Orphan Genes Sting Evolution.
“…orphan genes unique to social honey bees (Apis mellifera) play an important role in all the different glands and organs mentioned above where gene expression was specifically measured and quantified in each structure. Even the brain and midgut were found to contain significant levels of orphan-gene expression—which makes sense in light of the honey bees’ unique social behavior and diet. And not only are orphan genes uniquely expressed in specific organs, they were also found to play a major role in gene expression differences between forager and nurse workers. While bees initially grow and develop using the same genome, epigenetic changes (chemical tags in the chromosomes) allow them to diversify into two different specialized social roles in the colony.5″
See also: Large-Scale Coding Sequence Change Underlies the Evolution of Postdevelopmental Novelty in Honey Bees
My comment: I learned that this article had been published when I read Honey Bee Orphan Genes Sting Evolution. A subscription is required, which means you may need to take my word for this fact: There is no mention of “mutation” or “amino acids” in the text of the article. As is typical of current published works, their claims about natural selection and evolution are made in the absence of any experimental evidence that might otherwise link the claims to what is known about physics, chemistry, and the nutrient-dependent pheromone-controlled molecular biology of cell type differentiation. Perhaps that’s why their claims were cited in Honey Bee Orphan Genes Sting Evolution. There is no need to bring up the absence of experimental evidence of mutation-driven evolution. Creationists are typically aware of the lack of experimental evidence that might otherwise support theories about mutation-driven evolution.
Summary: The data that links light-induced amino acid substitutions in plants and animals to nutrient-dependent RNA-mediated amino acid substitutions and pheromone-controlled behavior in animals integrates what is currently known about physics, chemistry, and the conserved molecular mechanisms that enable biophysically constrained biodiversity. Alternatively, a recent textbook conclusion attributed biodiversity to Mutation-Driven Evolution.  “In other words, genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements.” (p. 199)
Whether or not you are a creationist, it should be obvious that ideas about constraint-breaking mutations must be considered outside the context of quantum physics, the chemistry of protein folding, and the conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA in the organized genome of species from microbes to man. Mutations are directly linked from perturbed protein folding to physiopathology, not to increasing organismal complexity. Amino acid substitutions are directly linked to increasing organismal complexity, not to physiopathology. Dobzhansky (1973) stated clearly that “…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.” See Combating Evolution to Fight Disease for an extension of Dobzhansky’s views to what is currently known about biologically-based cause and effect.
Biologists have now approached what theoretical physicists can only approach with mathematics. Quantum physics, for example, cannot address the reality of biologically  3D interactions. See: Inching toward the 3D genome 
Excerpt: “…the nucleome structure changes as cells age, differentiate, and divide, and researchers want to understand how and why.”
My comment: The extension of what is currently known about the organization of the 3D genome to nucleome structure changes during life history transitions, is also addressed by placing what is now referred to in the context of 4 dimensions (4D). Life history transitions have been linked from the biology of life to physics and chemistry and communication. See for instance: Life is physics and chemistry and communication.
If the sun’s biological energy is the link from entropic plasticity to anti-entropic epigenesis and epistasis, questions about top-down causation can be answered: Top-down causation: an integrating theme within and across the sciences?
Moreover, the questions can be answered in the context of what already is known about biologically-based cause and effect. See: Understanding and accounting for relational context is critical for social neuroscience.
Again, the honeybee model organism is a model — this time of the relational context that epigenetically links nutrient-dependent pheromone-controlled life history transitions from microbes to humans. See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
Excerpt: Nutrient-dependent pheromone-controlled reproduction underlies what is common (Locasale, 2012) to all models of natural selection, sexual selection, and species diversity (Frady, Palmer, & Kristan, 2012). Animal models are often used to model human physical and mental disorders. The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012).
My comment: The honeybee model organism links light-induced amino acid substitutions in plants and animals to odor-induced amino acid substitutions to the receptor-mediated entry of nutrients into cells that metabolize the nutrients to species-specific pheromones that control the physiology of reproduction. The pheromone-controlled physiology of reproduction links fixation of the amino acid substitutions to human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli.
See for example:Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors
Conclusion: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).
See for comparison to links from the sun’s biological energy to entropic plasticity, to anti-entropic epigenesis, and to epistasis. Simply put, there is no historical support for evolutionary theory in the context of quantum physics. That suggests evolutionary theory (neo-Darwinism) is based on pseudoscience. Darwin’s theory was based on ‘conditions of life.’

Life does not exist on this planet without the biological energy from the sun.

 

 

Quantum Physics Abuse: Probabilities, uncertainties and observers (Dissecting Pseudoscience)

Quantum Physics Abuse: “Science Proves God!” (DP: Pwnage Edition)

 

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Atheism: Arrogant, useless, and divisive ignorance

Scientific Seeker Stuart Kauffman on Free Will, God, ESP and Other Mysteries

February 4, 2015
Excerpt:

Horgan: What do you make of the antipathy toward religion expressed by Richard Dawkins and other “New Atheists?”
Kauffman: … moral behavior requires no belief in God. Morality probably evolved in Paleolithic to some extent. But to dismiss those who do believe in God, in any sense, is arrogant and useless and divisive.

Excerpt:

We need accelerating expansion of universe for free energy and “tuned constants” but those are necessary, not sufficient. The anti-entropic process may be, with others, sufficient. I am writing a new book about this.

My comment: The anti-entropic process is biophysically constrained. Biological energy from the sun fine-tunes the constants of all anti-entropic processes. Photosynthesis links the speed of light from contact with water to differences in spectral energy and receptor-mediated RNA-directed DNA methylation and the chemistry of RNA-mediated amino acid substitutions linked to protein folding.
For example, light-induced amino acid substitutions differentiate the cell types of plants, algae, and mollusks. Viral microRNAs cause changes in the microRNA/messenger RNA balance. The changes link thermodynamic cycles of protein biosynthesis and degradation to quantitative trait loci (QTLs). The QTLs link changes in the microRNA/messenger RNA balance to anti-entropic amino acid substitutions. This links RNA-mediated protein folding to fixation of the amino acid substitutions that differentiate the cell types of all cells in all individuals of species from microbes to man via differences in their species-specific nutrient-dependent pheromone-controlled physiology of reproduction.
The physiology of nutrient-dependent reproduction links ecological variation to ecological adaptation manifested in the morphological and behavioral phenotypes of all genera. Nutient-dependent QTLs benefit the stability of DNA via alternative splicings and amino acid substitutions. If the QTLs provide increased stability over time, the fixation of amino acid substitutions that leads to biodiversity occurs in the context of species-specific nutrient-dependent reproduction, which is controlled by pheromones in all animals. The direct link from QTLs to cell type differentiation via amino acid substitutions appears to have led researchers to make claim s about “…a yet-unidentified cellular mechanism that regulates gene expression.” Their claim helps to make difference between mutations and amino acid substitutions clear. Simply put, accumulated mutations do not differentiate cell types. Amino acid substitutions differentiate cell types.
For example see: A universal trend of amino acid gain and loss in protein evolution.
Excerpt:

“We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.”

The trend that links nutrient-dependent amino acid substitutions in proteins to cell type differentiation in individuals of different species before there was a last universal common ancestor links the sun’s biological energy to light-induced RNA-mediated amino acid substitutions in plants and animals, like algae and sea slugs. See: FISH Labeling Reveals a Horizontally Transferred Algal (Vaucheria litorea) Nuclear Gene on a Sea Slug (Elysia chlorotica) Chromosome.
In 1996, it became clear that cell type differentiation in animals was RNA-mediated and controlled by pheromones. Our model was extended to insects and to the life history transitions of the honeybee, which made the role of nutrient uptake and pheromone-controlled fixation of all cell type differentiation perfectly clear. See also: Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees. Facts about the RNA-mediated de novo creation of olfactory receptor genes now link them from nutrient uptake to fixation of amino acid substitutions that differentiate cell types in all individuals of all species. There is only one model for that. Nutrient-dependent/pheromone-controlled adaptive evolution: a model. That model links the sun’s biological energy to the anti-entropic process of cell type differentiation manifested in the increasing organismal complexity of species from microbes to man.
Science seekers can now ask theorists for experimental evidence to support Kauffman’s claims. Where did the anti-entropic process come from? One approach to finding its origins was suggested by Lewis Thomas (1980):

“I should think we might fairly gauge the future of biological science, centuries ahead by estimating the time it will take to reach a complete comprehensive understanding of odor. It may not seem a profound enough problem to dominate all the life sciences, but it contains, piece by piece, all the mysteries (p. 732).”

Others seem to not recognize which mysteries about the origin of the anti-entropic process have been solved. Food odors are linked via the natural selection of nutritious foods to the odor-induced de novo creation of olfactory receptor genes. The RNA-mediated creation of these receptors links nutrient uptake to cell type differentiation in all cells of all individuals of all animal species via the metabolism of nutrients to species-specific pheromones.
That claim can be placed into the context of neo-Darwinian theory. See for example: Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage.
Reported as:The findings combine to implicate the brain, rather than the nose, as being responsible for the afterimages.” See also: Sense of Smell: The Nose and Brain Make Quite a Team, in Disconnection
My comment: Everything published by serious scientists during the past decade attests to the fact that Darwin’s nutrient-dependent ‘conditions of life’ must come first.
For example,  Conclusion:In summary, the neuroscientists were able to show that the representation of an odor changes after the first breath, and that an olfactory retentivity persists at the central level, a phenomenon comparable to what occurs in other sensory systems, such as vision and hearing. These movements undoubtedly enable the identification of new odors in complex environments or participate in the process of odor memorization.
Also, “The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012). — cited in Kohl, 2013.
All experimental evidence of biologically-based cause and effect links biological energy from the sun to nutrient-dependent pheromone-controlled anti-entropic processes and cell type differentiation during life history transitions in honeybees and to cell type differentiation during life history transitions in species from microbes to humans.
The Ancient Flower That Heals The Human Soul
Excerpt: “So ancient a love affair exists between humans and saffron, that it can no longer reproduce without our help. Could its antidepressant and health-promoting properties be an example of saffron ‘returning the favor’?”
My comment: It is impossible for me to ignore the link from the anti-entropic process in honeybees to humans. Minimally, others should begin to think about it, since the most obvious link has been predicted across 35 years of published works. I reiterate, in 1980 Lewis Thomas wrote:

“I should think we might fairly gauge the future of biological science, centuries ahead by estimating the time it will take to reach a complete comprehensive understanding of odor. It may not seem a profound enough problem to dominate all the life sciences, but it contains, piece by piece, all the mysteries (p. 732).” — cited in Kohl and Francoeur (1995 / 2002).

See also:

“The act of smelling is remarkably like the act of thinking itself (p. 732).”

Stuart Kauffman has consistently make tractable scientific progress that led to his claims about the anti-entropic process. His claims can be compared to those made by Theodosius Dobzhansky.  Dobzhansky tried to get others to consider the fact that “…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.” — Nothing in Biology Makes Any Sense Except in the Light of Evolution (1973).
At the time of Dobzahsky’s death in 1975, no one seems to have noticed that amino acid substitutions are anti-entropic. If Dobzhansky was not still dead, I think he might clarify the reasons he claimed to be both a creationist and an evolutionist. Recently, however, others have begun to look at Dobzhansky’s claims in the light of what is known about the conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA in species from microbes to man. See for instance: Combating Evolution to Fight Disease
Conclusion: “…but perhaps, too, “nothing in evolution makes sense except in the light of biology.” Although the latter might be an exaggeration, an important gap is being filled by molecular understanding of the genesis of variation that confers the ability to evolve.”
See also: ‘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].”
My comment: As it turns out, nothing in molecular biology makes sense except in the light of what is known about how the sun’s biological energy is linked to the anti-entropic process that links cell type differentiation across all species via their nutrient-dependent pheromone-controlled physiology of reproduction. The sun’s biological energy is linked to cell type differentiation by “…the interactions between pre-mRNA and proteins fine-tune alternative splicing in a manner that can gradually create new protein functionalities.”
In our 1996 Hormones and Behavior review, we (TB) wrote: “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…”
Our focus was on the link from alternative splicing techniques of pre-mRNA to sex differences in cell types, but most serious scientists could be expected to understand that the link from sex differences in cell types would extend to all cell type differentiation in species that sexually reproduce. That understanding should lead other serious scientists to examine the conserved molecular mechanisms of cell type differentiation that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of all species, or stop making claims that mutations can somehow be linked the evolution of biodiversity.
See also:
Psychological and neuroendocrinological effects of odor of saffron (Crocus sativus)
Experimental Studies on a Single Microtubule (Google Workshop on Quantum Biology)

A Spectroscopic Mechanism for Primary Olfactory Reception

We can take the systems complexity of physics, chemistry, and molecular biology down a few levels by starting with top-down causation. I start by removing de Vries definition of “mutation.” The definition of mutation made the energy jumps appear to be what Schoedinger referred to in the context of quantum biology. Luca Turin’s works continue to link top-down causation to quantum biology via olfaction. See my review of this book about Luca Turin:The Emperor of Scent: A Story of Perfume, Obsession and the Last Mystery of the Senses by Chandler Burr New York: Random House (2003). I had hoped more progress would have been made during the past decade. His 1996 published work linked our review to hormone-organized and hormone-activated behaviors via my model of nutrient-dependent pheromone-controlled pulses of gonadotropin releasing hormone.

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Nutritional epigenetics, exercise, and immune system integrity

Anti-inflammatory mechanism of dieting and fasting revealed

Summary: Researchers have found that a compound produced by the body when dieting or fasting can block a part of the immune system involved in several inflammatory disorders such as type 2 diabetes, atherosclerosis, and Alzheimer’s disease.

My comment: For the obvious link from nutrition and exercise to reproduction and RNA-mediated transgenerational epigenetic effects on the morphological and behavioral phenotypes of all species that must “move” to find food or to find mates see: Chapter 5: “Epigenetic Modulation of Gene Expression by Exercise in “Nutrition, Exercise and Epigenetics: Ageing Interventions” Use the search inside feature to see what will be published in April, 2015

Excerpt: Among the highlights are chapter-length discussion of such topics as: how anti-inflammatory action of calorie restriction underlies the retardation of ageing and age-related diseases (Chapter 3); epigenetic modification of gene expression by exercise (Chapter 5); the role of functional foods and their bioactive components…

See also: Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

Excerpt: “…the unifying trigger that orchestrates the genomic response to exercise is incompletely defined.”

Conclusion: Our finding that the patterns of DNA methylation change in differentiated nondividing somatic cells provides further evidence that the epigenetic marks across the genome are subject to more dynamic variations than previously appreciated.

My comment: In my model, RNA-directed DNA methylation and RNA-mediated amino acid substitutions link the anti-entropic effects of nutrient-dependent survival of individuals to the survival of species. Species adapt to ecological variation in the availability of food. Entropic plasticity is linked from the availability of food to the nutrient-dependent physiology of reproduction via the metabolism of nutrients to species-specific pheromones.

The link from viral microRNAs to entropy and from nutrient-dependent microRNAs to their anti-entropic effects on cell type differentiation in the context of the required entropic elasticity has been fully detailed. All examples from all model organisms attest to the fact that species arise in the context of nutrient-dependent pheromone-controlled reproduction. Other attempts to explain extant biodiversity fail to include what is currently known about physics, chemistry, and conserved molecular mechanisms that link epigenetic effects of the sun’s biological energy to cell type differentiation in plants and to the animals that eat the plants or that eat other animals to ensure their nutrient-dependent pheromone-controlled survival.

See also: An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training

Abstract excerpt: “A transcriptional network analysis revealed modules harboring distinct ontologies and, interestingly, the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus.”

My comment: RNA-directed DNA methylation is consistently linked to health-enhancing phenotypic adaptations via RNA-mediated amino acid substitutions. The epigenetically effected microRNA/messenger RNA balance is the determinant of alternative splicings that link the RNA-mediated substitutions to the stability of DNA. When viral microRNAs accumulate due to nutrient stress and/or social stress, they may lead to mutations that perturb protein folding and lead to the instability of DNA if the DNA is not repaired. This links the accumulation of viral microRNAs across the life history of humans to age-linked physiopathology.

For example, see: A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers  reported as: Molecular inhibitor breaks cycle that leads to Alzheimer’s

Excerpt: Alzheimer’s disease is one of a number of conditions caused by naturally occurring protein molecules folding into the wrong shape and then sticking together – or nucleating – with other proteins to create thin filamentous structures called amyloid fibrils. Proteins perform important functions in the body by folding into a particular shape, but sometimes they can misfold, potentially kick-starting this deadly process.

My comment: Thermodynamic cycles of protein biosynthesis and degradation are nutrient-dependent. Nutrient-stress and social stress are linked to perturbed protein folding via RNA-mediated events. The molecular inhibitor that breaks the cycle that leads to Alzheimer’s probably inhibits misfolding via the prevention of “heat shock.” That’s what some molecular chaperones do.

See: Emergency Alert in the Cell

Excerpt: “During the heat shock response, different stress proteins are synthesized. Their task is to prevent permanent damage to the organism.”

My comment: All of the above attests to what is currently known about how cell type differentiation occurs during life history transitions, and what leads to perturbed protein folding and physiopathology. Everything currently known about Epigenetic Modulation of Gene Expression by Exercise in “Nutrition, Exercise and Epigenetics: Ageing Interventions can be placed into the context of evolutionary theory by simply ignoring it.

If you ignore what’s currently known about physics, chemistry, and the conserved molecular mechanisms of nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all species during their life history transitions, you will not be on the side of those who are Combating Evolution to Fight Disease.

Excerpt: “Another mechanism involves chaperones such as heat shock protein 90 (Hsp90), proteins that massage subideal (mutant) proteins into functional conformations but abandon their regular client proteins during heat and other stresses that destabilize proteins. This causes a stress-inducible release of phenotypic diversity, which may drive evolution (with phenotypes ultimately stabilized by subsequent genetic changes). Both of these molecular mechanisms of protein-based inheritance are major departures from the modern synthesis views of solely mutation-directed variation, solely genetic inheritance, and independence of the generation of variation from environmental conditions.”

My comment: If you are not on the same side as those who are Combating Evolution to Fight Disease, you may wish to join those who believe in the pseudoscientific nonsense about Mutation-Driven Evolution.

Alternatively, you can wait until the combat ends and join the winners simply by claiming that you knew all along that ecological adaptation was nutrient-dependent and pheromone-controlled and that the theorists were simply biologically uninformed science idiots who caused the suffering and death of millions.

See also: Evolution evolves: physiology returns to centre stage (with my emphasis)

Conclusions: “The wide-ranging set of articles published in this issue reveal a major challenge both for the physiological sciences and for evolutionary biology. As the integration between the two proceeds, neither can remain unchanged. Evolutionary theory requires extension or even replacement, while physiological science needs to address the exciting possibilities opened up for the future. We hope that our article, and those published here, will enable both disciplines to respond effectively to that challenge.”