Criticisms of a validated model

By: James V. Kohl | Published on: October 4, 2017

Microglia Turnover in the Human Brain

“With electron microscopy, we find a variety of immune cells in the brain, especially in contexts of disease,” she writes.

Richard Feynman predicted this in the context of a lecture on nanotechnology.
He presciently placed cryo-EM into the context of a lecture about Plenty of Room at the Bottom.
Examination at this level of observable energy-dependent top-down causation has since linked the sun’s anti-entropic virucidal energy from hydrogen-atom transfer in DNA base pairs in solution to amino acid substitutions in organized genomes, which protects the organized genomes from virus-driven entropy.
See for review: RNA-mediated molecular epigenetics and virus-driven entropy

Energy-dependent molecular epigenetics support Einstein’s complete molecular mechanical theory via established links from microRNA flanking sequences to DNA base pair substitutions and amino acid substitutions in adhesion proteins. The adhesion proteins include heat shock proteins that link the epigenetic landscape to biophysically constrained nutrient-dependent RNA-mediated protein folding chemistry and cell type differentiation via the structure and function of supercoiled DNA. Einstein’s theory fits into the context of Darwin’s “conditions of life” via the de novo creation of nucleic acids; the nutrient-dependent function of the ribosome; and the de novo creation of olfactory receptor genes. De novo gene creation is the “holy grail” of biophysically constrained chemistry and biologically-based cause and effect. The discoveries reviewed here link the nutrient-dependent microRNA/messenger RNA balance from metabolic networks to genetic networks and to healthy longevity or virus-driven pathology in the context of what is known about all model organisms.

See also: Identification of the Beer Component Hordenine as Food-Derived Dopamine D2 Receptor Agonist by Virtual Screening a 3D Compound Database

Although the G protein-biased D2R-agonist hordenine shares structural similarities to the balanced agonist dopamine, receptor–ligand interactions obtained after docking and energy minimisation in presence of a D2R homology model appear to be different. Hordenine lacks a meta-hydroxyl group compared to dopamine, rendering it unable to form hydrogen bonds to both residues Ser1935.42 and Ser1975.46 as dopamine does42 (Fig. 6).

Reported as: The food ingredient hordenine in beer activates the reward centre in the brain

Just like dopamine, hordenine stimulates the dopamine D2 receptor, however it uses a different signalling pathway. In contrast with dopamine, hordenine activates the receptor solely through G proteins, potentially leading to a more prolonged effect on the reward centre of the brain.

The energy-dependent de novo creation of creation of G protein-coupled receptors links hydrogen-atom transfer in DNA base pairs in solutions like beer and seawater to the epigenetic effects of food odor and pheromones and to differences in the morphological and behavioral diversity of species from microbes to humans. Hydrogen-atom transfer in DNA base pairs in solution links changes in the microRNA/messsenger RNA balance from alternative splicings of pre-mRNAs/microRNAs to amino acid substitutions and energy-dependent RNA-mediated DNA repair.
See for examples: Nutrient-dependent/pheromone-controlled adaptive evolution: a model (2013)
See also: Similar articles: (1-96)
For example: Processing by the main olfactory system of chemosignals that facilitate mammalian reproduction was published on June 12, 2015.
See also: Absence of Female-Typical Pheromone-Induced Hypothalamic Neural Responses and Kisspeptin Neuronal Activity in α-Fetoprotein Knockout Female Mice  April 10, 2015.
At least one of the co-authors of each of the two works linked above (M. Baum and J. Bakker), attended the same conference in Minot, ND, where I presented my model. The conference was held in 1995, soon after book publication with co-author, the late Robert T. Francoeur. See this review of the 2002 edition of: The Scent of Eros: Mysteries of Odor in Human Sexuality
In 1994, Eugene Daev published [Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)] in Russian.
In 2014 his group published Chemosignals from isolated females have antimutagenic effect in dividing the cells of bone marrow from male mice of the CBA strain
It had already become clear to most serious scientists that food energy-dependent metabolism, linked chemosignals (aka pheromones) to protection from the virus-driven degradation of messenger RNA, which links mutations to all pathology.

Humans also have various pheromone-induced physiological effects, especially those associated with reproduction [46, 47]. This suggests that the human olfactory system is still an effective pathway for influencing environmental factors on the human nervous system. Various psychoemotional states of the human nervous system can, in turn, disrupt the integrity of the chromosomal apparatus of target cells, for instance lymphocytes [41, 42]. Therefore, studies on the oppositely directional modulation of the mutagenic consequences of stress in rodents with the use of specific, volatile, and zoosocial important chemosignals are a promising approach both to modeling posttraumatic stress disorders in humans [36] and to searching for mehods of their treatment.

[46] is Kohl, J.V., Atzmueller, M., Fink, B., and Grammer, K., Human pheromones: integrating neuroendocrinology and ethology, Neuroendocrinol. Lett., 2001, vol. 22, pp. 309–321.
Others have included facts from my model and award-winning reviews without citing my works in their less detailed representations. But, so far as I know, only one person has criticized the model in a published work. See: Criticisms of the nutrient-dependent pheromone-controlled evolutionary model.
Thanks to Andrew Jones, others learned that my model is a refutation of neo-Darwinian pseudoscientific nonsense. For comparison, Andrew Jones wrote a thesis on abiogenesis. See: Jones, A  Lipid Encapsulation of Self-replicating Ribozymes

Despite their challenges, ribozymes have made an interesting niche for themselves in the field of abiogenesis. The evolution of a successful RNA polymerase ribozyme is a lofty goal. While its discovery would not be the be-all and end-all of abiogenesis research, it would represent an important stepping stone between prebiotic chemistry and life. The encapsulation of such a ribozyme is also an important step, as it would enable a system of heredity and evolution through natural selection. Based on progress in current research, it is only a matter of time before that ribozyme is discovered.

The ridiculous claim about the discovery of an evolved RNA polymerase ribozyme can now be examined in the context of even more ridiculous claims about the emergence and evolution of RNA-Dependent RNA Polymerase.
Origin and Evolution of RNA-Dependent RNA Polymerase

Based in the present results, we suggest a hypothetical scenario where initially a ribozyme with polymerase activity could have enhanced its activity by the binding of a simple cofactor, as magnesium (Shechner et al., 2009; Horning and Joyce, 2017), thus, exerting the functions of replication of some information stored on RNA molecules (Kim and Higgs, 2016; Tagami et al., 2017). With the emergence of the primitive translation system, the first proteins were formed by translation of the junction of proto-tRNAs, and RdRp was among the first enzymes that were formed (Farias et al., 2016b). Accompanied by the compartmentalization process, the control of solutes in the internal environment and the polymerization function by proteins could occur more efficiently than with ribozymes. Initially, the enzyme was formed only by the catalytic loop with capacity of binding to the cofactor and simple molecules as ribonucleotides, that later with duplications and diversifications of the initial catalytic domain, the other parts of the protein emerged. With the establishment of the first domain of RdRp, variants could be generated and mutations could occur, thus, it was possible to generate new proteins, with the conservation of the catalytic site (Zong et al., 2009). With the emergence of a variant with properties of reverse transcriptase, and subsequently a DNA polymerase, a fundamental step occurred to originate the first genomes based in DNA, being the bridge to move from a RNA/Protein World to a DNA/RNA/Protein World (Gilbert, 1986; Müller, 2006). When DNA molecules emerged, by variation, other classes of polymerases appeared. With the complexification of the biological system, functions such as replication, repair, and recombination emerged, very high error rates were selected against, and the new variants arose to work in specific processes.

For an even more ridiculous claim that was linked to emergence and evolution via abiogenesis, see the comments of my antagonist Jay R. Feierman, from 7/25/13

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.

So far as I know, Jay R. Feierman and Andrew Jones have never linked abiogenesis or anything else to the biophysically constrained RNA-mediated pheromone-controlled physiology of reproduction in all living genera. Until Feierman explains why he thinks my understanding of Darwinian biological evolution is not correct, I cannot address any aspect of his overwhelming ignorance.
See also the comments by Andrew Jones who posted as “anonymous_9001” For example: Re: Mechanism explains complex brain wiring

JK: Thanks. If you know how genes are created, tell us all. There is no reason to continue to tell anyone that I don’t know how new genes are created because I obviously do . . .

anon: No. You obviously do not. There are no two ways about it. You make the claim that splicing creates genes. It does not. Splicing has nothing to do with DNA. It makes different varieties of mRNA to be translated. It does not affect the genome in any way, shape, or form. This isn’t a debate. Your claim is a flat out falsehood.

Feierman and Jones did not know enough about alternative splicings of pre-mRNA to link them from food energy to the physiology of pheromone-controlled reproduction despite the claims in our section on molecular epigenetics from this 1996 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.

See for comparison: Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma

….similar to protein coding genes, mutations in noncoding regulatory regions may target genes in specific pathways rather than individually.

Food energy-dependent RNA-directed DNA methylation is the obvious link from non-coding regulatory regions and the alternative splicings that link energy-dependent changes in microRNAs (aka pre-mRNAs) to specific pathways. Fixation of amino acid substitutions in differentiated cell types can be compared with fixation of amino acids in viruses, which link mutations to all pathology.

Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

Flu Drift Limited

Five antigenic sites in the virus surface hemagglutinin protein, which together comprise 131 amino acid positions, are thought to determine the full scope of antigenic drift of influenza A virus. Koel et al. (p. 976) show that major antigenic change can be caused by single amino acid substitutions. These single substitutions substantially skew the way the immune system “sees” the virus. All substitutions of importance are located next to the receptor-binding site in the hemagglutinin. Because there are few positions of importance for antigenic drift, there are strict biophysical limitations to the substitutions at these positions, which restricts the number of new antigenic drift variants at any point in time. Thus, the evolution of influenza virus may be more predictable than previously thought.

See also: Viral Genome Junk Is Bunk  

So, where do viruses come from that essentially share the same sequences as those found in their host genomes? Perhaps the evolutionists have placed the cart before the horse on this issue, as proposed by several creationist scientists.4,6 In fact, in an ironic twist, the evidence mentioned above indicates that viruses likely arose from their hosts and not the other way around. As molecular biologist and biochemist Peter Borger notes, “The most parsimonious answer is: the RNA viruses got their genes from their hosts.”6

No experimental evidence of biophysically constrained biologically- based cause and effect suggests that any virus evolves. All experimental evidence shows that viruses steal the quantized energy that stabilizes their organized genomes via predictable amino acid substitutions.
That fact led to this brief presentation at a virtual conference on Precision Medicine: Energy as information and constrained endogenous RNA interference

See for comparison: 60 years ago, Francis Crick changed the logic of biology

Two years ago, the Zechiedrich lab replaced Crick’s illogical misrepresentation of energy-dependent biophysically constrained top-down causation with experimental evidence that linked the pheromone-controlled physiology of reproduction to all RNA-mediated biodiversity in all living genera.

Learn why all serious scientists are laughing at the pseudoscientific nonsense you were taught to believe was based on the logic of biology.

Again, see for comparison: Origin and Evolution of RNA-Dependent RNA Polymerase

Jay R. Feierman wrote:

I find this article interesting because of the “object of study.” We are used to thinking about evolution at hierarchical levels above that of protein enzymes. Yet, protein enzymes are “structural design features” and follow the same principles of evolution by natural selection as structural design features at higher hierarchical levels, such as certain kinds of behaviors and even species. Compared to other kinds of evolution, protein enzyme evolution is very conservative in that it does not change much through phylogeny. We essentially have the same enzymes for metabolizing glucose as do bacteria and other single cell animals.

No serious scientist I know has ever thought about evolution at any level above the energy-dependent creation of enzymes. Natural selection for energy-dependent codon optimality links the creation of the enzymes from the metabolism of food to the pheromone-controlled physiology of reproduction in species from microbes to humans. That is why we have “…the same enzymes for metabolizing glucose as do bacteria and other single cell animals.”

The de novo creation of all enzymes is energy-dependent and RNA-mediated in the context of food energy that links the physiology of pheromone-controlled reproduction to all biodiversity via the claims we make in the molecular epigenetics section of our 1996 Hormones and Behavior review.

The virus-driven theft of quantized energy links changes in base pairs to changes in amino acid substitutions in enzymes that cause the degradation of messenger RNA in all organized genomes. Without food energy-dependent RNA-mediated DNA repair, the degradation of messenger RNA links mutations to all pathology. See for examples of how cancer might be effectively prevented or treated in the context alternative splicings of pre-mRNA and a single enzyme.

Human Papillomavirus 16 Oncoprotein Expression Is Controlled by the Cellular Splicing Factor SRSF2 (SC35)

HPV oncogenesis is driven by two viral oncoproteins, E6 and E7, which are expressed through alternative splicing of a polycistronic RNA to yield four major splice isoforms (E6 full length, E6*I, E6*II, E6*X). The production of multiple mRNA isoforms from a single gene is controlled by serine/arginine-rich splicing factors (SRSFs), and HPV16 infection induces overexpression of a subset of these, SRSFs 1, 2, and 3.

Definition of isoform: any of two or more functionally similar proteins that have a similar but not an identical amino acid sequence

The overexpression of the subset of these mRNA isoforms is clearly linked from energy-dependent alternative RNA splicings to biophysically constrained viral latency in most humans. A single enzyme is the obvious link to cancer.
See: Unique mechanism links viral infection by HPV with cancer through function of a single enzyme, which is a report on Warren et al. Roles of APOBEC3A and APOBEC3B in Human Papillomavirus Infection and Disease Progression Viruses 2017; 9(8): 233. 537-542. DOI:

That fact means cancer prevention is nutrient energy-dependent in the context of biophysically constrained viral latency.

By decoding how HPV causes cancer, researchers find a new potential treatment strategy

The new study, published Oct. 2 in the journal Oncotarget, found that E6, an oncoprotein produced by the virus, interacts with several other molecules in host cells in a manner that ensures infected cells cannot die. If they are immortal and continue to multiply, cancer develops.

Other findings on virus-driven pathology have been linked from the theft of quantized energy as information to the suicide of veterans who have served overseas and been infected with bacteriophages (viruses in bacteria).

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