Energy-dependent de novo creation and neurogenesis

December 8, 2016

by James Kohl with One Comment Adaptations Alternative Splicings Diseases & Disorders Ecology RNA Directed RNA methylation RNA-directed DNA methylation RNA-mediated epigenetic regulation of gene expression RNA-mediated gene silencing RNA-mediated toxicity RNA–Mediated Epigenetic Heredity Variations

Developmentally defined forebrain circuits regulate appetitive and aversive olfactory learning

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

My summary:

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

See for comparison: Metabolism and neurogenesis

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

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

See my comments:

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

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

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

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

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

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

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

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

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

Addressing sex as a biological variable

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

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

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

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

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

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

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

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

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

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

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

Virus-mediated hecatombic evolution

October 16, 2016

by James Kohl with No Comment Adaptations Alternative Splicings Diseases & Disorders Ecology Model Organisms RNA-directed DNA methylation Variations

Virus-mediated archaeal hecatomb in the deep seafloor

These findings provide new evidence for a possible link between viral infections and chemoautotrophic production in the microbial food web.

My comment: I hereby stake my claim to the invention of the term”hecatombic evolution.” At the forthcoming meeting of the Royal Society next month, I expect full consideration to be given to use of “hecatombic evolution” to replace neo-Darwinian evolution and/or the “Modern Synthesis” or mutation-driven evolution until everyone in the world realizes the “hecatombic evolution” also is not possible within the context of what is known about the biophysically constrained energy-dependent links from autophagy to chromosomal rearrangements, which enable the nutrient-dependent pheromone-controlled biodiversity of species from microbes to humans.

SARCASM ALERT: If you are a pseudoscientist, it’s time to forget everything you know or should have learned about polycomb activities and jump on the band-wagon to support hecatombic evolution.

Don’t be the last to look as foolish as the supporters of mutation-driven evolution look now that everyone knows no experimental evidence of biologically-based cause and effect supports their ridiculous claims.

If you use hecatomb in any context whatsoever, you can make history and potentially become as infamous as Richard Dawkins. Hecatombic evolution is the only type of evolution left, and it is as ridiculous a misrepresentation of facts as everything that has come before it.

It’s my turn to invent a term for use in discussions of what pseudoscientists believe. They won’t claim to believe in mutation-driven evolution because they know there is no model for that. But they won’t make any other claim about what they believe in. Start asking if they believe in hecatombic evolution, and I will help them to define what they believe in. I will try to ensure there will be no doubt left. It will be obvious that pseudoscientists will believe anything anyone tells them except the scientific truth about how ecological variation must be linked to ecological adaptation in all living genera.

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

Does metabolism link beneficial mutations to cancer?

December 27, 2015

by James Kohl with No Comment Adaptations Alternative Splicings biophotonics Diseases & Disorders Ecology Light Energy Model Organisms Neuronal Plasticity Nutrigenomics Pharmacogenomics Physics RNA Directed RNA methylation RNA-mediated epigenetic regulation of gene expression RNA-mediated gene silencing RNA-mediated toxicity RNA–Mediated Epigenetic Heredity Variations

Viruses steal nutrients needed by the cell. The theft deregulates protein folding, which is how viruses perturb biophysically constrained nutrient energy-dependent protein folding chemistry. The theft of nutrients by viruses links mutations to all pathology.

Nutrients are required for RNA methylation and RNA-directed DNA methylation. Cell types do not hypermethylate unless nutrient-dependent hypermethylation is required to protect organized genomes from virus-driven entropy. Simply put, viruses cause nutrient-dependent hypermethylation when hypermethylation is required to protect organized genomes from virus-driven entropy. Evolutionary theorists are so confused about biologically-based cause and effect that is has become almost impossible to untangle their misrepresentations.

For example, the role of viruses is not included in these evolutionary dynamics.

Quantitative evolutionary dynamics using high-resolution lineage tracking

Excerpt:

Our results show that in an asexually evolving population of ~108 cells, a large number of independent beneficial mutations drive adaptation.

My comment: The ridiculous idea that beneficial mutations drives adaptation can be placed into the context of what serious scientists know about how viruses cause cancer via genome unfolding.

See: Genome misfolding unearthed as new path to cancer (but first see) Gene variation promotes uncontrolled cell division

Uncontrolled cell division is linked from gene misfolding to cancer

Excerpt (with my emphasis):

The germline mutation rs351855 accounts for aggressive and rapidly growing tumors that are resistant to treatment. An effective treatment needs to be tailored to match the mutation and its biological effects.

My comment: Nutrient-dependent epigenetically-effected mutations are not fixed in the germline via the physiology of reproduction. If they were fixed in the germline, the mutations could be linked from virus-perturbed protein-folding chemistry to genomic entropy via RNA-mediated cell type differentiation in all living genera.
Instead, virus-driven entropy is typically limited because most virus-caused germline mutations are eliminated in the context of sexual reproduction in all invertebrates and vertebrates.
That fact has been somewhat concealed in the context of reports that link mutations to evolution of new species. No experimental evidence of biologically-based cause and effect suggests that mutations can be linked to the evolution of any new species.
All experimental evidence links atoms to ecosystems. An atoms to ecosystems model places RNA-mediated amino acid substitutions into the context of nutrient-dependent ecological adaptations in some populations of modern humans, but not in all populations of modern humans.
It the context of nutrient-dependent RNA-mediated receptor-mediated cell type differentiation, rs351855 is an SNP that becomes another example of an RNA-mediated theory killer linked to differences in the cell types of different populations of modern humans.
See also: Patterns and functional implications of rare germline variants across 12 cancer types
Excerpt (with my emphasis):

Dot plot shows individual missense variants where abscissa and ordinate are amino acid positions and the ratio of tumour-to-normal variant allele fraction, respectively.

Reported as: Study uncovers inherited genetic susceptibility across 12 cancer types
My comment: The dot plot is not used to link rs351855 to the variants from the amino acid positions. Thus, the nutrient-dependent amino acids that establish the stability of cell types are not linked to the inherited genetic susceptibility via the ratio of tumour-to-normal variant allele fraction in the cancer types.

See for comparison: SNPedia

Rs351855

Excerpt:

… a SNP in the fibroblast growth factor receptor 4 (FGFR4) gene, is also known as the Gly388Arg variant. The rs351855(T) allele encodes the risk (Arg) allele.

The Arg form of this SNP is likely to cause a harder to treat version of node-positive breast cancer, including reducing the efficacy of Herceptin, based on a study of 372 patients.[PMID 16822847]

A study of ~500 Japanese prostate cancer patients found that individuals with a rs351855(T;T) genotype had a 2.2- and 1.9-fold increased risk of prostate cancer and benign prostate hyperplasia (BPH), and a 1.8-fold increased risk of metastatic prostate cancer compared to the (C;C) genotype.[PMID 18756523]

A meta-analysis published in 2011, surveying a total of 2,618 cases of prostate cancer, concluded that the odds ratio per rs351855(T) allele was 1.17 (CI: 1.07 – 1.29), and that when stratified by race, Caucasians and Asians were at highest risk.[PMID 21349172OA-icon.png]

My comment: Rs351855 appears to link an energy-dependent single base pair substitution and/or one SNP to a single nutrient energy-dependent RNA-mediated amino acid substitution and undifferentiated cell types of different cancers via virus-perturbed protein folding. It also appears that pseudoscientists have not learned enough about the nutrient-dependent innate immune system to establish the link from virus-perturbed protein folding to cancer or to anything else.

Excerpt:

Fibroblast growth factor 21 (FGF21) is a hormone induced by various metabolic stresses, including ketogenic and high-carbohydrate diets, that regulates energy homeostasis.

Reported as: Liver hormone reduces preference for sweets, alcohol, via brain’s reward pathway

This marks the fourth study from the Mangelsdorf-Kliewer laboratory to show that FGF21 directly affects the central nervous system. First, in two studies in Nature Medicine in 2013, they reported on FGF21’s ability to regulate metabolism, circadian (body clock) behavior, and female reproduction. In 2014, they reported in Cell Metabolism that FGF21 acts on the brain to cause weight loss.
“The finding that FGF21 acts via the brain was completely unexpected when we started down this path of investigation a dozen years ago,” Dr. Kliewer said. “These findings suggest that additional studies are warranted to assess the effects of FGF21 on sweet and alcohol preference and other reward behavior in humans.”

My comment: The links between nutrients and ligand-receptor interactions that establish classically conditioned rewards are established during life history transitions link RNA-directed DNA methylation to cell type differentiation via the physiology of reproduction in all living genera. Links from the epigenetic landscape to the physical landscape of DNA make the claims of neo-Darwinian theorists more ridiculous than ever.
For example, neo-Darwinian theorists link beneficial mutations to evolution and detrimental mutations to cancer risk in their ridiculous theories. They are caught in a trap. The trap forces theorists to explain the difference between beneficial mutations linked to evolution and mutations linked to pathology.
They avoid that trap by claiming that the beneficial mutations accumulate over millions of years. The tell people that whatever causes the mutations linked to pathology is selected against and never explain how mutations could be beneficial, or how beneficial mutations could lead to evolution.
It has become clear, however, that limiting the number of stem cell divisions limits cancer risk. But, it also limits claims about mutations and evolution.

See for example:

Variation in cancer risk among tissues can be explained by the number of stem cell divisions

My comment: In my model, variation in cancer risk is RNA-mediated. Ecological variation is linked from atoms to ecosystems via nutrient-dependent changes in the microRNA/messenger RNA balance that link DNA repair to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy.

Recent support for my model appeared in: Substantial contribution of extrinsic risk factors to cancer development

Excerpt:

Finally, we show that the rates of endogenous mutation accumulation by intrinsic processes are not sufficient to account for the observed cancer risks. Collectively, we conclude that cancer risk is heavily influenced by extrinsic factors. These results are important for strategizing cancer prevention, research and public health.

Reported as: Cancer studies clash over mechanisms of malignancy

Excerpt:

The paper attempts to rebut an argument that arose early this year, when a report in Science concluded that differences in inherent cellular processes are the chief reason that some tissues become cancerous more frequently than others (C. Tomasetti and B. Vogelstein Science 347, 78–81; 2015).

My comment: It is not necessary to rebut any claim made that includes “inherent cellular processes” because those are the claims make no sense. The original argument that cancer resulted from “bad luck” and the “inherent cellular processes” was not placed into the context of what is currently known to serious scientists about the links from atoms to ecosystems.

Anyone who does not acknowledge the basis for claims that link ecological variation to ecological adaptations in the context of nutrient-dependent RNA-mediated cell type differentiation via amino acid substitutions is not likely to be a serious scientist. As all serious scientists know, it is a waste of time to compare arguments about biologically-based cause and effect with any biologically uninformed theorist who claims that bad luck and/or “inherent cellular processes”cause cancer, or that good luck causes one species to evolve into another.

However, the controversy that was reported in “Cancer studies clash over mechanisms of malignancy,” was reported with no resolve. The researchers still seem to be unable to report their claims in the terms that link experimental evidence of biologically-based cause and effect to cell type differentiation via nutrient-dependent changes in the microRNA/messenger RNA balance.
The changes link nutrients to healthy longevity and viruses to all pathology. Viruses prevent fixation of RNA-mediated amino acid substitutions in organized genomes via the physiology of reproduction. The accumulation of viral microRNAs, which is associated with nutrient theft by viruses to support their replication, links stolen amino acids to viral replication instead of linking the nutrient-dependent microRNAs to DNA repair.

If serious scientists are not going to link atoms to ecosystems across generations, they are not likely to help find effective treatments or help to prevent the uncontrolled cell type differentiation that is driven by viruses in all cell types of all individuals of all living genera.

See for example:

Noncoding RNA –NORAD– Regulates Genomic Stability by Sequestering PUMILIO Proteins

Reported as:

Scientists discover a new role for RNA in safeguarding human chromosome number

Excerpt:

NORAD produces a long noncoding RNA, a type of molecule that was not previously known to be important in chromosome maintenance, the researchers report in the journal Cell.

My comment: Nutrient dependent microRNAs appear to link all non-coding RNA to genomic stability. As more serious scientists become aware of the need to link ecological variation from the availability of nutrients to speciation via chromosomal rearrangements that limit hybridization, theories about mutations and evolution of new species may disappear. There are too many examples of how chromosomal rearrangements are linked from the nutrient-dependent pheromone-controlled physiology of reproduction by chromosomal rearrangements for any intelligent person to keep making claims about mutations and evolution.

But wait. Why are other researchers (see below) still reporting results outside the context of metabolic networks and genetic networks that link RNA-mediated cell type differentiation in species from microbes to humans?

Brain Cancers Reveal Novel Genetic Disruption in DNA

Excerpt:

It was really surprising,” Dr. Bernstein said. “Why would a metabolism gene cause cancer?”

My comment: Genes don’t cause cancer. This “metabolism gene” obviously links the theft of energy by viruses to perturbed cycles of protein biosynthesis and degradation that are typically biophysically constrained.

The biophysical constraints link nutrient-dependent microRNAs from adhesion proteins to supercoiled DNA, which protects organized genomes from virus-driven entropy. How can cancer researchers not know anything about how cell type differentiation is biophysically constrained by RNA-mediated protein folding chemistry?

Genome misfolding unearthed as new path to cancer

Excerpt:

By creating these loops — roughly 10,000 of them in total — the genome harnesses form to regulate function. “It has become increasingly clear that the functional unit of the genome is not a chromosome or even a gene, but rather these loop domains, which are physically separated — and thereby insulated — from neighboring loop domains,” said Bernstein.

My comment: The question arises: Is Bernstein trying to tell us that the genome harnesses form by automagically creating these loops that regulate the function of the genome?

Serious scientists know how nutritional epigenetics links metabolism and virus-perturbed thermodynamic cycles of protein biosynthesis and degradation to failed DNA repair. The serious scientists placed the conserved molecular mechanisms of RNA-mediated cell type differentiation into the context of the RNA-mediated cell type differentiation we detailed in the molecular epigenetics section of our 1996 review.

See: From Fertilization to Adult Sexual Behavior

What has been known about the molecular epigenetics of RNA-mediated cell type differentiation since 1996 seems to have escaped the notice of cancer researchers for nearly two decades.

The entirety of what is known about cellular intelligence has since been linked from the innate immune system of microbes to antibiotic resistance in humans via what is known about sensing, secreting, and signaling molecules in all living genera.

But, see: Shouldn’t Be Over Here

Excerpt 1)

Mutations in the housekeeping gene IDH may mediate the development of brain tumors by increasing methylation throughout the genome and disrupting usual DNA folding patterns, a Broad Institute-led team of researchers reports in Nature.

My comment: Viruses cause the mutations.

Excerpt 2)

In particular, the Broad’s Bradley Bernstein and his colleagues found that gain-of-function mutations in IDH lead to genome-wide hypermethylation of CTCF binding sites and the deregulation of boundary elements that divide different topological domains. The elimination of a boundary near PDGFRA, a glioma oncogene, enables an enhancer then to swing by and activate it.

My comment: The claim that mutations cause the genome-wide hypermethylation is a foolish claim. Viruses cause nutrient-dependent hypermethylation when hypermethylation is required to protect organized genomes from virus-driven entropy. Viruses that deregulate biophysically constrained nutrient-dependent protein folding chemistry by stealing nutrients needed by the cell cause perturbed protein folding that is linked to mutations and pathology. Simply put, cell types do not hypermethylate their genomes unless nutrient-dependent hypermethylation is required to protect organized genomes from virus-driven entropy.

Excerpt 3)

Bernstein tells the New York Times that this way of becoming cancerous likely isn’t limited to brain tumors.

My comment: He also claimed that he doesn’t know why a metabolism gene would cause cancer. Alll serious scientists have begun to link metabolic networks and genetic networks via the nutrient-dependent microRNA/messenger RNA balance, which is perturbed by viruses. Did Bernstein really tell someone that the way cells types become cancerous is not known? Did he claim that what is not known about the link from metabolic networks to genetic networks is not known, but it probably is not limited to brain tumors?

Excerpt 4)

Such excessive methylation also suggests a possible treatment, he notes. As he and his colleagues report in Nature, they found that treating patient-derived IDH mutant gliomaspheres with a demethylating agent like the first-generation chemotherapy drug 5-azacytidine partially restored insulator function and downregulated PDGFRA.

My comment: Excessive methylation suggests that the researchers should explain what causes it before treating patients with anything that surprised them via a link to a metabolism gene. Treating excessive methylation caused by one virus with a demethylating that promotes replication of a different virus by altering the stability of an organized genome will most likely lead to a treatment resistant virus-driven cancer in another cell type or tissue.

Excerpt 5)

But first, Bernstein tells the Times, there needs to be a way to detect an overabundance of methyl tags and the breakdown of DNA topological domains.

My comment: No, first you need to detect the virus and link it from its viral microRNAs the cause of the nutrient-dependent overabundance of methyl tags and unrepaired DNA damage that is typical repaired in the context of nutrient-dependent RNA-mediated cell type differentiation via microRNAs linked from amino acid substitutions to adhesion proteins and supercoiled DNA that protect organized genomes from virus-driven entropy.

Excerpt 6)

“I am biased, obviously,” Bernstein says before adding that he is “really optimistic about the potential of this information.”

My comment: Of course he is biased, and other people like him are biased. They are paid to be biased. If they weren’t biased by ridiculous theories about mutations and evolution, they would be examining biologically-based cause and effect. Instead, these researchers are being paid to report “gain of function” mutations as if the gains were beneficial. If they can’t find a way to treat the mutations that they claim cause a “gain of function,” their research is less likely to be funded.

The potential loss of funding is a threat to their career and that threat requires them to present their findings in the context of ridiculous theories about mutation-driven evolution. They can earn a good living without ever learning the difference between an amino acid substitution and de Vries definition of “mutation.” The difference became clear in the early 1990s.

The late Robert L. Moss, with colleagues from UT Southwestern, explained the role of odors in gene activation. Food odors and social odors, called pheromones alter the “inherent cellular processes” which Bernstein and his colleagues have ignored despite the fact that hypermethylation is nutrient-dependent. The epigenetic effects of odors and pheromones must be included the reports that Bernstein claims link mutations to cancer because the link to cancer must start with epigenetically-effected metabolism and gene activation, not with mutations.

Dr. Moss and others told me to start with gene activation before they gave me the green light to proceed with confidence to explain my model to others. Will the role of viruses in pathology continue to escape pseudoscientists for another two decades, or will someone step forward and stop this nonsense about surprises. Serious scientists have presented the first evidence of what is known about the links between metabolic networks and genetic networks in all living genera during the past two decades. The links are nutrient dependent, RNA-mediated and controlled by the physiology of reproduction until ecological insults enable the accumulation of viruses to alter transgenerational epigenetic inheritance of organized genomes and cause pathology in the next two, or more, generations of humans.

Ignoring that fact will not make it go away. Ignoring this fact will make that fact worse. “The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis…”

A 5-10K comparison of design principles to evolution

September 21, 2015

by James Kohl with One Comment Adaptations Ecology Model Organisms Physics RNA Directed

Julie Theriot: Discovering Design Principles for Cells and Organisms
Excerpt:

…there is immense diversity in cellular structures. What are the underlying physical principles that allow these structures to emerge? Julie Theriot argues that protein folding theories fail to explain how cells build large-scale assemblies, and so scientists are working to develop a new theory of cell structure determination.

See also: Why are bacteria different from eukaryotes?
Excerpt:

…there is a bacterium with the wonderful name Gemmata obscuriglobus that is described as having a double membrane enclosing the DNA in a nucleus-like structure [3], although the structure is apparently contiguous with the plasma membrane [4], so in that sense it is very different from a eukaryotic nuclear membrane and this is certainly a special case. But leaving that example aside…

My comment: If you leave out any example that does not fit within the biophysical constraints of ecologically determined variants, you can continue to dispense with other similarities across species and focus on differences throughout the required progression of niche construction that enables our observations (i.e., from ecological to social to neurogenic and to socio-cognitive niche construction).
For example. the excerpt above continues uninterrupted below. It exemplifies the exclusion of ecological variation and across species similarities in niche construction during the progression of organismal complexity. The focus is on differences.

…the main consequence biologically of having a membrane-enclosed nucleus is that transcription and translation are uncoupled. So there is a fundamental kinetic and organizational difference between eukaryotes and bacteria in the way that genetic information is expressed in the form of protein and is therefore allowed to be converted into cellular structure, function and organization.

My comment: The questions arise:
1) How were transcription and translation uncoupled?
2) Does any experimental evidence suggest that the biophysical constraints on niche construction (e.g., of physics and chemistry) can simply be dismissed?
If ecologists and or ethologists cannot answer those questions, their biologically uninformed minions are left with no answers to any other questions about biophysically constrained adaptations. Ecological variants automagically become incorporated into a theory of how mutations somehow cause mutation-initiated natural selection and evolution. Few people look back to see the explanatory power of similarities. Anyone who does look back will understand the lack of explanatory power that is so pervasive in discussions among physicists that might simply begin with the question: “What about birds?”
Unfortunately, attempts to find answers to questions about cause and effect from ethologists have failed from the start. Discussion of differences between bird species and other species continues, and discussion is based on what ethologists can observe. Looking back on what Dobzhansky wrote in 1964, I suspect it was discussion of differences by ethologists that led him to claim: “…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!”
See for comparison:
David Haussler: What Can We Learn From Sequencing Our Genomes?
Excerpt:

By comparing the sequenced genomes of different organisms, researchers can identify changes in the genetic code that led to specific evolutionary innovations in the past. The implications for medicine and biology are profound.

I find something else equally profound. The Hebrews appear to have linked RNA-mediated cell type differentiation to biodiversity thousands of years ago. The fact that most deleterious mutations to our genes have arisen since then suggests that people should have learned more about biologically-based cause and effect before they were taught to believe in the pseudoscienitific nonsense about mutations, natural selection and evolution.
See: The 72 Angels and the Power of the Hebrew Letters
Excerpt:

The "great filter" is an epigenetic trap

August 19, 2015

by James Kohl with No Comment Adaptations Ecology Light Energy Physics RNA Directed Variations

The great filter

The silence of universe seems ominous. Was Earth lucky?

Thanks to George Ellis for alerting others to this.

Excerpt: Nick Lane in his magnificent new book The Vital Question thinks that a peculiar feature of all earthly life — that it traps energy in the form of protons pumped across membranes…
Excerpt 2) Next, after a couple of billion years, creatures bigger than microbes emerged, once (Nick Lane argues) an energy-per-gene limit was breached by the invention of the mitochondrion, a specialised energy-generating microbe living inside another cell.

My comment: First, an epigenetic trap links the sun’s biological energy to the light-induced de novo creation of nucleic acids and to the creation of amino acids. The amino acids are required to link RNA-mediated events to the the de novo creation of receptor proteins in the membranes of cells.
Did Nick Lane address the fact that the creation of the cells requires a nutrient source? See for comparison: Energy-releasing chemical reactions are at the core of the living process of all organisms.
Many theorists jump from the required nutrient source of the energy and proceed via de Vries definition of “mutation” and link the definition to jumps that they think cause the evolution of new species. The creation of more than one cell type or species requires RNA-mediated gene duplication to create more receptors with variations in their structure. The variants link RNA-mediated amino acid substitutions to cell type differentiation in all cells of all individuals of all living genera. The variants are not “jump-like changes.” Amino acid substitutions are biophysically constrained by the chemistry of nutrient-dependent protein folding and the physiology of nutrient-dependent reproduction.
My questions (Set 1) Who set the first epigenetic trap that Nick Lane claims “…traps energy in the form of protons pumped across membranes?” How much energy was required to set the trap? What physical forces allow the epigenetic trap to open and close? For example, after a virus enters a cell, what prevents its nutrient-dependent replication from linking entropic elasticity to genomic entropy via perturbed protein folding?
My comment: Stuart Kauffman and other informed scientists think there must be an anti-entropic force. See: Scientific Seeker Stuart Kauffman on Free Will, God, ESP and Other Mysteries.
Excerpt:

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

My questions (Set 2) When are theorists going to address the fact that the sequencing of the octopus genome links nutrient-dependent microRNAs to the protection from viral microRNAs, which enables the stability of organized genomes in all living genera? Does the nutrient-dependent microRNA-mediated stability of organized genomes exemplify how ecological variation leads to ecological adaptation or to extinction due to genomic entropy? Could an anti-entropic electrostatic force be all that’s required to link all of biodiversity to its orgins?
My questions (Set 3) Are evolutionary theorists trapped within the context of neo-Darwinian theories despite the fact that Darwin warned them not to start with natural selection? Have big bang cosmologists and evolutionary theorists wasted more than 100 years trying to determine how the first epigenetic trap was set, while others have linked ecological variation to ecological adaptation via single amino acid substitutions? Is it time to review what serious scientists understand about the need to start with top-down causation?
See, for example:
Context-specific microRNA function in developmental complexity
My question: How do you approach developmental complexity from an evolutionary perspective that does not start with top-down causation and skips what theorists claim is the first 2 billion years of evolved life on this planet?
Riding the Evolution Paradigm Shift With Eugene Koonin
Excerpt:

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

See for comparison:
Top-down causation: an integrating theme within and across the sciences?
Top-Down Causation and the Rise of Information in the Emergence of Life

The Chirality Of Life: From Phase Transitions To Astrobiology

Excerpt: A key missing piece is the origin of biomolecular homochirality: permeating almost every life-form on Earth is the presence of exclusively levorotary amino acids and dextrorotary sugars.

Matt Ridley’s “great filter” is what serious scientists might call an epigenetic trap. Evolutionary theorists should stop commenting on the experimentally established facts that serious scientists use to link viruses to pathology and the nutrient-dependent physiology of reproduction to the metabolic networks and genetic networks of healthy biodiversity and longevity. The nutrient-dependent physiology of reproduction is another epigenetic trap. It links the epigenetic landscape to the physical landscape via the conserved molecular mechanisms that link the sun’s biological energy from atoms to ecosystems.
Evolutionary theorists should stop doing what theoretical physicists continue to do to the integrity of science. See: Scientific method: Defend the integrity of physics
Excerpt:

The imprimatur of science should be awarded only to a theory that is testable. Only then can we defend science from attack.

If energy-dependent evolution occurs in 4 days, but not in ~2 billion years, the pseudoscientific nonsense that takes everything between 4 days and ~2 billion years can be placed where the sun doesn’t shine — at the bottom of the ocean. The sun also does not appear to shine into the minds of theorists who think they know what Dobzhansky (1973) meant with his claim Nothing in Biology Makes Any Sense Except in the Light of Evolution. Obviously, he could have said the “Light of Ecological Adaptation” since he linked a single nutrient-dependent amino acid substitution to cell type differentiation in three primate species. However, like Schrodinger, Dobzhansky was caught in the trap set by Darwinian theorists.
Hub McCann Teaches Respect (Secondhand Lions)
My comment: Should people like this be required to wear a DO NOT DISTURB sign? If so, biologically informed creationists may need to start wearing signs that warn biologically uninformed theorists to not attack science. For an example of science that is ignored by theorists, creationists could attack them because theorists ignore the fact that the bacterial flagellum “re-evolved” in four days. They also ignore the fact that similar facts can be linked across species to a species of bacteria that lives in the sediment at the bottom of the ocean. It appears to have not changed in ~2 billion years, which just happens to be the amount of time missing from Nick Lane’s evolutionary perspective on energy-dependent evolution.

RNA-mediated gene duplication, fixation, and ecological adaptation

July 11, 2015

by James Kohl with One Comment Adaptations Alternative Splicings Diseases & Disorders Ecology Model Organisms Nutrigenomics Pharmacogenomics RNA Directed

Chromosomal Arrangement of Phosphorelay Genes Couples Sporulation and DNA Replication
Excerpt:

The simplicity of this coordination mechanism suggests that it may be widely applicable in a variety of gene regulatory and stress-response settings.

Reported as:

Bacteria use DNA replication to time key decision

Excerpt:

“Successful sporulation requires two complete copies of the bacterial chromosome, so coordination between the sporulation decision and the completion of DNA replication is very important,” Narula said. “A good analogy might be a semester-long course in biology.

My comment: If, at the end of the semester, you believed that these bacteria “evolved” their ability to choose when to sporulate, you might continue to ignore this fact: Their biophysically constrained nutrient-dependent RNA-mediated thermodynamic cycles of protein biosynthesis and degradation are controlled by the physiology of their reproduction in the context of fixed RNA-mediated amino acid substitutions and gene duplication.
The fact that gene duplication is nutrient-dependent is difficult to ignore even when it is referred to as DNA replication. It is also difficult to ignore the fact that no experimental evidence of biologically-based cause and effect has ever linked mutations to the creation of new genes. That means mutations cannot be linked from genes to the chromosomal rearrangements that link RNA-mediated amino acid substitutions to biodiversity via the conserved molecular mechanisms of nutrient-dependent biophysically constrained RNA-mediated protein folding chemistry.
If you, like the atheist blogger PZ Myers and his idiot minions, continue to attack anyone who provides experimental evidence that links the creation of new genes to chromosomal rearrangements and to biodiversity in species from microbes to man, you will be more than 30 years behind the experimental evidence that links viruses to genomic entropy and the anti-entropic epigenetic effects of nutrients to RNA-mediated cell type differentiation in species from microbes to man.

See: One crank dies, another rises to take his place

Excerpt:
Behold James Vaughn Kohl.

Ecological adaptation occurs via the epigenetic effects of nutrients on alternative splicings of pre-mRNA which result in amino acid substitutions that differentiate all cell types of all individuals of all species. The control of the differences in cell types occurs via the metabolism of the nutrients to chemical signals that control the physiology of reproduction.
These facts do not refute evolution; they simply refute the ridiculous theory of mutation-initiated natural selection that most people here were taught to believe is the theory of evolution.

PZ Myers did not like my accurate representation of biologically-based cause and effect, which he linked to the accurate representations by others who he attacked in the past. Others did not like my accurate representations, either. In his Criticisms of the nutrient-dependent pheromone-controlled evolutionary model, Andrew Jones included a citation to PZ Myers blog.
Excerpt:

A multitude of misconceptions and misunderstandings can be seen in his comments on Dr. PZ Myers’ blog, Pharyngula (Kohl, 2014b).

My comment: Everything known about ecological variation and biologically-based ecological adaptation links RNA-mediated events to metabolic networks and genetic networks. The metabolic networks and genetic networks link RNA-directed DNA methylation to gene duplication via the fixation of RNA-mediated amino acid substitutions. The nutrient-dependent amino acid substitutions are linked to healthy longevity. Mutations are linked to pathology. Everything published by serious scientists during the past 30 years also links RNA-mediated gene duplication from metabolic networks to genetic networks and the biodiversity of all extant species. Species that failed to ecologically adapt became extinct. For example, when they ran out of food, they did not evolve into another species because gene duplication is nutrient-dependent.

See also: RNA-Mediated Gene Duplication and Retroposons: Retrogenes, LINEs, SINEs, and Sequence Specificity (2013) and RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon (1985)
My comment: Serious scientists have known for more than 30 years that gene duplication is RNA-mediated. If they don’t know that gene duplication is nutrient-dependent, they are not serious scientists. Moving forward, let’s look at what serious scientists know about gene duplication. We can forget about PZ Myers and his idiot minions or anyone else who was taught to believe in ridiculous theories about mutations and evolution.
Synthetic success:
Rewriting the blueprint of life by synthetic genomics and genome engineering
Excerpt:

The engineered E. coli incorporated non-standard amino acids into its proteins and showed enhanced resistance to bacteriophage T7 [25].

Natural failure
Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic
Excerpt:

…we functionally annotated fixed, derived amino acid and loss-of-function (LOF) substitutions in woolly mammoths.

How to ecologically adapt:
Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals
My comment: To ecologically adapt, species must reproduce.
How to become extinct:
Popping the Cork on a microbiome alliance
Excerpt 1)

While most people are familiar with human viruses, it is not as well known that bacteria also have viruses which can drastically influence bacterial populations. These bacterial viruses are necessary for a balanced ecosystem, which is vital for the overall health of the host,” said Hill.

Excerpt 2) The role of phage in shaping the microbiota in health and disease is relatively unexplored…
My comment on excerpt 1) Accumulation of viral microRNAs links bacterial viruses to perturbed protein folding and unbalanced ecosystems that lead to extinction. Without the anti-entropic epigenetic effects of nutrient-dependent microRNAs, all species would have long-ago become extinct.
My comment of excerpt 2) The role of phages has been explored in the context of what has been learned about virus-driven genomic entropy, which is prevented by the anti-entropic epigenetic effects of nutrients on DNA repair. Fixation of nutrient-dependent amino acid substitutions links RNA-mediated cell type differentiation and biodiversity in all genera. Mutations are linked to pathology.
See for example:

Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants

Excerpt: Of 1.15 million single-nucleotide variants found among more than 15,000 protein-encoding genes, 73% in arose the past 5,000 years, the researchers report. 164,688 of the variants — roughly 14% — were potentially harmful, and of those, 86% arose in the past 5,000 years.
My comment: The harmful variants link mutations to pathology. That is the reason they are called harmful variants. Amino acid substitutions are linked to healthy longevity, which is why they should not be called mutations.
For example, Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system, claims that two mutations enabled the bacterial flagella of a species to “re-evolve” over-the-weekend. They called the fixed amino acid substitutions that enabled food finding mutations. Sulfur-cycling fossil bacteria from the 1.8-Ga Duck Creek Formation provide promising evidence of evolution’s null hypothesis linked the lack of mutations and/or amino acid substitutions to the evolution that did not occur in ~2 billion years.
In reality, which for most people is what happens to them during their life-time, mutations are bad, and fixation of nutrient-dependent RNA-mediated amino acid substitutions is good.
For example: DNA methylation and single nucleotide variants in the brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) genes are associated with anxiety/depression in older women.
RNA-directed DNA methylation links fixed amino acid substitutions to hormones and behavior during life history transitions of all genera. Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults.
The failure of RNA-mediated fixation that is required for brain development during the transition from adolescence to adulthood, is linked to behavioral instability by hormones, which are also associated with anxiety/depression in older women. However, linking the hormones to the evolution of personality is a ridiculous misrepresentation of biologically-based cause and effect. See for example: Neuroendocrine mechanisms underlying behavioral stability: implications for the evolutionary origin of personality.
The neuroendocrine mechanisms are nutrient-dependent and they require gene duplications to link the biophysically constrained chemistry of nutrient-dependent RNA-mediated protein folding to behavioral changes during life history transitions.
For example, see: Brain feminization requires active repression of masculinization via DNA methylation
Excerpt:

Our observation that Dnmt inhibition reduced a substantial number of genes in females reveals an additional layer of complexity for which there is no current explanation.

My comment: They cannot explain why the lack of gene duplication led to changes in behavior. Oddly, they appear to have learned nothing about how the anti-entropic epigenetic effects of RNA-mediated amino acid substitutions explain all links from genes to the hormones that affect behavior. Evidently, the RNA-mediated gene duplication and RNA-directed demethylation that links RNA-mediated amino acid substitutions to the development of behavior is too complex for them to comprehend.
See, instead: From Fertilization to Adult Sexual Behavior.
Our section on molecular epigenetics links everything currently known about RNA-mediated cell type differentiation to the development of morphological and behavioral phenotypes in all genera. However, we did not mention the fact that RNA-mediated gene duplication must come first. We assumed that serious scientists knew that, and that only pseudoscientists would continue to tout their ridiculous theories about mutations and evolution.
We were wrong. Our facts about RNA-mediated cell types were ignored. For contrast: [W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. Assumptions, made but not verified, were taught as fact.
The assumptions taught to biologically uninformed theorists have continue to plague serious scientists who present experimentally established facts.
See for example, the discussions at: Researchers find the organization of the human brain to be nearly ideal and at ‘Map of life’ predicts ET. (So where is he?)
No matter how much experimental evidence is cited, the assumptions prevail. See also discussions of Learning categorical information gives children a feeling of deja vu and of Researcher disputes claim that humans can distinguish one trillion odors.
Pseudoscientists have successfully convinced many people that mutations can be linked to evolution without consideration of RNA-mediated gene duplication or the RNA-mediated events that link the metabolism of nutrients to cell type differentiation via fixation of amino acid substitutions in the context of the biophysically constrained chemistry of protein folding.

"New" epigenetic mechanism for lifelong learning?

July 2, 2015

by James Kohl with No Comment Adaptations Alternative Splicings Diseases & Disorders Ecology Human Brain Human Pheromones Model Organisms Neuronal Plasticity Nutrigenomics Pharmacogenomics Physics RNA Directed Variations

Critical Role of Histone Turnover in Neuronal Transcription and Plasticity
Reported as:

Lifelong learning is made possible by recycling of histones, study says

Also reported as:

New epigenetic mechanism revealed in brain cells

Excerpt:
In humans, researchers used a technique called 14C/12C bomb pulse dating to measure turnover. The technique is based on the fact that high levels of radioactive carbon (14C) were released into the atmosphere during the 1950s and 1960s, when open-air nuclear bomb testing occurred following the Second World War. Researchers can take samples from cells – in this case, purified H3.3 samples from brain cells of postmortem human brains, and determine present 14C/12C ratios from the time of death against past atmospheric levels from the time of the subject’s birth. As with the rodent observations, the researchers found that H3.3 turnover occurs in the human brain throughout life.
Additionally, the researchers deliberately manipulated H3.3 dynamics in both embryonic and adult neurons, confirming the role of histone turnover in neuronal plasticity. The findings thus establish histone turnover as a critical, and new, regulator of cell-type specific transcription in the brain.
“Histone turnover, shown through our work with H3.3, is essential for the behavior of brain cells,” said Dr. Maze. “Furthering our understanding of how the brain works, learns, forms new memories and reacts to changes in the environment can help us to find new ways to treat neurodegenerative diseases and mental illness.”
Attempts to discuss this among neuroscientists can be found on this Neuroscience FB page.
Addendum: My understanding of cancer links it from RNA-directed DNA methylation and RNA-mediated amino acids substitutions that are linked via “histone turnover” and cell type differentition in the brain. My understanding is based on the young earth creationist perspective, which I learned about from a physician. He claimed that something more than sun exposure must be responsible for the different types and number of different non-malignant and malignant skin cell types that were removed during ~ 20 different surgeries. When I told him that I managed the medical laboratory at the Nevada Test Site, which is where open-air nuclear bomb testing occurred following the Second World War, and that I had also worked in the down-wind area (Caliente, Nevada) and (Milford, Utah) for several years, he said: “That would do it!”
I hired other medical laboratory scientists to work at both locations, and they traveled from St. George, Utah. It is a “hotbed” of skin cancer and located between the two medical laboratory facilities that I subsequently managed.
Anecdotal and experimental evidence of biologically-based cause and effect have continued to support the views of the young earth creationists, who are less likely to believe in any pseudoscientific nonsense about mutations and evolution — compared to social scientists.
See also:
Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis
and
Histone Deacetylases Regulate Gonadotropin-Releasing Hormone I Gene Expression via Modulating Otx2-Driven Transcriptional Activity
The obvious epigenetic links from gut microbes to cell type differentiation in the human brain have been virtually ignored despite overwhelming experimental evidence of the systems complexity manifested in all genera. Evolutionary theorists are largely responsible for the overwhelming ignorance of how cell type differentiation occurs because they have placed it into the context of mutations and evolution.
See, for example: Mutation-Driven Evolution, which was published on the same day as: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
Protein folding is biophysically constrained via RNA-mediated nutrient-dependent amino acid substitutions See also:

Published on 22 Oct 2013

For 50 years, the “protein folding problem” has been a major mystery. How does a miniature string-like chemical — the protein molecule – encode the functions of living organisms: how our muscles exert force, how our immune systems reject pathogens, how our eyes see our surroundings, how plants convert solar energy, and all the rest. Huge progress is being made. Moreover, these amazing nano-machines could play important roles in health and disease and commerce in the future.

Living the life that randomness created? (Sarcasm alert)

June 3, 2015

by James Kohl with No Comment Adaptations Ecology Light Energy Physics RNA Directed Variations

The Living Set

Mathematical and computational approaches are making strides in understanding how life might have emerged and organized itself from the basic chemistry of early Earth.

By Wim Hordijk | June 1, 2015

Excerpt:

Put some E. coli in a dish with appropriate nutrients, and after a few days the dish will be teeming with new bacterial offspring.

My comment: Put some genetically altered P. fluorescens in a dish and leave them “over-the-weekend” with their missing flagella over-the-weekend. Forget to remove them from the incubator and 4 days later learn they have “re-evolved” their missing flagella.
See: Evolutionary Rewiring. Try to convince serious scientists “re-evolved” flagella exemply how autocatalycic processes link ecological variation to ecological adaptations via mutations that perturb the thermodynamic cycles of protein biosynthesis and degradation. Parenthetically, the thermodynamic cycles link the nutrient-dependent physiology of reproduction to RNA-mediated cell type differentiation in all cell types of all individuals of all genera. See this 5.5 minute-long review.
SARCASM ALERT!
If you can successfully link mutations and evolution via a mathematical model, you can teach neo-Darwinian theory to unsuspecting students who may think you are teaching them more about biodiversity than they might otherwise have learned if they knew that: “[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. Assumptions, made but not verified, were taught as fact.”
Alternatively:

If a living system is indeed an autocatalytic set, then the next question to ask is whether an ecosystem, a network of interdependent organisms, can be considered an autocatalytic superset of autocatalytic subsets.

My comment: If you asked whether ecosystems evolved to link autocatalytic sets to cell type differentiation in in all cells of all individuals of all genera via anything except the natural selection of nutrients, you would find that Darwin answered that question when he warned others they must first consider his “conditions of life.” If you ignore the “conditions of life” on this planet, you can probably link everything to anything via definitions and mathematical models. However, teaching that pseudoscientific nonsense to students who are biologically informed will require you to show them experimental evidence that mathematical models have more explanatory power than models of how ecological variation lead to ecological adaptations. That happens in models of biologically-based cause and effect. Those models are being used by the serious scientists who are Combating Evolution to Fight Disease.
The Living Set cites: S. Kauffman, “Autocatalytic sets of proteins,” J Theor Biol, 119:1-24, 1986. It could also have cited: Prolegomenon to patterns in evolution. Kauffman has since gone on to help others learn that “…our scientific understanding of reality is radically incomplete, and that some sort of anti-entropy, order-generating force remains to be discovered.” When theoretical physicists and evolutionary theorists discover the anti-entropic epigenetic effects of the sun’s biological energy, they will discover what is missing from their ridiculous theories of emergence.
See also:

Early Code

New research points to key properties of transfer RNA molecules and amino acids that may have supported the origin of life on Earth.

By Jef Akst | June 3, 2015

Excerpt:

“Dr. Wolfenden established physical properties of the 20 amino acids, and we have found a link between those properties and the genetic code,” Carter said. “That link suggests to us that there was a second, earlier code that made possible the peptide-RNA interactions necessary to launch a selection process that we can envision creating the first life on Earth.”

My comment to The Scientist:

Simultaneous emergence was suggested by Matti Pitkanen who pirated my model of biophysically constrained RNA-mediated cell type differentiation and claimed that “Hens and eggs emerged simultaneously.”
Serious scientists now appear to have discovered the link from the light-induced de novo creation of amino acids to the de novo creation of receptors that link RNA-mediated amino acid substitutions to cell type differentiation in all cells of all individuals of genera via the nutrient-dependent chemistry of RNA-mediated protein folding.
The nutrient-dependent physiology of metabolic networks and genetic networks link reproduction to fixation of the amino acid substitutions, which enables all extant biophysically constrained biodiversity, which is exemplified in differences in morphological and behavioral phenotypes.
Claims of simultaneous emergence should be supported by experimental evidence of biologically-based cause and effect, or abandoned along with claims of Mutation-Driven Evolution, like this one: “…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)
For comparison, see: Nutrient-dependent/pheromone-controlled adaptive evolution: a model, which was published on the same day as Nei’s textbook.

Alternative splicings: epigenetics meets pharmacogenomics

May 27, 2015

by James Kohl with No Comment Adaptations Alternative Splicings Ecology Model Organisms Nutrigenomics Pharmacogenomics RNA Directed Variations

Alternative splicing [is] …a regulated process during gene expression that results in a single gene coding for multiple proteins… [T]he proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions….

Excerpt:

It now appears that alternative splicing is, perhaps, the most critical evolutionary factor determining the differences between human beings and other creatures.

Excerpt:

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

My comment: Sex differences in other species that are due to the alternative splicings of otherwise identical genes are linked to sex differences in cancers via RNA-mediated hormone-dependent cell type differentiation. Higher levels of estrogen are linked to ovarian cancer. Higher levels of testosterone are linked to prostrate cancer. Estrogen and testosterone levels are nutrient-dependent and pheromone-controlled in mammals. Nutrient stress and social stress probably contribute to all cancers and all other pathologies linked from metabolic networks to genetic networks.

Ovarian cancer-specific markers set the stage for early diagnosis, personalized treatments

Excerpts:

While DNA carries all the instructions necessary for life, its actual sequence contains much more than just the genes that code for proteins. In contrast, mRNAs are complementary copies of just the genes. They carry the recipe for every protein that the cell will produce from the nucleus to the cytoplasm, where cellular machinery can read the recipe and build the corresponding proteins.
the researchers identified six mRNA isoform molecules that have the tumor specificity required for an early detection diagnostic of ovarian cancer.
These mRNA isoforms are predicted to encode proteins with unique amino acid sequences…

My comment: The link from viral microRNAs and entropic elasticity to the anti-entropic epigenetic effects of nutrient-dependent microRNAs is becoming clearer. The nutrient-dependent microRNAs control RNA-mediated cell type differentiation via amino acid substitutions. That fact will come as a surprise to many people because scientists do not use terms consistently.
Some terms change when new information becomes available about links between protein structure and function. You may never again see our phrase “alternative splicing techniques of pre-mRNA” in the context of an epigenetic “mechanism” linked to RNA-mediated amino acid substitutions and cell type differentiation. Some terms change because researchers need to report something new to help ensure future funding. If they can turn a phase, or invent a new term, it may confuse people. But, researchers must “follow the money.”
You may see mRNA isoforms linked to amino acid substitutions and reported as “amino acid sequences” in the context of difference in corresponding proteins. You may still see claims that proteins evolve.
What you are less likely to see is any additional claims that “…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). You are more likely to see claims that “The expression of a gene is controlled by several other elements or factors such as microRNAs, transcribed small RNAs, and epigenetics.” Figure 6.1 (p. 114).
The claim on page 114 is made in the same book with the ridiculous conclusion about mutations on page 199. That is cause for concern. The book is Mutation-Driven Evolution and it was published 40 years after Dobzhansky (1973) noted 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” (p. 127).
It is now clear to many serious scientists that cell type differentiation is RNA-mediated via nutrient-dependent amino acid substitutions that stabilize the organized genomes of all genera via the fixation of the amino acid substitutions in the context of the physiology of reproduction.
It is also clear that evolutionary theorists would rather have you continue to believe in their ridiculous theories than to accept the fact that their theories are horrid misrepresentations of biological facts. The facts must be considered in the context of disease prevention and treatment. The ridiculous theories must be discarded.
See also: Noncoding RNAs that associate with YB-1 alter proliferation in prostate cancer cells, which was reported as:

Team finds two new and very large classes of RNAs linked to cancer biomarker

Excerpt:

Many small RNAs known as microRNAs already have been shown to correlate with different grades of prostate cancer and could potentially serve as biomarkers for diagnosis and treatment,” Dr. John said. “We did this study after computer models led us to hypothesize that there was a connection between YB-1 and microRNAs. What started out as a curiosity-driven experiment ended up being an exhilarating treasure hunt over four years, culminating in the discovery of two big molecular finds from human cells.

My comment: The balance of viral microRNAs and nutrient-dependent microRNAs links the microRNA/messenger RNA balance to:
1) sex differences in alternatively spliced mRNAs;
2) sex differences in their amino acid sequences;
3) sex differences in their biological functions;
and
4) sex differences in cancers.
Ovarian cancer biomarkers and prostate cancer biomarkers link similarities and differences in viral microRNAs and nutrient-dependent microRNAs to RNA-mediated sex difference in cell type differentiation. RNA-mediated sex differences in cell types are linked to RNA-mediated differences in all cell types of all individuals of all species via the conserved molecular mechanisms of biophysically constrained nutrient-dependent protein folding chemistry. Progress in cancer research will not come from the evolution industry or from ridiculous theories.

Epigenetic regulation of aging by glycine and GnRH

May 26, 2015

by James Kohl with No Comment Adaptations Alternative Splicings Diseases & Disorders Ecology Human Brain Human Pheromones Light Energy Model Organisms Neuronal Plasticity Nutrigenomics Pharmacogenomics Physics RNA Directed Variations

Summary: “…the regulation of two genes involved with the production of glycine, the smallest and simplest amino acid, is partly responsible for some of the characteristics of aging. This indicates that the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations.”
My comment: The broad-based extension of the fact that aging is epigenetically controlled, extends everything known about RNA-mediated cell type differentiation across the life history transitions of all genera. The focus here is on vertebrates, but the conserved molecular mechanisms extend across all species.
———————————
Thanks to Teresa Binstock for alerting me to this. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects
Excerpt:

Given that human aging can be seen as a consequence of a programmed phenomenon, it is possible that epigenetic regulation also controls human aging.

My comment: See: Search Results for ‘glycine’ here at RNA-mediated.com and also Search Results for: glycine in the “Science” section at Pheromones.com for additional information. It should become apparent why I started with the domain Pheromones.com in 1995 and linked nutrient-dependent RNA-mediated amino acid substitutions to cell type differentiation after addressing the control of nutrient-dependent reproduction. Others now realize that the physiology of reproduction biophysically constraints transgenerational epigenetic inheritance of morphological and behavioral phenotypes. The new information about the control of RNA-mediated cell type differentiation by pheromones and anti-aging medicine has been delayed for more than two decades by human pheromone-deniers and other pseudoscientists.
In 1994, for example: I presented “Olfactory-hormonal relationships in learning, memory, aging, and behavior” during the “2nd Annual Conference on Anti-aging Medicine & Biomedical Technology for the year 2010” and in 1995, I presented “Olfactory-genetic-neuronal-hormonal reciprocity in learning, memory, behavior and in immune function” at the “3rd Annual Conference on Anti-aging Medicine & Biomedical Technology for the year 2010.”
Teresa Binstock’s prescient contributions on RNA-mediated cell type differentiation in our 1996 Hormones and Behavior review article led me to examine the role of achiral glycine in vertebrates. See: From Fertilization to Adult Sexual Behavior
Excerpt:

Evolutionary conservation, both of pheromonal communication and its importance to behavior, is indicated by the involvement of a key mammalian reproductive hormone. For instance, a yeast pheromone, the alpha-mating factor, is very similar in structure to mammalian gonadotropic releasing hormone (GnRH). When injected into rats, this chemical binds to pituitary GnRH receptors and brings about the release of LH. Loumaye, Thorner, and Catt (1982) note: “GnRH and the yeast alpha-mating factor appear to represent a highly conserved effector system which includes the peptide ligand, the cell-surface receptor, and the physiological regulation of reproductive function” (p. 1325).

My comment: Substitution of the only achiral amino acid in the GnRH decapeptide of vertebrates links the light-induced de novo creation of glycine and other amino acids to the nutrient-dependent pheromone-controlled behaviors of species from microbes to humans. One need only consider that fact in the context of what is currently known about the biophysically constrained chemistry of RNA-mediated amino acid substitutions and protein folding in all genera.
1994 Abstract

The early prenatal migration of gonadotropin releasing hormone (GnRH) neurosecretory neurons appears to enable a neuroendocrine sequence of events that allows human pheromones to influence postnatal GnRH secretion, maturation of the hypothalamic-pituitary-gonadal axis; and, in part, the hypothalamic-pituitary-adrenal axis; hormone-dependent synaptogenesis and synaptolysis; neurotransmission; learning; memory; and behavior. That GnRH regulates the collective neural output manifest in reproductive behavior seems consistent with effects of drug therapies that influence the GnRH pulse, and which are used to treat disorders of neuroendocrine and reproductive maturation as well as dysfunctional behaviors. Is the hypothalamic GnRH pulse generator both the biologic and the psychologic core of mammalian reproduction? What is the contribution of extrahypothalamic GnRH? Is there a lack of “hard” scientific evidence for relationships between biologically relevant odors, olfaction, aging, and human behavior?

1995 Abstract

A five-step pathway allowing the social environment (“nurture”) to influence the genetic substrates (“nature”) of mammalian behavior is: gene->cell->tissue->organ->organ system. Though there are many environmental influences on the first step of this pathway, odors are the only known social-environmental stimuli that appear to activate gene expression in neurosecretory cells of tissue in the brain an organ that is essential to any organ system involved in learning, memory, and behavior. Olfaction appears to influence learning, memory, and behavior. Thus, the production and distribution of human odors may link two aspects of our social environment (e.g., olfaction and odors) to the genetic substrates of our behavior through a five-step pathway common to many other vertebrates. Olfactory input influences the gonadotropin-releasing hormone (GnRH)-directed regulation of gonadal and adrenal steroidogenesis. Thus, olfactory deficits associated with aging may be linked to a need for hormone replacement therapy, including dehydroepiandrosterone (DHEA). Similarly, olfactory deficits may be linked to immune system function. Many other hormones/neurotransmitters (e.g., melatonin and dopamine) feed back on the GnRH neuronal pathway. This pathway appears to be both the biological and the psychological core of mammalian, including human, behavior. Thus, the influence of odors and olfaction on levels of hormones, including neurotransmitters, may be linked to age-related changes in learning, memory, behavior, and immune system function.

2015

Scientists reverse aging in human cell lines and give theory of aging a new lease of life

Excerpts:

…the regulation of two genes involved with the production of glycine, the smallest and simplest amino acid, is partly responsible for some of the characteristics of aging.This indicates that the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations.

See for comparison: Mutation-Driven Evolution
Concluding sentences:

“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).

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

Concluding paragraph:

Unconscious affects that are manifested during the development of diversified life and human behavior are, by their very nature, part of life that few people think about (Kohl et al., 2001). Therefore, the largest contributor to the development of our personal preferences may be the unconscious epigenetic effects of food odors and pheromones on hormones that organize and activate behavior. If so, the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

My comment: All accurate representations of biologically-based cause and effect have consistently shown that there are no other factual representations of epigenesis and epistasis that can be compared to my model. The most recent report on glycine and cell type differentiation during the life history transitions of vertebrates also suggests that the honeybee model organism links nutrient-dependent base pair substitutions in yeasts to the RNA-mediated amino acid substitutions in vertebrates that differentiate nutrient-dependent pheromone-controlled cell types via the conserved molecular mechanism that Teresa Binstock detailed in the “molecular epigenetics” section of From Fertilization to Adult Sexual Behavior.

See also for comparison to published works by JW Locasale: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Excerpt:

Disease is associated with mutations exemplified in cancer where perturbations of the glucose-dependent thermodynamic/thermoregulatory equilibrium are equally clear (Locasale, 2012).

Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects

Excerpt:

Reprogramming of gene expression in elderly fibroblasts occurred in GCAT (Fig. 3b), which regulates glycine production in mitochondria^{17, 18}. It was therefore likely that reduced glycine production in mitochondria by epigenetic downregulation of GCAT (Fig. 3a) resulted in the age-associated respiration defects (Fig. 1a).

My comment: Reference 17, is Locasale, J. W. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 13, 572–583; doi:10.1038/nrc3557 (2013).
The barrage of pseudoscientific nonsense touted by evolutionary theorists and their idiot minions continues to test the patience of anyone who challenges ideas about cell type differentiation that link mutations to pathology and to aging, and RNA-mediated amino acid substitutions to health and longevity in all genera.
See for examples of nonsense touted by the biologically uninformed:
In evolution, ‘house of cards’ model wins
Tiny spheres of human cells mimic the brain, researchers say
Our bond with dogs may go back more than 27,000 years
John Glenn: Evolution should be taught in schools

Scent of Eros

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Scientists reverse aging in human cell lines and give theory of aging a new lease of life