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

The eternal significance of microRNAs (5)

Excerpt: Researchers in South Korea, for example, have reminded the God-less Communist dictator of North Korea that one microRNA-mediated amino acid substitution in the influenza B virus could decimate the human populations that he thinks he rules.
Conclusion: Conserved energy biophysically constrains viral latency.

Ridiculously ignorant objections to my publication in what others claim is a predatory journal can be compared to my objection to publication of this article in PNAS.

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk
1) They linked environmental selection to the frequency of the EDAR V370A variant in the mouse model via positive selection for modulation of thermoregulatory sweating.
2) They linked environmental selection to similarities in human populations in North Asia, East Asia, and the New World. But they virtually ignored the mouse model of food energy-dependent pheromone-controlled biophysically constrained ecological adaptation.
I linked the same food energy-dependent pheromone-controlled base pair change and microRNA-mediated fixation of the same amino acid substitution to all biodiversity in all living genera via feedback loops. See: Feedback loops link odor and pheromone signaling with reproduction

Others see what passes peer-review published in journals that support the expense of efforts made by pseudoscientists and other theorists, but they claim that the OMICS journals are predatory. I claim that pseudoscientists and other theorists do not know the difference between predation and sympatric speciation because they place predation into the context of evolved biodiversity.

For comparison see: Whole-genome sequencing of the blue whale and other rorquals finds signatures for introgressive gene flow

Reported as: Baleen Whale Genomes Point to Evolution With Gene Flow

Large baleen whales in the Balaenopteridae family (commonly known as rorqual whales) have undergone sympatric speciation — speciation without clear geographic barriers between them — despite ongoing hybridization, according to new research from investigators in Sweden and Germany.

System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes

Reported as:

“The patterns of synaptic connections perfectly mirror the fundamental differences in the feeding behaviours of P. pacificus and C. elegans”, Ralf Sommer concludes. A clear-cut result like that was not what he had necessarily expected.

Neo-Darwinian theorists and other biologically uniformed pseudoscientists have failed to use any common sense in attempts to link what organisms eat from the physiology of reproduction to biophysically constrained biodiversity.  For comparison, serious scientists have forced the denuclearization of North Korea by reminding others to start with what is known about how food energy-dependent autophagy protects all life on Earth from the virus-driven degradation of messenger RNA.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

…as a reviewer, it is tiresome to raise the same objections repeatedly, wondering why researchers have not fulfilled some of the basic requirements for establishing the occurrence of an autophagic process.

 …appropriate assays depend in part on the question being asked and the system being used.

Researchers in South Korea, for example, have reminded the God-less Communist dictator of North Korea that one microRNA-mediated amino acid substitution in the influenza B virus could decimate the human populations that he thinks he rules.

See: A Single Amino Acid at the Polymerase Acidic Protein Determines the Pathogenicity of Influenza B Viruses

Watering Young Plant - Vintage Effect

A single base change refutes theistic evolution

Everyone who failed to learn how light-activated endogenous substrates biophysically constrain viral latency is playing “catch up” to serious scientists. The serious scientists know how quantized energy-dependent RNA-mediated cell type differentiation occurs in the context of the physiology of reproduction in all living genera. Rather than accept the fact that the innate immune system of bacteria (CRISPR) linked the pheromone-controlled physiology of reproduction from autophagy to biophysically constrained viral latency, theorists decided to waste money on virus-assisted gene-editing attempts to repair virus-damaged DNA.

Mammoth Biosciences launches a CRISPR-powered search engine for disease detection

Jennifer Doudna, George Church and many others still refuse to admit that they have refuted theistic evolution. They are just beginning to accurately portray the how detection of changes in the microRNA/messenger RNA balance links virus-driven energy theft to the degradation of messenger RNA. Clearly, however, they know how the degradation of messenger RNA is linked to all pathology.

Had they followed the works of Christ et al. (2013), The Pharmacology of Regenerative Medicine and Christ et al., (2018) Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming, they could intelligently interact with those who are scheduled to present during Schrödinger at 75 – The Future of Biology – September 2018.

(Nick Lane excepted.) He appears to be a biologically uninformed theorist who does not realize that Fast food makes the immune system more aggressive in the long term

Unhealthy eating causes some of these normally hidden pieces of DNA to unwind, similar to a loop hanging out of a ball of wool. This area of the genetic material can then be read much easier as long as this temporary unwrapping remains active. Scientists call these phenomena epigenetic changes. “The inflammasome triggers such epigenetic changes,” explains Dr. Latz. “The immune system consequently reacts even to small stimuli with stronger inflammatory responses.”

The immune system reacts to the proliferation of viruses. The viruses cause the inflammation, which has been linked to all pathology in more than 72,500 published works. See microRNA.

See also: Field-deployable viral diagnostics using CRISPR-Cas13

…the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. We developed HUDSON (heating unextracted diagnostic samples to obliterate nucleases), a protocol that pairs with SHERLOCK for viral detection directly from bodily fluids, enabling instrument-free DENV detection directly from patient samples in <2 hours. We further demonstrate that SHERLOCK can distinguish the four DENV serotypes, as well as region-specific strains of ZIKV from the 2015–2016 pandemic. Finally, we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.

Pardis C. Sabeti’s group already linked the anti-entropic virucidal energy of sunlight from the creation of enzymes to natural selection for energy-dependent codon optimality via the pheromone-controlled stability of organized genomes in a human population in what is now Central China.
See this report from 2013 on fixation of the EDAR V370A substitution.
Following the footprints of positive selection February 15th, 2013.
For comparison to positive selection for food and fixation of the EDAR V370A amino acid substitution, the pseudoscientific nonsense about evolution touted by Pardis C. Sabeti’s group appears in this YouTube video report: 2 Cell Studies Reveal Genetic Variation Driving Human Evolution
In the mouse model of food energy-dependent pheromone-controlled ecological adaptations, they replaced the valine normally found in mouse EDAR with the alanine that’s under selection in humans. They got mice with thicker hair, changes in mammary tissue, and and increased  number of eccrine sweat glands. Those changes parallel phenotypic changes in humans. The phenotypic changes in humans link the quantized energy-dependent creation of microRNAs to biophysically constrained viral latency in all living genera.
In humans, the changes are linked to visual perception of mass and energy and the perception of physical features that are sexually selected.
See: Olfaction Warps Visual Time Perception
A single base change results in the valine to alanine substitution, which changes the ancient mammalian gene EDAR and the EDAR encoded protein.
That fact was reported in the context of links from subatomic particles and all levels of biophysically constrained viral latency and biological organization in my 2014 invited review of nutritional epigenetics.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (unpublished)
Conclusion:

The ecological adaptations, which appear to be manifested in the human population are detailed in these two reports [162-163]. The ecological adaptations are likely to be nutrient-dependent and pheromone-controlled. If so, ecological variation probably leads to ecological, social, neurogenic, and socio-cognitive niche construction, which is manifested in increasing organismal complexity and species diversity. If not, there may be something as yet unknown about mutations and evolution that makes sense in the light of what is known about nutritional epigenetics and the molecular biology of species from microbes to man

162. Kamberov, Yana G.; Wang, S.; Tan, J.; Gerbault, P.; Wark, A.; Tan, L.; Yang, Y.; Li, S.; Tang, K.; Chen, H., et al., Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. Cell 2013, 152 (4), 691-702. doi: 10.1016/j.cell.2013.01.016
163. Grossman, Sharon R.; Andersen, Kristian G.; Shlyakhter, I.; Tabrizi, S.; Winnicki, S.; Yen, A.; Park, Daniel J.; Griesemer, D.; Karlsson, Elinor K.; Wong, Sunny H., et al., Identifying Recent Adaptations in Large-Scale Genomic Data. Cell 2013, 152 (4), 703-713. doi: 10.1016/j.cell.2013.01.035
See also:
161. Rosenberg, S. M.; Queitsch, C., Combating Evolution to Fight Disease. Science 2014, 343 (6175), 1088-1089. doi: 10.1126/science.1247472
Kalevi Kull: Censorship & Royal Society Evo Event

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

Serious scientists from South Korea are the winners. Two recent publications forced the denuclearization of North Korea.
Emergence of Human G2P[4] Rotaviruses in the Post-vaccination Era in South Korea: Footprints of Multiple Interspecies Re-assortment Events

Compared to the G2 RotaTeq vaccine strain, 17-24 amino acid changes, specifically A87T, D96N, S213D, and S242N substitutions in G2 epitopes, were observed. These results suggest that multiple interspecies re-assortment events might have contributed to the emergence of G2P[4] rotaviruses in the post-vaccination era in South Korea.

A Single Amino Acid at the Polymerase Acidic Protein Determines the Pathogenicity of Influenza B Viruses

When analyzed using reverse-genetically rescued viruses, it was shown that PA K338R alone could increase the pathogenicity of both IBVs in mice and viral replication property in the respiratory tracts of ferrets. In a subsequent mini-replicon assay, the effect of PA K338R was highlighted by the enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01 viruses. These results suggest that the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs.

Mutations are known to be the molecular determinants of all pathology in species from microbes to humans. See:  Virus-mediated archaeal hecatomb in the deep seafloor
Watch as Hashem Al-Ghaili puts everything known to serious scientists about the virus-mediated archaeal hecatomb back into the context of neo-Darwinian evolution.

See also: Study offers new approach to starve p53 deficient tumors

One major hallmark of cancer cells is their ability to adapt to stressful conditions such as nutrient deprivation. Rapidly growing tumor cells must compete for the ever-diminishing supply of nutrients in the surrounding environment to survive and proliferate. Targeting these adaptive mechanisms represents a promising approach for cancer therapeutics.

It’s a little late to claim that the virus-driven theft of quantized energy is linked from autophagy to adaptations in viruses. All serious scientists know that food energy-dependent pheromone-controlled biophysically constrained autophagy has been linked to viral latency and to ecological adaptations in all living genera. Intelligent people know that viruses have been linked to all pathology.
See also: From Istanbul, Turkey. Respect for all human life has been placed into the context of the energy-dependent de novo creation of microRNAs and the works of an Islamic creationist in Turkey.

Autophagy-Regulating microRNAs and Cancer
Cancer researchers in other countries clearly are approaching the cure for all pathology from a scientific creationist perspective despite being forced to place their claims into the context of evolution to get their works past peer review.
The Trump administration has been working towards world peace with other leaders for more than a year. See for example:
May 3, 2017
LIVE: President Donald J. Trump and Palestinian President Mahmoud Abbas make a joint statement at the White House.
Who does not want World Peace? Why The End of the Korean War Is Bad News for the United States
5th-6th Sept 2018 Dublin, Ireland

Nutrient-dependent pheromone-controlled feedback loops

Summary: The link from positive selection to one food energy-dependent base pair change and fixation of the mouse-model-to-human-specific EDAR V370A allele in populations on different continents attests to sympatric speciation at every level of examination that refutes the pseudoscientific nonsense of neo-Darwinian mutation-driven evolution.

Reported on 5/3/18 as: SWAT team of immune cells found in mother’s milk 

1)

“There is a feedback loop,” says Yu. It’s known that some immune cells like leucocytes, another white blood cell that fights infection, increase in the milk in response to an infection in the baby.

2)

…the largest immune cell population in breast milk is macrophages, which ILCs are known to direct. Macrophages, which literally means ‘big eaters,” are the largest of the white blood cells and much-better studied than ILCs. They are known for their ability to envelop unwanted items like bacteria, viruses…

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk 4/23/18

The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers’ milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.

Reported as: Gene linked to breastfeeding may have boosted survival of earliest Americans (4/23/18)

…they carried a genetic mutation—revealed in ancient teeth—that boosted the development of milk ducts in women’s breasts, which may have helped nursing mothers pass more nutrients to their infants.

The obvious link from infant nutrition to healthy longevity was reported in the context of a ridiculous gene-centric theory of species survival. Gene-centric theories are all that pseudoscientists have left. They use them to hold back the scientific progress made by serious scientists like those who reported this:
Feedback loops link odor and pheromone signaling with reproduction (2005)

These results may reflect a strategy wherein GnRH neurons can modify diverse functions in order to coordinate the internal state of the animal and its behavior with reproduction in order to optimize reproductive success.

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

EDAR V370A and sympatric speciation

Nick Lane and others like him refuse to reappraise their human mitochondrial DNA recombination dogma. All serious scientists know where the energy for recombination comes from. But, in his latest video clip, he touts the same unsubstantiated theoretical pseudoscientific nonsense.

See the: Aeon Video:

Life on earth – from mushrooms to humans and everything in between – seems enormously diverse. At the cellular level, however, almost all complex lifeforms are surprisingly similar. Why life is this way, though, remains mysterious. In this Aeon interview, the UK biochemist and author Nick Lane discusses his research on the connection between energy and genes, which, he hypothesises, made possible the radical transformation from single-celled organisms to complex life about 4 billion years ago.

See for comparison: Reappraising the human mitochondrial DNA recombination dogma

I’ve asked the authors: Are you prepared to address the comments that you might receive from people like Nick Lane in the context of “peer review?” How will you respond to those who do not accept the fact that the creation of ATP synthase and the creation of ATP must be linked to the creation of RNA and biophysically constrained viral latency in the context of SNPs and fixation of amino acid substitutions? What can be done when biologically uninformed theorists continue to link anything except biophysically constrained viral latency to all biodiversity?

I ask because there are still too many examples of human idiocy that are being considered outside the context of facts about energy-dependent RNA-mediated cell type differentiation.

See: Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant

See the claims about the selection of the EDAR variant placed back into the context of evolution.

Field-deployable viral diagnostics using CRISPR-Cas13

…we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.

The relevant energy-dependent single-nucleotide polymorphisms clearly protect all living genera from the clinically relevant viral single-nucleotide polymorphisms. The viral single-nucleotide polymorphisms link the virus-driven degradation of messenger RNA to all pathology via what is known to all serious scientists about the energy-dependent creation of the innate immune system in species from bacteria to humans.

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago.

If any experimental evidence of biophysically constrained viral latency supported the claim about positive selection 20,000 y ago, it could be linked to Nick Lane’s claims about how chimeras and electricity allowed a sterile planet to give way to complex life 4 billion years ago. Since there is no experimental evidence to support his ridiculous theories, intelligent people may want to continue to link environmental selection from food selection to the physiology of reproduction and fixation of RNA-mediated amino acid substitutions such as V370A that stabilize the organized genomes of all species on Earth.

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

Exome Sequencing Impact in Routine Care

Summary: They placed the pseudoscientific nonsense about selection for beneficial mutations into the context of positive selection for mutations, which are caused by the virus-driven degradation of messenger RNA. The mutations have been linked to all pathology. It’s as if all theorists want to become known as “biologically uninformed science idiots” via their associations with others who have touted claims about “beneficial mutations.”

US Air Force Studying Impact of Exome Sequencing in Routine Care

Who, among my fellow veterans, and especially among others from The American Legion and The American Legion Riders, did not anticipate that the US Air Force would lead the way forward to prevention of all virus-driven pathology via the use of this technology?

The doctors will receive an educational primer in genomics and on-site genetic counseling support. After exome testing is performed on patients, their doctors will get a report listing the pathogenic and likely pathogenic variants related to dominant and recessive monogenic conditions, risks for complex diseases, and response to drugs. These results will be entered into the service members’ electronic medical records.

I was trained to become a medial laboratory scientist during the last 4 years of my 7 years in the United States Air Force (Dec. 1970-Aug. 1977).  I worked in the laboratory and examined the experimental evidence reported in published works, I learned that all pathogenic variants are caused by the virus-driven degradation of messenger RNA. I also learned that pharmacogenomic profiles have already been linked to effective treatments for virus-driven energy theft via my model of nutrient-dependent pheromone-controlled biodiversity.
See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
Conclusion:

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

My model refuted every aspect of neo-Darwinian pseudoscientific nonsense, which may be why some doctors never heard about it, or why some of them don’t want to admit to what they know about effective treatments for all pathology.
During suicide prevention month, the National Commander of the American Legion focused on efforts to help reduce the number of suicides among veterans, which occur at ~ 22 each day. I was surprised to see how little response from the general public there has been since then. It’s as if no one has learned about experimental evidence of biologically-based cause and effect such as this:
Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity

Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorders.

The only obvious link from from energy-dependent ATPase activity to cell type function in all cell types of all living genera is the anti-entropic virucidal energy of sunlight, which biophysically constrains viral latency in the context of the pheromone-controlled physiology of reproduction. That fact suggests exome sequencing data must be linked to routine case via the creation of energy, the creation of ATP and the creation of RNA.
See: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation”

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

If the role of microRNAs is not examined in the context of virus-driven energy theft, the degradation of messenger RNA cannot be linked to all pathology. The suicide rate may never change, or it may not change until the virus-driven degradation of messenger RNA is linked to cancer and all other pathology in species from microbes to humans.
See also: exome sequencing microRNA  for examples like this:
Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer.
If you do not agree that exome sequencing is the key to understanding the difference between energy-dependent healthy longevity and virus-driven pathology, please explain what you don’t like about the scientific approach to effective treatment and/or prevention of all pathology in the context of Precision Medicine.
See also: Energy as information and constrained endogenous RNA interference from the Labroots: Precision Medicine Virtual Conference February 22-23. 2017
Narrative: The term microRNA has been used in 58,000 indexed works. All the works support claims that link the anti-entropic virucidal energy of sunlight from endogenous RNA interference to biophysically constrained protein folding chemistry and cell type differentiation.

Abstract:

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

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

This detailed representation of energy-dependent natural selection for codon optimality links biologically- based cause and effect from G protein-coupled receptors to RNA-mediated amino acid substitutions and the functional structure of supercoiled DNA. Energy-dependent polycombic ecological adaptations are manifested in supercoiled DNA. Chromosomal inheritance links the adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes.

For contrast, virus-driven energy theft is the link from messenger RNA degradation to negative supercoiling, constraint breaking mutations, and hecatombic evolution. The viral hecatomb links transgenerational epigenetic inheritance from archaea to Zika virus-damaged DNA, which typically is repaired by endogenous RNA interference and fixation of RNA-mediated amino acid substitutions in organized genomes.

See for comparison: Evolutionary Analysis Reveals Number, Nature of Mutations Under Positive Selection in Cancer

The research shows that “across cancer types a relatively consistent small number of mutated genes is required to convert a single normal cell into a cancer cell, but that the specific genes chosen differ according to cancer type,” Sanger Institute Director Michael Stratton, a co-author on the study, said in a statement.

…the researchers identified almost 200 mutated genes under positive selection in cancer — a collection that included known cancer contributors and genes not previously implicated as cancer driver candidates.

They placed the pseudoscientific nonsense about selection for beneficial mutations into the context of positive selection for mutations, which are caused by the virus-driven degradation of messenger RNA. The mutations have been linked to all pathology. It’s as if all theorists want to become known as “biologically uninformed science idiots” via their associations with others who have touted claims about “beneficial mutations.”

rp_tumblr_ngykp0yfND1r5gzz6o1_500.jpg

Energy-dependent epigenetic translation to mRNA stability

Negative selection in humans and fruit flies involves synergistic epistasis

Negative selection against deleterious alleles produced by mutation influences within-population variation as the most pervasive form of natural selection.

Naturally occurring positive selection for energy-dependent codon optimality replaced every aspect of neo-Darwinian theories that linked natural selection from mutations to evolution of increasing organismal complexity. Positive selection for epigenetically-effected beneficial alleles links the epigenetic landscape to the physical landscape of supercoiled DNA via nutrient-dependent pheromone-controlled metabolic networks and genetic networks.
Everything from atoms to ecosystems was included in this invited review of nutritional epigenetics because all serious scientists know that organisms survive on food energy and that species exemplify the pheromone-controlled reproduction and chromosomal inheritance that ensures survival of all living genera.
See: 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.

See also: Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain

This interactome points to functional miRNA:target pairs across >3,000 genes and represents a valuable resource for accelerating our understanding of miRNA functions in brain. We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics.

See also: Connections Underlying Translation and mRNA Stability

…intimate connections between mRNA and the ribosome can drive biological regulation. In closing, we consider the likelihood that these connections between protein synthesis and mRNA stability are widespread or whether other modes of regulation dominate the mRNA stability landscape in higher organisms.

No experimental evidence of evolution includes biophysically constrained biologically-based cause and effect, which integrates the required link from ecological variation to the physics, chemistry, and molecular epigenetics of what Darwin presciently linked from his “conditions of life” to ecological adaption via energy-dependent changes in messenger RNA (mRNA).
See also: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition (with my emphasis)

…the ribosome interprets two codes within the mRNA: the genetic code which specifies the amino acid sequence and a conserved “codon optimality code” that shapes mRNA stability and translation efficiency across vertebrates.

Natural selection for energy-dependent codon optimality conserves the amino acid substitutions in the context of the stability of supercoiled DNA. That stability protects all organized genomes from virus-driven energy theft and genomic entropy. Protection from viruses occurs via the pheromone-controlled biophysically constrained physiology of reproduction in all living genera. Experimental evidence of that fact was included in our section on molecular epigenetics from this 1996 Hormones and Behavior review.
From Fertilization to Adult Sexual Behavior

Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus (Runge and Zakian, 1996; Wu and Haber, 1995).

See for comparison: Tracing the Enterococci from Paleozoic Origins to the Hospital

Host energy-dependent speciation

Graphical abstract from “Tracing the Enterococci from Paleozoic Origins to the Hospital”

Reported as: Enterococci may have evolved antimicrobial resistance millions of years ago

…researchers have traced evidence of the bacteria’s evolutionary history back 425 million years and theorize that the same traits that allow the bacteria to thrive in hospitals likely emerged when they were carried onto land in the guts of the world’s first terrestrial animals. The study was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The physiology of reproduction in bacteria and all other living genera is nutrient-dependent and pheromone-controlled. Researchers who think they have traced evidence back to the bacteria’s evolutionary history across 425 million years have not considered the weekend resurrection of the bacterial flagellum to be proof of their pseudoscientific nonsense. Instead, they report “Speciation: Host energy source driven” in their graphical abstract.
Where did the energy come from?
See: Evolutionary Rewiring
The nutrient-dependent pheromone-controlled physiology of reproduction in P. fliuorescens was linked to the weekend evolution of the bacterial flagellum.
See also for an invertebrate example of nutrient energy-dependent pheromone-controlled top-down causation: Inhibition of miR-274-3p increases BmCPV replication by regulating the expression of BmCPV NS5 gene in Bombyx mori  From: Virus Genes. 2017 May 10. doi: 10.1007/s11262-017-1466-7
See also: Two fatty acyl reductases involved in moth pheromone biosynthesis

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.

Facts about pheromones in species from microbes to humans have now been placed into their proper context.
Poor human olfaction is a 19th-century myth, which was reported as: “The human sense of smell: It’s stronger than we think” May 11, 2017
See for comparison: Human pheromones: integrating neuroendocrinology and ethology

The ‘affective primacy hypothesis’ [5] asserts that positive and negative affective reactions can be evoked with minimal stimulus input and virtually no cognitive processing. Olfactory signals seem to induce emotional reactions whether or not a chemical stimulus is consciously perceived. We theorize that the importance of human non-verbal signals is based upon information processing, which occurs in the limbic system, and without any cognitive (cortical) assessment. Affect thus does not require conscious interpretation of signal content. Underlying this fact is that affect dominates social interaction and it is the major currency in social interactions [6]. Affective reactions can occur without extensive perceptual and cognitive encoding. They are made with greater confidence than cognitive judgments, and can be made sooner [5, 7]. Olfactory input from the social environment is well adapted to fit such assertions. For example, chemical cues allow humans to select for, and to mate for, traits of reproductive fitness that cannot be assessed simply from visual cues.

See also: The RNA Age: A Primer
What is currently known about energy-dependent biophysically constrained RNA-mediated cell type differentiation refutes every aspect of neo-Darwinian evolution by placing natural selection for codon optimality and the pheromone-controlled physiology of reproduction first.
All published works and reviews of RNA-mediated events must be placed into the context of the paradigm shift that led to the development of this game.
Cytosis: A Cell Biology Game

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

Some researches may continue to ignore details about energy-dependent RNA-mediated protection from virus-driven energy theft; the degradation of messenger RNA; and the pathology that is linked from mutations to the loss of enzymes, hormones and receptors in all living genera.
Others will obfuscate what is known to serious scientists.
See for comparison: Ontological Systems In Cognition

There is investigated the possibility of cognition of everything that somehow and other is able to influence to the cognizer – its Existing, which exists for him and may be cognized by him. It is proved that all parts of the Existing are interconnected, it is closed and is the only one for all cognizers in it, and everything differed from the Existing is indistinguishable for the cognizer from non-Existing and cannot be cognized by him. It is shown that the surrounding world of the cognizer, understood as a collection of objects and interconnections identified by him, corresponds to the cognizer’s `nature’ – its ontology and are only a part of the Existing. Objects and interconnections of different ontology differ from each other on level of notions, so are uncertain, inconsistent and paradoxical in relation to each other, and corresponding systems of representations with definite ontology cannot be unified in frames of one system, so are irredundant with each other. There are found the correlations of physical objects of quantum theories, also as cosmological dark matter and dark energy with objects with different ontology. There are analyzed the methods of mathematical description of objects with different ontology, the so-called `correlation principle’ of physical theories in irredundant systems of representations, the `principle of freedom’ for formation of the universe understood as the surrounding world of the cognizer. There are considered the philosophical aspects of the existence of irredundant representations, the physical picture of the world, which this concept leads to. The surrounding worlds corresponding to irredundant representation systems, being parts of the one Existing, are closely interconnected, mutually complemented and form each other, without mixing and being different `by nature’, and contradictions between them stand as moving forces of their evolution.

All aspects of anything that has ever been linked to the “moving forces” of evolution have clearly been linked from food energy and movement to biodiversity and from stress-related virus-driven energy theft to mutations that link the lack of movement at the molecular level to all pathology.
See for instance: Valerie Horsley Gets Under Skin

The Yale University cell and molecular biologist is probing the deep mysteries of epidermal cells.

My comment:
See also: Brain on stress: How the social environment gets under the skin

The authors note that on page 17184, right column, first paragraph, line 4, “effect” should instead appear as “affect.”

The failure to provide a neurobiological framework for understanding natural selection for energy-dependent codon optimality, which is the basis for the biological embedding of epigenetically-effected positive health, positive affect, self-efficacy and self-esteem via effects on reactive alleles in the genome, continues to link all pathology from the virus-driven degradation of messenger RNA to the negative supercoiling of DNA.
No one asked me to establish that framework for healthy longevity or pathology, but I did it anyway after I was told to start with gene activation in GnRH neuroscrectory neurons by Bruce McEwen.
See also: Genome Digest

What researchers are learning as they sequence, map, and decode species’ genomes

The researchers found that genes involved in key survival functions, such as the removal of cellular toxins, the stabilization of proteins, and the activity of the innate immune system, were expanded in deep-sea mussels.

Anna Di Cosmo’s group presciently placed these finding into the context of General and Comparative Endocrinology in Role of olfaction in Octopus vulgaris reproduction
From the concluding paragraph:

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). — p. 61

The fact that the energy-dependent stability of RNA-mediated protein folding chemistry links physics from autophagy to biophysically constrained viral latency went missing during the past 4 years, but is not likely to continue to be ignored.
See why: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
Conclusion:

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

There is still no other model for comparison, despite the publication of Mutation-Driven Evolution on the same day my 2013 review was published.

(1) Mutation is the source of all genetic variation on which any form of evolution is dependent. Mutation is the change of genomic structure and includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc. (2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation.

That claim differentiates ridiculous theories from my model of biophysically constrained biologically-based cause and effect. The differences were noted in 1991 when Roger Penrose wrote:

How often do we still hear that quantum effects can have little relevance in the study of biology, or even that we eat food in order to gain energy? – From What is Life? (reprint edition)

See also: The Latest Discovery In Quantum Physics Shows Reality Is Not What It Seems

New experiments and studies conducted in laboratories such as CERN seem to suggest that everything is actually composed of energy rather than material particles, including human beings.
fruit-dove

Nothing evolved into all biodiversity on Earth

Ricki Lewis introduces more confusion into the question about “Wwhich came first, the chicken or the egg. She uses the evolved chicken to make chicken soup.”

Did Christianity Speed Chicken Evolution? by Ricki Lewis.

The selected genes encode the thyroid-stimulating hormone receptor (TSHR) and β-carotene dioxygenase 2 (BCDO2). Their DNA sequences echo positive selection: mutation changing an amino acid from the ancestral to the derived species.

Ricki Lewis is a science writer with a PhD in genetics. She defined positive selection as “mutation changing an amino acid from the ancestral to the derived species”  which suggests that she believe mutation-driven changes in amino acids can be linked to the evolutionary history of birds during the past 6000 years. She may also believe in other aspects of Mutation-Driven Evolution.

See for comparison: Biologists use genomics to identify evolving new bird species in southern Idaho

The South Hills crossbill, potentially a newly discovered species of finch, has evolved over the past 6,000 years with a unique dependence on its food source, the Rocky Mountain lodgepole pine, in a coevolutionary arms race that also changed the tree….

See also: The seeds of speciation

…it’s not been clear whether South Hills crossbills are genetically isolated by coevolution with pine in that one tile of the mosaic. If they are, the birds’ adaptation to the tree’s defenses might be setting the South Hills crossbills on the road to the origin of a new species.

John Brunstein may help to rescue us from the pseudoscientific nonsense touted by theoretical physicists and other theorists, like Ricki Lewis, who would like serious scientists to believe that one species can evolve into another species by eating different seeds.

See: Back to Basics: RNA molecular diagnostics

John Brunstein, PhD, is the President and Chief Science Officer for British Columbia-based PathoID, Inc., which provides consulting for development and validation of molecular assays. Ricki Lewis, and others like her, can ignore everything known to serious scientists about nutrient energy-dependent RNA-mediated biophysically constrained biologically-based biodiversity. People who validate molecular assays cannot ignore facts like this one:

…one base in RNA (uracil) is functionally replaced by another in DNA (thymine). The difference between these bases is a single methyl (-CH3) group present on thymine but absent in uracil.”

John Brunstein consistently places energy-dependent changes in base pairs into the context of RNA-mediated events. The RNA-mediated events link sunlight and ATP from the biosynthesis of RNA to energy-dependent RNA methylation, which must link energy-dependent RNA-directed DNA methylation to all biodiversity via fixation of amino acid substitutions in supercoiled DNA. Facts about RNA-directed DNA methylation, supercoiled DNA, and all biodiversity link feedback loops from odor and pheromones to the physiology of reproduction, which biophysically constrains all biodiversity. See: Feedback loops link odor and pheromone signaling with reproduction See also: Combating Evolution to Fight Disease

See for comparison: Microbiology, molecular, MALDI-TOF, or all of the above?

My summary: Serious scientists know that some multiplexing PCR systems identify unique sequences of nucleotides associated with virus-driven energy theft and dominant types of antibiotic resistance, such as methicillin, vancomycin, and carbapenem resistance. The serious scientists link energy-dependent changes in angstroms to ecosystems in all genera at the same time that others are touting catchy phrases like “Functional Medicine” and “Evolutionary Medicine.”

See Structural diversity of supercoiled DNA. See for comparison, the recipe for chicken soup provided by Ricki Lewis in Did Christianity Speed Chicken Evolution?

While I’m not an expert in Christianity or math, or even Judaism, I do know how to make Jewish chicken soup.

Ricki Lewis clearly used the advantage of touting pseudoscientific nonsense outside the context of what is known about biophysically constrained energy-dependent changes in base pairs. Ricki Lewis simply ignores the fact that energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solution prevent the degradation of messenger RNA, which links mutations to all pathology. That fact has been placed into the context of quantum thermodynamics and information theory in another attempt to daze and confuse those who do not know that energy is information.

What he likes about quantum thermodynamics is that “you have these two fundamental quantities — energy and quantum information — and these two things meet together. — The Quantum Thermodynamics Revolution: information theory

First, information theory separates energy and quantum information. When information theorists claim to put the two things back together, the reassert the pseudoscientific nonsense that led them to separate energy as information into energy and information. For example, food energy as information is not considered by pseudoscientists and other theorists who want to keep their ridiculous theories about the emergence of everything from nothing before everything that automagically emerged evolved into all the biodiversity on Earth.

Autophagy is energy-dependent and RNA-mediated.

See for comparison: Autophagy-Regulating microRNAs and Cancer

My summary: The conserved cellular recycling pathway is nutrient energy-dependent and pheromone-controlled. No experimental evidence of biologically-based cause and effect suggests this pathway is “evolutionary conserved.” Nothing known about biophysical constraints suggests that it automagically evolved to be conserved.  The inference of a link between evolution and energy-dependent autophagy is another example of how much psedoscientific nonsense is included. Serious scientists should not need to mention evolution in their examples of natural selection for energy-dependent codon optimality, which is exemplified in the context of changes in the microRNA/messenger RNA balance. Serious scientists may need to consistently mention that virus-driven energy theft links the degradation of messenger RNA to all pathology in all living genera.

See also: The role of autophagy in hepatocellular carcinoma: friend or foe

…unbalanced autophagy will contribute to carcinoma cell survival under tumor microenvironment and in turn promote tumor growth and development.

Unbalanced autophagy does not link evolution from the emergence of energy to all biodiversity on Earth. Positive selection does not link mutations from amino acid substitutions in an ancestral species to substitutions in the derived species. RNA-mediated amino acid substitutions arethe nutrient-dependent pheromone-controlled ecological adaptations that link RNA biosynthesis to all energy-dependent biodiversity.

See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
See also: Cytosis: A Cell Biology Game

Cytosis is a worker placement game that takes place inside a Human Cell! Players utilize the organelles within a cell to collect cellular resources such as mRNA from the Nucleus, Lipids from the Smooth E.R., ATP from the Mitochondria, etc. and score points when they use these resources to complete Hormones, Receptors or Enzymes! 2 to 5 Players, Ages 10 +, Plays in 50 to 75 mins – (Shipping Aug/Sept 2017 – US, EU, CA & AU will ship from WITHIN their country / region)