5th-6th Sept 2018 Dublin, Ireland

The eternal significance of microRNAs (8)

Use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation and aging has been replaced by the use of model systems of biological processes.  Biological processes can be compared to so-called “evolutionary processes” to show that only biological processes need to be considered in the context of Darwin’s “conditions of life” or answers to the the question  What is Life? Schrödinger (1944).
K. L. Mettinger et al. (eds.), Exosomes, Stem Cells and MicroRNA, Advances in Experimental Medicine and Biology 1056, https://doi.org/10.1007/978-3-319-74470-4_6

This volume provides insight into the pivotal roles of stem cells, exosomes and other microvesicles in biofunction and molecular mechanisms and their therapeutic potential in translational nanomedicine. It further highlights evidence from recent studies as to how stem cell derived exosomes and microRNAs may restore and maintain tissue homeostasis, enable cells to recover critical cellular functions and begin repair regeneration.

Chapter 2 The Emerging Roles of microRNAs in Stem Cell Aging

involved in many biological processes such as developmental timing, differentiation, cell death, stem cell proliferation and differentiation, immune response, aging and cancer. Accumulating studies in recent years suggest that miRNAs play crucial roles in stem cell division and differentiation. In the present chapter, we present a brief overview of these studies and discuss their contributions toward our understanding of the importance of miRNAs in normal and aged stem cell function in various model systems.

Chapter 6  MicroRNAs, Regulatory Messengers Inside and Outside Cancer Cells

…like hormones, miRNAs can be secreted and regulate gene expression in recipient cells. Altered expression levels of miRNAs in cancer cells determine the acquisition of fundamental biological capabilities (hallmarks of cancer) responsible for the development and progression of the disease.

Model systems link the energy-dependent creation of microRNAs from microRNA biogenesis to the regulation of all cancer hallmarks. The virus-driven degradation of messenger RNA has been linked to all cancers and all other pathology in species from microbes to humans. Natural selection for energy-dependent codon optimality has been linked to healthy longevity.
See: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition
See for comparison:  The Neutral Theory in Light of Natural Selection May 2, 2018

…50 years after its introduction by Kimura. We argue that the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality. The ubiquity of adaptive variation both within and between species means that a more comprehensive theory of molecular evolution must be sought.

The ubiquity of adaptive variation attests to the facts about how the creation of quantized energy is linked to biophysically constrained viral latency. Adaptive variation links energy-dependent changes from angstroms to ecosystems in all living genera  via the physiology of their food energy-dependent pheromone-controlled reproduction.

For comparison to mRNA stability during the maternal-to-zygotic transition, see: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

The energy-dependent molecular mechanisms of recombination clearly link microRNA biogenesis to the stability of organized genomes during the life histories of all genera. Serious scientists object to the use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation.

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

…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.

 

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

Kohl's Laws of Biology (codon-optimality revisited)

Summary: Kohl’s Laws help to explain what was missing from Darwin’s ‘conditions of life.’ Darwin knew nothing about genetics, which means he knew nothing about the epigenetic effects of food odors or pheromones.
Ancient hepatitis B viruses from the Bronze Age to the Medieval period 5/7/18

We provide evidence for the creation of HBV genotype A via recombination, and for a long-term association of modern HBV genotypes with humans, including the discovery of a human genotype that is now extinct. These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone.

The complexity of biophysically constrained viral latency in all living genera refutes all pseudoscientific nonsense touted by neo-Darwinian theorists and Big Bang cosmologists.
See for example: Who were the Neanderthals? 5/5/18

Current evidence from both fossils and DNA suggests that Neanderthal and modern human lineages separated at least 500,000 years ago. Some genetic calibrations place their divergence at about 650,000 years ago.

No serious scientists believe in the nonsense that links genetic calibrations to “divergence” at about 650,000 years ago.
See for comparison: Efficient coding explains the universal law of generalization in human perception 5/11/18
Everything known to serious scientists about natural selection for energy-dependent codon optimality and RNA-mediated DNA repair is placed back into the context of evolution, which is subject to constraints (finding food and reproduction).
See also: Olfaction Warps Visual Time Perception (2017)
The creation of visual perception starts with the energy-dependent creation of enzymes.

High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane 5/11/18

…the enzyme transduces the energy of a proton gradient, generated by the electron transport chain, into the major energy currency of the cell, ATP.

The quantized energy-dependent creation of the enzyme was linked to the creation of ATP and RNA
Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)

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

Natural selection interacts with recombination to shape the evolution of hybrid genomes 5/11/18

Hybridization is an important force in evolution.

That is a ridiculous assumption. Quantized energy is an important force in ecological adaptation. That is a fact.

Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis 5/11/18

Competition between the NAD+ precursors—nuclear NMNAT-1 and cytosolic NMNAT-2…, regulates the balance between nuclear NAD+ synthesis for adipogenic gene regulation and cytosolic NAD+ synthesis used in metabolism.

Every aspect of what is currently know about life on Earth begins with the creation of quantized energy.
Energy efficiency drives the global seasonal distribution of birds 5/7/18
Reported as: A Thermodynamic Answer to Why Birds Migrate 5/7/18

…research makes a forceful argument that energy supply and demand is a driving ecological principle shaping the global structure of biodiversity.”

See also: The histone demethylase KDM6B regulates temperature-dependent sex determination in a turtle species 5/11/18

In this 1996 review, we linked the sex differences in yeasts to sex differences in humans via alternative splicings of pre-mRNAs, which are now called microRNAs. From Fertilization to Adult Sexual Behavior

I linked quantized energy from subatomic particles to all biodiversity via the creation of  microRNAs in:
2014 Preprint: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
2018 Publication: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems

Biological Laws

Biophysical constraints and biological laws appear to link ecological variation to ecological adaptations via conserved molecular mechanisms in all species. For example, nutrient-dependent ecological niche construction leads to pheromone-controlled social niche construction via the nutrient-dependent pheromone-controlled physiology of reproduction. The nutrient-dependent origin of amino acid substitutions in viruses [149-152], which also are manifested in plant and animal interactions, exemplifies a continuum of biological plausibility and ecological validity in the context of Laws of Biology. These Laws of Biology include Kohl’s Laws of Biology, which are so named because the surname of the first author or sole author on each of 7 peer-reviewed publications in the paragraph below is Kohl. The Kohls did not create the Laws of Biology; they merely independently incorporated what is known about them into what appears to be a cohesive series of published works.

Kohl’s Laws of Biology
Life is nutrient-dependent. That is a Biological Law. The ecological origin of all biological laws is apparent 1) in the context of systems biology [87]; 2) in the context of the metabolism of nutrients by microbes [153]; and 3) in the context of how the metabolism of nutrients results in species-specific pheromones that control the physiology of reproduction [154]. Taken together, the systems biology of nutrient metabolism to species-specific pheromones, which control the physiology of reproduction, can be expressed in a summary of Kohl’s Laws of Biology: 1) Life is nutrient-dependent.

See for review [27,155]. The physiology of reproduction is pheromone-controlled. See for review [26]. In the context of nutrient-dependent epigenetically-effected human reproduction, it is clearer that the epigenetic effects of human pheromones integrate neuroendocrinology and behavior [100], which includes the neuroendocrinology of mammalian behavior associated with the development of sexual preferences [156].

Kohl’s Laws help to explain what was missing from Darwin’s ‘conditions of life.’ Darwin knew nothing about genetics, which means he knew nothing about the epigenetic effects of food odors or pheromones.

 

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

An evolutionary theory killer

ATP and RNA-mediated chromosomal stability

Cytosis, a cell biology game for ages 10+ links ATP to viral latency and the protection of all organized genomes from the virus-driven degradation of messenger RNA that serious scientists have linked to all pathology.
It is time for a new measure of cell function: Quantifying Cellular ATP Production Rate…(2018)

Adenosine triphosphate (ATP) is the most common high energy intermediate of living organisms. Cells utilize the energy derived from the breakdown of cellular fuels to synthesize ATP from ADP and inorganic phosphate. The free energy released from ATP hydrolysis is then used to sustain various cellular functions such as growth, movement, and response to the environment. Mammalian cells tightly regulate production and consumption of ATP – i.e. supply and demand are balanced to maintain intracellular ATP levels quite constant. Therefore, measuring the rate of ATP production enables a view into cellular function that is not provided by simply measuring the amount of ATP in the cell. The Agilent Seahorse XF Real-Time ATP Production Rate Assay quantifies ATP Production Rates from mitochondrial respiration and glycolysis in real time with live cells providing a unique insight into cellular phenotype and function.

See also: Ferrick DA Remember that ATP does not create itself. The creation of ATP and the creation of RNA are energy-dependent and biophysically constrained by the anti-entropic virucidal energy of sunlight.
For example: Assessment of drug-induced mitochondrial dysfunction via altered cellular respiration and acidification measured in a 96-well platform

…respiration and acidification changes upon addition of the thiazoldinediones were cell-type specific, with the rank order of mitochondrial impairment in whole cells being in accord with the known adverse effects of these drugs.

Cell-type specific drugs alter the mitochodrial production of ATP, which alters the production of RNA via changes in the potential of hydrogen (pH).
See also:  Analysis and interpretation of microplate-based oxygen consumption and pH data

…this chapter also provides a detailed accounting of proton production during glucose oxidation in the context of plate-based assays.

Difference in proton production link differences in the energy of photons from the proton motive force and proton gradients to energy-dependent RNA-mediated cell type differentiation.
Pseudoscientists and other theorists complain about so-called predatory publishing and use their complaints to attack anyone who does not “toe the line” of dogmatic consensus. See for example: OMICS Publishing Group
See also: Prominent Cell Biologist Fired After Data Manipulation Investigation

The University of Tokyo confirmed last August that Yoshinori Watanabe tampered with research-related images, and dismissed him in late April.

In 2015, his group stomped on the toes of biologically uninformed theorists. The group published:
The inner centromere–shugoshin network prevents chromosomal instability

Artificial restoration of the ICS network suppresses chromosome segregation errors in a wide range of CIN+ cells, including RB- and BRCA1-deficient cells. Thus, dysfunction of the ICS network might be a key mechanism underlying CIN in human tumorigenesis.

Food energy-dependent RNA-interference has since emerged as an effective treatment for all chromosomal instability, which appears to be caused by the virus-driven theft of quantized energy.
Additional details about energy-dependent healthy longevity will be found in the Science Behind the Game Subatomic which will link biophysically constrained viral latency from Cytosis to all biophysically constrained biodiversity via what organisms eat and the physiology of their pheromone-controlled reproduction.
See also: New EU-wide tests to tackle ‘food apartheid’

…recent comparisons of food samples showed that big Western brands use cheaper ingredients in products sold in former communist countries.

The cheaper ingredients could alter the innate immunity of human populations in former Communist countries, where God-less Communism was supported by ridiculous theories.
See: Darwinian Theory Proved by Video Game? Robert J. Marks Begs to Differ (2017)

We’ve begun developing support materials for teachers and students to help them use ‘Darwin’s Demons’ to demonstrate and teach evolutionary concepts.

A National Science Foundation grant for evolution studies helped pay for the project.

Conclusion:

Adaptation, if anything, demonstrates intelligent design, not Darwinism. Of course they won’t tell you that at the University of Idaho, or most anywhere else. Instead they’ll stick you in front of a video game and tell you the stale, old fable.

Ecological models of food energy-dependent pheromone-controlled biophysically constrained adaptations have replaced evolutionary concepts except within the school system of the US and other backward countries.
See: Israeli Middle Schools School to Include Theory of Evolution

…learning about evolution is not the primary function of the decision, but rather to use it as a building block for students to learn more about their ecology.

All serious scientist know the difference between evolution and adaptation.
See:  Are Evolution and Adaptation the Same? (2018)
The energy-dependent de novo creation of the cell links ATP to RNA biosynthesis and the physiology of reproduction via food odors and pheromones in the context of this board 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!

It refutes neo-Darwinian pseudoscientific nonsense by starting with Darwin’s energy-dependent “conditions of life.”

Conditions of life are mediated by RNA interference. See also: RNA-Guided Human Genome Engineering 

An evolutionary theory killer

A single base change refutes theistic evolution (2)

Announcing publication of a model that links the creation of quantized energy from changes in subatomic particles to biophysically constrained viral latency and sympatric speciation in all living genera.

Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems

This angstroms to ecosystems model of ecological adaptation links nutrient energy-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA/messenger RNA balance and chromosomal rearrangements via the physiology of reproduction in species from microbes to humans.

The invited review of nutritional epigenetics was returned without review and the preprint was posted 4 years ago as:

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

The only significant change to the manuscript was a change in the title. Atoms to ecosystems became Angstroms to Ecosystems when quantized energy-dependent changes in angstroms were linked to ecological adaptation by what is known to all serious scientists in this 2014 parody.
All About that Base (Meghan Trainor Parody) 12/10/14
Repeat after them (and me): “… every angstrom is dynamic from the 5 prime to the three…”
See also the 2015 publication: Structural diversity of supercoiled DNA

DNA simultaneously exists in a largely inactive B-form with bases tucked in and protected and an active, highly varied structure with exposed bases.

See also: RNA-Guided Human Genome Engineering

George Church and others may have been the first to place the naturally occurring biophysically constrained energy-dependent processes of ecological adaptations into the context of a patent. (It is extremely unusual for anyone to attempt to patent a naturally occurring process.) That explains why there is no patent litigation, which still plagues those who claimed to discover the CRISPR-Cas 9 innate immune system of bacteria, which biophysically constrains viral latency and prevents the degradation of messenger RNA that links the energy-dependent creation of bacteria to the virus-driven creation of archaea and L-forms. All biophysically constrained virus-driven pathology has since been placed back into the context of embryogenesis and the dynamics of energy-dependent gene expression at the level of single-cell resolution as if bacteria somehow evolved into humans.

See:

Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis
Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo
The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution
Chronicling embryos, cell by cell, gene by gene
Reported as: How one cell gives rise to an entire body
See for comparison our section on molecular epigenetics in: From Fertilization to Adult Sexual Behavior (1996)
Watch pseudoscientists continue to make ridiculous claims that fail to link the creation of biophysically constrained thermonuclear energy to autophagy and all biodiversity in the context of the cell biology game Cytosis and most of the forthcoming presentations during Schrödinger at 75 – The Future of Biology – September 2018.
Remember to note that at the end of the parody All About that Base, the research group politely refers to Neil deGrasse Tyson as a big ass (er, a bass). Try not to use the acronym ROTFLMAO in attempts to discuss what is known to all serious scientists with theorists.

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.

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

Ecological Adaptations vs the Randomness of Evolution (2)

Summary: See for comparison: Make ‘Em Resistant to Viruses

In the new proposal — which Science says was released in advance of a meeting today — GP-write leaders say “ultrasafe” cells could be developed by making some 400,000 changes to the human genome.

A Fast OneStep Digestion of DNA or RNA for Global Detection and Characterization of Nucleotide Modifications (link opens pdf)
Product information:

The Nucleoside Digestion Mix is an optimized mixture of enzymes that provides a convenient one-step method to generate single nucleosides from DNA or RNA for quantitative analysis by liquid chromatography-mass spectrometry (LC-MS), eliminating the need for sequential multi-step, time-consuming digestion protocols.

Digests both DNA and RNA to single nucleosides

A source of anti-entropic energy is required to create nucleosides and nucleotides. The quantized energy as information was available to modify nucleotides after the creation of sunlight.
See also: Nucleoside vs. Nucleotide

A nucleoside consists of a nitrogenous base covalently attached to a sugar (ribose or deoxyribose) but without the phosphate group. A nucleotide consists of a nitrogenous base, a sugar (ribose or deoxyribose) and one to three phosphate groups.

Nucleoside = Sugar + Base
Nucleotide = Sugar + Base + Phosphate

The link from the”optimized mixture of enzymes” to Digestion of DNA or RNA links the quantification of epigenetic modifications and the activity of nucleic acid modifying enzymes from energy-dependent microRNA biogenesis to the functional structure of cellular RNA, which has been linked to viral latency and ecological adaptations in all living genera.
The facts about the energy-dependent creation of microRNAs and ecological adaptations have been placed into the context of High-Resolution Epigenomic Atlas of Human Embryonic Craniofacial Development.

These data are provided in easily accessible formats for both craniofacial researchers and clinicians to aid future experimental design and interpretation of noncoding variation in those affected by craniofacial abnormalities.

The facts were reported in Blueprint for the skull: A search for cleft palate’s cause reveals a map of the facial genome

He studies the human genome, but not the genes that tell the body what proteins to make. Instead, he focuses on regulators, parts of the DNA that tell genes when and where to act. These regulators, also known as enhancers, tend to be linked to specific parts of the body.

microRNA cleft palate
1 of 33: A functional polymorphism in the pre-miR-146a gene is associated with the risk of nonsyndromic orofacial cleft.
enhancer cleft palate
1 of 35 Genome-Wide DNA Methylation Analysis During Palatal Fusion Reveals the Potential Mechanism of Enhancer Methylation Regulating Epithelial Mesenchyme Transformation.
The link from the energy-dependent creation of microRNAs to food energy-dependent genome-wide RNA-directed DNA methylation is perfectly clear until the term enhancer is used in the context of a potential mechanism regulating epithelial mesenchyme transformation.
The conserved molecular mechanisms of energy-dependent epigenetically-effected cell type differentiation are missing and the substitution of a potential mechanism of methylation can be used to support neo-Darwinian nonsense about mutation-driven evolution.
Even after pseudoscientists admit that their theories of craniofacial development are ridiculous, since development is energy-dependent and epigenetically effected, they try to place their findings back into the context of gene-centric theories.
Alternatively, they must know that the virus-driven theft of quantized energy links Zika virus-damaged DNA to craniofacial development with the most severe effects on the size of the brain and skull.
See also: Incomplete host immunity favors the evolution of virulence in an emergent pathogen

Partially protective vaccination can sometimes select for increasingly virulent pathogens.

Reported as: In nature, an imperfect immune system drives the evolution of deadly pathogens

As annual flu shot patrons know, immune systems are not perfect and must be constantly reinforced to protect against rapidly evolving pathogens.

Also:

…birds that eat at feeders are more likely to be infected with the disease, which causes red, swollen eyes and often blindness that results in death.

The link from what the birds and the bees eat to healthy longevity was detailed in my 2013 refutation of neo-Darwinian pseudoscientific nonsense.

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

Scientific creationists in the US have started to tout my model without attribution.
See: Are Evolution and Adaptation the Same? 

Mechanisms of adaptation are made up of complex integrated components, including environmental sensors, signaling pathways, feedback and feed-forward loops, and information control systems in the creature’s DNA.

See also: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (2014)
See for comparison: Next-generation diagnostics with CRISPR

The sentinel discovery that prokaryotes (bacteria and archaea) have heritable adaptive immunity mediated through CRISPR and CRISPR-associated (Cas) proteins has led to transformative advances in molecular biology, most notably in gene editing (2).

The discovery of heritable adaptive immunity ended the pseudoscientific nonsense about mutation-driven evolution. It linked vaccinations and gene editing to unpredictable outcomes in species from microbes to humans by altering the perfection of our innate immune system. The alterations link the virus-driven degradation of our messenger RNA to all pathology.
But see: Cytosis for ages 10+

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

See for comparison: Make ‘Em Resistant to Viruses

In the new proposal — which Science says was released in advance of a meeting today — GP-write leaders say “ultrasafe” cells could be developed by making some 400,000 changes to the human genome.

512zS1RWlQL._SX331_BO1,204,203,200_

Ecological Adaptations vs the Randomness of Evolution

Summary: Ecological variation is linked to ecological adaptations in all living genera via the creation of microRNAs and the sense of smell.

Odor Perception on the Two Sides of the Brain: Consistency Despite Randomness

Highlights

  • •A random model predicts observed preservation of correlations in piriform responses
  • •The model supports consistent agreement about odor quality among individuals

The model fails to explain how the energy-dependent creation of microRNAs links pattern recognition to the creation of pre-mRNAs and biophysically constrained viral latency. Everything required for our visual perception of energy and mass in the context of the space-time continuum has been linked to the RNA-mediated transgenerational epigenetic inheritance of conserved molecular mechanisms.

See: Minding your caps and tails

A nascent mRNA, synthesized in the nucleus, undergoes different modifcations before it can be translated into proteins in the cytoplasm. For a mRNA to be functional, it requires modifed 5´ and 3´ ends and a coding region (i.e., an open reading frame (ORF) encoding for the protein of interest) flanked by the untranslated regions (UTRs). The nascent mRNA (premRNA) undergoes two signifcant modifcations in addition to splicing.

Simply put, nascent mRNAs do not exist outside the context of their energy-dependent creation.

See also:  Feedback loops link odor and pheromone signaling with reproduction (2005)

Mathematical models explain nothing when they fail to link the anti-entropic virucidal of sunlight to energy-dependent RNA-mediated biophysically constrained viral latency.

Linda Buck shared the 2004 Nobel Prize in Physiology and Medicine with Richard Axel, who is a co-author of the article about consistency despite randomness. She is scheduled to present during Schrödinger at 75 – The Future of Biology – September 2018

For comparison, Richard Axel appears to have been stuck with ridiculous theories and mathematical models.

See also: Are Evolution and Adaptation the Same?

Evolutionists believe adaptable traits arose through the progressive accumulation of random genetic mutations that somehow provided an advantage to living things facing specific environmental challenges. But not only are nearly all mutations either harmful or at best neutral, it’s impossible to achieve a functioning system of many orchestrated components one step at a time. All-or-nothing systems cannot evolve bit by bit.

Ecological variation is linked to ecological adaptations in all living genera via the creation of microRNAs and the sense of smell.

See: Olfaction Warps Visual Time Perception

See also: Energy as information and constrained endogenous RNA interference

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