Cytosis can be used to teach everything from base editing to RNA editing to everyone over age 10. They will learn how to link the creation of energy to biophysically constrained viral latency via the physiology of pheromone-controlled reproduction.

Polymaths and paradigm shifts: from Asimov to Bear (3)

Polymaths and paradigm shifts: from Asimov to Bear (2)

Teilhardism And The New Religion: A Thorough Analysis of the Teachings of Pierre Teilhard de Chardin”, p.18, TAN Books

The evolutionist thesis has become more stringently unthinkable than ever before. — Dr. Wolfgang Smith (2015).

A Chat with Information Scientist Pedro Marijuán (2017)

I’ve based my informational scheme of the cell on this thinking of “distinction on the adjacent” — where molecular recognition is the essential phenomenon over which biological complexity has been developed.

Biological complexity develops in the context of the olfactory code. Molecular recognition of food odors and pheromones biophysically constrains viral latency.

See: Fundamental principles of the olfactory code  Volume 164, February 2018, Pages 94-101 open access

Sensory coding represents a basic principle of all phyla in nature: species attempt to perceive their natural surroundings and to make sense of them. Ultimately, sensory coding is the only way to allow a species to make the kinds of crucial decisions that lead to a behavioral response.

Alternative splicing of microRNAs (aka pre-mRNAs) are required for a behavior response.

The splicing code  Volume 164, February 2018, Pages 39-48

…the splicing code depends on a myriad of different factors that in part are influenced by the background in which they are read such as different cells, tissues or developmental stages. Given the complexity of the splicing process, the construction of an algorithm that can define exons or their fate with certainty has not yet been achieved.

Algorithms define nothing. The availability of quantized energy as information must be linked to biophysically constrained viral latency and all biologically based cause and effect.

What is code biology?  Volume 164, February 2018, Pages 1-10

The great discontinuities of the history of life, in other words, can be explained as the result of the appearance of new codes.

New codes do not automagically occur. The new codes are energy-dependent and RNA-mediated in the context of the fixation of amino acid substitutions that differentiate the cell types of all living genera.

On universal coding events in protein biogenesis  Volume 164, February 2018, Pages 16-25

The complete ribosomal protein synthesis cycle and codon-amino acids associations are universally preserved in all life taxa on Earth. This process is accompanied by a set of hierarchically organized recognition and controlling events at different complexity levels. It starts with amino acid activation by aminoacyl tRNA synthetases…

The energy-dependent creation of the tRNA synthetases links hydrogen-atom transfer in DNA base pairs in solution to all energy-dependent biodiversity.

How prokaryotes ‘encode’ their environment: Systemic tools for organizing the information flow  Volume 164, February 2018, Pages 26-38

An important issue related to code biology concerns the cell’s informational relationships with the environment. As an open self-producing system, a great variety of inputs and outputs are necessary for the living cell, not only consisting of matter and energy but also involving information flows.

Quantized energy is the information that flows through every cell type in all prokaryotes.

Causation, constructors and codes  Volume 164, February 2018, Pages 121-127

A formal definition of codes in general, and organic codes in particular, allows the relational diagram to be extended so as to capture this translation of formal cause into process. The extended relational diagram is used to exemplify causal entailment in a diverse range of processes, such as enzyme action, construction of automata, communication through the Morse code, and ribosomal polypeptide synthesis through the genetic code.

The diverse range of processes starts with the creation of energy-dependent enzyme action. The anti-entropic virucidal energy of sunlight was first linked to the creation of all biodiversity on Earth in 1944: What is Life?

Indeed, in the case of higher animals we know the kind of orderliness they feed upon well enough, viz. the extremely well-ordered state of matter in more or less complicated organic compounds, which serve them as foodstuffs. After utilizing it they return it in a very much degraded form -not entirely degraded, however, for plants can still make use of it. (These, of course, have their most power supply of ‘negative entropy’ the sunlight.) (pp. 73 and 74)

If you think you can link anything except sunlight to all biodiversity on Earth, see: Evolution – Genetic Novelty/Genomic Variations by RNA Networks and Viruses
If you know that serious scientists do not link viruses to the evolution of anything except pathology, see:
Schrödinger at 75 – The Future of Biology – September 2018
The future of biology will not be left in the hands of biologically uninformed theorists.

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

The MicroRNAome Strikes Back: A Sokalian hoax (9)

Summary: Darwin’s “conditions of life” link the creation of sunlight from the creation of ATP to the creation of microRNAs and RNA-mediated cell type differentiation in the context of biophysically constrained viral latency. There is no magical creation of an RNA force field or protein force field that could be used to link the magic of evolution to biologically-based diversity in species from microbes to humans.
RNA force field with accuracy comparable to state-of-the-art protein force fields

The complex and often highly dynamic 3D structures of RNA molecules are central to their diverse cellular functions. Molecular dynamics (MD) simulations have played a major role in characterizing the structure and dynamics of proteins, but the physical models (“force fields”) used for simulating nucleic acids are substantially less accurate overall than those used in protein simulations, creating a major challenge for MD studies of RNA. Here, we report an RNA force field capable of describing the structural and thermodynamic properties of RNA molecules with accuracy comparable to state-of-the-art protein force fields.

In the context of Jason D. Sanders adolescent fascination with the “Star Wars” movie series (see below), “May the magic of the mitochondrial force be with you!”
In the context of John Hewitt’s attempt to link the automagical creation of enzymes to all biodiversity outside the context of the anti-entropic virucidal energy of sunlight, see: Cell Surface Deformation during an Action Potential

A theoretical analysis demonstrates that this observation can be explained by a reversible change in the mechanical properties of the cell surface (transmembrane pressure, surface tension, and bending rigidity). Taken together, these findings contribute to the ongoing debate about the physical nature of cellular excitability.

The mechanical properties of reversible changes in the cell surface did not create themselves. There is also no such thing as RNA force field without the creation of sunlight, the creation of ATP and the creation of RNA. The energy-dependent creation of RNA is required for the biophysically constrained construction of all membranes in all cells. The article about the RNA force field appears to be another hoax akin to Nonomura’s article: Small RNA pathways responsible for non-cell-autonomous regulation of plant reproduction.
The pathways do not create themselves. The RNA force field does not create itself. There is no such thing as non-cell-autonomous regulation outside the context of the creation of sunlight, energy, ATP, and RNA, which biophysically constrains viral latency.
See also: Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis

Mitochondria–lysosome contacts thus allow bidirectional regulation of mitochondrial and lysosomal dynamics, and may explain the dysfunction observed in both organelles in various human diseases.

Reported as: Study Reveals Direct Contact Between Mitochondria and Lysosome Within the Cell

“In some ways, we assume that scientists have discovered all the major inner workings of our cells in the 21st century. And yet in this work, we made a new observation that these two organelles are directly talking to each other,”

The increasing number of publications that claim to link new findings to energy-dependent biophysically constrained RNA-mediated cell type differentiation can be viewed in the context of publications that fail to link what is known to serious scientists and instead claim that “evolution did it.”
See for example: The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer

These findings suggest that Gag retroelements have been repurposed during evolution to mediate intercellular communication in the nervous system.

Reported as: Interview with Jason D. Shepherd, PhD

Arc looks like and behaves like a virus. The protein “infects” nearby cells, in this case neurons, with instructions of how to make more of itself, i.e. it shuttles its own mRNA from one cell to another.

If you never looked at another published work, you might still know more than Jason D. Shepherd knows about protein biosynthesis and degradation. He skips the parts about the energy-dependent creation of ATP and RNA and proceeds to link a protein that behaves like a virus to mRNA communication among cell types.
See for comparison: Structure of the Deactive State of Mammalian Respiratory Complex I

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis.

Instead of the simple-minded approach taken by Jason D. Shepherd, these authors link the creation of ATP to the biophysically constrained creation of RNA via published works from 1964 and 1968.
See: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)
See also: Long-range coherence and energy storage in biological systems (1968)
Half a century later RNA Cloaking by Reversible Acylation (January 26, 2018)

We describe a selective and mild chemical approach to controlling RNA hybridization, folding, and enzyme interactions.

Control of RNA hybridation, folding, and enzyme interactions is energy-dependent. That is no secret to serious scientists!
Reported as:  A chemical cloak of invisibility could reveal RNA’s secrets

Biologists used to think they knew DNA’s less famous cousin, RNA, but in the last two decades it’s become clear the molecule is keeping far more secrets than it has ever revealed. Recent discoveries have it taking on never-before-anticipated roles in regulating how a cell functions.

Diagram: A hairpin loop from a pre-mRNA. Highlighted are the nucleobases (green) and the ribose-phosphate backbone (blue). Note that this is a single strand of RNA that folds back upon itself.
In the past two decades (January 26, 1998 to January 26, 2018) more than  62,000 published works mention “microRNAs,” which used to be called pre-mRNAs. In our 1996 Hormones and Behavior review, we linked the food energy-dependent creation of pre-mRNAs to the pheromone-controlled physiology of reproduction in all living genera via RNA-mediated cell type differentiation. The claim that “Recent discoveries have it [RNA] taking on never-before-anticipated roles in regulating how a cell functions”  is an insult to every serious scientist who has lived and or died during the past half century.

It is no secret that the creation of sunlight has been linked from the creation of ATP to the creation of RNA and all biophysically constrained biodiversity via the physiology of pheromone-controlled reproduction. The cell biology board game “Cytosis” is proof of the fact that anyone age 10+ who plays the game will know more about energy-dependent RNA-mediated cell type differentiation than anyone who reports their findings as if new information had recently become available.

Amino acid modification FA_Epigenetics_Table1

Eutrophication and phosphorylated biodiversity

In Chinese philosophy, yin and yang (also yinyang or yin yang, 陰陽 yīnyáng “dark–bright”) describe how seemingly opposite or contrary forces may actually be complementary, interconnected, and interdependent in the natural world, and how they may give rise to each other as they interrelate to one another.

Last night I dreamed that someone added color to this symbol and represented it as a spinning disk (in a publication from the Nature publishing group).  The specifics of the dream helped me to complete this accurate representation of biophysically constrained viral latency.
See for comparison: Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions
Reported as: Scientists find potential ‘missing link’ in chemistry that led to life on Earth

“It reminds me of the Fairy Godmother in Cinderella, who waves a wand and ‘poof,’ ‘poof,’ ‘poof,’ everything simple is transformed into something more complex and interesting,” Krishnamurthy said.

In the context of energy-dependent Biblical Creation or Chinese philosophy, the speed of light on contact with water links the Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism to a cleansing Flood of Biblical proportions. After-the-Flood, eutrophication probably stimulated the growth of aquatic plant life.
That speculation helps to explain the rapid re-population of the Earth via the “the process by which a body of water becomes enriched in dissolved nutrients (such as phosphates)…
For comparison, Krishnamurthy’s ‘poof,’ ‘poof,’ ‘poof’ theory of how increasing complexity initially arose twice — before and after the extinction of many different species, will always be placed into the context of a “Fairy Tales.”  Serious scientists can use what is known about biophysically constrained viral latency to link eutrophication from phosphorylation and oligomerization to what has been referred to as the Cambrian Explosion — the rapid diversification of most major living animal body plans (phyla) in the fossil record.
However, serious scientists can also link the facts about eutrophication, phosphorylation and oligomerization to all food energy-dependent pheromone-controlled biodiversity on Earth via the weekend resurrection of the bacterial flagellum.
See: Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system
See also: A communal catalogue reveals Earth’s multiscale microbial diversity reported as: Mapping the Microbiome of…Everything
The funding includes money from the John Templeton Foundation, which in the past seems to have ensured that all results would be reported in the context of randomness and evolution. But, even with millions of dollars spent trying to support that dogma, efforts are doomed to fail.
Eugene Koonin said it best: The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis…
That fact is readily linked to the ‘poof,’ ‘poof,’ ‘poof’ theory of how increasing complexity arose, because the theory does not include any information on how the virus-driven degradation of messenger RNA has since been linked to all pathology.
Indeed, the fossil record may be the best example of how the viral hecatomb links the virus-driven degradation of messenger RNA to calcification of tissues and to ossification of the tissue that neo-Darwinian theorists claim is evidence that our ancestors evolved into us. Their ridiculous claims have not been supported by any experimental evidence of biophysically constrained biologically-based top-down causation.
If serious scientists allow the ‘poof,’ ‘poof,’ ‘poof’ theory, the pseudoscientists may continue to prevail against all odds. In the world of science, their theories would never be considered. Instead, it seems that biologically uninformed science idiots can suggest anything.When they continue to repeat their suggestions, the uninformed masses may believe them — rather than attempt to learn anything about eutrophication, phosphorylation, or food energy-dependent pheromone-controlled feedback loops, ecological adaptations, and biodiversity.
For instance, in the context of energy-dependent top-down causation, physics and chemistry can be linked from molecular epigenetics to supercoiled DNA in organized genomes via Histone methylation and amino acid substitutions.​​

Lysine methylation of H3 and H4 is implicated in both transcriptional activation and repression depending on the methylation site, while arginine methylation promotes transcriptional activation1.

Methylation is food energy-dependent and RNA-mediated in species from microbes to humans. That fact and all facts about supercoiled DNA, which prevents the virus-driven degradation of messenger RNA, can be placed into the following two representations of cause and effect — or represented as a spinning yin-yang symbol.
The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.
…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.
See this black and white representation of energy-dependent biodiversity.
See for comparison, this 3-D imagery:

My comment on Inching toward the 3D genome has not been removed.

Re: “…the nucleome structure changes as cells age, differentiate, and divide, and researchers want to understand how and why.”
Cell type differentiation is nutrient-dependent. RNA-directed DNA methylation links RNA-mediated amino acid substitutions to cell type differentiation via protein folding during life history transitions. Amino acid substitutions stabilize protein folding; mutations perturb it, during nutrient-dependent theromodynamic cycles of protein biosynthesis and degradation.
Life is physics and chemistry and communication — http://dx.doi.org/10.1111/nyas.12570
The metabolism of nutrients links metabolic networks to genetic networks via species-specific pheromones that control the physiology of reproduction. Simply put, pheromones link nutrient-dependent life via physics, chemistry, and the conserved molecular mechanisms of communication in species from microbes to man.
Until nutrient-dependent protein folding is linked via the conserved molecular mechanisms of amino acid substitutions and pheromone-controlled DNA stability in organized genomes, which links the epigenetic landscape to the physical landscape of DNA, researchers must take a piece-meal approach to integrating the requirements for life and successful life history transitions — despite the fact that life history transitions have been detailed in the context of the honeybee model organism. See: Honey bees as a model for understanding mechanisms of life history transitions http://www.ncbi.nlm.nih.gov/pubmed/15925525

Gene Robinson is the senior author of this report on phosphorylation in the honeybee model organism. See: Socially responsive effects of brain oxidative metabolism on aggression

Despite ongoing high energetic demands, brains do not always use glucose and oxygen in a ratio that produces maximal ATP through oxidative phosphorylation. In some cases glucose consumption exceeds oxygen use despite adequate oxygen availability, a phenomenon known as aerobic glycolysis. Although metabolic plasticity seems essential for normal cognition, studying its functional significance has been challenging because few experimental systems link brain metabolic patterns to distinct behavioral states. Our recent transcriptomic analysis established a correlation between aggression and decreased whole-brain oxidative phosphorylation activity in the honey bee (Apis mellifera), suggesting that brain metabolic plasticity may modulate this naturally occurring behavior.

Elekonich and Robinson (2000) cited our 1996 Hormones and Behavior review:

The development of species-typical and sex-specific adult behaviors in vertebrate animals is influenced by gonadal steroid hormones, non-gonadal hormones, and non-hormonal factors working on the underlying neural circuitry (reviewed in Diamond et al., 1996; Kawata, 1995; Schlinger, 1998).

The facts that link the creation of sunlight from the creation of ATP to the creation of RNA have been known since 1964.
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.

The facts about Honey bees as a model for understanding mechanisms of life history transitions have been ignored.
See also: Feedback loops link odor and pheromone signaling with reproduction
What can be said about the amount of willful ignorance that has been displayed by theorists, since “What is Life?” was published in 1944?

Indeed, in the case of higher animals we know the kind of orderliness they feed upon well enough, viz. the extremely well-ordered state of matter in more or less complicated organic compounds, which serve them as foodstuffs. After utilizing it they return it in a very much degraded form -not entirely degraded, however, for plants can still make use of it. (These, of course, have their most power supply of ‘negative entropy’ the sunlight.) (pp. 73 and 74)

In the reprint edition, Roger Penrose (8 August 1991) 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?

See also my comments on: Methyldynamics behind virtually all pathologies?

Vast Complexity of Chromatin 3D Shapes
http://jonlieffmd.com/blog/vast-complexity-of-chromatin-3d-shapes
N6-methyladenosine marks primary microRNAs for processing http://dx.doi.org/10.1038/nature14281
Our 1996 Hormones and Behavior review linked pre-mRNAs (microRNAs) to RNA-mediated cell type differentiation in species from yeasts to mammals via what was known about the conserved molecular mechanisms of nutrient-dependent RNA-mediated protein folding and the pheromone-controlled physiology of reproduction.
From Fertilization to Adult Sexual Behavior http://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html
See also:
Unraveling the secrets of RNA-mediated events http://rna-mediated.com/unraveling-the-secrets-of-rna-mediated-events/

It is difficult for me, as a medical laboratory scientist, to understand how others who are involved in diagnostic medicine seem to have accepted ridiculous theories that cannot be linked to results reported from testing in the medical laboratory.
See: Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels

Mutations in the period (per) gene of Drosophila melanogaster affect both circadian and ultradian rhythms. Levels of per gene product undergo circadian oscillation, and it is now shown that there is an underlying oscillation in the level of per RNA. The observations indicate that the cycling of per-encoded protein could result from per RNA cycling, and that there is a feedback loop through which the activity of per-encoded protein causes cycling of its own RNA.

What have other medical laboratory scientists and medical professionals been taught to believe about the underlying oscillation that have since been linked from cryo-EM to all energy-dependent biophysically constrained viral latency? Is there any model of biologically-based cause and effect that links anything except food energy-dependent feedback loops from the physiology of pheromone-controlled reproduction to all biodiversity? If not, help stop the nonsense.
Play the cell biology game: Cytosis: A Cell Biology Board Game

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

Stop playing the games of theorists.

Lethal virus kills 5 billion people?

Entertaining yourself to death

Summary: Food energy is required for the creation of enzymes that metabolize the food, which links the metabolism to the pheromone-controlled physiology of reproduction in species from microbes to humans via alternative splicings of pre-mRNAs, which are now called microRNAs in more than 65,000 published works. The horrid tradjedy of of yet another preventable death by suicide extends those works to preventing the cause of death of those killed by Stephen Paddock.
Vegas gunman transferred $100K, set up cameras at hotel room
Excerpts with my emphasis:

Lombardo said he is “absolutely” confident authorities will find out what set off Paddock, a 64-year-old high-stakes gambler and retired accountant who killed himself….

…speculated that there was “some sort of major trigger in his life — a great loss, a breakup, or maybe he just found out he has a terminal disease.”

…a “psychological autopsy” may be necessary to try to establish the motive. If the suicide didn’t destroy Paddock’s brain, experts may even find a neurological disorder or malformation

He said there could be a genetic component to the slaughter…

“The genetics load the gun, personality and psychology aim it, and experiences pull the trigger, typically,” Clemente said.

He later worked for a defense contractor.

“No affiliation, no religion, no politics. He never cared about any of that…

Two former facebook friends are among those who claim that “nobody cares” that I have detailed the facts about the virus-driven cause of death for Stephen Paddock and his victims. When will others learn why there was no obvious motive to his madness?
The excerpts above clearly indicate that virus-driven epigenetic drift led to the deadly constraint-breaking mutations via everything known to serious scientists about epitranscriptomics and biophysically constrained viral latency.
Simply put, like most people, Stephen Paddock failed to protect himself from the virus-driven degradation of messenger RNA that serious scientists have linked to all pathology in all living genera. Psychiatrist/antagonist Jay R. Feierman put that fact into the context of this post to the “Evolutionary Psychology” Yahoo Group.

168958 Origin and Evolution of RNA-Dependent RNA Polymerase OPEN ACCESS

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

The death of Stephen Paddock and his victims can now be attributed to medical professionals, like Jay R. Feierman, and anyone else who claims: “We are used to thinking about evolution at hierarchical levels above that of protein enzymes.”
The creation of protein enzymes requires an energy source. That fact refutes every aspect of the pseudoscientific nonsense touted by biologically uninformed science idiots. [An idiot is someone with no professional expertise: A biologically uninformed science idiot is someone like Feierman, who has professional expertise but no common sense.] Feierman linked to this article: Origin and Evolution of RNA-Dependent RNA Polymerase (with my emphasis)

With the emergence of a variant with properties of reverse transcriptase, and subsequently a DNA polymerase, a fundamental step occurred to originate the first genomes based in DNA, being the bridge to move from a RNA/Protein World to a DNA/RNA/Protein World (Gilbert, 1986; Müller, 2006). When DNA molecules emerged, by variation, other classes of polymerases appeared. With the complexification of the biological system, functions such as replication, repair, and recombination emerged, very high error rates were selected against, and the new variants arose to work in specific processes.

My summary: The authors eliminate the energy-dependent creation of enzymes (1) reverse transcriptase and (2) a DNA polymerase. In the second act of their tragic comedy routine, they eliminate the biophysical constraints that link the physiology of pheromone-controlled reproduction from natural selection for energy-dependent codon optimality to the creation of enzymes and food energy-dependent RNA-mediated DNA repair via feedback loops.
See: Feedback loops link odor and pheromone signaling with reproduction
The feedback loops link the sense of smell in bacteria from the physiology of their pheromone-controlled reproduction to our visual perception of energy and mass in the context of the space-time continuum.
See: Olfaction Warps Visual Time Perception

The behavioral gain produced by a congruent relative to an incongruent odor is accompanied by elevated neural oscillatory power around the object’s flicker frequency in the right temporal region ~150-300 ms after object onset, and is not mediated by visual awareness. In parallel, odors bias the subjective duration of visual objects without affecting one’s temporal sensitivity. These findings point to a neuronal network in the right temporal cortex that executes flexible temporal filtering of upstream visual inputs based on olfactory information. Moreover, they collectively indicate that the very process of sensory integration at the stage of object processing twists time perception, hence casting new insights into the neural timing of multisensory events.

Virus-driven degradation of messenger RNA links alterations in the timing of multisensory events to the suicide of Stephen Paddock and to the unnecessary suffering and premature death of his victims. That fact was placed into the context of Feierman’s thinly veiled attack on the practice of Precision Medicine.
See: Energy as information and constrained endogenous RNA interference, which was presented during the Labroots: Precision Medicine Virtual Conference February 22-23. 2017
Description:

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

Stephen Paddock killed 59 people and more than 500 people were injured. On 10/4/17, there were only 637 views of my 7 minute-long presentation. With release of the cell biology game “Cytosis,” which is scheduled to be available later this month, everyone who is not dead yet will be able to learn how to protect themselves from the cause of death by suicide: viruses. The virus-driven degradation of messenger RNA will also be the cause of death for people who have not learned the difference between energy-dependent healthy longevity and the virus-driven energy theft that will kill them either directly or indirectly.

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

See also this comment to the human-ethology Yahoo group (reproduced below)

See for comparison: Transcription factor clusters regulate genes in eukaryotic cells

Attempts continue to link epigenetic drift and epitranscriptomics to RNA-mediated cell type differentiation outside the context of natural selection for energy-dependent codon optimality and the biophysically constrained pheromone-controlled physiology of reproduction. All past attempts have failed.

The reason for those attempts and the reason all past attempts have failed may require more clarification from people like Jay R. Feierman. Others realize that the enzymes linked from metabolism to survival of all species did not create themselves and did not evolve, which means that no species evolved via natural selection for beneficial mutations. Pseudoscientists have been left behind with their hypothetical scenarios.’

See for example: Origin and Evolution of RNA-Dependent RNA Polymerase

“Based in the present results, we suggest a hypothetical scenario where initially a ribozyme with polymerase activity could have enhanced its activity by the binding of a simple cofactor, as magnesium (Shechner et al., 2009; Horning and Joyce, 2017), thus, exerting the functions of replication of some information stored on RNA molecules (Kim and Higgs, 2016; Tagami et al., 2017).”

See for comparison: Lipid Encapsulation of Self Replicating Ribozymes

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

I have discussed the claims about abiogenesis and ribozymes in the context of “…a system of heredity and evolution through natural selection…” with scientists who have repeatedly assured me that the claims are nothing more than examples of what Richard Feynman placed into the context of “human idiocy.” Food energy is required for the creation of enzymes that metabolize the food, which links the metabolism to the pheromone-controlled physiology of reproduction in species from microbes to humans via alternative splicings of pre-mRNAs, which are now called microRNAs in more than 65,000 published works.

See for example: miRNA as viral transcription tuners in HPV-mediated cervical carcinogenesis

Discovery of microRNAs (miRs) in recent years and differential expression of a set of specific miRs in HPV infection and cervical lesions indicate that among various regulatory mechanisms, role of these differentially expressed miRs in the post-transcriptional control is pivotal.

When will people like Feierman and Jones begin to examine the extant literature that links energy-dependent biophysically constrained biologically-based cause and effect as detailed in the molecular epigenetics section of our 1996 review:
From Fertilization to Adult Sexual Behavior
How many more people will needlessly suffer and/or die prematurely due to the ignorance and arrogance of biologically uninformed science idiots?

Alternative splicing of pre-mRNA

Sexual communication signals: New Insights!

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

New insights in the evolution of sexual communication signals

Abstract excerpt:

Our research focuses on identifying a) the genes underlying sexual signals and responses in both sexes2-4, and b) ecological factors that may cause divergence in sexual communication. Factors that we found to affect sexual communication are closely related species with similar mating signals5, low nutritional quality, (toxic) secondary plant metabolites and pathogens6.

Elizabeth Pennisi reported on this 2017 conference presentation and claimed:

The results “demonstrate the importance of the social environment,” Halfwerk says. “One form does not attract males on its own, only in close proximity of the other form.” That result also parallels what’s been found in humans: that an attractive woman in a crowd of less attractive women also seems to attract more attention. But pinning down exactly why this happens should be much easier in moths than people, she notes. “That’s the nice thing about insects.”

See: Sexy females help ‘Plain Jane’ moths snag their mates

No experimental evidence of biologically-based sexual communication suggests that sex signals evolved. The fine-tuned systems of communication among individuals and species pose an evolutionary dilemma because they are food energy-dependent. Ecological variation must be linked from food energy to biophysically constrained ecological adaptations by the pheromone-controlled physiology of reproduction in all living genera. Also, everything known to serious scientists about energy-dependent top-down creation links the anti-entropic virucidal energy of sunlight from the creation of ATP to the creation of messenger RNA. That fact does not appear to be coincidental.

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.

Detailed experimental evidence also links the virus-driven degradation of messenger RNA from mutations to all pathology. That fact leaves neo-Darwinian theorists and “Big Bang” cosmologists without any acceptable theory of anything or any theory of everything.

See for comparison: A New Physics Theory of Life and Jeremy England’s idea that “You start with a random clump of atoms, and if you shine light on it for long enough, it should not be so surprising that you get a plant.” 

Theorists and philosophers cannot link energy as information or “big bang” cosmology to biodiversity without the creation of energy. Most of them ignore the fact that they do not know where the energy in a hydrogen atom came from.

Without the de novo creation of energy, they cannot link hydrogen-atom transfer in DNA base pairs in solution from microRNA flanking sequences to SNPs, and they cannot link food energy as information to fixation of RNA-mediated amino acid substitutions in organized genomes. For comparison, all serious scientists have linked what is known about the food energy-dependent fixation of amino acid substitutions to the structure and function of supercoiled DNA, and all serious scientists have linked energy-dependent RNA-mediated cause and effect to all biodiversity via the physiology of pheromone-controlled reproduction.

That fact helps to explain why Richard Feynman referred to some theoretical physicists as examples of human idiocy.

See: Food energy

That suggests Elizabeth Pennisi is a biologically uninformed. She reported: “That’s the nice thing about insects.” If she was not a biologically uninformed science idiot, she would have linked food energy to the physiology of reproduction in all invertebrates and vertebrates. That is how the pheromone-controlled physiology of reproduction is linked from ecological variation to all biodiversity via what is known to all serious scientists about ecological adaptation.
See: Feedback loops link odor and pheromone signaling with reproduction and Olfaction Warps Visual Time Perception

For comparison to the science reporting by Elizabeth Pennisi,  J.A. Parker is the only person besides me, who has reported on this 2017 conference presentation:

See also: All in the (bigger) family by Elizabeth Pennisi with my comment:

The 2015 Society for Integrative and Comparative Biology (SICB) presenters may not recognize how much progress has been made since the 2013 ecological epigenetics symposium. For example, since then authors claimed “…ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.” http://dx.doi.org/10.1038/nature13400

Six months later, other authors traced signaling factors found in vertebrates to the origin of nerve cell centralization via the diffuse nerve net of animals like the sea anemone. http://dx.doi.org/10.1038/ncomms6536 That fact suggests ecological variation is linked to ecological adaptations in morphological and behavioral phenotypes via signaling protein concentrations that differentiate various cell types in body axes and the central nervous system.

Links across species from the epigenetic landscape to the physical landscape of DNA in organized genomes appear to have their origins in the conserved molecular mechanisms of RNA-directed DNA methylation and RNA-mediated protein folding. Two weeks after the publication that refuted ideas about independently evolved neural systems or muscle specification — and perhaps refuted the independent evolution of anything else, SICB presenters linked crustaceans to insects.

Apparently, they’ve learned that the same set of microRNAs controls expression of the genes for rate-limiting enzymes that control the hormone production of different hormones in insects and crustaceans.

Why were they left with any questions about how crustaceans and insects could all be part of one big family? They linked RNA-mediated cell type differentiation to what we described in our section on molecular epigenetics in our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior http://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html

See also: Sex differences in microRNA-mRNA networks: examination of novel epigenetic programming mechanisms in the sexually dimorphic neonatal hypothalamus

Integrating miRNAs and their broad actions on gene function into our conceptualization of the factors directing sexual differentiation of the brain could be a highly informative next step in efforts to understand the complexities behind these processes.

They linked sex differences in microRNAs to the sexual differentiation of all cell types in all living genera that sexually reproduce via microRNA-mRNA networks.
See also: The phylogenetic utility and functional constraint of microRNA flanking sequences

…miRNAs can be employed as both qualitative [9] and quantitative markers, with the latter demonstrated clearly here. Our investigation demonstrates the utility of miRNA sequences as classical phylogenetic markers, and shows this usage is robust to different algorithms of phylogenetic analysis and the analysis of fast-evolving lineages. Such a method provides novel characters for assessing phylogenetic relationships that will be of use in a range of contexts for resolving branches across the tree of life.

See also: Role of olfaction in Octopus vulgaris reproduction

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

Kohl (2013) is: Nutrient-dependent/pheromone-controlled adaptive evolution: a model (June 14, 2013)

…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, ; Duvarci, Nader, & LeDoux, ; Griggs et al., ; Monahan & Lomvardas, ) in adaptive evolution will certainly be discussed in published works that will follow.

Elekonich and Robinson (2000) cited:  From Fertilization to Adult Sexual Behavior (1996)
At the time of our 1996 Hormones and Behavior review, microRNAs were called pre-mRNAs. See our section on molecular epigenetics:

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

Social odors are still called pheromones and we linked the food energy-dependent pheromone-controlled physiology of reproduction to all biophysically constrained biodiversity on Earth via sex differences in microRNAs (pre-mRNAs).
The sex differences in microRNAs will soon be linked to sex differences in healthy longevity and to sex differences in diseases in the context of the cell biology game: “Cytosis.” Next, the game “Subatomic” will teach others how to build an atom.
The fact that this invited review linked energy-dependent changes in atoms to ecosystems may still go unnoticed, since the invited review was returned without review.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
But, for God’s sake, see for comparison: 7/25/13
Jay R. Feierman:

“Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding [of] Darwinian biological evolution.”

Do not ignore the fact that Jay R. Feierman has no understanding of how ecological variation must be linked to energy-dependent ecological adaptation via the pheromone-controlled physiology of reproduction.
See also: December 5, 2016

[MODERATOR NOTE: I’m not going to post more from Kohl until he answers the very direct and simple question posed to him by anon, which is whether he (Kohl) believes that RNA splicing can change DNA.]

What I believe about RNA splicing is irrelevant unless someone else links the creation of energy to ATP and the creation of RNA outside the context of energy-dependent alternative splicings of pre-mRNA and the link from energy to the creation of the pre-mRNAs and to energy-dependent biophysical constraints on supercoiled DNA in all living genera.

As Heyn points out, “we still do not fully understand the mechanisms that drive epigenetic variation in populations.”

Natural selection for energy-dependent codon optimality links RNA-directed DNA methylation to all biophysically constrained biodiversity via the pheromone-controlled physiology of reproduction. That fact seems to be missing from this representation of a failed paradigm (neo-Darwinian evolution).
Claims that facts about natural selection and epigenetic variation in populations are not fully understood can be viewed in the context of reports by those who understand the facts about Darwin’s “conditions of life.” They are energy-dependent and RNA-mediated
See for example: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition and Olfaction Warps Visual Time Perception
It has become obvious to all serious scientists that the sense of smell in bacteria must be linked from mRNA stability to our visual perception of mass and energy in the context of natural selection across the time-space continuum via the pheromone-controlled physiology of reproduction. The complexity of that fact may not be understood by biologically uninformed theorists, but no theorist should claim that the mechanisms of food energy-dependent pheromone-controlled biophysically constrained cell type differentiation are not understood by all serious scientists.
Re: …a strong link between population-specific DNA methylation, mRNA levels, and genotypes.
See also: Methylation Variation Documented Between Human Populations

“Our analysis of five worldwide populations revealed a strong correspondence between population-specific DNA methylation, [messenger RNA] levels, and genotypes,” the authors wrote. “The correlation with genetic divergence was stronger for DNA methylation, and, consistent with this, our results suggest stronger local genetic control of population-specific DNA methylation levels than of mRNA expression levels.”

The strong link and/or strong correspondence between food energy-dependent DNA methylation, messenger RNA levels and genotypes is biophysically constained by the pheromone-controlled physiology of reproduction in all livng genera. See for example: 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.

Glycolysis and the citric acid cycle appear to provide the free energy for nuclear ATP synthesis and the food-energy-depenent biosynthesis of messenger RNA. If so, all pathology is caused by the virus-driven degradation of messenger RNA, which links mutations but not from ecological variation to ecological adaptations.
See also: Back to Basics: Next-generation sequencing methods and applications (with my emphasis)

…another common NGS application (although one currently more of a research application than a front-line clinical tool) is to examine the transcriptome of a sample—that is, the identity and relative abundance of mRNA transcripts present. Sometimes referred to as “exome sequencing,” this approach is efficient in that it applies resources only to that small portion of the genome which is functionally expressed. Of course, not all significant genetic aberrations occur within coding regions; but by observing levels (or even presence/absence) of transcripts in comparison to reference “normal” conditions, important mutations in non-coding regions such as gene promoters or splice site regulators can be inferred. When such findings are plausibly related to a disease condition, more directed studies to confirm the root cause can then be undertaken as or if needed.

See also: microRNA “exome sequencing Items: 1 to 20 of 55 There is no need to infer that splice site regulators are not food energy-dependent and yet that is what biologically uninformed neo-Darwinian theorists have consistently done with their claims about Mutation-driven evolution. For comparison, all serious scientists are Combating Evolution to Fight Disease.
See also: Global Epigenomic Reconfiguration During Mammalian Brain Development July 4, 2013

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Finally, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain, and that CG demethylation at these hmC-poised loci depends on Tet2 activity.

See also: Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres, which was reported as: “Study of inherited herpes virus finds links to ancient humans” August 30, 2017

We used molecular dating methods to compare, for example, the inherited HHV-6B genomes in five individuals from Sardinia, Orkney and England, and estimated that the most recent common ancestor with the inherited HHV-6B existed 24,500 ±10,600 years ago.

The molecular dating methods are evaluated outside the context of what is known about energy-dependent pheromone-controlled feedback loops, which have been linked from the sense of smell in bacteria to our visual perception of mass and energy in the context of the space-time continuum. But, rather than repeat myself, I will simple support my claims with a link to: Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants, which was reported in January, 2013, as: Past 5,000 years prolific for changes to human genome. The changes can be place into the context of exome sequencing, but not mutation-driven evolution.
The recent origin of most human protein-coding variants can be linked from food energy-dependent changes in exomes that are biophysically constrained by the pheromone-controlled physiology of reproduction in all living genera. The recent origin of the variant can also be linked from the virus-driven degradation of messenger RNA to all pathology.

Of 1.15 million single-nucleotide variants found among more than 15,000 protein-encoding genes, 73% in arose the past 5,000 years, the researchers report. 164,688 of the variants — roughly 14% — were potentially harmful, and of those, 86% arose in the past 5,000 years.

See also: Whole-Exome Sequencing Reveals a Rapid Change in the Frequency of Rare Functional Variants in a Founding Population of Humans (2013)
I repeat:

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
Alternative splicing of pre-mRNA

Autophagy: from pre-mRNAs to microRNAs, enhancers, QTLs et al.

Nothing known to serious scientists links anything except energy-dependent changes in chirality to autophagy and biodiversity via RNA-mediated amino acid substitutions that differentiate all cell types in all living genera. That fact forces pseudoscientists to invent new terms to confuse the biologically uninformed masses who were taught to believe in the neo-Darwinian pseudoscientific nonsense of mutation-driven evolution.
Autophagy in the liver: functions in health and disease 
See the section: Regulation of autophagy by amino acids

See for comparison: From Fertilization to Adult Sexual Behavior

Excerpt from our section on molecular epigenetics.

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

My family members and friends of Robin Williams might be appalled to learn that death from Parkinson’s and death from Lewy Body Disease both include instances of suicide that is caused by untreated virus-driven energy theft. The virus-driven energy theft also is the cause of all pathology in species from archaea to humans. It is manifested as energy-dependent changes in alternative splicings of otherwise identical genes.

The prevention of unnecessary suffering and death could be as simple as restoring the balance of amino acids and sugar to prevent all pathology via RNA-mediated cell type differentiation.

That’s not going to happen without some discussion of what is known to serious scientists about the links from angstroms to ecosystems. All of them are energy-dependent. So, “go ahead,  make my day!”

Ask your professors where the energy came from and how it is linked to the changes in pH that predict when difference in healthy longevity become differences in the types of pathology via links from autophagy to supercoiled DNA or to negative supercoiling.

See also: Processing and transcriptome expansion at the mRNA 3′ end in health and disease: finding the right end

This review suggests the term “pre-mRNA” changed to “microRNA” as serious scientists learned more about how energy-dependent cell type differentiation was biophysically constrained.

We illustrate the medical importance by presenting examples that are associated with perturbations of this process and indicate resulting implications for molecular diagnostics as well as potentially arising novel therapeutic strategies.

This was ~20 years after we linked alternative splicings of pre-mRNA to all cell type diversity via the pheromone-controlled physiology of reproduction in yeasts at the advent of energy-dependent sexual reproduction.

See also: Implications of polyadenylation in health and disease

This review addresses the key steps of polyadenylation and alternative polyadenylation in different cellular conditions and diseases focusing on the molecular effectors that ensure a faultless pre-mRNA 3′ end formation.

Watch as researchers continue to invent new names for the molecular effectors in attempts to obfuscated the facts about biophysically-contrained protein folding chemistry that have been known to all serious scientists since Schrodinger (1944) linked the anti-entropic energy of the sun to all biodiversity.

Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus

Abstract excerpt:

Eusocial insects organize themselves into behavioral castes whose regulation has been proposed to involve epigenetic processes…

Research article summary excerpt:

…behavioral plasticity can be manipulated in the ant C. floridanus by pharmacological and genetic tools that target chromatin regulatory enzymes to stimulate, inhibit, and reprogram behavior. These findings reveal the epigenome as a likely substrate  underlying caste-based division of labor in eusocial insects.

Conclusion:

…our ability to alter a canonical altruistic behavior in a truly social organism by experimental perturbation of a single gene suggests that the application of increasingly versatile reverse genetic approaches in eusocial insects will allow us to expose the general organizational principles underlying complex social systems (10).

See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
All general organizational principles underlying complex social systems are nutrient-dependent and pheromone-controlled in the context of the regulation of gene expression that enables the transgenerational epigenetic inheritance of all morphological and behavioral phenotypes.

‘Mysterious’ non-protein-coding RNAs play important roles in gene expression

Berger and Daniel Bose, PhD, a postdoctoral fellow in her lab, study the regulation of gene expression from enhancers, non-coding regions of the genome more distant from protein-coding regions.

The only mystery should focus on why they thought they could continue to suppress the facts by referring to natural selection for energy-dependent codon optimality in terms like “enhancers.” Since 2013, everything known to serious scientists about nutrient-dependent microRNAs has been linked to all healthy longevity and virus-driven energy theft has been linked to to all pathology. Serious scientists are not using the term “enhancer.” See for example any of the 56,000 published works that use the term “MicroRNA

Ask why Phys.org / Medical Xpress must report old news from 2013 in the context of unpublished research by two people who cannot be found on the PubMed indexed list of research that links sunlight from chirality to autophagy and chromosomal rearrangements to all biodiversity via energy-dependent changes in the microRNA/messenger balance, which link supercoiled DNA to the protection of all organized genomes from virus-driven entropy.

See: Enhancer RNAs alter gene expression: New class of molecules may be key emerging ‘enhancer therapy’

Enhancers are sequences in the genome that act to boost or “enhance” the activity or expression of nearby genes. They “often behave in a cell-specific manner and play an important role in establishing a cell’s identity and functional potential,” said Christopher Glass, MD, PhD, a professor in the department of Medicine and Cellular and Molecular Medicine at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of RNA on a broad scale in neurons and macrophages, a type of immune system cell. Dubbed eRNAs…

I do not know any serious scientists who accepts the term invented to replace pre-mRNAs after the term microRNAs was introduced at the turn of this century and more than 56,000 published papers now use the term microRNA in the context of links from metabolic networks to genetic networks in all living genera via non-coding RNAs..

SnapShot: Non-coding RNAs and Metabolism

In recent years, understanding the crucial role played by cellular homeostasis in disease initiation and progression became the focus of scientists and clinicians. This SnapShot sketches the involvement of both short microRNAs and long ncRNAs in the major metabolic pathways altered in diseases.

Functional Importance of eRNAs for Estrogen-dependent Transcriptional Activation Events

Who do they think does not know that the functional importance of microRNAs and the functional difference of eRNAs is the same. eRNAs are the term theorists use for microRNAs.

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

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

See also: SPECIAL ISSUE—THE ZIKA VIRUS GLOBAL PANDEMIC: THE LATEST EMERGING INFECTION
Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia

It is still not well understood what role(s) the Hofbauer cell has in facilitating or inhibiting transplacental transmission of infectious agents such as the Zika virus. However, based on the demonstration in this communication of proliferation and prominent hyperplasia of Hofbauer cells in the placenta from a microcephalic fetus infected early in gestation, the identification of residual Zika virus in villous stromal cells, using an RNA probe, and the previously published results of in vitro infection and replication of Zika virus in human Hofbauer cells, it appears highly probable that the Hofbauer cell has an important, or even primary, role in those cases where transplacental transmission of the Zika virus does occur. The unexpected absence in placental tissues of any necrosis or leukocytic response by the mother or fetus to transplacental Zika virus infection is also interesting and of unknown significance.

The absence of a response in the organized genomes of the host clearly indicates ecological adaptation to the virus has already occurred and the supercoiled DNA of the host helps to protect a host from DNA damage. The infants are comparatively unprotected. If they survive to reproduce, and their bones turn up in what a future paleontologist thinks is a fossil record that spans hundreds of thousands of years, the paleontologist would almost undoubtedly claim to have found a new species of non-human primate.
For comparison, all serious scientists known that energy-dependent autophagy is the link to supercoiled DNA, which protects all organized genome from virus-driven energy theft and genomic entropy.
Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

Filtering light through a prism to identify tissue type

Energy-dependent RNA methylation (6)

After I published Nutrient-dependent/pheromone-controlled adaptive evolution: a model, Lynnette Ferguson and Justin O’Sullivan invited me to submit this review of nutritional epigenetics for inclusion in a special issue of the journal “Nutrients.”
Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (April 10, 2014)
Abstract:

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

My comment: My invited review was promptly returned without review. That’s why I published my review to the figshare.com site. I realized that the guest editors had “baited” me so that I would supply the latest information to them. Here are some examples of how the information was used by Lynnette Ferguson.
The Interaction between Epigenetics, Nutrition and the Development of Cancer (2015) Received 28 July 2014. This article belongs to the Special Issue Nutritional Epigenetics
Abstract excerpt:

The epigenetic modifications investigated include DNA methylation, histone modifications and the influence of microRNAs.

Conclusion:

…it is imperative to understand the implications of diet on epigenetic modifications, and the effect of those modifications on the development of cancer today and in future generations. Such an understanding and an appropriate resultant response would help decrease the level of risk in future generations.

My comment: Claiming that interactions occur does nothing to explain cause and effect. Ferguson co-authored an article that took my explanations out of their context and put them back into the context of theories about interactions that have no explanatory power.
For comparison, see: Role of olfaction in Octopus vulgaris reproduction (18 October 2014)
Excerpt:

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).

My comment: The authors linked the claims from my 2013 review to their experimental evidence of biologically-based cause and effect. It took only one citation to my published 2013 review by ethical researchers (Polese, Bertapelle & Di Cosmo) to defeat the attempts of people who attempted to steal the information and use it without attribution — as if it supported their ridiculous theories.
However, in this case, Eleckonich and Robinson (2000) had also cited our 1996 Hormones and Behavior review of RNA-mediated cell type differentiation: From Fertilization to Adult Sexual Behavior. We included a section on molecular epigenetics that linked microRNAs, which at the time were called pre-mRNAs, to the physiology of reproduction in yeasts, all invertebrates, and all vertebrates. When they cited my 2013 review and Elekonich and Robinson (2000),  Polese, Bertapelle & Di Cosmo (2015) established a context-based history of advances in understanding molecular epigenetics.
For contrast, Lynnette Ferguson has repeatedly attempted to sneak though the back door of serious scientists with this article: Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition and this comment from Are We Eating Our Way to Prostate Cancer—A Hypothesis Based on the Evolution, Bioaccumulation, and Interspecific Transfer of miR-150
Excerpt:

The discovery of miRNA in sperm effectively overshadowed the previous experimental findings that worms and plants used miRNA in a transgenerational inheritance pattern [58], as it indicated that mammalian miRNAs evolved from other mammals, mimicking their divergent inheritance pattern. There is another seemingly neglected mechanism of miRNA inheritance—which is of paramount importance in the context of miR-150 and oncogenesis—can plant miRNA be recognized and allowed to play epigenetic roles by the mammalian immune system upon oral ingestion? [59]. The discovery that miRNA evolution is linked to complex food web interactions is crucial to our current knowledge, as it involves miRNA in the nutrigenomics of oncogenesis (Figure 2).

See for comparison: The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression (Dec 2, 2014).
In the context of my 2013 review, the authors  helped to establish facts about RNA-mediated cell type differentiation that we presented in our 1996 review. They linked Einstein’s claims from Schrodinger’s claims (1944) to Dobzhansky’s claims (1973) about amino acid substitutions.
The claims about energy-dependent RNA-mediated amino acid substitutions are still being ignored by most theorists. After it became clear that biologically uninformed pseudoscientists would  continue stealing information from me and begin linking the information on microRNAs to amino acids and cancer, I decided to forgo further attempts to publish in journals.
In February 2015, I founded this domain: RNA-mediated.com and the FB discussion group: RNAmediated. I’ve continued to disseminate facts about energy-dependent cell type differentiation that you are not likely to see represented anywhere else, until after I have detailed them.
I also prepared and presented several poster sessions with recorded narratives that are available from Labroots conferences with the following themes.
Neuroscience: From hydrogen atom transfer in DNA base pairs to ecosystems (March 2, 2016)
Excerpt: 

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on DNA base pairs in solution and RNA-mediated amino acid substitutions to chromosomal rearrangements via pheromone-controlled changes in the microRNA / messenger RNA balance.

Neuroscience: RNA mediated molecular epigenetics and virus driven entropy (March 2, 2016)
Excerpt:

Energy-dependent molecular epigenetics support Einstein’s complete molecular mechanical theory via established links from microRNA flanking sequences to DNA base pair substitutions and amino acid substitutions in adhesion proteins.

Molecular Diagnostics What is life when it is not protected from virus driven entropy (March 30, 2016)
Excerpt:

The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy.

Genetics and Genomics RNA-mediated physics, chemistry, and molecular epigenetics (May 3, 2016)
Excerpt:

Olfaction and the innate immune system link energy as information from the epigenetic landscape to the physical landscape of supercoiled DNA.

See also: Endogenous retroviruses function as species-specific enhancer elements in the placenta (February 10, 2013)
Excerpt:

We speculate that ERV variation, exposed by the permissive epigenetic state within the placenta, allows the fetus increased evolvability against maternal defenses. Specifically, by relaxing epigenetic repression of ERV activity, the placenta gains access to a highly polymorphic source of enhancer elements that may dramatically influence its developmental phenotype (Fig. S5). As the placenta is a transient organ, the long-term advantage conferred by increased developmental evolvability would outweigh the potentially mutagenic effects of ERV activity. We propose this model as a plausible explanation for the persistence of placenta-specific ERV activity, which has been observed in all major mammalian taxa31.

My comment: Developmental phenotypes are energy-dependent in all living genera. After I was alerted to more recent claims about virus-driven pathology, my focus changed from energy-dependent RNA-mediated cell type differentiation to nutrient energy-dependent protection of complex functional structures like the bacterial flagellum and teeth. When I realized that virus-driven energy theft was the cause of all pathology, I paid more attention to reports that attested to the claims I had already included in my published works and publications on RNA-mediated cause and effect.
For example see: Water-Mediated Collagen and Mineral Nanoparticle Interactions Guide Functional Deformation of Human Tooth Dentin
The authors link what is known to physicists and chemists to the conserved molecular mechanisms of energy-dependent RNA-mediated cell type differentiation via differences in the diet of C. elegans and P. pacificus, a predatory nematode with teeth. Unfortunately, the “…optimization of tooth dentin to reliably resist…” that requires experience-dependent exposure to loads was placed into the context of “evolutionary optimization.”
Attempts have failed to explain to others why “evolutionary optimization” is not possible in the context of what is known to serious scientists about biophysically constrained RNA-methylation and energy-dependent protein folding chemistry, which must be linked to species-specific behavior via the physiology of reproduction.
No matter how much more information or raw insight is added to what is already known, theorists will not look at the experimental evidence, or perhaps they will simply continue to ignore it. People like Lynnette Ferguson, will continue to do what they have always done. They will steal the energy that serious scientists use in attempts to accurately portray what is currently known about biophysically constrained energy-dependent biologically-based cause and effect.
See for instance: Philosopher earns 14th retraction for plagiarism
My comment: As the experimental evidence continues to become an overwhelming threat to the pseudoscientific nonsense touted by theorists, we will see more claims like this:
Conclusion:

This review is far from comprehensive or complete and yet hopefully shows the enormous complexity of viral latency and its regulation at the genetic and epigenetic levels. This information provides great opportunity for the development of innovative and highly selective therapeutic intervention. As viral latency is responsible for life-long pathogenesis and mortality risk, the tasks ahead are in sight, but challenges remain. — Epigenetics and Genetics of Viral Latency (May 11, 2016)

My comment: My reviews were conclusive and I established the fact that virus-driven energy theft must be biophysically constrained by the availability of nutrients and lack of social stress that predicts the changes in pH that lead to viral replication. The need to model cause and effect in the context of energy-dependent changes that link angstroms to ecosystems has become increasingly clear.
See also: Viral Reprogramming of the Daxx Histone H3.3 Chaperone during Early Epstein-Barr Virus Infection
Conclusion:

These findings also demonstrate that host chromatin assembly is an important form of host cell intrinsic resistance to viral infection.

My comment: I have placed that claim into my model and repeatedly stated clearly that energy-dependent RNA-mediated amino acid substitutions are linked to supercoiled DNA, which protect the organized genomes of all living genera from virus-driven energy theft and genomic entropy. The virus-driven energy theft links mutations to all pathology. I reiterate:

“…viral latency is responsible for life-long pathogenesis and mortality risk…” – Lieberman (2016)

My comment: Energy-dependent RNA-mediated amino acid substitutions are responsible for life-long healthy longevity and decreased mortality risk.
See also: Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells
Reported on 6/7/16 (with my emphasis) as:

“I don’t see a lot of research on the role of ‪#‎epigenetics‬ in suppressing endogenous retroviruses, so I was intrigued by this one. The investigators in this article in Development turn off the gene Setdb1, a histone methylator, and let slip the dogs of MLV. I’m certain one of our regular visitors will find this interesting.

Working on mouse cells, the team of researchers from Germany’s Ludwig Maximilians University and elsewhere discovered that releasing Setdb1’s hold on endogenous retroviruses definitely allows murine leukemia virus (MLV) to ramp up protein production, ultimately killing the host cells. Of course.
Previously, it hadn’t quite been clear whether cells lacking Setdb1 died due to viral protein production or some other reason, and this work is a solid step toward the former explanation.
Check out the article here in Development.
http://dev.biologists.org/content/143/10/1788
-CW New England Biolabs”
My comment: I am a regular visitor at the New England Biolabs FB page and a regular contributor of comments on the information they disseminate. But, given the return without review of my invited review by the guest editors who requested it, I have become increasingly suspicious of what may be subtle attempts to “bait” me, again.
Fortunately, others are moving forward. See for example: The Quantum Nature of Drug-Receptor Interactions: Deuteration Changes Binding Affinities for Histamine Receptor Ligands (May 9, 2016) reported by John Hewitt on June 7, 2016 as: Using the ‘deuterium switch’ to understand how receptors work
Excerpt: 

…olfaction is probably the space where these deuterium switches and chiral switches most informatively converge to elucidate how receptors might operate. In fact, the authors explicitly highlight the fact that their histamine receptor model may have something to say about olfactory receptors. Importantly, both of these receptor classes belong to the so-called GPCR (G-protein coupled receptor) family that vertebrates use to detect odorants; half of our own 800 GPCRs are provisioned almost exclusively to olfaction.
The author’s main comments, here, center on the aromatic groups of molecules, features that are typically associated with delocalized electrons. For example, the imidazole ring of histidine (histamine’s the amino acid precursor) is aromatic at all pH values; four of its pi electrons form two double bonds and two from a nitrogen lone pair. The authors propose that a major fallout of deuteration is that the aromatic moiety shrinks the effective C–D distance relative to its C–H value. Aromatic C–H bonds act as proton donors and form weak hydrogen bonds with water molecules and proton acceptors at the receptor binding site.

My comment: Thanks for trying to help others to understand the overwhelming complexity, John Hewitt. I noticed that they cited “Molecular vibration-sensing component in Drosophila melanogaster olfaction,” which was co-authored by Luca Turin, but these authors failed to link cell type differentiation from all invertebrates to all vertebrates via what is known about nutritional epigenetics, microRNA flanking sequences, RNA methylation, the innate immune system, supercoiled DNA, behavior, and consciousness.

Others may want to see “Dose-Dependent Effects of the Clinical Anesthetic Isoflurane on Octopus vulgaris: A Contribution to Cephalopod Welfare” and other works by Anna Di Cosmo’s group. Michael Crawford’s group has also made progress by ignoring claims about “quantum Darwinism” and focusing on the energy-dependent de novo creation of GPCRs, like olfactory receptor genes. See for example: A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution

For comparison, see: Periodic Scarred States in Open Quantum Dots as Evidence of Quantum Darwinism

Reported as: Bridge to the quantum world: Darwinian concept of natural selection figures into theory about core of physical reality

Excerpt:

It describes the transition from quantum to classical world as a “decoherence” process that involves a kind of evolutionary progression somewhat analogous to Charles Darwin’s concept of natural selection.

My comment: I’ve mentioned repeatedly that serious scientists have always had the choice to stop investigating claims that Feedback loops link odor and pheromone signaling with reproduction in species from microbes to humans.

SARCASM ALERT: Why should pseudoscientists be the only people who accept the claim that mutations and natural selection replaced the sun’s biological energy as the anti-entropic source that links ultraviolet light to prevention of virus-driven energy theft in all living genera via decoherence in the context of “…a kind of evolutionary progression”? The pseudoscientists need only continue to ignore that fact that Darwin insisted that they ensure “conditions of life” were considered before natural selection.

Darwin’s “conditions of life” are energy-dependent and controlled by the physiology of reproduction. There is no experimental evidence of biologically-based cause and effect that links the energy-dependent physiology of reproduction from mutations to the diversity of morphological phenotypes and all  experimental evidence of biologically-based cause and effect links energy-dependent RNA methylation from the innate immune system to supercoiled DNA.

 
 
 
 
 
 

rp_levels-of-organization.jpg

RNA-mediated DNA modifications

Using their approach, which combines bioanalytical chemistry, comparative genomics, and a special type of DNA sequencing, the team has discovered a DNA modification that helps bacteria to protect their genomes from viral infection.

My comment: There is one way to link nutrient-dependent microRNA flanking sequences from adhesion proteins to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. It starts with energy-dependent changes in hydrogen-atom transfer in DNA base pairs and links them to the nutrient-dependent RNA-mediated amino acid substitutions that differentiate all cell types of all individuals of all living genera.
The amino acid substitutions link RNA-mediated DNA repair from the de novo creation of olfactory receptor genes to the physiology of reproduction. Viruses steal the energy required to support the physiology of reproduction. The theft of energy by viruses links mutations to loss of function in the context of nutrient stress or social stress, which is linked to all pathology.
If their approach starts with bioanalytical chemistry, they will not link quantum physics to comparative genomics.  Until they start from what is known about quantum physics, their link to protection of organized genomes from viral infection will be incomplete.
I’ve already linked angstroms to ecosystems and it is time for them to catch up.  It is also time for everyone to stop reporting that they have found a new way to discover how hydrogen-atom transfer in DNA base pairs in solution is linked from the sun’s biological energy to all DNA modifications via RNA-mediated events linked to all cell type differentiation in all individuals of all living genera.
See also: Pre-transition effects mediate forces of assembly between transmembrane proteins

Excerpt: 

The orderphobic effect generates forces of assembly and facilitates protein mobility

My comment: When I read this I thought it suggested the effect generates the forces of the orderphobic effect, a circular argument common among theoretical physicists and evolutionary theorists. The authors clarified the fact that top-down causation is more complicated then a claim that magically links it to protein assembly and mobility.

Their clarification:

Biological membranes and transmembrane proteins are far more complicated than the models considered in this paper. Part of the complexity is associated with multiple components, which allow for more than one order–disorder transition. For example, with a membrane composed of three components, coexistence can be established between liquid-ordered and liquid-disordered phases [47], and both of these phases exist in bio-membranes [6, 7, 8]. The fact that liquid-ordered and liquid-disordered phases can coexist with finite line tension [47] implies the existence of a first-order transition between them [48] and thus the relevance of the orderphobic effect.

My comment: First-order transition in biological membranes links the biological energy of the sun and speed of light on contact with water to the de novo creation of nucleic acids. The creation of nucleic acids links ribonucleic acid (RNA) from biophysically constrained protein folding chemistry to the transmembrane proteins and receptor-mediated cell type differentiation. For example, the de novo creation of G protein-coupled receptors (GPCRs) links chemotaxis and phototaxis to RNA-mediated cell type differentiation and the energy-dependent stability of organized genomes in all living genera.

That fact may be apparent to anyone who has performed blood gas analysis in the lab. Measures of oxygen, carbon dioxide, and pH are carefully calibrated and controls are frequently run to ensure that the results are accurately reported. But, without a model of biologically-based cause and effect that links the results to a patient outcome, even medical laboratory scientists may not understand how their results link physics to chemistry and the conserved molecular mechanisms of healthy longevity.

For an example of what must be included as the basis for the model, see: The architecture of the human RNA-binding protein regulatory network

Conclusion:

We suggest that RBP chains use the modulation of RBP targets as a “connector” to different processes. Like a piping system bringing the “fluid” (regulation) to the various distribution centers (the RBPs) which then open their “valve” (regulate their targets) to influence the functions of interest and pump the “fluid” to the next level (next RBP of the chain). Non-chain interactions could then act as chain modulators (e.g. by stopping transmission halfway through, or further enhancing its flow). Under this model, RBP-RBP interactions constitute a post-transcriptional backbone, with RBPs acting as “split-flow” pumps to drive regulation and tune protein abundances.

My comment: The author’s attest to the systems complexity in terms that make sense to engineers and non-scientists: connectors; fluid regulation; valves; and split flow pumps. But what is the energy source for all the interactions? They also mention the evolution of proteins, as if they were trying to explain the mechanisms of nutrient-dependent RNA-mediated cell type differentiation to a neo-Darwinian theorist.

They stopped short and failed to mention the evolution of proteins in the context of evolutionary rates of sequence divergence. That suggests to me their accurate representation of how biophysically constrained nutrient-dependent RNA-mediated protein folding chemistry links amino acid substitutions to cell type differentiation in all living genera via the physiology of reproduction, lack only one thing. What is the power source that runs the molecular mechanisms they describe? How is hydrogen-atom transfer in DNA base pairs in solution linked to supercoiled DNA and protection against virus-driven entropy?

See also: Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-Regulates Mating Pheromone Response in Saccharomyces cerevisiae

My comment: If others cannot get from the nutrient-dependent pheromone-controlled physiology of reproduction in yeasts to brain development in humans via the conserved molecular mechanisms of biologically-based cause and effect we detailed in 1996, they may waste another decade or two on research that cannot be placed into the context of any model.

See also: How the Brain Is Computing the Mind A Conversation With Ed Boyden [2.12.16]

Excerpt 1)

One of my dreams is you could take a bacterium or a virus and expand it until you can take a picture on a cell phone. Imagine how that could help with diagnostics, right? You could find out what infection somebody has just by making it bigger, take a picture and you’re done.

My comment: In 2006, Greg Bear incorporated that dream into the plot of his science fiction novel, “Quantico

Excerpt 2)

…we put molecules that are light sensitive into neurons and then we can make them activatable or silence-able with pulses of light.

Our groups have sent these molecules out to literally thousands of basic as well as clinically interested neuroscientists, and people are studying very basic science questions like how is a smell represented in the brain? But they’re also trying to answer clinically relevant questions…

My comment: In 1980, Lewis Thomas suggested that the answer to the question of how smells are represented in the brain is the most clinically relevant question of all.

Excerpt: 

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

See also: The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system

Excerpt:

…studies specifically addressing the expression and function of miR in GnRH neurons are needed to dissect their role in the genesis, migration and maturation of this specific cell type. At present, a systematic study to identify specific miRs relevant for early GnRH neuron development, in vitro or in vivo, has not been reported, as yet. Thus, our results provide the first evidence of the participation of miR-9 and miR-200-class in these early events. We further link two transcription factors with the action of these miRs.

My comment: Our 1996 Hormones and Behavior review of RNA-mediated events link olfaction from pre-mRNAs, which are now called microRNAs,  e.g., miRNA-9 and miRNA-200, to epigenetically-effected cell type differentiation in species from microbes to humans via the conserved molecular mechanisms that link food odors and pheromones to the physiology of reproduction.  More studies will only continue to support the model from the molecular epigenetics section, which has already been supported in any published works by serious scientists during the past 20 years.

rp_levels-of-organization.jpg

A two-faced protein enables RNA-mediated DNA repair (2)

A two-faced protein enables RNA-mediated DNA repair
See also: Abundant contribution of short tandem repeats to gene expression variation in humans (subscription required)
Excerpt:

…suggesting that STRs have a key role in the evolution of expression. Indeed, several candidate gene studies in humans reported that STR variations modulate gene expression19,33–37 and alternative splicing…

Reported as: 

Researchers find repetitive DNA provides a hidden layer of functional information

Excerpt: 

He is calling these variants eSTRs, or expression STRs, to note that they regulate gene expression.

My comment: He is not calling the variants mutations, which means he is not linking mutations to evolution. Instead, he is one step away from calling them microRNAs. A recent PubMed search using the term “microRNA” revealed more than 45,000 published reports. Most of them were published in just the past few years.
Apparently, many serious scientists have been using terms like pre-mRNAs, small RNAs, non-coding RNAs, microRNAs, and QTLs. Some serious scientists have defined the terms they are using to link nutrient energy-dependent RNA-mediated cause and effect to cell type differentiation in all living genera. Some have not. In the mid-1990s, we linked them From Fertilization to Adult Sexual Behavior in species from microbes to humans via the physiology of reproduction without defining the term pre-mRNA. Instead, we used the term in its proper context.
The fact that Yaniv Erlich uses eSTRS rather that pre-mRNAs or other terms is irrelevant. He may confuse others with yet another change of the term. But no matter what you call the variants, they link atoms to ecosystems via nutrient energy-dependent base pair changes and RNA-mediated events, which link the physiology of reproduction to RNA-mediated amino acid substitutions and cell type differentiation in all cells of all individuals of all living genera.
For example, Yaniv Erlich co-authored this journal article.
See also: Cell contact-dependent acquisition of cellular and viral nonautonomously encoded small RNAs
Abstract excerpt:

Synthetic microRNA (miRNA) mimetics, viral miRNAs expressed by infected B cells, and endogenous miRNAs could all be transferred into T cells. These mechanisms may allow small RNA-mediated communication between immune cells.

Conclusion:

Given the propensity of viruses to exploit such opportunities, it seems likely that the studies presented herein will prompt more investigation of the nonautonomous effects of small RNAs in contexts where an advantage may be gained by immune modulation. Moreover, our results also raise the possibility that transfer of small RNAs will be a general principle encountered when other cell types establish the types of contacts represented by example in immune cells.

See our section on: Immunological Factors
Excerpt:

The immune system has long been known to perceive certain sexual differences, e.g., the presence or absence of H-Y antigen (Simpson, 1991). Mice have been shown to enact kin selection on the basis of major histocompatibility complex characteristics within the perceiving mice and from other mice as chemosensitive identified. Humans have been shown to possess similar immune- related chemosensitive skills (Gilbert, Yamazaki, Beauchamp, and Thomas, 1996; Wedekind, Seebeck, Bettens, and Paepke, 1995).

My comment: The fact that the innate immune system links the epigenetic landscape to the physical landscape of DNA via RNA-mediated cell type differentiation has been obvious to most serious scientists for at least two to four decades. The fact that the innate immune system is nutrient-dependent, which links it from cell type differentiation to the physiology of reproduction via food odors and pheromones has been obvious for at least one decade. See: Feedback loops link odor and pheromone signaling with reproduction
See for comparison: Convergent evolution of neural systems in ctenophores
Excerpt:

…comb jellies are carnivorous marine animals with a complex neuromuscular organization and sophisticated patterns of behavior. To sustain these functions, they have evolved a number of unique molecular innovations supporting the hypothesis of massive homoplasies in the organization of integrative and locomotory systems.

Conclusion:

Together with numerous ctenophore ‘innovations’, ctenophores may serve as a model to understand the origins or emergence of complex integrative functions and can be used in synthetic biology and regenerative medicine to design novel regulatory systems.

My comment: The sequencing of the octopus genome has since linked the conserved molecular mechanisms of RNA-mediated cell type differentiation from microbes to man via what has been learned about microRNAs and cell adhesion proteins in the context of supercoiled DNA that protects all organized genomes from virus-driven entropy.
See: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity
And: The octopus genome and the evolution of cephalopod neural and morphological novelties
Excerpt:

Taken together, these novel genes, the expansion of C2H2 ZNFs, genome rearrangements, and extensive transposable element activity yield a new landscape for both trans- and cis-regulatory elements in the octopus genome, resulting in changes in an otherwise ‘typical’ lophotrochozoan gene complement that contributed to the evolution of cephalopod neural complexity and morphological innovations.

And see: A Protocadherin-Cadherin-FLRT3 Complex Controls Cell Adhesion and Morphogenesis
My comment: It seems clear that nutrient-dependent microRNAs and cell adhesion proteins protect the organized genomes of all living genera from virus-driven entropy.  However, there still seem to be questions about how to place that fact into the context of evolution via natural selection of anything except food or via mutations that are linked to loss of function via virus-perturbed protein folding chemistry. This poses some conflict among those who teach neuroscience outside the context of religion, and only one professor seems to be teaching both in the same course.
See:

rp_levels-of-organization.jpg

MicroRNAs and the exposome

 MicroRNAs as Potential Signatures of Environmental Exposure or Effect: A Systematic Review

Excerpt:

Researchers are currently publishing extensive lists of miRNAs that are responsive to environmental exposures and showing their utility as biomarkers of effect. Future research should focus on identifying the molecular mechanism behind miRNA expression changes in response to exposure to determine whether the changes in miRNA expression are merely a symptom of the (patho)physiological processes the organism undergoes after exposure, or whether miRNAs are the drivers responsible for these changes. Izzotti and Pulliero (2014) recently reviewed the putative mechanisms of action behind miRNAs’ response to environmental exposure. However, the effect of the identified miRNAs on putative mRNA targets should also be studied to determine whether the change in miRNA expression has functional consequences and which mRNAs are true miRNA targets under the given circumstances.

My comment: I’m not sure how much more research is required to show that viral microRNAs perturb protein folding and that nutrient-dependent microRNAs repair damaged DNA, which enables the link from nutrient uptake to thermodynamic cycles of protein biosynthesis and degradation via the metabolism of nutrients. The metabolism of nutrients links metabolic networks and genetic networks to the physiology of nutrient-dependent pheromone controlled RNA-mediated amino acid substitutions that are clearly linked from cell type differentiation to biodiversity.
See: Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors.
Excerpt 1)

It is now clearer how an environmental drive probably evolved from that of food ingestion in unicellular organisms to that of socialization in insects. It is also clear that, in mammals, food odors and pheromones cause changes in hormones such as LH, which has developmental affects on sexual behavior in nutrient-dependent, reproductively fit individuals across species of vertebrates.

The original environmental drive of food odors and their effect on LH shares remarkable homology with the function of a sex pheromone in yeast that links pheromones to LH and to reproductive fitness via nutrition in mammals (Maeda et al., 2010).

Excerpt 2)

…ingested plant microRNAs influence gene expression across kingdoms (Zhang et al., 2012). In mammals, this epigenetically links what mammals eat to changes in gene expression (McNulty et al., 2011) and to new genes required for the evolutionary development of the mammalian placenta (Lynch, Leclerc, May, & Wagner, 2011) and the human brain (Zhang, Landback, Vibranovski, & Long, 2011).

See also: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

Excerpt

…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.

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

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

The idea that the conserved molecular epigenetics of RNA-mediated cell type differentiation links food odors and pheromones to biodiversity was detailed in 1996: From Fertilization to Adult Sexual Behavior. Our model of hormone-organized and hormone-activated mammalilan behavior was extended to insects in 2000 and to the life history transitions of the honeybee model organism in 2005. The model was extended to octopuses in 2015. The phylogenetic utility and functional constraint of microRNA flanking sequences links all crustaceans to all insects via the conserved molecular mechanisms of biophysically constrained microRNA balanced protein biosynthesis and degradation and amino acid substitutions that differentiate cell types.
The concept of the “exposome” was proposed in 2005: “Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology.” See also, from 2005, Feedback loops link odor and pheromone signaling with reproduction and from 2011, Frequency-Dependent Recruitment of Fast Amino Acid and Slow Neuropeptide Neurotransmitter Release Controls Gonadotropin-Releasing Hormone Neuron Excitability.
Thanks also to Rhonda Green for bringing to my attention this source for information Chapter 13: Amino Acid Neurotransmitters.
I think the late Robert L. Moss and his co-authors were the first to link a GnRH fragment consisting of the last 6 amino acids of the decapeptide to neurotransmission and to GnRH receptor-mediated behaviors that also link nutrient-dependent pheromone-controlled RNA-mediated amino acid substitutions to behavior in all vertebrates via substitution of achiral glycine in the GnRH (aka LHRH) decapeptide. See: Differential effects of a luteinizing-hormone-releasing hormone (LHRH) antagonist analogue on lordosis behavior induced by LHRH and the LHRH fragment Ac-LHRH5-10. Cited in Human pheromones: integrating neuroendocrinology and ethology
Excerpt:

… Moss and Dudley [32] suggest that a fraction of the GnRH molecule functions directly as a neurotransmitter in rats to elicit a behavioral effect(i.e., lordosis). This behavioral effect is characteristicof a “signal” pheromone, which activates a response.

After many discussions about how the role of pheromones and GnRH were linked across species, Robert L. Moss encouraged me to write the book that was co-authored by the late Robert T. Francoeur: The Scent of Eros: Mysteries of Odor in Human Sexuality The role that human pheromones play in human sexuality has consistently been denied by many colleagues who refuse to acknowledge the difference between theories about mutations and evolution compared to facts about amino acid substitutions. The facts link ecological variation to ecological adaptations via changes in the microRNA/messenger RNA balance that link atoms to ecosystems in all genera via what is currently known about physics, chemistry, microRNAs (aka pre-mRNAs) and molecular epigenetics.

For example, the co-author of Feedback loops link odor and pheromone signaling with reproduction also co-authored Estrogen Permits Vasopressin Signaling in Preoptic Kisspeptin Neurons in the Female Mouse.

The article published last week attests to facts about amino acid-mediated regulation of GnRH neuron excitability that link vertebrate GnRH to Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes. The differences in morphological and behavioral phenotypes is clearly nutrient-dependent and pheromone-controlled, and the differences arise in the context of a difference in parental feeding.
Colleagues who have failed to link nutrient uptake from GnRH to estrogen and other hormones that affect behavior will probably continue to ignore the latest information that supports what we detailed in our 1996 Hormones and Behavior review — if only because they have failed to learn anything about cell type differentiation during the past two decades. They knew nothing about RNA-mediated sex differences in cell types in 1996 and still know nothing about RNA-mediated amino acid substitutions and cell type differentiation in 2015.