For God and Country

Energy-dependent structure and function: Until death (1)

The structure-energy landscape of NMDA receptor gating

…using single-molecule Forster resonance energy transfer (smFRET), we map the energy landscape of the first transmembrane segment of the Rattus norvegicus NMDA receptor under resting and various liganded conditions. These results show kinetically and structurally distinct changes associated with apo, agonist-bound, and inhibited receptors linked by a linear mechanism of gating at this site. Furthermore, the smFRET data suggest that allosteric inhibition by zinc occurs by an uncoupling of the agonist-induced changes at the extracellular domains from the gating motions leading to an apo-like state, while dizocilpine, a pore blocker, stabilizes multiple closely packed transmembrane states.

Achiral glycine in position 6 of the gonadotropin releasing hormone (GnRH) decapeptide links the energy landscape from ecological variation to the stability of the 7 transmembrane states in the GnRH receptor to the creation of all biophysically constrained vertebrate biodiversity via feedback loops that link food odors and pheromones to the survival of all species on Earth. Organisms die without food and species become extinct when too many conspecifics die. The virus-driven degradation of messenger RNA, links mutations to all pathology and to death and the extinction of species.
Reported as: Molecule Movements Through Nerve Cells Could Lead to Multi-functional Drugs

The NMDA receptor is set of four protein subunits, each with four domains, and each of those domains has a particular function. Collectively, they span the cell membrane. Each subunit can have many “states,” or shapes, that regulate which electrical signals — and how many of them — pass through. The subunits sit on each side of the channel and activate when they bind both glutamate and glycine neurotransmitter ligands and trigger the signaling pathway that allows positively charged ions to pass into the cell.

The energy-dependent “states” are the functional shapes of receptors that link electrical signals to receptor-mediated behavior and to all biodiversity. Their function can be examined in the context of links from electrons to ecosystems via cryo-electron microscopy (cryo-EM).
All energy-dependent functions in all living genera link top-down causation from food energy-dependent feedback loops to the pheromone-controlled physiology of reproduction in species of microbes to survival of all species. For example, the effects of energy-dependent binding of glutamate and glycine neurotransmitter ligands to their substrates can be examined in the relatively simplistic context of this 2005 review of ecological variation and ecological adaptations.
Feedback loops link odor and pheromone signaling with reproduction

It appears that GnRH neurons integrate a variety of information about the internal state of the animal and its external environment. At least 10,000 neurons in 26 different brain areas appear to transmit signals directly to GnRH neurons. Among these are areas involved in odor and pheromone processing, sexual behavior, arousal, reward, and other functions. This suggests that GnRH neurons are poised to modulate reproductive physiology and behavior in accordance with the overall state of the animal.

These studies also indicate that GnRH neurons are likely to influence numerous brain functions. They appear to transmit signals to as many as 30,000 or more neurons in 34 brain areas, consistent with previous studies showing GnRH+ fibers and GnRH receptors in multiple brain regions (Badr and Pelletier, 1987; Jennes et al., 1988; Jennes et al., 1997). BL+ neurons likely to receive synaptic input from GnRH neurons were seen in areas associated with numerous different functions, including odor and pheromone processing, sexual behavior, appetite, defensive behavior, motor programs, and the relay of information to higher cortical areas. These results may reflect a strategy wherein GnRH neurons can modify diverse functions in order to coordinate the internal state of the animal and its behavior with reproduction in order to optimize reproductive success.

See for comparison to what is known about the feedback loops: Replication defective viral genomes exploit a cellular pro-survival mechanism to establish paramyxovirus persistence
My summary: Viral persistence (paramyxovirus persistence) and biophysically constrained epigenetically-effected viral latency require the energy-dependent fine-tuning of epigenesis and epistasis that links the pheromone-controlled physiology of reproduction from species of microbes to humans via what is known about soil microbes, fescue toxicosis, and the bull sperm microRNAome.
The most confusing representation of biophysically constrained energy-dependent epigenetically-effected top-down causation I have ever seen was reported as: Team shows how seemingly acute viral infections can persist

…our cells are wired to survive if they are engaged in an antiviral response…

One expert from the report, which is about the well known aspects of food energy-dependent autophagy attests to all the facts known to serious scientists. The facts refute the pseudoscientific nonsense touted by most theorists. For example, see the three articles that link the food energy-dependent pheromone-controlled physiology of reproduction in soil bacteria to all biodiversity in mammals.

  1. The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression
  2. Circulating microRNA as candidates for early embryonic viability in cattle
  3. The Breadth of Viruses in Human Semen 

The presence of viruses in semen is probably more widespread than currently appreciated, and the absence of virus in genital secretions should not be assumed for traditionally non–sexually transmitted viruses. The investigation of virus detection and persistence in semen across a range of viruses is useful for clinical and public health reasons, in particular for viruses that lead to high mortality or morbidity rates or to epidemics.

The presence of viruses in bacteria (bacteriophages) and in semen attests help to explain how serious scientists have linked the virus-driven theft of quantized energy from the degradation of messenger RNA to mutations and all pathology in all living genera. The facts can now be placed into the context of the fact that other organisms typically do not commit suicide. Energy-dependent autophagy typically links chirality to the protection of all cell types in all individuals of all species from suicide. That fact left me and others with questions about why people commit suicide.
See: Energy-dependent structure and function: Until death (2)
See also: Energy-dependent structure and function: Until death (3)

Filtering light through a prism to identify tissue type

Hydrogen-atom energy in DNA base pairs

See also: Consciousness is simply food rearranged
Role of Double Hydrogen Atom Transfer Reactions in Atmospheric Chemistry
Abstract excerpt: 

Hydrogen atom transfer (HAT) reactions are ubiquitous and play a crucial role in chemistries occurring in the atmosphere, biology, and industry.

My comment: The link from physics to chemistry and the conserved molecular mechanisms of biologically-based RNA-mediated cell type differentiation has been the focus my works for more than 20 years, even before I knew what I would need to explain about the energy-dependent links from angstroms to ecosystems via hydrogen-atom energy in all living genera.
See also: For first time, researchers see individual atoms keep away from each other or bunch up as pairs

Different configurations of electrons give rise to specific elements, making carbon atoms, for instance, distinct from hydrogen atoms.

My comment: Without the different configurations of electrons,  energy-dependent changes in angstroms could not be linked from hydrogen-atom transfer (HAT) in DNA base pairs in solution to all biodiversity in all ecosystems. Simply put, the sun’s biological energy must be linked from atmospheric chemistry to biophysically constrained protein folding chemistry on Earth.
When these interactions are seen for the first time the experimental evidence must confirm theories. Otherwise physicists will try to come up with new untestable theories to stall scientific progress.  Serious scientists make progress when experimental evidence is accepted. Chemists typically know what to accept. So do molecular biologists.
What do evolutionary theorists or other social scientists know about physics, chemistry, or molecular epigenetics? How do pseudoscientists known what to accept when they already have accepted only theories?
For comparison, serious scientists know that angstroms measure distance, and every angstrom is dynamic in the context of energy-dependent RNA-mediated cell type differentiation. How can any serious scientist understand the claims of theorists made in the context of articles like this:
Humans and Neanderthals had sex. But was it for love? An investigation

We know for sure humans and Neanderthals had sex because of a Swedish scientist named Svante Pääbo, who “more or less invented the field of paleogenetics,” Elizabeth Kolbert wrote in a terrific New Yorker article in 2011.

My comment:  Elizabeth Kolbert lied and used Svante Pääbo’s works to support her ridiculous claim:

We know for sure humans and Neanderthals had sex…

Serious scientists know that Svante Pääbo is the senior author of two articles. The two articles linked Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees and Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates.
Natural selection for the de novo creation of olfactory receptor genes and the loss of genes is not an indicator that humans and Neanderthals had sex. It is an indicator that natural selection for energy-dependent codon optimality occurred in the context of the physiology of reproduction in all primates. For contrast, all serious scientists know that members of two different species do not have sex. Chromatin remodeling and chromosomal rearrangements limit fertility among species via their nutrient-dependent pheromone-controlled physiology of reproduction and their behavior. The behavior is linked to energy-dependent codon optimality via the physiology of reproduction, not by sex between consenting humans and Neanderthals.
Is is silly to ask questions about sex for love without consideration of fertility, since the sexual interactions must be linked to survival of the species via biophysically constrained RNA-mediated protein folding chemistry in the context of the physiology of reproduction. The biophysical constraints are energy-dependent, but the theorists’ and journalists’ preference for fiction is clear.

Robert Sawyer is a science fiction author who won the Hugo Award — one of sci-fi’s highest honors — for his 2002 book Hominids, a story that imagines a parallel world where Neanderthals survived and we didn’t. In the book (which spawned a trilogy), a Neanderthal physicist opens up a rift between the worlds and falls in love with a human.

For comparison, see this presentation text about Greg Bear’s novels in which he detailed for his non-technical audience how the nutrient energy-dependent pheromone-controlled physiology of reproduction is linked from RNA-amino acid substitutions to all cell type differentiation in all individuals of all species. The Darwin Code
See also: Structural and Functional MRI Differences in Master Sommeliers: A Pilot Study on Expertise in the Brain

This study identified enhanced structural and functional patterns in the olfactory network of sommeliers. These findings are consistent with the learning they undergo in achieving the status of Master Sommelier. Furthermore, the volume of a region of the brain involved in olfactory memory was associated with experience, suggesting that the continued training results in morphological changes of the brain. These results speak to the plasticity of the adult brain in response to sensory expertise.

Reported as: Smelling Lots Of Wine Makes Your Brain Alzheimer’s Resistant

Overall, these differences suggest that specialized expertise and training might result in enhancements in the brain well into adulthood,” the study states. “This is particularly important given the regions involved, which are the first to be impacted by many neurodegenerative diseases.

See also:  What Sensory Receptors Do Outside of Sense Organs
My comment to the Scientist (I have posted: 361 comments so far)

20 years ago, we published: From Fertilization to Adult Sexual Behavior, which was a review of RNA-mediated cell type differentiation. We included a section on molecular epigenetic in the Hormones and Behavior review.

Unfortunately, few people realize that natural selection for energy-dependent codon optimality links the de novo creation of genes from the creation of G protein-coupled receptors to chemotaxis and to phototaxis before biophysically constrained energy-dependent biodiversity via RNA-mediated protein folding biochemistry can be linked to all biodiversity by amino acid substitutions.
When others report that mutations are linked to pathology, they seem to miss the fact that virus-driven energy theft causes the mutations. Nutrient-energy dependent viral latency has gone missing from explanations that would otherwise link what is known about biologically-based cause and effect from physics to chemistry and everything known about molecular epigenetics.
See also: Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization
My comment: Pseudoscientists could challenge representations like this if they had experimental evidence for comparison. They don’t. They have only their ridiculous theories, which they report in the story about sex between modern humans and Neanderthals. It is unadulterated pseudoscientific nonsense and nothing more than an unsubstantiated fictional account. It is not science fiction. The theorists claims are not scientifically based.
See for comparison: Role of olfaction in Octopus vulgaris reproduction and Two fatty acyl reductases involved in moth pheromone biosynthesis
Both articles cite Kohl (2013) Nutrient-dependent/pheromone-controlled adaptive evolution: a model
See also: The Ancient Origins of Consciousness: How the Brain Created Experience

12. Plotnick, Dornbos, and Chen (2010). Others who advocate smell-first are Lucia Jacobs (Jacobs, 2012), who says the building of smell maps of environmental space came first and James Kohl (Kohl, 2013), whose model says chemical ecology is the main driver of adaptive evolution.  — p. 263

My comment: Chemical ecology is the main driver of energy-dependent ecological adaptations. It is not not the driver of mutation-driven evolution, and so far there is no other model for comparison to my model of chemical ecology. I deliberately used the term adaptive evolution to see if someone would take the bait and offer another model for comparison. No one did.
See also: How Psychiatrist Jon Lieff Turned an Interest in Cellular Intelligence into Award-Winning Blogging!
My comment: Lieff still presents cellular intelligence in the context of evolution. He ignores what is known about hydrogen-atom energy in DNA base pairs in solution. That shows how successful a blogger can be if they simply fail to address what is known about biophysically constrained RNA-mediated cell type differentiation. His focus is on evolution! That means he does not need to explain anything about how evolution occurs, or explain what he thinks cellular intelligence is or where it came from!
See for comparison: Direct interrogation of the role of H3K9 in metazoan heterochromatin function
Reported as: Tight DNA packaging protects against ‘jumping genes,’ potential cellular destruction
Tight DNA is supercoiled DNA and it protects the orgnaized genomes of all living genera from virus-driven energy theft and genomic entropy. Simply put, supercoiled DNA biophysically constrains virus-driven energy theft, which is the only way to establish a link from ecological variation to ecological adaptation without inventing another ridiculous theory.

… viral latency is responsible for life-long pathogenesis and mortality risk…

Nutrient energy-dependent microRNAs are the obvious link from olfaction to biophysically constrained RNA-mediated protein folding chemistry, plasticity, and prevention of all pathology.
See for example: Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

Supercoiled DNA is the link to viral latency, which is the link to healthy longevity.

See also, from the Neuroscience FB group “As simple as random can be”
See also:  Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
My comment: There is no experimental evidence of biologically-based cause and effect that links anything except energy or energy theft to the species-specific COMT Val158Met amino acid substitution during life history transitions and the development of morphological and behavioral phenotypes.

COMT val158met polymorphism and molecular alterations in the human dorsolateral prefrontal cortex: Differences in controls and in schizophrenia

…the COMT val158met polymorphism is not found in species other than humans (Palmatier et al., 1999).

My comment: That fact makes the COMT val158met polymorphism a “smoking gun” in the context of energy-dependent de novo gene creation and virus-driven energy theft that links gene losses to loss of function via differences in G protein-coupled receptors.
Dopamine Neuron-Specific Optogenetic Stimulation in Rhesus Macaques
G protein-coupled receptor kinases as regulators of dopamine receptor functions
Subsecond Regulation of Synaptically Released Dopamine by COMT in the Olfactory Bulb
Programmable RNA-binding protein composed of repeats of a single modular unit
Excerpt from the conclusion:

… Pumby may present a simplified context in which to insert Pumilio modules to study how specific amino acids contribute to the emergent properties of modular RNA binding, independent of position-specific effects.

See also: Another gate-keeping attempt by Feierman

Filtering light through a prism to identify tissue type

RNA-mediated physics, chemistry, and molecular epigenetics (5)

Researchers criticize the Mukherjee piece on epigenetics: Part 2


…the organisms that have taught us the most about development – flies (Drosophila) and worms (C. elegans)—do not have the enzymes required for DNA methylation.

My comment:

James V. Kohl

Posted May 9, 2016 at 7:36 pm | Permalink

Please see Structural diversity of supercoiled DNA
Serious scientists have linked the epigenetic landscape to the physical landscape of supercoiled DNA via everything known about the innate immune system and energy-dependent changes in hydrogen-atom transfer in DNA base pairs that link angstroms to ecosystems via metabolic networks and genetic networks.
This report is a problem for pseudoscientists: Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system
Weekend evolution of the bacterial flagellum is not consistent with any theoretical approach. Siddhartha Mukherjee refuses to let neo-Darwinism die without more obfuscation of facts.
See also: The New Yorker screws up big time with science: researchers criticize the Mukherjee piece on epigenetics

…epigenetic processes analogous to those performed by the Yamanaka factors are performed by bacteria that entirely lack histones and DNA methylation.

My comment: That attests to the need to consider energy-dependent hydrogen-atom transfer in DNA base pairs in solution. Even without the histones and DNA methylation, the physiology of reproduction in bacteria is nutrient energy-dependent and controlled by pheromones. It’s time for everyone to start over in the context of rabbinical debate. Start with: “You fool…” Link Schrodinger’s claims about the anti-entropic energy of sunlight to Dobzhansky’s claims about amino acid substitutions that differentiate all cell types in all individuals of all living genera, and leave the biologically uninformed science idiots with their ridiculous theories. Serious scientists have done that during the past two decades or more.
See also: Dreadful science journalism at Vox: all interpretations of science are equal, but some are cuter than others

The truth is that Mukherjee didn’t even mention transcription factors (or micro-RNAs that turn gene regulation down or off).

My comment: What have other theorists told us about microRNAs for comparison? Why are his claims being discussed outside the claims of other theorists?
See also: Functional Implications of Human-Specific Changes in Great Ape microRNAs

…miR-299-3p and miR-541-3p are conserved miRNAs with neuronal functions and thus evolutionary changes in these miRNAs may have had an impact in gene regulatory networks ultimately related to the evolution of the nervous system. Conversely, miR-503-3p and miR-508-3p regulate a low number of genes, have a restrictive pattern of expression and, although they seem to be involved in development, their functional role is still very vague. We show that specific nucleotide substitutions in the mature region and/or changes in the length of existing miRNAs may affect miRNA expression and hypothesize that both could be mechanisms by which miRNAs acquire new regulatory functions. Our study addresses for the first time the role that human-specific substitutions in miRNAs could have had in our recent evolutionary history and enlarges our understanding of how the non-coding genome may have contributed to shape human-specific traits.

Reported on 5/9/16 as:  Specific changes to non-coding RNA may be part of what makes us human

MicroRNAs are post-transcriptional gene regulators known to be involved in almost every biological function. They are highly conserved among species and, while some differences exist, the effect of the variations is often unclear. The authors of the present study analysed over 1500 microRNAs to identify variations between humans and other great ape species, including orangutans, gorillas, bonobos and chimpanzees, and the possible effect of these variations on function.

The authors found that changes in the sequence and length of four microRNAs may be specific to humans. Two were highly expressed in brain tissue and may exert effects on genes with neural functions, while two exhibit restricted expression patterns that the authors posited implied a role in development. The authors also found that “age” might matter; in an evolutionary sense, “younger” microRNAs had less sequence conservation, expression and disease association, and were more isolated than “older” microRNAs.

My comment: Nutrient energy-dependent changes in microRNA flanking sequences link hydrogen-atom transfer in DNA base pairs in solution from the innate immune system to cell type differentiation via the physiology of reproduction in all living genera. Focus on RNA-mediated events outside the context of DNA methylation in bacteria enables a connection across all species. The physiology of reproduction links chemical ecology from variation in the epigenetic landscape to adaptation, which is manifested in supercoiled DNA. The supercoiled DNA protects all organized genomes from virus-driven energy theft and genomic entropy.
When you read about the criticisms of anyone’s work who has attempted to address what is known to serious scientists about epigenetically effected top-down causation in the context of healthy longevity compared to virus-driven pathology, keep in mind that evolutionary theorists have ignored the role that energy plays in cell type differentiation, which explains their need for a scapegoat. Revisit the claim that “…Mukherjee didn’t even mention transcription factors (or micro-RNAs that turn gene regulation down or off).” When was the first time you saw an evolutionary theorist mention energy-dependent microRNA-mediated gene expression?
For example, see: Mutation-Driven Evolution

MicroRNAs (miRNAs) and other small RNAs encoded by the noncoding regions of DNA are known to control the level of protein production by degrading mRNAs. Changes in these small RNAs may then alter the expression of phenotypic characters.  (p. 136)


…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements” (p. 199).

For comparison: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

THIS MODEL DETAILS HOW CHEMICAL ECOLOGY DRIVES ADAPTIVE EVOLUTION VIA: (1) ecological niche construction, (2) social niche construction, (3) neurogenic niche construction, and (4) socio-cognitive niche construction. This model exemplifies the epigenetic effects of olfactory/pheromonal conditioning, which alters genetically predisposed, nutrient-dependent, hormone-driven mammalian behavior and choices for pheromones that control reproduction via their effects on luteinizing hormone (LH) and systems biology.


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

Coyne and others want to make an issue out of Mukherjee‘s ignorance and his failure to mention microRNAs. What are they claiming for comparison, and how does weekend evolution of the bacterial flagellum fit into the context of any theorist’s ridiculous claims? Serious scientists have reached the point where they can discuss human specific microRNAs in the context of healthy longevity or virus-driven pathology.
See also: Evolution of the human-specific microRNA miR-941 reported as: New brain gene gives us edge over apes, study suggests 11/14/12

…this gene emerged fully functional out of non-coding genetic material, previously termed “junk DNA,” in a startlingly brief interval of evolutionary time.

My comment: The “emergence” of a fully functional gene from non-coding genetic material is a representation that only a neo-Darwinian theorist could make.
Bacterial self-organization: co-enhancement of complexification and adaptability in a dynamic environment

In many experiments, bacteria are exposed to lethal constraints in order to select mutants that happen to have the appropriate trait for surviving. The selective conditions are conceived as an imitation of the environmental action in natural selection. Usually, the effect of one specifc selection factor is tested under uniform and constant conditions. The above-described approach is well developed and provides an efficient test bed for studying issues related to the selection for which they were designed. It is not suitable, however, for revealing the significant continuous role of the environment in bacterial `self-improvement’ between the rare events of selection, due to a large sudden change in a specific factor.

The evolution of gene expression and the transcriptome-phenotype relationship

Evolutionary models are only useful in the extent to which they can accurately predict the biological relationships they supposedly mirror.

Signaling Crosstalk: Integrating Nutrient Availability and Sex

 The mechanism by which one signaling pathway regulates a second provides insight into how cells integrate multiple stimuli to produce a coordinated response.

Masculinization of Gene Expression Is Associated with Exaggeration of Male Sexual Dimorphism
Reported as: The Ultimate Wingman

Behavior and social environment may have an even greater effect on the male turkey’s phenotype than his genes do.

My comment to The Scientist: At the evolutionary advent of sexual reproduction in yeasts, increased nutrient uptake determines  “male” morphogenesis and the pheromone-controlled physiology of reproduction. See for example: Signaling Crosstalk: Integrating Nutrient Availability and Sex and our 1996 review for information on the molecular epigenetics of sexual orientation and sex differences in behavior.
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…. 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… That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”
The molecular mechanisms of sex determination via nutrient-dependent alternative splicings do not change in species from microbes to man, which means that sexual dimorphism is also nutrient-dependent and pheromone-controlled in turkeys. (See Bird odour predicts reproductive success.)


Ignoring top-down causation

Dosage compensation can buffer copy-number variation in wild yeast

Susumu Ohno proposed over 40 years ago that gene duplication could provide a major force in the evolution of new gene functions, by relaxing constraint on gene sequences and allowing one or both gene copies to evolve (Ohno, 1970). The genomic era has largely borne out that hypothesis, and many studies have characterized the outcomes of whole and partial genome amplification (Jaillon et al., 2009). The immediate consequence of duplication is assumed to be increased expression of the affected genes, and in some cases the increased expression provides a selective advantage (e.g., Sandegren and Andersson, 2009; Chang et al., 2013; Edi et al., 2014). Over longer periods, the relaxed constraint afforded by functional redundancy allows one or both gene copies to evolve (Ohno, 1970), driving sub- and neo-functionalization (Lynch and Force, 2000; Lynch et al., 2001), expression divergence (Gu et al., 2004, 2005; Li et al., 2005; Wang et al., 2012), and network rewiring (Presser et al., 2008; Freschi et al., 2011; De Smet and Van de Peer, 2012).

Local chromatin environment of a Polycomb target gene instructs its own epigenetic inheritance

Epigenetic memory can be stored in the concentrations of diffusible regulatory factors that are maintained through feedback loops (trans memory) (Novick and Weiner, 1957; Ptashne, 2004; Zacharioudakis et al., 2007 ; Xu et al., 2009). Alternatively, memory could be stored locally in the chromatin environment of individual genes (cis memory), in the form of DNA methylation or post-translational modifications of histones (Moazed, 2011). While in both trans and cis memory the chromatin state is inherited, in the former case chromatin responds to the transcriptional state defined by heritable concentrations of the trans-factors, whereas in the latter case it is the local chromatin environment that instructs its own inheritance and is, therefore, the key epigenetic memory element.
My comment: The local chromatin environment links the epigenetic landscape to the physical landscape of DNA via nutrient-dependent pheromone-controlled feedback loops in species from microbes to man.
The mechanism by which one signaling pathway regulates a second provides insight into how cells integrate multiple stimuli to produce a coordinated response.
Abstract excerpt:
These studies reveal a complex interplay between reproduction and other functions in which GnRH neurons appear to integrate information from multiple sources and modulate a variety of brain functions.

Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.