Virus-driven disorder prevention and health promotion

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The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion

Excerpt:

Evidence has also been growing about the role of epigenetic modification in response to the social environment.

My comment: Unexpectedly, Szyf et al., (2016) fail to mention all the evidence of epigenetically-effected RNA-mediated cause and effect that has accumulated since we published our 1996 Hormones and Behavior review. That may explain why they also failed to link energy-dependent hydrogen-atom transfer in DNA base pairs in solution to the microRNA flanking sequences and adhesion proteins. A series of failures to integrate information across disciplines explains why they did not link the protocadherin gene family cluster from nutrient-dependent cluster-wide RNA-directed DNA methylation differences to supercoiled DNA and protection against virus-driven entropy via the physiology of reproduction in all living genera.

See for comparison: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity

See also: DNA methylation pathways and their crosstalk with histone methylation

My comment: After others linked all invertebrates to all vertebrates in the context of microRNA flanking sequences and the sequencing of the octopus genome, I did not expect Szyf or anyone from his group to ignore everything known about how nutrient-dependent microRNAs are linked to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. Instead, in his most recent published work, his group doesn’t mention microRNAs or viruses.

Szyf et al., (2016) correctly conclude that the DNA methylation markers described in humans do not serve as biomarkers. But they fail to integrate what is known about how base pairs and amino acid substitutions justify integrating evertyhing known about DNA methylation by placing it into the context of the RNA-mediated amino acid substitutions. The substitutions link differences in the nutrient-dependent microRNA/messenger RNA balance to cell type differentiation in all living genera via the physiology of reproduction.

Why  would anyone claim that future studies should focus on discoveries of other biomarkers? MicroRNAs link what is known about nutritional epigenetics to behavior in the context of single amino acid substitutions during life history transitions? But, Szyf et al (2016) conclude:

Excerpt:

Future studies should focus on discovery of a panel of DNA methylation-based biomarkers that could guide epigenetically informed interventions.

My comment: What were researchers thinking could be accomplished without consideration of models that link RNA-directed DNA methylation from microRNAs to supercoiled DNA?  Obviously, anyone who is not willing to start with energy-dependent changes in base pairs has no guidance that would lead them to epigenetically informed interventions.  Life is energy-dependent and RNA-mediated events link physics to chemistry and the conserved molecular mechanisms of biologically-based behavior. In the context of everything known about biologically-based behavior, there is no defined boundary between epigenetics and genetics.  What they are actually claiming is that they seem to have missed the fact that genes do not create themselves, and that the de novo creation of genes links nutrient-dependent metabolic networks to genetic networks in the context of experience during life history transitions.

See also: From Toxins to Culture: How Environment Shapes the Infant Brain

Prenatal and perinatal environmental factors, from toxins to maternal care and culture, profoundly influence the brains of infants, sometimes resulting in lifelong pathologies. The effects of these factors have only recently been rigorously assessed in humans, and the mechanisms by which they affect the brain are only beginning to be understood. This symposium discusses recently established links between autism and vehicular air pollution in both the developed and developing world; and how the microbiome, a target for infections and nutrition-related pathologies, directly affects the developing brain and can contribute to development of autism. The session also discusses how maternal inputs and cultures modify the impact of the physical environment on the brain, and how epigenetic mechanisms mediate the long-term impacts of prenatal and perinatal factors. These findings have broad implications for policies to preserve the health of children and adults around the world.

Elaine Y. Hsiao, University of California, Los Angeles (UCLA)
The Role of Gut Microbiomes in Neurodevelopmental Disorders
Bruce McEwen, Rockefeller University
Mother-Infant Interactions Influence Both Cognitive and Physical Development
Moshe Szyf, McGill University
Nurture Alters Nature through Epigenetic Modifications of DNA
See also:
En’Cas’ing The Stress: Engineering a Human Cell Line Knockout of Heat Shock Response Genes
Gabriela Canales, University of Maryland, Baltimore County, Baltimore, MD
Excerpt:

Both HSF1 and eEF1A1 knockout lines will also be used for future studies to improve upon the current model of the HSR pathway and potentially reveal therapeutic targets for diseases like ALS, Alzheimer’s disease, Parkinson’s disease, type 2 diabetes, and amyloidosis.

My comment: Until you link nutrient-dependent microRNAs to adhesion proteins and supercoiled DNA, which protects organized genomes from virus-driven entropy in all living genera, you will not be able to link ecological variation from chemotaxis and phototaxis to the innate immune system and proteostasis via the heat shock response to stress that must be linked to ecological adaptation.
Szyf et al., (2016) exemplifies the failure to link ecological variation to ecological adaptation despite what they know about DNA methylation. They did not use what is known about epigenetics to inform anyone about disorder prevention and health promotion. The information about health promotion came to us from the research group who reported this:
Microbes and Alzheimer’s Disease
Excerpt:

“(iii) Olfactory dysfunction is an early symptom of AD [58]. The olfactory nerve, which leads to the lateral entorhinal cortex, the initial site from where characteristic AD pathology subsequently spreads through the brain [59, 60], is a likely portal of entry of HSV1 [61] and other viruses [62], as well as Chlamydia pneumoniae, into the brain [63], implicating such agents in damage to this region.”

My comment: The link from virus-driven energy theft to olfactory dysfunction is missing from the implication of cause and effect. But that link from olfaction is not missing from the context of disorder prevention and health promotion. Even if it is only an implication, it is better than Szyf et al., (2016) —  who failed to mention how olfactory receptor gene loss is linked from viral replication to deficits in olfactory acuity and specificity. The deficits link the failure to recognize self vs non-self differences in the context of interactions with people. People respond to social odors called pheromones, but Szyf et al., (2016) seem to want others to look away from that fact and try and find biomarkers that do not link the sense of smell and/or viruses to all healthy longevity or all virus-driven pathology.
The question arises: Why did it take so long for others to link the olfactory system to the immune system in the context of receptor-mediated behaviors, disorder prevention and health promotion during the life history transitions that links viruses to the pathology of neurodegenerative diseases? Is the fear of human pheromones still so great as to defy all common sense? Or is it the fear of neo-Darwinian theorists and the evolution industry that has prevented attestations to the fact that neurodegenerative diseases do not randomly occur in the context of mutations and evolution.
See also: A virus common among livestock depends on a micro-RNA to replicate
Excerpt:

One way wily viruses can get a leg up is by subverting the microRNAs (miRNAs) of their host. These miRNAs are small stretches of RNA made by host cells to regulate gene expression. If a virus can co-opt one, it can manipulate its host without having to make its own protein. This strategy saves valuable space in the viral genome and allows the virus to better hide from the host’s immune system.

My comment: In the open access article, they do not mention how the nutrient-dependent stability of the virus or the stability of the host genome is achieved. The failure to link virus-host interactions from physics to the chemistry of RNA-mediated protein folding in the context of the energy theft by the virus causes them to miss the obvious link from all viruses to all pathology.

Conclusion (with my emphasis):

In conclusion, our findings indicate that the endolysosomal degradation of viral (and potentially other microbial) virulence factors may serve as an important host antipathogen defense mechanism. Previous studies have shown that the canonical autophagy machinery can function in antibacterial and antiviral host defense by delivering intracellular pathogens or components of intracellular pathogens to the lysosome for degradation (2, 36). Moreover, Beclin 1 and the autophagy pathway has been proposed to function in controlling viral oncogenesis in at least two contexts: monoallelic deletion of Becn1 accelerates neoplastic lesions in the livers of mice that transgenically express hepatitis B envelope protein autophagy (30) and decreased autophagic degradation of a microRNA (miR-224) is postulated to contribute to hepatitis B virus-associated hepatocellular carcinoma in mice and in humans (42). Our findings suggest that independently of the autophagy machinery, the delivery of viral oncoproteins to the lysosome for degradation (via an endolysosomal trafficking route) may play a crucial role in innate immunity.

My comment: The link from nutrient-dependent microRNAs to RNA-mediated DNA repair via G protein-coupled receptors that link chemotaxis to phototaxis is more than sufficient to link everything known about supercoiled DNA to protection against all virus-driven pathology.
Not just neurodegenerative diseases such as Alzheimer’s.
Not just virus-linked diseases in livestock.
The de novo creation of G protein-coupled olfactory receptor genes links virus-driven energy theft to all pathology. The viruses steal the energy that would otherwise be used to create new genes or for energy-dependent RNA-mediated DNA repair.

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