Nutrient-dependent pheromone-controlled autophagy (2)

By: James V. Kohl | Published on: October 10, 2016

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Autophagy: cellular and molecular mechanisms (2010)

Conclusion:

… autophagy has emerged as a new and potent modulator of disease progression that is both scientifically intriguing and clinically relevant.

My comment: Autophagy is energy-dependent and linked to supercoiled DNA by epigenetic effects on the innate immune system, which are linked to the physiology of energy-dependent reproduction. If you think that the innate immune system automagically “emerged,” you might also think that autophagy has automagically emerged as the only known link from the epigenetic landscape to the physical landscape of supercoiled DNA in all living genera. Emergence and evolution are terms that theoretical physicists and neo-Darwinian theorists use to link what they don’t know anything about to fertilization and adult behavior.
See for comparison: From Fertilization to Adult Sexual Behavior
Concluding sentence:

We see the primary contribution of this discourse, not to give answers but rather to broaden the scope of investigation. It would be helpful if some other investigators would similarly shed more light on a microanalysis of social-environmental factors impacting on sexual development.

My comment: Nutrient stress and social stress have repeatedly been linked to all pathology via their effects on hormones that affect behavior. Suddenly, 20 years after we published our review of epigenetic effects on RNA-mediated hormone-organized and hormone-activated behavior, RNA-mediated “… autophagy has emerged as a new and potent modulator of disease progression that is both scientifically intriguing and clinically relevant.”
What makes autophagy more relevant now than it was when Dobzhansky (1973) linked it from RNA-mediated amino acid substitutions to all biodiversity in Nothing in Biology Makes Any Sense Except in the Light of Evolution
Excerpt:

For example, 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 (p. 127).”

See also: Non-coding portions of genome are found to play role in cancer
Excerpt:

We now have an innovative way of destroying RNA targets inside live cells and assessing whether a tumor is dependent on them for survival,” says Spector.

My comment: Virus-driven energy theft has always been an innovative way to cause pathology in all cell types of all living genera. Biophysically constraining the virus-driven pathology has always been the key to healthy longevity and the survival of all species.
See: Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution
Author’s comment:

The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.

My comment: The authors responded to my comment, which was removed. It is still available here.

jvkohl • 3 years ago

See also: “Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution”

The idea of biophysical constraints seems antithetical to the idea of nature somehow selecting mutations that cause amino acid substitutions. However, I am not a biophysicist or evolutionary theorist.

The problem may be my focus on nutrient-dependent receptor-mediated amino acid substitutions in species from bacteria to humans (non-viral organisms). Since I am not a virologist or physicist, I’m not sure that the laws of physics apply to viruses and their replication.

If they do, natural selection for random mutations is not likely to result in amino acid substitutions because the thermodynamics of changes in organism-level thermoregulation preclude such randomness. Stability of protein biosynthesis and degradation that probably depends on protein folding must somehow be controlled. Besides, I don’t know how random mutations in viruses could be naturally selected for inclusion in the human virome (or in the virome of any organism capable of thermoregulating its thermodynamic intercellular signaling).

If the Second Law of Thermodynamics does not apply to viruses, which means the chemical bonds that enable the amino acid substitutions can form at random and somehow be naturally selected, the details of biophysical constraints in this article seems out of place, since I do not think in terms of constrained random mutations and natural selection in mutation-driven evolution.

Hopefully, someone with a background in biophysics will address my confusion in case others are confused. In addition, I wonder if the consequences of understanding the evolutionary mechanisms that govern viruses extend to consequences important to understanding the evolution of species from bacteria to humans via constrained random mutations and natural selection?

See: ‘Game-changing’ immunotherapy doubles head and neck cancer survival

The survival benefit was more pronounced in patients whose tumours had tested positive for human papillomavirus (HPV). These patients survived an average of 9.1 months with nivolumab and 4.4 months with chemotherapy.

My comment: Testing positive for virus-driven energy theft in the context of pathology is not a game changer. It is an admission of negligence on the part of others who should have changed the game sooner. Game-changing immunotherapy links what is known about physics and chemistry to biology via molecular epigenetics. That fact should help all serious scientists who are still waiting to claim that all pathology is caused by viruses.
But the game change could have occurred much earlier so that more winners than losers would have survived during the past two decades. Long before the advent of the “game-changing” therapy, all pathology, includes the pathological behaviors that develop throughout life could have been linked to the pathological behaviors that pseudoscientists have been trained to exhibit in their claims about emergence and evolution.
For comparison, early detection of the virus that causes the pathology in a species-specific tissue type will be the obvious link to effective treatment and cures. Unfortunately, there is not much funding for preventative medicine and even less funding is dedicated to finding how specific viruses such as the Zika virus cause craniofacial deformities. Similarly, changes in the development of the brain are caused by virus-driven genomic entropy in species that have not yet become extinct.
Some researchers still seem to think that we can save other species from virus-driven genomic entropy and extinction despite the fact that no experimental evidence of biologically-based cause and effect suggests we can save humanity from a similar fate. All experimental evidence links what is know about behavioral development in one species to behavioral development in all species.
Behavioral development is nutrient-dependent and pheromone-controlled via the physiology of reproduction in all living genera. That fact and the claims of all serious scientists tells us approximately how far from extinction we may be. Not far enough.

See for another example of that fact: Behavioral development in embryonic and early juvenile cuttlefish (Sepia officinalis)

Abstract excerpt:

S. officinalis is well-suited to addressing questions of behavioral ontogeny. As embryos, they can perceive and learn from their environment and experience no direct parental care. A marked progression in learning and behavior is observed during late embryonic and early juvenile development.

From Fertilization to Adult Sexual Behavior was cited in Organizational and activational effects of hormones on insect behavior (2000) and cited in Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Excerpt:

Until recently, there was no direct evidence that human pheromones caused a definite behavior. In contrast, there was sufficient evidence to extend the mammalian model for epigenetic effects of nutrients and pheromones on GnRH and on hormonal organization and activation of behavior (Diamond et al., 1996) to invertebrates (Elekonich & Robinson, 2000). In that context, ‘From fertilization to adult sexual behavior’ (Diamond et al., 1996, p. 333) was extended to invertebrates with details from ‘egg to adult’ (Elekonich & Robinson, 2000, p. 1514).

My comment: How soon will the virus-driven energy theft that has been linked to the extinction of marine invertebrates and vertebrates be linked to the extinction of all terrestrial invertebrates and vertebrates?

See for example: Past 5,000 years prolific for changes to human genome

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. More broadly, the results suggest that humans are carrying around larger numbers of deleterious mutations than they did a few thousand years ago. But this doesn’t mean that humans now are more susceptible to disease, says Akey.

My comment: Yes it does mean that humans now are more susceptible to disease. Only a theorist or someone who was equally biologically uninformed would make the claim that all humanity is not more susceptible to mutation-caused pathology than ever before.

The increasing number of deleterious mutations is killing us. Theorists have claimed that some mutations are beneficial because that claim supports their ridiculous theories.

See for comparison:

1) Role of olfaction in Octopus vulgaris reproduction

2) Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

3) Neuroendocrine factors distinguish juvenile psychopathy variants

…two primary CU variants (aggressive and non-aggressive types) emerged with profiles characterized by low to average psychopathology and high DHEA levels. Findings contribute to a growing literature base suggesting that biomarkers may distinguish youth on separable developmental pathways to psychopathy.

See for comparison:
1) Phylogenetic plasticity in the evolution of molluscan neural circuits
2) The central pattern generator underlying swimming in Dendronotus iris: a simple half-center network oscillator with a twist
My comment: No experimental evidence of biologically-based cause and effect suggests that any central pattern generator “evolved” to link behavior to biophysically constrained energy-dependent RNA-mediated cause and effect. No experimental evidence of biologically-based cause and effect suggests that any mutation is beneficial.

See for comparison: A comprehensive transcriptional map of primate brain development

Excerpt:

Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion.

My comment: Virus-driven energy theft alters the distinct developmental timing of gene expression in disparate cell populations, and the developmental timing of RNA-mediated gene expression is the only known link from RNA-mediated amino acid substitutions to supercoiled DNA, which protects all organized genomes from virus-driven entropy.