10,000 reasons to believe in biophysical constraints

By: James V. Kohl | Published on: November 1, 2018

Excerpt: Gunnar Blohm blocked me before I could add: Enhancer redundancy predicts gene pathogenicity
More than 79,000 published works are displayed in a search for “microRNA” on the PubMed data base. The number of publications has increased from 5 in 2001 to 5851 in 2012, which is when I first learned about them during a conference presentation at the Society for Neuroscience annual meeting in New Orleans, Louisiana. In 2018, more than 10,000 have been added.
This October 5, 2017 preprint was published on October 4, 2018 Predicting microRNA targeting efficacy in Drosophila.
It can be used as an example of how to link what is known to all serious scientists about biophysically constrained viral latency via The biochemical basis of microRNA targeting efficacy.

The existence of a quantitative model that has been developed and trained using Drosophila data will provide a valuable resource for placing miRNAs into gene regulatory networks of this important experimental organism.

Quantitative models link energy-dependent top-down causation from the sense of smell to biophysically viral latency and all biodiversity via a model of one energy-dependent base pair change and fixation of one food energy-dependent amino acid substitutions in human populations from North and East Asia and from the New World, see:
Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems
At this year’s society for Neuroscience annual meeting, there are 17 presentations in this category Olfaction: Olfactory Sensory Neuron Development and Function. All of them directly or indirectly link the light-activated creation of microRNAs to all extant biodiversity via biophysically constrained viral latency in the context of the physiology of pheromone-controlled reproduction. For example, start with A Quick HYL1-Dependent Reactivation of MicroRNA Production Is Required for a Proper Developmental Response after Extended Periods of Light Deprivation

…plants alter microRNA (miRNA) biogenesis in response to light transition.

Do not wait to link that fact to the newest presentations on the pheromone-controlled physiology of reproduction in species from microbes to humans.
139.06 / Y7 – A single amino acid residue in TM2 determines ligand responsiveness in two highly related sex pheromone receptors of sea lamprey

Switching amino acid residue at this position in OR320a and OR320b also switched their ligand responsive properties, indicating that additional residues in TM2, different from the generalized odorant-binding sites in TM3, TM5 and TM6, are also critical for ligand responsiveness in broadly tuned highly related olfactory receptors. Our data identifies receptors for a steroidal sex pheromone in vertebrates and provides a useful pheromone recognition model in vertebrates.

139.11 / Y12 – Regulation of olfactory sensory neuron maturation and axon targeting by non-coding RNA

“…in the mammalian main olfactory system, the lncRNA H19 is one of the most abundant transcripts in early embryonic and neonatal olfactory epithelium, but its physiological function is unknown.

Conclusion: These results suggest that H19 may function through regulating microRNAs during OSN development to influence the development of OSNs and their axon targeting.

139.05 / Y6 – Invariances in a combinatorial olfactory receptor code

…activation thresholds are drawn from a power law statistical distribution (Figure C). A fixed activation function and power law distribution of activation thresholds underlie invariances in the encoding of odorant identity and intensity.

139.17 / Y18 – Experience-dependent sex-specific variability of olfactory receptor expression in mice

…these observations [in mice] raise the possibility of an activity-dependent mechanism mediated by sex-specific volatiles to govern the sexually dimorphic expression of specific ORs.

For a historical perspective on the link to sexual orientation, see also: Large genome-wide analysis of sexual orientation identifies for the first time variants associated with non-heterosexual behavior and reveals overlap with heterosexual reproductive traits.
Reported as: DNA differences are linked to having same-sex sexual partners
The differences in the supercoiled DNA of species from yeasts to mammals, which are linked to sexual orientation, are food energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction in species from microbes to humans. The mouse model is consistently used to help detail that fact.
See: Pheromonal Regulation of Genetic Processes: Research on the House Mouse (Mus musculus L.) (1994)
See also: Predator Odor Destabilizes the Cell Genome of the Mouse Bone Marrow (2018)
Pseudoscientists and other biologically uninformed theorists have consistently missed what is known about the links from food energy-dependent pheromone-controlled sympatric speciation to all biophysically constrained viral latency and all biodiversity.
See why: Beyond the Catwalk: A how-to-model guide for Neuroscience that dispels the mysteries

Gunnar Blohm made Beyond the Catwalk: A how-to-model guide for Neuroscience that dispels the mysteries public

He challenged me to explain myself after I commented negatively on the use of mathematical models.
For fun at his expense, see:

What’s your point? Sorry, please spell out

If you had skipped the part about mathematical modeling, your guidelines might be accepted by serious scientists. Dobzhansky (1964) wrote “…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” https://www.jstor.org/stable/3881145?origin=JSTOR-pdf&seq=1#page_scan_tab_contents

McEwen et al, 1964 wrote: https://www.sciencedirect.com/science/article/pii/0926655064901665 “The synthesis of RNA in isolated thymus nuclei is ATP dependent.”
No valid model fails to start with the creation of the energy that is required for the link from light-activated microRNA biogenesis to viral latency.

@gunnarBlohm blocked me before I could add: Enhancer redundancy predicts gene pathogenicity… https://www.biorxiv.org/content/early/2018/11/01/459123 Their data suggest that most eQTL signals at GWAS loci are non-causal and not linked to SNPs, which means their model has no explanatory power. Gunnar is crying
Others will cry with him or laugh, which is what serious scientists have been doing. The serious scientists have abandoned all useless mathematical models and focussed on the links from subatomic particles to cytosis and biophysically constrained viral latency.
See: Physiology is rocking the foundations of evolutionary biology

Perhaps the elegant mathematics and the extraordinary reputation of the scientists involved blinded us to what now seems obvious: the organism should never have been relegated to the role of mere carrier of its genes.

See also for ages 10+ Cytosis and Subatomic
Remember: Measles outbreaks come with serious consequences (2017)

“The Disneyland outbreak in 2017, during which 125 people got measles and 500 were quarantined, cost $2.3 million,” she explained. “And something people forget is if we have our public health system dedicating their time to managing a measles outbreak, they are not doing other public health issues.”

Most of the ~10,000 tweets I have posted to my @jvkohl twitter feed are not focused on the politics of the mid-term elections in the USA.  However, anyone who understands enough about the prevention of the forthcoming viral pandemic may want to see information on the Honduran Hordes that will be bringing it to us courtesy of the Democrats overwhelming ignorance. They seem to have forgotten that the hordes of Europeans killed millions of Native American Indians with the viruses they carried to the New World.

History shows that both those who do not learn history and those who do learn history are doomed to repeat it.

This time, however, the blame will be placed on the Democrats who ignored the scientific fact that a change in one amino acid probably caused the 1918 Spanish flu.
See: Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During 1918 Spanish flu Evolution

Editor’s summary: Five antigenic sites in the virus surface hemagglutinin protein, which together comprise 131 amino acid positions, are thought to determine the full scope of antigenic drift of influenza A virus. Koel et al. (p. 976) show that major antigenic change can be caused by single amino acid substitutions. These single substitutions substantially skew the way the immune system “sees” the virus. All substitutions of importance are located next to the receptor-binding site in the hemagglutinin. Because there are few positions of importance for antigenic drift, there are strict biophysical limitations to the substitutions at these positions, which restricts the number of new antigenic drift variants at any point in time. Thus, the evolution of influenza virus may be more predictable than previously thought.

Viruses do not evolve. They adapt to hosts via amino acid substitutions when their host’s response is reduced or delayed until death.

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