Enzyme-constrained interethnic biodiversity (6)

 
See: Celgene Near Acquisition of Impact Biomedicines

Chief Executive Officer Mark Alles has pledged to look outside Celgene’s own labs for new drugs to bolster its pipeline, telling investors in October that “we look for opportunity all the time.”

The CEOs of companies like this have been looking in all the wrong places for several decades. All of “Big Pharma” is dangerously close to collapse under the weight of evidence known to serious scientists who have linked physics and chemistry to the conserved molecular mechanisms of biophysically constrained RNA-mediated cell type differentiation that protect all living genera from the virus-driven degradation of messenger RNA.
The CEOs don’t want you to be freaked out by the price tag for medications that will bankrupt the economy of the United States of America. But, quite frankly, this freaks me out.
See also:  An $850,000 Price Tag on Gene Therapy Shouldn’t Freak You Out—Yet

Spark’s Luxturna was approved by the U.S. Food and Drug Administration in December for patients who have a genetic mutation in the RPE65 gene, which causes degenerative retinal disease.

The therapy, which is injected into the eye, contains millions of engineered virus particles containing correct copies of the gene. The treatment improves vision but doesn’t fully restore it.

The real test may come when Spark and other companies start winning approval to sell gene-replacement therapies for diseases like hemophilia and sickle-cell anemia, which affect tens of thousands of people in the U.S.

Spark’s inadvertently appears to claim gene-replacement therapies can prevent the virus-driven theft of messenger RNA that causes the mutation in the RPE65 gene. If so, the food energy-dependent pheromone-controlled hemoglobin S ecological adaptation will require treatment with enzymes or food supplements that increase the production of specific enzymes.
That might be the most effective treatment. However, sooner or later, people will learn that sickle-cell anemia is a food energy-dependent ecological adaptation that can be linked from one base pair change and one amino acid substitution to all other pathology. “Big Pharma” will then no longer control the economic success of the United States of America.
Indeed, this publication may drive the decline of the gene-editing component of the stock market:  Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans
Pre-Existing Adaptive Immunity in Humans is RNA-mediated. The facts about interethnic variation in hemoglobin molecules link pre-existing humoral and cell-mediated adaptive immune responses from Cas9 to the RNA-mediated factors that must be taken into account before the CRISPR-Cas9 system moves forward into clinical trials. The CRISPR-Cas9 system damage to human DNA caused by gene editing could be prevented by something as relatively simple as enrolling more participants in studies like this one: Nevada Health Project Participants to Gain Access to Helix Genomics Marketplace
See for comparison: Exome Sequencing Data Links ADCY3 to Severe Obesity

Loss-of-function mutations in ADCY3 cause severe obesity, according to a series of new studies in Nature Genetics.

Exome sequencing yields much more data than genotyping does and the data conclusively shows that there is no such thing as a gain-of-function mutation. That is why food energy-dependent changes in SNPs have consistently been linked to interethnic biodiversity and to differences in longevity in modern human populations like the Amish.
See also:  Pfizer Ends Hunt for Drugs to Treat Alzheimer’s and Parkinson’s by Jonathan.Rockoff@wsj.com
The end of the hunt links Bruce McEwen’s works to the beginning of the search for effective treatments that must help to biophysically constrain viral latency if they are used to treat some neurodegenerative diseases.
Bruce McEwen’s works, link energy-dependent cell type differentiation from feedback loops that link olfaction to the pheromone-controlled physiology of reproduction.
Historical perspective: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” McEwen et al., (1964)

The synthesis of RNA in isolated thymus nuclei is ATP dependent.

For a practical application of facts that McEwen’s life’s works have detailed since 1964, see:
Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis
The fact that human pheromones biophysically constrain the pathology of neurodegenerative diseases has been known to all serious scientists since the time that this was published in 1994.
Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.)
The conserved molecular mechanisms of RNA-mediated cell type differentiation have not changed since the dawn of the energy-dependent creation of ATP and RNA.
 
That fact was indirectly represented in New Description of the Rostral Migratory Stream in Adult Mice Brains Delineating the Starter of the Stream as an Infundibulum: A New Described Limb, by H&E and Antidoublecortin Antibody 

Conclusion: The neuroblasts take different arrangement through their period of life from their site of origin to their final destination the olfactory bulb through the RMS.

The creation of the neuroblasts and their energy-dependent niche construction in the olfactory bulb is tractable to the niche creation of bacteria, which neo-Darwinian theorists seem to think occurs in the context of the evolution of functional structures such as the flagellum via a “quantum leap.”
See: Biologists Trace Evolution of Bacterial Flagellar Motors

This clear separation between primitive and sophisticated species represents a ‘quantum leap’ in evolution…

That claim represents a return to de Vries definition of mutation, which Schrodinger (1944) placed into the context of his organized thoughts about biophysically constrained biodiversity with my emphasis.

“…about forty years ago [in1902] the Dutchman de Vries discovered that… a very small number of individuals, say two or three in tens of thousands, turn up with small but ‘jump-like’ changes, the expression ‘jump-like’ not meaning that the change is so very considerable, but that there is a discontinuity inasmuch as there are no intermediate forms between the unchanged and the few changed. De Vries called that a mutation. The significant fact is the discontinuity. It reminds a physicist of quantum theory -no intermediate energies occurring between two neighbouring energy levels. He would be inclined to call de Vries’s mutation theory, figuratively, the quantum theory of biology. We shall see later that this is much more than figurative. The mutations are actually due to quantum jumps in the gene molecule.

See for comparison: Evolution of higher torque in Campylobacter-type bacterial flagellar motors (January 8, 2018)

Phylogenetic inference was made using maximum-likelihood in GARLI (v2.01.1067)23, using Jones, Taylor and Thornton (JTT) amino acid substitution rates24.

Phylogenetic inferences still seem to be based on a definition of mutation from  1902. For comparison, all serious scientists have learned that the food energy-dependent pheromone-controlled physiology of reproduction links the fixation of RNA-mediated amino acid substitutions in the cell types of all individuals of all species from biophysically constrained viral latency to all biodiversity in all living genera.
I have placed the proof of concept for my model into a series of blog posts on “Interethnic Diversity” in an attempt to help biologically uninformed theorists join serious scientists from the 21st century who are Combating Evolution to Fight Disease
Recruits are required to take intelligence tests and compete basic training with an essay on top-down causation that links the sun’s anti-entropic virucidal energy from the physiology of reproduction to all biodiversity on Earth without mention of mutation or evolution.
Recommended reading includes a monograph from Bruce McEwen about his life’s works, and one recently published work that was co-authored by Bruce McEwen:
See: Redefining neuroendocrinology: Epigenetics of brain-body communication over the life course
The details of natural biological rhythms; “allostatic overload” (as a natural part of autophagy and limits on population density);
a natural molecule acetyl-L-carnitine (LAC);  our natural day-night rhythm; and natural cycles of protein biosynthesis and degradation are linked from a naturalistic rodent model to interethnic biodiversity. There is no mention of natural selection and only one mention of evolution and one mention of mutation.
See also: Loss of APOBEC1 RNA-editing function in microglia exacerbates age-related CNS pathophysiology
RNA interference links base editing from microRNA editing to the energy-dependent fixation of RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all living genera.

Bruce McEwen’s works and his advice: “Start with gene activation (in GnRH neurosecretory neurons)” led to publication of our 1996 Hormones and Behavior review of RNA-mediated cell type differentiation. We linked food energy to the pheromone-controlled physiology of reproduction and all biodiversity in species from yeasts to primates via alternative splicing of pre-mRNA.
From Fertilization to Adult Sexual Behavior

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 fact that sex differences do not evolve has since been linked to all the other differences in cell types that did not evolve. The National Microbiome Initiative has been linked to the Precision Medicine Initiative and to refutations of all the pseudoscientific nonsense that has been touted by theorists during the past few decades of stalled scientific progress.
See for another example. Epigenetic supersimilarity of monozygotic twin pairs

…we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This “epigenetic supersimilarity” apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer.

Reported as: Identical twins can share more than identical genes: Molecular similarity

For decades, researchers have studied genetically identical twins to estimate what proportion of disease risk is determined by one’s genes. To the extent that epigenetic supersimilarity affects risk of disease, as our results indicate, genetic risk estimates based on twin studies have been inflated.

This is how sex researchers stalled scientific progress. They failed to recognize that all molecular similarities and differences are food energy-dependent and the transgenerational epigenetic inheritance of all similarities and differences must be links from the physiology of pheromone-controlled reproduction to the energy-dependent biodiversity that is displayed in all life on Earth.
Public health bodies such as the CDC are mandated to meet the needs of all people, in all their diversity.
All diversity is food energy-dependent and biophysically constrained in the context of the pheromone-controlled physiology of reproduction, which links autophagy to viral latency. The Trump administration is clearly making an attempt to ensure that the CDC does not obfuscate the language used by serious scientists. Serious scientists know how to link physics and chemistry from molecular epigenetics to biophysically constrained viral latency by one or more RNA-mediated amino acid substitutions. The amino acid substitutions are consistently referred to as mutations in examples of human idiocy:
See: Brief report: Geographic variation in EGFR mutation frequency in lung adenocarcinoma may be explained by interethnic genetic variation The full article can be downloaded from here: http://bit.ly/2z97l9b
EDAR V370A and ABCC11 G180A are the two energy-dependent RNA-mediated amino acid substitutions that the authors refer to as mutations, which they link to interethnic genetic variation in the context of de Vries 1902 definition of mutation and A Civic Biology: Presented in Problems (1914).
pp. 195-196

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. If we follow the early history of man upon the earth, we find that at first he must have been little better than one of the lower animals.

p. 263

If such people were lower animals, we would probably kill them off to prevent them from spreading. Humanity will not allow this, but we do have the remedy of separating the sexes in asylums or other places and in various ways preventing intermarriage and the possibilities of perpetuating such a low and degenerate race. Remedies of this sort have been tried successfully in Europe and are now meeting with success in this country.