The tipping point (revisited): 90K (1)

Role of miRNAs in tumor and endothelial cell interactions during tumor progression 8/3/19

…during dissemination, tumor cells have to escape from the primary tumor mass, cross the basal membrane, interact with endothelial cells to enter blood vessels (intravasation), survive in the bloodstream, get in contact with endothelial cells again to exit the bloodstream (extravasation) and seed in distant organs. Interactions between tumor and stroma cells are strongly coordinated by microRNAs (miRNAs)… Examples of pro-angiogenic miRNAs are miR-9 or miR-494, often overexpressed in tumors, which accumulate in tumor cell microvescicles and, therefore, get transferred to endothelial cells where they induce migration and angiogenesis. Differently, miR-200 and miR-128 are often downregulated in tumors and inhibit angiogenesis and lymphoangiogenesis. Instead, miR-126 controls intravasation while miR-146a, miR-214, miR-148b govern extravasation, in a positive or negative manner. Finally, at the end, we summarize opportunities for therapeutic interventions based on miRNAs acting on endothelial cells.

The opportunities for therapeutic interventions based on miRNAs acting on endothelial cells link the Creation of sunlight and water from energy as information to biophysically constrained viral latency and all biodiversity on Earth via the creation of microRNAs (microRNA biogenesis) and the food energy-dependent physiology of reproduction, which links naturally occurring RNA interference from details in Biblical Genesis to energy-dependent fixation of amino acid substitutions in organized genomes. For example, there are three amino acid substitutions that have been linked to cancer prevention and to the prevention of all pathology

1) achiral glycine,

2) COMT Val158Met

and

3) EDAR V370A

1) Achiral glycine in position 6 of the gonadotropin releasing hormone (GnRH) decapaptide is the link to the food energy-dependent pheromone-controlled creation of enzymes like catechol-O-methyltransferase

2) COMT Val158Met links different forms of  COMT enzymes to control of the levels of certain hormones that link what people eat to the metabolism of food, which links effects of pheromones on hormones to affects on behavior in species from microbes to humans via the physiology of reproduction and the transgenerational epigenetic inheritance of all morphological and behavioral phenotypes via sympatric speciation.

3) EDAR V370A

For a historical perspective on biophysically constrained viral latency and sympatric speciation, see this 6 minute-long video review: Energy as information and constrained endogenous RNA interference 2/15/17

Feedback loops link quantized energy as information to biophysically constrained RNA-mediated protein folding chemistry. Light induced energy-dependent changes link angstroms to ecosystems from classical physics to chemistry/chirality and to molecular epigenetics/autophagy.

The National Microbiome Initiative links microbial quorum sensing to the physiology of reproduction via endogenous RNA interference and chromosomal rearrangements. The rearrangements link energy-dependent fixed amino acid substitutions to the Precision Medicine Initiative via genome wide inferences of natural selection.

This detailed representation of energy-dependent natural selection for codon optimality links biologically- based cause and effect from G protein-coupled receptors to RNA-mediated amino acid substitutions and the functional structure of supercoiled DNA. Energy-dependent polycombic ecological adaptations are manifested in supercoiled DNA. Chromosomal inheritance links the adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes.

For contrast, virus-driven energy theft is the link from messenger RNA degradation to negative supercoiling, constraint breaking mutations, and hecatombic evolution. The viral hecatomb links transgenerational epigenetic inheritance from archaea to Zika virus-damaged DNA, which typically is repaired by endogenous RNA interference and fixation of RNA-mediated amino acid substitutions in organized genomes.

I noted there were 58,000 indexed published works that mentioned the term “microRNA” on 2/15/17. There are now more than 90,000

See: MicroRNA

The fact that MicroRNA-130a modulates a radiosensitivity of rectal cancer by targeting SOX4 (8/3/19) links the Creation of the sun’s anti-entropic virucidal energy to human hemoglobin variants via Anemia Severity in β-Thalassemia Correlates with Elevated Levels of microRNA-125b in Activated Phagocytic Monocytes (8/4/19).

A Map of the microRNA Regulatory Networks Identified by Experimentally Validated microRNA-Target Interactions in Five Domestic Animals: Cattle, Pig, Sheep, Dog, and Chicken 8/5/19 links facts about more than 1800 biophysically constrained hemoglobin variants to food energy-dependent pheromone-controlled protection from the virus-driven degradation of messenger RNA, which links the creation of toxic peptides from mutations to all mental and physical pathology in all mammals.

Excerpt:

…this miRNA regulome mapping study will enable and guide further studies of genome function in mammals with a view to applications in human as well as veterinary medicine. Furthermore, these miRNA regulomes can help to clarify fundamental pathways in cell biology and reveal molecular insights on phenotypic trait variability in common complex diseases and response phenotypes of drugs or other health interventions for precision medicine in the future.

See for comparison from 3/30/16 when only 51905 publications that mentioned microRNA were indexed.

:

The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair.

In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans.

Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry.

Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.

If you continue to track the scientific progress, which already links 51,905 published works to more than 90,000 published works, the increase of 38,095 across 41 months or the increase of 32000 more publications in the 26 months since 2/15/17 may provide you with a look into the future of what happens when serious scientists refuse to accept the claims of biologically uninformed theorists who tout their pseudoscientific nonsense about the emergence of energy and how emergence was linked to the evolution of all biodiversity via mutations.

See: Mutation-Driven Evolution 6/14/13 and We are all mutants 3/16/14 for comparison to Nutrient-dependent/pheromone-controlled adaptive evolution: a model 6/14/13 and Lipid Encapsulation of Self-Replicating Ribozymes (December 2012) by the author of Criticisms of the nutrient-dependent pheromone-controlled evolutionary model 6/4/14

Andrew Jones has continued to attack my scientific credibility for 5 more years via social media, despite this comment on his criticisms, which was framed in the context of peer-review.

Editor’s note

The 2013 review article by James Vaughn Kohl published in Socioaffective Neuroscience & Psychology and criticized in the above Letter to the Editor was subjected to standard peer review and the revised version was accepted by me after it had been accepted by both reviewers.

Clearly, the most vocal of all biologically uninformed science idiots will be blamed for all preventable pathology in the months to years to come. If not, serious scientists will be forced to admit that any biologically uninformed science idiot in the world can influence other idiots during the next 6 years of preventable suffering and premature death.

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