Ecological adaptation: A new definition of heredity (3)

By: James V. Kohl | Published on: March 9, 2018

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Excerpt:
Moving forward: Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex

…these data suggest that a subset of the identified novel miRNAs may contribute to the pathophysiology of numerous diseases, laying the groundwork for future studies to elucidate the functional connections of miRNAs to the numerous diseases associated with sequence variants within non-coding regions of the MHC.

OMCD: OncoMir Cancer Database

Dysregulation of miRNAs is commonly observed in cancers and it largely cancer dependent.

The virus-driven theft of quantized energy as information has been linked from changes in the microRNA/messenger RNA balance to all pathology. That fact replaces the circular logic that links cancer-dependent dysregulation of miRNAs to cancer. Simply put, the proliferation of viruses cause cancer. The proliferation of viruses is energy-dependent in the context of established links from atoms to ecosystems in all living genera.
See: Subatomic: An Atom Building Board Game

A deck-building game where particle physics & chemistry collide! Use quarks to build subatomic particles & particles to build Atoms!

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements.

Moving forward: Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex

My “Disqus” comment (and nearly 2000 others): Gene expression is energy-dependent, RNA-mediated, and biophysically constrained.
See: FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.

MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression.

MicroRNAs do not create themselves.
See also: Energy as information and constrained endogenous RNA interference
8 of my 9 most recent comments to Disqus have been removed.
See for comparison: Incomplete host immunity favors the evolution of virulence in an emergent pathogen
Reported as: In nature, an imperfect immune system drives the evolution of deadly pathogens

…birds that eat at feeders are more likely to be infected with the disease, which causes red, swollen eyes and often blindness that results in death.

…lower virulence strains could be their own worst enemies, creating a population of hosts that are resistant to them but not the higher virulence strains that remain.

By removing my Disqus comments, the moderators limit discussion of the facts about virus-driven energy theft, which links mutations to all pathology. That allows the biased reporting on preprints that continue to try to support the ridiculous concept of neo-Darwinian evolution.
It also prevents the realization of goals by serious scientists who have linked the biogenic creation of uranium ores to the prevention of radiation sickness via microRNA therapy. See, for examples: miRNA-mediated therapies
A miRNA-145/TGF-beta1 Negative Feedback Loop Regulates the Cancer-Associated Fibroblast Phenotype

…miR-145 is a key regulator of the CAF phenotype, acting in a negative feedback loop to dampen acquisition of myofibroblastic traits, a key feature of CAF associated with poor disease outcome.

Gene-edited induced pluripotent stem cells (iPSCs) provide relevant isogenic human disease models in patient-specific or healthy genetic backgrounds. Towards this end, gene targeting using antibiotic selection along with engineered point mutations remains a reliable method to enrich edited cells. Nevertheless, integrated selection markers obstruct scarless transgene-free gene editing. Here, we present a method for scarless selection marker excision using engineered microhomology-mediated end joining (MMEJ). By overlapping the homology arms of standard donor vectors, short tandem microhomologies are generated flanking the selection marker. Unique CRISPR-Cas9 protospacer sequences nested between the selection marker and engineered microhomologies are cleaved after gene targeting, engaging MMEJ and scarless excision. Moreover, when point mutations are positioned unilaterally within engineered microhomologies, both mutant and normal isogenic clones are derived simultaneously. The utility and fidelity of our method is demonstrated in human iPSCs by editing the X-linked HPRT1 locus and biallelic modification of the autosomal APRT locus, eliciting disease-relevant metabolic phenotypes.

Reported as: Gene Editing Is Now Precise Enough to Modify a Single Letter of DNA

To make these very precise edits, an SNP modification is first inserted alongside a fluorescent reporter gene that helps researchers to identify modified cells. The researchers engineered a duplicate DNA sequence known as a microhomology (hence the technique’s name) on each side of the fluorescent gene, targeting sites for CRISPR to go in and cut DNA. The researchers were then able to use a DNA repair system known as microhomology-mediated end joining (MMEJ) to remove the fluorescent gene. That left only the single-base edit, in the form of an SNP, behind.

See also: Inhibition of the Host Translation Shutoff Response by Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy
Nuclear envelope-derived autophagy (NEDA) appears to be a cellular stress response, which is triggered late during HSV-1 infection. An energy-dependent single nucleotide repeat (SNR) might compensate for the viral alteration of the macroautophagic response. At this level of hydrogen-atom energy transfer in DNA base pairs in solution, the link to supercoiled DNA and viral latency becomes increasingly important.
Theorists are angry because they have been left behind. They know very little about what is important. That was expected by all serious scientists, especially those who have accumulated decades of testing experience while working in medical laboratories.
See for example: Applications of ligation-mediated PCR

Using a molecular energy source (which differs depending on the enzyme source organism), DNA ligase reforms the missing covalent bond and the strand is whole again. Two aspects of this are critical:

The nick to be repaired occurs on a single strand but in the context of a double-stranded molecule.
The bases of the nicked strand, and particularly those directly flanking the nick site, must be properly base-paired to the opposite (un-nicked) strand.

It’s not hard to imagine why this is: the base pairing is required to hold the two parts (sugar 3′ -OH and the next phosphate) in place for the ligase enzyme active site to catalyze joining them. If either one of these isn’t base-paired down and is flopping about with thermal motion, the reaction geometry doesn’t occur, and no new bond can be made.

Biologically uninformed theorists cannot even speak the same language. They do not start with a molecular energy source for base pairing and microRNA-mediated amino acid substitutions that differentiate all cell types. Instead, mutations are linked to increasing organismal complexity via the magic of evolution.

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Ecological adaptation: A new definition of heredity (3)

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