ATP-fueled microRNA biogenesis and cancer therapy

By: James V. Kohl | Published on: September 13, 2018

An ATP-fueled nucleic acid signal amplification strategy for highly sensitive microRNA detection
My summary: Add energy to fuel the creation of the target microRNA and link the proposed strategy to biophysically constrained viral latency outside the context of obfuscation such as: “…the high affinity and strength of the aptamer-target interaction.”
Do you know what an aptamer-target interaction is?
See: Thermodynamic study of aptamers binding to their target proteins

Aptamers are nucleic acids that bind to a target molecule with high affinity and specificity, which are selected from systematic evolution of ligands by exponential enrichment (SELEX).

Aptamers are nucleic acids. They are not selected from the systematic evolution of anything. Aptamer-target interaction is quantized energy-dependent and it biophysically constrains viral latency in the context of The biochemical basis of microRNA targeting efficacy

This model substantially improved prediction of [quantized energy-dependent] cellular repression, thereby providing a biochemical basis for quantitatively integrating miRNAs into gene-regulatory networks [that link Darwin’s “conditions of life” to biophysically constrained viral latency]

Simply put, Bartel’s group dismissed the nonsense about aptamer-target interactions and linked light-activated microRNA biogenesis in plants to biophysically constrained viral latency and all biodiversity in all living genera via the physiology of reproduction (i.e., Scientific Creationism).
His group’s works recapitulate the claims from Structural diversity of supercoiled DNA (2015)

Our data provide relative comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes.

If  you place energy-dependent nucleic acid binding into the proper context (i.e., outside the ridiculous context of aptamer-target interaction) you find that microRNAs are the small molecules that modulate DNA metabolic processes. In the context of our 1996 review of RNA-mediated cell type differentiation: From Fertilization to Adult Sexual Behavior, pre-mRNAs was the term used for microRNAs and/or the elusive aptamers.
See our section on molecular epigenetics:

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 (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.

A potential ramification of epigenetic imprinting and alternative splicing may be occurring in Xq28, a chromosomal region implicated in homosexual orientation…

Sex researchers were among the first to panic when we wrote this our “Discussion” section:

Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus (Runge and Zakian, 1996; Wu and Haber, 1995).

Clearly, the sex researchers needed new terms that could use to obfuscate the facts about biophysically constrained energy-dependent RNA-mediated cell type differentiation.
See for comparison: Machine Learning Predicts the Yeast Metabolome from the Quantitative Proteome of Kinase Knockouts
Their potential explanation in the paradoxical claim that “Machine Learning Predicts” sexual orientation in yeasts is that the quantized energy-dependent automagically occurs in the context of the the nature of enzyme-metabolite relationships and the mechanisms of self-regulatory metabolic networks. The self-regulatory metabolic networks supposedly link evolution to the topological organization of chemistry-dependent metabolism, which dictate the multifactorial and dynamic relationship between enzyme function and food energy-dependent species-specific metabolites.
For more comic relief that can be compared to claims about self-regulatory metabolic networks,  see: All about that base.
Remember the repeated claim that “…every angstrom is dynamic from the 5′ to the 3”
See how the 5′ and the 3′ link light-activated microRNA biogenesis in plants to biophysically constrained viral latency  in the context of Rosalind Franklin’s work with the tobacco mosaic virus (also mentioned in the parody — as “We’re bringing Franklin back.”
Help her to acheive the credit she deserves for not believing in the misrepresentations of Nobel Laureates Watson and Crick.
Read: Co-Transcriptional Molecular Assembly Results in a Kinetically Controlled Irreversible RNA Conformational Switch (September 12, 2018)

…an artificial RNA conformational switch, which consists of a 5′ aptamer unit for sensing thiamine pyrophosphate (TPP) and a 3′ working unit (TAR RNA) that binds Tat peptide connected by a switching sequence, was designed and cotranscriptionally functionalized.

Serious scientists, for comparison, have linked quantized energy-dependent feedback loops to all biophysically constrained biodiversity via feedback loops and the Tat peptide-mediated delivery of nutrients to cell types in all living genera.
See: Feedback loops link odor and pheromone signaling with reproduction
When I challenged Markus Ralser to address the pseudoscientific nonsense included in his group’s misrepresentations of nutrient-dependent pheromone-controlled reproduction, he wrote: https://twitter.com/RalserLab/status/1039025891614048256

There is a difference between founded theories, and wild claims out of the blue (i.e, look how anti-vaxxers argue) Scientists ‘make fun’ of the latter. And no, the supercoiled DNA structure does not predict metabolite levels, nor does anti-viral latency, nor light induced miRNAs

Then, he blocked me from seeing his Tweets. Others may never learn from him or members of his group how microRNAs have been linked to the prevention of all pathology.
See for comparison:
Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene 
A Concise Review of MicroRNA Exploring the Insights of MicroRNA Regulations in Bacterial, Viral and Metabolic Diseases
Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival
Reported as: Gene that Influences Circadian Rhythm Could Be Glioblastoma Therapy Target

…points to a subtype of a particular gene that apparently is enabling the survival of cancer cells, although it is more commonly associated with circadian rhythms.

The Glioblastoma Therapy Target is the missing quantized energy-dependent RNA-mediated amino acid substitution. The amino acid substitution links light-activated microRNA biogenesis in plants to the protection of all organized genomes via the pheromone-controlled physiology of reproduction in soil bacteria and humans. In all jawed vertebrates, achiral glycine is the amino acid substitution that links sunlight from food energy to the pheromone-controlled physiology of reproduction via substitution in position 6 of the GnRH decapeptide.
See:  Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels (1990)

Mutations in the period (per) gene of Drosophila melanogaster affect both circadian and ultradian rhythms. Levels of per gene product undergo circadian oscillation, and it is now shown that there is an underlying oscillation in the level of per RNA. The observations indicate that the cycling of per-encoded protein could result from per RNA cycling, and that there is a feedback loop through which the activity of per-encoded protein causes cycling of its own RNA.

The quantized energy-dependent per-encoded cycling of RNA links everything known to serious scientists about protein folding chemistry to viral latency via what is known about supercoiled DNA.
See: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems
I linked the quantized energy-dependent creation of the pheromone-controlled EDAR V370A variant from a single base pair change to the amino acid substitution in mice and in human populations. The EDAR V370A variant stabilizes the differences in cell types linked to differences in behavior that are linked from the creation of the sun’s anti-entropic virucidal energy to all biodiversity in my model.
For comparison, Markus Ralser published this: An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life (2018)

…it appears that the topology of metabolism is rooted in the non-enzymatic chemistry accessible to early life forms that existed irrespective of (and hence, before) the Darwinian selection process.

The so-called “Technologies Transforming Biology” featured in the context of “solar physics” in the August 3 issue of Science Magazine are largely beyond the grasp of understanding that is required to link experimental evidence of top-down causation: sunlight,  to the future of biology via Schrödinger at 75 – The Future of Biology – September 2018.
People like Marcus Ralser have their feet planted in the path that links the virus-driven theft of quantized energy to all pathology. It is the path that links the solar analemma from the respresentation of the Mobius strip to the symbol of infinity in the context of the creation of energy that cannot be destroyed.


I’ve added Tweets from my exchanges with Markus Ralser to show what caused him to panic and block me.


Which role does gene expression play in the regulation of metabolism? We think much more as some recent studies suggested – one can predict entire metabolomes from enzyme abundance. Big data rocks! https://doi.org/10.1016/j.cels.2018.08.001


Gene expression is quantized energy-dependent and food energy biophysically constrains viral latency. That fact was established outside the context of big data. See: https://www.pnas.org/content/early/2018/08/24/1802905115 Feedback-mediated signal conversion promotes viral fitness.


Great Link… But the paper is about a fundamentally different problem. Have a read


We linked energy-dependent changes in the RNA-mediated yeast metabolome to the pheromone-constrained development of sex differences in all cell types in our molecular epigenetic section from this 1996 Hormones and Behavior review. https://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html The problem is yours.


Well there is a difference between Jules Verne and NASA no? (i.e. between speculating one might be able to fly to the moon (and speculating one might find reptiles there), or flying actually to the moon and finding rocks there


The difference between theories + facts in the context of physics, chemistry, and biology is that light-activated microRNA biogenesis has been linked to all extant biodiversity via biophysically constrained viral latency as detailed in our 1996 review of cell type differentiation


#whatislife75 Are you claiming that serious scientists are confused? “Intronic miRNA mediated gene expression regulation controls protein crowding inside the cell” https://www.ncbi.nlm.nih.gov/pubmed/30189267 I’m claiming that other representations of top-down causation are foolish.


Nice Link. But like the other two, also this paper does not predict metabolite concentrations from enzyme expression.


Of course it does. So does everything known to serious scientists about the “Structural diversity of supercoiled DNA” It’s quantized energy-dependent and biophysically constrained. That’s why all serious scientists make fun of theorists. See the parody: https://youtu.be/gwy2lD1reos


Stop placing the problem into the context of the magic of evolution. “An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life” https://www.biochemj.org/content/475/16/2577 The creation of enzymes is quantized energy-dependent and biophysically constrained.


There is a difference between founded theories, and wild claims out of the blue (i.e, look how anti-vaxxers argue) Scientists ‘make fun’ of the latter. And no, the supercoiled DNA structure does not predict metabolite levels, nor does anti-viral latency, nor light induced miRNAs


Thanks. Serious scientists make fun of people like you, who are among the “losers” who Richard Feynman portrayed in his comments about human idiocy. https://www.youtube.com/watch?v=roX2NXDUTsM


https://www.huffingtonpost.com/suzan-mazur/kalevi-kull-censorship–r_b_10797646.html “Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge.” — Kalevi Kull


See also: Understanding and accounting for… https://journal.frontiersin.org/article/10.3389/fnhum.2014.00127/full George F R Ellis: This is absolutely correct and forms part of the larger concept that top-down causation is a key factor not just in the way the brain works but in broader contexts in biology and even physics.


Ralser’s group parrots “… genes control how nutrients are broken down into important molecules, but we’ve shown that… how the nutrients break down affects how our genes behave.” https://phys.org/news/2016-02-food-affect-genes-yeast-case.html#nRlv See: Kohl (2018) https://t.co/5VkgY01ZXQ …Ecological Adaptations


#whatislife75 @Ralserlab In an ongoing assault on your intelligence, Marcus Ralser wrote: https://twitter.com/RalserLab/status/1039025891614048256 “…supercoiled DNA structure does not predict metabolite levels… nor [do] light induced miRNAs…” See instead: Machine Learning Predicts https://doi.org/10.1016/j.cels.2018.08.001


Light-activated microRNA biogenesis in plants links the creation of sunlight and hydrophobicity from biophysically constrained viral latency to all biodiversity via supercoiled DNA and what is known about microRNAs in algae and mammals. See: https://microrna.pro/the-tipping-point-revisited-77000-publications/
————————Follow ups
9/11/18 https://twitter.com/jvkohl/status/1039487796833083393
“You are blocked from following @RalserLab and viewing @RalserLab’s Tweets.” Marcus claimed I had predicted nothing about the metabolome in this review: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems https://www.omicsonline.org/peer-reviewed/pnutrientdependent-phero
https://twitter.com/LotusOak/status/1039134068078727173
WATER MEMORY: Documentary (2014) about Nobel Prize laureate Luc Montagnier https://youtu.be/R8VyUsVOic0 #Homeopathy


I linked the EDAR V370A variant to differences in mice and in human populations.
Other theorists have blocked me when they realized the EDAR V370A was linked to differences in modern human populations that supposedly diverged ~20,000 years ago. See: https://www.pnas.org/content/early/2018/04/18/1711788115


Most theorists get scared when experimental evidence of top-down causation links light-activated microRNA biogenesis from biophysically constrained viral latency to fixation of RNA-mediated amino acid substitutions, which protects all species from mRNA degradation and mutations.


See my contributions to 5 of 15 articles in today’s RNA on “The Tweeted Times.” https://tweetedtimes.com/v/1342 If you are a theorist and the facts do not scare you, you can wait to block me until you are faced with the end of your career.


The end of your career as a theorist will come when the dissemination of facts about supercoiled DNA reaches “critical mass” in the context of how olfaction is linked to our visual perception of mass and energy in the context of the space-time continuum. https://www.youtube.com/watch?v=gwy2lD1reos&feature=youtu.be


Again, to his credit @WiringTheBrain’s Kevin Mitchell has not blocked me yet. But I’m beginning to think he may not realize what I’ve done to end his career as a theorist. See also: Olfaction Warps Visual Time Perception https://www.ncbi.nlm.nih.gov/pubmed/28334302


#whatislife75 B. Feringa does not know the origin of homochirality. See: https://doi.org/10.1371/journal.pcbi.1006458
Here, mutated achiral glycine is linked to the creation of other amino acids. Pseudoscientists claim the amino acids arrived via transport via asteroids. @RalserLab blocked me.


#whatislife75 In my 2014/2018 invited review of nutritional epigenetics, I linked EDAR V370A from the mouse to human model of biophysically constrained differences in human populations in North and East Asia for comparison to populations in the New World that recently diverged.


See for comparison: Machine Learning Predicts the Yeast Metabolome from the Quantitative Proteome of Kinase Knockouts https://doi.org/10.1016/j.cels.2018.08.001 Is the spurious claim about evolved underlying chemistry and topological organization of metabolism cause for alarm?


Did Steve Jobs die from pancreatic cancer because examples of human idiocy are still being published as if energy automagically emerged, chemistry evolved, and metabolism is not food energy-dependent? https://www.youtube.com/watch?v=roX2NXDUTsM


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