5th-6th Sept 2018 Dublin, Ireland

2018 March for Science vs microRNAs (2)

The anti-entropic virucidal energy of sunlight on contact with water has been linked from the creation of ATP synthase to the creation of ATP and to the creation of RNA. Energy-dependent RNA-mediated DNA repair has been linked to biophysically constrained viral latency via the creation of microRNAs and feedback loops linked to the food energy-dependent microRNA-mediated physiology of reproduction. The physiology of energy-dependent pheromone-controlled reproduction biophysically constrains viral latency in the context of the creation of the innate immune system and autophagy.
See: miRNA regulation of innate immunity (4/14/18)
None of the facts about the energy-dependent creation of the microRNAs or the microRNA-mediated regulation of innate immunity are included in: The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation (4/17/18)
The regulatory landscape that drive memory cytotoxic T lymphocyte formation might just as well be framed in the context of magic or in the equally ridiculous context of gene-centric theories.
See this report: Your immune system holds the line against repeat invaders, thanks to this molecule

Runx3’s control of T cell differentiation is important because when our bodies fight off viruses and cancers—and our T cells burst into action—the vast majority tend to become effector cells. These effector cells are short-lived and do not persist once the infection resolves.

The control of all cell type differentiation is energy-dependent, RNA-mediated and biophysically constrained by the physiology of reproduction in all living genera. The cell biology game “Cytosis” for ages 10+ teaches the facts that link Schrödinger (1944) What is Life? to Schrödinger at 75 – The Future of Biology – September 2018
In 1944, Schrödinger wrote:

Indeed, in the case of higher animals we know the kind of orderliness they feed upon well enough, viz. the extremely well-ordered state of matter in more or less complicated organic compounds, which serve them as foodstuffs. After utilizing it they return it in a very much degraded form -not entirely degraded, however, for plants can still make use of it. (These, of course, have their most power supply of ‘negative entropy’ the sunlight.)

See for comparison (this gene-centric pseudoscientific nonsense):
– Part I: FINDING THE CODE (Run time: 12:10
The race to sequence the human genome was also billed as a race to end disease. What happened?

– Part II: FIXING THE CODE (Run time: 13:07)
CRISPR — and the promise and pain of gene therapy that came before it. 

– Part III: SELLING THE CODE (Run time: 10:55)
Genetic testing has moved out of the labs into the masses. But even with your genome in hand, what can you believe?
The gene-centric pseudoscientific nonsense does not start with the creation of energy.  But every aspect of biophysically constrained life on Earth starts with the quantized energy-dependent creation of microRNAs. The epigenetically effected energy-dependent microRNA-mediated creation of the “Code” and the microRNA-mediated fixing of the “Code” is missing from the claims of biologically uninformed theorists who link beneficial mutations from natural selection to evolution. They have sold their gene-centric pseudoscientific nonsense to many people.
For example, some gene-centric biologically uninformed theorists share beliefs about abiogenesis for comparison to quantized energy-dependent microRNA biogenesis in articles like this: DNA Denaturing through UV-C Photon Dissipation: A Possible Route to Archean Non-enzymatic Replication
Conclusion:

Many of the fundamental molecules of life, those common to all three domains; bacteria, eukaryote, and archea, including RNA and DNA, amino acids, enzymes, vitamins, cofactors, and protoporphyrins, absorb photons in the UV-C 1. RNA or DNA in complexes with these molecules act as acceptor quenchers, providing the electronically excited pigment donor molecule with an extremely rapid (sub picosecond) non-radiative dexcitation channel, through internal conversion into vibrational energy of the nucleic acid and surrounding water molecules2.

See John Hewitt’s comment: You have just described the founding principle and thermodynamic function of life
In a classic example of human idiocy (See Feynman: food energy), biologically uninformed science idiots linked the dissipation of quantized energy to the origin of life via abiogenesis. The creation of biophysically constrained biophotonicaly based life in the context of the energy-dependent creation of microRNAs was reported in the context of photon dissipation and entropy as: Abiogenesis: A Theory on The Origins of Life

By now, we all know how evolution works. At least, most of us have a basic understanding of how it functions. At its most fundamental level, evolution is change over time. More specifically, it is changes within a biological population over successive generations.

Ultimately, biological complexity is one of the most important things to come out of evolution. Things started simple. Then genes mutated, cells interacted with their environment, mitochondria stopped being living organisms and started being part of a cell and—Tada—complex life.

A conflict arose between John Hewitt’s accurate representations of biophysically constrained life in The vibrational theory of olfaction for the win  and few months ago, Hewitt blocked me from seeing his tweets.

The same kinds of amino acid substitutions that control the separations and interactions of side chains in fluorescent proteins also play an essential role in tuning the proposed mechanism for vibration detection—inelastic electron tunneling. Life literally runs on electron tunneling through the respiratory chain complexes in mitochondria. These proteins employ complicated mechanisms including esoteric-soundings things like electron bifurcation and confurcation to pump protons across the mitochondrial inner membrane. When mitochondria go dark, cells can often continue to run for a short while, but it is only in the dim glow of the battery backup metabolism.

Here are some links to the reason for the conflict. Simply put, John Hewitt put everything known to serious scientists about energy-dependent microRNA biogenesis back into the context of abiogenesis.
2005 MicroRNA biogenesis: coordinated cropping and dicing
2015 Dysregulation of microRNA biogenesis and gene silencing in cancer
2015 RNA-mediated degradation of microRNAs: A widespread viral strategy?
Claims about abiogenesis exemplify what Richard Feynman referred to as human idiocy. So does John Hewitt and anyone else who believes in Michaelian’s pseudoscientific nonsense.
See other examples of Michaelian’s pseudoscientific nonsense and human idiocy by clicking here.
The energy-dependent creation of one domain of life links the physiology of reproduction in bacteria to biophysically constrained viral latency. The virus-driven degradation of messenger RNA is linked to the destruction of all life on Earth.
The degradation of messenger RNA links mutations to the creation of archaea and L-forms via entropy, which clearly links the weakening of the proton motive force to the elimination of the cell wall in L-forms (the last remnants of creation).
See also: Past 5,000 years prolific for changes to human genome
If you cannot link the miRNA regulation of innate immunity to all extant biodiversity via the physiology of pheromone-controlled reproduction and fixation of energy-dependent microRNA-mediated amino acid substitutions, thank a biologically uniformed science idiot.
 

5th-6th Sept 2018 Dublin, Ireland

Complexity: Routes and Patterns (4)

Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors (2015)

…the current models are both consistent with available and new experimental data and offer a number of predictions – notably, through revelation of highly constrained residues (Supplementary Data 910) – to guide and visualise structure-function analyses of these unusual sensory receptors.

No experimental evidence of top-down causation links anything except the quantized energy-dependent creation of enzymes, hormones, and receptors to biophysically constrained viral latency and ecological adaptations.

See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (2014)

See for comparison: Tuning Insect Odorant Receptors (2018)

Analyzing the variation of insect OR protein amino acids during evolution revealed a model for transmembrane domain arrangement that is unrelated to GPCRs (Hopf et al., 2015).

Try to refute my model with the latest pseudoscientific nonsense about coevolved amino acids.

SARCASM ALERT:Alternatively, evolve and fly away.

Cytosis can be used to teach everything from base editing to RNA editing to everyone over age 10. They will learn how to link the creation of energy to biophysically constrained viral latency via the physiology of pheromone-controlled reproduction.

Is meat protein unhealthy? (2)

See also: Microbiome-Grade DNA Extraction Kits

…the thermal and chemical methods effectively lyse the gram-negative organisms and boost their population in the final profile, amplifying the bias.

This suggests that all links from food energy-dependent de novo creation of the pheromone-controlled biophysically constrained bull sperm microRNAome have been misinterpreted in the context of virus-driven fescue toxicosis.

The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression

…the miRNA profile of mature ejaculated sperm may in fact have downstream consequences upon embryonic development. The potential for sperm miRNA affecting zygote development has recently been reported in the literature [18] and has interesting implications for the use of sperm miRNA profiles as indicators of potential male fertility.

Fescue toxicosis links the virus-driven creation of enzymes to the degradation of messenger RNA in bull sperm and to the transgenerational epigenetic inheritance of mutations, which all serious scientists have linked from damage to supercoiled DNA to all pathology in humans and other species.

Eating the meat from other animals that have not ecologically adapted to the virus-driven theft of quantized energy has been linked from the viruses in their genomes to human pathology via the degradation of messenger RNA in bacteria that become archaea and L-forms.

See also: Dobzhansky (1973)

…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.

See also: The Breadth of Viruses in Human Semen

The presence of viruses in semen is probably more widespread than currently appreciated, and the absence of virus in genital secretions should not be assumed for traditionally non–sexually transmitted viruses. The investigation of virus detection and persistence in semen across a range of viruses is useful for clinical and public health reasons, in particular for viruses that lead to high mortality or morbidity rates or to epidemics.

No serious scientist has ever reported a link from the Virus-mediated archaeal hecatomb in the deep seafloor to the evolution of anything except pathology. All serious scientists have, for comparison, linked ecological variation to food energy-dependent  polycombic ecological adaptations via biophysically constrained viral latency in species from microbes to humans.

From Fertilization to Adult Sexual Behavior (1996)

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation…

See also: Cytosis: A Cell Biology Board Game for ages 10+

 A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

5th-6th Sept 2018 Dublin, Ireland

Is meat protein unhealthy? (1)

Patterns of plant and animal protein intake are strongly associated with cardiovascular mortality
Reported as: Meat protein is unhealthy, but protein from nuts and seeds is heart smart

In the context of everything known about how the creation of anti-entropic virucidal light must be linked to all biodiversity on Earth, watch this ridiculous misrepresentation of the honeybee model organism. Food energy-dependent microRNA-mediated pheromone-controlled biophysically constrained viral latency is portrayed as if visual input was most important.

Bee swarms work like giant brains

See instead:

RNA-mediated nutritional psychiatry

RNA-mediated nutritional psychiatry (2)

Psychophysical Laws of Biology: RNA-mediated nutritional psychiatry (3)

Learn how to prevent more school shootings via what is known about how the “Psychophysical Laws” of Biology are linked to food energy-dependent biophysically constrained behaviors via microRNA-mediated cell type differentiation and the fixation of RNA-mediated amino acid substitutions like COMT Val158Met during the transition from adolescence to adulthood.

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults (Epub Oct 16 2014)

5th-6th Sept 2018 Dublin, Ireland

Polymaths and paradigm shifts: from Asimov to Bear (4)

Saying Goodbye to the RNA World Theory

RNA has a limited ability for catalysis compared to peptides, and would have struggled to maintain its catalytic activity under the changing temperature conditions of early Earth. Carter and Wills also argued that if an RNA world existed, it would have been unlikely for it to incorporate peptides later on.

See for comparison: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)

Isolated thymus nuclei transport amino acids into an intranuclear pool by a process which seems to depend on energy from nuclear ATP synthesis (20).

The energy-dependent creation of ATP synthase has since been linked to this claim from McEwen et al., (1964):

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

By starting with the energy-dependent de novo creation of enzymes, others have linked Schrödinger’s claims from “What is Life” (1944)  to all biophysically constrained biodiversity.
Say Hello again to Schrödinger at 75 – The Future of Biology
Let Timothy J. Cunningham, who disappeared from the CDC last month, reintroduce you. See his publications on:
1)”Racial Disparities in Age-Specific Mortality”
2) “Sex-specific relationships between adverse childhood experiences”
3) “Associations between antioxidants and all-cause mortality”
and
4) “Health and Safety Issues for Travelers”
Serious scientists know that all racial/ethnic disparities are food energy-dependent, RNA-mediated, and pheromone-controlled  in the context of enymes, metabolism, and amino acid substitutions. Fixation of the RNA-mediated amino acid substitutions differentiates all cell types in all living genera — including sex differences in cell types.
See for examples our section on molecular epigenetics from this 1996 Hormones and Behavior review of RNA-mediated cell type differentiation. 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…

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…

See for comparison, this nonsense: Caenorhabditis elegans glia modulate neuronal activity and behavior

Introduction: a brief on evolution of neuroglia

“Nothing in biology makes sense except in the light of evolution”. — Theodosius Dobzhansky (1900–1975)

Evolution of the nervous system proceeded through an increase in number and complexity of the nervous elements and through their specialization into electrically excitable neurons connected through defined synaptic contacts and electrically non-excitable neuroglia forming networks through intercellular gap junctions. Intercellular chemical neurotransmission is, however, characteristic for both forms of the neural cells that express appropriate receptors and are capable of secreting neurotransmitters. The evolution of the nervous system was not a straight journey from less complex and accomplished networks to the more refined ones; at the turning point between invertebrates and vertebrates, a fundamental metamorphosis occurred that changed the overall structure of the central nervous system (CNS).

The difference in the energy of two photons has since been linked from the proton motive force to the creation of enzymes and metabolism of food. The pheromone-controlled physiology of reproduction in species from bacteria to humans has linked DNA methylation from the creation and fixation of RNA-mediated amino acid substitutions to viral latency and all biodiversity. Timothy J. Cunningham placed that fact into the context of his history of published works.
For comparison, see: On the Difference between Physics and Biology: Logical Branching and Biomolecules (2018) and The Large Scale Structure of Space-Time(1975) George FR Ellis was a coauthor of both published works.
He, and others like him, failed to link Physics and Chemistry from molecular epigenetics to what is known about energy-dependent RNA-mediated biophysically constrained cell type differentiation to all biodiversity on Earth. Framing what is known to all serious scientists about cell type differentiation in the context of what Ellis might think is a logical representation of biomolecules attests to his lack of logic across the time-space continuum of his life.
See for comparison: Olfaction Warps Visual Time Perception (2017).
See also Odor-induced mood state modulates language comprehension by affecting processing strategies (2016)
The 2016 citation to The impact of natural odors on affective states in humans can now be linked to the accurate representations of top-down biophysical constraints on food energy-dependent pheromone-controlled feedback loops. The feedback loops are required to biophysically constrain viral latency.
See: What is life when it is not protected from virus driven entropy (video)

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.

See for comparison: Gay, Straight, and the Reason Why: The Science of Sexual Orientation (2011)

Still, even in fruit flies, other sensory input besides pheromones — acoustic, tactile, and visual stimuli — play a role in sexual attraction, and sex specific responses to these stimuli appear to be innate rather than learned by association [36.]. We simply don’t know where the boundary between prespecified attraction and learned association lie in our own species, nor do we have compelling evidence for the primacy of one sense over another. (pp. 210- 211)

See also: Gay, Straight, and the Reason Why: The Science of Sexual Orientation, 2nd edition (2016)
From the second edition of LeVay’s book:

… chemosignal enthusiasts point to a variety of studies in which sniffing body secretions or substances purified from secretions appears to have some psychological effect… (p. 115)

LeVay cites Kohl et al., (2001) Human pheromones: integrating neuroendocrinology and ethology.
He has never mentioned the fact that the effects of virus-driven entropy on cell type differentiation were linked human sexual orientation in The Scent of Eros: Mysteries of Odor in Human Sexuality (1995/2002) and in the book chapter he cited in the first edition of Gay, Straight, and the Reason Why: The Science of Sexual Orientation.
See for comparison: Always follow your nose: the functional significance of social chemosignals in human reproduction and survival (2015) This article is part of a Special Issue “Chemosignals and Reproduction”
John Cacioppo, a Founder of Social Neuroscience, Dies

The University of Chicago psychology professor made fundamental contributions to understanding the neural mechanisms of social experiences.

My comment to The Scientist:

See also: Evolution of neuroarchitecture, multi-level analyses and calibrative reductionism (2012)

I hope John Cacioppo is remembered for this refutation of neo-Darwinian pseudoscientific nonsense:

Although peptide chemistry has been with us since amino acids first formed, the social role of oxytocin did not exist prior to the evolutionary sculpting of the vertebrate brain.

He may have been one of the first social scientists to recognize the fatal flaw that others continue to include in their works. All other serious scientists, like him, start with the energy-dependent creation of enzymes and amino acids. Only pseudoscientists still start with the evolution of the vertebrate brain.

I remember when he and his wife turned towards me and smiled — after I asked the speaker from Argentina about the role of oxytocin in a rodent model. No studies were being done for the obvious reason that few people knew where oxytocin came from.

I invited the speaker to lunch and we laughed a lot about the works that tried to link oxytocin to differences in behavior without linking the differences to altered  RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse

RIP John Cacioppo

See also: Multilevel integrative analyses of human behavior: social neuroscience and the complementing nature of social and biological approaches (2000)
Nothing published during that 12-year period and nothing published before or since then suggests the the neuroarchitecture of intelligent creatures somehow evolved.
For comparison, see: Human pheromones and nutrient chemicals: epigenetic effects on ecological, social, and neurogenic niches that affect behavior (2012) Presented at the Society for Social Neuroscience Annual Meeting 2012
See also: Neuroglia in C. elegans (2018)

The nematode C. elegans is one of the most important model organisms for understanding neurobiology. Its completely mapped neural connectome of 302 neurons and fully characterized and stereotyped development have made it a prototype for understanding nervous system structure, development, and function. Fifty-six out of C. elegans‘ total of 959 somatic cells are classified as neuroglia. Although research on worm glia has lagged behind studies focused on neurons, there has been a steep upswing in interest during the past decade. Information arising from the recent burst of research on worm glia supports the idea that C. elegans will continue to be an important animal model for understanding glial cell biology. Since the developmental lineage of all cells was mapped, each glial cell in C. elegans is known by a specific name and has research associated with it. We list and describe the glia of the hermaphrodite form of C. elegans and summarize research findings relating to each glial cell. We hope this lecture provides an informative overview of worm glia to accompany the excellent and freely available online resources available to the worm research community.

The worm research community seems to be largely unaware of this fact: System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes
The have failed to link food odors from the pheromone-controlled physiology of reproduction to ecological adaptatation manifested in morphological and in behavioral diversity.

An evolutionary theory killer

Conceptual critique: Innateness vs the death gene (2)

Excerpt: Martie Haselton notes

“…there’s a hidden adaptive intelligence that has been shaped over eons. Martie Haselton places that ecological adaptation into the context of the claim that “…our bodies are designed to fight off invaders, whether they take the form of a cold virus… (p 73.) and she mentions the link from the designer to one theory about menstruation: “female bleeding serves to flush out “bad” sperm that may carry bacteria, viruses and other pathogens.” (p. 84)

See also: Conceptual critique: Innateness vs the death gene (1)
Re: Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases

This approach may help limit seasonal influenza epidemics, transmission of tuberculosis, as well as major pandemics.

See for comparison: Subatomic

…is a deck building game where players are competing to build a number of available atoms. Each player starts with the same small deck of cards that consist of Proton Cards, Neutron Cards, Electron Cards and Energy Cards and a beginning hand limit of 5 cards. They use these cards to build upon their current Atom, in an attempt to construct one of the available Atom Cards, and/or use their hand of cards to purchase more powerful atom building cards for later use, or increase their hand limit. The deck building cards are simple and clean, but offer a number of interesting combinations. Players also have an energy track that allows them to store energy, which introduces a “push-their-luck” type of mechanic…

See also: Cytosis: A Cell Biology Board Game

Players start out with a number of workers and on their turn, they will place one of their workers on any available location within that cell. Some of the locations provide players with resources (e.g., mRNA, ATP); some with actions (e.g., convert resources, collect cards). Resources are used to build enzymes, hormones, and/or receptors, which score Health Points.

Science Concepts: cell biology, nucleus, free ribosomes, smooth ER, rough ER, golgi apparatus, plasma membrane, mitochondria, enzymes, hormones, receptors, cell detoxification, antibodies and viruses
Alternatively, theorists may continue to ignore the Science Concepts: in the context of  The Hidden Intelligence of Hormones — How They Drive Desire, Shape Relationships, Influence Our Choices, and Make Us Wiser (Feb 13, 2018) for comparison to From Fertilization to Adult Sexual Behavior (1996)

Martie Haselton notes

“…there’s a hidden adaptive intelligence that has been shaped over eons. Martie Haselton places that ecological adaptation into the context of the claim that “…our bodies are designed to fight off invaders, whether they take the form of a cold virus… (p 73.) and she mentions the link from the designer to one theory about menstruation: “female bleeding serves to flush out “bad” sperm that may carry bacteria, viruses and other pathogens.” (p. 84)

See for comparison: Conditional expression of women’s desires and men’s mate guarding across the ovulatory cycle (2006)In 2006, it became clear to most serious scientists that Martie Haselton knew nothing about biophysically constrained RNA-mediated viral latency. Now, she places everything known back into the context of neo-Darwinian pseudoscientific nonsense and eons of evolution. Fortunately,  you can read and discuss her book in the context of what other pseudoscientists have been doing for the past two decades. Simply copy and paste from Wikipedia in attempts to promote ridiculous theories.

See for comparison: Evolution: Genetic Novelty/Genomic Variations by RNA-Networks and Viruses 2018 >

Preliminary List of Confirmed Speakers (41)
Chantal Abergel >
Aix-Marseille University, Centre National de la Recherche Scientifique, Information Génomique & Structurale, Marseille, France
Gustavo Caetano Anolles >
Department of Crop Sciences, Evolutionary Bioinformatics Laboratory, University of Illinois at Urbana-Champaign Urbana, USA.
Marlene Belfort >

Department of Biological Sciences and RNA Institute, University at Albany, New York, USA
Felix Broecker >
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA
Department of Chemistry & Biochemistry, University of California, Santa Barbara, USA
Julian Chen >
Department of Chemistry and Biochemistry, Arizona State University, Tempe, USA
Jean-Michel Claverie >
Centre National de la Recherche Scientifique & Aix-Marseille University, Marseille, France
Bryan Cullen >
Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, USA
Valerian Dolja >

Department of Botany and Plant Pathology, Oregon State University, Corvallis, USA
Cedric Feschotte >
Department of Human Genetics, University of Utah, School of Medicine, Salt Lake City, USA
Matthias Fischer >
Max Planck Institute for Medical Research, Department of Biomolecular Mechanisms, Heidelberg, Germany
David Gilmer >
Institut de biologie moléculaire des plantes, Integrative virology, Strasbourg, France
Reynald Gillet >
Université de Rennes 1, Translation and Folding Team, Rennes cedex, France Institut Universitaire de France
Jordi Gomez >
Instituto de Parasitología y Biomedicina ‘López-Neyra’ (CSIC), Granada, Spain
Matti Jalasvuori >

Centre of Excellence in Biological Interactions, Department of Biological and Environmental Science, University of Jyväskylä, Finland
I.King Jordan >
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA
Eugene Koonin >
National Center for Biotechnology Information, National Library of Medicine, Bethesda, USA.
Dusan Kordis >
Department of Molecular and Biomedical Sciences, Josef Stefan Institute, Ljubljana, Slovenia
Mart Krupovic >

Unit BMGE, Department of Microbiology, Institut Pasteur, Paris, France
Erez Levanon >
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
German Martinez >
Dept. of Plant Biology, Swedish University of Agricultural Sciences, Uppsala, Sweden
John Mattick >
Garvan Institute of Medical Research, Darlinghurst, Australia
Jeff Miller >
California NanoSystems Institute, University of California, Los Angeles, USA
Karin Moelling >
Max Planck Institute for molecular Genetics, Berlin, Germany
Sabine Müller >
Universität Greifswald, Institut für Biochemie , Greifswald , Germany
Ulrich Müller >
Department of Chemistry & Biochemistry, University of California, San Diego, USA
Mariusz Nowacki >
Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland
David Prangishvili >
Department of Microbiology, BMGE, Institut Pasteur, Paris, France
Lennart Randau >
Max Planck Institute for Terrestrial Microbiology, Marburg, Germany
Forest Rohwer >
Department of Biology, San Diego State University, San Diego, CA, USA
Corrado Spadafora >
Institute of Translational Pharmacology, CNR, Rome, Italy
James Shapiro >
Department of Biochemistry and Molecular Biology , University of Chicago , IL , USA
Jason Shepherd >
Biochemistry and Ophthalmology & Visual SciencesUniversity of Utah, School of Medicine Salt Lake City, USA
Ravindra Singh >
Department of Biomedical Sciences, Iowa State University, Ames, USA
Keizo Tomonaga >
Laboratory of RNA Viruses, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Japan
Peter Unrau >
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, Canada
Luis P. Villarreal >
Center for Virus Research, University of California, Irvine, Irvine, CA, USA
Andreas Werner >
RNA biology group, Institute for Cell and Molecular Biosciences, Newcastle University, UK
Eric Westhof >
Architecture and Reactivity of RNA, Institute of Molecular and Cellular Biology of the CNRS, University of Strasbourg, France
Bojan Zagrovic >
Department of Structural and Computational Biology, Max F. Perutz Laboratories, Vienna, Austria

Steven Zimmerly >
Department of Biological Sciences, University of Calgary, Calgary, Canada

For comparison to Martie Haselton’s February 13, 2018 publication of her pseudoscientific nonsense about hormonal women, see: Energy as information and constrained endogenous RNA interference from my February 15, 2017 virtual conference presentation on Precision Medicine.

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

Cytosis can be used to teach everything from base editing to RNA editing to everyone over age 10. They will learn how to link the creation of energy to biophysically constrained viral latency via the physiology of pheromone-controlled reproduction.

How to biophysically constrain the flu virus (1)

Excerpt: John E Walker (Factor-dependent archaeal transcription termination) will probably explain the molecular mechanism of how ATP is made, which may be important to know for those who have learned how important ATP is by playing “Cytosis.” The creation of ATP can be linked to the creation of RNA and the prevention of messenger RNA degradation in the context of the Virus-mediated archaeal hecatomb in the deep seafloor.
What the flu does to your body, and why it makes you feel awful

…when you have an influenza infection, you can rest assured that it is because your body is fighting hard. It’s combating the spread of the virus in your lungs and killing infected cells.

Why suffer needlessly or die prematurely. See: Cytosis: A Cell Biology Board Game 

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses! (2 to 5 Players, Ages 10 & up, Plays in 50 to 75 mins)

Download the “Science Behind the Game” to learn how food energy-dependent alternative splicings of pre-mRNA protect all cell types, or see Alternative splicing and the evolution of phenotypic novelty.
Link the alternative splicings to species-specific behaviors via the physiology of reproduction in From Fertilization to Adult Sexual Behavior and anything else I have published or presented during the past two decades.
All behavior is energy-dependent. The energy comes from sunlight. Quantized energy as information from sunlight is linked to healthy longevity via its anti-entropic virucidal effect.
For example: Special UV light safely kills airborne flu virus, finds study

Scientists have known for decades that broad-spectrum UVC light, which has a wavelength of between 200 to 400 nanometers, or nm), is highly effective at killing bacteria and viruses by destroying the molecular bonds that hold their DNA together.

For comparison to vaccinations:
Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases

A key advantage of the UVC based approach, which is in clear contrast to vaccination approaches, is that UVC light is likely to be effective against all airborne microbes. For example, while there will almost certainly be variations in UVC inactivation efficiency as different influenza strains appear, they are unlikely to be large7,10. Likewise, as multi-drug-resistant variants of bacteria emerge, their UVC inactivation efficiencies are also unlikely to change greatly9.

In the context of vaccinations:
Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution

The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.

Clearly, vaccinations may not protect you and prevention via use of UV light is desirable.
When you learn how UV light protects you at the level of particle physics, you will understand the horrors of neo-Darwinian theory and big bang cosmology .
See Subatomic
The link from quantum physics to quantum chemistry was reported last month. Modern diversification of the amino acid repertoire driven by oxygen.
Schrödinger at 75, The Future of Biology is scheduled for September 2018
John E Walker (Factor-dependent archaeal transcription termination) will probably explain the molecular mechanism of how ATP is made, which may be important to know for those who have learned how important ATP is by playing “Cytosis.” The creation of ATP can be linked to the creation of RNA and the prevention of messenger RNA degradation in the context of the Virus-mediated archaeal hecatomb in the deep seafloor.
People who have played “Cytosis” can predict what will happen at the Schrödinger at 75 conference. They will jump ahead of most academics if they play “Subatomic” and link particle physics to all biophysically constrained biodiversity.
The fun factor is important to most people. They don’t care about supercoiled DNA or the virus-driven degradation of messenger RNA. But other scientists are having fun watching the creator of the genious games teach facts to theorists. We are especially pleased about his help in teaching the facts about energy-dependent cell biology to anyone who wants to have fun, prevent or survive the flu, or to become a serious scientist.
Alternatively, play the Mutation-driven evolution game (available only as an outdated 2013 textbook).
But remember:  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
Simply put, you could be dead by the time pseudoscientists start to tell the truth. For example, this is the truth:

There had been years of biophysical experiments and biochemical experiments, and it was always assumed that there was just one dynein molecule,” Lander adds.

Lander just admitted that their assumptions may have made many serious scientists wrong about every aspect of energy-dependent life on Earth.
See also: Real Heroes Have the Guts to Admit They’re Wrong

…one reason we can’t admit we have the facts wrong is that it’s too painful to our self-conception as smart, right-thinking people—or to our political tribal identity.

In the past year alone, mathematicians have pulled papers when they’ve learned their proofs don’t hold and economists have retracted work after finding they’d misclassified their data. The Harvard stem-cell biologist Douglas Melton had a hit 2013 paper that got cited hundreds of times—but when colleagues couldn’t replicate the finding, he yanked it.

They discount the fact that any claims that have been placed into the context of neo-Darwinian theories have been invalidated first by Schrödinger in “What is Life? (1944) and since then by all serious scientists who have linked  the sun’s anti-entropic virucidal energy from the physiology of reproduction to biophysically constrained viral latency and all biodiversity.
See also: Windowed Granger causal inference strategy improves discovery of gene regulatory networks

Significance

Discovery of gene regulatory networks (GRNs) is crucial for gaining insights into biological processes involved in development or disease. Although time-resolved, high-throughput data are increasingly available, many algorithms do not account for temporal delays underlying regulatory systems—such as protein synthesis and posttranslational modifications—leading to inaccurate network inference. To overcome this challenge, we introduce Sliding Window Inference for Network Generation (SWING), which uniquely accounts for temporal information. We validate SWING in both in silico and in vitro experimental systems, highlighting improved performance in identifying time-delayed edges and illuminating network structure. SWING performance is robust to user-defined parameters, enabling identification of regulatory mechanisms from time-series gene expression data.

Reported as: New machine learning algorithm uncovers time-delayed interactions in cells

SWING puts together a more complete picture of the cause-and-effect interactions happening among genes by incorporating time delays and sliding windows. Rather than only looking at the individual perturbations and responses, SWING uses time-resolved, high-throughput data to integrate the time it takes for those responses to occur.

Researchers will continue to scramble in attempts to put their findings into the context of what has already been presented in: Olfaction Warps Visual Time Perception
and in:

 

 

Cytosis can be used to teach everything from base editing to RNA editing to everyone over age 10. They will learn how to link the creation of energy to biophysically constrained viral latency via the physiology of pheromone-controlled reproduction.

BiondVax Universal Flu Vaccine Patent

Summary: …the dream to create an effective universal flu vaccine to ultimately eradicate the flu is placed into the context of claims about changes to the virus. The changes are energy-dependent ecological adaptations. No one claims that the virus mutates or that it evolves. Only biologically uninformed theorists make such ridiculous claims.
BiondVax Universal Flu Vaccine Patent Granted in India

The patent describes influenza vaccines comprised of multiple copies of several epitopes, such as M-001 which contains nine common and conserved influenza virus epitopes.

The use of the word epitope obfuscates cause and effect in the context of natural information processing, which is energy-dependent and biophysically constrained by the physiology of pheromone-controlled reproduction in species from microbes to humans. If they used the term conserved amino acid substitutions more people might understand the fact the fixation of amino acid substitutions biophysically constrains viral latency. Who knows what epitopes are or what they do or how they do it?
See for comparison: Learning from Bacteria about Natural Information Processing (Israel) and Generation of influenza A viruses as live but replication-incompetent virus vaccines, (China) which was reported as: Engineered virus has artificial amino acid allowing it to serve as a vaccine
Researchers in other countries, but not in the United States of America, have made scientific progress that helps to make sense of claims about energy-dependent natural information processing and RNA-mediated amino acid substitutions that biophysicaily constrain viral latency and typically prevent all pathology.
In this video, the dream to create an effective universal flu vaccine to ultimately eradicate the flu is placed into the context of claims about changes to the virus. The changes are energy-dependent ecological adaptations. No one claims that the virus mutates or that it evolves. Only biologically uninformed theorists make such ridiculous claims.

See for comparison: How to Build a Better Flu Shot (with my emphasis)
1) … the influenza virus has many rapidly mutating strains. And because the strains mutate so quickly
2) …the mushroom head of hemagglutinin mutates rapidly, so antibodies against one type of head won’t work against a mutant version.
3) To infect the cell, the stalk of the hemagglutinin mushroom becomes completely rearranged from its normal state. “It’s a machine,” Krammer explains. “It doesn’t tolerate mutations well. If you introduce mutations, you destroy the machine, so the virus doesn’t like to change it.”
4) Other teams are testing headless stalks made by anchoring the stalk to a ferritin protein nanoparticle or by creating genetic mutations at the top, as potential vaccines too.
5) In a study published January 19 in Science, University of California, Los Angeles, virologist Ren Sun and colleagues identified eight genetic mutations that make the flu virus sensitive to a host cell’s interferons.
6) “The team was able to mutate this virus for interferon sensitivity without changing the immune response, which is a challenge.”
7) Fauci says one essential piece of information scientists need to build a universal flu vaccine is to understand how serial exposure to the virus and vaccination affects the immune system.
8) “This is what we call immunological imprinting. It’s controversial, but we need to know what the influence is to create a broadly effective flu vaccine,” Fauci says.
9) Understanding the effect of pre-existing immunity on virus evolution is also important, given that vaccination itself could influence how flu strains evolve, Fauci and colleagues note in a paper published last summer in Immunity
10) The paper describes a path toward making a universal flu vaccine. “I see this work falling into three buckets,” Fauci says. “There’s the bucket on antibody development, the bucket on boosting the immune response to flu, and finally the bucket on prior exposure and how that affects the immune system,” he says.
Fauci wants others to believe that viruses mutate and evolve but that immunological imprinting is controversial. He has many others to help people in the United States accept the claims about mutations and evolution and put the claims of serious scientists who understand the facts about immunological imprinting into the context of controversy.
My comment to The Scientist:

In this report from the NIH: Flu infection study increases understanding of natural immunity the focus on the change in the influenza virus was properly placed into context of energy-dependent changes in the virus, which are called ecological adaptations when they occur in human populations.

For example, one energy-dependent amino acid substitution causes increased virulence in the influenza virus, as clearly stated here: The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.

Simply put, all serious scientists know that viruses do not mutate and evolve. Viruses steal the energy that biophysically constrains viral latency and some humans in some human populations fail to ecologically adapt as quickly as others.

Is Fauci, or anyone else who made claims in the article from The Scientist, a serious scientist? Unfortunately, the answer is no. Serious scientists do not believe that mutations can be linked to evolution. That gives them an edge if they are working in other countries, but not the United States of America.
See how serious scientists in some countries will maintain their edge, and continue to put theorists from the United States of America to shame — along with all the so-called science journalists who report the nonsense about mutations and evolution.
Controversy over evolution in Israel (2010)

There are many people who don’t believe the evolutionary account is correct,” he was quoted as saying. “There are those for whom evolution is a religion and are unwilling to hear about anything else. Part of my responsibility, in light of my position with the Education Ministry, is to examine textbooks and curricula.”

See also: Israeli Middle Schools School to Include Theory of Evolution (2014)

 “…learning about evolution is not the primary function of the decision, but rather to use it as a building block for students to learn more about their ecology.”

Those who learn about ecology are less likely to make claims about mutations or evolution.
Turkish schools to stop teaching evolution, official says (2017)

The secular opposition has long argued that the government of Recep Tayyip Erdoğan is pursuing a covert Islamist agenda contrary to the republic’s founding values.

Does anyone in the United States think that the Trump administration is pursuing a covert Christian agenda?  If so, see:
Cytosis: A Cell Biology Board Game

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

 

For God and Country

Diet-driven RNA interference and cancer prevention (4)

Excerpt: What I perceive as apathy can be attributed to the lack of empathy for anyone who suffers from the preventable or controlled virus-driven pathology that, sooner or later, kills us all.
In the case of our Vietnam veterans, naturally occurring prevention or effective treatment of glioblastoma might be achieved by dietary intervention with a curcumin supplement.
“micrornas”[MeSH Terms] OR “micrornas”[All Fields] OR “microrna”[All Fields] Items: 1 to 20 of 68871
See:  The tipping point (revisited): 68,000 publications
69,000 published works on microRNAs will be the next “tipping point.” Predictably, it will be reached during the same 28 day period in which my tweets (@jvkohl have received more than 70,000 impressions.
On 1/18/18: Tweet impressions 71.2K 602.0%
The 602.0% increase has not been accompanied by a significant increase in followers or a significant increase in engagements.
What I perceive as apathy can be attributed to the lack of empathy for anyone who suffers from the preventable or controlled virus-driven pathology that, sooner or later, kills us all.
In the case of our Vietnam veterans, naturally occurring prevention or effective treatment of glioblastoma might be achieved by dietary intervention with a curcumin supplement.
See: A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model

DP-Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and curcumin may be useful in the development of combination therapy for glioblastoma.

See also: Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models

This is the first study, to our knowledge, to demonstrate the utility of a pharmacological inhibitor of glutamine transport in oncology, representing a new class of targeted therapy and laying a framework for paradigm-shifting therapies targeting cancer cell metabolism.

Reported as: Researchers find a way to ‘starve’ cancer

Glutamine is an essential amino acid for many cell functions including biosynthesis, cell signaling and protection against oxidative damage. Because cancer cells divide more rapidly than do normal cells, they need more glutamine.

A protein called ACST2 is the primary transporter of glutamine into cancer cells. Elevated ASCT2 levels have been linked to poor survival in many human cancers, including those of the lung, breast and colon. Genetic studies that silence the ACST2 gene in cancer cells have produced dramatic anti-tumor effects.

See also: MicroRNA[s] and glutamine Items: 1 to 20 of 65
The facts about food energy-dependent microRNA-mediated RNA-directed DNA methylation and fixation of RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all living genera were removed from this report. Use off the cryo-EM technology links energy-dependent changes in electrons to healthy longevity in all ecosystems. It is apparent that some researchers do not want more people to learn about that fact.
See: Structural basis of RNA polymerase III transcription initiation

The unwound DNA directly contacts both sides of the Pol III cleft. Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is more divergent. The structures presented unravel the molecular mechanisms underlying the first steps of Pol III transcription and also the general conserved mechanisms of gene transcription initiation.

The information that links the virus-driven theft of quantized energy from the negative supercoiling (unwinding) of supercoiled DNA was removed in this attempt to support the neo-Darwinian pseudoscientific nonsense about the three domains of life. The bastardization of the use of cryo-EM technology occurred in the following context(s).
1) There is no mention of the quantized anti-entropic virucidal energy as information that is required to create ATP and RNA.
2) The energy-dependent creation of ATP and the creation of RNA is not linked to healthy longevity in all living genera via the physiology of pheromone-controlled reproduction.
3) The fixation of RNA-mediated amino acid substitutions that stabilize the differentiated cell types of all living genera are viewed in the context of negative supercoiling that occurs in an ATP-independent manner.
4) A spontaneously formed transcription bubble links the energy-dependent stability of supercoiled DNA to cell type differentiation in species from bacteria to humans.
5) The claim that promoters can be opened without ATP hydrolysis is used to suggest that no energy-dependent supercoiling is required to link the three kingdoms of life — assuming that there are three kingdoms of life.
6) The fact that the virus-driven degradation of messenger RNA in humans causes them to become non-human primates and the fact that it also cause bacteria to archaea and L-forms is ignored.
See: Virus-mediated archaeal hecatomb in the deep seafloor

We show here for the first time the crucial role of viruses in controlling archaeal dynamics and therefore the functioning of deep-sea ecosystems, and suggest that virus-archaea interactions play a central role in global biogeochemical cycles.

By deliberately removing virus-archaea interactions from the representations reported as: Scientists zoom in to watch DNA code being read, pseudoscientists have reverted to promotion of their ridiculous gene-centric theories.
See for comparison: “Cytosis

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

See also: Attacked from All Sides: RNA Decay in Antiviral Defense

…RNA decay machinery plays important roles in antiviral defense. This can involve either direct effects on vRNA stability or indirect regulation of the intracellular milieu. Furthermore, an emerging theme suggests that many RNA binding proteins can be repurposed from their endogenous roles in the nucleus to antiviral roles in the cytoplasm. Future studies are necessary to further elucidate how these RNA binding proteins recognize foreign RNAs and how they interface with the RNA decay machinery to restrict vRNA replication.

Accurate representations of how natural selection for food energy-dependent codon optimality links the physiology of pheromone-controlled reproduction to the transgenerational epigenetic inheritance of healthy longevity will continue to be attacked from all sides.
Biologically uninformed theorists and philosophers can do nothing else but attack after proclaiming the nonsense of mutation-driven evolution during the past decades. They have failed to link their nonsense to the prevention of all pathology or to effective treatments via optimization of autophagy: the innate antiphage defense mechanism of all living genera.

Alternative splicing of pre-mRNA

Diet-driven RNA interference and cancer prevention (3)

Excerpt: They claim to have found novel autoregulatory feedback loops that link changes in microRNAs to the alternative splicing factors SRSF1 and SRSF2.  Ectopic expression of SRSF1 can automagically repress the level of multiple microRNAs and SRSF2 can automagically upregulate miRNA expression.

The fact that a peer-reviewed work published in 2018 links autoregulatory feedback loops to automagically altered gene expression and apoptosis via alternative splicings of pre-mRNAs suggests it is time for all serious scientists to retire. The magic of pseudoscientists has prevailed for more than 2 decades.

See for comparison: In clinical trial, cream reduces squamous cell carcinoma risk

Results of a new randomized, double-blinded, controlled clinical trial in veterans showed a 75 percent reduction in the risk of needing surgery to treat a squamous cell carcinoma for a year after applying a skin cream for up to four weeks.

How Fluorouracil Works: (with my emphasis)

The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division. Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die. The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. They also induce cell suicide (self-death or apoptosis).

Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles.

Chemotherapy is most effective at killing cells that are rapidly dividing. Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The “normal” cells will grow back and be healthy but in the meantime, side effects occur. The “normal” cells most commonly affected by chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea, and/or hair loss. Different drugs may affect different parts of the body.

Fluoruracil belongs to the category of chemotherapy called antimetabolites. Antimetabolites are very similar to normal substances within the cell. When the cells incorporate these substances into the cellular metabolism, they are unable to divide. Antimetabolites are cell-cycle specific. They attack cells at very specific phases in the cycle. Antimetabolites are classified according to the substances with which they interfere. Fluoruracil is classified as a pyrimidine analog because it interferes with DNA and RNA synthesis by mimicking the building blocks necessary for synthesis.

The term antimetabolites is confusing. Metabolism is enzyme-dependent. Cell type differentiation is energy-dependent and the creation of microRNA links ATP to the creation of enzymes that metabolize food to the species-specific pheromones.
Pheromones biophysically constrain viral latency. That is how they prevent all pathology in the context of metabolism. Enzyme-dependent cycles of metabolism are the key to healthy longevity. Simply put, pheromones prevent the transgenerational epigenetic inheritance of nearly all viruses that have not been biophysically constrained by food energy-dependent metabolism.

Hardin, Hall and Rosbash (1990) put that fact into the perspective of Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. The feedback loops are food energy-dependent and biophysically constrained by naturally occurring RNA interference (i.e., natural selection for energy-dependent codon optimality). The feedback links the metabolism of food to pheromone-controlled biophysically constrained viral latency.
 

Rosbash shared the 2017 Nobel Prize in Chemistry, which attests to the fact that all serious scientists probably know how to prevent or to effectively treat cancer as a disorder of cyclic changes in the chemistry of energy-dependent RNA mediated cell type differentiation. Prevention should include limiting exposure to nutrient stress and/or social stress because stress alters microRNA-mediated alternative splicings that link food energy to the biophyiscally constrained chemistry of protein folding.

See: Microrna-mediated regulation of splicing factors SRSF1, SRSF2 and hnRNP A1 in context of their alternatively spliced 3’UTRs

The microRNAs targeting SRSF1 and SRSF2 are involved in a regulatory feedback loop. microRNAs miR-183-5p and miR-200c-3p that target SRSF2, affect the expression of genes involved in apoptotic regulation.

They claim to have found novel autoregulatory feedback loops that link changes in microRNAs to the alternative splicing factors SRSF1 and SRSF2.  Ectopic expression of SRSF1 can automagically repress the level of multiple microRNAs and SRSF2 can automagically upregulate miRNA expression.

The fact that a peer-reviewed work published in 2018 links autoregulatory feedback loops to automagically altered gene expression and apoptosis via alternative splicings of pre-mRNAs suggests it is time for all serious scientists to retire. The magic of pseudoscientists has prevailed for more than 2 decades.

See for comparison:

From Fertilization to Adult Sexual Behavior (1996)

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 [model organisms.]

See also:
Feedback loops link odor and pheromone signaling with reproduction (2005)
The feedback loops are food energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction in species from microbes to humans.

Sarcasm alert: The treatment of automagically dysregulated apoptosis should probably begin with a change in diet.

Changes in diet have been linked from the energy-dependent creation of enzymes that specifically link an energy-dependent base pair change to microRNA-mediated DNA repair via fixation of an RNA-mediated amino acid substitution. The substitutions are linked to energy-dependent cell type differentiation and healthy longevity without the magic.

Just add food energy or the virus-driven theft of quantized energy to eliminate the term autoregulatory and you could prevent or effectively treat all virus-driven pathology. 

Energy-dependent RNA interference links the enzyme-dependent metabolism of food and drugs to cell type differentiation via feedback loops that link pheromones to biophysically constrained viral latency.

Do not claim to have a logical philosophy if you cannot link the creation of the sun’s anti-entropic virucidal energy to every aspect of the biophysically constrained pheromone-controlled physiology of reproduction in species from microbes to human by starting with the obvious need to control viral replication in the ocean and linking the control to healthy longevity in modern human populations via fixation of RNA-mediated amino acid substitutions in all differentiated cell types.

See also: Metabolic Labeling and Profiling of Transfer RNAs Using Macroarrays

Transfer RNAs (tRNA) are abundant short non-coding RNA species that are typically 76 to 90 nucleotides in length. tRNAs are directly responsible for protein synthesis by translating codons in mRNA into amino acid sequences.

See also: Molecular mechanism of promoter opening by RNA polymerase III

RNA polymerase III (Pol III) and transcription factor IIIB (TFIIIB) assemble together on different promoter types to initiate the transcription of small, structured RNAs.

Nothing happens without the energy-dependent creation of the enzymes and the biophysically constrained viral latency that links the creation of G protein-coupled receptors to the functional structure of supercoiled DNA. The claims about molecular mechanisms of promoter opening appear to be deliberate attempts to obfuscate cause and effect.
Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and improves response to immune checkpoint blockade

Female sex and history of prior pregnancies are associated with favorable melanoma outcomes. Here, we show that much of the melanoma protective effect likely results from estrogen signaling through the G protein-coupled estrogen receptor (GPER) on melanocytes. Selective GPER activation in primary melanocytes and melanoma cells induced long-term changes that maintained a more differentiated cell state as defined by increased expression of well-established melanocyte differentiation antigens, increased pigment production, decreased proliferative capacity, and decreased expression of the oncodriver and stem cell marker c-Myc. GPER signaling also rendered melanoma cells more vulnerable to immunotherapy. Systemically delivered GPER agonist was well tolerated, and cooperated with immune checkpoint blockade in melanoma-bearing mice to dramatically extend survival, with up to half of mice clearing their tumor. Complete responses were associated with immune memory that protected against tumor rechallenge. GPER may be a useful, pharmacologically accessible target for melanoma.

Sex-specific cell type differentiation links yeasts to primates via the nutrient-dependent pheromone-controlled physiology of reproduction that links the food energy-dependent structure and function of enzymes and G protein-coupled receptors to the biophysically constrained Structure and dynamics of GPCR signaling complexes, which are required to biophysically constrain viral latency in the context of effect of androgens and estrogens on difference in the cell type of males and females.
Any focus on G protein-coupled estrogen receptors compared to G protein-coupled androgen receptors  should be viewed with suspicion in the context of what has been known to all serious scientists about hormones and behavior since our Hormones and Behavior review of RNA-mediated cell type differentiation. From Fertilization to Adult Sexual Behavior (1996)
Simply put, the alternative splicings of pre-mRNAs, which are now called microRNAs, biophysically constrain energy-dependent viral latency and prevents the transgenerational epigenetic inheritance of nearly all virus-driven pathology until excess nutrient stress or social stress takes its toll on the innate immune system.
Eventually, our food energy-dependent RNA-mediated DNA repair fails, and the accumulation of viral microRNAs predicts the failure of cell type differentiation in the tissues that are required to sustain our physical health and mental health.