5th-6th Sept 2018 Dublin, Ireland

The eternal significance of microRNAs (8)

Use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation and aging has been replaced by the use of model systems of biological processes.  Biological processes can be compared to so-called “evolutionary processes” to show that only biological processes need to be considered in the context of Darwin’s “conditions of life” or answers to the the question  What is Life? Schrödinger (1944).
K. L. Mettinger et al. (eds.), Exosomes, Stem Cells and MicroRNA, Advances in Experimental Medicine and Biology 1056, https://doi.org/10.1007/978-3-319-74470-4_6

This volume provides insight into the pivotal roles of stem cells, exosomes and other microvesicles in biofunction and molecular mechanisms and their therapeutic potential in translational nanomedicine. It further highlights evidence from recent studies as to how stem cell derived exosomes and microRNAs may restore and maintain tissue homeostasis, enable cells to recover critical cellular functions and begin repair regeneration.

Chapter 2 The Emerging Roles of microRNAs in Stem Cell Aging

involved in many biological processes such as developmental timing, differentiation, cell death, stem cell proliferation and differentiation, immune response, aging and cancer. Accumulating studies in recent years suggest that miRNAs play crucial roles in stem cell division and differentiation. In the present chapter, we present a brief overview of these studies and discuss their contributions toward our understanding of the importance of miRNAs in normal and aged stem cell function in various model systems.

Chapter 6  MicroRNAs, Regulatory Messengers Inside and Outside Cancer Cells

…like hormones, miRNAs can be secreted and regulate gene expression in recipient cells. Altered expression levels of miRNAs in cancer cells determine the acquisition of fundamental biological capabilities (hallmarks of cancer) responsible for the development and progression of the disease.

Model systems link the energy-dependent creation of microRNAs from microRNA biogenesis to the regulation of all cancer hallmarks. The virus-driven degradation of messenger RNA has been linked to all cancers and all other pathology in species from microbes to humans. Natural selection for energy-dependent codon optimality has been linked to healthy longevity.
See: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition
See for comparison:  The Neutral Theory in Light of Natural Selection May 2, 2018

…50 years after its introduction by Kimura. We argue that the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality. The ubiquity of adaptive variation both within and between species means that a more comprehensive theory of molecular evolution must be sought.

The ubiquity of adaptive variation attests to the facts about how the creation of quantized energy is linked to biophysically constrained viral latency. Adaptive variation links energy-dependent changes from angstroms to ecosystems in all living genera  via the physiology of their food energy-dependent pheromone-controlled reproduction.

For comparison to mRNA stability during the maternal-to-zygotic transition, see: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

The energy-dependent molecular mechanisms of recombination clearly link microRNA biogenesis to the stability of organized genomes during the life histories of all genera. Serious scientists object to the use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

…it is tiresome to raise the same objections repeatedly, wondering why researchers have not fulfilled some of the basic requirements for establishing the occurrence of an autophagic process.

 

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.

The tipping point (revisited): 68,000 publications

MicroRNA  Items: 1 to 20 of 68011 (earlier today, on 12/21/17)

See for example: In Vitro Validation of miRNA-Mediated Gene Expression Linked to Drug Metabolism 12/20/17

The approaches described can be employed broadly for the validation of miRNA-mediated negative regulation of any gene. Determining miRNA-mediated regulation of enzymes and transporters affecting drug metabolism is a critical step in designing personalized therapy and for understanding the mechanisms responsible for variations in the responses to therapeutic agents.

The “…miRNA-mediated regulation of enzymes and transporters affecting drug metabolism…” links the National Microbiome Initiative to the Precision Medicine Initiative and to all healthy longevity or to all virus-driven pathology in all living genera via differences in energy as information.
For review, see: Energy as information and constrained endogenous RNA interference

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.

For a historical perspective on what is known about energy-dependent RNA-mediated (aka microRNA-mediated) cell type differentiation, see:
The quantum / classical RNA-mediated ‘tipping point’ 3/26/15
The tipping point? 50, 000 publications 5/16/16
The tipping point? 50, 000 publications (2) 5/16/16
The tipping point? 50,000 publications (3) 5/17/16
The tipping point? 50,000 publications (4) 5/26/16
The tipping point? 50,000 publications (5) 7/27/16
The tipping point (revisited): 60,000 4/20/17
By May 16, 2016, the innate antiphage defense strategy was linked from quantum physics to classical physics by 50,000 publications that mentioned microRNAs. Nineteen months later, every aspect of the microRNA-mediated gene expression that had already been linked to drug metabolism attests to the fact that not all scientists have followed the extant literature.
Many scientists are still among the pseudoscientists who who failed to notice the most obvious links from the antiphage defense strategy to healthy longevity. Perhaps they were also too busy to notice the most obvious links from the virus-driven degradation of messenger RNA to the need for drug therapies.
If so, that may explain why the drug therapies have been largely ineffective. The drug therapies may be like vaccinations. They appear to link the virus-driven degradation of messenger RNA to more mutations, which clearly link the virus-driven theft of quantized energy to all pathology.
With more than 18,000 published works in the past 19 months, (8,000 in the past 8 months) it is time to again address the tipping point between quantum physics and classical physics in the context of food energy-dependent pheromone-controlled microRNA-mediated cell type differentiation via what is known about autophagy.
In the context of drug metabolism, the energy-dependent microRNA-mediated creation of enzymes was linked from the metabolism of food to all biodiversity on Earth via pheromone-controlled physiology of reproduction.
See for example page 19 of the sample report from Alpha Genomix that you can download as a pdf here. The food energy-dependent creation of the CYP enzymes protects our organized genome by biophysically constraining viral latency.

See for comparison: Our Top 17 in ’17: The Year in Science at PLOSBLOGS 

…the far-reaching war on science being conducted by the Trump administration, an assault on facts which, as several of our bloggers have noted, constitutes a removal of scientific evidence from the formation and discussion of public policy and an evisceration of funding and communication of vital research in medical research and regulation, public health, climate, energy, agriculture and education.

The only war on science that I know about, is the one in which serious scientists are Combating Evolution to Fight Disease. To place that claim into the context of what has happened during 2017, see the retraction of this article.
Biomechanical Characteristics of Hand Coordination in Grasping Activities of Daily Living [retracted]
It was retracted because the authors mentioned the creator of the hand. The creation of the hand occurs only in the context of biophysically constrained viral latency.

See for comparison: Retraction Watch

In retrospect, we were totally blinded by our belief [in our findings]…we were not as careful or rigorous as we should have been (and as Tivoli was) in interpreting these experiments.

Where else besides PLOS have you seen a retraction for the mention of a creator? Where did PLOS report on the retraction for misrepresentations in “Nature Chemistry?” Who still believes that microRNA and messenger RNAs created each other so that they could automagically constrain viral latency?
Who else besides PLOS is waging a far-reaching war on science?
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems 4/10/14

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. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.

Obama Advisers Urge Action Against CRISPR Bioterror Threat 11/17/16

Scientific advisers to President Obama warn that the U.S. urgently needs a new biodefense strategy and should regularly brief President-elect Donald Trump on the dangers posed by new technologies like CRISPR, gene therapy, and synthetic DNA, which they say could be coöpted by terrorists.

See for comparison:  2017 Global Infectious Diseases Threats to the United States 12/22/16

Flu.  Influenza remains one of the greatest threats to the US population killing on average 3,000-49,000 Americans annually.  People at the greatest risk of severe flu and death are pregnant women, residents of long-term care facilities, the very old (adults over the age of 65), the very young (children less than 2), Native American populations, and those with underlying chronic conditions such as asthma, COPD, heart disease, obesity, and other conditions.  Timely vaccination remains the most proven and effective way to avoid serious injury from influenza.

The new Trump Administration will face a formidable array of global and indigenous infectious disease threats in 2017.  A Global Health Security Agenda will help provide a framework for tackling some of these tough issues, but enhanced efforts will be needed to prevent new epidemics, especially from vector-borne and zoonotic neglected tropical diseases, measles, and the ever-constant threats from AMR and flu.

The biggest threat that the Trump administration has faced in the first year is the fake news. The most recent example accused him of censorship at the CDC for his director’s efforts to biophysically constrain energy-dependent viral latency. The CDC director’s efforts to help others with budget concerns were linked to censorship, and the President of the United States was compared to Hitler. Wake up and “Remember the Alamo.”
SARCASM ALERT: No, that was a different war. Wake up and remember the Manhattan Project, which also linked censorship about energy to the winning of a war.

rp_levels-of-organization.jpg

Controled Stem Cell Expansion

Serine … is one of the proteinogenic amino acids. [It]… is classified as a polar amino acid.
My comment: Serine synthesis in the body is linked to glycine, which also may be naturally produced when UV light illuminates simple ices (e.g., combinations of water, methanol, hydrogen cyanide, and ammonia). That suggested to some people that glycine and other amino acids may be easily produced in cold regions of space, and the suggestion, like virtually all suggestions, seems to be believable to theorists.  For contrast, Sutherland’s group linked UV light to the creation of glycine on Earth.
Their research was reported as: Researchers may have solved origin-of-life conundrum
Excerpt:

…a pair of simple compounds, which would have been abundant on early Earth, can give rise to a network of simple reactions that produce the three major classes of biomolecules—nucleic acids, amino acids, and lipids—needed for the earliest form of life to get its start.

My comment: That claim may link the UV light-induced de novo creation of glycine on Earth to the RNA-mediated cell type differentiation of all vertebrates.  Claims about RNA-mediated cell type differentiation have been made for more than 30 years, and the molecular mechanisms that link cell type differentiation in all species have been detailed. See: RNA mediated
See for comparison: Atypical PKC-iota Controls Stem Cell Expansion via Regulation of the Notch Pathway
Excerpt 1)

These studies, together with data presented here, provide genetic evidence that evolutionarily conserved polarity pathways may play a central role in NOTCH1 activation and stem cell self-renewal in mammals. Further genetic studies using Cre transgenes that are specific for progenitors in the neural plate, primitive erythrocytes, cardiomyocytes, and other progenitors to ablate aPKC function will be needed to determine how generally this mechanism is used in diverse tissues.

Excerpt 2)

…a complete picture for the requirement of aPKCs at different stages of mammalian development has not yet emerged.
Excerpt:

…the Notch pathway produces a protein that signals to stem cells to make more stem cells. In the presence of Prkci, the Notch pathway remains silent, and stem cells differentiate into specific cell types.

My comment:  Cell type differentiation is nutrient-dependent and RNA-mediated in the context of biophysically constrained protein folding chemistry. The chemistry links atoms to ecosystems via everything known about thermodynamic cycles of protein biosynthesis and degradation. The cycles lead to successful organism thermoregulation when the cycles are not perturbed by viruses. Perturbed cycles of protein biosynthesis and degradation link viruses to mutations to all pathology.
Arguably, further studies of controlled stem cell expansion will eventually link everything currently known From Fertilization to Adult Sexual Behavior in all mammals via what is currently known about nutrient-dependent RNA-mediated cell type differentiation in all vertebrates.
For example, substitution of achiral glycine in the GnRH decapeptide links food odors and pheromones from atoms to ecosystems via the physiology of reproduction.  Predictably, the complete picture that will emerge in mammals will link conserved polarity pathways to the stability of organized genomes in all vertebrates outside the context of theoretical physics and neo-Darwinian theories about mutations and evolution.
Indeed, it seems likely theorists will learn that all RNA-mediated cell type differentiation in all vertebrates is nutrient-dependent and that Feedback loops link odor and pheromone signaling with reproduction, from microbes to humans, since serious scientists have known that for more than a decade.
As we wait for the complete picture to be seen by those who continue to frame their experimental evidence of biologically-based cause and effect in the context of ridiculous theories about evolutionarily conserved polarity pathways, we should remember that many theorists will continue to believe whatever they are taught to believe.
Most of them may never learn anything about how nutrient-dependent RNA-mediated cell type differentiation occurs, which means they may never link species-specific pheromones to morphological and behavioral phenotypes in species from microbes to humans. Indeed, most theorists will never become serious scientists who frame their experimental evidence in the context of biologically-based facts that others have established.
achiral-glycine

Physics, Chemistry, and Molecular biology (PCMb)

Physics, Chemistry, and Molecular biology (PCMb) link ecological variation to ecological adaptations via a model of gene-cell-tissue-organ-organ system complexity that I first presented in 1992. After adding gene activation by pheromones, I co-authored a book that linked the pheromone-controlled physiology of reproduction across species from microbes to man: The Scent of Eros: Mysteries of Odor in Human Sexuality (1995/2002)
Since then, others have written books that claimed that pheromones evolved: Pheromones and Animal Behaviour (2003/2014) and one claimed that mammals don’t produce or respond to pheromones: The Great Pheromone Myth (2010).
Ignorance of biophysically-contrained biologically-based cause and effect continue to prevent scientific progress. Others have started to speak out against the pseudoscientific nonsense of evolutionary theorists and psychologists who have limited progress that could have been made by serious scientists from many disciplines. The theorists have continued to tout their pseudoscientific nonsense about mutations, natural selection and evolution, for more than 17 years after we detailed the facts about how epigenetically-effected RNA-mediated events link nutrient-uptake to the pheromone-controlled physiology of reproduction in species from microbes to man.

Many others must speak up each time they read or hear about the statistical nonsense of evolutionary theory as if it were supported by experimental evidence of biologically-based cause and effect. Tell the theorists to start making sense. Cite Genomes in turmoil: Quantification of genome dynamics in prokaryote supergenomes and quote from it: “The rates of 4 types of elementary evolutionary events (hereinafter Genome Dynamics Events or GDE)…”
Help make others approach the psychology and the practice of medicine from the only perspective that makes sense: Physics, Chemistry, and Molecular biology (PCMb) — not the pseudoscientific nonsense of theorists. RNA-directed DNA methylation links RNA-mediated events to amino acid substitutions that differentiate the cell types of all individuals in all species.

See also: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
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. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.