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in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation and aging has been replaced by the use of model systems of biological processes.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.

 

(E) KEGG analysis of the common up- and downregulated mRNAs in NDV infection. The left panel shows the KEGG enrichment analysis of each of the top 20 significant differences in the upregulated mRNAs, and the right panel shows the KEGG enrichment analysis of each of the top 20 significant differences in the downregulated mRNAs.

The eternal significance of microRNAs (6)

Accurate representations of how mutations are linked to the ecological adaptations in viruses that kill us are required to end the stranglehold that pseudoscientists have held on medical research. The pseudoscientists and other theorists make claims about mutation-driven evolution or natural selection and evolution as if the effect of virus-driven energy theft was beneficial to species that have somehow evolved from other species.
Neo-Darwinian theories will cause the death of us all. But first they will kill all the chickens.
Common microRNA-mRNA Interactions in Different Newcastle Disease Virus-Infected Chicken Embryonic Visceral Tissues
figure 3 E (above) includes biosynthesis of amino acids but a word search for “amino acid” turns up nothing.

(E) KEGG analysis of the common up- and downregulated mRNAs in NDV infection. The left panel shows the KEGG enrichment analysis of each of the top 20 significant differences in the upregulated mRNAs, and the right panel shows the KEGG enrichment analysis of each of the top 20 significant differences in the downregulated mRNAs.

The pathways for the biosynthesis of amino acids link microRNA biogenesis from energy-dependent changes in base pairs to amino acid substitutions that stabilize or destabilize the organized genomes in the context of everything that could be learned by playing the cell biology game “Cytosis.”
Ages 10+ can learn how to protect all organized genomes from viruses in the context of the food energy-dependent pheromone-controlled physiology of reproduction of humans, which biophysically constrains viral latency in species from microbes to humans.
One base pair change and one amino acid substitution (e.g., EDAR V370A) in a human host may be all that’s required to protect the organized genome from the virus-driven degradation of mRNA that has been linked to all pathology.
That means the virus-driven theft of quantized energy may link the change in the base pair to an amino acid substitution in the virus that stabilizes the virus. The 1918 Spanish flu was one example of what happens next. But no one knew why it happened until more recently.
See:  Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution (2013)

Koel et al. (p. 976) show that major antigenic change can be caused by single amino acid substitutions.

See also: A Single Amino Acid at the Polymerase Acidic Protein Determines the Pathogenicity of Influenza B Viruses (2018)

…the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs.

Accurate representations of how mutations are linked to ecological adaptations in viruses are required to end the stranglehold that pseudoscientists have held on medical research. The pseudoscientists and other theorists make claims about mutation-driven evolution or natural selection and evolution as if the effect of virus-driven energy theft was beneficial to species that have somehow evolved from other species.
The most recent example of that nonsense may be the focus of several blog posts here.
See:  Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

…we investigate whether the population occupying Beringia during the LGM represents another example of human adaptation to an extreme environment, this time adapting to very low UV exposure (Fig. 1). There are two lines of genetic evidence for this: variation in the fatty acid desaturase (FADS) gene cluster that modulates the manufacture of polyunsaturated fatty acids and variation in the ectodysplasin A receptor (EDAR) gene that influences ectodermally derived structures, such as teeth, hair, and mammary gland ductal branching. A study on selection on the FADS gene cluster in the ancestral population of Native Americans has been published previously (13), but, here, we shift the emphasis from phenotypic effects on older adults to focus on those that influence fertility via breast milk.

They link the food energy-dependent creation of microRNAs in all mammals from the physiology of reproduction to biophysically constrained viral latency via one base pair change an a single amino acid substitution, EDAR V370A. They refuse to acknowledge the facts that link the creation of the sun’s anti-entropic virucidal energy from the creation of microRNAs to viral latency in the mouse-to-human model, and fail to link what is known about what animals eat from the physiology of reproduction to the transgenerational epigenetic inheritance of healthy longevity and fertility.
See: The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression (2014)

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.

See also: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition (2016)

The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

An external file that holds a picture, illustration, etc. Object name is EMBJ-35-2087-g012.jpg
The chicken-livered (timid; fearful; cowardly) theorists who refuse to admit that their ridiculous theories have led to the unnecessary suffering and premature death of millions to billions of people and other mammals, have brought us all to the brink of extinction.
Does any intelligent person think that humans will evolve another protective variant allele like the EDAR V370A variant before humanity — as we know it know – ceases to exist?
Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk

The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago.

 
 
 
 
 
 

Light-induced-conformer-intercoversion-of-hydrogen-bond

Open Science: Closed to facts about microRNAs

See my 5-part series on: The tipping point? 50, 000 publications

Imagine how we could accelerate innovation, stimulate economic growth and all the solutions we need to live on a healthy and sustainable planet, if we were to open up our science fully and allow a free flow of scientific knowledge.” says Kamila Markram, a neuroscientist and the CEO of Frontiers, one of the largest Open Access science publishers in the world and a leader in the Open Science movement.

Talk is cheap. See: Understanding and accounting for relational context is critical for social neuroscience
I wrote:

New data on how genetic predispositions are epigenetically linked to phenotypically distinct neuroanatomy and behaviors is provided in the honeybee model. Across-species comparisons from insects to vertebrates clearly show that the epigenetic influence of food odors and pheromones continues throughout the life of organisms that collectively survive whereas individuals do not. These comparisons also attest to the relative salience of sensory input from the rearing environment. For example, when viewed from the consistency of animal models and conditioned behaviors, food odors are obviously more important to food selection than is our visual perception of food. Animal models affirm that food odor makes food either appealing or unappealing. Animal models reaffirm that it is the pheromones of other animals that makes them either appealing or unappealing.

Socioaffective neuroscience and psychology may progress more quickly by keeping these apparent facts in mind: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).

— Kohl, JV (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors Socioaffective Neuroscience & Psychology 2012

Open access publication in Frontiers has not led to any discussion of facts represented since 2005 in articles like this and this one which was co-authored by 2004 Nobel Laureate, Linda Buck. Feedback loops link odor and pheromone signaling with reproduction.
See for comparison, the validation of my model and its importance in the context of integrating disparate disciplines.
George F R Ellis wrote:

“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. This is explored here [Top-down causation Organized by George F. R. Ellis, Denis Noble and Timothy O’Connor]: http://rsfs.royalsocietypublishing.org/content/2/1.toc ” 25 Apr 2014 at 07:49am

See also, my comment posted to YouTube:

Talk is cheap. I am a medical laboratory scientist whose efforts to use open access publication have not led to any discussion of facts about energy-dependent biophysically constrained RNA-mediated cell type differentiation or facts about how virus-driven energy theft can be linked from the degradation of messenger RNA to mutations and all pathology in all living genera. See: Energy as information and constrained endogenous RNA interference https://www.youtube.com/watch?v=cdtsfweO5SQ

Q: What happened to the facts about energy as information?

See: A different tack for Alzheimer’s research

“Despite observations that link mitochondrial dysfunction and sporadic neurodegenerative disease, there hasn’t been a robust hypothesis that could explain the origin of mitochondrial stress associated with human aging and able to account for neurological disease observed across the entire human population,” Larsen continues. “The ‘Alu neurodegeneration hypothesis’ provides this link. Alus belong to a class of retrotransposons or mobile elements. They get the name ‘jumping gene’ because they can move about the genome and insert themselves into new locations. Alus are found only in primates, and they are abundant in the human genome (approximately 11 percent of human DNA). For a long time, they were considered junk DNA because their function was largely unknown. Only recently has the scientific community begun to appreciate how much Alu elements have influenced human evolution.”

A: The assumption that humans evolved has influenced the interpretation of any facts based on experimental evidence of energy-dependent de novo creation and/or maintenance of organized genomes. The facts have repeatedly showed that supercoiled DNA protects organized genomes from virus driven degradation of messenger RNA and that the degradation of messenger RNA links mutations to all pathology. The facts also links natural selection for energy-dependent codon optimality to the transgenerational epigenetic inheritance of all biophysically constrained biodiversity.

See also:  Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The bias between codons or amino acids, and mRNA expression levels has been previously recognized across species and is thought to result from selection for efficient, accurate translation, and folding of highly expressed genes (Ikemura, 1982; Akashi, 1994; Akashi & Gojobori, 2002; Drummond & Wilke, 2008; Kudla et al, 2009; Novoa & Ribas de Pouplana, 2012). The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

See also: The Excitable Mitochondria by science journalist, John Hewitt.

…the brain’s logical architecture may, in the end, be familiar to us. We do not, after all, have that many models for computation.

Also, there is only one model that links what organisms eat from food energy to the biophysically constrained brain development of humans. Nutrient-dependent/pheromone-controlled adaptive evolution: a model

…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.

See also: MicroRNA Items: 1 to 20 of 59836

What can be said about researchers who fail to use any model of biophysically constrained biologically-based cause and effect to link energy to supercoiled DNA and virus-driven energy theft to all pathology?

See for example: Mutation-Driven Evolution

Mutation is the change of genomic structure and includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc. (2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation.

See also and combination of these search terms for articles that have been published about clear links to energy-dependent increasing organismal complexity and how virus-driven energy theft contributes to all pathology.

microRNA; miRNA; virus; viruses; psychiatric disorders; autism spectrum disorder; biomarkers; genetic variation; expression profiling; animal studies

Location, Location, Location

Since first proposing that a cell’s function and biology depend on its surroundings, Mina Bissell continues to probe the role of the extracellular matrix.

Virus-driven energy theft prevents the typical interactions that link the function of the extracellular matrix to healthy longevity. As predictably occurs at the time of completion for any paradigm shift, Mina Bissell and others like her will claim that they have known about the role of viruses in cell type differentiation for several decades.

Revealing literature gaps. At UCB, Bissell became interested in cell culture techniques and how viral transformation changes metabolism, working with virus-transformed chicken cells to study how glucose metabolism differs from that of normal cells in culture. She began to read the literature on the Warburg effect—the observation that cancer cells produce energy by aerobic glycolysis and lactic acid fermentation rather than through the typical ATP-producing oxidative phosphorylation cycle.

Bissell’s lab again confirmed that transformed cells rely more heavily on aerobic glycolysis for energy, but that the switch to this energy pathway did not result from the impairment of the hydrogen-transfer pathway. The results, says Bissell, went against the other half of Warburg’s hypothesis: that the reason for the increased glycolysis is impaired hydrogen transfer.

Her lab could not have confirmed anything associated with Warburg’s hypothesis (in 1976). The differences in the energy of photons had not yet been linked from hydrogen-atom transfer in DNA base pairs in solution to the biophysically constrained physiology of reproduction and all biodiversity via changes in base pairs and fixation of amino acid substitutions in supercoiled DNA that protect all organized genomes from virus-driven energy theft and genomic entropy. Since then, the Nobel Prize-winning works of Thomas Hunt Morgan (1933 Physiology or Medicine) and Schrodinger/Dirac (1933 Physics) have linked changes in atomic energy from chirality (Ben Feringa, Chemistry 2016) to autophagy (Yoshinori Ohsumi, 2016 Physiology or Medicine and chromosomal inheritance via the pheromone-controlled physiology of nutrient energy-dependent reproduction in species from microbes to humans.

According to Bissell’s ‘dynamic reciprocity’ model, signals from the ECM traveled through transmembrane receptors to a cell’s interior and nucleus, altering its gene expression.

According to my model of biophysically constrained biologically-based cause and effect Bissell’s ‘dynamic reciprocity’ model fits into the context of neo-Darwinian pseudoscientific nonsense instead of into the context of established facts.

See: Feedback loops link odor and pheromone signaling with reproduction

See for comparison:

IMG_2329-e1413855233208-958x718

Wikipedia refutes theistic evolution

RNA-Directed DNA Methylation

Besides RNA molecules, a plethora of proteins are involved in the establishment of RdDM, like Argonautes, DNA methyltransferases, chromatin remodelling complexes and the plant-specific Polymerase IV and Polymerase V. All these act in concert to add a methyl-group at the 5′ position of cytosines. In contrast to animals, cytosines at all sequence context (CG, CHG, CHH) may get de novo methylated in plants.

There is no such thing as de novo methylation. Methylation is energy-dependent. Virus-driven energy theft prevents methylation and links mutations to all pathology via everything known to young earth creationists, which some of them have been reporting since the late 1990’s. That fact explains why theorists were forced to change RNA-Directed DNA Methylation to RNA interference in a face-saving attempt. Many pseudoscientists have claimed the creationists cannot be scientists and their attacks on young earth creationists have been among the most vicious of all attacks. But now, the young earth creationists have this:

RNA interference (RNAi) RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules. Historically, it was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. Only after these apparently unrelated processes were fully understood did it become clear that they all described the RNAi phenomenon.

The so-called unrelated processes linked to RNAi phenomenon were place into the context of what was known about molecular epigenetics in our section on molecular epigenetics from this 1996 Hormones and Behavior review.
From Fertilization to Adult Sexual Behavior

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 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.

The alternative splicings are energy-dependent.
See also: Contribution of epigenetic mechanisms to variation in cancer risk among tissues

Because de novo modification appears to take place almost exclusively on CpG islands that are already silenced by polycomb in the normal tissue (8), we suggest that this modification works by preventing these genes from becoming activated, thereby inhibiting normal tissue differentiation, causing clonal selection for cells that may predispose to cancer (31). Indeed, many of these methylation targets have been shown to be “driver” genes in a number of different cell types (Fig. S6).

Virus-driven energy theft prevents what they claim are the de novo modifications and the energy theft links contraint-breaking mutations from viral latency to all pathology. Only biologically uninformed pseudoscientists have continued to portray energy-dependent changes in methylation as if the changes occurred in the context of de novo modification.
See for comparison. These creationists start with energy and link it to experience-dependent cell type differentiation via what is known about sensing and signalling in all living genera.
Multipurpose plant sensors startle scientists

Evolutionary scientists did not predict such elaborate sensory integration in a single protein system.

Sensing and signalling in all living genera is links the physiology of reproduction in soil bacteria to the phyisology of pheromone-controlled reproduction in all livng genera. See for example:
The genome of Chenopodium quinoa

The TSARL1 transcript was alternatively spliced in the sweet progeny of Kurmi and 0654. A SNP in the last position of exon 3 (G2078C) co-segregates with the presence of saponins in the Kurmi × 0654 progeny. The G2078C SNP alters the canonical intron/exon splice boundary (Fig. 4e), probably leading to the alternative splicing at an upstream cryptic splice site in the sweet lines (Fig. 4e). This alternative splicing of TSARL1 results in a premature stop codon…

See also: Start codons in DNA may be more numerous than previously thought

Start codons are important to understand because they mark the beginning of a recipe for translating RNA into specific strings of amino acids (i.e., proteins).

See also: Codon optimality controls differential mRNA translation during amino acid starvation (2016)
They help to make the fact clear that all organisms must eat.
See also:Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition (2016)
They make it clear that the bias between codons or amino acids, and mRNA expression is the link from natural selection for energy as information that links the selection of food to efficient, accurate translation, and folding of  expressed genes.  Simply put, the energy-dependent amino acid optimality code  differentiates between theories of evolution and facts about how ecological variation must be linked to ecological adaptation via the physiology of pheromone-controlled energy-dependent reproduction and supercoiled DNA in all living genera.
Obviously, pseudoscientists who cannot link energy-dependent changes in codon optimality have indirectly been responsible for all virus-driven pathology because they failed to link the viral hecatomb from archaea to the transgenerational epigenetic inheritance of Zika virus-damaged DNA or to all other pathology, including cancer and degenerative diseases.
Thank God, Bill Gates and President Trump are among the billionaires who have decided to help others who have been combating evolutionary theorists to fight disease for several decades.
See also: Combating Evolution to Fight Disease

Alternative splicing of pre-mRNA

Autophagy: from pre-mRNAs to microRNAs, enhancers, QTLs et al.

Nothing known to serious scientists links anything except energy-dependent changes in chirality to autophagy and biodiversity via RNA-mediated amino acid substitutions that differentiate all cell types in all living genera. That fact forces pseudoscientists to invent new terms to confuse the biologically uninformed masses who were taught to believe in the neo-Darwinian pseudoscientific nonsense of mutation-driven evolution.
Autophagy in the liver: functions in health and disease 
See the section: Regulation of autophagy by amino acids

See for comparison: From Fertilization to Adult Sexual Behavior

Excerpt from 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.

My family members and friends of Robin Williams might be appalled to learn that death from Parkinson’s and death from Lewy Body Disease both include instances of suicide that is caused by untreated virus-driven energy theft. The virus-driven energy theft also is the cause of all pathology in species from archaea to humans. It is manifested as energy-dependent changes in alternative splicings of otherwise identical genes.

The prevention of unnecessary suffering and death could be as simple as restoring the balance of amino acids and sugar to prevent all pathology via RNA-mediated cell type differentiation.

That’s not going to happen without some discussion of what is known to serious scientists about the links from angstroms to ecosystems. All of them are energy-dependent. So, “go ahead,  make my day!”

Ask your professors where the energy came from and how it is linked to the changes in pH that predict when difference in healthy longevity become differences in the types of pathology via links from autophagy to supercoiled DNA or to negative supercoiling.

See also: Processing and transcriptome expansion at the mRNA 3′ end in health and disease: finding the right end

This review suggests the term “pre-mRNA” changed to “microRNA” as serious scientists learned more about how energy-dependent cell type differentiation was biophysically constrained.

We illustrate the medical importance by presenting examples that are associated with perturbations of this process and indicate resulting implications for molecular diagnostics as well as potentially arising novel therapeutic strategies.

This was ~20 years after we linked alternative splicings of pre-mRNA to all cell type diversity via the pheromone-controlled physiology of reproduction in yeasts at the advent of energy-dependent sexual reproduction.

See also: Implications of polyadenylation in health and disease

This review addresses the key steps of polyadenylation and alternative polyadenylation in different cellular conditions and diseases focusing on the molecular effectors that ensure a faultless pre-mRNA 3′ end formation.

Watch as researchers continue to invent new names for the molecular effectors in attempts to obfuscated the facts about biophysically-contrained protein folding chemistry that have been known to all serious scientists since Schrodinger (1944) linked the anti-entropic energy of the sun to all biodiversity.

Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus

Abstract excerpt:

Eusocial insects organize themselves into behavioral castes whose regulation has been proposed to involve epigenetic processes…

Research article summary excerpt:

…behavioral plasticity can be manipulated in the ant C. floridanus by pharmacological and genetic tools that target chromatin regulatory enzymes to stimulate, inhibit, and reprogram behavior. These findings reveal the epigenome as a likely substrate  underlying caste-based division of labor in eusocial insects.

Conclusion:

…our ability to alter a canonical altruistic behavior in a truly social organism by experimental perturbation of a single gene suggests that the application of increasingly versatile reverse genetic approaches in eusocial insects will allow us to expose the general organizational principles underlying complex social systems (10).

See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
All general organizational principles underlying complex social systems are nutrient-dependent and pheromone-controlled in the context of the regulation of gene expression that enables the transgenerational epigenetic inheritance of all morphological and behavioral phenotypes.

‘Mysterious’ non-protein-coding RNAs play important roles in gene expression

Berger and Daniel Bose, PhD, a postdoctoral fellow in her lab, study the regulation of gene expression from enhancers, non-coding regions of the genome more distant from protein-coding regions.

The only mystery should focus on why they thought they could continue to suppress the facts by referring to natural selection for energy-dependent codon optimality in terms like “enhancers.” Since 2013, everything known to serious scientists about nutrient-dependent microRNAs has been linked to all healthy longevity and virus-driven energy theft has been linked to to all pathology. Serious scientists are not using the term “enhancer.” See for example any of the 56,000 published works that use the term “MicroRNA

Ask why Phys.org / Medical Xpress must report old news from 2013 in the context of unpublished research by two people who cannot be found on the PubMed indexed list of research that links sunlight from chirality to autophagy and chromosomal rearrangements to all biodiversity via energy-dependent changes in the microRNA/messenger balance, which link supercoiled DNA to the protection of all organized genomes from virus-driven entropy.

See: Enhancer RNAs alter gene expression: New class of molecules may be key emerging ‘enhancer therapy’

Enhancers are sequences in the genome that act to boost or “enhance” the activity or expression of nearby genes. They “often behave in a cell-specific manner and play an important role in establishing a cell’s identity and functional potential,” said Christopher Glass, MD, PhD, a professor in the department of Medicine and Cellular and Molecular Medicine at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of RNA on a broad scale in neurons and macrophages, a type of immune system cell. Dubbed eRNAs…

I do not know any serious scientists who accepts the term invented to replace pre-mRNAs after the term microRNAs was introduced at the turn of this century and more than 56,000 published papers now use the term microRNA in the context of links from metabolic networks to genetic networks in all living genera via non-coding RNAs..

SnapShot: Non-coding RNAs and Metabolism

In recent years, understanding the crucial role played by cellular homeostasis in disease initiation and progression became the focus of scientists and clinicians. This SnapShot sketches the involvement of both short microRNAs and long ncRNAs in the major metabolic pathways altered in diseases.

Functional Importance of eRNAs for Estrogen-dependent Transcriptional Activation Events

Who do they think does not know that the functional importance of microRNAs and the functional difference of eRNAs is the same. eRNAs are the term theorists use for microRNAs.

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.

See also: SPECIAL ISSUE—THE ZIKA VIRUS GLOBAL PANDEMIC: THE LATEST EMERGING INFECTION
Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia

It is still not well understood what role(s) the Hofbauer cell has in facilitating or inhibiting transplacental transmission of infectious agents such as the Zika virus. However, based on the demonstration in this communication of proliferation and prominent hyperplasia of Hofbauer cells in the placenta from a microcephalic fetus infected early in gestation, the identification of residual Zika virus in villous stromal cells, using an RNA probe, and the previously published results of in vitro infection and replication of Zika virus in human Hofbauer cells, it appears highly probable that the Hofbauer cell has an important, or even primary, role in those cases where transplacental transmission of the Zika virus does occur. The unexpected absence in placental tissues of any necrosis or leukocytic response by the mother or fetus to transplacental Zika virus infection is also interesting and of unknown significance.

The absence of a response in the organized genomes of the host clearly indicates ecological adaptation to the virus has already occurred and the supercoiled DNA of the host helps to protect a host from DNA damage. The infants are comparatively unprotected. If they survive to reproduce, and their bones turn up in what a future paleontologist thinks is a fossil record that spans hundreds of thousands of years, the paleontologist would almost undoubtedly claim to have found a new species of non-human primate.
For comparison, all serious scientists known that energy-dependent autophagy is the link to supercoiled DNA, which protects all organized genome from virus-driven energy theft and genomic entropy.
Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

Alternative splicing of pre-mRNA

Energy-dependent hydrogen bonds in supercoiled DNA

Chirality Check

Most biological macromolecules are homochiral, and enzymes help to maintain this state of affairs; for example, checkpoints ensure that only l-amino acids are incorporated into proteins during translation.

The fixation of the only achiral amino acid, glycine in position 6 of the gonadotropin releasing hormone decapeptide protein links the nutrient energy-dependent pheromone-controlled physiology of reproduction from yeasts to humans. That fact about RNA-mediated protein folding chemistry is missing from the chirality check, It also is missing from representations of the anti-entropic virucidal force that biophysically constrains all biodiversity by protecting all organized genomes from virus-driven energy theft and genomic entropy.
That’s why theories of evolution have no explanatory power. An unknown force of nature must be included the theories for comparison to Schrodinger’s claims in What is Life? (pp. 73 and 74)

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: Force of nature gave life its asymmetry

…even demonstrating how a common physical phenomenon would have favoured left-handed amino acids over right-handed ones would not tell us that this was how life evolved…

The fact that there is no explanation for how life evolved outside the context of an unknown force of nature can be placed into the context of the energy-dependent creation of all differentiated cell types in all living genera.
See: RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria (2016) by Junjie U. Guo and David P. Bartel,

Owing to the extensive hydrogen-bonding and base-stacking interactions, RG4 structures can be very stable, with in vitro melting temperatures well exceeding physiological temperatures. This stability typically depends on the presence of K+, which is the optimal size to bind at the center of two stacked G-quartets…

They fail to mention that energy-dependent hydrogen-atom transfer in DNA base pairs in solution must be linked to the stability of supercoiled DNA. Instead, the unfolding of the RNA G-quadruplexes was reported as: RNA Sequences Don’t Predict In Vivo Transcript Structure

Interactions between nucleotides can turn sections of transcripts into loops, bends, and knots, some of which have regulatory functions in the cell.

See for comparison: Electrolytes induce long-range orientational order and free energy changes in the H-bond network of bulk water.  K+ is an important electrolyte in the context of interactions in solutions. That fact was reported as:  A single ion impacts a million water molecules. The fact that the interactions between nucleotides are pH-dependent makes it important to consider what happens when slight changes in the cell types of species-specific tissues occur in the context of nutrient stress or social stress.
The stress causes changes in protein folding that predictably links energy-dependent interactions between nucleotides from natural selection for codon optimaility to fixation of RNA-mediated amino acid substitutions and healthy longevity? If pH does not facilitate energy-dependent codon optimality, a change in pH may predict a change in the structure of functional proteins, which can effect biophysically constrained cell type differentiation.
See for instance: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

Unfortunately, the nutrient energy-dependent interactions between nucleotides and amino acids, which are the building blocks of proteins, are typically not considered in the context of virus-driven energy theft, which has been linked from viral latency to all pathology via transgenerational epigenetic inheritance in species from archaea to humans.
See for instance: Epigenetics and Genetics of Viral Latency
… viral latency is responsible for life-long pathogenesis and mortality risk…
My comment to The Scientist on RNA Sequences Don’t Predict In Vivo Transcript Structure :

See also: MicroRNAs: Genomics, Biogenesis, Mechanism, and Function (2004) by David P. Bartel

…about a quarter of the human miRNA genes) are in the introns of pre-mRNAs. These are preferentially in the same orientation as the predicted mRNAs…

For comparison, see: From Fertilization to Adult Sexual Behavior

… epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans…  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.

Hydrogen-atom energy-dependent changes in base pairs have since been linked from RNA-mediated protein folding chemistry to all biophysically constrained cell type differentiation in all living genera via amino acid substitutions.

The RNA-mediated fixation of amino acids links autophagy from the innate immune system to supercoiled DNA. Virus-driven energy theft has been linked to all pathology via changes in the microRNA/messenger RNA balance. The changes link fertilization to adult sexual behavior.  See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.
See also, the other publications by David P. Bartel
2016 Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on Competing Endogenous RNA-Regulated Gene Expression
Excerpt:

…we assumed that (1) molecular species are well mixed within the cytosol and their concentrations are not influenced by cell growth and division; (2) each mRNA and miRNA is produced at a constant rate, and unbound mRNAs and miRNAs undergo constant first-order decay; (3) upon association with a miRNA, the mRNA degradation rate increases, regardless of the site type; and (4) miRNA binding is reversible, and upon miRNA dissociation the mRNA degradation rate reverts to its original value. We also assumed that the Michaelis constant (KM) describing mRNA degradation with respect to the miRNA-mRNA complex is well approximated by the complex dissociation constant (KD), and that both bound and unbound mRNA are translated.

Simply put, they seem to have assumed that energy-dependent changes in the microRNA/messenger RNA balance need not be considered in the context of any model of biologically-based cause and effect.
See for comparison: 2014 Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
Abstract excerpt:

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.

The clear difference between the assumptions made by Bartel (and others like him) and the facts about energy-dependent biophysically constrained RNA-mediated protein folding chemistry make it pointless for serious scientists to discuss experimental evidence of biologically-based cause and effect with anyone who does not agree that it is energy-dependent and biophysically constrained by the physiology of energy-dependent reproduction in all living genera.
See also: How the elite control the masses
Control involves giving the masses partial information, which is what Bartel and others appear to be doing in attempts to promote evolutionary theories.

See for comparison ( December 30, 2016 at 5:37pm):

Peter Berean wrote:

James, I have no problem with “energy-dependent RNA-mediated amino acid substitutions” … however, that does not show that energy = information.

And, neither does the article about “construction of phylogenetic trees”…

My recommendation is DO take the advice of your brothers in Christ… And correct your views and models accordingly.

IF you do so, you could actually have more people believe what you have to say about your models.

The comment about taking advice from my “brothers in Christ” is a classic. It comes from someone who may never understand anything about energy-dependent hydrogen bonds in supercoiled DNA, or how energy as information must be linked to all biodiversity.

Peter Berean is only one among many who are biologically uninformed. Their masses are not told that virus-driven energy theft can be linked to all pathology in the context of conserved molecular mechanisms, which have been detailed by all serious scientists. Peter Berean may think that his faith in God and/or his brothers in Christ will save him from his ignorance.

That may be true, but it may also not apply to those who have been told the truth and continue to ignore it. People like that encourage others to ignore the truth about energy-dependent hydrogen bonds in supercoiled DNA. The truth is that if you don’t know where that energy came from, you are no better off than any other theorist or atheist.

That makes this Chirality Check a reality check, and makes this a lie: “…checkpoints ensure that only l-amino acids are incorporated into proteins during translation.”

See: Evolution of constrained gonadotropin-releasing hormone ligand conformation and receptor selectivity as cited in Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

When the chiral amino acid (Ala) in position six of Ciona I GnRH was substituted with the achiral glycine or with d-Ala, which enhances the type II’ β-turn conformation, there was a marked increase in the binding affinity of the peptides at the vertebrate GnRH receptor (Barran et al., 2005).

The substitution of achiral glycine and the increased binding affinity were placed into the following context in the Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor:

The discovery of the fact that one decapeptide molecule, among the GnRHs, was constructed perfectly at the beginning of 400 million years evolution and that it is not possible to improve its physiological potency using the any natural amino acid is, in my opinion, important, fascinating and beautiful.

The claim about 400 million years of evolution has not been substantiated by experimental evidence of biologically-based cause and effect and virus-driven energy theft was not considered in the context of the invention of neo-Darwinian theory.
The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis…
[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. Assumptions, made but not verified, were taught as fact.
See also: Spectrum of Antimatter Observed for First Time

The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today’s Universe is observed to consist almost entirely of ordinary matter. This motivates physicists to carefully study antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter.

Without the anti-entropic energy of the sun, the laws of physics could not be linked from chemistry to molecular epigenetics, which must link energy-dependent autophagy from the innate immune system to supercoiled DNA. If not, you are left with the magic of emergence and evolution instead of the fact that Life is physics and chemistry and communication in the context of energy as information.
In 2016, scientists collectively failed to link the anti-entropic virucidal energy of the sun to autophagy and all biophysically constrained biodiversity via the physiology of reproduction in all living genera. They also failed to link virus-driven energy theft from the negative supercoiling of DNA to all pathology.
Instead, most scientific successes are examples of politicized science. Congratulations to those who are willing to place politicized science into the context of their theories.  The theories make their World a better place for other theorists to live in. Serious scientists, for comparison, will remember the theorists who failed to make the Chirality Check a reality check.

rp_levels-of-organization.jpg

Biophotonics, glycobiology, quantized biodiversity (2)

From Fertilization to Adult Sexual Behavior (1996)
In our section on Molecular epigenetics, we wrote:

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.

My comment: Serious scientists have since learned that all cell type differences arise from alternative splicings of otherwise identical genes. Pseudoscientists still make claims about the emergence of life and link natural selection to structural biology and the function of genome organization.

See for comparison: A Big Bang in spliceosome structural biology (2016)

Excerpt:

Splicing cycles through a series of steps in which the spliceosome assembles on the intron-containing pre-mRNA, defining the boundaries between exons—the sequences ultimately retained in the mature mRNA—and introns (see the figure, panel A).

My comment: Energy-dependent changes in angstroms to ecosystems link the defined boundaries between exons and introns from ecological variation to ecological adaptation and all biodiversity.  The “Big Bang” in structural biology is a contextualized polite way to tell theoretical physicists and other theorists that energy-dependent changes in functional structures must link ecological variation to ecological adaptation via what is known to serious scientists about all the links from angstroms to ecosystems in all living genera. Others have been trying to tell theorists how to link biologically-based cause and effect for several years.

See for example (2007): The MicroRNA miR-124 Promotes Neuronal Differentiation by Triggering Brain-Specific Alternative Pre-mRNA Splicing
Excerpt:

Both microRNAs and alternative pre-mRNA splicing have been implicated in the development of the nervous system (NS), but functional interactions between these two pathways are poorly understood.

My comment: All serious scientists know that the functional interactions among microRNAs and alternative pre-mRNA splicing are nutrient energy-dependent and controlled by the physiology of reproduction. Do you know how energy-dependent RNA methylation links biophysically constrained protein folding chemistry to cell type differentiation via RNA-mediated amino acid substitutions? If not, you probably do not know why  information about amino acid substitutions was left out of the claim that linked chromatin to the control of behavior in this misrepresentation:
Chromatin controls behavior
Conclusion:

…the discoveries of Yang et al. are an important addition to an emerging literature implying a dynamic epigenome in the central nervous system (14, 15), which is contrary to the prevailing dogma in the epigenetics field.

My comment: There is no prevailing dogma in the epigenetics field. The dogma was eliminated when serious scientists linked energy-dependent changes from angstroms to ecosystems via epigenetic effects of sensory input on the innate immune system; the de novo creation of G protein-coupled receptors; the physiology of reproduction, and fixation of RNA-mediated amino acid substitutions that link supercoiled DNA to protection from virus-driven energy theft and genomic entropy in all organized genomes of all living genera.
See also: Chromatin remodeling inactivates activity genes and regulates neural coding.
Summary: Epigenetic regulation in the brain

The activity of neurons in the brain controls the transcription of genes that influence the pruning of dendritic connections between neurons, and such modifications can influence animal behavior. Yang et al. propose a role for chromatin remodeling by the nucleosome remodeling and deacetylase complex (NuRD) in the inactivation of such activity-dependent transcription in the mouse cerebellum (see the Perspective by Sweatt). Deposition of the histone variant H2A.z at promoters of activity-dependent genes required the NuRD complex. Loss of the NuRD complex function resulted in hypersensitivity of mice to sensory stimuli and excessive neuronal connectivity in animals performing a task on a treadmill.

This article was reported as: Ability to turn off genes in brain crucial for learning, memory
Excerpt (with my emphasis):

One process that controls chromatin structure and transcription is chromatin remodeling by energy-dependent protein complexes (4). Such complexes that depend on adenosine 5′-triphosphate (ATP) can control gene expression by moving, ejecting, or restructuring nucleosomes, the scaffolds around which DNA wraps. Each nucleosome contains a core particle of eight histone protein subunits (5). Remodeling events include posttranslational modifications, swapping individual One process that controls chromatin structure and transcription is chromatin remodeling by energy-dependent protein complexes (4). Such complexes that depend on adenosine 5′-triphosphate (ATP) can control gene expression by moving, ejecting, or restructuring nucleosomes, the scaffolds around which DNA wraps. Each nucleosome contains a core particle of eight histone protein subunits (5). Remodeling events include posttranslational modifications, swapping individual histone subunit isoforms into and out of the core particle, and facilitating the unbinding of DNA from the core particle.
into and out of the core particle, and facilitating the unbinding of DNA from the core particle.

My comment: Chromatin remodeling is energy-dependent. But, they buried the facts about how energy-dependent chromatin remodeling links sensory input from learning and memory to fixation of RNA-mediated amino acid substitutions. The substitutions differentiate all cell types of all individuals of all living genera, which explains why they invented the term histone subunit isoforms.
Serious scientists understand why pseudoscientists bury facts by stringing words together without telling others what a histone subunit isoform is, or what differentiates one histone subunit isoform from any other histone subunit isoform. In this case, the wordplay prevents others from learning that the availability of nutrients and nutrient energy-dependent changes links link fixation of RNA-mediated amino acid substitutions from learning and memory to chromatin remodeling and the control of behavior. Pseudoscientists tend to remove facts from consideration and remove the facts from the context of via well established pathways that link the epigenetic landscape to the physical landscape of supercoiled DNA  in all living genera.
See for example: Roles of Mutation and Selection in Speciation: From Hugo de Vries to the Modern Genomic Era
Excerpt:

…we will not consider geographical and ecological factors because of space limitation. Our primary purpose is to clarify the roles of mutation and selection in the evolution of reproductive isolation and show that the molecular basis of speciation is more complicated than generally thought at present. (p. 813)

My comment: Inventing the term histone subunit isoform outside the context of geographical and ecological factors is another way to dismiss the complexity of speciation.
See for example: This article mentions a subunit isoform in the context of Loss of the V-ATPase B1 Subunit Isoform Expressed in Non-Neuronal Cells of the Mouse Olfactory Epithelium Impairs Olfactory Function
Excerpt:

The present study is the first to indicate the relevance of the VATPase, and presumably of V-ATPase-mediated proton secretion, in olfactory function. Undoubtedly, further functional and behavioral studies will allow a more comprehensive assessment of the physiological and clinical significance of V-ATPase expression in sustentacular and microvillar cells of the olfactory epithelium. At this point, we can only speculate on such possibilities. For example, modulating olfactory H+ secretion could offer the ability of up- or down-regulating the threshold of detection for certain odorants. Moreover, since the NML plays a role as a barrier against inhaled pathogens, and microbial and chemical toxins, regulating mucus pH may be relevant for protection against various specific diseases.

My comment: If you are unable to link the modulation of olfactory H+ secretion from hydrogen-atom transfer in DNA base pairs in solution to the de novo creation of G protein-coupled receptors and all energy-dependent biodiversity via RNA-mediated amino acid substitutions, please see:
Every amino acid matters: essential contributions of histone variants to mammalian development and disease.
Excerpt:

The introduction of these minor sequence variants into chromatin is physiologically relevant and fundamental to eukaryotic cellular plasticity. However, with the exception of substitutions towards modification permissive amino acids (for example, both H3.1A31 and H3.2A31 to H3.3S31, which can be phosphorylated), it remains unclear how histone variants acquire and/or differentially enrich for specific chemical modifications that are distinct from their canonical counterparts.

My comment: They just muddied the perfectly clear waters of how phosphorylation and fixation of RNA-mediated amino substitutions is links from biophysically constrained protein folding chemistry to all biodiversity via hydrogen-atom transfer in DNA base pairs in solution.   The claim that “every amino acid matters” is placed into the context of what is not known about biophysically constrained protein folding chemistry and biologically-based cause and effect. That is a way to help ensure these researcher get more funding. It’s a common tactic. If you focus on what is not known, people will think it’s not known to serious scientists who are funded to produce results that are supported by their experimental evidence of biologically-based cause and effect.

See also my comment on RNA and dynamic nuclear organization

Excerpt:

Moving forward, if RNA-mediated events organize the cell nucleus, mutations manifested in perturbed protein folding are not likely to lead to natural selection and the evolution of biodiversity. The requirement for DNA to be found in organized genomes is biophysically constrained via the conserved molecular mechanisms of protein biosynthesis and degradation in species from microbes to man.

For simplicity, see:

See also: Structural diversity of supercoiled DNA and m1A and m1G disrupt A-RNA structure through the intrinsic instability of Hoogsteen base pairs, which was reported as:

DNA’s dynamic nature makes it well-suited to serve as the blueprint of life.

My comment: The claim that DNA is the blueprint of life resurrects long-dead gene-centric theories. I expected others to make more rapid progress after the Zechiedrich lab linked energy-dependent changes from angstroms to ecosystems, but Al-Hashimi’s group is still reporting links in the context of pseudoscientific nonsense linked to neo-Darwinian theory. The theory does not address the need for biophysically constrained RNA-mediated protein folding chemistry in the context of the physiology of reproduction.
Perhaps Al-Hashimi’s group will be next to do that in RNA Structural Modules Control the Rate and Pathway of RNA Folding and Assembly, which supposedly is “In Press.” RNA methylation is clearly the link to all biodiversity. But, until then, they may fall behind even further, especially if they keep trying to placate the neo-Darwinists.
See: ‘Quantum jitters’ could form basis of evolution, cancer
Excerpt:

“This is a remarkable study that illuminates a fundamental mechanism responsible for the random mutations that drive evolution and contribute to cancer,” said Bert Vogelstein, M.D., a cancer researcher at Johns Hopkins University School of Medicine who was not involved in this research.

My comment: How did Vogelstein arrive at his ridiculous conclusion? Did Visualizing transient Watson-Crick-like mispairs in DNA and RNA duplexes inadvertently or deliberately lead him to it?
Excerpt:

These results, together with previous structural studies showing that WB and WC-like mispairs can exist within polymerase1–3 and ribosome5,6,13 active sites, strongly suggest that energetic competition between WB and WC-like mispairs is robust and is a key determinant of misincorporation probability during replication and translation (Supplementary Discussion 9).

My comment: How difficult would it have been to clarify the issues involved that suggest energetic competition causes the mutations, which means they do not randomly occur? I reiterate: Vogelstein thinks the “…study illuminates a fundamental mechanism responsible for the random mutations that drive evolution and contribute to cancer…”
Despite everything known to serious scientists about energetic competition for nutrients, I’m sure Vogelstein is not the only biologically uninformed cancer researcher who believes in neo-Darwinian theory. Others may also think that results framed in the context of energetic competition support ridiculous theories. Unfortunately, most people are not going to fight their way through an article like this one to discover that Vogelstein and all others like him are wrong.
Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios
Excerpt:

These observed protein dynamics are incompatible with random and cross-regulatory PU.1–GATA1 co-expression acting as the central mechanism that initiates MegE versus GM lineage choice3.

My comment: Most people may miss the fact that they claimed “…observed protein dynamics are incompatible with random… co-expression, which initiates lineage choice. Simply put, they eliminated Vogelstein’s ridiculous idea about random mutations from any further consideration.
See also: A miR-155–Peli1–c-Rel pathway controls the generation and function of T follicular helper cells, which was reported as A potential new way to sway the immune system found
Excerpt:

“People know miRNAs are involved in immune response, but they don’t know which miRNAs and how exactly,” explained TSRI Research Associate Zhe Huang, study co-first author with Liu and Seung Goo Kang of TSRI and Kangwon National University.

See also: Regulation of B-cell development and tolerance by different members of the miR-17~92 family microRNAs
Excerpt:

In this experimental setting, the changes in the ratio of virus-transduced CD45.2+ cells (GFP+) versus WT competitors (CD45.1+) during the pro- to pre-B transition provided a measurement for the developmental defect. In the control WT:WT mix group, as no major difference existed between these two populations, the GFP+/CD45.1+ ratios remained unchanged during the pro- to pre-B transition, resulting in a pre-B/pro-B ratio close to 1 (Fig. 5b upper panels and Fig. 5c). In contrast, cells derived from the Mb1tKO HSCs, when transduced with control virus, underwent a severe developmental block in competition with WT cells. Therefore, the GFP+/CD45.1+ ratio shifted drastically as WT cells became dominant in the pre-B population, resulting in a pre-B/pro-B ratio below 0.2 (Fig. 5b middle panels and Fig. 5c).

My comment: All serious scientists know that nutrient energy-dependent microRNA flanking sequences link the innate immune system to differences in morphological and behavioral phenotypes via the physiology of reproduction in species from microbes to man via supercoiled DNA, which protects organized genomes of all living genera from virus-driven entropy.
Recent reports, which link specific families of miRNAs to healthy longevity or to pathology will obviously lead mroe researchers to discover the specific miRNAs that link virus-driven energy theft to all pathology.
See: The phylogenetic utility and functional constraint of microRNA flanking sequences and Role of olfaction in Octopus vulgaris reproduction
Excerpt:

Future work on O. vulgaris olfaction must also consider how animals acquire the odours detected by the olfactory organ and what kind of odour the olfactory organ perceives. The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000).

See for comparison: (2016) Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition
Excerpt:

The bias between codons or amino acids, and mRNA expression levels has been previously recognized across species and is thought to result from selection for efficient, accurate translation, and folding of highly expressed genes (Ikemura, 1982; Akashi, 1994; Akashi & Gojobori, 2002; Drummond & Wilke, 2008; Kudla et al, 2009; Novoa & Ribas de Pouplana, 2012). The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

My comment: These authors echo the claim that random mutations are not the source of energy-dependent cell type differentiation. They add that the across-species bias of RNA-mediated amino acid substitutions offers an alternative to ridiculous claims about mutation-driven evolution. For another example of facts about RNA-mediated amino acid substitutions, see how Dobzhansky (1973) framed his claims.
Excerpt:

…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 (p. 127).”

If you don’t like Young Earth Creationists, see also: (2016) Major Evolutionary Blunders: The ‘Degenerate’ Genetic Code?
Excerpts:

A detailed literature review in 2014 found that even if different codons prescribed the same amino acid in a protein, the codon differences still mattered in how the protein was made. The final folding shape of proteins is vital to their function. David D’Onofrio and David Abel documented that the DNA and its corresponding RNA sequence carried information not only for the proper amino acid sequence but also to control the timing of its folding. They “demonstrate that this TP [translational pausing] code is programmed into the supposedly degenerate redundancy of the codon table.”8 What this means is that the code of differing codons, even if they specify the same amino acid, still supplies important information, information that “purposely slows or speeds up the translation-decoding process….Variable translation rates help prescribe functional folding of the nascent protein. Redundancy of the codon to amino acid mapping, therefore, is anything but superfluous or degenerate.”8
…if synonymous codons can have important functional meaning, then the whole methodology goes out the window, and hundreds of studies that used these methods to infer “selection” during the supposed “evolution of genes” could be wrong.11

If you like neo-Darwinian theorists, see: Tempo and mode of genome evolution in a 50,000-generation experiment
Excerpt:

One line of evidence derives from the expectation that synonymous substitutions—point mutations in protein-coding genes that do not affect the amino-acid sequence—are neutral and should therefore accumulate at a rate equal to the underlying mutation rate20,35. This expectation is not strictly true owing to selection on codon usage, RNA folding, and other effects, but…

My comment: Let’s tell the truth with no buts, rather the invent more reasons to lie. Creationists and other serious scientists seem to arrive at the same conclusion by citing different literature that adds another level of epigenetic complexity in the context of non-random selection of RNA-mediated amino acid substitutions, which must be fixed in the organized genomes of all living genera to link the innate immune system to supercoiled DNA, which protects all organized genomes from virus-driven entropy.
The literature includes details about how the across species bias between codons or amino acids and microRNA or pre-mRNAs and mRNA expression levels links selection to efficient, accurate translation, and folding of highly expressed genes.   For comparison, no serious scientist has ever suggested that virus-driven energy theft is linked from mutations and selection to the evolution of one species from another. Thus, it has become perfectly clear that the amount of pseudoscientific nonsense people must believe to continue to believe in mutation-driven evolution is based on definitions and assumptions. Serious scientists do not rely on definitions and assumptions to support their claims.
See for comparison: Mutation-Driven Evolution (2013)

Excerpt:

Mutation is the change of genomic structure and includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc. (2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation. —

Conclusion:

In other words, genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements.

See also: Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble

[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. The anglophone tradition was taught. I was taught, and so were my contemporaries, and so were the younger scientists. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. No, it wasn’t dishonesty. I think it was wish fulfillment and social momentum. Assumptions, made but not verified, were taught as fact.

For more assumptions in the context of ridiculous theories, see: Phylogenetic plasticity in the evolution of molluscan neural circuits (2016)
Conclusion:

Molluscan neural circuitry represents a different evolutionary trajectory from vertebrates and even other lophotrochozoans. Using the same morphogenic genes as other phyla, molluscs have created novel nervous systems that control a wide variety of body forms. Yet the largest brained invertebrates, the cephalopods, have converged with insects and vertebrates on the organization of circuitry for learning and memory. Even with this cross-phyletic convergence, there are intra-phyletic differences between octopus and cuttlefish in the sites of plasticity. Phylogenetic plasticity is also found in gastropods where homologous neurons have been re-used for different functions and where neuromodulatory actions also display species-specificity. One outcome from this work is to show that there are many solutions to the same problem. The story of molluscs is about how looks can be deceiving; the same genes and neurons can be used and reused in different ways to create diverse nervous systems that sometimes converge on the same solution. I think it is more exciting to realize that octopus and mammals independently came up with a learning machine that has a fan-out/fan-in organization and LTP than to think that these similarities are just a family resemblance. Call me a splitter, but I believe that uncovering the many solutions that nature has found will tell us more about fundamental organizational properties than lumping them all together.

My comment: Anyone who makes a ridiculous statement like the one above should be ‘called out’ and questioned to learn how he or she has managed to maintain their overwhelming ignorance despite the availability of publications like this one:
The phylogenetic utility and functional constraint of microRNA flanking sequences and this one The octopus genome and the evolution of cephalopod neural and morphological novelties
Excerpt:

Among the octopus complement of ligand-gated ion channels, we identified a set of atypical nicotinic acetylcholine receptor-like genes, most of which are tandemly arrayed in clusters (Extended Data Fig. 7). These subunits lack several residues identified as necessary for the binding of acetylcholine26, so it is unlikely that they function as acetylcholine receptors. The high level of expression of these divergent subunits within the suckers raises the interesting possibility that they act as sensory receptors, as do some divergent glutamate receptors in other protostomes27. In addition, we identified 74 Aplysia-like and 11 vertebrate-like candidate chemoreceptors among the octopus GPCR superfamily of ~330 genes (Extended Data Fig. 6).

My comment: The GPCR superfamily links receptor-mediated signaling from chemotaxis to phototaxis and all energy-dependent biophysically constrained biodiversity via RNA methylation and RNA-directed DNA methylation, histone acetylation and every aspect of the energy-dependent physiology of reproduction. Taken together, everything known about the energy-dependent receptor-mediated physiology of reproduction links the innate immune system to supercoiled DNA.
Those who tout neo-Darwinian theories for comparison must continue to use definitions and assumptions as if that approach was acceptable to anyone else who was not also a pseudoscientist.
See also: (2016) 33. Octopus Signals
Excerpt:

We define a ‘signal’ as any act or structure which alters the behavior of other organisms, which evolved because of that effect, and which is effective because the receiver’s response has also evolved.

My comment: Via the bastardization of everything known to serious scientists about biologically-based cause and effect, the definition of signal is linked to its evolution via an effect, which is not linked from any epigenetic effect on hormones to any affect on behavior. That makes it impossible to link food odors to the energy-dependent de novo creation of olfactory receptor genes, which are GPCRs. The de novo gene creation of GPCRs links metabolic networks to genetic networks via the pheromone-controlled physiology of behavior in the context of epigenetic effects of pheromones on hormones. The hormones affect the species-specific behaviors of all invertebrates and vertebrates.
Definitions lead to confusion about the use of the terms “effect” and affect, which link epigenetic effects on hormones the the affects of hormones on behavior. Neo-Darwinian theorists skip everything known to serious scientists about the differences between effect and affect and link the definition of a ‘signal’ to species-specific behaviors and all biodiversity.
See for comparison: Feedback loops link odor and pheromone signaling with reproduction

Conclusion:

It appears that GnRH neurons integrate a variety of information about the internal state of the animal and its external environment. At least 10,000 neurons in 26 different brain areas appear to transmit signals directly to GnRH neurons. Among these are areas involved in
odor and pheromone processing, sexual behavior, arousal, reward, and other functions. This suggests that GnRH neurons are poised to modulate reproductive physiology and behavior in accordance with the overall state of the animal.
These studies also indicate that GnRH neurons are likely to influence numerous brain functions. They appear to transmit signals to as many as 30,000 or more neurons in 34 brain areas, consistent with previous studies showing GnRH+ fibers and GnRH receptors in multiple brain regions (Badr and Pelletier, 1987; Jennes et al., 1988; Jennes et al., 1997). BL+ neurons likely to receive synaptic input from GnRH neurons were seen in areas associated with numerous different functions, including odor and pheromone processing, sexual behavior, appetite, defensive behavior, motor programs, and the relay of information to higher cortical areas. These results may reflect a strategy wherein GnRH neurons can modify diverse functions in order to coordinate the internal state of the animal and its behavior with reproduction in order to optimize reproductive success.

My comment: Have neo-Darwinian theorists found a species in which feedback loops do not link what the organism eats to its physiology of reproduction? If not, what do they claim links energy-dependent changes in angstroms to ecosystems in all living genera?
Who cares?

See also: The scent of a hatchling: intra-species variation in the use of chemosensory cues by neonate freshwater turtles

The 5300-year-old Helicobacter pylori genome of the Iceman
Abstract excerpt:

The “Iceman” H. pylori is a nearly pure representative of the bacterial population of Asian origin that existed in Europe before hybridization, suggesting that the African population arrived in Europe within the past few thousand years.

See also: Evolution of gut bacteria in humans and hominids parallels ape evolution
See also: Rapid evolution of microbe-mediated protection against pathogens in a worm host

My comment: Taken  together, these two articles link the difference in the bacteria that nematodes eat to the morphological and behavioral diversity of C. elegans for comparison to the predatory nematode with teeth, P. pacificus. From there, the conserved molecular mechanisms link the gut bacteria of the “Iceman” to the morphological and behavioral diversity of all human populations.

See also:

Special Report on Cell Biology: Sweetening the pot

Glycosylation in cellular mechanisms of health and disease

Glycomics: A rapidly evolving field with a sweet future
Excerpt 1)

Glycans play many critical roles in both the normal function of cells and in disease. They assist in the folding of many proteins, aid in protein trafficking, mediate cell adhesion, differentiate blood groups, modulate the immune system, are implicated in many signaling pathways, and provide a protective extracellular matrix for many types of cells. Glycans are also implicated in the process of infectivity for many pathogenic bacteria (2) and most viruses (3), including those that cause the common cold, influenza, and HIV/AIDS.

Excerpt 2)

Glycomics is now being used in combination with genomics, epigenomics, proteomics, lipidomics and metabolomics to provide a more holistic view of how cellular pathways function and how they change in response to disease.

It has become nearly impossible for me to keep up with the information that refutes neo-Darwinian pseudoscientific nonsense at the same time more articles are published that tout the nonsense.
See for comparison: The role of microRNAs in metabolic interactions between viruses and their hosts
Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching
Conclusion:

epigenetic inheritance of active and repressed chromatin state during mitosis has been demonstrated (Cavalli and Paro, 1998; Grewal and Klar, 1996). Our measurements suggest that the timescale on which the relative accessibility of IGHC loci persists is ~10 somatic mutations. Calibration of the mutational clock should allow recovery of information about epigenetic state and phenotypic dynamics in units of time and cellular generations. Together with recent studies of mammalian (Spencer et al., 2009) and bacterial cells in culture (Hormoz et al., 2015), our work suggests that phenotypic correlations between sister cells due to shared inheritance are widespread. We predict that such correlations often will be detected when genealogical relationships between individual cells can be resolved. We propose that inheritance of epigenetic state provides a mechanism for orchestrating cellular behavior without the need for signaling.

My comment: Attempts to define the term “signal” will fail because everyone knows what a signal is and all serious scientists know that food odors and pheromones are signals that link feedback loops from the innate immune system to chromatin folding and supercoiled DNA, which protects organized genomes from virus-driven entropy. The proposal the “…inheritance of epigenetic state provides a mechanism for orchestrating cellular behavior without the need for signaling” exemplifies the ignorance of all neo-Darwinian theorists who have failed to link energy-dependent signals to biophysically contrained protein folding chemistry via RNA methylation and RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all living genera.
Finally,  see:Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters
It was reported on August 4, 2016 by Engaging Epigenetic Experts as:

…the authors say that they suspect such antisense transcription plays an important role in “in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.”

My comment: This site started removing my comments after several weeks of allowing me to accurately link articles like this one to what is known about RNA-mediated cell type differentiation. Others have already invented terms like oncohistones and histone subunit isoforms in attempt to continue obfuscating the links from energy-dependent RNA-mediated amino acid substitutions to healthy longevity because they know virus-driven energy theft has been linked to all pathology.

Engaging Epigenetics Experts appears to be caught in the crossfire. They’ve supported too much neo-Darwinian nonsense to suddenly admit that it never made sense, but that’s what antisense transcription confirms. There are many other sources of what should have been “Science” news but the news was placed into the context of pseudoscientific nonsense touted by neo-Darwinian theorists who have trapped themselves in their ignorance.
In the article mentioned by Engaging Epigenetics Experts, this claim is substantiated:

Despite differences in epigenetic features, tendency for association with transregulatory factors, and capacity to produce stable RNA transcripts, all three classes of TSS described in this work display similarities in sequence content, including enrichment for GC content and Pol II-associated sequence motifs (Fig 2). As such, antisense transcription appears to be encoded in genetic sequence. This connection between sequence content and epigenetic features provides the compelling suggestion that antisense transcription encoded by sequence may direct the positioning of nucleosomes and deposition of histone marks. Antisense transcription may also participate in signal-dependent modulation of epigenetic content where activation of sequence-encoded antisense TSS precedes nearby changes in chromatin structure. In this way, the collection of transcription initiation-associated sequence motifs near promoters may define regulatory potential for a given gene. This connection to sequence also provides a means to interrogate antisense transcription function. Future studies with selective mutation of associated sequence motifs may elucidate the function of antisense transcription and its coincidence with promoter-associated features. Directed mutagenesis could also establish the extent of the effect of antisense transcription on the chromatin environment at promoters.
We characterized downstream antisense transcription initiating near gene promoters in human T47D/A1-2 cells. daTSSs fall between regularly positioned nucleosomes downstream of gene TSSs. Histones within this region are enriched for marks closely associated with active promoter regions, such as H3K4me3 and H3K27ac modifications. Chromatin remodeling complexes show enriched binding upstream of observed daTSS positions, suggesting that antisense transcription contributes to the establishment and maintenance of a promoter-specific chromatin environment. Downstream antisense transcription is common to many human promoters, and daTSSs correlate with the downstream edge of promoter-associated chromatin features. Coincidence of daTSSs with these features suggests interplay between antisense transcription and regulatory pathways.

My comment: There are too many ways to obfuscate what is known about the epigenetically-effected links from energy-dependent changes in angstroms to ecosystems in all living genera. These two paragraphs are important to understand in that context. They link RNA methylation and RNA-mediated amino acid substitutions to cell type differentiation in all living genera via chromatin remodeling, but you will not be encourage to look at the facts because there is no mention of epigenetically-effected RNA-mediated amino acid substitutions in the context of chromatin remodeling.  That’s why I added emphasis to this claim: “…transcription initiation-associated sequence motifs near promoters may define regulatory potential for a given gene.” 
It links hydrogen-atom transfer in DNA base pairs in solution from energy-dependent changes in the microRNA/messenger RNA balance to gene regulation via everything known to serious scientists. It links RNA-mediated amino acid substitutions and morphological diversity by linking energy-dependent RNA methylation from learning and memory to behavior via chromatin remodeling. The chromatin remodeling occurs in the context of the physiology of reproduction and what is known about supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy.
But their claim that “…transcription initiation-associated sequence motifs near promoters may define regulatory potential for a given gene” is placed into the context of a theory about the fact that energy-dependent RNA-mediated amino acids substitutions, which are referred to in the context of  transcription initiation-associated sequence motifs may define the energy-dependent regulatory potential of different genes in different individuals of different species. All pseudoscientists know how to obfuscate facts about the energy-dependent regulatory potential of different genes, because they have been placing them into the context of virus-driven energy theft and mutation-driven evolution since the time that de Vries (1902) defined “mutation.”
Addendum: People complain that I am not explaining how quantum physics, quantum chemistry, quantum biology, and quantum consciousness in terms they can understand. See:

Double slit experiment and the REAL secret

Real-world explanation: Brian Greene : What’s Beyond The Double Slit Experiment ?

See also:
 Our Reality Is Information Tom Campbell
Probability & Uncertainty: The quantum mechanical view of nature Richard Feynman
New Experiments Show Consciousness Affects Matter Dean Radin