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attempts to explain any aspect of species-specific biophysically constrained cell type differentiation and aging has been replaced by the use of model systems of biological processes.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

 

Alternative splicing of pre-mRNA

Irreconcilable differences: food energy vs de novo assembly

Developmental dynamics and contemporary evolutionary psychology: status quo or irreconcilable views? Reply to Bjorklund (2003), Krebs (2003), Buss and Reeve (2003), Crawford (2003), and Tooby et Al. (2003).

The authors argue that evolutionary psychology currently offers no coherent framework for how to integrate genetic, environmental, and experiential factors into a theory of behavioral or cognitive phenotypes.

An evolutionary perspective on the systems of adaptive immunity

We propose a revival of the concept of the ‘Big Bang’ of vertebrate immunity, arguing that its origin involved a ‘difficult’ (i.e. low-probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.

All genomic duplications in vertebrates are food energy-dependent and RNA-mediated. None occur linearly. Natural selection for energy-dependent codon optimality links changes in base pairs to the fixation of amino acid substitutions, which have been linked to all morphological and behavioral diversity by biophysically constrained viral latency.
For example, a single amino acid substitution in the gonadotropin releasing hormone decapeptide links achiral glycine in position 6 to all vertebrate cell type differentiation.
See: Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity

We demonstrate here that a protochordate GnRH receptor does not distinguish GnRHs with achiral or chiral amino acids, whereas GnRH receptors of jawed vertebrates are highly selective for GnRHs with the central achiral glycine. The poor activity of the protochordate GnRH was increased >10-fold at vertebrate receptors by replacement of the chiral amino acid with glycine or a d-amino acid, which favor the type II′ β-turn.

lncRNAs in development and disease: from functions to mechanisms

This suggests that amplification of this lncRNA alone (even without MYC) can promote tumorigenesis in breast cancer by increasing MYC expression [44], which has been proposed to occur by protein stabilization. However, it is unlikely that this is the only mechanism of action for this lncRNA as this multi-exonic transcript encoding over 20 different isoforms is itself under the control of c-MYC and harbours multiple microRNAs within its locus [45].

Define isoform: any of two or more functionally similar proteins that have a similar but not an identical amino acid sequence.
The fact that a multi-exonic transcript encoding over 20 different proteins with similar but not identical amino acid sequences links the term isoforms from wordplay via multiple food energy-dependent microRNAs and RNA-mediated amino acid substitutions that control the virus-driven degradation of messenger RNA.
The phylogenetic utility and functional constraint of microRNA flanking sequences

…the clear identity and easy alignment of these sequences makes them good candidates for estimating phylogeny, and they can reliably be found and identified across all members of a clade of interest. Their relatively slow evolution [3] also means that they can easily be identified in de novo assemblies of genomes.

The ridiculous claim about the slow evolution of energy-dependent RNA-mediated amino acid substitutions cannot be put back into any aspect of identification in de novo assemblies of genomes. The assembly of all organized genomes is energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction.

Dispensing with all pseudoscientific nonsense about evolution (2)

See also: Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk
Reported as: Hundreds of Genomic Regions Linked to Age at Menarche

Age at onset of puberty is affected by a combination of genetic, nutritional, and other environmental factors and that timing, in turn, is associated with risk of cancer later in life.

Who will be next to link energy-dependent changes in the microRNA/messenger RNA balance from nutritional epigenetics to other environmental factors and stress-linked pathology in all organized genomes?
They report that the strongest age at menarche (AAM) signal encodes a key repressor of energy-dependent microRNA biogenesis, which links methylation to limits on cell pluripotency.
Other significant genome wide signals were mapped to lysine-specific demethylase genes or to Mendelian pubertal disorder genes such as GNRH1 (178) and KAL1 (378). KAL1 and GnRH link olfaction and pheromones from fertilization to adult sexual behavior.
See also: Feedback loops link odor and pheromone signaling with reproduction
Stop pretending it takes a team of hundreds of people to determine that all biodiversity on Earth is nutrient energy-dependent and biophysically constrained by the physiology of pheromone-controlled reproduction. All serious scientists know that feedback loops link chirality and autophagy from changes in the morphological and behavioral phenotypes of microbes to mammals during their life history transitions.

See also: A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution

rp_tumblr_ngykp0yfND1r5gzz6o1_500.jpg

Expunging the distinguished public

Royal Society Expunges Public From Evo Record

Many of the attendee-participants were, in fact, more distinguished than many of the actual speakers. So the audience came to be heard as well as to listen. But the official recording (now posted) has been wiped clean of public comment — the most robust part of the meeting — and what we are left with, with few exceptions, is a series of academic lectures and old science.

Thanks for continuing to make the Royal Society Meeting organizers look as foolish as they are. Life will go on without them, although the increasing number of virus-driven pathologies may wipe out billions the next time something like the Spanish Flu hits populations across the globe — as it did in 1918. Or maybe the transgenerational epigenetic inheritance of Zika virus-damaged DNA will do it, slowly.

Until then, intelligent scientists will want to keep track of works by Nobel Laureates like Ben Feringa (Chemistry) and Yoshinori Ohsumi (Physiology or Medicine) who have linked quantized energy as information from the sun to autophagy, which biophysically constrains all energy-dependent RNA-mediated protein folding chemistry.

Gunter Witzany seems to be so far ahead of the Nobel Laureates that they can’t see him. Thank you for mentioning the conference he is organizing in your book, since it will probably put an end to the pseudoscientific nonsense touted by all theorists. Others may want to see (and you may want to interview) the senior authors of these two recently published works:

(Ohsumi) The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes

and

(Feringa) Dynamic control of chirality and self-assembly of double-stranded helicates with light

See for comparison:

See also: Why the Royal Society Meeting Mattered, in a Nutshell

He quoted paleontologist Graham Budd who has observed: “When the public thinks about evolution, they think about [things like] the origin of wings….But these are things that evolutionary theory has told us little about.”

Many fascinating talks at the Royal Society conference described a number of evolutionary mechanisms that have been given short shrift by the neo-Darwinian establishment. Unfortunately, however, the conference will be remembered, as Suzan Mazur intimated in her coverage, for its failure to offer anything new. In particular, in our judgment, it failed to offer anything new that could help remedy the main “explanatory deficit” of the neo-Darwinian synthesis — its inability to account for the origin of phenotypic novelty and especially, the genetic and epigenetic information necessary to produce it. These are still problems that evolutionary theory tells us little about.

See for comparison: Ancient Enzyme Morphed Shape to Carry Out New Functions in Humans

Schimmel compared it to reshaping an airplane’s wing to serve as the airplane’s tail instead. “Nature has provided ways for reshaping objects, like C-Ala, and when that happens, new functions occur,” he said.

The claim that “Nature” causes new functions could have been addressed at the Royal Society Meeting. Instead, we will probably continue to see pseudoscientific nonsense touted about the reshaping of wings into tails.

rp_levels-of-organization.jpg

Energy-dependent RNA methylation (7)

“…viral latency is responsible for life-long pathogenesis and mortality risk…” – Lieberman (2016)

My comment: Energy-dependent RNA-mediated amino acid substitutions are responsible for life-long healthy longevity and decreased mortality risk.

See for comparison: How cancer was created by evolution

Excerpt 1)

But even though it is evolutionary processes that have made cancer such a problem, it is also evolutionary thinking that is now leading to pioneering treatments that could stack the odds against cancer and in favour of our health.

Excerpt 2)

Genetic diversity is “the spice of life, it’s the substrate upon which natural selection acts”, says Swanton. By this he means evolution by natural selection, first proposed by Charles Darwin in 1859.

See for comparison:

Evolution by natural selection cannot be the outcome if something is not first selected. Selection is always for nutrients. It is as simple as that.” — James V. Kohl (7/24/13)

My comment: Thinking about evolutionary processes in the context of cancer pathology, which is obviously a problem that arises in the context of virus-driven energy theft, is like not thinking at all.

See for comparison:  Engaging epigenetics experts

The comments represent the only success I have had with attempts to explain what is currently known about RNA-mediated cell type differentiation in any FB group.

Excerpt:

I don’t see a lot of research on the role of ‪#‎epigenetics‬ in suppressing endogenous retroviruses, so I was intrigued by this one. The investigators in this article in Development turn off the gene Setdb1, a histone methylator, and let slip the dogs of MLV. I’m certain one of our regular visitors will find this interesting.
Working on mouse cells, the team of researchers from Germany’s Ludwig Maximilians University and elsewhere discovered that releasing Setdb1’s hold on endogenous retroviruses definitely allows murine leukemia virus (MLV) to ramp up protein production, ultimately killing the host cells. Of course.

See for comparison:  Creationism and Creationism

My comment: Many people seem more interested in arguing about the religious beliefs of others compared to learning about energy-dependent cell type differentiation for comparison to virus-driven energy theft and pathology.

See also: Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells

Excerpt:

…global demethylation is, contrary to previous assumptions, a consequence of neither loss of de novo methylation nor active Tet-dependent demethylation but caused by impaired maintenance methylation.

My comment: Maintenance methylation is energy-dependent and it is RNA-directed.

See: RNA directed DNA methylation and cell types or Google rna-directed dna methylation or search PubMed rna directed dna methylation

RNA-directed DNA methylation is a conserved molecular mechanism that typically prevents transgenerational epigenetic inheritance of damage due to virus-driven energy theft. It is like a reset button on your router, or initiating “restart” on your computer after the problem with virus-driven energy theft of programming information has been corrected. In all living genera, “restart” works wll until the efficiency of energy transfer to the information in programming has been corrupted by the accumulation of viruses and mutations in your ancestors.

The only way to prevent the damage your ancestors knew about was to follow the laws of biology that link virus-driven energy theft to pathology across generations of people who failed to follow those laws. Now, some offspring are susceptible to Zika virus energy theft, which causes craniofacial abnormalities and brain damage in infants — but not always.

There are clear links from nutritional epigenetics that predict when damage is most likely to be transgenerationally (epigenetically) inherited. Anatagonist Sean Ovis (Sirius Cyantis),  put them into God’s plan to kill us all via the creation of viruses, which means he linked the viruses to craniofacial abnormalities and brain damage in infants via the same model — as if God’s intent was to start killing his Creation from the time of birth.

See also: Creationism

My comment: That’s the clearest example of hate-mongering I have seen in this group, so far. And he twisted my model of virus-driven energy theft to do it. Group members wanted a definition of virus-driven energy theft. They refused to accept the fact that it has been linked to all pathology in my model and in the accurate representations of biologically-based cause and effect by all other serious scientists. However, some of the scientists who failed to make the obvious connection are trying to link what is known from a loss of function mutation to the creation of new oncohistones.

Neo-Darwinin theories about mutations, natural selection, and evolution have lost nearly all their appeal among serious scientists. Facts replaced theories about human brain development and the National Microbiome Initiative predictably will undoubtedly continue to be linked to the Precision Medicine Initiative in all publications — except those published by theorists.

Within the next year or two, we should see the mutation-driven evolution approach that theorists have linked to the development of the human brain and behavior become recognized as the theory that is the source of all preventable pathology. Serious scientists continue to make progress, and they will enlist others who are “Combating Evolution to Fight Disease.”
The only researchers left fighting against scientific progress will be the neo-Darwinian theorists, and they may be subjected to something akin to the Spanish Inquisition, or the Salem Witch Trials. “What caused you to keep thinking your magical thoughts about cell type differentiation, you witch?”
See for comparison: Regulation of prefrontal cortex myelination by the microbiota

Excerpt 1)

“… we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC.”

My comment: I believe everything that is reported in the context of the belief that it has been demonstrated for the first time should be placed into the context of a model of biologically-based cause and effect. If the model links what is known about RNA-mediated amino acid substitutions and cell type differentiation in all living genera, it could be used to predict what would be demonstrated next for the first time and demonstrated next for the first time after that, ad infinitum.

Eventually, everyone who has ever demonstrated for the first time that the microbiome is the key component of what they have demonstrated for the last time may link the microbiome from metabolic networks to genetic networks via the physiology of energy-dependent reproduction in all living genera and demonstrate for the last time that all other demonstrations linked from virus-driven energy theft to pathology have shown the same thing.

No one has ever shown anything else besides that fact that cell type differentiation is energy-dependent and that RNA-mediated fixation of amino acid substitutions occurs in the context of the physiology of reproduction linked to supercoiled DNA by the innate immune system.

Excerpt 2)

Studies utilizing approaches such as monocolonization in either GF or microbiota-depleted animals using antibiotics would allow deciphering whether specific bacterial strains have the capacity to normalize the observed altered myelination patterns in these animals.

My comment: Those studies could be linked from pattern recognition in other species to demonstrate for the last time that all pathology is caused by virus-driven energy theft, which alters everything known about how metabolic networks are linked to genetic networks by biophysically constrained RNA-mediated protein folding chemistry. Physics and chemistry link quantized energy from angstroms to ecosystems via the physiology of reproduction and biologically-based cause and effect in all living genera.

Summary: Unique microRNAs (miRNAs) appear to link the nutrient-dependent pheromone-controlled life history transitions of bees to RNA-mediated metabolic networks and genetic networks in all genera via base pair substitutions and amino acid substitutions that differentiate all cell types in all living genera. Jon Lieff continues to present what is known about cell type differentiation in articles that an educated audience can understand. I’ve added more technical representations from the most recently reported sources of information.

See also: Microbes Effect on the Brain in my blog post from May 25, 2015: Pattern recognition: biogeochemical structure and function

See also: Counting viruses and bacteria in photosynthetic microbial mats

My comment: Photosynthesis in the ecological regions at the lowest level of a body of water such as the ocean appears to link the minimum amount of quantized virucidal energy from ultraviolet (UV) light and the maximum amount of water molecules found on Earth. The speed of biologically-based symbiotic interactions has now been measured in the context of femtosecond blasts of UV light, which links RNA-mediated DNA repair to amino acid substitutions and cell type differentiation at every subsequent level of examination. All levels of examination have always required a link from an anti-entropic source of energy. All serious scientists have linked atoms to ecosystems in all living genera, via the physiology of reproduction and supercoiled DNA, which protects all organized genomes from virus-driven entropy.  Only recently have serious scientists linked angstroms to ecosystems in the context of the physiology of reproduction and supercoiled DNA.

The serious scientists that did that appear to be having great fun demonstrating “…for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level.”

See for example:


C. David Allis’s group seems to want others to believe cell type differentiation is not all about the base. He may want them to believe it’s all about histones. Others have also suggested that approach.
See: Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus reported as: Social behavior in carpenter ants reprogrammed using epigenetic drugs
Excerpt:

It’s All About the Histone The almost decade-long collaboration between the Berger, Liebig, and Reinberg labs, supported by the Howard Hughes Medical Institute, blends molecular biology with observations of animal behavior to understand how caste-based differences arise in ants.

Allis’s group is now reporting the existence of oncohistones (cancer causing histones). They invented the term.
See: An oncohistone deranges inhibitory chromatin

Missense mutations (that change one amino acid for another) in histone H3 can produce a so-called oncohistone and are found in a number of pediatric cancers. For example, the lysine-36–to-methionine (K36M) mutation is seen in almost all chondroblastomas. Lu et al. show that K36M mutant histones are oncogenic, and they inhibit the normal methylation of this same residue in wild-type H3 histones. The mutant histones also interfere with the normal development of bone-related cells and the deposition of inhibitory chromatin marks.

My comment: By placing the change in the base pair that precedes the energy-dependent change in the amino acid substitution, biologically uninformed researchers will focus on the oncohistones, not the virus-driven energy theft that links all mutations to all pathology. The focus of drug development on histones is on damage control or repair.
Allis’s group can develope treatments for disorders of cell type differentiation that link virus-driven energy theft from base pairs to detrimental amino acid substitutions without mentioning the role of energy-dependent amino acid substitutions in cell type stability in all living genera. Cell type stability is controlled by the physiology of reproduction, which links the amino acid substitution to the histones and supercoiled DNA , which protects all organized genomes from virus-driven energy theft and genomic entropy.
See also: Censorship & Upcoming Royal Society Evo Meeting discussion on the Creationism FB group

rp_levels-of-organization.jpg

Wasted Templeton Funding (2)

See also: Wasted Templeton Funding (1)

Templeton grant funds evolution rethink

Excerpt:

The extended evolutionary synthesis is a term coined in 2007 to imply that the preeminent current evolutionary theory, the so-called modern synthesis, needed to broaden its focus because it concentrated too much on the role of genes in evolution and lacked adequate incorporation of new insights from development and other areas of biology.

My comment: That is an understatement! The problems with the so-called modern synthesis are perfectly clear:
1) [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.
2) 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…
3) …evolutionary science has now “moved on to such an extent” that she and Peter Saunders don’t really care anymore about “trying to convince the neo-Darwinists.”
All serious scientists have since linked angstroms to ecosystems via what is known about the biophysically constrained chemistry of energy-dependent protein folding and links from the innate immune system to supercoiled DNA, which protects all organized genomes from virus-driven energy theft and entropy in the context of the physiology of reproduction.
See for example:

See also: Precision Medicine Program to Get $9.3M in NHLBI Funding for Omics Research
One of the things they are asking for is:

“Causal modeling using whole genome sequences and functional genomics data to enhance discovery of influential genetic and epigenetic variants that influence [heart, lung, blood, and sleep] HLBS disorders;”

My comment: They are asking for what has already been included in every model of biologically-based cell type differentiation that has ever been detailed by serious scientists.  Now, the  Templeton Foundation has awarded $8.7M to fund research that can only benefit humanity by answering Schrodinger’s question “What is Life?” in the context of what is known about how the energy-dependent RNA-mediated innate immune system and supercoiled DNA protect life from virus-driven energy theft.”How often do we still hear that quantum effects can have little relevance in the study of biology, or even that we eat food in order to gain energy?” — Roger Penrose
 

rp_levels-of-organization.jpg

Non-mainstream scientist shares Nobel prize in Medicine

Youyou Tu is the 12th women awarded the Nobel Prize in Physiology or Medicine (2015) for her discoveries concerning a novel therapy against Malaria.

Historical perspective: Lasker~DeBakey Clinical Medical Research Award

Excerpt:

Tu discovered a passage in the Handbook of Prescriptions for Emergencies (340 CE) by Ge Hong that referenced Qinghao’s malaria-healing capacity. It said “Take a handful of Qinghao, soak in two liters of water, strain the liquid, and drink.” She realized that the standard procedure of boiling and high-temperature extraction could destroy the active ingredient.

My comment: Recent learning about the thermodynamic stability of the active ingredient suggests that traditional Chinese medicine integrated what is now known about the biophysically constrained  chemistry of protein folding during thermodynamic cycles of protein biosynthesis and degradation in bacteria and plants.
The cycles link ecological variation to ecological adaptations via nutrient-dependent RNA-mediated amino acid substitutions in all living genera. The thermodynamic stability of the plant extract was maintained for medicinal use.
Excerpt 2)

Tu pioneered a new approach to malaria treatment that has benefited hundreds of millions of people and promises to benefit many times more. By applying modern techniques and rigor to a heritage provided by 5000 years of Chinese traditional practitioners, she has delivered its riches into the 21st century.

My comment: Other researchers from China recently linked everything else known about RNA-mediated protein folding biochemistry via amino acid substitutions to the thermodynamic stability of all organized genomes. The “Holy Grail” of nutrient-dependent RNA-mediated protein folding is thermodynamically regulated.
See:
Structural basis of pre-mRNA splicing 
Structure of a yeast spliceosome at 3.6-angstrom resolution
Reported as: Chinese Scientists Discover Structural Basis of Pre-mRNA Splicing

On August 21st, the research team led by Prof. Yigong Shi from School of Life Sciences, Tsinghua University in China published two side-by-side research articles in Science, reporting the long-sought-after structure of a yeast spliceosome at 3.6 angstrom resolution determined by single particle cryo-electron microscopy (cryo-EM), and the molecular mechanism of pre-messenger RNA splicing. Until now, decades of genetic and biochemical experiments have identified almost all proteins in spliceosome and uncovered some functions. Yet, the structure remained a mystery for a long time. The works, primarily performed by Dr. Chuangye Yan, and Ph.D students Jing Hang and Ruixue Wan under Prof. Yigong Shi’s supervision, settled this Holy Grail question and established the structural basis for the related area. This work was supported by funds from the Ministry of Science and Technology and the National Natural Science Foundation of China.

See also: Feedback loops link odor and pheromone signaling with reproduction and Sensory feedback shapes individuality to provide equal space for behavioral excellence
Other mainstream scientists continue attempts to genetically engineer mosquitoes to limit their nutrient-dependent physiology of RNA-mediated ecological adaptation. These mainstream scientists ignore the contribution of RNA-mediated amino acid substitutions reported in Amino Acid Residues Contributing to Function of the Heteromeric Insect Olfactory Receptor Complex.
They use viruses to genetically engineer mosquitoes with mutations that limit reproduction. See: orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET and Genome-engineering with CRISPR-Cas9 in the mosquito Aedes aegypti.
If this diagram looks impressively complex compared to claims that linked traditional medicine across 5000 years of what should have been advances in treatment of diseases made by mainstream scientists, realize is that mainstream scientists get paid to do work that is represented like this.

 
 
 
 
 

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

Understanding cell type differentiation

The Wisdom of the Fly Crowds

IMG_2329-e1413855233208-958x718

From deep time into real time: What evolutionary processes?

Rapid evolution of a native species following invasion by a congener

Abstract excerpt: “…the lizard Anolis carolinensis moved to higher perches following invasion by Anolis sagrei and, in response, adaptively evolved larger toepads after only 20 generations.”
My comment: This indicates that the behavior evolved before the species, in response, evolved larger toepads.
Reported as: Florida lizards evolve rapidly, within 15 years and 20 generations
Karl Grammer’s comment: “Proofs for evolutionary processes…

What evolutionary processes?

RNA-directed DNA methylation links the epigenetic landscape to the ecological adaptations manifested in the morphology of the toepads. The changes require epigenetically-effected nutrient-dependent RNA-mediated amino acid substitutions that differentiate cell types. The morphological changes manifested in the cell types linked to larger toepads exemplify cell type differentiation that must be controlled by the physiology of reproduction and properly timed reproductive sexual behavior.
Everything currently known about biophysical constraints; the chemistry of protein folding; and the conserved molecular epigenetics of molecular biology attests to the fact that 1) moving to higher perches and 2) larger toepads requires a series of simultaneous nutrient-dependent pheromone-controlled ecological adaptations.
News Article excerpt: “To put this shift in perspective, if human height were evolving as fast as these lizards’ toes, the height of an average American man would increase from about 5 foot 9 inches today to about 6 foot 4 inches within 20 generations — an increase that would make the average U.S. male the height of an NBA shooting guard,” said Stuart.”
My comment: Sex differences in height and other morphological and behavioral traits assure us that the epigenetically-effected changes in the lizards cannot be put into any perspective outside the context of nutrient-dependent pheromone-controlled sex differences in cell type differentiation. All differences in cell types link ecological variation to ecological adaptations via the pheromone-controlled physiology of reproduction in species from microbes to man.
By reporting their findings outside the context of biologically-based cause and effect that links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man, the authors suggest that evolution somehow occurred. What they have actually shown is another example of nutrient-dependent pheromone-controlled ecological adaptations, which are manifested in the morphological and behavioral phenotypes of all species.
Journal article excerpt: “Brown and Wilson called evolutionary divergence between closely related, sympatric species “character displacement” (1), and our data constitute a clear example of this. Resource competition has been the interaction suggested most often as the source of divergent selection during character displacement [sometimes specifically called “ecological character displacement” (13)].”
Character displacement is a vague term used eight years before Dobzhansky (1964) claimed “…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!” Others have recently claimed “Ecological variation is the raw material by which natural selection can drive evolutionary divergence [1–4].”
Use of vague terms like character displacement, indirect genetic effects, cooperating genetic events, and genome dynamics events instead of ecological character displacement (i.e., ecological speciation) continue to contribute to the confusion manifested in yet another report of biologically-based cause and effect that is meaningfully interpreted as if the findings support a ridiculous theory of evolution. However, that theory must now be divorced from claims that evolution occurs over eons of time via mutations and natural selection, because no evolutionary events have been described that link one species to the evolution of another.
This statement makes that fact clear: “The rates of 4 types of elementary evolutionary events (hereinafter Genome Dynamics Events or GDE)…” That statement changes evolutionary events to the virtually unusable term genome dynamics events. It follows from the fact reported in A universal trend of amino acid gain and loss in protein evolution: “We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.” (So, why not use the term ecological speciation, since that is what obviously occurs via RNA-mediated genome dynamics events? Must researcher compete to invent new terms and claim that they are the first to detail the obvious?)
If it is not yet obvious to everyone that nutrient-dependent metabolism emerged as the link to ecological adaptations and ecological speciation “…before the last universal common ancestor of all extant organisms,” it might be clearer after reading Arrival of the Fittest: Solving Evolution’s Greatest Puzzle. Unfortunately, Wagner insists on using the terms commonly used by population geneticists. He focuses on “innovability” in that context. I’m not sure who invented that term for ecological speciation. However, for a quick claim that requires less thought about use of vague terms, see: “Genetic and metabolic networks drive all biological processes. You can think of them as bridges between the organism and the individual molecules – proteins and genes – that form all living cells.” — from the Genetic and Metabolic Networks page of Professor Andreas Wagner’s Wagner Lab Research site. You can also think of ecological speciation as the process that is driven by all biological processes that involve genetic and metabolic networks. (Hint: all biological processes clearly involve genetic and metabolic networks.)
The research reported here answers the question about “What evolutionary processes?” in the context of genetic and metabolic networks that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man. See also, Dobzhansky (1973) “…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.” It was clear to Dobzhansky that the amino acid substitutions differentiated the cell types of these primates, although he could not have known what epigenetic effects led to the RNA-mediated amino acid substitutions and differentiation of the cell types.
What is the answer to questions about evolutionary processes in the context of these amino acid substitutions? See: From Fertilization to Adult Sexual Behavior (1996): “Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species…” To avoid further confusion about biologically-based cause and effect, which continues to be placed into the context of evolutionary theory, 41 years after Dobzhansky (1973) and 18 years after our Hormones and Behavior review, see Nutrient-dependent/pheromone-controlled adaptive evolution: a model. (2013).
Examples of amino acid substitutions, which differentiate the cell types of all individuals of all species from microbes to man, are included in the review. The examples answer the question “What evolutionary processes?” by placing biologically-based cause and effect into the context of Darwin’s ‘conditions of life’ and ecological speciation instead of the context of neo-Darwinism, which bastardized his theory by making it appear that mutations could lead from natural selection to the evolution of biodiversity over eons of time. That exemplifies pseudoscientific nonsense!
Ecological adaptations are nutrient-dependent and pheromone-controlled by the physiology of reproduction, which enables amino acid substitutions and chromosomal rearrangements to move what some people may still claim are evolutionary processes from deep time into real time via ecological speciation.
That forward movement into the scientific reality of real time has been mentioned in three recent reviews of biologically-based cause and effect that move Dobzhansky’s claims from 1964 and 1973 into the real time of today’s accurately reported research. See for example: Combating Evolution to Fight Disease and RNA and dynamic nuclear organization and Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans. See also Dobzhansky (1972) “Reproductive isolation evidently can arise with little or no morphological differentiation.”
Many serious scientists have realized that organisms like the lizards starve to death when competition for nutrients displaces them, unless they quickly adapt and establish a new ecological niche, which is obviously what all extant species have done via their nutrient-dependent RNA-mediated pheromone-controlled reproduction. The species that didn’t adapt are extinct, because too many individuals starved to death before their cell types could reproduce.

Rapid Evolution in Real Time

RNA-directed DNA methylation links the epigenetic landscape to the ecological adaptations manifested in the morphology of the toepads. The changes require epigenetically-effected nutrient-dependent RNA-mediated amino acid substitutions that differentiate cell types. The morphological changes manifested in the cell types linked to larger toepads exemplify cell type differentiation that must be controlled by the physiology of reproduction and properly timed nutrient-dependent reproductive sexual behavior, which probably occurs near the location of the higher perches.
Re: rapid evolution and character displacement (i.e., ecological speciation)

Everything currently known about biophysical constraints; the chemistry of protein folding; and the conserved molecular epigenetics of molecular biology attests to the fact that 1) moving to higher perches and 2) the ecological adaptation of larger toepads requires a series of simultaneous nutrient-dependent pheromone-controlled  RNA-mediated events that obviously have occurred.
The similarities to what also occurs in hummingbirds that ecologically adapt to higher elevations is clear. However, like all similarities manifested in morphological and behavioral phenotypes, which arise in the context of nutrient-dependent pheromone-controlled ecological adaptations, these lizards attest to the fact that the differences are due to RNA-mediated events, not to evolutionary events.
Creative use of the term “character displacement” can be compared to what Dobzhansky, a self-proclaimed creationist, wrote about amino acid substitutions in 1973. “…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.”
If he was not still dead, Theodosius Dobzhansky (January 24, 1900 – December 18, 1975), who was also a self-proclaimed evolutionist, would probably dismiss the observations of others who claim that ‘character displacement’ is proof of evolution, as he did in (1964) when he wrote:  “…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!” Observations that higher perches are linked to morphological phenotypes in these lizards are characterized by the observations of others who have virtually ignored the need for behavioral phenotypes to concurrently change to enable ecological speciation.
Moving forward
We can expect to see researchers report soon that a single nutrient-dependent RNA-mediated change leads from ecological variation to the morphological and behavioral phenotypes of these lizards, since that is how ecological adaptations occur in all species. However, we can also expect to see a few more attempts to place ecological adaptations into the context of evolutionary theories, since the theory has become more popular than biological facts.
Few people realize that Darwin’s theory placed ‘conditions of life’ before natural selection. Only after population geneticists bastardized his theory did it become popular enough to include in the context of:
1) “character displacement”
2) “indirect genetic effects”
and
3) “genome dynamics events.”
See also from the original news report: Florida Lizards Evolve Rapidly, Within 15 Years and 20 Generations
Excerpt: “This latest study is one of only a few well-documented examples of what evolutionary biologists call “character displacement,” in which similar species competing with each other evolve differences to take advantage of different ecological niches. A classic example comes from the finches studied by Charles Darwin. Two species of finch in the Galápagos Islands diverged in beak shape as they adapted to different food sources.”
My comment: Darwin did not study finches. Anyone who studies birds today has probably realized that nutrient-dependent pheromone-controlled RNA-mediated events link amino acid substitutions to chromosomal rearrangements that clearly differentiate the morphological and behavioral phenotypes of white-throated sparrows via the pattern of nutrient-dependent biologically-based cause and effect that Dobzhansky began to notice in 1964.
He wrote: “Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.” What we continue to see reported as science is  ignorance associated with claims that “character displacement” is an evolutionary process, when it is evidence of nutrient-dependent pheromone-controlled ecological adaptations in species from microbes to man, which occur via conserved molecular mechanisms.
What then, is the link from amino acid substitutions to behavioral phenotypes?  Apparently, in human adolescents and adults it is a functional single nucleotide polymorphism (SNP) / a G-to-A base-pair substitution that leads from the amino acid methionine (Met) to a valine (Val) substitution. For example: Carriers of the Met allele have been found to display a fourfold decrease in enzymatic activity compared to Val allele carriers going along with an increase of prefrontal DA activity (Lachman et al. 1996; Lotta et al. 1995).
The difference that the amino acid substitution makes is associated with metabolism (e.g., lower enzymatic activity) due to the difference a single base pair change makes in the context of thermodynamic cycles of protein biosynthesis and degradation. The substitution makes the nutrient-dependent pheromone-controlled organized genome less thermodynamically stable, which explains the difference in exploratory behavior.
If nutrient stress associated with “invasion of a congener” in lizards had not led to increased exploratory behavior and an amino acid substitution that stabilized the organized genome of the lizards with higher perches, there would be no biologically-based explanation of how one species climbed higher up the trees and established its pheromone-controlled ecological, social, and neurogenic niche without thought. Instead, the lizards that perched higher might appear to have automagically corrected a nutrient-dependent problem in their organism-level thermoregulation. The behavior that led them to climb higher up the tree led to a nutrient-dependent pheromone-controlled epigenetic correction in organism-level cell type differentiation via changes in metabolism that lead from RNA-directed DNA methylation to beneficial amino acid substitutions. Unfortunately, that is more difficult to explain via comparison to simply stating that “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.” And people already believe in constraint-breaking mutations.
Telling the truth
Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults was reported as Genes exhibit different behaviours in different stages of development, which links RNA-mediated events in our review From Fertilization to Adult Sexual Behavior to Organizational and activational effects of hormones on insect behavior and Honey bees as a model for understanding mechanisms of life history transitions.
The honeybee model organism links nutrient-dependent pheromone-controlled cell type differentiation via RNA-mediated events and what is currently known about Epigenomics and the concept of degeneracy in biological systems. “The reiterations of living systems are developmentally constructed and come into being through internal interactions within organisms, interactions between organisms, and interactions between organisms and their surroundings. Novelty and variation arise from these interactions. The functional redistribution of biological activity onto a group of interacting organisms and their environment effectively offloads a degree of genetic control onto epigenetic processes.’ The problem for evolutionary theorists who tout “character displacement” or anything else has become the fact that “The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, and diseases of the X chromosome (Honeybee Genome Sequencing Consortium, 2006). Included among these different aspects of eusocial species survival are learning and memory, as well as conditioned responses to sensory stimuli (Maleszka, 2008; Menzel, 1983).” — Kohl (2012)
Links from nutrient-dependent pheromone-controlled morphological and behavioral phenotypes in the honeybee now extend across species via the conserved molecular mechanisms of RNA-mediated events that link amino acid substitutions to cell type differentiation and ecological speciation. Thus, it is clear that the popularity of evolutionary theory has prevented scientific progress that could have been made if all researchers were taught enough about biologically-based cause and effect to become serious scientists. Instead, many of them were taught to explain their findings as if organisms like lizards evolved into different species of lizards and dinosaurs evolved into different species of birds.
————————————————————————————————————————–
Addendum: Val158Met polymorphism in COMT gene could be a candidate for low penetrance breast cancer susceptibility in Shanghai population, especially among premenopausal women and early-onset breast cancer patients.
The Val158Met amino acid substitution also shows up in the neurodegenerative disorder, Alzheimer’s disease.
A GOOGLE search for Val158Met might also surprise others who had no idea of how important a single amino acid substitution can be in the context of morphological and behavioral phenotypes because they were taught that species evolve via mutations and natural selection.
Fortunately, companies like Alpha Genomix are leading the way in attempts to link metabolism and pharmacogenetics to the RNA-mediated events that differentiate the cell types of all individuals of all species via amino acid substitutions, which are manifested as differences in genotypes and phenotypes as differences in morphological and behavioral phenotypes, not merely difference in the genes that evolutionary theorists still claim link mutations to the evolution of increasing organismal complexity.
Catechol-O-Methyltransferase (COMT) is an enzyme responsible for the metabolism of catecholamines and Catechol-estrogens in both the central nervous system and other organs. Dopamine is cleared mainly by COMT in the frontal cortex and a reduced activity of this enzyme results in higher synaptic levels of dopamine, which affects prefrontal cortex cognitive response to certain drugs. A single nucleotide polymorphism of the COMT gene produces an amino acid change from Valine to Methioinine (Val158Met) and reduces enzyme activity by 3 to 4 folds. The COMT assay tests for Mutations associated with decreased activity of COMT.
Several complex associations between COMT the Val158Met Variant as a risk factor for numerous diseases have been found but they all seem to have a limited predictive value. However, the response to some psychotropic medications seems to be dependent to some extent upon COMT status. In general, the wild-type genotype predicts a good response to methylphenidate and amphetamines in the treatment of attention deficit hyperactivity disorder.