5th-6th Sept 2018 Dublin, Ireland

RNA-mediated nutritional psychiatry (2)

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.

Neo-Darwinian theorists dispense with Darwin’s food energy-dependent  “conditions of life.” They link mutations and disease to evolution via mathematical models. They exemplify human idiocy.
See for example: Neopterygian phylogeny: the merger assay
Reported as: Adaptive radiations in the Mesozoic

Bony fishes are the most diverse of all extant vertebrate groups. A comprehensive phylogenetic analysis of the group now provides new insights into its 250-million-year evolutionary history.

The claim about the 250-million-year evolutionary history can be compared to what happens when food energy-dependent fixation of a single RNA-mediated amino acid substitution occurs across a vertebrate lineage.
See: Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

It is very surprising and fascinating that the coordinated evolutionary selection of amino acids participating in binding GnRH has resulted in such perfection, that no substitution with a natural amino acid in any position improves binding potency.

Evolution does not select amino acids. Natural selection for food energy-dependent pheromone-constrained viral latency links the substitution of achiral glycine in position 6 of the GnRH decapeptide to the biodiversity of all morphological and all behavioral phenotypes in all vertebrates.
See also: Handbook of Biologically Active Peptides (2013) Chapter 106 GnRH (LHRH)
Page 794 Figure 2 shows that food energy-dependent substitution of achiral glycine at position 6 stabilizes the folded conformation; increases binding affinity; and decreases metabolic clearance.

This feature is incorporated in all agonist and antagonist analogs.

Simply put, the substitution of achiral glycine in the GnRH decapeptide biophysically constrains viral latency in the context of ligand-receptor interactions and the physiology of pheromone-controlled reproduction.
See also: Role of olfaction in Octopus vulgaris reproduction
From the concluding paragraph:

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).

Kohl (2013) is Nutrient-dependent/pheromone-controlled adaptive evolution: a model
The facts that link vertebrates to invertebrates via olfaction and the 2013 model will almost undoubtedly be restated when Tuning Insect Odorant Receptors is published.
Until then, see:Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity (2005)
Biophysical constraints link feedback loops from odors and pheromones to the functional structure of the GnRH decapepetide via achiral glycine in position 6. The link from food to the de novo creation of energy-dependent receptors is required in all organisms. They must select the right food, which helps to ensure their ability to reproduce.

5th-6th Sept 2018 Dublin, Ireland

RNA-mediated nutritional psychiatry

Summary: Young Genes are Highly Disordered as Predicted by the Preadaptation Hypothesis of De Novo Gene Birth
Stop this nonsense about de novo gene birth and you will help to stop the school shootings without more gun control.
See my presentation at the 2017 Precision Medicine Virtual Conference (2/15/17) Energy as information and constrained endogenous RNA interference
See also: Pat Sweeney et al (3/13/2017) Protein misfolding in neurodegenerative diseases: implications and strategies. 

A notable development is the creation of collaborative ecosystems that include patients, clinicians, basic and translational researchers, foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent, reverse or delay the progression of neurodegenerative proteinopathies.

For consideration of protein folding in the context of my life’s works, see: From de novo to “de nono”: most novel protein coding genes identified with phylostratigraphy represent old genes or recent duplicates

Claudio Casola refers “… to the putative de novo genes that failed to pass the validation criteria as the ‘de nono’ genes.” Use of the term ‘de nono’ to refute Pat Sweeney’s neo-Darwinian pseudosceintific nonsense is brilliant! For instance, all serious scientists know that protein folding chemistry is energy-dependent.
 
 

The structural diversity biophysically constrains viral latency and the constraints are referred to in the context of RNA-mediated autophagy. Autophagy clearly makes “de novo” gene creation a no-no term. That is why serious scientists are not likely to use the term de novo. It is like claiming that something automagically occurs.

In the context of what is known about energy-dependent cell type differentiation, see also:

Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis (2011)

and

Formulation and evaluation of anti-suicidal nasal spray of Thyrotropin releasing hormone (2017)
The fact that food odors and pheromones biophysically constrain physical and mental pathology via alternative splicings of RNA has been addressed in published works since 1990.
See for a recent example: RNA splicing is a primary link between genetic variation and disease (2016)
See for examples of constraints:
Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults (E-pub 2014)
The catechol-o-methyltransferase Val158Met polymorphism modulates the intrinsic functional network centrality of the parahippocampal cortex in healthy subjects (2015)
Subsecond Regulation of Synaptically Released Dopamine by COMT in the Olfactory Bulb (2016)
The COMT Val158Met polymorphism exerts a common influence on avoidant attachment and inhibited personality, with a pattern of positive heterosis (2017)
In the context of energy-dependent constraints, the COMT VaL158Met amino acid substitution exemplifies the facts detailed in the context of: Hydrogen bonds directly detected for the first time (2017). The facts about hydrogen-atom transfer in DNA base pairs in solution have since been linked to all energy-dependent pheromone-controlled biodiversity in: Principles of Transgenerational Small RNA Inheritance in Caenorhabditis elegans (2017)
See also: Catechol O-methyltransferase (COMT) functional haplotype is associated with recurrence of affective symptoms: A prospective birth cohort study (1/15/2018)
Analysis of COMT Val158Met polymorphisms and methylation in Chinese male schizophrenia patients with homicidal behavior (2/20/2018)
Adjunctive nutrients in first‐episode psychosis: A systematic review of efficacy, tolerability and neurobiological mechanisms (3/21/18)
Reported as: Antioxidants and amino acids could play role in the treatment of psychosis 3/22/2018
See for comparison: March for Our Lives 3/24/18

Theme Gun violence awareness
Support of gun control

The focus on support of gun control ignores everything known to all serious scientists about biophysically constrained mental health and the virus-driven constraint-breaking mutations in the killers with guns. The future of school shootings depends on mental health treatment.

Why nutritional psychiatry is the future of mental health treatment

…29 clinical trials of antidepressant use in young people found no benefits at all. These trials revealed that instead of relieving symptoms of anxiety and depression, antidepressants caused children and young people to feel suicidal.

See for comparison: 7/25/13 Jay R. Feierman:

Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding [of] Darwinian biological evolution.

My understanding of biology is linked to my understanding of physics and chemistry via 40 years testing experience as a medical laboratory scientist (ASCP emeritus). Simply put, all organisms must eat and reproduce or species do not survive. The discovery of bacteria that eat electrons and create uranium ore was place into the context of this news:
Biologists discover electric bacteria that eat pure electrons rather than sugar, redefining the tenacity of life (2017)
The link from eating electrons to hydrogen-atom transfer in DNA base pairs in solution appears in the context of energy delivery to all cell types in organisms that have blood in their circulatory system. The claim that the human circulatory system evolved incorporates ‘de nono’ gene creation.
There is no such thing as de novo gene creation and ‘de nono gene creation’ can now be used in the context of post-publication ridicule of this model:
Basic Science Model of Blood as an Electron-Delivery Circuit Describes the Evolution of the Human Circulation (2017)
The anti-entropic virucidal energy of sunlight is the link from ecological variation to ecological adaptation in the context of the physiology of reproduction and biophysically constrained viral latency. Pseudoscientists will not stop trying to place that fact into the context of ridiculous neo-Darwinian theories.
Thankfully, ages 10+ can learn how energy-dependent life is biophysically constrained by playing the cell biology game “Cytosis” and the game that links energy-dependent changes from electrons to ecosystems in all living genera: “Subatomic“.
See my attempt to deliver that message in: There is no such thing as de novo control of electrons or the self-assembly of genes. (11/21/17)
But see: Young Genes are Highly Disordered as Predicted by the Preadaptation Hypothesis of De Novo Gene Birth
Stop this nonsense and you will help to stop the school shootings without more gun control.

Alternative splicing of pre-mRNA

Sexual communication signals: New Insights!

Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge.Kalevi Kull

New insights in the evolution of sexual communication signals

Abstract excerpt:

Our research focuses on identifying a) the genes underlying sexual signals and responses in both sexes2-4, and b) ecological factors that may cause divergence in sexual communication. Factors that we found to affect sexual communication are closely related species with similar mating signals5, low nutritional quality, (toxic) secondary plant metabolites and pathogens6.

Elizabeth Pennisi reported on this 2017 conference presentation and claimed:

The results “demonstrate the importance of the social environment,” Halfwerk says. “One form does not attract males on its own, only in close proximity of the other form.” That result also parallels what’s been found in humans: that an attractive woman in a crowd of less attractive women also seems to attract more attention. But pinning down exactly why this happens should be much easier in moths than people, she notes. “That’s the nice thing about insects.”

See: Sexy females help ‘Plain Jane’ moths snag their mates

No experimental evidence of biologically-based sexual communication suggests that sex signals evolved. The fine-tuned systems of communication among individuals and species pose an evolutionary dilemma because they are food energy-dependent. Ecological variation must be linked from food energy to biophysically constrained ecological adaptations by the pheromone-controlled physiology of reproduction in all living genera. Also, everything known to serious scientists about energy-dependent top-down creation links the anti-entropic virucidal energy of sunlight from the creation of ATP to the creation of messenger RNA. That fact does not appear to be coincidental.

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

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

Detailed experimental evidence also links the virus-driven degradation of messenger RNA from mutations to all pathology. That fact leaves neo-Darwinian theorists and “Big Bang” cosmologists without any acceptable theory of anything or any theory of everything.

See for comparison: A New Physics Theory of Life and Jeremy England’s idea that “You start with a random clump of atoms, and if you shine light on it for long enough, it should not be so surprising that you get a plant.” 

Theorists and philosophers cannot link energy as information or “big bang” cosmology to biodiversity without the creation of energy. Most of them ignore the fact that they do not know where the energy in a hydrogen atom came from.

Without the de novo creation of energy, they cannot link hydrogen-atom transfer in DNA base pairs in solution from microRNA flanking sequences to SNPs, and they cannot link food energy as information to fixation of RNA-mediated amino acid substitutions in organized genomes. For comparison, all serious scientists have linked what is known about the food energy-dependent fixation of amino acid substitutions to the structure and function of supercoiled DNA, and all serious scientists have linked energy-dependent RNA-mediated cause and effect to all biodiversity via the physiology of pheromone-controlled reproduction.

That fact helps to explain why Richard Feynman referred to some theoretical physicists as examples of human idiocy.

See: Food energy

That suggests Elizabeth Pennisi is a biologically uninformed. She reported: “That’s the nice thing about insects.” If she was not a biologically uninformed science idiot, she would have linked food energy to the physiology of reproduction in all invertebrates and vertebrates. That is how the pheromone-controlled physiology of reproduction is linked from ecological variation to all biodiversity via what is known to all serious scientists about ecological adaptation.
See: Feedback loops link odor and pheromone signaling with reproduction and Olfaction Warps Visual Time Perception

For comparison to the science reporting by Elizabeth Pennisi,  J.A. Parker is the only person besides me, who has reported on this 2017 conference presentation:

See also: All in the (bigger) family by Elizabeth Pennisi with my comment:

The 2015 Society for Integrative and Comparative Biology (SICB) presenters may not recognize how much progress has been made since the 2013 ecological epigenetics symposium. For example, since then authors claimed “…ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.” http://dx.doi.org/10.1038/nature13400

Six months later, other authors traced signaling factors found in vertebrates to the origin of nerve cell centralization via the diffuse nerve net of animals like the sea anemone. http://dx.doi.org/10.1038/ncomms6536 That fact suggests ecological variation is linked to ecological adaptations in morphological and behavioral phenotypes via signaling protein concentrations that differentiate various cell types in body axes and the central nervous system.

Links across species from the epigenetic landscape to the physical landscape of DNA in organized genomes appear to have their origins in the conserved molecular mechanisms of RNA-directed DNA methylation and RNA-mediated protein folding. Two weeks after the publication that refuted ideas about independently evolved neural systems or muscle specification — and perhaps refuted the independent evolution of anything else, SICB presenters linked crustaceans to insects.

Apparently, they’ve learned that the same set of microRNAs controls expression of the genes for rate-limiting enzymes that control the hormone production of different hormones in insects and crustaceans.

Why were they left with any questions about how crustaceans and insects could all be part of one big family? They linked RNA-mediated cell type differentiation to what we described in our section on molecular epigenetics in our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior http://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html

See also: Sex differences in microRNA-mRNA networks: examination of novel epigenetic programming mechanisms in the sexually dimorphic neonatal hypothalamus

Integrating miRNAs and their broad actions on gene function into our conceptualization of the factors directing sexual differentiation of the brain could be a highly informative next step in efforts to understand the complexities behind these processes.

They linked sex differences in microRNAs to the sexual differentiation of all cell types in all living genera that sexually reproduce via microRNA-mRNA networks.
See also: The phylogenetic utility and functional constraint of microRNA flanking sequences

…miRNAs can be employed as both qualitative [9] and quantitative markers, with the latter demonstrated clearly here. Our investigation demonstrates the utility of miRNA sequences as classical phylogenetic markers, and shows this usage is robust to different algorithms of phylogenetic analysis and the analysis of fast-evolving lineages. Such a method provides novel characters for assessing phylogenetic relationships that will be of use in a range of contexts for resolving branches across the tree of life.

See also: Role of olfaction in Octopus vulgaris reproduction

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).

Kohl (2013) is: Nutrient-dependent/pheromone-controlled adaptive evolution: a model (June 14, 2013)

…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, ; Duvarci, Nader, & LeDoux, ; Griggs et al., ; Monahan & Lomvardas, ) in adaptive evolution will certainly be discussed in published works that will follow.

Elekonich and Robinson (2000) cited:  From Fertilization to Adult Sexual Behavior (1996)
At the time of our 1996 Hormones and Behavior review, microRNAs were called pre-mRNAs. See our section on molecular epigenetics:

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.

Social odors are still called pheromones and we linked the food energy-dependent pheromone-controlled physiology of reproduction to all biophysically constrained biodiversity on Earth via sex differences in microRNAs (pre-mRNAs).
The sex differences in microRNAs will soon be linked to sex differences in healthy longevity and to sex differences in diseases in the context of the cell biology game: “Cytosis.” Next, the game “Subatomic” will teach others how to build an atom.
The fact that this invited review linked energy-dependent changes in atoms to ecosystems may still go unnoticed, since the invited review was returned without review.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
But, for God’s sake, see for comparison: 7/25/13
Jay R. Feierman:

“Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding [of] Darwinian biological evolution.”

Do not ignore the fact that Jay R. Feierman has no understanding of how ecological variation must be linked to energy-dependent ecological adaptation via the pheromone-controlled physiology of reproduction.
See also: December 5, 2016

[MODERATOR NOTE: I’m not going to post more from Kohl until he answers the very direct and simple question posed to him by anon, which is whether he (Kohl) believes that RNA splicing can change DNA.]

What I believe about RNA splicing is irrelevant unless someone else links the creation of energy to ATP and the creation of RNA outside the context of energy-dependent alternative splicings of pre-mRNA and the link from energy to the creation of the pre-mRNAs and to energy-dependent biophysical constraints on supercoiled DNA in all living genera.

As Heyn points out, “we still do not fully understand the mechanisms that drive epigenetic variation in populations.”

Natural selection for energy-dependent codon optimality links RNA-directed DNA methylation to all biophysically constrained biodiversity via the pheromone-controlled physiology of reproduction. That fact seems to be missing from this representation of a failed paradigm (neo-Darwinian evolution).
Claims that facts about natural selection and epigenetic variation in populations are not fully understood can be viewed in the context of reports by those who understand the facts about Darwin’s “conditions of life.” They are energy-dependent and RNA-mediated
See for example: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition and Olfaction Warps Visual Time Perception
It has become obvious to all serious scientists that the sense of smell in bacteria must be linked from mRNA stability to our visual perception of mass and energy in the context of natural selection across the time-space continuum via the pheromone-controlled physiology of reproduction. The complexity of that fact may not be understood by biologically uninformed theorists, but no theorist should claim that the mechanisms of food energy-dependent pheromone-controlled biophysically constrained cell type differentiation are not understood by all serious scientists.
Re: …a strong link between population-specific DNA methylation, mRNA levels, and genotypes.
See also: Methylation Variation Documented Between Human Populations

“Our analysis of five worldwide populations revealed a strong correspondence between population-specific DNA methylation, [messenger RNA] levels, and genotypes,” the authors wrote. “The correlation with genetic divergence was stronger for DNA methylation, and, consistent with this, our results suggest stronger local genetic control of population-specific DNA methylation levels than of mRNA expression levels.”

The strong link and/or strong correspondence between food energy-dependent DNA methylation, messenger RNA levels and genotypes is biophysically constained by the pheromone-controlled physiology of reproduction in all livng genera. See for example: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation”

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

Glycolysis and the citric acid cycle appear to provide the free energy for nuclear ATP synthesis and the food-energy-depenent biosynthesis of messenger RNA. If so, all pathology is caused by the virus-driven degradation of messenger RNA, which links mutations but not from ecological variation to ecological adaptations.
See also: Back to Basics: Next-generation sequencing methods and applications (with my emphasis)

…another common NGS application (although one currently more of a research application than a front-line clinical tool) is to examine the transcriptome of a sample—that is, the identity and relative abundance of mRNA transcripts present. Sometimes referred to as “exome sequencing,” this approach is efficient in that it applies resources only to that small portion of the genome which is functionally expressed. Of course, not all significant genetic aberrations occur within coding regions; but by observing levels (or even presence/absence) of transcripts in comparison to reference “normal” conditions, important mutations in non-coding regions such as gene promoters or splice site regulators can be inferred. When such findings are plausibly related to a disease condition, more directed studies to confirm the root cause can then be undertaken as or if needed.

See also: microRNA “exome sequencing Items: 1 to 20 of 55 There is no need to infer that splice site regulators are not food energy-dependent and yet that is what biologically uninformed neo-Darwinian theorists have consistently done with their claims about Mutation-driven evolution. For comparison, all serious scientists are Combating Evolution to Fight Disease.
See also: Global Epigenomic Reconfiguration During Mammalian Brain Development July 4, 2013

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Finally, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain, and that CG demethylation at these hmC-poised loci depends on Tet2 activity.

See also: Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres, which was reported as: “Study of inherited herpes virus finds links to ancient humans” August 30, 2017

We used molecular dating methods to compare, for example, the inherited HHV-6B genomes in five individuals from Sardinia, Orkney and England, and estimated that the most recent common ancestor with the inherited HHV-6B existed 24,500 ±10,600 years ago.

The molecular dating methods are evaluated outside the context of what is known about energy-dependent pheromone-controlled feedback loops, which have been linked from the sense of smell in bacteria to our visual perception of mass and energy in the context of the space-time continuum. But, rather than repeat myself, I will simple support my claims with a link to: Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants, which was reported in January, 2013, as: Past 5,000 years prolific for changes to human genome. The changes can be place into the context of exome sequencing, but not mutation-driven evolution.
The recent origin of most human protein-coding variants can be linked from food energy-dependent changes in exomes that are biophysically constrained by the pheromone-controlled physiology of reproduction in all living genera. The recent origin of the variant can also be linked from the virus-driven degradation of messenger RNA to all pathology.

Of 1.15 million single-nucleotide variants found among more than 15,000 protein-encoding genes, 73% in arose the past 5,000 years, the researchers report. 164,688 of the variants — roughly 14% — were potentially harmful, and of those, 86% arose in the past 5,000 years.

See also: Whole-Exome Sequencing Reveals a Rapid Change in the Frequency of Rare Functional Variants in a Founding Population of Humans (2013)
I repeat:

Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge.Kalevi Kull
amino acid homeostasis

RNA splicing, genetic variation, and disease

More than 600 blog posts on this domain attest to the fact that nutrient energy-dependent RNA-mediated cell type differentiation is the key to healthy longevity in all living genera. Only those who have missed the accurate representations of others who have linked angstroms to ecosystems via the innate immune system, the physiology of reproduction, and supercoiled DNA will continue to place RNA splicing into the context of disease, without acknowledging that RNA splicing is the key to Precision Medicine.

RNA splicing is a primary link between genetic variation and disease

Excerpt:

RNA splicing links genetics to disease

Many genetic variants associated with disease have no apparent effect on any specific protein coding sequence. Li et al. systematically analyzed the effects of DNA variants on the main steps of gene regulation, from the chromatin state through protein function. One-third of expression quantitative train loci (QTLs) are mediated through transcriptional processes, not chromatin. Splice QTLs and expression QTLs are about comparable in their complex disease risk. Posttranscriptional mechanisms therefore play a large role in translating genotype to phenotype.

Abstract:

Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act. We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines (LCLs). About ~65% of expression quantitative trait loci (eQTLs) have primary effects on chromatin, whereas the remaining eQTLs are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing QTLs, most of which have little or no effect on gene-level expression. These splicing QTLs are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.

My comment: MicroRNA flanking sequences link energy-dependent changes in base pairs from hydrogen-atom transfer to the RNA-mediated amino acid substitutions that differentiate the cell types of all living genera. The microRNA/messenger RNA balance links metabolic networks to genetic networks via the innate immune system, the energy-dependent physiology of reproduction and supercoiled DNA. The supercoiled DNA protects all organized genomes from virus-driven energy theft and genomic entropy.
Substitution of ‘expression quantitative trait loci (eQTLs)’ in attempts to link RNA splicing only to disease is disingenuous and borders on the absurd given the publication history of Yoav Gilad and/or Jonathan Pritchard. Both of them should know better than to keep trying to support neo-Darwinian nonsense with wordplay in the context of what they portray as new revelations.
See: Epigenetic modifications are associated with inter-species gene expression variation in primates
See: Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency

Filtering light through a prism to identify tissue type

Bacteria see the light and they adapt

Cyanobacteria use micro-optics to sense light direction

Excerpt:

From the observed dimensions of the spot of 488 nm light focused by Synechocystis cells (Figure 3c) we can estimate that Synechocystis “vision” has an angular resolution (FWHM) of about 21°, essentially limited by light wavelength and the area of the plasma membrane, which is tiny in comparison to an animal retina. However, this resolution is sufficient to incorporate quite complex spatial information into a 360° image of the cell’s surroundings, and our data in Figure 1e indicate that the cell can integrate information from distinct and spatially separated light sources. The directional motile responses of the cells (Figure 1c,d) show a distribution of displacement angles with FWHM ~30°. This is less accurate than the initial imaging of the light source, which suggests an unsurprising degree of spreading and noise during the signal transduction that comes between initial light perception and the response of the motility apparatus.

My comment: The spot of 488 nm light focused by Synechocystis cells links phototaxis and chemotaxis from photosynthesis to all nutrient-dependent RNA-mediated biodiversity. See for instance:

Ultraviolet Absorption Induces Hydrogen-Atom Transfer in G⋅C Watson–Crick DNA Base Pairs in Solution

Introduction:

For over fifty years, the role of interstrand proton or hydrogen-atom transfer in double-helix DNA has been debated as a possible precursor for mutagenesis and carcinogenesis.[1] However, recent theoretical studies postulated that ultrafast interstrand electron-driven proton transfer (EDPT) instead contributes to the prevention of mutagenic photolesions in DNA excited by absorption of solar ultraviolet (UV) radiation. [2]

Excerpt:

At an excitation wavelength of 260 nm,  about 80% of the photons are absorbed by G (see the Supporting Information, Figure S5).[5c,8a] Excitation at the red edge of the absorption spectrum at 290 nm promotes the same photochemistry, but the product bands observed in TEAS and TVAS are weaker because of the lower absorption by G at this wavelength. Excitation of C leads to monomer-like deactivation (see Section S12). Therefore, the discussion in this paper focuses on the results after 260 nm excitation.

My comment: The mechanism that emerges is not links UV light to everything currently know to serious scientists about biophotonics. The mechanism is not placed into the context of anything except a biophysically constrained epigenetic trap. The trap links the speed of light on contact with water from different wavelengths to differences in  hydrogen-atom transfer in double-helix DNA. Hydrogen-atom transfer in DNA base pairs in solution links phototaxis and chemotaxis.
Chemotaxis links the nutrient-dependent physiology of reproduction to all biomass and all biodiversity. The mechanism that emerges can be compared to claims that evolutionary mechanisms link the emergence of life from mutations to increasing organismal complexity via natural selection in the context of ridiculous neo-Darwinian theories that ignored Darwin’s “conditions of life.”
For examples of that ignorance, see these reports on the article (with my emphasis): Cyanobacteria use micro-optics to sense light direction
Excerpt:

…findings are most likely an example of convergent evolution between bacteria and more complex multi-cellular organisms including animals and humans.

My comment: The findings link the speed of light on contact with water from hydrogen-atom transfer in DNA base pairs in solution to nutrient-dependent cell type differentiation via the biophysically constrained chemistry of RNA-mediated protein folding in all living genera.
Dobzhansky’s “light of evolution” can be placed into the context of the amino acid substitutions that differentiate the cell types of chimpanzees and modern humans from the cell types of gorillas.

Like all other serious scientists, Dobzhansky (1973) linked the anti-entropic energy of sunlight to all biodiversity via nutrient-dependent ecological adaptations and the physiology of reproduction.
Pseudoscientists hate the fact that they didn’t realize Dobzhansky was joking about mutations and evolution. They never learned the difference between mutations and amino acid substitutions, and Dobzhansky knew they would not. The jokes played on pseudoscientists by serious scientists may have started with Dobzhansky (1964).
Excerpt:

Cyanobacteria evolved around 2.7 billion years ago and the fact that they are able to produce oxygen and fix carbon dioxide using energy from the sun – photosynthesis – is thought to have caused mass extinctions and the oldest known ice age.

My comment: Phototaxis and chemotaxis are not linked from the sun’s biological energy to photosynthesis and EVOLUTION or EXTINCTION. Chemotaxis and phototaxis are linked from hydrogen-atom transfer in DNA base pairs in solution to nutrient energy-dependent RNA-mediated DNA repair and supercoiled DNA that protects the organized genomes of all living genera from virus-driven entropy.
For a reality check, see these reports on the article (with my emphasis): Cyanobacteria use micro-optics to sense light direction
Excerpt:

They get energy from photosynthesis, meaning they need plenty of light to perform the same chemical reaction as plants.


Previous studies have shown Synechocysti contain photosensors and that they are able to perceive the position of a light source and move towards it – a phenomenon called phototaxis. This study showed how this process works. Bacteria moving towards a light is pictured
Excerpt:

The ability of optical objects to distinguish fine detail is determined by “angular resolution”. In the human eye this is an impressive 0.02 degrees. The team estimate that in Synechocystis it is about 21 degrees.

My comment: Is anyone willing to place the change in the degrees of resolution into the context of beneficial mutations and evolution of human visual acuity and specificity?
Excerpt:

Within minutes, the bacteria grow tiny tentacle-like structures called pili that reach out towards the light source.

My comment: The light source is the energy source for growth of the pili, which occurs within minutes. The light source links metabolic networks from their energy source to genetic networks that control colony growth. Colony growth is biophysically constrained in bacteria via the systems complexity of nutrient-dependent quorum sensing, a function of pheromone-controlled morphological and behavioral phenotypes. The structure and function of the phenotypes extends to humans via biophysically constrained RNA-mediated amino acid substitutions in the context of protein folding chemistry.
Conclusion: The laws of physics and the chemistry of protein folding link the sun’s biological energy to RNA-mediated cell type differentiation via the physiology of nutrient-dependent reproduction, which is controlled by pheromones in species from microbes to humans.
See also: Researchers illuminate ‘dark side’ of the transcriptome

 

A new method to detect, quantify and visualize RNA splicing helps to shed light on the “dark side” of the transcriptome: complex splicing variations that have been known to exist but have not been well studied.

Credit: Illustration conceived by Matthew Gazzara in the Barash lab, Perelman School of Medicine, University of Pennsylvania

My comment: Credit for linking RNA splicing to cell type differentiation in species from microbes to humans should be given to Teresa Binstock, who co-authored our 1996 Hormones and Behavior review and was solely responsible for the section on molecular epigenetics.

See: From Fertilization to Adult Sexual Behavior
Excerpt:

Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.
A potential ramification of epigenetic imprinting and alternative splicing may be occurring in Xq28, a chromosomal region implicated in homosexual orientation (Brook, 1993; Hu, Pattatucci, Patterson, Li, Fulker, Cherny, Kruglyak, and Hamer, 1995; Turner, 1995). Xq28 contains one of the X chromosome’s two pseudoautosomal regions (PARs), adjoins the telomere, and has various means of gene expression control (D’Esposito, Ciccodicola, Gianfrancesco, Esposito, Flagiello, Mazzarella, Schiessinger, and D’Urso (1996). Xq28, therefore, is a chromosomal region that has many of the heterochromatic and telomeric characteristics that participate in sexual determination and behavior in other species.

See also: The Light and Darkness of “Evolution 2.0”
Excerpt: The sun’s biological energy links its anti-entropic virucidal epigenetic effects to RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all living genera.”
See also: Sighted Microbes
Excerpt:

…the study offered an “elegant demonstration” of the mechanism for phototaxis in these bacteria. “Cyanobacteria are 2.7 billion years old…

My comment to “The Scientist”
Their results link phototaxis to chemotaxis. They also link microbial foraging behavior to human metabolic networks and genetic networks via hydrogen-atom transfer in DNA base pair in solutions like sea water and circulating blood.
Facts about light intensity and energy-dependent changes in base pairs link everything known to serious scientists about physics, chemistry, and the conserved molecular mechanisms of biologically-based RNA-mediated cause and effect. The insertion of the spurious claim that the “Cyanobacteria are 2.7 billion years old” should not be placed into the context of what is known to serious scientists about nutrient-dependent biophysically constrained cell type differentiation.
Theorists invite more ridicule when they make such claims and ignore facts like these:

…a family of microbes has persisted essentially unchanged for the past 2.3 billion years—half the age of Earth.

Bacteria that lack a vital protein for growing flagella—tail-like structures that enable the microbes to swim—can attain flagella in as little as four days given enough pressure to evolve…

The facts link energy-dependent base pair substitutions and RNA-mediated amino acid substitutions via the nutrient-dependent pheromone-controlled physiology of reproduction in species from microbes to humans. Only neo-Darwinists and others who are equally biologically uninformed will continue to place what is known about hydrogen-atom transfer in DNA base pairs in solution into the context of evolution without explaining how “evolution” occurs in 4 days or does not occur in 2.3 billion years.

See also: Criticisms of the nutrient-dependent pheromone-controlled evolutionary model

Conclusion:

Based on his writings, both published and unpublished, James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others’ research. It was a mistake to let such a sloppy review through to be published.

My comment: So far as I know, the criticisms of this biologically uninformed undergraduate have not been placed into the context of a model that links hydrogen-atom transfer in DNA base pairs in solution to RNA-mediated amino acid substitutions and cell type differentiation in all individuals of all living genera via the conserved molecular mechanisms I detailed.
The molecular mechanisms link information transfer in microbes to information transfer in the human brain via two epigenetic traps. Others have detailed aspects of the epigenetic trap that traps the anti-entropic virucidal energy of UV light. But, so far as I know, no one else has linked the first epigenetic trap to the de novo creation of odor receptor genes.  The de novo creation of olfactory receptor genes in all vertebrates and invertebrates links the second epigenetic trap to supercoiled DNA during thermodynamic cycles of nutrient-dependent protein folding biosythesis and degradation. The supercoiled DNA protects organized genomes from virus-driven entropy.

That fact has now been placed into the context of RNA-mediated DNA repair, which typically occurs in the absence of nutrient stress and or social stress.
Stress alters pH via virus-driven energy theft. The proliferation of viruses prevents RNA-mediated DNA repair. For example, viruses would prevent repair of damage due to excess infrared light.
 
 

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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.

 
 
 
 
 

human-evolution

Is SUMOylation RNA-directed DNA methylation?

System-wide identification of wild-type SUMO-2 conjugation sites

Excerpt:

SUMOylated proteins were found to be predominantly nuclear, and involved in chromatin remodelling, RNA splicing, transcription and DNA repair. When compared with other SUMOylation studies, a significant overlap with PRISM-identified SUMO sites (48%) and SUMO target proteins (85%) was confirmed. We discovered one-fifth of the PRISM-identified SUMOylated lysines to overlap with ubiquitylation and acetylation.

My comment: SUMOylation appears to be a new name for RNA-directed DNA methylation, which links nutrient-dependent RNA-mediated amino acid substitutions and the physiology of reproduction to cell type differentiation in all cells of all individuals of all genera. The overlap with ubiquitylation and acetylation may be confusing to theorists who have not learned how ecological variation is linked to ecological adaptations via nutrient-dependent DNA repair.
Reported as: Technique to identify system-wide post-translational modification sites

SUMOylation is a reversible post-translational modification (PTM) regulating all nuclear processes. Identification of SUMOylation sites by mass spectrometry (MS) has been hampered by bulky tryptic fragments, which thus far necessitated the use of mutated SUMO.

Authors present a SUMO-specific protease-based methodology which circumvents this problem, dubbed Protease-Reliant Identification of SUMO Modification (PRISM).
PRISM allows for detection of SUMOylated proteins as well as identification of specific sites of SUMOylation while using wild-type SUMO. The method is generic and could be widely applied to study lysine PTMs.
Authors employ PRISM in combination with high-resolution MS to identify SUMOylation sites from HeLa cells under standard growth conditions and in response to heat shock. They identified 751 wild-type SUMOylation sites on endogenous proteins, including 200 dynamic SUMO sites in response to heat shock.

My comment: Some people may not realize that nutrient stress and social stress are linked from the epigenetic landscape to the physical landscape of DNA via RNA-mediated amino acid substitutions that stabilize organized genomes in the context of DNA repair during thermodynamic cycles of protein biosynthesis and degradation.