Caption: Contemporary analyses of cell metabolism have called out three metabolites: ATP, NADH, and acetyl-CoA, as sentinel molecules whose accumulation represent much of the purpose of the catabolic arms of metabolism and then drive many anabolic pathways. Such analyses largely leave out how and why ATP, NADH, and acetyl-CoA (Figure 1) at the molecular level play such central roles. Yet, without those insights into why cells accumulate them and how the enabling properties of these key metabolites power much of cell metabolism, the underlying molecular logic remains mysterious. Four other metabolites, S-adenosylmethionine, carbamoyl phosphate, UDP-glucose, and Δ2-isopentenyl-PP play similar roles in using group transfer chemistry to drive otherwise unfavorable biosynthetic equilibria. This review provides the underlying chemical logic to remind how these seven key molecules function as mobile packets of cellular currencies for phosphoryl transfers (ATP), acyl transfers (acetyl-CoA, carbamoyl-P), methyl transfers (SAM), prenyl transfers (IPP), glucosyl transfers (UDP-glucose), and electron and ADP-ribosyl transfers (NAD(P)H/NAD(P)+) to drive metabolic transformations in and across most primary pathways. The eighth key metabolite is molecular oxygen (O2), thermodynamically activated for reduction by one electron path, leaving it kinetically stable to the vast majority of organic cellular metabolites

Kohl's Laws of Biology (codon-optimality revisited)

Summary: Kohl’s Laws help to explain what was missing from Darwin’s ‘conditions of life.’ Darwin knew nothing about genetics, which means he knew nothing about the epigenetic effects of food odors or pheromones.
Ancient hepatitis B viruses from the Bronze Age to the Medieval period 5/7/18

We provide evidence for the creation of HBV genotype A via recombination, and for a long-term association of modern HBV genotypes with humans, including the discovery of a human genotype that is now extinct. These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone.

The complexity of biophysically constrained viral latency in all living genera refutes all pseudoscientific nonsense touted by neo-Darwinian theorists and Big Bang cosmologists.
See for example: Who were the Neanderthals? 5/5/18

Current evidence from both fossils and DNA suggests that Neanderthal and modern human lineages separated at least 500,000 years ago. Some genetic calibrations place their divergence at about 650,000 years ago.

No serious scientists believe in the nonsense that links genetic calibrations to “divergence” at about 650,000 years ago.
See for comparison: Efficient coding explains the universal law of generalization in human perception 5/11/18
Everything known to serious scientists about natural selection for energy-dependent codon optimality and RNA-mediated DNA repair is placed back into the context of evolution, which is subject to constraints (finding food and reproduction).
See also: Olfaction Warps Visual Time Perception (2017)
The creation of visual perception starts with the energy-dependent creation of enzymes.

High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane 5/11/18

…the enzyme transduces the energy of a proton gradient, generated by the electron transport chain, into the major energy currency of the cell, ATP.

The quantized energy-dependent creation of the enzyme was linked to the creation of ATP and RNA
Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)

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

Natural selection interacts with recombination to shape the evolution of hybrid genomes 5/11/18

Hybridization is an important force in evolution.

That is a ridiculous assumption. Quantized energy is an important force in ecological adaptation. That is a fact.

Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis 5/11/18

Competition between the NAD+ precursors—nuclear NMNAT-1 and cytosolic NMNAT-2…, regulates the balance between nuclear NAD+ synthesis for adipogenic gene regulation and cytosolic NAD+ synthesis used in metabolism.

Every aspect of what is currently know about life on Earth begins with the creation of quantized energy.
Energy efficiency drives the global seasonal distribution of birds 5/7/18
Reported as: A Thermodynamic Answer to Why Birds Migrate 5/7/18

…research makes a forceful argument that energy supply and demand is a driving ecological principle shaping the global structure of biodiversity.”

See also: The histone demethylase KDM6B regulates temperature-dependent sex determination in a turtle species 5/11/18

In this 1996 review, we linked the sex differences in yeasts to sex differences in humans via alternative splicings of pre-mRNAs, which are now called microRNAs. From Fertilization to Adult Sexual Behavior

I linked quantized energy from subatomic particles to all biodiversity via the creation of  microRNAs in:
2014 Preprint: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
2018 Publication: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems

Biological Laws

Biophysical constraints and biological laws appear to link ecological variation to ecological adaptations via conserved molecular mechanisms in all species. For example, nutrient-dependent ecological niche construction leads to pheromone-controlled social niche construction via the nutrient-dependent pheromone-controlled physiology of reproduction. The nutrient-dependent origin of amino acid substitutions in viruses [149-152], which also are manifested in plant and animal interactions, exemplifies a continuum of biological plausibility and ecological validity in the context of Laws of Biology. These Laws of Biology include Kohl’s Laws of Biology, which are so named because the surname of the first author or sole author on each of 7 peer-reviewed publications in the paragraph below is Kohl. The Kohls did not create the Laws of Biology; they merely independently incorporated what is known about them into what appears to be a cohesive series of published works.

Kohl’s Laws of Biology
Life is nutrient-dependent. That is a Biological Law. The ecological origin of all biological laws is apparent 1) in the context of systems biology [87]; 2) in the context of the metabolism of nutrients by microbes [153]; and 3) in the context of how the metabolism of nutrients results in species-specific pheromones that control the physiology of reproduction [154]. Taken together, the systems biology of nutrient metabolism to species-specific pheromones, which control the physiology of reproduction, can be expressed in a summary of Kohl’s Laws of Biology: 1) Life is nutrient-dependent.

See for review [27,155]. The physiology of reproduction is pheromone-controlled. See for review [26]. In the context of nutrient-dependent epigenetically-effected human reproduction, it is clearer that the epigenetic effects of human pheromones integrate neuroendocrinology and behavior [100], which includes the neuroendocrinology of mammalian behavior associated with the development of sexual preferences [156].

Kohl’s Laws help to explain what was missing from Darwin’s ‘conditions of life.’ Darwin knew nothing about genetics, which means he knew nothing about the epigenetic effects of food odors or pheromones.

 

An evolutionary theory killer

A single base change refutes theistic evolution (2)

Announcing publication of a model that links the creation of quantized energy from changes in subatomic particles to biophysically constrained viral latency and sympatric speciation in all living genera.

Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems

This angstroms to ecosystems model of ecological adaptation links nutrient energy-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA/messenger RNA balance and chromosomal rearrangements via the physiology of reproduction in species from microbes to humans.

The invited review of nutritional epigenetics was returned without review and the preprint was posted 4 years ago as:

Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

The only significant change to the manuscript was a change in the title. Atoms to ecosystems became Angstroms to Ecosystems when quantized energy-dependent changes in angstroms were linked to ecological adaptation by what is known to all serious scientists in this 2014 parody.
All About that Base (Meghan Trainor Parody) 12/10/14
Repeat after them (and me): “… every angstrom is dynamic from the 5 prime to the three…”
See also the 2015 publication: Structural diversity of supercoiled DNA

DNA simultaneously exists in a largely inactive B-form with bases tucked in and protected and an active, highly varied structure with exposed bases.

See also: RNA-Guided Human Genome Engineering

George Church and others may have been the first to place the naturally occurring biophysically constrained energy-dependent processes of ecological adaptations into the context of a patent. (It is extremely unusual for anyone to attempt to patent a naturally occurring process.) That explains why there is no patent litigation, which still plagues those who claimed to discover the CRISPR-Cas 9 innate immune system of bacteria, which biophysically constrains viral latency and prevents the degradation of messenger RNA that links the energy-dependent creation of bacteria to the virus-driven creation of archaea and L-forms. All biophysically constrained virus-driven pathology has since been placed back into the context of embryogenesis and the dynamics of energy-dependent gene expression at the level of single-cell resolution as if bacteria somehow evolved into humans.

See:

Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis
Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo
The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution
Chronicling embryos, cell by cell, gene by gene
Reported as: How one cell gives rise to an entire body
See for comparison our section on molecular epigenetics in: From Fertilization to Adult Sexual Behavior (1996)
Watch pseudoscientists continue to make ridiculous claims that fail to link the creation of biophysically constrained thermonuclear energy to autophagy and all biodiversity in the context of the cell biology game Cytosis and most of the forthcoming presentations during Schrödinger at 75 – The Future of Biology – September 2018.
Remember to note that at the end of the parody All About that Base, the research group politely refers to Neil deGrasse Tyson as a big ass (er, a bass). Try not to use the acronym ROTFLMAO in attempts to discuss what is known to all serious scientists with theorists.

5th-6th Sept 2018 Dublin, Ireland

Nutrient-dependent pheromone-controlled feedback loops

Summary: The link from positive selection to one food energy-dependent base pair change and fixation of the mouse-model-to-human-specific EDAR V370A allele in populations on different continents attests to sympatric speciation at every level of examination that refutes the pseudoscientific nonsense of neo-Darwinian mutation-driven evolution.

Reported on 5/3/18 as: SWAT team of immune cells found in mother’s milk 

1)

“There is a feedback loop,” says Yu. It’s known that some immune cells like leucocytes, another white blood cell that fights infection, increase in the milk in response to an infection in the baby.

2)

…the largest immune cell population in breast milk is macrophages, which ILCs are known to direct. Macrophages, which literally means ‘big eaters,” are the largest of the white blood cells and much-better studied than ILCs. They are known for their ability to envelop unwanted items like bacteria, viruses…

Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk 4/23/18

The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers’ milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.

Reported as: Gene linked to breastfeeding may have boosted survival of earliest Americans (4/23/18)

…they carried a genetic mutation—revealed in ancient teeth—that boosted the development of milk ducts in women’s breasts, which may have helped nursing mothers pass more nutrients to their infants.

The obvious link from infant nutrition to healthy longevity was reported in the context of a ridiculous gene-centric theory of species survival. Gene-centric theories are all that pseudoscientists have left. They use them to hold back the scientific progress made by serious scientists like those who reported this:
Feedback loops link odor and pheromone signaling with reproduction (2005)

These results may reflect a strategy wherein GnRH neurons can modify diverse functions in order to coordinate the internal state of the animal and its behavior with reproduction in order to optimize reproductive success.

Caption: Contemporary analyses of cell metabolism have called out three metabolites: ATP, NADH, and acetyl-CoA, as sentinel molecules whose accumulation represent much of the purpose of the catabolic arms of metabolism and then drive many anabolic pathways. Such analyses largely leave out how and why ATP, NADH, and acetyl-CoA (Figure 1) at the molecular level play such central roles. Yet, without those insights into why cells accumulate them and how the enabling properties of these key metabolites power much of cell metabolism, the underlying molecular logic remains mysterious. Four other metabolites, S-adenosylmethionine, carbamoyl phosphate, UDP-glucose, and Δ2-isopentenyl-PP play similar roles in using group transfer chemistry to drive otherwise unfavorable biosynthetic equilibria. This review provides the underlying chemical logic to remind how these seven key molecules function as mobile packets of cellular currencies for phosphoryl transfers (ATP), acyl transfers (acetyl-CoA, carbamoyl-P), methyl transfers (SAM), prenyl transfers (IPP), glucosyl transfers (UDP-glucose), and electron and ADP-ribosyl transfers (NAD(P)H/NAD(P)+) to drive metabolic transformations in and across most primary pathways. The eighth key metabolite is molecular oxygen (O2), thermodynamically activated for reduction by one electron path, leaving it kinetically stable to the vast majority of organic cellular metabolites

Virus-driven cystinosis

A friend asked about nephropathic cystinosis, which is a disease caused by the virus-driven theft of quantized energy. All serious scientists have linked viruses from the degradation of messenger RNA to mutations and all pathology.

Nephropathic cystinosis (NC) is the most frequent cause of Fanconi syndrome (FS) in young children. It will be linked from the virus-driven degradation of messenger RNA to azoospermia and/or progressive neuromuscular degeneration via the conserved molecular mechanisms of RNA-mediated cell type differentiation compared to mechanisms that link viruses to mitochondrial degeneration.

See: Impact of atypical mitochondrial cyclic-AMP level in nephropathic cystinosis

Treatment with the non-hydrolysable cAMP analog 8-Br-cAMP restored mitochondrial potential and corrected mitochondria morphology. Treatment with cysteamine, which reduces the intra-lysosomal cystine, was able to restore mitochondrial cAMP levels, as well as most other abnormal mitochondrial findings.

The link to treatment of the atypical mitochondrial cyclic-AMP level has not yet been detailed because biologically uninformed science idiots have linked mutations to evolution. But see: Combating Evolution to Fight Disease  and the preprint: Reappraising the human mitochondrial DNA recombination dogma 

The facts about human mitochondrial DNA recombination, which link quantized energy and supercoiled DNA to viral latency, played a significant role in North Korea’s denuclearization. But that fact may not be accepted until the article on human mitochondrial DNA recombination is published in a peer-reviewed journal.

It will then take several more years for medical practitioners to learn how to effectively treat all diseases with food energy-dependent changes in the microRNA/messenger RNA balance.

See for details: Energy as information and constrained endogenous RNA interference

Until all pseudoscientists accept the facts, there will be many others who try to profit from misinformation or from partial information about virus-driven pathology. Most people will not read my reviews and journal articles like this:  MicroRNA Regulation of RNA Virus Replication and Pathogenesis

Instead, most are willing to accept the claims of others who have “blown the whistle” on vaccines more than two decades after I first published this review of RNA-mediated cell type differentiation in a peer-reviewed journal. From Fertilization to Adult Sexual Behavior

See:  Doctor Blows Whistle on Flu Shot: ‘It’s Designed to Spread Cancer’

Treague confirmed that this year’s flu strain, that has left thousands of citizens dead, was caused by the vaccines itself, saying: “I believe that the low effective rate of the vaccine this year is due to the mutations that the virus made in the processing of the vaccine itself.

Claims that viruses make mutations are the claims of fools who do not know that the virus-driven degradation of messenger RNA has been linked from mutations to all pathology in more than 72,000 published works.

See: microRNA

Biology to a Physicist

Abiogenesis vs microRNA biogenesis

Summary: The pseudoscientific nonsense about abiogenesis that has been touted by Karo Michaelian and others like him has caused the unnecessary suffering and premature death of millions to billions of people by placing the pathogenic consequences of deregulated miRNAs into the context of ridiculous theories.
See for comparison: Structural diversity of supercoiled DNA and the parody from the same research group:
——————————-
Abiogenesis (2017)
Microscopic dissipative structuring and proliferation at the origin of life (Oct 13, 2017)

Some fundamental molecules of life are suggested to have been formed, proliferated, and evolved through photochemical microscopic dissipative structuring and autocatalytic proliferation under the UV-C/UV-B solar environment prevalent at Earth’s surface throughout the Archean. Evidence is given in the numerous salient characteristics of these, including their strong absorption in this spectral region and their rapid non-radiative excited state decay through inherent conical intersections. The examples of the dissipative structuring and dissipative proliferation of the purines and of single strand DNA are given. UV-C and UV-B-induced stationary state isomerizations and tautomerizations are shown to be crucial to the formation of the purines from hydrogen cyanide in an aqueous environment under UV-C light, while UV-C induced phosphorylation of nucleosides and denaturing of double helix RNA and DNA are similarly important to the production and proliferation of single strand DNA. This thermodynamic dissipation perspective provides a physical-chemical foundation for understanding the origin and evolution of life.

The suggestion is ridiculous. No serious scientist would claim that some fundamental molecules of life formed, proliferated, and evolved in the context of thermodynamic dissipation after the UV-C induced phosphorylation of nucleosides and denaturing of double helix RNA and DNA.
The functional structure of supercoiled DNA is energy-dependent.
All serious scientists start with the link from the sun’s anti-entropic virucidal energy on contact with water to the creation of ATP synthase; the creation of microRNAs; the creation of all other enzymes; the creation of all receptors; the creation of all hormones. That’s how serious scientists link microRNA biogenesis to all biophysically constrained food energy-dependent pheromone-controlled morphological and behavioral diversity on Earth.
MicroRNA biogenesis (2018)

The tipping point of 72,000 indexed published works that mention microRNAs was reached on 4/18/18
See: microRNA
Example: Arthropod viruses and small RNAs (2013)

Understanding the role of small RNAs in arthropod host-virus molecular interactions will facilitate manipulation of these pathways for both management of arthropod pests of agricultural and medical importance, and for protection of beneficial arthropods such as honey bees and shrimp. This review highlights recent research on the role of small RNAs in arthropod host-virus interactions with reference to other host-pathogen systems.

Example: MicroRNAs as mediators of insect host-pathogen interactions and immunity (2014)

In this review, we will discuss the latest developments in regards to the role of microRNA in insect host-pathogen interactions and provide some insights into this rapidly developing area of research.

Example: miRNA regulation of innate immunity (2018)

MicroRNAs (miRNAs) are small noncoding RNA and are pivotal posttranscriptional regulators of both innate and adaptive immunity. They act by regulating the expression of multiple immune genes, thus, are the important elements to the complex immune regulatory network. Deregulated expression of specific miRNAs can lead to potential autoimmunity, immune tolerance, hyper-inflammatory phenotype, and cancer initiation and progression. In this review, we discuss the contributory pathways and mechanisms by which several miRNAs influence the development of innate immunity and fine-tune immune response. Moreover, we discuss the consequence of deregulated miRNAs and their pathogenic implications.

The pseudoscientific nonsense touted by Karo Michaelian and others like him has caused the unnecessary suffering and premature death of millions to billions of people by placing the pathogenic consequences of deregulated miRNAs into the context of ridiculous theories.
See for comparison: Structural diversity of supercoiled DNA and the parody from the same research group:

See also: Michaelian K
and Retraction: Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication (Nov 23, 2017)
The life’s works of all those who have ever touted their ridiculous claims about abiogenesis can now be placed into the context of the eternal significance of microRNAs. The energy dependent de novo creation of microRNA flanking sequences has repeatedly been linked from the physiology of pheromone-controlled reproduction to biophysically constrained viral latency and sympatric speciation in all living genera.
See: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)

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

See also: Long-range coherence and energy storage in biological systems (1968)
See also: Cytosis (for ages 10+)

Players take turns placing workers on available organelles within a human cell in order to collect resources (such as Carbohydrates or ATP!) or take actions (such as purchasing Cell Component cards or translating mRNA into Proteins!)

Players use their resources to build Enzymes, Hormones, and Hormone Receptors and also to help detoxify the cell – all of which score health points. The player with the most health points at the end of the game wins!

See for comparison: DNA Denaturing through UV-C Photon Dissipation: A Possible Route to Archean Non-enzymatic Replication (2014)

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

On January 15, 2016 John Hewitt commented:  You have just described the founding principle and thermodynamic function of life
On April 17, 2018, I commented on the ridiculous claim this so-called science journalist made because he blocked me from seeing his tweets a few months ago.

Alternative splicing of pre-mRNA

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

Psychophysical Laws and the Superorganism  (open access)

…superorganisms may also exhibit such behaviour, suggesting that these laws arise from fundamental mechanisms of information processing and decision-making.

Reported on Jun 14, 2013 as Nutrient-dependent/pheromone-controlled adaptive evolution: a model

and again on: Mar 27, 2018 as Honeybees may unlock the secrets of how the human brain works

The study… found that superorganisms may obey the same laws as the human brain.

Kohl’s “Laws of Biology” and Darwin’s “conditions of life” can now be compared in the context of how quantized energy as information was linked to biodiversity in this invited review of nutritional epigenetics: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (2014)
See also for review:

Functional and evolutionary aspects of chemoreceptors (2012)
Sensory receptors—design principles revisited (2013)
Moving forward: See: Tuning Insect Odorant Receptors (in press)

Among the insect olfactory receptors the odorant receptors (ORs) evolved in parallel to the onset of insect flight. A special property of this receptor type is the capability to adjust sensitivity of odor detection according to previous odor contacts. This article presents a current view on regulatory processes affecting the performance of ORs and proposes a model of mechanisms contributing to OR sensitization.

Future attempts to place psychophysical laws of biology back into the context of neo-Darwinian pseudoscientific nonsense will continue to pit ridiculous theories about experience-dependent tuning of odor receptors against everything known to serious scientists about RNA-mediated biophysically constrained viral latency and supercoiled DNA.
See for comparison:
Bacterial self-organization: co-enhancement of complexification and adaptability in a dynamic environment (2003)
Seeking the foundations of cognition in bacteria: From Schrödinger’s negative entropy to latent information (2006)
Learning from Bacteria about Natural Information Processing (2009)
Stability of the hybrid epithelial/mesenchymal phenotype (2016)

Epithelial-to-Mesenchymal Transition (EMT) and its reverse – Mesenchymal to Epithelial Transition (MET) – are hallmarks of cellular plasticity during embryonic development and cancer metastasis.

Cellular plasticity was linked from the energy-dependent pheromone-controlled physiology of reproduction in bacteria to our visual perception of energy and mass in the context of the space-time continuum.
See: Olfaction Warps Visual Time Perception (2017)

The behavioral gain produced by a congruent relative to an incongruent odor is accompanied by elevated neural oscillatory power around the object’s flicker frequency in the right temporal region ~150-300 ms after object onset, and is not mediated by visual awareness. In parallel, odors bias the subjective duration of visual objects without affecting one’s temporal sensitivity.

See also: Schrödinger at 75 – The Future of Biology – September 2018
The scheduled speakers will undoubtedly link the Science Behind the Game “Cytosis” to the Science Behind the Game “Subatomic” via everything known to all serious scientists based on Schrodinger’s prescient claims in What is Life? (1944).
See also: What is life when it is not protected from virus driven entropy

The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair. In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans. Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry. Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.

See also: Energy as information and constrained endogenous RNA interference

Feedback loops link quantized energy as information to biophysically constrained RNA-mediated protein folding chemistry. Light induced energy-dependent changes link angstroms to ecosystems from classical physics to chemistry/chirality and to molecular epigenetics/autophagy. The National Microbiome Initiative links microbial quorum sensing to the physiology of reproduction via endogenous RNA interference and chromosomal rearrangements. The rearrangements link energy-dependent fixed amino acid substitutions to the Precision Medicine Initiative via genome wide inferences of natural selection.

This detailed representation of energy-dependent natural selection for codon optimality links biologically- based cause and effect from G protein-coupled receptors to RNA-mediated amino acid substitutions and the functional structure of supercoiled DNA. Energy-dependent polycombic ecological adaptations are manifested in supercoiled DNA. Chromosomal inheritance links the adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes. For contrast, virus-driven energy theft is the link from messenger RNA degradation to negative supercoiling, constraint breaking mutations, and hecatombic evolution. The viral hecatomb links transgenerational epigenetic inheritance from archaea to Zika virus-damaged DNA, which typically is repaired by endogenous RNA interference and fixation of RNA-mediated amino acid substitutions in organized genomes.

See also “Outer Membrane Vesicles” microRNA (4 of 4 from a 3/27/18 search)

How Our Other Genome Controls Our Epi-Genome (2016)

Secretable Small RNAs via Outer Membrane Vesicles in Periodontal Pathogens (2017)

Tiny RNAs and their voyage via extracellular vesicles: Secretion of bacterial small RNA and eukaryotic microRNA (2017)

Molecular Paths Linking Metabolic Diseases, Gut Microbiota Dysbiosis and Enterobacteria Infections (2018)

See also: March 28, 2018 sponsored by System Biosciences
Webinar: Deciphering how bacteria utilize outer membrane vesicles (OMVs) to communicate and infect
 
Outer Membrane Vesicles (OMVs) are membrane vesicles secreted by bacteria that contain DNA, RNA, proteins and endotoxins. Bacteria respond to many environmental factors by secreting specifically-enriched OMVs, which makes these bacteria more fit for their environment. For example, OMVs may be enriched with invasion proteins at the host-pathogen interface. OMVs have recently gained attention as a novel mechanism for transmission of molecular information within bacteria as well as between bacteria and mammalian cells. Owing to their similarities to well-studied extracellular vesicles (EVs), OMVs are being utilized by researchers to study host-bacterial interactions in pathogenesis, cancer therapy, host immune response modulation, as well as bacterial OMV engineering for use as vaccines. This webinar will give an overview of recent studies on the role of OMVs in host-pathogen interactions and discuss their bioengineering potential as vehicles for cargo delivery. We will also introduce our new & revolutionary ExoBacteria™ OMV Isolation Kit, which will enable you to achieve faster, simpler & better OMV isolation.
Learn how OMVs are being utilized by researchers to study host-bacterial interactions in pathogenesis, cancer therapy, host immune response modulation, as well as bacterial OMV engineering for use as vaccines.
Witzhany2018

Polymaths and paradigm shifts: From Asimov to Bear (5)

Summary: Neil deGrasse Tyson and Lawrence Krauss are among those who have continued to substitute pseudoscientific nonsense for legitimate facts, which is what Hawking did in every book he ever wrote, and each time he made a spurious claim based on his abilities as a conniving theorist whose works still have not been confirmed-and-validated. Now that he is gone, others may proclaim the greatness of his intellect and lionize the magnitude of his influence because they also are biologically uninformed science idiots. Like Hawking, they refused to learn how Darwin’s “conditions of life” have been linked to the prevention of all virus-driven pathology.

Renowned Physicist Stephen Hawking Dies

The comments by Neil deGrasse Tyson and Lawrence Krauss can be linked to this discussion: 2013 Isaac Asimov Memorial Debate: The Existence of Nothing and to the 2017 representation of biomolecules in On the Difference between Physics and Biology: Logical Branching and Biomolecules.
The food energy-dependent pheromone-controlled creation of the biomolecules will be discussed during Schrödinger at 75 – The Future of Biology – September 2018 after the virus-driven degradation of messenger RNA and all pathology is discussed during Evolution – Genetic Novelty/Genomic Variations by RNA Networks and Viruses
For comparison, Stephen Hawking gained fame by collaborating with Roger Penrose and with George FR Ellis, who co-authored The Large Scale Structure of Space-Time.
In the forward to the reprint edition of What is Life?, Roger Penrose wrote

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? (8 August 1991)

In the cell biology game Cytosis, anyone age 10+ can learn that the creation of energy as ATP protects all organized genomes from the virus-driven degradation of messenger RNA, which all serious scientists since Schrödinger have linked from mutations to all pathology.That’s all you need to know about Roger Penrose.
George FR Ellis is the co-author of On the Difference between Physics and Biology: Logical Branching and Biomolecules. He helped to link the food energy-dependent creation of microRNAs to biophysically constrained viral latency, but is determined to undermine the works of other serious scientists with his use of the ambiguous term biomolecules.
Taken together, Stephen Hawking, Roger Penrose, and George FR Ellis have done more than most to bastardize Darwin’s claims about the need to start with food energy-dependent  “conditions of life.” Their unproven ideas from physics should never have been substituted for experimental evidence.
The evidence links the premise of the game “Subatomic” from what is known about particle physics to biophysically constrained viral latency and healthy longevity via this claim, which was made by Schrödinger.

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

Neil deGrasse Tyson and Lawrence Krauss are among those who have continued to substitute pseudoscientific nonsense for legitimate facts, which is what Hawking did in every book he ever wrote, and each time he made a spurious claim based on his abilities as a conniving theorist whose works still have not been confirmed-and-validated. Now that he is gone, others may proclaim the greatness of his intellect and lionize the magnitude of his influence because they also are biologically uninformed science idiots. Like Hawking, they refused to learn how Darwin’s “conditions of life” have been linked to the prevention of all virus-driven pathology.
See: DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis
Reported as: Here’s How Viruses Inactivate the Immune System, Causing Cancer

“Ultimately viruses are causing these tumors to form and are further manipulating the immune system to allow tumors to keep growing,” Kuss-Duerkop says. “But these same mechanisms may be key in combating tumors with immune-based therapies or in keeping cancer from developing in the first place.”

If not for the bastardization of Darwin’s claims by theorists, Kuss-Duerkop and others like her probably would have learned that sunlight is the source of energy for the growth of food that links food energy to the pheromone-controlled physiology of reproduction in species from microbes to humans. The energy links changes in the microRNA/messenger RNA balance from virus-driven energy theft to all unnecessary suffering and premature death.The fact that Stephen Hawking suffered throughout his life with a neurodegenerative disease may be fitting in the context of his ignorance.
The 4 Scientific Lessons Stephen Hawking Never Learned

  1. We have a tendency, when we turn people into heroes, to lionize their achievements and ignore their failings, but to do so cheats humanity out of recognizing all the facets of a complicated character.
  2. May we memorialize him in the best way possible: by increasing our own knowledge and curiosity to live better lives.

Until then, see: Prominent Neuroscientist Fired by Columbia, HHMI
This is the first clear indicator of how the Trump administration will drain the academic swamp.
Jessell is the serior author of: Activity Regulates the Incidence of Heteronymous Sensory-Motor Connections

The positioning of newly born neurons is a tightly regulated process that is critical for the assembly of the nervous system. In the spinal cord, nuclear organization of motor neurons into pools is an elaborated morphogenetic feature at the basis of the wiring of spinal sensory motor circuits (Sürmeli et al., 2011, Hinckley et al., 2015, Bikoff et al., 2016). The events controlling motor neuron positioning during development have yet to be clearly defined.

The activity is food energy-dependent and RNA-mediated in the context of sensory input and the physiology of pheromone-controlled reproduction, which biophysically constrains viral latency in species from microbes to humans.
See for example: Meet the creature that can regenerate its brain and resist cancer.(video) The superimposed electron cloud over the yin yang symbol of Chinese philosophy and medicine is a clear representation of the complexity. If neuroscientists cannot link energy-dependent changes in electrons to ecosystems in all living genera, they will be dismissed and replaced with serious scientists.
For example, the facts about regenerating the brain and resisting cancer suggests Jessell’s termination occurred due to his ongoing failure to link the virus-driven degradation of messenger RNA to loss of motor control in all neurodegenerative diseases.
See for comparison: “Blood Music” (1985) by Greg Bear, who presciently linked energy-dependent changes in the microRNA/messenger RNA balance to the creation of an advanced human species via naturally occurring biophysically constrained viral latency.
See also: Actor Steven Kearney reads excerpts from Greg Bear’s 1985 novel Blood Music.

Bear was one of the first sci-fi authors to delve deep into the possibilities of synthetic biology. In this section, a biologist named Michael Bernard is infected with a killer virus that has wiped out most of North America. The virus is made up of tiny biological computers called “noocytes,” where were intended to improve the human body — giving it routine maintenance and maximizing human potential. Instead, it wiped out most of North America.

Remember, without the food energy-dependent pheromone-controlled RNA-mediated DNA repair that biophysically constrains viral latency:
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5th-6th Sept 2018 Dublin, Ireland

From photons to the proton motive force (1)

Conclusion: If you would like to learn how to link quantized energy-dependent changes in atoms to ecosystems in all living genera via the physiology of reproduction, join others age 10+ who will be playing this game in September 2018.
Fly’s Blood-Brain Barrier Has Circadian Rhythms

“the anatomic characteristics of insect and vertebrate BBB structures are quite distinct.”

The molecular mechanisms are conserved.
My comment to The Scientist:

Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels (1990)

The levels of complexity have since been placed into the context of how energy-dependent changes in the microRNA/messenger RNA balance link atoms to ecosystems in all living genera via feedback loops.

For instance, see: Feedback loops link odor and pheromone signaling with reproduction

When theorists fail to start with energy-dependent changes they are forced to use de Vries 1902 definition of mutation in attempts to link the virus-driven theft of quantized energy to evolution. Two forthcoming conferences will place that pseudoscientific nonsense into its proper perspective.

Evolution – Genetic Novelty/Genomic Variations by RNA Networks and Viruses

Schrödinger at 75 – The Future of Biology – September 2018

See also:  Here Comes Single-Cell Optogenetics

.. two-photon excitation with computer-generated holography (a way to precisely sculpt light in 3D) allow light to be focused tightly enough  to hit one cell.

OLYMPUS experiment sheds light on structure of protons

…most of the time, only one of the photons has high energy….

Permeability transition in human mitochondria persists in the absence of peripheral stalk subunits of ATP synthase

Production of ATP depends on the oxidation of energy-rich compounds to produce a chemical potential difference for hydrogen ions, the proton motive force (pmf), across the inner mitochondrial membrane (IMM).

Researchers who have not linked differences in the energy of photons to the proton motive force are not likely to be among those who are presenting in September: Schrödinger at 75 – The Future of Biology
See for comparison: Subatomic

Subatomic is a deck building game where players are competing to build a number of available Elements, which score them points. Each player starts with the same small deck of cards that consist of Proton, Neutron, and Electron Cards. They use these cards to build upon their current Atom (by playing these cards face-up as Subatomic Particles) in an attempt to construct one of the available Element Cards. Or players may use their hand of cards to purchase more powerful cards for later use (by playing them in combinations of face-down as energy and face-up as Subatomic Particles!) Subatomic introduces a unique variation on deck building with a highly accurate chemistry theme, with the ultimate goal of building Elements to score points, but allowing many varying types of strategies.

If you would like to learn how to link quantized energy-dependent changes in atoms to ecosystems in all living genera via the physiology of reproduction, join others age 10+ who will be playing this game in September 2018.

Caption: Contemporary analyses of cell metabolism have called out three metabolites: ATP, NADH, and acetyl-CoA, as sentinel molecules whose accumulation represent much of the purpose of the catabolic arms of metabolism and then drive many anabolic pathways. Such analyses largely leave out how and why ATP, NADH, and acetyl-CoA (Figure 1) at the molecular level play such central roles. Yet, without those insights into why cells accumulate them and how the enabling properties of these key metabolites power much of cell metabolism, the underlying molecular logic remains mysterious. Four other metabolites, S-adenosylmethionine, carbamoyl phosphate, UDP-glucose, and Δ2-isopentenyl-PP play similar roles in using group transfer chemistry to drive otherwise unfavorable biosynthetic equilibria. This review provides the underlying chemical logic to remind how these seven key molecules function as mobile packets of cellular currencies for phosphoryl transfers (ATP), acyl transfers (acetyl-CoA, carbamoyl-P), methyl transfers (SAM), prenyl transfers (IPP), glucosyl transfers (UDP-glucose), and electron and ADP-ribosyl transfers (NAD(P)H/NAD(P)+) to drive metabolic transformations in and across most primary pathways. The eighth key metabolite is molecular oxygen (O2), thermodynamically activated for reduction by one electron path, leaving it kinetically stable to the vast majority of organic cellular metabolites

Ecological adaptation: A new definition of heredity (3)

Excerpt:
Moving forward: Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex

…these data suggest that a subset of the identified novel miRNAs may contribute to the pathophysiology of numerous diseases, laying the groundwork for future studies to elucidate the functional connections of miRNAs to the numerous diseases associated with sequence variants within non-coding regions of the MHC.

OMCD: OncoMir Cancer Database

Dysregulation of miRNAs is commonly observed in cancers and it largely cancer dependent.

The virus-driven theft of quantized energy as information has been linked from changes in the microRNA/messenger RNA balance to all pathology. That fact replaces the circular logic that links cancer-dependent dysregulation of miRNAs to cancer.  Simply put, the proliferation of viruses cause cancer. The proliferation of viruses is energy-dependent in the context of established links from atoms to ecosystems in all living genera.
See: Subatomic: An Atom Building Board Game

A deck-building game where particle physics & chemistry collide! Use quarks to build subatomic particles & particles to build Atoms!

See also: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements.

Moving forward: Novel and Haplotype Specific MicroRNAs Encoded by the Major Histocompatibility Complex

…these data suggest that a subset of the identified novel miRNAs may contribute to the pathophysiology of numerous diseases, laying the groundwork for future studies to elucidate the functional connections of miRNAs to the numerous diseases associated with sequence variants within non-coding regions of the MHC.

My “Disqus” comment (and nearly 2000 others): Gene expression is energy-dependent, RNA-mediated, and biophysically constrained.
See: FUS Regulates Activity of MicroRNA-Mediated Gene Silencing.

MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression.

MicroRNAs do not create themselves.
See also:  Energy as information and constrained endogenous RNA interference
8 of my 9 most recent comments to Disqus have been removed.
See for comparison: Incomplete host immunity favors the evolution of virulence in an emergent pathogen
Reported as: In nature, an imperfect immune system drives the evolution of deadly pathogens

…birds that eat at feeders are more likely to be infected with the disease, which causes red, swollen eyes and often blindness that results in death.

…lower virulence strains could be their own worst enemies, creating a population of hosts that are resistant to them but not the higher virulence strains that remain.

By removing my Disqus comments, the moderators limit discussion of the facts about virus-driven energy theft, which links mutations to all pathology.  That allows the biased reporting on preprints that continue to try to support the ridiculous concept of neo-Darwinian evolution.
It also prevents the realization of goals by serious scientists who have linked the biogenic creation of uranium ores to the prevention of radiation sickness via microRNA therapy. See, for examples: miRNA-mediated therapies
A miRNA-145/TGF-beta1 Negative Feedback Loop Regulates the Cancer-Associated Fibroblast Phenotype

…miR-145 is a key regulator of the CAF phenotype, acting in a negative feedback loop to dampen acquisition of myofibroblastic traits, a key feature of CAF associated with poor disease outcome.

See also: Microhomology-assisted scarless genome editing in human iPSCs

Gene-edited induced pluripotent stem cells (iPSCs) provide relevant isogenic human disease models in patient-specific or healthy genetic backgrounds. Towards this end, gene targeting using antibiotic selection along with engineered point mutations remains a reliable method to enrich edited cells. Nevertheless, integrated selection markers obstruct scarless transgene-free gene editing. Here, we present a method for scarless selection marker excision using engineered microhomology-mediated end joining (MMEJ). By overlapping the homology arms of standard donor vectors, short tandem microhomologies are generated flanking the selection marker. Unique CRISPR-Cas9 protospacer sequences nested between the selection marker and engineered microhomologies are cleaved after gene targeting, engaging MMEJ and scarless excision. Moreover, when point mutations are positioned unilaterally within engineered microhomologies, both mutant and normal isogenic clones are derived simultaneously. The utility and fidelity of our method is demonstrated in human iPSCs by editing the X-linked HPRT1 locus and biallelic modification of the autosomal APRT locus, eliciting disease-relevant metabolic phenotypes.

Reported as: Gene Editing Is Now Precise Enough to Modify a Single Letter of DNA

To make these very precise edits, an SNP modification is first inserted alongside a fluorescent reporter gene that helps researchers to identify modified cells. The researchers engineered a duplicate DNA sequence known as a microhomology (hence the technique’s name) on each side of the fluorescent gene, targeting sites for CRISPR to go in and cut DNA. The researchers were then able to use a DNA repair system known as microhomology-mediated end joining (MMEJ) to remove the fluorescent gene. That left only the single-base edit, in the form of an SNP, behind.

See also: Inhibition of the Host Translation Shutoff Response by Herpes Simplex Virus 1 Triggers Nuclear Envelope-Derived Autophagy
Nuclear envelope-derived autophagy (NEDA) appears to be a cellular stress response, which is triggered late during HSV-1 infection. An energy-dependent single nucleotide repeat (SNR) might compensate for the viral alteration of the macroautophagic response. At this level of hydrogen-atom energy transfer in DNA base pairs in solution, the link to supercoiled DNA and viral latency becomes increasingly important.
Theorists are angry because they have been left behind. They know very little about what is important. That was expected by all serious scientists, especially those who have accumulated decades of testing experience while working in medical laboratories.
See for example: Applications of ligation-mediated PCR

Using a molecular energy source (which differs depending on the enzyme source organism), DNA ligase reforms the missing covalent bond and the strand is whole again. Two aspects of this are critical:

The nick to be repaired occurs on a single strand but in the context of a double-stranded molecule.
The bases of the nicked strand, and particularly those directly flanking the nick site, must be properly base-paired to the opposite (un-nicked) strand.

It’s not hard to imagine why this is: the base pairing is required to hold the two parts (sugar 3′ -OH and the next phosphate) in place for the ligase enzyme active site to catalyze joining them. If either one of these isn’t base-paired down and is flopping about with thermal motion, the reaction geometry doesn’t occur, and no new bond can be made.

Biologically uninformed theorists cannot even speak the same language. They do not start with a molecular energy source for base pairing and microRNA-mediated amino acid substitutions that differentiate all cell types. Instead, mutations are linked to increasing organismal complexity via the magic of evolution.

5th-6th Sept 2018 Dublin, Ireland

Anti-entropic sunlight: Schrödinger’s Creationist Secret? (5)

Anti-entropic sunlight: Schrödinger’s Creationist Secret? (3)


The list of those scheduled to present has changed. Michael Rosbash has been added. John E. Walker is not scheduled, which suggests that everyone else already knows that the creation of the sun’s anti-entropic virucidal energy is the link from the creation of ATP to the creation of RNA and all biophysically constrained viral latency via feedback loops and the physiology of reproduction.
Rosbash, as all serious scientists know,  started with energy-dependent changes in cycles of RNA biosynthesis. Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels (1990). Pseudoscientists failed to link the energy from feedback to biophysically constrained viral latency.
But see: Permeability transition in human mitochondria persists in the absence of peripheral stalk subunits of ATP synthase

Production of ATP depends on the oxidation of energy-rich compounds to produce a chemical potential difference for hydrogen ions, the proton motive force (pmf), across the inner mitochondrial membrane (IMM).

Other serious scientists have consistently linked photophosphorylation from oxidative phosphorylation to all biodiversity via the physiology of pheromone-controlled reproduction in species from soil bacteria to humans
Speakers (new copy-protected list)
Speakers (old list)
See also: Viral Resistance Project
The differences in innate immunity and ecological adaptation are obviously nutrient energy-dependent and transgenerationally inherited in the context of the epigenetically-effected physiology of pheromone-controlled reproduction and the affects of hormones on behavior. For instance, pheromones biophysically constrain viral latency via the fixation of amino acid substitutions.
See for comparison: Evolution – Genetic Novelty/Genomic Variations by RNA Networks and Viruses
There are several neo-Darwinian theorists who are scheduled to present, which means they may be ready to accept the ridicule from serious scientists.
See for example: A universal trend of amino acid gain and loss in protein evolution

Amino acid composition of proteins varies substantially between taxa and, thus, can evolve.

See also: Why I got rid of my friends
Some of my former friends kept dumping their garbage about evolution on others in the same way that I. King Jordan and Eugene Koonin did it with their comment about the evolution of the amino acid composition of proteins. See for comparison: All About that Base (Meghan Trainor Parody) 12/10/14 and Energy as information and constrained endogenous RNA interference 2/15/17
Help others who are Combating Evolution to Fight Disease