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

EDAR V370A and sympatric speciation

Nick Lane and others like him refuse to reappraise their human mitochondrial DNA recombination dogma. All serious scientists know where the energy for recombination comes from. But, in his latest video clip, he touts the same unsubstantiated theoretical pseudoscientific nonsense.

See the: Aeon Video:

Life on earth – from mushrooms to humans and everything in between – seems enormously diverse. At the cellular level, however, almost all complex lifeforms are surprisingly similar. Why life is this way, though, remains mysterious. In this Aeon interview, the UK biochemist and author Nick Lane discusses his research on the connection between energy and genes, which, he hypothesises, made possible the radical transformation from single-celled organisms to complex life about 4 billion years ago.

See for comparison: Reappraising the human mitochondrial DNA recombination dogma

I’ve asked the authors: Are you prepared to address the comments that you might receive from people like Nick Lane in the context of “peer review?” How will you respond to those who do not accept the fact that the creation of ATP synthase and the creation of ATP must be linked to the creation of RNA and biophysically constrained viral latency in the context of SNPs and fixation of amino acid substitutions? What can be done when biologically uninformed theorists continue to link anything except biophysically constrained viral latency to all biodiversity?

I ask because there are still too many examples of human idiocy that are being considered outside the context of facts about energy-dependent RNA-mediated cell type differentiation.

See: Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant

See the claims about the selection of the EDAR variant placed back into the context of evolution.

Field-deployable viral diagnostics using CRISPR-Cas13

…we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.

The relevant energy-dependent single-nucleotide polymorphisms clearly protect all living genera from the clinically relevant viral single-nucleotide polymorphisms. The viral single-nucleotide polymorphisms link the virus-driven degradation of messenger RNA to all pathology via what is known to all serious scientists about the energy-dependent creation of the innate immune system in species from bacteria to humans.

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

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

If any experimental evidence of biophysically constrained viral latency supported the claim about positive selection 20,000 y ago, it could be linked to Nick Lane’s claims about how chimeras and electricity allowed a sterile planet to give way to complex life 4 billion years ago. Since there is no experimental evidence to support his ridiculous theories, intelligent people may want to continue to link environmental selection from food selection to the physiology of reproduction and fixation of RNA-mediated amino acid substitutions such as V370A that stabilize the organized genomes of all species on Earth.

5th-6th Sept 2018 Dublin, Ireland

2018 March for Science vs microRNAs (2)

The anti-entropic virucidal energy of sunlight on contact with water has been linked from the creation of ATP synthase to the creation of ATP and to the creation of RNA. Energy-dependent RNA-mediated DNA repair has been linked to biophysically constrained viral latency via the creation of microRNAs and feedback loops linked to the food energy-dependent microRNA-mediated physiology of reproduction. The physiology of energy-dependent pheromone-controlled reproduction biophysically constrains viral latency in the context of the creation of the innate immune system and autophagy.
See: miRNA regulation of innate immunity (4/14/18)
None of the facts about the energy-dependent creation of the microRNAs or the microRNA-mediated regulation of innate immunity are included in: The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation (4/17/18)
The regulatory landscape that drive memory cytotoxic T lymphocyte formation might just as well be framed in the context of magic or in the equally ridiculous context of gene-centric theories.
See this report: Your immune system holds the line against repeat invaders, thanks to this molecule

Runx3’s control of T cell differentiation is important because when our bodies fight off viruses and cancers—and our T cells burst into action—the vast majority tend to become effector cells. These effector cells are short-lived and do not persist once the infection resolves.

The control of all cell type differentiation is energy-dependent, RNA-mediated and biophysically constrained by the physiology of reproduction in all living genera. The cell biology game “Cytosis” for ages 10+ teaches the facts that link Schrödinger (1944) What is Life? to Schrödinger at 75 – The Future of Biology – September 2018
In 1944, Schrödinger wrote:

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

See for comparison (this gene-centric pseudoscientific nonsense):
– Part I: FINDING THE CODE (Run time: 12:10
The race to sequence the human genome was also billed as a race to end disease. What happened?

– Part II: FIXING THE CODE (Run time: 13:07)
CRISPR — and the promise and pain of gene therapy that came before it. 

– Part III: SELLING THE CODE (Run time: 10:55)
Genetic testing has moved out of the labs into the masses. But even with your genome in hand, what can you believe?
The gene-centric pseudoscientific nonsense does not start with the creation of energy.  But every aspect of biophysically constrained life on Earth starts with the quantized energy-dependent creation of microRNAs. The epigenetically effected energy-dependent microRNA-mediated creation of the “Code” and the microRNA-mediated fixing of the “Code” is missing from the claims of biologically uninformed theorists who link beneficial mutations from natural selection to evolution. They have sold their gene-centric pseudoscientific nonsense to many people.
For example, some gene-centric biologically uninformed theorists share beliefs about abiogenesis for comparison to quantized energy-dependent microRNA biogenesis in articles like this: DNA Denaturing through UV-C Photon Dissipation: A Possible Route to Archean Non-enzymatic Replication
Conclusion:

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.

See John Hewitt’s comment: You have just described the founding principle and thermodynamic function of life
In a classic example of human idiocy (See Feynman: food energy), biologically uninformed science idiots linked the dissipation of quantized energy to the origin of life via abiogenesis. The creation of biophysically constrained biophotonicaly based life in the context of the energy-dependent creation of microRNAs was reported in the context of photon dissipation and entropy as: Abiogenesis: A Theory on The Origins of Life

By now, we all know how evolution works. At least, most of us have a basic understanding of how it functions. At its most fundamental level, evolution is change over time. More specifically, it is changes within a biological population over successive generations.

Ultimately, biological complexity is one of the most important things to come out of evolution. Things started simple. Then genes mutated, cells interacted with their environment, mitochondria stopped being living organisms and started being part of a cell and—Tada—complex life.

A conflict arose between John Hewitt’s accurate representations of biophysically constrained life in The vibrational theory of olfaction for the win  and few months ago, Hewitt blocked me from seeing his tweets.

The same kinds of amino acid substitutions that control the separations and interactions of side chains in fluorescent proteins also play an essential role in tuning the proposed mechanism for vibration detection—inelastic electron tunneling. Life literally runs on electron tunneling through the respiratory chain complexes in mitochondria. These proteins employ complicated mechanisms including esoteric-soundings things like electron bifurcation and confurcation to pump protons across the mitochondrial inner membrane. When mitochondria go dark, cells can often continue to run for a short while, but it is only in the dim glow of the battery backup metabolism.

Here are some links to the reason for the conflict. Simply put, John Hewitt put everything known to serious scientists about energy-dependent microRNA biogenesis back into the context of abiogenesis.
2005 MicroRNA biogenesis: coordinated cropping and dicing
2015 Dysregulation of microRNA biogenesis and gene silencing in cancer
2015 RNA-mediated degradation of microRNAs: A widespread viral strategy?
Claims about abiogenesis exemplify what Richard Feynman referred to as human idiocy. So does John Hewitt and anyone else who believes in Michaelian’s pseudoscientific nonsense.
See other examples of Michaelian’s pseudoscientific nonsense and human idiocy by clicking here.
The energy-dependent creation of one domain of life links the physiology of reproduction in bacteria to biophysically constrained viral latency. The virus-driven degradation of messenger RNA is linked to the destruction of all life on Earth.
The degradation of messenger RNA links mutations to the creation of archaea and L-forms via entropy, which clearly links the weakening of the proton motive force to the elimination of the cell wall in L-forms (the last remnants of creation).
See also: Past 5,000 years prolific for changes to human genome
If you cannot link the miRNA regulation of innate immunity to all extant biodiversity via the physiology of pheromone-controlled reproduction and fixation of energy-dependent microRNA-mediated amino acid substitutions, thank a biologically uniformed science idiot.
 

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

Odor activation of ATP (1)

Serious scientists start from the levels of biological organization required to link atoms to ecosystems in all living genera. They must link what is known about quantized energy to subatomic particles. See for example slide number 6 from: Human Pheromones: Linking Neuroendocrinology and Ethology (revisited)  (2010)
Subatomic particles must be the link to the creation of ATP synthase, which must link the creation of ATP to the creation of RNA.
See McEwen et al., (1964) 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.

Odor activation of ATP completes the pathway that links the anti-entropic virucidal energy of sunlight to all quantized energy-dependent biophysically constrained RNA biosynthesis and viral latency. Viral latency links the physiology of pheromone-controlled reproduction to healthy longevity in species from microbes to other mammals and to humans.
See: ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium

In sum, our results show that TRPM5-MCs dose-dependently respond to ATP and odor mixture and may release ACh to potentiate endocytosis in SCs, possibly promoting xenobiotic removal from the MOE. These results have unveiled cholinergic regulation in the MOE coordinating SC activity important for protecting the epithelium and airway. That TRPM5-MCs are sensitive to ATP and express multiple purinergic receptors also suggests an additional mechanism for the MOE to act in a concerted fashion with the rest of the respiratory mucosa to defend against xenobiotic insults. Taken together, these novel results of cholinergic paracrine signaling in the MOE increase our understanding of how the MOE maintains its function and prevents chemical-induced damage.

Simply put, the MOE links food odors and other sensory input to the pheromone-constrained viral latency presciently reported in:
Pheromonal regulation of genetic processes: research on the house mouse (Mus musculus L.) (1994)

A study of the influence of pheromone stressor(s) on proliferating germ and somatic cells was performed on laboratory lines of house mouse in the context of the physiological hypothesis of mutation process, proposed by M.E. Lobashev in 1947. Data from experiments are presented, and results obtained during last 10-15 years are discussed. The adaptive role of cytogenetic and other observed pheromonal effects is considered. The possible existence of interorganism systems of genetic regulation is discussed, the search for and study of which may help in more complete understanding of the regularities of functioning of genetic material.

See for earlier and later publications in the English Language:
Gonadotropin releasing hormone and human sexual behavior (1991) in Neuropeptides and Psychiatric Disorders
Induction of FOS immunoreactivity in central accessory olfactory structures of the female rat following exposure to conspecific males (1992)

The findings indicate that exposure of female rats to reproductively relevant stimuli resulted in induction of fos-like immunoreactivity within the AOS and that both olfactory and nonolfactory cues probably contributed to this effect.

Influence of male rats on the luteinizing hormone-releasing hormone neuronal system in female rats: role of the vomeronasal organ (1993)

Olfactory information processed by the vomeronasal system is reported to influence reproductive functions in a variety of mammals. The present studies were designed to determine if male-associated cues affect the luteinizing hormone-releasing hormone (LHRH) neuronal system…

Vomeronasal organ-mediated induction of fos in the central accessory olfactory pathways in repetitively mated female rats (1994)

Removal of the VNO significantly reduced the enhancement of lordosis and the induction of fos immunoreactivity in luteinizing hormone-releasing hormone (LHRH) neurons in ovariectomized estrogen-primed rats.

Pheromones (2010) in Stress Science: Neuroendocrinology
See for comparison: The Expanding Landscape of Alternative Splicing Variation in Human Populations

Alternative splicing variation has been linked from the food energy-dependent pheromone-controlled physiology of reproduction to all extant biodiversity in species from microbes to humans.

Biologically uninformed theorists still think in terms of evolution.
See: The human microbiome in evolution
Most of them have no idea how to link subatomic particles to biophysically constrained viral latency.

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 instead: Cytosis: A Cell Biology Board Game

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

See for comparison: Genetic variation in a human odorant receptor alters odour perception
Gene-centric theories about altered odor perception have failed to link energy-dependent top-down causation to biophysically constrained viral latency and healthy longevity. The ridiculous theories will continue to cause unnecessary suffering and premature death until pseudoscientists admit that they learned virtually nothing about RNA-mediated cell type differentiation during the past 20 years of scientific progress.
See for example, anything published by Leslie B. Vosshall
Specifically, Laying a controversial smell theory to rest (2015)

Some have pointed out that it is a waste of time to expend effort to refute a controversial theory that has few advocates, and that attention should be turned instead toward how smell works (, ).

This is how smell works: ATP and Odor Mixture Activate TRPM5-Expressing Microvillous Cells and Potentially Induce Acetylcholine Release to Enhance Supporting Cell Endocytosis in Mouse Main Olfactory Epithelium