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.

Cytosis

Host-derived creation of all pathology (2 of 2)

Summary: All serious scientists know that all epigenetic diversity is food energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction.

See for comparison: 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.”

A Bacterial Messenger Molecule Extends Healthspan

…indole, a molecule produced by commensal bacteria, extends “healthspan” not only in mice but in the nematode worm Caenorhabditis elegans and in fruit flies as well. Taking away the bacterial production of the molecule ablated these anti-aging gains.

Does anyone need to repeatedly be reminded that food energy is required for the production of any molecule associated with nutrient-dependent pheromone-controlled anti-aging gains? The epigenetically effected gains are consistently manifested in the survival of species via the physiology of reproduction.
The food energy-dependent production of indole is the obvious link from nutrient-dependent pheromone-controlled feedback loops to biophysically constrained viral latency and ecological adaptation in all living genera. Testing for indole is used to determine the ability of an organism to split (deaminate) the amino acid tryptophan.  Indole contributes to fecal odor and it is a chemical messenger that has been indirectly or directly included in detailed representations of biologically-based pheromone-controlled energy-dependent cause and effect like these.
See: Feedback loops link odor and pheromone signaling with reproduction (2005)
There is a model for that! See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model (2013)
The food energy-dependent pheromone-controlled physiology of reproduction in species from microbes to humans biophysically constrains the virus-driven degradation of messenger RNA. That fact links constraint-breaking mutations to all pathology in all living genera. A test protocol established that fact in the context of this book chapter, which links the test for indole to differences in the microRNA/messenger RNA balance in humans.

For example, the test protocol links the creation of energy as information to all biodiversity via the physiology of reproduction and links the virus-driven degradation of messenger RNA to all pathology. The complexity of the testing can be reduced via the focus on the energy-dependent creation of microRNAs.

See the abstract:

Disease research and treatment development have turned to the impact and utility of microRNA. The dynamic and highly specific expression of these molecular regulators can be used to predict and monitor disease progression as well as therapeutic treatment efficacy and safety…

MicroRNAs are identified and monitored through the use of locked nucleic acid (LNA)™-based detection probes. The LNA™ technology enhances the sensitivity and specificity of target binding for short, highly similar, microRNA sequences, which help to differentiate cell types in the context of everything known to serious scientists about how to link physics and chemistry from molecular epigenetics to all biodiversity via fixation of RNA-mediated amino acid substitutions.

The availability of this testing was predicted in: Energy as information and constrained endogenous RNA interference (7-min video)

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: The phylogenetic utility and functional constraint of microRNA flanking sequences
See also: From Fertilization to Adult Sexual Behavior (1996)
See for comparison: Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption (2017)

There is no such thing as transgenerational epigenetic inheritance of morphological or behavioral phenotypes outside the context of feedback loops that link food odors from the metabolism to pheromones and biophysically constrained viral latency. The consumption of choline by bacteria links food energy to protection from viral latency via the test for indole. The virus-driven theft of quantized energy can be linked from reduced amount of choline that link viruses in the bacteria to their ability to overwhelm the immune system. The effects of virus-driven energy theft link the CRISPR-Cas9 technology of gene-editing to DNA repair via exogenous RNA-interference because energy-dependent endogenous RNA-interference protects all organized genomes from virus-driven entropy.
Corporate America is not willing to tell the truth about that. You will probably suffer unnecessarily and die prematurely because the goal of every corporation is to make more money.

See also: Americans Are Dying Younger, Saving Corporations Billions

Absent a war or an epidemic, it’s unusual and alarming for life expectancies in developed countries to stop improving, let alone to worsen. “Mortality is sort of the tip of the iceberg,” says Laudan Aron, a demographer and senior fellow at the Urban Institute. “It really is a reflection of a lot of underlying conditions of life.”

Darwin’s “conditions of life” were food energy-dependent. Serious scientists have since learned that all “conditions of life” also are fixed in the organized genomes of all living genera via the physiology of reproduction. Without the link from ecological variation to ecological adaptation via fixation of amino acid substitutions in supercoiled DNA, natural selection for energy-dependent codon optimality would link mutations to evolution instead of linking mutations to all pathology.

Instead, the reality of cell type differentiation was reported as: Microbes compete for nutrients, affect metabolism, development in mice

 …new research that shows mice that harbor high levels of microbes that eat choline are deprived of this essential nutrient.
 

I placed that fact into the context of this excerpt from my 2013 review: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Sex-dependent production of a mouse ‘chemosignal’ with incentive salience appears to have arisen de novo via coincident adaptive evolution that involves an obvious two-step synergy between commensal bacteria and a sex-dependent liver enzyme that metabolizes the nutrient chemical choline.

The result of this synergy is (1) a liver enzyme that oxidizes trimethylamine to (2) an odor that causes (3) species-specific behaviors. Thus, the complex systems that biology required to get from nutrient acquisition and nutrient metabolism to species-specific odor-controlled behavior is exemplified by adaptive evolution of an attractive odor to mice that repels rats (see for review Li et al., 2013).

Addendum: Fish odor syndrome is the link from the virus-driven theft of quantized energy. The odor links ecological variation to failed ecological adaptation and all pathology when there is insufficient food energy. Any scientist who does not already know that based on the facts known to every medical laboratory scientist is an example of “human idiocy” (Feynman) or a biologically uninformed science idiot (Kohl).

Serious scientists have begun to effectively use energy-dependent microRNAs to the prevention of all virus-driven pathology. That fact is being reported in the context of gene therapy using ‘junk DNA’  at a time when all serious scientists realize there is no such thing as ‘junk DNA.’

Gene therapy using ‘junk DNA’ could lower risk for heart disease

The LeXis gene belongs to a unique group of genes that until recently were considered “junk DNA” because scientists believed they served little purpose. However, evidence from the human genome project led to the discovery that genes like LeXis are actually active. The study of these genes, now referred to as long noncoding ribonucleic acids, or lncRNAs, is a rapidly evolving area in biology.

Long Noncoding RNA Facilitated Gene Therapy Reduces Atherosclerosis in a Murine Model of Familial Hypercholesterolemia

Long noncoding (lnc) RNAs form the vast majority of transcriptionally active regions and are arbitrary defined as transcripts >200 bps that biochemically resemble mRNA and yet do not template protein.2

Diet and drug-induced changes in LeXis link energy as information to liver X receptor activation of genes via the “promoter binding of RNA-binding proteins.” That fact supports the claim that a transcriptional coactivator for genetically predisposed cholesterol biosynthesis in the mouse liver links promoters, enhancers, quantitative trait loci, et al., to the transciptional coactivator referred to as “Rally” without mention of energy-dependent changes in the microRNA/messenger RNA balance.
If you believe that the long noncoding ribonucleic acids (RNAs) are genes, you may be convinced that mutations in RNA are the same as mutations in genes. But mutations are the cause of all pathology. Linking mutations in RNA to pathology outside the  context of energy-dependent healthy longevity allows others with no expertise in laboratory testing to continue to believe that mutation-driven evolution is the link from natural selection to the origin of new species. That belief is probably common among others who believe that the Universe itself may be conscious.

See for comparison: Scientists Now Believe the Universe Itself May Be Conscious

For the behavior of subatomic particles and the systems they constitute promises to be fully explained by physics and the other physical sciences.

 See for comparison: Subatomic

Subatomic is a deck building game where players are competing to build a number of available atoms. Each player starts with the same small deck of cards that consist of Proton Cards, Neutron Cards, Electron Cards and Energy Cards and a beginning hand limit of 5 cards. They use these cards to build upon their current Atom, in an attempt to construct one of the available Atom Cards, and/or use their hand of cards to purchase more powerful atom building cards for later use, or increase their hand limit. The deck building cards are simple and clean, but offer a number of interesting combinations. Players also have an energy track that allows them to store energy, which introduces a “push-their-luck” type of mechanic enabling players to pay energy to shuffle through their deck quicker, or to offset the cost of more powerful deck building cards.

We don’t need a conscious mind to measure or look. With or without us, the Universe is always looking
 

The question arises: “Who needs this kind of nonsense?” Does anyone at any level of examination believe that “the Universe is always looking” is the best representation of what we can expect from a “Conscious Universe?”

See for comparison: 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!

 Chromogenic In Situ Hybridization Methods for microRNA Biomarker Monitoring of Drug Safety and Efficacy was reported on the Exiqon FB page. Exiqon is a biotechnology company that specializes in RNA products and services. I recommend that they purchase this domain (RNA-mediated.com) in an attempt to promote their products, which obviously link energy-dependent healthy longevity to all biodiversity and also link virus-driven energy theft to all pathology via changes in the microRNA/messenger RNA balance.

See also: ‘Chromatin modifiers and remodellers in DNA repair and signalling’ The fact that food energy as information must be linked from ecological variation to ecological adaptation via the pheromone-controlled physiology of reproduction in all living genera appears to be the focus of this Theme issue.

But wait: Here is one of the articles from  the Theme issue:

Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing

Nucleosome remodelling (NR) regulates transcription in an ATP-dependent manner, and influences gene expression required for development and cellular functions, including those involved in anti-cancer and anti-ageing processes. ATP-utilizing chromatin assembly and remodelling factor (ACF) and Brahma-associated factor (BAF) complexes, belonging to the ISWI and SWI/SNF families, respectively, are involved in various types of DNA repair.

See for comparison, from 1964: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation”

McEwen et al., knew that “The synthesis of RNA in isolated thymus nuclei is ATP dependent.” That statement of fact was the beginning of the abstract from 1964. When he told me my model could not be validated unless I started with energy-dependent gene activation in gonadotropin releasing hormone (GnRH) neurons, I had no reason to doubt him. When I learned that Robert L. Moss had already linked pheromones to energy-dependent gene activation in GnRH neurons, I continued to pursue top-down causation as if it was energy-dependent — because it obviously is energy-dependent.

I never considered that my model of food energy-dependent pheromone-controlled biophysically constrained gene activation would not be accepted by theorists. See for comparison:

Induction of FOS immunoreactivity in central accessory olfactory structures of the female rat following exposure to conspecific males (1992)

See also: Gonadotropin releasing hormone and human sexual behavior (1991) in Neuropeptides and Psychiatric Disorders (1991)

Is anyone else interested in linking the facts from our 1996 Hormones and Behavior review From Fertilization to Adult Sexual Behavior or from any other works I have published before Nutrient-dependent/pheromone-controlled adaptive evolution: a model (2013) to what is known about all biophysically constrained biologically- based cause and effect?
If so, see: Worldwide patterns of human epigenetic variation

We found that population-specific DNA methylation mirrors genetic variation, and has greater local genetic control than mRNA levels. We estimated the rate of epigenetic divergence between populations, which indicates far greater evolutionary stability of DNA methylation in humans than has been observed in plants. This study provides a deeper understanding of worldwide patterns of human epigenetic diversity…

All serious scientists know that all epigenetic diversity is food energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction.
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.
See for comparison: Quantum Biology: An Introduction (video) by Philip Ball and Quantum common sense

To turn quantum to classical, we don’t need a conscious mind to measure or look; we just need an environment full of stuff. With or without us, the Universe is always looking.

See also these restricted and unrestricted articles: ARTICLES 

Alternative splicing of pre-mRNA

Half truths support theories without facts

How to lie by telling the truth

Excerpt:

People… trot out half-truths, in full expectation and knowledge that they will create a false impression. And then, when others act on the false impression, the “truth-telling liars” can sit back and pretend that they aren’t liars. They get the benefit of lying, without any damage to their precious self-image.

My comment: It is more difficult for others to determine who benefits from half truths when more than one individual or research group fails to link biologically-based cause and effect. When two groups use the same model organism, but no model, they are not likely to report the truth about biologically-based cause and effect, .

Craig Venter’s Synthetic Genome 3.0 Evokes Classic Experiments

Venter’s group seems to have run into a common problem with attempts to explain nutrient-dependent RNA-mediated cell type differentiation. They try to keep it constrained by evolution, which leads them to use terms like mutation instead of amino acid substitution. See their references for a link to work on viruses that should have led to recognition of the difference between the amino acid substitutions the cause changes in virulence and the mutations, which are biophysically constrained.
Dobzhansky (1973) used “amino acid” and “mutation” in the context of claims that we know can be supported only with experimental evidence that links atoms to ecosystems in all living genera via the physiology of reproduction. The nutrient-dependent physiology of reproduction is biophysically constrained by the innate immune system, which is the RNA-mediated link to supercoiled DNA. Supercoiled DNA protects all organized genomes from virus-driven entropy.
See also: A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans
Excerpt: 

Synthesis of dsRNA is required for replication of RNA viruses and transposons, and therefore dsRNA constitutes a ‘‘danger signal’’ in many organisms, including humans, where it activates the interferon response (Wang et al., 2002). As in worms, RNAi is important for anti-viral defense (Lu et al., 2005); it is possible that the mere ‘‘sensing’’ of dsRNA (for example, by pattern recognition mechanisms [Melo and Ruvkun, 2012]) is sufficient to activate the RNAi system, regardless of whether the dsRNA molecule is further processed to trigger an RNAi response or not.

My comment: Nutrient-dependent pheromone-controlled RNA-mediated cell type differentiation in the nematodes, C. elegans and P. pacificus clearly shows how the innate immune system links metabolic networks and genetic networks to supercoiled DNA that protects the organized genome of all living genera from virus-driven entropy.
See: System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes
Reported as: The neurobiological consequence of predating or grazing
Excerpt:

While C. elegans feeds exclusively on bacteria, P. pacificus is able to switch its behaviour to prey on other worms if bacterial food gets scarce.

See also: Distinct Circuits for the Formation and Retrieval of an Imprinted Olfactory Memory
Excerpt:

Classical olfactory imprinting drives approach behavior, such as homing to the natal stream for salmon (Nevitt et al., 1994), bonding between mammals and their young (Lorenz, 1935), kin recognition in zebrafish (Gerlach et al., 2008), and acceptance of imprinted foods (Wilson and Sullivan, 1994). Positive imprinting to odors experienced early in life also has been described in C. elegans, although little is known about its mechanisms beyond a requirement for the orphan G protein-coupled receptor SRA-11 in AIY neurons (Remy and Hobert, 2005).

My comment: The nutrient-dependent de novo creation of G protein-coupled receptors links classical olfactory imprinting to supercoiled DNA via everything known about RNA-mediated cell type differentiation, which is controlled by the physiology of reproduction. Examples link all invertebrates to all vertebrates via the conserved molecular mechanisms we detailed in our section on molecular epigenetics in the Hormones and Behavior review.  From Fertilization to Adult Sexual Behavior
Excerpt:

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.

Rechavi’s group recognizes the fact that RNA-mediated events are important for anti-viral defense. Bargmann’s group ignores the fact that virus-driven energy theft links perturbed protein folding chemistry to mutations and gene loss.
But her group does not link what nematodes eat to nutrient-dependent biodiversity via the de novo creation of olfactory receptors, which are G protein-coupled receptors. Instead, Bargmann wins another award.  McGovern Institute awards prize to neurogeneticist Cori Bargmann
Excerpt:

Building on her olfaction work, Bargmann has also studied the neural basis of social behavior, which in worms is strongly regulated by chemical cues. In one set of papers, for example, she identified a single neuron that integrates information from multiple chemical cues including food, oxygen and pheromones, to control the expression of social behavior.

My comment: Her award-winning works fail to link virus-driven energy theft from perturbed protein folding chemistry to mutations and gene loss.  Perhaps no one else but me will ever know that she could have linked the works from Rechavi’s group from what is known about how olfaction and the immune system enable the fine-tuning of metabolic networks and genetic networks, which is linked from the physiology of reproduction to supercoiled DNA.
She could have stopped the threat of the Zika virus and other viruses by acknowledging the fact that supercoiled DNA protects all organized genomes in all living genera from virus-driven entropy. Instead, her works will continue to be well-funded.
Others will be forced to increase their efforts and focus on Combating Evolution to Fight Disease.