Posts tagged: Sickle cell disease

 How Can Physics Underlie the Mind? Top-Down Causation in the Human Context by George Ellis (p. 404)

Repeated thousands of times over geological timescales, it is this relentless repetition of the top-down process of adaptive selection [29] that gives Darwinian evolution its enormous power.

Theorists never seem to ask questions about where the enormous power came from or where it goes when organisms die. They seem to think that relentless repetition of biophysically constrained energy-dependent protein biosynthesis and degradation automagically emerged so that organisms could begin to evolve via adaptive selection in the context of Darwinian evolution, which has no power source outside the context of Darwin’s “conditions of life.”

See for comparison: Who rules the waves? – Viruses might just be bit players in the drama of the seas. Then again, they could be major actors (1996)

Most consider viruses to be a legion of cripples, sterilised by ultraviolet radiation and rendered impotent by hosts that are largely immune to their threat. But a few researchers take the opposite view. And if they turn out to be right, viruses could radically alter the balance of life in the oceans, ripping away huge parts of the food web that supports whales, sea birds and the fisheries on which many people rely.

See also: Virus-mediated archaeal hecatomb in the deep seafloor (2016)

We show here for the first time the crucial role of viruses in controlling archaeal dynamics and therefore the functioning of deep-sea ecosystems, and suggest that virus-archaea interactions play a central role in global biogeochemical cycles.

The nonsense about the non-existant power of evolution touted by George Ellis appears to have led to this report. Nonlinear self-adapting wave patterns  by David Kessler and Herbert Levine

We propose a new type of traveling wave pattern, one that can adapt to the size of physical system in which it is embedded.

They propose that an emergent wave pattern of light energy self-adapts to the size of a biophysically constrained system. Their proposal must link energy as information to all cell type differentiation and all biodiversity via the physiology of reproduction.

Their proposal is not consistent with anything known to serious scientists, or even to George Ellis, about top-down causation. Serious scientists have linked the anti-entropic virucidal energy of sunlight from ecological variation to ecological adaptation. This has been done in the context of links from angstroms to ecosystems in all living genera See for example: Structural diversity of supercoiled DNA.

Six decades after the elucidation of its double helical structure, DNA continues to surprise us by revealing new information. Our cryo-ET, biochemical, and computational studies show the astounding versatility and dynamism of DNA depending on the degree of supercoiling. DNA simultaneously exists in a largely inactive B-form with bases tucked in and protected and an active, highly varied structure with exposed bases. Our data provide relative comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes.

Simply put, DNA supercoiling is energy-dependent. The energy does not create itself, which suggests it is not likely to self-adapt to any biophysical constraints. Indeed, the fact that energy as information in cell types is biophysically constrained suggests that the energy is epigenetically trapped and/or released as is required for metabolic networks to be linked to genetic networks. Simply put, there are likely to be thermodynamic cycles of energy transfer that link femotosecond blasts of ultraviolet light to DNA damage repair.

See: UV-Induced Charge Transfer States in DNA Promote Sequence Selective Self-Repair

See also: Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo

Although sequence-specific association of co-regulated genomic loci is appealing, random interactions between loci with shared chromatin properties might be an equally effective way of modulating transcription levels.

Sequence-specific association of co-regulated genomic loci is energy-dependent. Serious scientists have showed that none of the interactions between loci with shared chromatin properties randomly occur. For example, two epigenetic traps link the sun’s anti-entropic virucidal energy from the energy-dependent interactions to the de novo creation of G protein-coupled receptors (GPCRs). The epigenetically-effected de novo creation of the GPCRs links chemotaxis and phototaxis to all morphological and behavioral phenotypes via the physiology of reproduction and transgenerational epigenetic inheritance of supercoiled DNA.

For comparison, the proposal from Nonlinear self-adapting wave patterns  was framed outside the context of how thermodynamics must be linked to chemotaxis and/or phototaxis. The authors told us that an adiabatic process apprears to occur without the transfer of heat or matter. In an adiabatic process, the energy transfer between a thermodynamic system and its surroundings works in only one direction. The automagically created energy exists and gets the work done without the transfer of heat or matter.
That unidirectional process seems to exclude everything known about biophotonics, which provides the conceptual basis for a theory that extends the first law of thermodynamics to energy-dependent RNA-mediated cell type differentiation via what is known about protein folding chemistry. By pretending that self-adapting wave patterns exist outside the context of biophotonics, and by pretending that the author’s proposal fits into the context of a key concept in thermodynamics that is not linked to chemotaxis or phototaxis, we are led to believe that some chemical and physical processes occur so rapidly that they may be conveniently described by the “adiabatic approximation.” That means there is not enough time for the transfer of energy as information or as heat to go to or from the system.

But what about the energy as information carried by the light? Roger Penrose presciently addressed claims about light in non-technical terms when he asked: “How often do we still hear that quantum effects can have little relevance in the study of biology, or even that we eat food in order to gain energy?” (Roger Penrose 8 August 1991) See the forward to the reprint of Schrodinger’s: What is Life?

New type of traveling wave pattern could contain biological coordinates is the report on the most recent findings that link the traveling energy to biological coordinates in the context of the biophysically constrained chemistry of RNA-mediated protein folding. The most recent finding can be placed into the context of what serious scientists already know.

See for example: MicroRNA-based regulation of epithelial–hybrid–mesenchymal fate determination (2013), which also was co-authored by Herbert Levine. (I noticed that Eshel Ben-Jacob is the senior author because I am more familiar with Eshel’s works.)

See also: Stability of the hybrid epithelial/mesenchymal phenotype (2016) Two of the co-authors are Eshel Ben-Jacob and Herbert Levine, but Eshel Ben-Jacob died prior to publication.

See: In Memory of Professor Eshel Ben Jacob

Note: There is no indication of whether Herbert Levine attended and I do not know if he knows anything about RNA-mediated cell type stability. I do not want to speculate about this. I will mention that all the claims made by Eshel Ben-Jacob about energy-dependent natural information processing and biophysically constrained cell type differentiation have been placed into the context of accurate information about RNA-mediated biologically-based cause and effect.

See for example:Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management 6/13/16 Reported by Journals and Conferences on Genetics & Molecular Biology on 12/15/16

Biochemically, SCD occurs due to a non- conservative substitution of a #polarglutamate (Glu) by non-polar valine (Val) in an invariant region, the sixth position of Hb-β chain-subunit (GAG/GTG; Glu (E) Val (V); rs334). Replacement of this single non-polar amino acid ‘valine’ results in a biochemical difference that leads to formation of a sticky patch on the surface of the β-chains. The sticky patch is observed on both the #oxygenated (“R” Form) and deoxygenated (“T” Form) of HbS. This distort folding and binding pattern of the Hb molecule, due to altered properties. Other known mechanism of #polymerization of Hb in SCD involves nucleation, which is due to the aggregation of HbS molecules.

They linked one nutrient energy-dependent RNA-mediated amino acid substitution to the stability of a hemoglobin variant that protects some human populations from malaria. It is one of ~1264 human hemoglobin variants that exemplify how ecological variation is linked from biophysically constrained energy-dependent RNA-mediated protein folding chemistry to ecological adaptations.

That fact can be placed into the context of Dobzansky’s claims in 1964 and in his 1973 expose of the evolution industry. He showed that the cure for all pathology must begin from the understanding of energy-dependent hydrogen-atom transfer in DNA base pairs in solution. Energy-dependent changes in base pairs link the sun’s quantized anti-entropic virucidal energy from autophagy to single nucleotide polymorphisms and fixation of RNA-mediated amino acid substitutions. The fixation of the substitutions helps to ensure healthy longevity in all living genera via the physiology of reproduction and supercoiled DNA, which prevents the virus-driven entropy of all organized genomes.
Dobzhansky 1964

Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.

Dobzhansky 1973

…the socalled alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.

See also: Combating Evolution to Fight Disease 9/13/14

Darwin probably anticipated the insemination of population genetics that led to the bastardization of his detailed observations in the “Modern Synthesis.” He politely insisted that ‘conditions of life’ be considered before natural selection.

There are two ‘conditions of life.’ It is nutrient-dependent and pheromone-controlled. Rosenberg and Queitsch now note the work with Dobzhansky’s rarely acknowledged claim: “I am a creationist and an evolutionist.” They also declare the need for “Deep understanding of the mechanisms that generate variation at the molecular level…”

Deep understanding of the ‘conditions of life’ does not come from theory.

Problems with the “modern synthesis” now lead us back to the facts about biologically-based cause and effect that Darwin and Dobzhansky approached with humility, which are the same biological facts that evolutionists approached with ignorance about behavioral affects and the arrogance that accompanies that ignorance. Rosenberg and Queitsch echo the sentiments of those who have been subjected to academic suppression.

Clearly, however, “nothing in evolution makes sense except in the light of biology” is not an exaggeration. It is a common sense statement about the biologically plausible genesis of functional cell types. Population genetics and evolutionary theories abandoned the biophysical constraints of ecological variation and the physiology of reproduction, which enable epigenetically-effected nutrient-dependent pheromone-controlled receptor-mediated ecological adaptations and species diversity via the complexities of protein folding and niche construction.

It’s time for biophysicists to tell theorists and pathologists how to differentiate between theories about the genesis of different cell types and the biological facts about the nutrient-dependent pheromone-controlled ecological adaptations that enable the genesis of different cell types in individuals of different species. Simply put, it’s time to stop trying to explain ecological adaptations in the context of mutations and evolution.

See also: Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans
Conclusion:

Substitutions in other lineages have proven to be highly informative for understanding deleterious effects in the contemporary human genome; among numerous features that have been considered, the strongest predictors of the pathogenicity of a mutation are species divergence features [83–86]. Nevertheless, methods used to predict the deleteriousness of a mutation at a site typically rely on a single summary of how variable a site is across the phylogenetic tree. Our analysis suggests that the location of a mutation on the evolutionary tree is informative of how deleterious the same mutation is for humans. It is our hope that the integration of divergence patterns and sequence context into methods that predict the fitness or health effects of human mutations could increase accuracy and predictive power.

Do not trust anyone who does not know the difference between a mutation and a fixed amino acid substitution to explain any aspect of RNA-mediated biologically-based cause and effect. The number of theorists who want you to believe in their pseudoscientic nonsense is hundreds of times more than the number of serious scientists with experimental evidence of how energy-dependent RNA-mediated protein folding chemistry must be linked to morphological and behavioral phenotypes in all living genera by keeping virus-driven energy theft in check.

See also: Keeping CRISPR in Check
Excerpt 1)

Notably, the work is “going specifically after Cas9 and then applying the discoveries in human cells,” Harvard’s George Church, who was not involved in the study, wrote in an email to The Scientist.

Excerpt 2)

Knowing how the viral enemy evades CRISPR-based immunity will provide valuable insights into ways to better fight [viruses],” wrote Horvath.

This is a complete reversal of claims by George Church that were put into the context of this report:
Get Well in the RNAi Way-RNAi, A Billion Dollar Baby in Therapy
Excerpt:

…the design, stability and degradation of RNAi based effective molecules appears to be the major lime light to challenge the conventional drug safety concerns and ensures to be the most powerful gene recovery in future which execute billion dollar business hope.

See for comparison: Obama Advisers Urge Action Against CRISPR Bioterror Threat
See also: Jon Stewart interviews Greg Bear It’s not very funny anymore, is it?
Also: March 9, 2016 See Gene intelligence: The risks and rewards of genome editing resonate beyond the clinic.

Last month, one of the top intelligence officials in the United States warned that genome-editing technology is now a potential weapon of mass destruction.

CRISPR—a weapon of mass destruction?

James Clapper placed “genome editing” among six threats listed in the section on weapons of mass destruction.

See also 12/9/16 The B/Z reaction, and the problem with peer review 

…oscillating chemical reactions predictable by mathematical formula are partially responsible for organizing cells to form organs, bone, and tissue.

The predictable oscillating chemical reactions have now been placed into the context of  Nonlinear self-adapting wave patterns  by David Kessler and Herbert Levine, who I mentioned near the beginning of this blog post.
Abstract (with my emphasis):

We propose a new type of traveling wave pattern, one that can adapt to the size of physical system in which it is embedded. Such a system arises when the initial state has an instability for a range of wavevectors, k , that extends down to k = 0, connecting at that point to two symmetry modes of the underlying dynamical system. The Min system of proteins in E. coli is such a system with the symmetry emerging from the global conservation of two proteins, MinD and MinE. For this and related systems, traveling waves can adiabatically deform as the system is increased in size without the increase in node number that would be expected for an oscillatory version of a Turing instability containing an allowed wavenumber band with a finite minimum.

None of the serious scientists I have ever known would take Schrodinger’s claims about the anti-entropic energy of sunlight and link everything from the creation of energy to an oscillatory version of a Turing instability without addressing the loss of energy as information, which links virus-driven energy theft to genomic entropy. The fact that someone who has co-authored with Eshel Ben-Jacob left out the role of virus-driven energy theft probably never occurred to anyone who read the article. And so, here we are.
See also: Herbert Levine

Research Statement

Biological systems operate in nonequilibrium states, using free energy derived from metabolism to run all the various processes needed for survival. Understanding the chemical and physical mechanisms that govern these processes is an essential component for advancing our quantitative understanding biological systems. Ultimately, this new level of understanding should prove crucial for tackling currently intractable diseases such as metastatic cancer.

The energy derived from metabolism is nutrient-dependent. The physical and chemical mechanisms that link RNA-mediated amino acid substitutions to cell type differentiation in all living genera are linked from the sun’s anti-entropic virucidal energy via the claims of serious scientists like Gunter Witzany.
See also: Life is physics and chemistry and communication