Multisensory integration and causal inference in the brain

Excerpt (with my emphasis):  It is largely unknown how the brain implements prior knowledge and expectations. Various mechanisms have been proposed such as spontaneous activity (Berkes et al., 2011), the fraction of neurons encoding a particular feature (Girshick et al., 2011), their response gain and tuning curves or connectivity and top-down projections from higher order areas (Rao and Ballard, 1999).”

My comment: The brain implements prior knowledge and expectations through nutrient-dependent pheromone-controlled feedback loops linked to RNA-mediated chromatin loops and protein folding.

Feedback from Network States Generates Variability in a Probabilistic Olfactory Circuit

Excerpt: “The integration of sensory information with network states may represent a general mechanism for generating variability in behavior.”

The integration is nutrient-dependent. Integration links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man via the biophysically constrained chemistry of nutrient-dependent RNA-mediated amino acid substitutions. The substitutions are fixed via the biophysically constrained physiology, which links the RNA-mediated chemistry of protein folding to of nutrient-dependent reproduction via metabolic networks and genetic networks. For example, in vertebrates, the importance of the  GnRH-controlled link to metabolic networks and genetic networks has been exquisitely detailed. Only one nutrient-dependent amino acid substitution in the GnRH decapeptide is required to link differences in many different species.

Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

Excerpt: “When the chiral amino acid (Ala) in position six of Ciona I GnRH was substituted with the achiral glycine or with d-Ala, which enhances the type II’ β-turn conformation, there was a marked increase in the binding affinity of the peptides at the vertebrate GnRH receptor (Barran et al., 2005).”

See also: Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity

Excerpt: “These findings indicate that the substitution of glycine for a chiral amino acid in GnRH during evolution allows a more constrained conformation for receptor binding and that this subtle single amino acid substitution in a site remote from the ligand functional domains has marked effects on its structure and activity.”

My comment: Glycine is the “simplest” amino acid. The “R group” is a hydrogen atom, which is why glycine is not a chiral compound. That means there is no such thing as L-glycine or D-glycine. For comparison,  other natural amino acids are chiral.  Most amino acids are L and sugars are D.

Some evolutionary theorists seem to think that glycine formed spontaneously from acetate or glycerol, which also suggests that a deep space astronomical “accident” led to the presence of L-amino acids instead of D-amino acids. See: Enrichment of the amino acid l-isovaline by aqueous alteration on CI and CM meteorite parent bodies

Excerpt: “…amino acids delivered by asteroids, comets, and their fragments would have biased the Earth’s prebiotic organic inventory with left-handed molecules before the origin of life.”

Theorists who are unable to link our sun’s anti-entropic energy to the origin of life via the de novo creation of amino acid substitutions have also proposed other ridiculous theories that fail to link nutrient-dependent amino acid substitutions to cell type differentiation via what is currently known about the physiology of reproduction, fixation of amino acid substitutions, and cell type differentiation.

Watching a paradigm shift in neuroscience

Excerpt (with my emphasis): “…the variability provided by the feedback connections dominate an adaptive feature of the behavior, its variability. This work adds C. elegans to the elongating list of animals, whose nervous systems are organized such that ongoing activity is modulated by external stimuli. It seems, in such nervous systems, even a numerically small feedback component provides a fundamental contribution to the overall architecture. What does this mean for brains whose anatomy appears to be dominated by feedback loops?”

My answer: That was a rhetorical question. Bjorn Brembs knows what it means. It means that anyone who denies what is known about nutrient-dependent pheromone-controlled feedback loops in species from microbes to man will continue to look even more foolish to serious scientists.

See for example: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

Excerpt: “For instance, ‘our experiments suggest that excitatory odor responses are transiently suppressed (in terms of overall firing rates), but more complex temporal shaping of responses may occur because of interplay of intrinsic properties, sensory drive, and the feedback activity’ (Markopoulos, Rokni, Gire, & Murthy, 2012, p. 1186). In context, this was suggested in ‘Feedback loops link odor and pheromone signaling with reproduction’ (Boehm, Zou, & Buck, 2005).”

My comment: Since the time that 2004 Nobel Laureate, Linda Buck co-authored (Boehm, Zou, & Buck, 2005), the link from odor and pheromone signaling via the feedback loops linked to reproduction has been clearly established. Nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions differentiate all cell types in all individuals of all species. In species from microbes to man, for example,  fixation of the amino acid substitutions occurs in the context of the nutrient-dependent pheromone-controlled physiology of reproduction.

The physiology of reproduction in animals is linked to the physiology of reproduction in plants via the anti-entropic biological energy of the sun and the light-induced de novo creation of amino acids.

See: Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism

Excerpt: “Rather than invoking fundamentally different scenarios and chemistries for the syntheses of the molecular components of informational, compartment-forming and metabolic subsystems, and then concluding that one or other subsystem must have come first, we describe a scenario in which variations on a chemical homologation theme result in the components of all three subsystems being produced and then blended together.”

My comment: Before anything is produced or blended together, the sun’s biological energy must start the chemical reactions that lead to the de novo creation of amino acids. In several other blog posts, I have linked viral microRNA suppression by nutrient-dependent microRNAs from entropic elasticity to increasing organimal complexity via the biophysically constrained chemistry of nutrient-dependent RNA-mediated protein folding, whether it occurs in the context of photosynthesis or nutrient uptake, including DNA uptake, from heterospecifics.

A recent report links nutrient-dependent microRNAs from protein biosynthesis and degradation to memory, albeit with no mention of the link from microRNAs to amino acid substitutions that differentiate cell types in the brain. The report is slightly misleading, but see: miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement

Excerpt (with my emphasis): “Protein synthesis is also required for other forms of synaptic plasticity, such as long-term synaptic depression (LTD), which leads to decreases in synaptic strength. The unique changes in synapses that occur during each type of synaptic plasticity cannot be accounted for by global upregulation of translation. Indeed, translation of selective messenger RNAs (mRNAs) has been implicated in synaptic plasticity5. For instance, after LTP is induced, Ca2þ/calmodulin-dependent protein kinases II (CaMKII) promotes phosphorylation of cytoplasmic polyadenylation element (CPE)-binding protein, which in turn stimulates the polyadenylation and translation initiation of mRNAs containing CPE7,8. However, little is yet known about the mechanisms of gene-specific regulation of translation and about which genes are translated during LTP.”

My comment: Their claim that “little is yet known” can be placed into the context of what is known to others. The microRNA/messenger RNA balance links ecological variation to nutrient-dependent protein biosynthesis via amino acid substitutions that stabilize protein folding in the organized genomes of all genera. See: Context-specific microRNA function in developmental complexity

Excerpt: Overwhelming evidence is also now accumulating to support hypotheses for miRNA and other small non-coding RNA molecules in autocrine, paracrine, and exocrine signalling events (Dinger et al., 2008). For example, miRNAs have been shown to exist in 50–100 nm diameter vesicles known as exosomes, which are secreted by a variety of cell types and tissues, and have been found to be involved in processes such as cancer (Lotvall and Valadi, 2007; Skog et al., 2008). Importantly, miRNAs from these vesicles can even be taken up into recipient cells to mediate silencing effects (Kosaka et al., 2010). Interestingly, the plant miR-168—highly expressed in rice—has also recently been shown to be present in human blood plasma (Zhang et al., 2011). This investigation also revealed plant miRNA to be stable in cooked foods, with dietary consumption of plant material resulting in exogenous plant miRNAs being absorbed into the bloodstream of mice from the gastrointestinal tract. Plant miR-168 was even shown to regulate the expression levels of target genes in the liver such as LDLRAP1 (low-density lipoprotein receptor adapter protein 1), resulting in decreased LDL removal from blood plasma in mice. Indeed, such a significant discovery revolutionizes the complexity with which miRNAs are considered to function in mammals throughout various developmental and pathophysiological processes.

My comment: The anti-entropic energy of the sun is linked to nutrient-dependent microRNAs that repair DNA damage. The damage done by viral microRNAs links entropic elasticity to the RNA-mediated protein biosynthesis and degradation required for epigenesis and epistasis. The link from DNA damage repair may be the most important consideration given the obvious atoms to ecosystems connection to cell type differentiation via amino acid substitutions.

The paradigm shift in neuroscience that links top-down causation to biodiversity via cell type differentiation has left theoretical physicists with nothing to contribute to scientific progress. Instead, they are forced to invent more ridiculous theories. For example, in response to what is currently known to serious scientists about light-induced de novo creation of amino acids and biologically-based cause and effect manifested in cell type differentiation linked to amino acid substitutions, theorists have asserted that information transmission can occur without the transmission of energy.

See: Photon ‘afterglow’ could transmit information without transmitting energy

Excerpt: “…up until now, it has been believed that real quanta, such as real photons of light, are the only carriers of information from the early Universe.”

See also: Attempts to exempt speculative theories of the Universe from experimental verification undermine science, argue George Ellis and Joe Silk.

I asked: Has everyone decided to ignore that fact? There is a clear link from the light-induced de novo creation of amino acids to their anti-entropic epigenetic effect on cell type differentiation in plants and animals. Simply put, cell type differentiation is controlled by the biophysically constrained chemistry of RNA-mediated amino acid substitutions and protein folding.

Inventing a theory of information transfer that occurs without energy transfer is required because serious scientists have focused on the fact that “Life is physics and chemistry and communication” That means pseudoscientists are forced to fight against the facts by inventing new theories that disassociate energy and information.But see: Scientific method: Defend the integrity of physics The discussion of information transfer without transmitting energy ignores that fact that Life is physics and chemistry and communication. See also: What is Life?: With Mind and Matter and Autobiographical Sketches

Excerpt (with my emphasis): “…a very small number of individuals, say two or three in tens of thousands, turn up with small but ‘jump-like’ changes, the expression ‘jump-like’ not meaning that the change is so very considerable, but that there is a discontinuity inasmuch as there are no intermediate forms between the unchanged and the few changed. De Vries called that a mutation. The significant fact is the discontinuity. It reminds a physicist of quantum theory -no intermediate energies occurring between two neighbouring energy levels. He would be inclined to call de Vries’s mutation theory, figuratively, the quantum theory of biology. We shall see later that this is much more than figurative. The mutations are actually due to quantum jumps in the gene molecule”(p. 33-34).

My comment: Theoretical physicists must now break the link between energy and information or change the definition of “mutation.” That fact helps to explain why two theorists recently discussed changing the definition of evolution. See: Beyond Genetic Evolution. A Conversation With Eva Jablonka

Excerpt 1 with my emphasis) “Types do not have to be genotypes, they can be epigenotypes, behavioral types,  symbolic types. If we agree on that broad definition,  I don’t see why change over time with respect to them is not evolution. Symbolic evolution is a very different type of evolution,  among other things it is a developmental  system that can direct its own evolution. But this does not make it non-evolutionary.”

Excerpt 2) “This is a good opportunity to move to the second dimension of evolution, epigenetics. Now we do have mechanisms, and we can begin to understand how epigenetics counts as an inheritance system.”

Regarding Excerpt 1):  “I don’t see why change over time with respect to them is not evolution.”

See: Sulfur-cycling fossil bacteria from the 1.8-Ga Duck Creek Formation provide promising evidence of evolution’s null hypothesis.

No change occurred in microbes during 1.8 billion years.

See also: Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system. 

Genetically modified bacteria re-evolved their missing flagella “over-the-weekend.”

Claims that “evolution” did not occur in 1.8 billion years but it occurred in 4 days do not support use of the definition of evolution as “…change over time…” or a change to “symbolic evolution”(e.g., “…a developmental  system that can direct its own evolution.”) Developmental systems in all organisms are nutrient-dependent and they do not direct their own evolution. Organisms and species either find enough food to eat or they die and become extinct.

Regarding Excerpt 2): “…the second dimension of evolution, epigenetics.” 

Conserved molecular mechanisms of epigenetically-effected biophysically constrained nutrient-dependent pheromone-controlled RNA-directed DNA methylation and events link the RNA-mediated chemistry of protein folding to cell type differentiation in species from microbes to humans. The conserved molecular mechanisms show how the epigenetic landscape becomes the physical landscape of DNA in organized genomes without use of any definition of “mutation” or any definition of “evolution.”

The conserved molecular mechanisms link top-down causation to biologically-based cause and effect without the pseudoscientific nonsense of definitions and assumptions. Serious scientists don’t care how long anyone thinks it might take for mutations to lead to the evolution of a new species.

Mutations perturb protein folding. They cannot lead to the evolution of a new species. Loss of function mutations are linked to genes that are no longer needed, not to the de novo creation of new genes.  Thus, no loss of function in microbes that are supposedly 1.8 billion years-old can be compared to the gain of the bacterial flagellum “over-the-weekend.” Watch your clock, or set your timer. If you look again at a microbe that supposedly “re-evolved” its flagellum, and you see the flagellum, you need not reset your clock to 1.8 billion years.

Gaining the functional flagellum was linked from nutrient-dependent amino acid substitutions to pheromone-controlled cell type differentiation of a complex structure. No loss of function in 1.8 billion years could be linked to the absence of light-induced amino acid substitutions in bacteria that live the bottom of the sea floor.

Understanding how viral microRNAs and nutrient-dependent microRNAs are linked from the microRNA/messenger RNA balance to nutrient-dependent RNA-mediated cell type differentiation via the physiology of reproduction is obviously important to understanding how metabolic networks and genetic networks interact in the context of the epigenetic landscape. But see: New insight into how proteins find their DNA binding sites in the genome.

Excerpt: Rohs and colleagues found that introducing shape-recognizing amino acids from one transcription factor to another swapped binding specificities between Hox proteins.

My comment: This suggests the need for a model of RNA-mediated cell type differentiation that links nutrient-dependent molecular epigenetics from genome positioning and timings and molecular distance via amino acids, which also suggests that the gene-centric approach by evolutionary theorists has been a waste of time, money, effort, and careers. If so, that fact helps to explain why serious scientists are Combating Evolution to Fight Disease.

See my comments on that article to the “Science Magazine site

3/7/14 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.

7/15/14 Re: “Molecular biology and evolutionary biology have been separate disciplines and scientific cultures: The former is mechanistic and focused on molecules; the latter is theoretical and focused on populations.”

Now see: A mechanistic link between gene regulation and genome architecture in mammalian developmenthttp://www.sciencedirect.com/science/article/pii/S0959437X14000495 for the refutation of neo-Darwinian pseudoscientific nonsense.Experimental evidence of biologically-based cause and effect does not support ideas about mutations, natural selection, and the evolution of biodiversity.Experimental evidence of biologically-based cause and effect supports the fact that ecological variation leads to nutrient-dependent pheromone-controlled ecological adaptations in species from microbes to man via conserved molecular mechanisms.

9/7/14 Re:”…the driver of evolution is not mutations or variation but selection, be it natural, artificial, kin or sexual selection. Mutation is but one of the factors that contribute to variation.”I thought Robert Frye knew better than that, because he attended a 1993 symposium I organized and my 2007 Reiss Plenary session of The Mind’s Eyes: Modeling the Development of Diverse Sexual Preferences.Perhaps this is a different Robert Frye or one who thinks that sexual orientation arises via mutations and natural selection in human males but via nutrient-dependent pheromone-controlled cell type differentiation in yeasts as we reported in our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior

http://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertiliz… “Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus…”Robert: What about Anne’s rams. Are they among the selected mutants that you think may have evolved their exclusive homosexual orientation?

9/13/14 “An alternative theory proposes environmentally induced change in an organism’s behavior as the starting point (1), and “phenotypic plasticity” that is inherited across generations through an unspecified process of “genetic assimilation” (2).” http://www.sciencemag.org/content/332/6034/1161.short

This is now more than merely an alternative theory of genetic assimilation. It links transgenerational epigenetic effects from nutrient uptake and RNA-mediated events to amino acid substitutions that differentiate the cell types of all cells in all individuals of all organisms.

See, for example: Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans http://www.cell.com/cell/abstract/S0092-8674(14)00806-XThe nutrient stress-induced RNA-mediated events, which link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man, also link morphological and behavioral diversity via conserved molecular mechanisms exemplified in the context of biologically plausible ecological speciation in nematodes.

See: System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes http://linkinghub.elsevier.com/retrieve/pii/S0092867412015000

A difference in their feeding behavior and in the anatomy of their mouth parts is linked from nutrient-dependent pheromone-controlled feedback loops to ecological, social, and neurogenic niche construction. The change in focus from mutations, natural selection, and the evolution of biodiversity via unknown evolutionary events to nutrient-dependent pheromone-controlled RNA-mediated events that differentiate cell types may be required for others to realize the difference between evolutionary theories and biologically-based facts about RNA-mediated events.RNA-mediated events are biophysically constrained, which means they are a biologically plausible way to link the physics and chemistry of protein folding to increasing organismal complexity via molecular biology. RNA-mediated events can also be compared to any unknown evolutionary events that might arise in the context of an alternative theory about constraint-breaking mutations, or other theories that include no mention of RNA-mediated events.

For a model of RNA-mediated cell type differentiation that links nutrient-dependent molecular epigenetics to genome positioning and timings and to molecular distance see From Fertilization to Adult Sexual Behavior.For the link from RNA-mediated cell type differentiation via amino acid substitutions in species from microbes to humans see Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

For the link from atoms to ecosystems in all genera, see: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

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