Targeted Epigenetic Remodeling of Endogenous Loci by CRISPR/Cas9-Based Transcriptional Activators Directly Converts Fibroblasts to Neuronal Cells


In this study, we demonstrate direct cellular reprogramming to induced neuronal cells through targeted activation of endogenous genes.


Moreover, a recent study demonstrated that reprogramming efficiency can be limited by divergence to a competing cell identity (Treutlein et al., 2016). The molecular mechanisms and practical consequences of these limitations are largely unknown.

My comment: They demonstrate what naturally must occur to link energy-dependent changes from angstroms to ecosystems in all living genera, but claim that the limitations on the molecular mechanisms of biophysically constrained energy-dependent RNA-mediated cell type differentiation are largely unknown.  But see Treutlein et al., (2014):  Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing and Treutlein et al., (2016) Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA-seq. Taken together, false claims about the unknown molecular mechanisms were also revealed in:

Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins.

Abstract excerpt:

…we detected 1,364 unique neurexin-α and 37 neurexin-β mRNAs produced by alternative splicing of neurexin pre-mRNAs. This molecular diversity results from near-exhaustive combinatorial use of alternative splice insertions in Nrxn1α and Nrxn2α. By contrast, Nrxn3α exhibits several highly stereotyped exon selections that incorporate novel elements for posttranscriptional regulation of a subset of transcripts. Complexity of Nrxn1α repertoires correlates with the cellular complexity of neuronal tissues, and a specific subset of isoforms is enriched in a purified cell type. Our analysis defines the molecular diversity of a critical synaptic receptor and provides evidence that neurexin diversity is linked to cellular diversity in the nervous system.

My comment: The link from the energy-dependent alternative splicings of pre-mRNAs to all cellular diversity in all individuals of all species is, in a word:


Without energy-dependent changes in alternative splicings of pre-mRNAs there would be no link from nutritional epigenetics to the physiology of reproduction, and nothing could stop virus-driven energy theft from causing the extinction of all life on Earth.

See also: High-Throughput Mutational Analysis of a Twister Ribozyme


We propose that an unbiased and comprehensive functional analysis of ribozyme mutants can complement the existing structural and biochemical information of ribozymes and provide novel insights.

My comment: They make no mention of the fact that virus-driven energy theft causes the mutations.

Reported as: Analysis of the Ribozyme Finds a High Tolerance for Mutations


Because ribozymes can control gene expression in both live cells and viruses, a better understanding of how they work could lead to improvements in their therapeutic applications.

My comment:  This claim, in the report by Carmen Leitch, is the clearest indicator that she is not going to acknowledge my works, or cite them — despite 4 presentations during Labroots virtual conferences earlier this year.

If ribozymes did not link nutrient energy-dependent microRNA flanking sequences from hydrogen-atom transfer in DNA base pairs in solution to all biodiversity via the physiology of reproduction and supercoiled DNA, virus-driven energy theft would have ended all life on Earth. That fact is perfectly clear to anyone who understands how to link energy-dependent changes from angstroms to ecosystems. It suggests all science journalists should stop reporting anything until they after they read Structural diversity of supercoiled DNA and watch the video that ridicules neo-Darwinian theorists (and — in the end — Neil de Grasse Tyson).

Those who failed to catch the train of neo-Darwinian evolution will be happy they did not get on board and go for the ride of their life through academia. Biased education gave others a life-time ticket towards their final destination. For contrast, serious scientists have replaced the neo-Darwinian god of evolution via use of experimental evidence that links the superior intelligence, or faith, of others to their survival.

For example see: Shiva the Destroyer: Targeting the Destruction of RNA Polymerase for Cancer Treatment

In Hinduism, Shiva is the supreme deity—the destroyer or the transformer—capable of both benevolence and destruction. Now, Peltonen and colleagues develop a small molecule–based approach to target for destruction RNA polymerase I, a key enzyme essential to the production of ribosomal RNA (rRNA), which is the major component of the eukaryotic ribosome, the creator of proteins.

Now, the link from energy-dependent codon usage to the creation of proteins can be considered in the context of RNA-mediated protein folding biochemistry and Dobzhansky’s light of evolution, which links Schrodinger’s claims about the anti-entropic virucidal energy of sunlight from the physiology of reproduction in soil bacteria to the nutrient energy-dependent physiology of pheromone-controlled reproduction in all primates via RNA-mediated amino acid substitutions.

See also: Epigenetics and Genetics of Viral Latency


… viral latency is responsible for life-long pathogenesis and mortality risk…

See also: Fiction Reviews ‘Darwin’s Children’


…today humanity is learning to live with SHEVA very much as we, since the mid-1980s, had to learn to live with AIDS. The big difference being that unlike AIDS (which destroys the immune system so laying its victims open to other (sometimes fatal) diseases, SHIVA mutates humans into what may be the next step in human evolution with the activation of dormant DNA (genes). SHIVA humans have additional ways to communicate with each other and can form tightly bonded communities. They also are more sensitive to ‘normal humans’ unconscious and biological signals.

My comment: The ‘biological signals’ are human pheromones, which Greg Bear tactfully presented in the context of the nutrient energy-dependent creation of a new human subspecies, rather that in the context of a species that mutated and evolved into another species.  Greg Bear is know for his “fact-checking” and no facts link mutations and natural selection to the evolution of one species that neo-Darwinian theorists claim evolved from another species.

Simply put, the neo-Darwinian theorists never checked their facts. The simply touted their theories and that’s what led to the metaphorical train wreck. All serious scientists now know that energy-dependent codon usage and RNA-mediated protein folding chemistry is biophysically constrained by the physiology of reproduction, which is controlled by pheromones in species from microbes to humans. That fact has been placed into the context of what is known about fixation of RNA-mediated amino acid substitutions in the context of gene regulation via highly variable GC-rich regions that enable comparisons between virus-driven mutations and protein-length variation to those associated with healthy longevity.

See also: Loss of function at RAE2, a previously unidentified EPFL, is required for awnlessness in cultivated Asian rice

My comment: Viruses cause differences in rice that are linked to “…a suite of dysfunctional RAE2 variants that were selected during domestication and condition the awnless phenotype in Asian rice.”

Virus-driven loss of function can be linked across-species from the mutation in rice to virus-driven DNA damage that typically would be repaired in the context of the physiology of reproduction, which selects against the damaged DNA via the obvious links to biophysically constrained RNA-mediated protein folding chemistry.

See also: Codon optimality at genome transition

Reported under the subheading “RNA stability,” which links the epigenetic landscape to the physical landscape of supercoiled DNA via energy-dependent RNA-mediated amino acid substitutions in all living genera.

This is a comprehensive one paragraph refutation of neo-Darwinian pseudoscientific nonsense, which was reported as  Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition.  The original article and the one-paragraph report of its overwhelming significance are behind paywalls.

The fact that energy-dependent codon usage typically prevents virus-driven energy theft from linking mutations to all pathology was not considered when neo-Darwinists invented their theories. Their theories were based on de Vries 1902 definition of mutation and their assumptions about how long it would take for accumulated mutations to cause one species to evolve into another.

That idea is so ridiculous that theorists are horribly embarrassed, so don’t expect to find many other reports on this July 19, 2016 refutation of their nonsense.

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