From precis to pre-mRNA and proof of concept in F1, F2, F3

By: James V. Kohl | Published on: November 7, 2016

(click to enlarge)

The Gene Ontology Handbook, edited by Christophe Dessimoz & Nives Škunca Open Access, Download it here

See also: BioGenomics 2017 – Global Biodiversity Genomics Conference February 21-23, 2017

Conclusion: The current limiting factor in using this technology is the availability of fast-acting ts alleles. Previous forward genetic screens for ts alleles have provided a range of useful fast-acting ts mutant strains (Canman et al., 2008; Encalada et al., 2000; Kemphues et al., 1988; O’Connell et al., 1998; O’Rourke, Yochem, et al., 2011; Raich et al., 1998). With the advent of genome engineering techniques such as CRISPR, it now seems possible to design ts alleles of desired proteins. This is complicated by a lack of understanding of the mechanism(s) by which ts mutations give rise to a ts phenotype. However, many ts alleles contain mutations in amino acid residues conserved within protein families and between species, which could guide the design of ts alleles. The approaches described previously allow dissection of cell processes with high temporal resolution. However, they are limited by lack of spatial specificity, as the whole embryo is subjected to the same temperature changes. Future work will combine ts alleles with techniques that control temperature changes at a subcellular level.

Reported as: Are you ready to work with C.elegans TS mutants during live cell imaging?

See the video: Published on 31 Jul 2014

Description:

During C. elegans embryo division, the CYK-4 protein is required for the completion of cytokinesis (but not to form a furrow or initiate ingression). At the “permissive” 16°C temperature, the CYK-4 protein is functional, but at 25°C it becomes non-functional and cytokinesis is impaired.

My comment: Theromodynamic cycles of energy-dependent protein biosynthesis and degradation link the nutrient-dependent physiology of reproduction in bacteria to the nutrient-dependent pheromone-controlled physiology of yeasts and all multicellular organisms. Virus-driven energy theft is linked from mutations to all pathology. Now that Larry Kisner Sr., and Peter Berean are award of that fact, they are stuck with ridiculous theories instead of a model of biologically-based cause and effect. That is what has happened to all theorists since the time that neo-Darwinism was invented. See for comparison

From Precis to Proof in 20 years

Precis: The Scent of Eros: Mysteries of Odor in Human Sexuality

1. This book incorporates both non-human animal and human models of reciprocity among odors, olfaction, neuroendocrinology, and behavior. It details the likely influences both of human chemical communication and of olfaction on genes in neurosecretory neurons. These neurons are found in brain tissue responsible for integrating, coordinating, and directing reproductive endocrine function in organs that comprise the organ systems known to influence mammalian reproductive sexual behavior and human sexuality. Though this book is not written to meet any requirements of a “hard scientific” approach to interdisciplinary topics, it is fully referenced for the knowledgeable scientist and for those interested either in further study or in support for any conclusions. Also included are chapter notes, a glossary, and an index.

See also: From Fertilization to Adult Sexual Behavior
Excerpt (with my emphasis):

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.

See for validation: RNA catalyses nuclear pre-mRNA splicing

Excerpt (with my emphasis):

This RNA-based mechanism is sufficient to effect metal catalysis of pre-mRNA splicing, without the need for direct protein involvement. Given this evidence, it is noteworthy that the RNaseH-like domain of Prp8, which interacts with all reactive sites of the substrate, can bind a metal in crystallo42. Further, mutations that compromise metal binding in crystallo impair exon ligation, leading to the possibility that Prp8 may play a catalytic role during exon ligation42.

My comment: Virus-driven energy theft links the mutations that compromise metal binding from inorganic to organic chemistry and supercoiled DNA, which protects all organized genomes from virus-driven entropy.

See also: One Gene, Two Mutations

My comment to The Scientist from Nov. 14, 2013

In my model, [a mammalian model of thermodynamics and organism-level thermoregulation] nutrient stress and thermal stress result in cycles of protein biosynthesis and de novo creation of olfactory receptor genes. These seemingly futile thermodynamic cycles enable nutrient uptake and cell survival. If not, the cell dies.

Thermal stress causes what happens in nutrient stress, which exemplifies the innate ability of cells to epigenetically adapt to their sensory environment via nutrient-dependent pheromone-controlled reproduction sans mutations.

If mutations caused the adaptations, cancer would be an adaptation instead of a disease. The problem is that most people still think in terms of mutations, not nutrient-dependent pheromone-controlled adaptations. Now we have mutations causing mutations sans selection, which is what happens when you don’t consider physics or biology, and explain what happens as if it fit a theory of mutation-driven evolution, which it does not.

No budget video

Excerpt:

In recent years, scientists have identified other regions where evolution is running fast. To measure its speed, researchers have looked at the DNA of species living in each place. The longer it has been since two species diverged from a common ancestor, the more time each lineage has had to accumulate mutations. Young species have relatively few mutations.

Abstract excerpt:

Our work underscores the biophysical limitations of Drp1 and positions Dyn2, which has intrinsic membrane fission properties, at the final step of mitochondrial division.

Excerpt:

The addition of a methyl group to an arginine residue can remove a hydrogen bond donor and decrease the electrostatic surface potential at the residue, resulting in a change in size and hydrophobicity that can affect its interaction with binding partners (21).

“Our findings change what everyone has believed about mitochondrial division,” said postdoctoral fellow Jason Lee, first author on the study. “Now we know that it takes at least three different constriction steps in order to ultimately divide mitochondria.”

My comment: Mitochondria

1) generate energy in cells,
2) play a role in longevity, and they are
3) crucial for blood sugar maintenance and fat loss.
That fact linked virus-driven energy theft to damaged mitochondria and mutations, which cause all pathology. For example, virus-driven energy theft can cause problems in cells of archaea and in the human brain, liver, heart, skeletal muscles and respiratory systems.
Excerpt:

The study results are important because a better understanding of mitochondrial division is a step closer to understanding what might change in cells under pathological conditions like cancer, said Wu.

Excerpt:

“The ability of our cells to efficiently convert nutrients into energy is rooted in the cell’s ability to manage the shape, number and positioning of mitochondria through a balance of fusion and division,” said Lee. “This balance goes awry in cancer and neurodegeneration.”

Polycombic ecological adaptation as a science, not a theory (2)

See also Sal Giardina asked “What does DNA have to do with the Origin of Life?”

My comment: Supercoiled DNA is the link from energy-dependent changes in angstroms to all ecosystems in all living genera. That fact has been established in the context of experimental evidence that links physics and chemistry to molecular epigenetics and biophysically constrained RNA-mediated cell type differentiation at the level of quantum consciousness.

My comment: Anna Di Cosmo’s group Luca Turin’s group and John Hewitt have helped others to understand how quantised energy must be linked from the de novo creation of G protein-coupled receptors to the rearrangement of food that Max Tegmark inadvertently placed into the context of nutrient-dependent pheromone-controlled biophysically constrained protein folding chemistry. See: Consciousness is a mathematical pattern: Max Tegmark at TEDxCambridge 2014

See for comparison: Most British scientists cited in study feel Richard Dawkins’ work misrepresents science

Excerpt:

Although the researchers did not ask questions about Dawkins, 48 scientists mentioned him during in-depth interviews without prompting, and nearly 80 percent of those scientists believe that he misrepresents science and scientists in his books and public engagements. This group included 23 nonreligious scientists and 15 religious scientists.

I think that is an understatement and suspect it will not be discussed here.

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: President Obama talks about atheism, fundamentalist extremism, mentions the watering down of science by school boards, the need for critical thinking skills, and likens science deniers on facebook to some guy in his underwear writing from his mother’s basement.

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From precis to pre-mRNA and proof of concept in F1, F2, F3

From Precis to Proof in 20 years

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