RNA-mediated cell types and precision medicine

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Health: Make precision medicine work for cancer care

Excerpt: After years of failure with the usual arsenal of surgery, chemotherapy and radiation, the physicians included the drug Herceptin (trastuzumab) in the woman’s treatment. Herceptin is more commonly used for breast cancer, but it targets the HER2 mutation. Since taking the drug, she has been free of disease.

Reported on April 20, 2015 in MLO – Medical Laboratory Observer as: Big data key to precision medicine’s success

“Technological advances are enabling scientists to sequence the genomes of cancer tumors, revealing a detailed portrait of genetic mutations that drive these diseases. But genomic studies are only one piece of the puzzle that is precision medicine, a Weill Cornell Medical College researcher writes in Nature. In order to realize the promise of this field, there needs to be an increased focus on creating robust clinical databases that include medical histories from patients around the country, which physicians can then use along with genomic data to tailor individual treatments.

In his Nature commentary, Mark Rubin, MD, director of the Institute for Precision Medicine, posits that searchable databases that compile information from a wide range of medical centers would allow researchers and clinicians to look for patterns and trends in cancer across a large patient population. They could then better design studies and clinical trials, create personalized treatment plans, and inform medical decisions so that each patient has access to the best care.

“With this vast clinical data, if we have a patient sitting in front of us who has a mutation that we’ve never seen before, we can ask the question: has anyone ever seen it before?” says Dr. Rubin. “With the development of big databases of clinical information, researchers will be able to say with certainty that there are, for instance, 12 people in the country who have this mutation and we think that they would benefit from a certain treatment.”

Dr. Rubin points to the New York City Clinical Data Research Network (NYC-CDRN) as an archetype for this kind of massive database. The network, which is led by principal investigator Dr. Rainu Kaushal, launched 16 months ago. It brings together 22 New York City healthcare systems and organizations to create a robust infrastructure where data from more than six million patients are aggregated.

In his Nature commentary, Dr. Rubin calls for broad investment to create the infrastructure for big data projects like NYC-CDRN. While President Barack Obama’s support of precision medicine, detailed in his new Precision Medicine Initiative and for which he’s earmarked $215 million from the 2016 budget, is a good start, more funding is needed to fulfill the promise of this burgeoning field, Dr. Rubin says.”

My comment: What is currently known about nutritional epigenetics and pharmacogenomics links our 1996 Hormones and Behavior review article to precision medicine from RNA-mediated cell type differentiation during the development of species from microbes to man via the conserved molecular mechanisms we detailed in our section on molecular epigenetics.

See also: Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors

Excerpt: “The gene, cell, tissue, organ, organ-system pathway is a neuroscientifically established link between sensory input and behavior. Marts and Resnick (2007) stress the importance of this pathway in the context of a systems biology approach to pharmacogenomics.”

Nutrient-dependent/pheromone-controlled adaptive evolution: a model

Excerpt: “…the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.”

My comment: Others who are still working without a model of biologically-based cause and effect that links ecological variation to ecological adaptations are getting closer to eliminating ideas about mutations and evolution. But most have a long ways to go before they understand top-down causation in the context of viral microRNAs that perturb protein folding and nutrient-dependent microRNAs that lead to the anti-entropic epigenetic effects on cell type differentiation via RNA-mediated amino acid substitutions that stabilize the organized genomes of species from microbes to man.

See also my invited review of nutritional epigenetics: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

Many evolutionary theorists will continue to believe that evolution is undeniable until they learn what is currently known by serious scientists about physics, chemistry, molecular biology, and communication across species.

See also: Is Evolution Undeniable?

Excerpt: “Meyer shows that mainstream scientific literature has produced many technical papers challenging neo-Darwinian evolution. As for the Cambrian explosion, most paleontologists agree that building all those new types of organisms, in a geological blink of an eye, would require immense volumes of new biological information. Just as computer code doesn’t write itself, neither does the genetic programming in DNA.”

My comment: The need for new biological information and communication across species makes evolution via natural selection on mutations impossible. The need for nutrient-dependent pheromone-controlled ecological adaptations links ecological variation to cell type differentiation in species from microbes to man without the pseudoscientific nonsense of theories.

This free journal article links biological information across species to adaptations:

Early skeletal muscle adaptations to short-term high-fat diet in humans before changes in insulin sensitivity. The findings were reported in: Five days of eating fatty foods can alter how your body’s muscle processes food

The alteration in 5 days can be compared in the context of re-evolution of the bacterial flagellum in four days, which was reported here. What was attributed to mutations and evolution in bacteria is clearly an ecological adaptation linked to nutrient uptake and the pheromone-controlled physiology of reproduction, which is RNA-mediated in species from microbes to man.

Watch as more researchers begin to accurately represent cause and effect instead of placing it into the context of ridiculous theories.

Journal article conclusion: “Taken together with the smaller increase in mRNA expression, these finding suggest a potential mechanism for the observed dysregulated skeletal muscle substrate metabolism after the fasting-to-fed transition. Importantly, this dysregulated skeletal muscle substrate metabolism was observed before measurable changes in whole-body insulin sensitivity.”

They link isoforms of the same protein to the “potential mechanism” without linking RNA-mediated amino acid substitutions to the isoforms. The microRNA/messenger RNA balance is the epigenetically-effected link to biophysically constrained chemistry of RNA-mediated protein folding, which links the isoforms and cell type differentiation. The molecular mechanisms of RNA-mediated cell type differentiation are conserved and they have been detailed in a series of published works during the past 2 decades.

Dementia ‘halted in mice brains’

Excerpt: “They found some microglia changed to become exceptionally adept at breaking down a component of protein, an amino acid called arginine, in the early stages of the disease.

As arginine levels plummeted, the immune cells appeared to dampen the immune system in the brain.”

I wonder how many times the links from RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate cell types will need to be detailed before serious scientists begin to recruit theorists who will try to help with “Combating Evolution to Fight Disease“

The change in the microglia is obviously virus-driven, and the epigenetic effects of nutrient-dependent microRNAs typically protects against the changes — unless a lifetime of nutrient-stress and/or social stress leads to epigenetically-effected cell type differentiation and neurodegenerative diseases or other pathology attributed to the failure of the immune system to regulate nutrient-dependent cell type differentiation.  With the dementia that accompanies Alzheimer’s, however, loss of olfactory acuity and specificity links olfactory/pheromonal input and the damage that is already done to neuronal pathways via the compromised immune system.

The question arises: Why isn’t anyone currently examining the role of feedback loops that link odor and pheromones to the physiology of reproduction in an attempt to link “Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis” The epigenetic effects of food odors and pheromones on luteinizing hormone (LH) link RNA-mediated amino acid substitutions from sex differences in cell types to all differences in cell types in all cells of all tissues of all organs in all organ systems of mammals via the biophysically constrained chemistry of RNA-mediated protein folding.

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