5th-6th Sept 2018 Dublin, Ireland

The eternal significance of microRNAs (8)

Use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation and aging has been replaced by the use of model systems of biological processes.  Biological processes can be compared to so-called “evolutionary processes” to show that only biological processes need to be considered in the context of Darwin’s “conditions of life” or answers to the the question  What is Life? Schrödinger (1944).
K. L. Mettinger et al. (eds.), Exosomes, Stem Cells and MicroRNA, Advances in Experimental Medicine and Biology 1056, https://doi.org/10.1007/978-3-319-74470-4_6

This volume provides insight into the pivotal roles of stem cells, exosomes and other microvesicles in biofunction and molecular mechanisms and their therapeutic potential in translational nanomedicine. It further highlights evidence from recent studies as to how stem cell derived exosomes and microRNAs may restore and maintain tissue homeostasis, enable cells to recover critical cellular functions and begin repair regeneration.

Chapter 2 The Emerging Roles of microRNAs in Stem Cell Aging

involved in many biological processes such as developmental timing, differentiation, cell death, stem cell proliferation and differentiation, immune response, aging and cancer. Accumulating studies in recent years suggest that miRNAs play crucial roles in stem cell division and differentiation. In the present chapter, we present a brief overview of these studies and discuss their contributions toward our understanding of the importance of miRNAs in normal and aged stem cell function in various model systems.

Chapter 6  MicroRNAs, Regulatory Messengers Inside and Outside Cancer Cells

…like hormones, miRNAs can be secreted and regulate gene expression in recipient cells. Altered expression levels of miRNAs in cancer cells determine the acquisition of fundamental biological capabilities (hallmarks of cancer) responsible for the development and progression of the disease.

Model systems link the energy-dependent creation of microRNAs from microRNA biogenesis to the regulation of all cancer hallmarks. The virus-driven degradation of messenger RNA has been linked to all cancers and all other pathology in species from microbes to humans. Natural selection for energy-dependent codon optimality has been linked to healthy longevity.
See: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition
See for comparison:  The Neutral Theory in Light of Natural Selection May 2, 2018

…50 years after its introduction by Kimura. We argue that the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality. The ubiquity of adaptive variation both within and between species means that a more comprehensive theory of molecular evolution must be sought.

The ubiquity of adaptive variation attests to the facts about how the creation of quantized energy is linked to biophysically constrained viral latency. Adaptive variation links energy-dependent changes from angstroms to ecosystems in all living genera  via the physiology of their food energy-dependent pheromone-controlled reproduction.

For comparison to mRNA stability during the maternal-to-zygotic transition, see: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

The energy-dependent molecular mechanisms of recombination clearly link microRNA biogenesis to the stability of organized genomes during the life histories of all genera. Serious scientists object to the use of definitions in attempts to explain any aspect of species-specific biophysically constrained cell type differentiation.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

…it is tiresome to raise the same objections repeatedly, wondering why researchers have not fulfilled some of the basic requirements for establishing the occurrence of an autophagic process.

 

Watering Young Plant - Vintage Effect

A single base change refutes theistic evolution

Everyone who failed to learn how light-activated endogenous substrates biophysically constrain viral latency is playing “catch up” to serious scientists. The serious scientists know how quantized energy-dependent RNA-mediated cell type differentiation occurs in the context of the physiology of reproduction in all living genera. Rather than accept the fact that the innate immune system of bacteria (CRISPR) linked the pheromone-controlled physiology of reproduction from autophagy to biophysically constrained viral latency, theorists decided to waste money on virus-assisted gene-editing attempts to repair virus-damaged DNA.

Mammoth Biosciences launches a CRISPR-powered search engine for disease detection

Jennifer Doudna, George Church and many others still refuse to admit that they have refuted theistic evolution. They are just beginning to accurately portray the how detection of changes in the microRNA/messenger RNA balance links virus-driven energy theft to the degradation of messenger RNA. Clearly, however, they know how the degradation of messenger RNA is linked to all pathology.

Had they followed the works of Christ et al. (2013), The Pharmacology of Regenerative Medicine and Christ et al., (2018) Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming, they could intelligently interact with those who are scheduled to present during Schrödinger at 75 – The Future of Biology – September 2018.

(Nick Lane excepted.) He appears to be a biologically uninformed theorist who does not realize that Fast food makes the immune system more aggressive in the long term

Unhealthy eating causes some of these normally hidden pieces of DNA to unwind, similar to a loop hanging out of a ball of wool. This area of the genetic material can then be read much easier as long as this temporary unwrapping remains active. Scientists call these phenomena epigenetic changes. “The inflammasome triggers such epigenetic changes,” explains Dr. Latz. “The immune system consequently reacts even to small stimuli with stronger inflammatory responses.”

The immune system reacts to the proliferation of viruses. The viruses cause the inflammation, which has been linked to all pathology in more than 72,500 published works. See microRNA.

See also: Field-deployable viral diagnostics using CRISPR-Cas13

…the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. We developed HUDSON (heating unextracted diagnostic samples to obliterate nucleases), a protocol that pairs with SHERLOCK for viral detection directly from bodily fluids, enabling instrument-free DENV detection directly from patient samples in <2 hours. We further demonstrate that SHERLOCK can distinguish the four DENV serotypes, as well as region-specific strains of ZIKV from the 2015–2016 pandemic. Finally, we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.

Pardis C. Sabeti’s group already linked the anti-entropic virucidal energy of sunlight from the creation of enzymes to natural selection for energy-dependent codon optimality via the pheromone-controlled stability of organized genomes in a human population in what is now Central China.
See this report from 2013 on fixation of the EDAR V370A substitution.
Following the footprints of positive selection February 15th, 2013.
For comparison to positive selection for food and fixation of the EDAR V370A amino acid substitution, the pseudoscientific nonsense about evolution touted by Pardis C. Sabeti’s group appears in this YouTube video report: 2 Cell Studies Reveal Genetic Variation Driving Human Evolution
In the mouse model of food energy-dependent pheromone-controlled ecological adaptations, they replaced the valine normally found in mouse EDAR with the alanine that’s under selection in humans. They got mice with thicker hair, changes in mammary tissue, and and increased  number of eccrine sweat glands. Those changes parallel phenotypic changes in humans. The phenotypic changes in humans link the quantized energy-dependent creation of microRNAs to biophysically constrained viral latency in all living genera.
In humans, the changes are linked to visual perception of mass and energy and the perception of physical features that are sexually selected.
See: Olfaction Warps Visual Time Perception
A single base change results in the valine to alanine substitution, which changes the ancient mammalian gene EDAR and the EDAR encoded protein.
That fact was reported in the context of links from subatomic particles and all levels of biophysically constrained viral latency and biological organization in my 2014 invited review of nutritional epigenetics.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (unpublished)
Conclusion:

The ecological adaptations, which appear to be manifested in the human population are detailed in these two reports [162-163]. The ecological adaptations are likely to be nutrient-dependent and pheromone-controlled. If so, ecological variation probably leads to ecological, social, neurogenic, and socio-cognitive niche construction, which is manifested in increasing organismal complexity and species diversity. If not, there may be something as yet unknown about mutations and evolution that makes sense in the light of what is known about nutritional epigenetics and the molecular biology of species from microbes to man

162. Kamberov, Yana G.; Wang, S.; Tan, J.; Gerbault, P.; Wark, A.; Tan, L.; Yang, Y.; Li, S.; Tang, K.; Chen, H., et al., Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. Cell 2013, 152 (4), 691-702. doi: 10.1016/j.cell.2013.01.016
163. Grossman, Sharon R.; Andersen, Kristian G.; Shlyakhter, I.; Tabrizi, S.; Winnicki, S.; Yen, A.; Park, Daniel J.; Griesemer, D.; Karlsson, Elinor K.; Wong, Sunny H., et al., Identifying Recent Adaptations in Large-Scale Genomic Data. Cell 2013, 152 (4), 703-713. doi: 10.1016/j.cell.2013.01.035
See also:
161. Rosenberg, S. M.; Queitsch, C., Combating Evolution to Fight Disease. Science 2014, 343 (6175), 1088-1089. doi: 10.1126/science.1247472
Kalevi Kull: Censorship & Royal Society Evo Event

Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge. — Kalevi Kull

Serious scientists from South Korea are the winners. Two recent publications forced the denuclearization of North Korea.
Emergence of Human G2P[4] Rotaviruses in the Post-vaccination Era in South Korea: Footprints of Multiple Interspecies Re-assortment Events

Compared to the G2 RotaTeq vaccine strain, 17-24 amino acid changes, specifically A87T, D96N, S213D, and S242N substitutions in G2 epitopes, were observed. These results suggest that multiple interspecies re-assortment events might have contributed to the emergence of G2P[4] rotaviruses in the post-vaccination era in South Korea.

A Single Amino Acid at the Polymerase Acidic Protein Determines the Pathogenicity of Influenza B Viruses

When analyzed using reverse-genetically rescued viruses, it was shown that PA K338R alone could increase the pathogenicity of both IBVs in mice and viral replication property in the respiratory tracts of ferrets. In a subsequent mini-replicon assay, the effect of PA K338R was highlighted by the enhancement of viral polymerase complex activity of both Vc_BR60 and Ym_WI01 viruses. These results suggest that the PA K338R mutation may be a molecular determinant of IBV pathogenicity via modulating the viral polymerase function of IBVs.

Mutations are known to be the molecular determinants of all pathology in species from microbes to humans. See:  Virus-mediated archaeal hecatomb in the deep seafloor
Watch as Hashem Al-Ghaili puts everything known to serious scientists about the virus-mediated archaeal hecatomb back into the context of neo-Darwinian evolution.

See also: Study offers new approach to starve p53 deficient tumors

One major hallmark of cancer cells is their ability to adapt to stressful conditions such as nutrient deprivation. Rapidly growing tumor cells must compete for the ever-diminishing supply of nutrients in the surrounding environment to survive and proliferate. Targeting these adaptive mechanisms represents a promising approach for cancer therapeutics.

It’s a little late to claim that the virus-driven theft of quantized energy is linked from autophagy to adaptations in viruses. All serious scientists know that food energy-dependent pheromone-controlled biophysically constrained autophagy has been linked to viral latency and to ecological adaptations in all living genera. Intelligent people know that viruses have been linked to all pathology.
See also: From Istanbul, Turkey. Respect for all human life has been placed into the context of the energy-dependent de novo creation of microRNAs and the works of an Islamic creationist in Turkey.

Autophagy-Regulating microRNAs and Cancer
Cancer researchers in other countries clearly are approaching the cure for all pathology from a scientific creationist perspective despite being forced to place their claims into the context of evolution to get their works past peer review.
The Trump administration has been working towards world peace with other leaders for more than a year. See for example:
May 3, 2017
LIVE: President Donald J. Trump and Palestinian President Mahmoud Abbas make a joint statement at the White House.
Who does not want World Peace? Why The End of the Korean War Is Bad News for the United States
Cytosis can be used to teach everything from base editing to RNA editing to everyone over age 10. They will learn how to link the creation of energy to biophysically constrained viral latency via the physiology of pheromone-controlled reproduction.

Autophagy in health and disease (1)

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors

Each of these pathways have an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease…

The author includes what is known about the links from biophysically constrained RNA-mediated energy-dependent pheromone-controlled reproduction in yeasts to mammals.
See also this comment by Frank Xavier on Eat Yourself to Live: Autophagy’s Role in Health and Disease

Amino acids are not all the same, EAA and NEAA messages epigenetically control sometimes univocal responses, but more often they rule opposing effects.

I wrote:

Thanks for mentioning that. In a recent interview about his forthcoming book, Carl Zimmer claimed

…we need to be much more skeptical about other forms of heredity, like epigenetics.

(edited) Food energy-dependent biophysically constrained viral latency has been linked to healthy longevity in all living genera via autophagy, in the context of fixation of RNA-mediated amino acid substitutions and game play in Cytosis, for ages 10+.

In that context, we included a section on molecular epigenetics in this 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior

Our claims have since been supported at every level of examination that now links the sun’s anti-entropic virucidal energy from electrons to ecosystems via cryo-EM technology and the creation of microRNAs.

See: Regulation of Luteinizing Hormone Receptor mRNA Expression in the Ovary: The Role of miR-122 and Regulation of FSH expression by differentially expressed miR-186-5p in rat anterior adenohypophyseal cells and Modulation of miRNAs by Vitamin C in Human Bone Marrow Stromal Cells
The microRNA-mediated link from Vitamin C to ecological adaptations in a modern human population in China established the facts about alternative splicings of pre-mRNA that we included in our 1996 review. See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
See also:  Reproductive role of miRNA in the hypothalamic-pituitary axis
See also: Chemistry at the nexus of water and energy

Our ability to harness reactions that absorb or release energy is often contingent on water as a mediator. We can appreciate this simply by considering the steam that drives our electricity-generating turbines, the rivers that flow through our hydroelectric plants, and the freshwater–saltwater interface from which we can harvest blue energy. Whether we split water (as plants do), make it (as a product of combustion) or just drink it, this compound is inexorably tied to energy. Chemistry is at the heart of these topics and this collection brings together content from across Nature Research that focuses on the chemistry of energy production and water treatment.

Philip C. Ball and Carl Zimmer continue to display their overwhelming ignorance of cell biology in two books:
Beyond Weird

We now realise that quantum mechanics is less about particles and waves, uncertainty and fuzziness, than a theory about information…

See for comparison: Life is physics and chemistry and communication and What is life when it is not protected from virus driven entropy
See also: She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity

We need a new definition of what heredity is…

Both so-called science journalists have ignored everything known to serious scientists about biophysically constrained viral latency. They reach a very large target audience of others who are biologically uninformed.
In the context of those who are equally uninformed, so-called science journalists have the power to contribute to increasing amounts of  unnecessary suffering and premature deaths. Only the emergence of Timothy J. Cunningham as director of the CDC is likely to stop them. May God help us all if Timothy J. Cunningham has somehow vanished without a trace and fails to return to put pseudoscientists and their idiot minions into their proper place.

Alternative splicing of pre-mRNA

Agilent technology and energy-dependent autophagy

The first step towards understanding the link from the creation of energy to metabolism-related cellular function is called energy phenotyping. It requires the  technology to measure energy-dependent changes in RNA-mediated metabolic switches via the RNA interference (RNAi) screening strategy. Endogenous RNAi must then be linked  to the prevention of the virus-driven degradation of messenger RNA that causes all pathology.
Scientists discover possible master switch for programming cancer immunotherapy

…they employed an RNA interference screening strategy which can test the actual function of thousands of factors simultaneously.

See also: Energy as information and constrained endogenous RNA interference (video 6:46 minutes)
Abstract:

Feedback loops link quantized energy as information to biophysically constrained RNA-mediated protein folding chemistry. Light induced energy-dependent changes link angstroms to ecosystems from classical physics to chemistry/chirality and to molecular epigenetics/autophagy. The National Microbiome Initiative links microbial quorum sensing to the physiology of reproduction via endogenous RNA interference and chromosomal rearrangements. The rearrangements link energy-dependent fixed amino acid substitutions to the Precision Medicine Initiative via genome wide inferences of natural selection. This detailed representation of energy-dependent natural selection for codon optimality links biologically- based cause and effect from G protein-coupled receptors to RNA-mediated amino acid substitutions and the functional structure of supercoiled DNA. Energy-dependent polycombic ecological adaptations are manifested in supercoiled DNA. Chromosomal inheritance links the adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes. For contrast, virus-driven energy theft is the link from messenger RNA degradation to negative supercoiling, constraint breaking mutations, and hecatombic evolution. The viral hecatomb links transgenerational epigenetic inheritance from archaea to Zika virus-damaged DNA, which typically is repaired by endogenous RNA interference and fixation of RNA-mediated amino acid substitutions in organized genomes.

See also: Measuring the Metabolic Switch in Cancer Cells – Agilent (pdf)

Yoshida used TRAP1-null cells and transient TRAP1 mutants on an Agilent Seahorse XF96 Analyzer to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1 deficiency promotes increased mitochondrial respiration, fatty acid oxidation, accumulation of TCA intermediates, ATP, and ROS, while suppressing glucose metabolism.

The virus-driven degradation of messenger RNA is the only perfectly obvious reason for changes in oxidative phosphorylation and aerobic glycolysis that prevent the metabolism of glucose. Natural selection for energy-dependent codon optimality links the creation of energy to the metabolism of glucose via the creation of enzymes that metabolize food energy. Energy-dependent RNA-mediated error-free DNA repair and fixation of amino acid substitutions is required to link the creation of enzymes and the species-specific production of pheromones from the physiology of reproduction to biophysically constrained viral latency and all morphological and behavioral phenotypes in all living genera.
In that context, energy-dependent natural selection for codon optimality links biologically-based cause and effect from hydrogen-atom transfer in DNA base pairs in solution to the transgenerational epigenetic inheritance of healthy longevity. For contrast, the virus-driven theft of quantized energy links changes in non-coding RNAs to all pathology.
For example, see: Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene
See also: A Concise Review of MicroRNA Exploring the Insights of MicroRNA Regulations in Bacterial, Viral and Metabolic Diseases
The link from the virus-driven theft of quantized energy to glioblastoma may be the best example of how viruses are readily linked to the cell death gene in all cell types of all individuals of all living genera. That fact is more obvious with further examination of details provided for free in book chapters from Codon Publishing.
See: Noncoding RNAs in Glioblastoma  Free book chapter from Codon Publishing

The vast majority of the human genome is transcribed into noncoding RNAs. Among these, microRNAs (miRNA) and long noncoding RNAs (lncRNA) are frequently deregulated in cancer, where they regulate a wide variety of functions.

See also: Epigenetic Mechanisms of Glioblastoma Free book chapter from Codon Publishing

Aberrant DNA methylation is a common event in the genesis and progression of tumors. The application of next-generation sequencing enables the identification and mapping of DNA methylation and its derivatives, 5fC and 5hmC, to base-pair resolution. This chapter describes nine novel hypermethylation genes and six hypomethylation genes, identified by constructing a DNA methylation profile, in glioblastoma. Abnormal promoter methylation and histone modifications were associated with differential expression of miRNAs in glioblastoma: miR-185 reversed global DNA methylation and the methylation level of the hypermethylation genes by targeting DNMT; and miR-101 regulated histone methylation of hypomethylation genes by targeting EED, EZH2, and DNMT3A. The long noncoding RNA CASC2c directly bound to miR-101 via microRNA response elements, and there was a reciprocal repression between CASC2c and miR-101. Despite being competitors they both led to the overexpression of their target hypomethylation genes CPEB1, PRDM16, and LMO3. Taken together, glioblastoma is a complicated pathological process with deregulated methylation and histone modifications. Focal differentially methylated region and differentially methylated site studies will be helpful for the identification of regulatory elements of transcription. Studies of intragenic and distant intergenic alterations in DNA methylation will help elucidate the nature of epigenetic deregulation in glioblastoma.

The Seahorse XF Cell Energy Phenotype Test kit is a simple assay kit that simultaneously measures the two major energy producing pathways in live cells – mitochondrial respiration and glycolysis, allowing rapid determination of energy phenotypes of cells and investigation of metabolic switching.
The simultaneous measurement of two major energy-producing pathways in live cells allows serious scientists to report their findings in the context of what is known about mitochondrial respiration and glycolysis. Glycolysis is epigenetically effected and RNA-mediated. No magic of evolution or nonsense about natural selection for anything except food and reproduction is required to explain how rapid metabolic switching determines whether or not viral latency is biophysically constrained across the time-space continuum.
See: From Fertilization to Adult Sexual Behavior (1996)

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: Epigenetic modifications poster (Abcam)
Also from Abcam: Mechanisms of Recombination conference
The bottom line is The secret to safe DNA repair  (2015)

…if you don’t have this enzyme, then this error-free repair is stopped. You can’t do it. If you can’t do the error-free repair, among other things that happen is that you expect these cells to be cancer prone.

Clearly, the creation of the enzyme is energy-dependent and biophysically constrained by the pheromone-controlled physiology of reproduction. Pseudoscientists seem to know nothing about that, and most serious scientists are not telling you the facts that link the virus-driven degradation of messenger RNA to the “death gene” via the mechanisms that fail during recombination.
But see: microRNA autophagy  and also see: See:  Agilent Seahorse XF Publications Alert for December 2017
Selected publications
Autophagy maintains the metabolism and function of young and old stem cells
Ho, T. T., Warr, M. R., Adelman, E. R., Lansinger, O. M., Flach, J., Verovskaya, E. V., Figueroa, M. E. and Passegue, E.
Nature. 2017 Mar 9, 543 (7644):205-210.
Involvement of autophagy in the outcome of mitotic catastrophe
Sorokina, I. V., Denisenko, T. V., Imreh, G., Tyurin-Kuzmin, P. A., Kaminskyy, V. O., Gogvadze, V. and Zhivotovsky, B.
Sci Rep. 2017 Nov 6, 7 (1):14571.
Sugar or Fat?-Metabolic Requirements for Immunity to Viral Infections
Shehata, H. M., Murphy, A. J., Lee, M. K. S., Gardiner, C. M., Crowe, S. M., Sanjabi, S., Finlay, D. K. and Palmer, C. S.
Front Immunol. 2017 Oct 16, 8:1311.
System-wide Benefits of Intermeal Fasting by Autophagy
Martinez-Lopez, N., Tarabra, E., Toledo, M., Garcia-Macia, M., Sahu, S., Coletto, L., Batista-Gonzalez, A., Barzilai, N., Pessin, J. E., Schwartz, G. J., Kersten, S. and Singh, R.
Cell Metab. 2017 Dec 5, 26 (6):856-871 e5.
Late-onset Alzheimer’s disease is associated with inherent changes in bioenergetics profiles
Sonntag, K. C., Ryu, W. I., Amirault, K. M., Healy, R. A., Siegel, A. J., McPhie, D. L., Forester, B. and Cohen, B. M.
Sci Rep. 2017 Oct 25, 7 (1):14038.

BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells
An, M. X., Li, S., Yao, H. B., Li, C., Wang, J. M., Sun, J., Li, X. Y., Meng, X. N. and Wang, H. Q.
J Cell Biol. 2017 Dec 4, 216 (12):4091-4105.
Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon cancer cells
Untereiner, A. A., Pavlidou, A., Druzhyna, N., Papapetropoulos, A., Hellmich, M. R. and Szabo, C.
Biochem Pharmacol. 2017 Oct 20, [epub ahead of print]
ISG15 governs mitochondrial function in macrophages following vaccinia virus infection
Baldanta, S., Fernandez-Escobar, M., Acin-Perez, R., Albert, M., Camafeita, E., Jorge, I., Vazquez, J., Enriquez, J. A. and Guerra, S.
PLoS Pathog. 2017 Oct 27, 13 (10):e1006651.
High throughput measurement of metabolism in planarians reveals activation of glycolysis during regeneration
Osuma, E. A., Riggs, D. W., Gibb, A. A. and Hill, B. G.
Regeneration. 2017 Nov 02, [epub ahead of print]
Current technical approaches to brain energy metabolism
Barros, L. F., Bolanos, J. P., Bonvento, G., Bouzier-Sore, A. K., Brown, A., Hirrlinger, J., Kasparov, S., Kirchhoff, F., Murphy, A. N., Pellerin, L., Robinson, M. B. and Weber, B.
Glia. 2017 Nov 7, [epub ahead of print]
Glucose-regulated protein 75 determines ER–mitochondrial coupling and sensitivity to oxidative stress in neuronal cells
Honrath, B., Metz, I., Bendridi, N., Rieusset, J., Culmsee, C. and Dolga, A. M.
Cell Death Discovery. 2017 Nov 06, [epub ahead of print]

Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users
Panee, J., Gerschenson, M. and Chang, L.
J Neuroimmune Pharmacol. 2017 Nov 4, [epub ahead of print]
RNA cytosine methyltransferase Nsun3 regulates embryonic stem cell differentiation by promoting mitochondrial activity
Trixl, L., Amort, T., Wille, A., Zinni, M., Ebner, S., Hechenberger, C., Eichin, F., Gabriel, H., Schoberleitner, I., Huang, A., Piatti, P., Nat, R., Troppmair, J. and Lusser, A.
Cell Mol Life Sci. 2017 Nov 4, [epub ahead of print]
Deep transcriptome annotation enables the discovery and functional characterization of cryptic small proteins
Samandi, S., Roy, A. V., Delcourt, V., Lucier, J. F., Gagnon, J., Beaudoin, M. C., Vanderperre, B., Breton, M. A., Motard, J., Jacques, J. F., Brunelle, M., Gagnon-Arsenault, I., Fournier, I., Ouangraoua, A., Hunting, D. J., Cohen, A. A., Landry, C. R., Scott, M. S. and Roucou, X.
Elife. 2017 Oct 30, 6.
The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12
Shen, H., Campanello, G. C., Flicker, D., Grabarek, Z., Hu, J., Luo, C., Banerjee, R. and Mootha, V. K.
Cell. 2017 Nov 2, 171 (4):771-782 e11.

See also: Research areas for this month include:

See for comparison: Autophagy

Autophagy is a process by which cellular material is degraded by lysosomes or vacuoles and recycled. Several autophagy pathways operate within a cell, including macroautophagy, microautophagy and chaperone-mediated autophagy.

Latest Research and Reviews

For example:

Dual role of autophagy in hallmarks of cancer

Quantitative assessment of cell fate decision between autophagy and apoptosis

The Nature Publications Group has fallen far behind the data and technical expertise of all the serious scientists in the world. It seems likely that they will attempt to portray autophagy as something besides the innate phage defense system and fail miserably.

Autophagy is the antiphage defense strategy December 8, 2016

What would you do if your publisher arrived at the “Autophagy Party” more than a year late and you had to introduce them as a supporter of neo-Darwinian nonsense and “Big Bang” cosmology?
Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge. — Kalevi Kull
 

Cytosis can be used to teach everything from base editing to RNA editing to everyone over age 10. They will learn how to link the creation of energy to biophysically constrained viral latency via the physiology of pheromone-controlled reproduction.

A null mutation and healthy longevity?

Summary: Food odors and pheromones biophysically constrain all pathology in species from microbes to humans. What kind of biologically uninformed science idiot leaves out everything known to serious scientists about the virus-driven degradation of messenger RNA and tells others they must falsify the neutral null theory that led to claims about a biophysically constrained beneficial “null mutation” in the Amish population of Berne, Indiana?
Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia
Reported as: How to Control Traffic on Cellular Highways

Intracellular and extracellular traffic control

Reported in: How to control traffic on cellular highways http://neurosciencenews.com/enzyme-transportation-7915/

See for comparison: A null mutation in SERPINE1 protects against biological aging in humans
Reported as: Amish gene can make them live 10 years longer and avoid diabetes

A gene variant that arose decades ago in an Amish group…

All gene variants are quantized energy-dependent and the pheromone-controlled physiology of reproduction protects all organized genomes from the virus-driven degradation of messenger RNA. The degradation of messenger RNA links mutations to all pathology. Any claim that “a gene variant arose” is a claim made by a biologically uninformed science idiot. Gene variants in humans are biophysically constrained by the availability of food energy. Other humans may not know that.
Watch and listen to Richard P. Feynman presciently claim that the “null mutation” theory of healthy longevity is an example of “human idiocy.”

Help others to find any experimental evidence that suggests a “null mutation” can be beneficial and/or protect them from biological aging. See for alternative representations of biologically-based facts: Best matches for “null mutation“: and others.
If you cannot find experimental evidence of a beneficial “null mutation” see: Consciousness in the universe: A review of the ‘Orch OR’ theory They inadvertently linked quantum physics from consciousness to quantum souls.
Reported as: Anesthesia Points to Deeper Level ‘Quantum Channels’ as Origins of Consciousness subtitle “Electron resonance pervades the brain”

“Using molecular modeling, the US-Canadian team of Travis Craddock, Stuart Hameroff and Jack Tuszynski had previously shown anesthetic binding in ‘quantum channels’, non-polar arrays of amino acid pi resonance clouds, winding through microtubules.”

See also: The vibrational theory of olfaction for the win

The same kinds of amino acid substitutions that control the separations and interactions of side chains in fluorescent proteins also play an essential role in tuning the proposed mechanism for vibration detection—inelastic electron tunneling. Life literally runs on electron tunneling through the respiratory chain complexes in mitochondria.

For comparison, see the conclusion to: Quantized Energy Links Olfaction from Angstroms to Ecosystems Part 2
Beneficial “null mutations” can now be placed into the context of the creation of a universe that — with or without us — is always watching, like Santa Claus.
For a historical perspective on that pseudoscientific nonsense, see:
Splendor and misery of adaptation, or the importance of neutral null for understanding evolution

To claim adaptation, the neutral null has to be falsified.

A universal trend of amino acid gain and loss in protein evolution

Amino acid composition of proteins varies substantially between taxa and, thus, can evolve.

The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis… — Eugene Koonin
What kind of biologically uninformed science idiot leaves out everything known to serious scientists about the virus-driven degradation of messenger RNA and tells others they must falsify the neutral null theory that led to claims about a biophysically constrained beneficial “null mutation” in the Amish population of Berne, Indiana?
Food odors and pheromones biophysically constrain all pathology in species from microbes to humans.
See for comparison: Chemosignals from isolated females have antimutagenic effect in dividing the cells of bone marrow from male mice of the CBA strain

…specific, volatile, and zoosocial important chemosignals are a promising approach both to modeling posttraumatic stress disorders in humans [36] and to searching for mehods of their treatment.

Humans also have various pheromone-induced physiological effects, especially those associated with reproduction [46, 47]. This suggests that the human olfactory system is still an effective pathway for influencing environmental factors on the human nervous
system.

[46] is Kohl, J.V., Atzmueller, M., Fink, B., and Grammer, K., Human pheromones: integrating neuroendocrinology and ethology, Neuroendocrinol. Lett., 2001, vol. 22, pp. 309–321.
See also: Cytogenetic approaches for determining ecological stress in aquatic and terrestrial biosystems

The assessment of genomes’ integrity plays the key role in the studies of mutagenicity in a polluted environment. We present a step-by-step recommendations for the analysis of the cytogenetic data and discuss the prospects of applying genetic tests for ecological monitoring, based on the example of analysis using crustacean species.

I suspect that the manufacturer of my human pheromone-enhanced fragrance products asked to speak with me next week due to the all-to-obvious link from human pheromones to biophysically constrained viral latency and the prevention of all pathology, which was detailed in the context of the creation of sunlight, which was subsequently linked from the creation of ATP to the creation of RNA.
Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis
The last time I spoke with him, he asked how to monetize the facts. Bergdhal’s pathology may have prompted renewed interest. Attempts to discuss that fact with other veterans have failed. I think that some of them would rather see him crucified rather than link the energy-dependent weekend resurrection of the bacterial flagellum in P. fluorescens to the the energy-dependent Resurrection of Christ.
Bergdhal’s pathology can also be placed into the context of the problematic transitions from adolescence to adulthood that are altered by fixation of one energy-dependent RNA-mediated amino acid substitution.
See: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
The A or Met allele is associated with lower enzymatic activity and the polymorphism is associated with many different personality traits. The USAF is leading the way forward towards effective treatment of mental disorders in veterans, which is something the psychiatrists who evaluated Bergdhal know about.  See for instance: US Air Force Studying Impact of Exome Sequencing in Routine Care
 

Alternative splicing of pre-mRNA

Epigenetic facts vs variable recombination theories

6/14/13 Nutrient-dependent/pheromone-controlled adaptive evolution: a model

….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’.

7/25/13
Jay R. Feierman: Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding [of] Darwinian biological evolution.
7/26/13
Jay R. Feierman: I am absolutely certain that if you showed this statement to any professor of biology or genetics in any accredited university anywhere in the world that 100% of them would say that “Random mutations are the substrate upon which directional natural selection acts” is a correct and true statement.

Facts:

Epigenetic modifications poster
DNA repair pathways poster
Epigenetic Dynamics in Stem Cells and Differentiation webinar
Epigenetic Editing: Permanently Modulate Gene Expression webinar
Histone modifications: a guide
Epigenetic Mechanisms in Early Mammalian Development webinar
DNA Methylation Changes During Cell Differentiation webinar
Chromatin: from nucleosomes to chromosomes
Epigenetics round-up of 2014

Changes in histone acetylation may aid memory reconsolidation in post-traumatic stress disorder

See also: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (2014)

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.

Theme issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’ (2017)
Recombination rate variation in sexual organisms is energy-dependent and RNA-mediated. Variation is biophysically constrained by the pheromone-controlled physiology of reproduction in species from microbes to humans. See: From Fertilization to Adult Sexual Behavior (1996)

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.
A potential ramification of epigenetic imprinting and alternative splicing may be occurring in Xq28, a chromosomal region implicated in homosexual orientation (Brook, 1993; Hu, Pattatucci, Patterson, Li, Fulker, Cherny, Kruglyak, and Hamer, 1995; Turner, 1995). Xq28 contains one of the X chromosome’s two pseudoautosomal regions (PARs), adjoins the telomere, and has various means of gene expression control (D’Esposito, Ciccodicola, Gianfrancesco, Esposito, Flagiello, Mazzarella, Schiessinger, and D’Urso (1996). Xq28, therefore, is a chromosomal region that has many of the heterochromatic and telomeric characteristics that participate in sexual determination and behavior in other species.

Theories:

Review article: Variation in recombination frequency and distribution across eukaryotes: patterns and processes
Jessica Stapley, Philine G. D. Feulner, Susan E. Johnston, Anna W. Santure and Carole M. Smadja
Phil. Trans. R. Soc. B December 19, 2017 372 20160455; doi:10.1098/rstb.2016.0455
http://rstb.royalsocietypublishing.org/content/372/1736/20160455
Review article: The impact of recombination on human mutation load and disease
Isabel Alves, Armande Ang Houle, Julie G. Hussin and Philip Awadalla
Phil. Trans. R. Soc. B December 19, 2017 372 20160465; doi:10.1098/rstb.2016.0465
http://rstb.royalsocietypublishing.org/content/372/1736/20160465
Opinion piece: Connecting theory and data to understand recombination rate evolution
Amy L. Dapper and Bret A. Payseur
Phil. Trans. R. Soc. B December 19, 2017 372 20160469; doi:10.1098/rstb.2016.0469
http://rstb.royalsocietypublishing.org/content/372/1736/20160469
Review article: Coevolution between transposable elements and recombination
Tyler V. Kent, Jasmina Uzunović and Stephen I. Wright
Phil. Trans. R. Soc. B December 19, 2017 372 20160458; doi:10.1098/rstb.2016.0458
http://rstb.royalsocietypublishing.org/content/372/1736/20160458
Review article: Evolution of recombination rates between sex chromosomes
Deborah Charlesworth
Phil. Trans. R. Soc. B December 19, 2017 372 20160456; doi:10.1098/rstb.2016.0456
http://rstb.royalsocietypublishing.org/content/372/1736/20160456
Research article: Low recombination rates in sexual species and sex–asex transitions
Christoph R. Haag, Loukas Theodosiou, Roula Zahab and Thomas Lenormand
Phil. Trans. R. Soc. B December 19, 2017 372 20160461; doi:10.1098/rstb.2016.0461
http://rstb.royalsocietypublishing.org/content/372/1736/20160461
(openaccess) Review article: The consequences of sequence erosion in the evolution of recombination hotspots
Irene Tiemann-Boege, Theresa Schwarz, Yasmin Striedner and Angelika Heissl
Phil. Trans. R. Soc. B December 19, 2017 372 20160462; doi:10.1098/rstb.2016.0462
http://rstb.royalsocietypublishing.org/content/372/1736/20160462
(openaccess) Research article: The Red Queen model of recombination hot-spot evolution: a theoretical investigation
Thibault Latrille, Laurent Duret and Nicolas Lartillot
Phil. Trans. R. Soc. B December 19, 2017 372 20160463; doi:10.1098/rstb.2016.0463
http://rstb.royalsocietypublishing.org/content/372/1736/20160463
(openaccess) Research article: Background selection as null hypothesis in population genomics: insights and challenges from Drosophila studies
Josep M. Comeron
Phil. Trans. R. Soc. B December 19, 2017 372 20160471; doi:10.1098/rstb.2016.0471
http://rstb.royalsocietypublishing.org/content/372/1736/20160471
(openaccess) Review article: Recombination rate plasticity: revealing mechanisms by design
Laurie S. Stevison, Stephen Sefick, Chase Rushton and Rita M. Graze
Phil. Trans. R. Soc. B December 19, 2017 372 20160459; doi:10.1098/rstb.2016.0459
http://rstb.royalsocietypublishing.org/content/372/1736/20160459
(openaccess) Review article: Are the effects of elevated temperature on meiotic recombination and thermotolerance linked via the axis and synaptonemal complex?
Christopher H. Morgan, Huakun Zhang and Kirsten Bomblies
Phil. Trans. R. Soc. B December 19, 2017 372 20160470; doi:10.1098/rstb.2016.0470
http://rstb.royalsocietypublishing.org/content/372/1736/20160470
Research article: What drives the evolution of condition-dependent recombination in diploids? Some insights from simulation modelling
Sviatoslav R. Rybnikov, Zeev M. Frenkel and Abraham B. Korol
Phil. Trans. R. Soc. B December 19, 2017 372 20160460; doi:10.1098/rstb.2016.0460
http://rstb.royalsocietypublishing.org/content/372/1736/20160460

Alternative splicing of pre-mRNA

Stem cells do not create themselves

Summary: The energy-dependent cellular pathways have been detailed at all levels of examination from atoms to ecosystems in the context of physics, chemistry, and molecular epigenetics. The mere mention of RNA-mediated amino acid substitutions may cause theorists to panic because it eliminates their pseudoscientific nonsense in the context of the claim that proteins do not create themselves.

Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis

1) The constant regeneration of stomach epithelium is driven by long-lived stem cells1, 2, 3, but the mechanism that regulates their turnover is not well understood.

2) The ability of stromal niche cells to control and adapt epithelial stem cell dynamics constitutes a sophisticated mechanism that orchestrates epithelial regeneration and maintenance of tissue integrity.
 

It is well understood by all serious scientists that turnover, which links autophagy to niche construction is food energy-dependent and pheromone-controlled via the physiology of reproduction in bacteria. That fact has been linked from the sense of smell in bacteria to our visual perception of energy and mass in the context of the space-time continuum of ecological, social, neurogenic, and socio-cognitive niche construction.

See: Olfaction Warps Visual Time Perception

The food energy-dependent pheromone-controlled physiology of reproduction is obviously the link between bacteria and healthy longevity and/or between bacteriophages, which link the virus-driven degradation of messenger RNA from  mutations to all pathology.

 Are stem cells the link between bacteria and cancer?

‘Our findings show that an infectious bacterium can increase stem cell turnover’, says Sigal. ‘Since H. pylori causes life-long infections, the constant increase in stem cell divisions may be enough to explain the increased risk of carcinogenesis observed,’ and Meyer adds: ‘Our new findings shed light on the intriguing ways through which chronic bacterial infections disturb tissue function and provide invaluable clues on how bacteria, in general, may increase the risk of cancer’.

Their findings show that the virus-driven degradation of messenger RNA in bacteria links the creation of virus-infected stem cells to cancer.

See also: 2nd International Congress on Contemporary Issues in Women Cancers & Gynecologic Oncology

This is a serious contemporary issue:
microRNA breast cancer
microRNA ovarian cancer
microRNA metastases
Two presentations from this conference series mention microRNAs:

CDE010 Title: Improving Breast Cancer diagnosis by circulating microRNAs

VP: MicroRNA-21 expression in primary breast cancer tissue among female patients and its correlation with chromosome 17 aneusomy

See also: Science Says: DNA test results may not change health habits

Getting the DNA information produced no significant effect on diet, physical activity, drinking alcohol, quitting smoking, sun protection or attendance at disease-screening programs.

That fits with other results showing that, on balance, getting the information “has little if any impact on changing routine or habitual behaviors,” said psychologist Theresa Marteau of Britain’s Cambridge University, a study author.

Under his leadership at the NIH, many people have been convinced that cancer is due to “bad luck.”

See:

Teaching people to believe in pseudoscientific nonsense (bad luck theory) ensures the success of the medical profession at the cost of the unnecessary suffering and death of your loved ones.

Healthy longevity is food energy-dependent and RNA-mediated. The virus-driven degradation of messenger RNA is linked to all pathology in all living genera.

DNA testing is largely irrelevant and most people will learn that in the context of the cell biology game “Cytosis,” where players compete to fight against viruses — as each of us must do in real life via food energy as information, which is the source for ATP and the de novo creation of RNA.

See also: Inhibiting a protein found to reduce progression of Alzheimer’s and ALS in mice

Hallmarks of chronic neurodegenerative disease include progressive synaptic loss and neuronal cell death, yet the cellular pathways that underlie these processes remain largely undefined.

The pathways are energy-dependent and the virus-driven theft of energy links changes in the microRNA/messenger RNA balance to all pathology. Proteins do not create themselves. That is why a PubMed search for microRNA and Alzheimer’s or for microRNA and ALS links everything known to serious scientists about biophysically constrained protein folding chemistry to healthy longevity or to the virus-driven degradation of messenger RNA, which links mutations to all pathology.

The energy-dependent cellular pathways have been detailed at all levels of examination from atoms to ecosystems in the context of physics, chemistry, and molecular epigenetics. The mere mention of RNA-mediated amino acid substitutions may cause theorists to panic because it eliminates their pseudoscientific nonsense in the context of the claim that proteins do not create themselves.

See for comparison: Detecting ancient positive selection in humans using extended lineage sorting

Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives.

Codon Optimality Is a Major Determinant of mRNA Stability

Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The amino acid optimality code links energy-dependent changes in chirality to autophagy and homeostasis unless the virus-driven degradation of messenger RNA prevents the optimization of the code by altering the microRNA/messenger RNA balance.

See also: pubmed – microRNA (https://www.ncbi.nlm.nih.gov/pubmed/?term=microRNA)
year count
2017 7158
2016 9983
2015 10495
2014 8776
2013 7450
2012 5853
2011 4405
2010 3440
2009 2277
2008 1562
2007 995
2006 651
2005 398
2004 213
2003 105
2002 36
2001 5
1972 1

A rendering of how changes in an electron's motion (bottom view) alter the scattering of light (top view), as measured in a new experiment that scattered more than 500 photons of light from a single electron. Previous experiments had managed to scatter no more than a few photons at a time. Credit: Extreme Light Laboratory|University of Nebraska-Lincoln

Energy-dependent physical and biophysical constraints (7)

See first: Energy-dependent physical and biophysical constraints (6)
Stems Cells in the Hypothalamus Slow Aging in Mice
My comment to The Scientist

Cai says microRNAs could be a potential mechanism by which hypothalamic neural stem cells have such wide-ranging effects on aging, yet he believes that neurogenesis may also be involved.

See also: Feedback loops link odor and pheromone signaling with reproduction

At least 10,000 neurons in 26 different brain areas appear to transmit signals directly to GnRH neurons.  GnRH neurons appear to transmit signals to as many as 30,000 or more neurons in 34 brain areas, consistent with previous studies showing GnRH+ fibers and GnRH receptors in multiple brain regions. These results may reflect a strategy wherein GnRH neurons can modify diverse functions in order to coordinate the internal state of the animal and its behavior with reproduction in order to optimize reproductive success.

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

…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.

More than 63,000 indexed articles on PubMed link energy-dependent changes in the microRNA/messenger RNA balance to healthy longevity. Many of them also link the virus-driven theft of quantized energy from mutations to pathology such as John McCain’s glioblastoma. He will probably be treated with microRNAs, but that fact may not be reported because the effective treatment is a refutation of neo-Darwinian pseudoscientific nonsense about mutations, natural selection, and evolution.

Alternative splicing of pre-mRNA

Secular humanism and ecoterrorism

Noncoding RNAs Not So Noncoding

Excerpt:

“Were there going to be dozens of [micropeptides]? Were there going to be hundreds, like there are hundreds of microRNAs?” says Ingolia. “We just didn’t know.”

See also: Number of microRNAs in Human Genome Skyrockets
Excerpt:

“…researchers from Thomas Jefferson University in Philadelphia have released data that adds another 3,707 novel miRNA sequences to the human genome, in addition to the 1,900 sequences previously described. The results from this study were published recently in PNAS through an article entitled “Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs”.”

My question: If you think there are hundreds of microRNAs when there are thousands of them, you may be less likely to ask where tissue-specific microRNAs come from. But, if you do ask where they come from, you might also ask how they get to specific tissues that require energy-dependent maintenance and/or RNA-mediated DNA repair. That is a question that all serious scientists should be able to answer. The answer, for example, can be placed into the context of Christ’s work on heterochronic parabiosis.  See Christ et al., (2014) The Pharmacology of Regenerative Medicine.
Regenerative medicine links the National MicroRNAome Initiative from metabolic networks to genetic networks in the context of the Precision Medicine Initiative via nutrient-dependent RNA-mediated amino acid substitutions.

See also: Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel

This article is part of the Research Topic Brain nutrient sensing in the control of energy balance: new insights and perspectives

The article links energy-dependent changes in microRNA flanking sequences from the innate immune system to supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy in the context of the physiology of reproduction and fixation of nutrient-dependent RNA-mediated amino acid substitutions.

Other articles in the Research Topic will undoubtedly link changes in the microRNA/messenger RNA balance from energy-dependent changes in angstroms to energy-dependent changes in ecosystems via what is already known about supercoiled DNA. For example, more than 50, 500 indexed PubMed articles provide details about how energy-dependent microRNAs are linked to healthy longevity and how virus-driven energy theft links mutations to all pathology.

See:MicroRNA

See for example: Cross Talk between Cancer and Mesenchymal Stem Cells through Extracellular Vesicles Carrying Nucleic Acids
Conclusion:

…EVs derived from both MSCs and tumor cells display common ncRNAs; however, the functions they exhibit may be diverse depending on the cellular environment. Since ncRNAs interact with numerous molecular partners, their function is complex and depends on the cellular context. The response to EVs not only depends on their ncRNA/protein content but also on the metabolic pathways activated in recipient cells as well as their specific function. The same EVs, for instance, may trigger opposite actions in normal and tumor cells (22). Pandolfi and co-workers (164) have suggested that there is a RNA language that uses miRNAs response elements in different transcripts as “letters.” These diverse sets of miRNAs may form diverse “words,” thus performing different molecular and cellular functions. This hypothesis may, therefore, explain the different functions carried out by the same miRNAs in different contexts on tumor development. Taking into account that EV transport is bidirectional and that tumor cells can change the content of MSC-EVs and vice versa (160, 161), it is possible that the individual ncRNA display different and even opposite functions in vivo.

My comment: Serious scientists have passed the tipping point that conclusively links energy-dependent microRNAs to healthy longevity and virus-driven energy theft to mutations and all pathology via what is known about RNA-directed DNA methylation and biophysically-contrained protein folding chemistry.

See also: Structural diversity of supercoiled DNA

Excerpt:

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.

See what the biologically uninformed secular humanist and ecoterroist Sean Ovis does with everything known to serious scientists about the modulation of DNA metabolic processes:

Virus Driven Energy Theft

Conclusion:

If you are a creation scientist, you can take comfort in the fact that as you get older, the control of these viral fragments is considerably weakened, and eventually one or more of these jumping genes will be let loose in your body to wreak havoc on your DNA. When that happens, you can thank God, because they will have brought you closer to him.

See what Jimmy Carter did about his cancer, for comparison: Jimmy Carter announces he is cancer-free

Excerpt:

Carter announced in August that doctors had told him that four spots of cancer had spread to his brain. He said his fate “is in the hands of God, whom I worship.”

My comment: A clear difference between ecoterrorists and a former president of the United States has emerged. Are the selfish ecoterrorists a threat to national security?

The ecoterrorists do not want others to learn about virus-driven energy theft in the context of the Precision Medicine Initiative or the National MicroRNAome Initiative.

They are hate-mongers who want you to believe that nothing can help you and nothing can save you from the suffering and death that they have brought to you via their ignorance and belief in nothing.

For comparison see the studies that are being published on energy-dependent RNA methylation.   Don’t be surprised by what’s coming from serious scientists who know how cell type differentiation occurs.

For example: Mechanism and biological role of Dnmt2 in Nucleic Acid Methylation

Abstract:

A group of homologous nucleic acid modification enzymes called Dnmt2, Trdmt1, Pmt1, DnmA, and Ehmet in different model organisms catalyze the transfer of a methyl group from the cofactor S-adenosyl-methionine (SAM) to the carbon-5 of cytosine residues. Originally considered as DNA MTases, these enzymes were shown to be tRNA methyltransferases about a decade ago. Between the presumed involvement in DNA modification-related epigenetics, and the recent foray into the RNA modification field, significant progress has characterized Dnmt2-related research. Here, we review this progress in its diverse facets including molecular evolution, structural biology, biochemistry, chemical biology, cell biology and epigenetics.

My comment: Frank Lyko is a co-author. He is also the co-author of Epigenetic Regulation by Heritable RNA

Excerpt: 

RNA-mediated inheritance could provide an attractive mechanism that allows a rapid adaptation to changing environmental conditions without affecting the genetic makeup of an organism.

My comment: We will continue to see that neo-Darwinian theorists are left with no fall-back position. No experimental evidence of biologically-based cause and effect has ever linked mutations from natural selection to evolution. Now, what is known about RNA methylation will be added to what is known about RNA-directed DNA methylation, and there will be no place for theorists to hide. They will be embarrassed and asked to leave — anywhere they are found.

rp_levels-of-organization.jpg

Ecological speciation. Get it, theorists?

A Prkci gene keeps stem cells in check

Excerpt:

In the presence of Prkci, the Notch pathway remains silent, and stem cells differentiate into specific cell types.

My comment: Several days of attempted discussion led to this question
Do you get it now, jvk?
My response: Everyone who is not a biologically uninformed science idiot gets it. The Zechiedrich lab‘s focus links energy-dependent base pair changes from atoms to ecosystems. The Rosenberg lab‘s focus on stress shows why others must eliminate any focus on population genetics to fight disease.
“Combating Evolution to Fight Disease” cites Dobzhansky (1973) who wrote: “…the so-called 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.”
The nutrient-dependent link from microRNAs to base pairs and RNA-mediated amino acid substitutions links metabolic networks from atoms to ecosystems via cell adhesion proteins and genetic networks that protect organized genomes from stress-linked virus-driven genomic entropy.
Energy-dependent supercoiled DNA and cell type differentiation via the physiology of reproduction and fixation of RNA-mediated substitutions lead to ecological speciation. Theft of energy by viruses links the proliferation of viral microRNAs to failed DNA repair and pathology. Across a lifetime of nutrient-stress and/or social stress, the innate immune system of all cells in all tissues of all organs in all our organ systems is suppressed and we often needlessly suffer and die because neo-Darwinian theorists claim that random mutations are sometimes beneficial when the stress-driven accumulation of mutations always leads to pathology.