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

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

The difference between an energy-dependent RNA-mediated amino acid substitution and a mutation has been largely ignored as pseudoscientists linked accidents to evolution.

See for example: Can watery asteroids explain why life is ‘left-handed’? (2009)

Sandwalk readers will know that I [Larry Moran] prefer an evolutionary explanation.

My summary of his evolutionary explanation:

The simplest amino acid is glycine where the R group is just a hydrogen atom. Glycine is not a chiral compound and there’s no such thing as L-glycine or D-glycine. All other natural amino acids are chiral. Larry Moran claims that glycine might have formed spontaneously. If so, the exclusive presence of L-amino acids instead of D-amino acids is just an accident. But it is an accident that somehow started with the spontaneous formation of glycine. The spontaneous formation of anything would be considered to be a miracle by those who  do not believe in evolutionary explanations.

Anyone who does not recognize the fact that people like Larry Moran think in terms of the accidental creation of the only achiral amino acid, which stabilizes the organized genomes of all vertebrates, should not read further.

It is a waste of time to examine facts after you decide to believe in more pseudoscientific nonsense than any serious scientist has ever considered. If you have not learned the difference between a mutation and an energy-dependent amino acid substitution, are you a well-trained medical practitioner?

See: Updates of the HbVar database of human hemoglobin variants and thalassemia mutations

Hemoglobinopathies are the commonest single-gene genetic disorders in humans, resulting from pathogenic genome variants in the human α-like and β-like globin gene clusters (reviewed in 1). Single nucleotide substitutions or indels [INsertions/DELetionS] can lead to several hemoglobin variants owing to amino acid replacements, while molecular defects in either regulatory or coding regions of the human HBA2, HBA1, HBB or HBD genes can minimally or drastically reduce their expression, leading to α-, β- or δ-thalassemia, respectively.

Difference in mass resulting from the change of a single amino acid 

The mass of normal alpha chain is 15126.3 Da and that of the normal beta chain 15867.5, the changes induced by single point mutations are given above (only those allowed by the genetic code are given). As an example the change from Asp to His will increase the normal mass by 22 units and the reverse change will decrease the mass by the same amount.

The example links an increase in the stability and/or a decrease in the stability of the organized genome to a mutation and also to an amino acid substitution. The stability of all organized genomes is food energy-dependent and biophysically constrained via differences in hydrogen atom transfer in DNA base pairs in solution. The differences are measured in the context of blood gas analyses, and you should already know that the potential of hydrogen (pH) will determine the patient outcome — before you order the test.

If you do not understand this, find someone from the medical laboratory me to discuss it with. You may feel like a fool, but you will be less likely to kill someone via your ignorance.

See Fig. 2 Difference in the network of hydrogen bonds between high- and low-altitude Hb variants, HH-H and LL-L, respectively.

The differences in the network of hydrogen bonds between high- and low-altitude Hb variants should be placed into the context of why medical laboratory scientists must be trained to calibrate blood gas analyzers based on the barometric pressure at the location of the lab. For comparison to a somewhat less technical approach to the link from the circulatory system to nutrient energy-dependent microRNAs and pheromone-controlled biodiversity, see: Primo Vascular/Meridian System 2016

Thornton Streeter claimed that this a small contribution to understanding energy medicine. It links everything known about the creation of energy-dependent hemoglobin variants to all food energy-dependent biodiversity via the pheromone-controlled physiology of reproduction and the vascular/meridian system of humans.

See also: Ugur Murat Ozdemiroglu Admin of WORLD CONGRESS OF OBSTETRICS & GYNECOLOGY FORUM reported Yesterday at 3:36am on 12/11/17

By far the most important disease resulting from a mutation to an abnormally functioning hemoglobin is sickle cell disease, in which a single base change in the DNA results in a substitution of valine for glutamic acid at the sixth position in the beta globin chain.

Like all other quantized energy-as-information/food energy-dependent ecological adaptations, this hemoglobin variant is frequently reported to be a mutation. The link from one base pair change to the pheromone controlled physiology of reproduction and fixation of an amino acid substitution in the organized genomes of human populations protects them from extinction. The extinctions are caused by the virus-driven degradation of messenger RNA that most people indirectly link from malarial parasites to hemoglobin variants such as Hemoglobin S. Most people do not link viruses to all pathology, despite the historical record.

See: Biology, molecular and organismic (1964)

Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.

See also: Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation” (1964)

Isolated thymus nuclei transport amino acids into an intranuclear pool by a process which seems to depend on energy from nuclear ATP synthesis (20).

Link opens pdf:  Participation of glycolysis, and the citric acid cycle, in nuclear adenosine triphosphate synthesis (1963)

…thymus nuclei appear to have an endogenous substrate, and some experiments are presented which suggest that this substrate is probably not glycogen or glucose.

Ten years after McEwen et al., (1963) linked the creation of ATP to the creation of RNA via an endogenous substrate in all cell types of all living genera, Dobzhansky placed everything known about the creation of all biodiversity on Earth into the context of: Nothing in Biology Makes Any Sense Except in the Light of Evolution (1973)

…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.

A single base pair change and one amino acid substitution differentiates the cell types of gorillas compared to chimpanzees and modern humans. That fact has finally forced pseudoscientists to begin to examine the role that viruses play in all pathology.

See: Virus-mediated archaeal hecatomb in the deep seafloor

We show here for the first time the crucial role of viruses in controlling archaeal dynamics and therefore the functioning of deep-sea ecosystems, and suggest that virus-archaea interactions play a central role in global biogeochemical cycles.

The virus-driven degradation of messenger RNA in bacteria is linked to the creation of archaea and the virus-driven degradation of messenger RNA in humans is linked to the creation of non-human primates by the conserved molecular mechanisms that were reported in MicroRNAs: Milk’s epigenetic regulators

Our perception of milk has changed from a “simple food” to a highly sophisticated maternal-neonatal nutrient and communication system orchestrating early programming of the infant. Milk miRNAs delivered by exosomes and milk fat globules derived from mammary gland epithelial cells play a key role in this process. Exosomes resist the harsh intestinal environment, are taken up by intestinal cells via endocytosis, and reach the systemic circulation of the milk recipient. The most abundant miRNA found in exosomes and milk fat globules of human and cow’s milk, miRNA-148a, attenuates the expression of DNA methyltransferase 1, which is critically involved in epigenetic regulation. Another important miRNA of milk, miRNA-125b, targets p53, the guardian of the genome, and its diverse transcriptional network. The deficiency of exosomal miRNAs in infant formula and the persistent uptake of milk miRNAs after the nursing period via consumption of cow’s milk are two epigenetic aberrations that may induce adverse long-term effects on human health.

Only the best medical practitioners and researchers have grasped the fact that Carl Woese was wrong when he reported there were three domains of life. There is only one domain of life and the virus-driven degradation of messenger RNA is linked to all pathology in all living genera.

November 22, 2017 Sci-Hub, often referred to as the “Pirate Bay of Science,” lost three of its domain names this week.

Sci-hub.io, sci-hub.cc, and sci-hub.ac now have the infamous “serverhold” status which suggests that the responsible registries intervened. The status, which has been used previously when domain names are flagged for copyright issues, strips domains of their DNS entries.

November 23, 2017 RNA quality  Items: 1 to 20 of 604

Unless you can find access to Sci-Hub, you might find it difficult to access information on RNA quality.

See: The determinants of alternative RNA splicing in human cells

Alternative splicing represents an important level of the regulation of gene function in eukaryotic organisms. It plays a critical role in virtually every biological process within an organism, including regulation of cell division and cell death, differentiation of tissues in the embryo and the adult organism, as well as in cellular response to diverse environmental factors. In turn, studies of the last decade have shown that alternative splicing itself is controlled by different mechanisms. Unfortunately, there is no clear understanding of how these diverse mechanisms, or determinants, regulate and constrain the set of alternative RNA species produced from any particular gene in every cell of the human body. Here, we provide a consolidated overview of alternative splicing determinants including RNA-protein interactions, epigenetic regulation via chromatin remodeling, coupling of transcription-to-alternative splicing, effect of secondary structures in pre-RNA, and function of the RNA quality control systems. We also extensively and critically discuss some mechanistic insights on coordinated inclusion/exclusion of exons during the formation of mature RNA molecules. We conclude that the final structure of RNA is pre-determined by a complex interplay between cis- and trans-acting factors. Altogether, currently available empirical data significantly expand our understanding of the functioning of the alternative splicing machinery of cells in normal and pathological conditions. On the other hand, there are still many blind spots that require further deep investigations.

See also Neuropathological and transcriptomic characteristics of the aged brain

…we compared gene measures of RNA quality (RIN) and of dementia status (before and after accounting for RIN).

See also: Study finds infection and schizophrenia symptom link November 22, 2017

…activation of the maternal immune system in rats was sufficient to produce impaired timing, which is likely critical to other schizophrenia symptoms and impairments.Impaired ability to judge time accurately is a primary symptom in patients and this is also thought to be related to other symptoms, such as hallucinations, and cognitive impairment.

All Brain Perception is Rhythmic and Cyclical Says Newest Neuroscience

“We have suspected for some time that the senses are not constant but are processed via cyclical, or rhythmic functions; these findings lend new weight to that theory.”

It’s not a theory. Experimental evidence of biophysically constrained top-down causation links the energy-dependent RNA-mediated constraints on viral latency to healthy longevity via everything known to serious scientists since the time that the energy-dependent creation of ATP was linked to the energy-dependent creation of RNA.

See: Olfaction Warps Visual Time Perception

For comparison: This is a ridiculous theory.

Evolution of Epigenetic Mechanisms in Animals and Their Role in Speciation

DNA methylation is involved in gene regulation, silencing of transposons, imprinting, polyphenism, and consolidation of speciation. It may even act as a driver of evolution via stochastic developmental and environmentally induced epigenotype diversification, transgenerational inheritance of epigenetic patterns with phenotypic effects, and differential selection and genetic fixation of these phenotypes.

All ridiculous theories can be compared in the context of: To forget or to remember? Memory depends on subtle brain signals, scientists find

“The idea is, constantly as we learn information, there is a slow process that whittles away memories, and it continues whittling them away unless another part of the brain signals the memory is important and overrides it,” Davis said.

It may be that the process of acquiring and forgetting memories ebbs and flows in a state of balance, he said. Important memories like the taste of mom’s pumpkin pie might be forever retained, but trivialities like what you wore 10 years ago can fade into oblivion without consequence.

“If you have too much memory that is old and unnecessary, why keep them around? Why shouldn’t you have a system for removing those for optimal function of the brain?” Davis asked. “We’re getting all this information, all this learning during the day, and the brain may be saying, ‘No, no, bring me back to my basal, my happy state.'”

Many questions remain to be solved, Davis noted. “We need to figure out what is downstream—walk down the pathway to find the complete signaling system for forgetting,” he said. “We are very early in this research.”

Researchers who think “WE” are very early in this research are biologically uninformed science idiots. The COMT Val158Met amino acid substitution links food odor and pheromones to the biophysically constrained creation of one enzyme, which has been linked to differences in the dopaminergic reward system during the transition from adolescence to adulthood.

See:Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

I’m not sure why anyone would not already know how to link food odors and pheromones to enzymes and metabolism in humans in the context of the Human Microbiome Initiative and Precision Medicine Initiative.  But I understand why losers tend to claim that winners are still very early in this research.

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

See for comparison: Book Review by Mark Sergeant

The Scent of Eros is certainly an engaging text that informs the reader about the majority of key studies performed on human olfaction. Where it is let down is a lack of supporting evidence for some of the ideas considered, and a lack of critical consideration for some of the evidence that is presented. A reader unfamiliar with olfaction research could come away from this text unaware of several key debates within the field…

The Scent of Eros: Mysteries of Odor in Human Sexuality
By James Vaughn Kohl and Robert T. Francoeur

On page 298, we linked levels of DHEA to schizophrenia and to the odor of schizophrenics via the metabolism of DHEA to androsterone and etiocholanolone, which are indicators of nutrient stress and/or social stress. All stress-linked illnesses have since been linked from the virus-driven degradation of messenger RNA to pathology in species from microbes to humans.

See also: Epigenetic modifications poster

See also: Epigenetics round-up of 2014

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

See also: Formulation and evaluation of anti-suicidal nasal spray of Thyrotropin releasing hormone

The fact that the virus-driven degradation of messenger RNA has been linked to all pathology in all living genera has been established by serious scientists.

See also: Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis

Clearly, another question must be asked:

The first question: Who created your virus-driven death gene?

The next question: Who wants the virus-driven death gene to continue to be activated?

For example: The antagonism of the biologically uninformed science idiot who is the moderator of the Human Ethology Yahoo group increases each time scientific progress is made towards prevention of neurodegenerative diseases or suicide prevention. Instead of linking the virus-driven degradation of messenger RNA to suicide and Alzheimer’s, he posts information like this.

Choice of a suicide method: Trends and characteristics

Efforts towards suicide prevention in our veterans and others are replaced with information on their choice of a suicide method.

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