DNA methylation and microRNA biomarkers for noninvasive detection of gastric and colorectal cancer
Excerpt:
At this moment, DNA methylation and non-coding RNA including with microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) represent the largest body of available literature on epigenetic biomarkers with the highest potential for cancer diagnosis.
My comment: The SLC19A3 microRNA was mentioned in the context of cancer and brain development in The impact of new technologies on clinical decision-making in health care. The location of the base pair for the SLC19A3 gene starts at 228549926 and ends at 228582745 bp from pter ( according to hg19-Feb_2009) Also, “According to the NCBI Homo sapiens Annotation Release 106, SLC19A3 is flanked by genes including: ArfGAP with FG repeats 1 (AGFG1), microRNA 5703 (MIR5703), chromosome 2 open reading frame 83 (C2orf83), 5S ribosomal pseudogene 121 (RNA5SP121), and small nuclear ribonucleoprotein polypeptide G pseudogene 8 (SNRPGP8).”
Those facts suggest to me that the SLC19A3 microRNA link from the nutrient-dependent de novo creation of the SLC19A3 gene could be examined in the context of an atoms to ecosystems model of RNA-mediated cell type differentiation by a team of physicists, chemists and molecular biologists. But first, the team would need to become interested in linking atoms to ecosystems in the context of what is currently known to serious scientists about biologically-based cause and effect. Obviously, the systems complexity of cause and effect that links the epigenetic landscape to the physical landscape of DNA via metabolic networks and genetic networks in all living genera is beyond the capabilities of any one person to detail. And, the team members would need to know or to learn how to communicated without using the jargon of their disciplines or inventing new terms via definitions to capture the attention of science journalists who link to report “first evidence” as if the evidence had not existed from the dawn of creation.
Perhaps the team could start with what is known about Progress in microRNA delivery
Excerpt:
Viral vectors are efficient delivery agents but toxicity and immunogenicity limit their clinical usage. Herein, we review the recent advances in the mechanisms and strategies of nonviral miRNA delivery systems and provide a perspective on the future of miRNA-based therapeutics.
My comment: That fact can also be placed into the context of RNA-directed DNA methylation and histone acetylation, which is linked to cell type specific changes and healthy longevity by the conserved molecular mechanisms that link RNA-mediated amino acid substitutions to the stability of organized genomes in all living genera. Any team that starts with links from the epigenetic landscape to the physical landscape of DNA in all invertebrates and vertebrates could clarify what is known about the conserved molecular mechanism that link marine invertebrates to insects. But, they would not be the first to do that.
See: The phylogenetic utility and functional constraint of microRNA flanking sequences
This appears to have been reported in advance as: All in the (bigger) family
Excerpt:
A flurry of other presentations compared different classes of molecules—respiratory proteins, microRNAs, and the heat shock proteins produced in response to stress—in insects and standard crustaceans.
My comment: The link from nutrient-dependent microRNAs and cell adhesion proteins was removed with publication of the sequencing of the octopus genome. Instead of linking biologically-based cause and effect, they linked theories about the evolution of cephalopod neural and morphological novelties. Team-mates might need to agree to mention the fact that neo-Darwinian theory is not supported by the experimental evidence revealed in the context of the octopus genome sequence. It would take a very special team of researchers who were willing to end their careers by not supporting neo-Darwinian dogma and focusing on experimentally established facts.
See: The octopus genome and the evolution of cephalopod neural and morphological novelties
Excerpt:
We found, amid extensive transcription of octopus transposons, that a class of octopus-specific short interspersed nuclear element sequences (SINEs) is highly expressed in neural tissues (Supplementary Note 4 and Extended Data Fig. 8). Although the role of active transposons is unclear, elevated transposon expression in neural tissues has been suggested to serve an important function in learning and memory in mammals and flies28.
Conclusion:
…these novel genes, the expansion of C2H2 ZNFs, genome rearrangements, and extensive transposable element activity yield a new landscape for both trans- and cis-regulatory elements in the octopus genome, resulting in changes in an otherwise ‘typical’ lophotrochozoan gene complement that contributed to the evolution of cephalopod octopus-specific short interspersed nuclear element sequences (SINEs).
My comment: The facts do not change. Octopus-specific short interspersed nuclear element sequences (SINEs) replaced nutrient-dependent microRNAs, but the change of terms does not destroy the team’s efforts to establish links from the molecular mechanisms of cell type differentiation for comparison to claims that appear to link the complexity of octopus-specific short interspersed nuclear element sequences (SINEs) to the evolution of octopus-specific short interspersed nuclear element sequences (SINEs). Pheromones are species-specific, which suggests it doesn’t matter what undefined terms are used to link olfaction to species-specific behaviors.
However, for an example of word games played by evolutionary theorists, see: Short interspersed DNA elements and miRNAs: a novel hidden gene regulation layer in zebrafish? Clearly, no experimental evidence of biologically-based cause and effect supports the claims that DNA elements or nuclear element sequences link novel genes or any other aspect of the links from the nutrient-dependent de novo creation of olfactory receptor genes to the downstream effects on neural complexity and morphological innovations that these researchers also attributed to evolution. They used the terms short interspersed nuclear element sequences, nuclear element sequences, and DNA elements to avoid the use of the term microRNAs (miRNAs). Fortunately, their use of terms was ineffective, since serious scientists already had linked atoms to ecosystems in all living genera via details that were subsequently reported.
See: Structural diversity of supercoiled DNA
Nutrient-dependent microRNAs were linked to cell type differentiation via cell adhesion proteins and supercoiled DNA that protects organized genomes from virus-driven entropy.
See also: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity
Conclusion:
Taken together, our data untangle the complicated roles of E-cadherin and p120 in the context of distinct junctional complexes, spatially separating their functions and providing an explanation for their conflicting behaviour in cell growth. In addition, they identify PLEKHA7 as a specific marker of ZA that mediates suppression of growth-related signalling. Finally, they reveal an interaction of the ZA with the microprocessor complex, and uncover a mechanism whereby the ZA regulates a set of miRNAs to suppress cellular transformation and maintain the epithelial phenotype.
My comment: The link from nutrient energy to microRNAs and differences in behavior development during life history transitions has also been established in the context of experimental evidence of biologically-based cause and effect.
See also: Mitochondrial function in the brain links anxiety with social subordination
Conclusion:
Limited energy production due to reduced mitochondrial function may impair adaptive neuronal capacity to life challenges (32) and contribute to the development of psychopathologies (9, 10, 13, 14). Therefore, our results highlight differences in mitochondrial function in the NAc as a potential mechanism underlying the susceptibility or resilience to develop depression, and may open new prospects for the advancement of preventive therapeutic approaches to mood disorders.
My comment: It is extremely difficult for a serious scientist to miss the connection from energy-dependent cell type differentiation to healthy longevity. For contrast, it seems to be very easy for evolutionary theorists to ignore the role of energy that is linked to RNA-mediated cell type differentiation via nutrient-dependent amino acid substitutions because they think one species evolves from another species via mutations. Similarly, sex differences in cell types also must somehow be naturally selected in the context of beneficial mutations.
But wait, see for contrast: Mitochondria can orchestrate sex differences in cell fate of vascular smooth muscle cells from rats
Conclusion:
Importantly, this research also suggests that (i) it is essential to indicate the sex of cells and plan experiments on male and female cells, to understand the basics of the observed differences in the male and female pathophysiology, and (ii) the idea that isolated cells could maintain a sort of “memory” of their origin, i.e., a sexual dimorphism, could provide new insight in understanding pathogenesis and outcome of some diseases, including cardiovascular diseases.
My comment: By now the team has arrived at experimentally established links to sex difference in cell types and somatic difference that have been linked from energy-dependent function of mitochondria across species in the context of a single amino acid substitution linked to life history transitions in behavior. Go, team, GO:
See also: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults
My comment: The fact that a single amino acid substitution during life history transitions of humans can be linked from the honeybee model organism to life history transitions in all invertebrates and vertebrates via what is currently known about the links from atoms to ecosystems and supercoiled DNA has begun to alter the course of history in social science.
For example see: CAMH to ‘wind down’ gender identity clinic after damning review of services
My comment: Although serious scientists have continued to reassert the need for interdisciplinary collaboration to link sex differences in cell types to somatic differences, I know of only two groups that have moved forward as separate teams. For comparison, sex researchers have stagnated, which is one reason the editor of the Archives of Sexual Behavior was removed from his position at the Centre for Addiction and Mental Health (CAMH).
See also: Infamous Reparative Therapy Clinic For Transgender Youth Set To Close
Excerpt:
GIC’s “developmental model” was backwards. It blamed symptoms like depression and anxiety on the gender non-conforming behavior itself, rather than on the stigma attached to it or the conflict of not being able to fulfill one’s gender identity. This philosophy allowed the clinic to claim it was treating these negative mental health outcomes without affirming the trans behavior.
My comment: They had no developmental model. Philosophy has finally put an end to one career, and the end of many other careers will follow. Serious scientists have linked atoms to ecosystems in the context of morphological and behavioral phenotypes that vary during life history transitions. Others who have failed to pay attention to details that link RNA-mediated cell type differentiation to sexual orientation via links from sexual orientiation in yeasts to mammals, will be among those with the most vocal complaint as the heads continue to roll. But they probably won’t learn anything new about cell type differentiation. Most are at the end of their careers and they probably hope to get out before being thrown out the door, like Ken Zucker.
Personally, I like Ken, but his decision not to publish our study results in 2007 probably led others to ignore facts that link molecular epigenetics to sexual orientation via what is known to serious scientists about olfaction, food odors, and pheromones in species from microbes to primates. Besides, if researchers can’t publish the results of their experiments, they cannot recruit team members who need to publish or perish. That puts individuals up again teams that typically tout pseudoscientific nonsense because they have the strength of numbers to support their theories, which are typically published in the context of mathematical models of population genetics, not biologically-based cause and effect.
See, for example: Deciphered Gorilla Y chromosome shows strong conservation with Human but not with Chimpanzee
Excerpt:
Our results attest to strong conservation in structure and gene content between the gorilla and human Y chromosomes, and portray the chimpanzee Y as an outlier in the hominine Y chromosome evolution, even though chimpanzee and human shared the most recent common ancestor. Compared with the human Y, the chimpanzee Y lost four X-degenerate genes, three ampliconic gene families, and one palindrome, while the gorilla Y retained all these elements with the exception of one gene family. The ampliconic gene family size varies dramatically among the three hominines, as well as intraspecifically for four genes in gorilla. We speculate that the Y chromosome evolution in hominines is associated with their mating patterns. Additionally, the gorilla Y chromosome sequence was used to design polymorphic genetic markers for tracing male-specific dispersal in this endangered species.
My comment: At this point it is not acceptable for anyone to link evolution to species-specific chromosomal rearrangements. Gene losses and gains exemplify nutrient-dependent RNA-mediated events that link viruses to the loss of genes or to the creation of pseudogenes, which is consistent with everything known to serious scientists about how DNA repair is linked from supercoiled DNA to the protection of organized genomes from virus-driven entropy. Intelligent team members might get angry if biologically uninformed researchers continue to jump across species via links from mutations to chromosomal rearrangements without linking them to nutrient energy-dependent species-specific reproduction that is controlled by the metabolism of nutrients to species-specific pheromones.
See also: The ribosome as a missing link in the evolution of life. The authors “Suggest that DNA and cells evolved to protect and optimize pre-existing ribosome functions.”
My comment: Others who suggest that DNA and cells automagically evolved seem to have not noticed that there is no experimental evidence that links biologically-based cause and effect to the evolution of anything that pre-existed. The automagical link from mutations to chromosomal rearrangement in primates is worse for anyone who knows what was addressed in A universal trend of amino acid gain and loss in protein evolution.
Excerpt:
We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.
My comment: The trend that emerged appears to be the basis for all the ridiculous claims of evolutionary theorists who link something unknown to whatever happened that biophysically constrains RNA-mediated cell type differentiation via amino acid substitutions, which are linked to all morphological and behavioral diversity via the nutrient-dependent physiology of reproduction that protects organized genome from virus-driven entropy.
And what about those viruses? They were left out of the modern synthesis.
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…
That’s why it will take a good team to unravel the mess that has been left to serious scientists by evolutionary theorists and other social scientists.
In the early 1990’s Bruce McEwen told me to start with gene activation if I wanted anyone to validate my mammalian model. It developed into a model that now links energy-dependent hydrogen-atom transfer in DNA base pairs in solution from RNA-mediated DNA repair to supercoiled DNA that protects the organized genomes of all living genera from virus-driven entropy.
The symposium validated my model in the context of what has since been learned about transgenerational epigentic inheritance of the Zika virus, and the virus-driven pathology of Alzheimer’s disease.
Simply put, the nutrient-dependent innate immune system links RNA-mediated DNA repair to healthy longevity or virus-driven energy theft to all pathology via what is currently known about biophysically constrained protein folding chemistry and the physiology of nutrient-dependent reproduction.
From Fertilization to Adult Sexual Behavior http://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html
Excerpt: “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.”
If you haven’t read any of the ~48,000 publications that link the pre-mRNAs (microRNAs) from nutrient-dependent flanking sequences to the biophysically constrained chemistry of RNA-mediated protein folding and RNA-mediated amino acid substitutions that stabilize all organized genomes when fixation occurs in supercoiled DNA, you may not be linking the physiology of reproduction from ecological variation to ecological adaptation.
Excerpt: “Milk is a highly specialized nutrient and signaling system of mammalian evolution that apparently shapes the epitranscriptome of the milk recipient via FTO-mediated modifications of RNA nucleotides. Future research should unravel milk´s biological impact on the recently recognized dual axis of coordinated regulation between the genome and the epigenome and the transcriptome and the epitranscriptome, respectively [336].”
My comment: When placed into the context of neo-Darwinian evolution, it makes no sense to place any highly specialized nutrient or any signaling system into the context of a dual axis of coordinated regulation. You cannot simply make claims about the magic of evolution. First, someone must explain how they defined the boundary between epigenetics and genetics outside the context of nutrient-dependent supercoiled DNA that protects all organized genomes from virus-driven entropy.
For example, how could the protection of the innate immune system “evolve.”
How could ecological variation be linked to ecological adaptation if the innate immune system did not fine-tune the balance of nutrient-dependent
1) microRNAs,
2) adhesion proteins, and
3) RNA-mediated cell type differentiation that links
4) hydrogen-atom transfer in
5) DNA base pairs
6) in solution to
7) thermodynamic cycles of protein biosynthesis
8) and degradation in the context of changes in
9) oxygen,
10) pH,
11) carbon dioxide,
12) salinity,
13) other chemical cues,
14) all integrated sensory input,
15) and the physiology of reproduction, which is controlled by pheromones in species from microbes to humans?
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