Inugo Research - miRNA

DICER - DROSHA - for Dummies

The compartmentalization of science is the issue. Some of us, however, are allowed the privilege of researching and helping dozens of scientists write their “documents” on a scale that takes us across all compartments. Right from the beginning, the recommendation was some type of polyphenolic substance (Fulvic/humic acids etc.). Great news: the science is finally catching up. Drink more red wine, eat more chocolate, smoke more natural tobacco, drink gin and real tonic (quercetin), touch, make love, dance. It stops the little scissors in your cells (DICER & DROSHA) from being disrupted and cutting up the mRNA of spike protein into smaller, more toxigenic down/up-regulators. Capiche?

Walter M. Chestnut is correct - “the spike protein is turning all it touches into tumor microenvironments.”

Is Spike Protein Endothelial Disease (SPED) Actually Part of a More Complex Process? Spike Protein “Metastasis?”

But how? Why? What? Well, it is complicated and my research (and my life as a minimalist) led me to work with my academic group to understand the most minute levels we currently comprehend. And while the world is terrified of the spike mRNA (as they should be - “vaccine” bioweapon), the actual cutting edge science is more terrified of the “broken down” fragments of miRNA & siRNA up-regulating and down-regulating genes (siRNA is silencing genes. Get it? Bioweapon on a genetic level).

Some Catch-up:

microRNA - Drosha & Dicer.

"Mammalian genomes are pervasively transcribed with most transcripts apparently not associated with coding functions An increasing number of ncRNAs have been shown to play a variety of relevant cellular functions, often with estimated very low expression levels DICER and DROSHA are two RNase type III enzymes that process ncRNAs hairpin structures to generate small double-stranded RNAs" - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442236/

GP-120 (in Spike Protein) "HIV-1 actively suppresses expression of the polycistronic miRNA cluster, miR-17/92, an inhibition of the miRNA pathway that is required for efficient viral replication (Triboulet et al., 2007). Instead of altering host miRNA expression, viruses could use an alternative mechanism involving miRNA-mediated host-pathogen interactions" - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763548/

"Small RNAs, such as microRNAs (miRNAs), are fundamental regulators of host gene expression programs, including antiviral innate immunity genes...This analysis revealed that the small RNA has precise 5′ and 3′ ends characteristic of a bonafide miRNA, suggesting that it is not a degradation product… we show the presence of a stem–loop structure that is processed by DICER1-mediated cleavage in vitro. Third, RNAi experiments to deplete human Dicer during SARS-CoV-2 infection also show reduced accumulation of the viral miRNA and human miRNAs - we show the presence of a stem–loop structure that is processed by DICER1-mediated cleavage in vitro. Third, RNAi experiments to deplete human Dicer during SARS-CoV-2 infection also show reduced accumulation of the viral miRNA and human miRNAs”

Spike Protein and down-regulation of miRNA

"Mature miRNAs are produced from primary transcripts (pri-miRNAs), which are processed by Drosha proteins into precursor miRNAs (pre-miRNAs), each of which consists of 5p and 3p arms and a terminal loop. The pre-miRNAs are transported to the cytoplasm by exportin 5 and are divided by Dicer to release the terminal loop and 5p/3p duplex.

"The downregulation of these miRNAs in patients with COVID-19 leads to IL-6/IL-6R hyperactivation by directly targeting the 3'UTR of IL-6/IL-6R, thereby enhancing the cytokine storm induced by SARS-CoV-2 infection

"Hsa-miR-18 and hsa-miR-125b play central roles in acute renal injury in patients with SARS-CoV-2 infections by directly binding to ACE2.

"Accumulating evidence indicates that ceRNA networks link the functions of protein-coding mRNAs with those of noncoding RNAs such as miRNAs, long noncoding RNAs 52, pseudogenic RNAs, and circular RNAs 51, thereby affecting and regulating the expression of target genes. Because host miRNAs can bind to the coding DNA sequence (CDS) regions of viral RNAs, even without interfering with viral RNA function, overconsumption of host miRNAs (known as the sponge effect) may lead to a reduction in the availability of such miRNAs

"miRNAs are involved in sensory system development, oxidative responses, autophagy, lung development, stress-activated MAPK signaling, and oxidative stress-induced neuron death. A previous study reported that patients with SARS-CoV-2 infection have excessive reactive oxygen species (ROS) levels, which facilitates the cascade of biological events that drive pathological host responses



Fulvic Acids & Polyphenols - the fix

Been saying this, on a cellular level since day 1. "Natural compounds can block SARS-CoV-2 infection by regulating miRNA expression - Polyphenols are the most abundant dietary antioxidants and are commonly found in fruits, vegetables, chocolate and wine"

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346380/

Part of the Bioweapon is Glycoprotein-120

VAIDS causes SPED on a miRNA level. "whereas serum TNF-α levels were associated with systemic adverse reactions and with specific antibody titers. Interestingly, EV miR-92a-2-5p levels in sera were negatively correlated with degrees of adverse reactions, and EV miR-148a levels were associated with specific antibody titers. Our data suggest a potential of circulating EV miRNAs as biomarkers for vaccine efficacy and adverse events…”

"Our study showed a correlation of specific antibody titers with serum TNF-α levels after the second dose. TNF-α has been reported to be required for the formation of primary B-cell follicles and essential for the production of antigen-specific IgG32. Recombinant TNF-α can also promote B-cell proliferation33. TNF-α is secreted from myeloid cells and B- and T cells in response to antigens34. Hence, TNF-α is expected to be secreted from lymphocytes in response to vaccination, resulting in augmented production of specific antibodies against the viral spike protein.

"EVs include exosomes, microvesicles (also called ectosomes), and apoptotic bodies.

- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346380/

GP-120 - a prion (The Prion) - Folding those 3D Proteins

"HIV-1 can reshape the miRNA expression profile of infected cells (21). One interpretation of this latter finding is that the virus has learned to repress the expression of virus-targeted miRNAs, while enhancing the expression of propitious miRNAs that up-regulate protein factors that benefit HIV-1 replication

"HIV-1 was shown to affect the levels of several miRNAs to change their expression profile (30). Tat protein was also shown to deregulate expression levels of selected miRNAs, including the neuronal mir-128, in primary cortical neurons

"Interestingly, some targets of the up-regulated miRNAs have been associated with neurological diseases. For instance, miR-378 has been shown to target the CYP2E1 gene, a cytochrome p450 isoform whose polymorphism is associated with Parkinson disease (32) and is found tightly associated with dopamine-containing cells in the substantia nigra (33). Accordingly, we observe a 2-fold decrease in the expression of CYP2E1 in neurons treated with Tat in addition to an increase in miR-1 expression.

"miRNAs were also shown to be involved in the pathogenesis of neuroblastoma and astrocytoma

"Among known miR-34a targets, p53 and SIRT1 genes were the most studied and shown to be involved in apoptosis or cell survival (59). miR-34a was recently shown to behave like a tumor suppressor in brain tumors and glioma stem cells (74). In addition to its involvement in tumors and neurodegenerative diseases, miR-34a was also shown to play a role in psychiatric problems.

"However, it is well described that HIV-1 benefits from deregulating the miRNAs of the host cell (26). This theory is supported by the fact that miRNA-processing enzymes Drosha and Dicer are silenced to reduce generation in the cell of mature miRNAs (Ref. 26 and references within). This phenomenon can lead to a robust HIV-1 replication and preventing some miRNAs (e.g. miR-150 or miR-223) from silencing, reducing, or even delaying viral replication

- https://www.sciencedirect.com/science/article/pii/S0021925820504614

How did we get here?

Well, on the backs of scientific geniuses like J. Craig Venter, Clyde Hutchinson and Jennifer Doudna. Scientists pushed to do their work with mRNA, before they understood miRNA and siRNA. Or did they understand? And who or whom pushed them to do work that they had no business doing in the first place? One guess to the answer - military funding and removal of red tape. DARPA’s idea is: “It’s the Host Not the Pathogen” & “modulating host response” & “closed-loop monitoring”. Does that describe our findings about the covid vaccines have been caught performing as “extra-medical additions”? Covid stands for covert identification device.

Matt Hepburn goes on to intra-species and inter-species work at DARPA. And as he quips “maybe we (DARPA) need to make you more mouse-like… for your safety”.

Part of the extra-medical gene therapies - Thanks DARPA

J. Craig Venter - creator of life (atheist’s god)

Funny that one of the great achievements proposed by scholars over our history has been the creation of life itself. Can man become god-like and create his own life? Apparently. Yet J. Craig Venter not only created new life biological out of a computer program, he also took one species over and completely converted it to another; utilizing what he calls “the software building its own hardware”. // crickets //

So wait, he has all of our human genome mapped. He understands, as he puts it to the NASA Ames Elite, “if we silence the wrong gene entire civilizations will not exist". He so quickly brushes over Clyde Hutchinson work on ‘whole genome transposon mutagenesis’ like it is nothing.

“So, transposons are these small pieces of DNA that jump around in the genetic code. Over half of our human genome is composed of these transposons. They’re constantly jumping around and if they jump into the middle of a key gene, we can get a disease or next generations won’t exist with these.”

Say that again:

• Software building genetic mRNA

• small bits of DNA that jump around in genetic code (DROSHA & DICER scissors)

• we can get a disease or next generations won’t exist

Right. Nothing to see here, watch video and move on.

CRISPR, Cas9/Cas12 - A Genetic Vaccination Card

Re-watch the beginning minutes of “I Am Legend” and especially the part where the arrogant doctor cured cancer. This lady is exactly Jennifer Doudna, co-inventor of CRISPR Technology (clustered regularly interspaced short palindromic repeats).

CRISPR, or as I refer to it: “DICER & DROSHA for Dummies”, allows a protein Cas9 to cleave nucleic acid and mass produce… anything. End of life? Done. Black mice turned into white mice? Done. End of species and start of new species? Done. As Jennifer Doudna so eloquently giggles with only the disgusting arrogance of a rigged-nobel-prize winner “a way for scientists to delete or insert specific bits of DNA into cells with incredible precision.”

// Catch-up reading of CRISPR & “small RNA” - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819186/

“CRISPR system allows that DNA to be plucked out of a virus (that they create), and inserted in little bits (miRNA or siRNA) into a chromosome - the DNA of the bacterium. And these integrated bits (software bundles of who knows what) of viral DNA get inserted (into all mammals) at a site called CRISPR… it’s a mechanism that allows cells to record, over time, the viruses they have been exposed to. And importantly those bits of DNA are passed to the cells’ progeny, so cells are produced not only in one generation, but over many generations of cells. This allows the cells to keep a record of the infection, and as my colleague, Blake Wiedenheft likes to say, ‘the CRISPR locus is effectively a genetic vaccination card’.”

Ralph, old Ralph

Good ole Ralph Baric. We cannot forget the ultimate scientist that is a beautiful caricature of this new science paradigm of compartmentalization and doing science because we “can”, without any regards to if we “should”. How do we summarize Ralph’s work? Most is paid for by private and dark-military-money bioweapons programs, so how do we truly understand how many microbial-murder-pies old Ralphie-boy has had his greasy finger into? I know, timeline… then you can decide.

Pre-Ralph Inspiration - while Ralphie-boy is in Zoology

1975 - Cardiomyopathy in crowded rabbits - https://pubmed.ncbi.nlm.nih.gov/128082/

1987 - Relatedness of rabbit coronavirus to other coronaviruses - https://pubmed.ncbi.nlm.nih.gov/2829566/

Opportunity / Military Money for Ralph

1986 - School of Public Health Funding - Coronavirus-induced myocarditis in rabbits

1987 - NAIAD Funding - Nat’l Heart Grant - Coronavirus-induced myocarditis in rabbits

1990 - Nat’l American Heart Ass. Grant - Coronavirus-induced myocarditis and dilated cardiomyopathy

Patents

2001 - Directional assembly of large viral genomes and chromosomes

2002 - Methods for producing recombinant coronavirus

2004 - Methods for producing recombinant coronavirus

2006 - Compositions of coronaviruses with a recombination-resistant genome

2006 - Methods and compositions for infectious cDNA of SARS coronavirus

2006 - Compositions of coronaviruses with a recombination-resistant genome

2011 - Multivalent Immunogenic Compositions Against Noroviruses and Methods of Use

2015 - Methods and compositions for chimeric coronavirus spike proteins

2015 - Methods and Compositions for Dengue Virus Epitopes

2017 - Chimeric dengue virus E glycoproteins comprising mutant domain I and domain II hinge regions

Research of Interest - Lock him up yet?

1980 - In Vitro Selection of an Attenuated Variant of Sindbis Virus

1983 - Requirement for Host Transcription in the Replication of Sindbis Virus

1983 - Presence of leader sequences in the mRNA of Mouse Hepatitis Virus

1983 - Reduced synthesis of Sindbis virus negative strand RNA in cultures treated with host transcription inhibitors

1984 - Studies on the Mechanism of RNA Synthesis of a Murine Coronavirus

1984 - Sindbis Virus Mutants Selected for Rapid Growth in Cell Culture Display Attenuated Virulence in Animals

1985 - Characterization of leader-related small RNAs in coronavirus-infected cells: Further evidence for leader-primed mechanism of transcription

1988 - Specific interaction between coronavirus leader RNA and nucleocapsid protein

1993 - Studies into the Mechanism for MHV Transcription

1993 - Isolation and identification of six Pneumocystis carinii genes utilizing codon bias

1998 - Human Biliary Glycoproteins Function as Receptors for Interspecies Transfer of Mouse Hepatitis Virus

1999 - Persistent Infection Promotes Cross-Species Transmissibility of Mouse Hepatitis Virus

2000 - Subgenomic Negative-Strand RNA Function during Mouse Hepatitis Virus Infection

2000 - Strategy for Systematic Assembly of Large RNA and DNA Genomes: Transmissible Gastroenteritis Virus Model

2002 - Heterologous Gene Expression from Transmissible Gastroenteritis Virus Replicon Particles

2003 - Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus

2006 - Severe Acute Respiratory Syndrome Coronavirus Group-Specific Open Reading Frames Encode Nonessential Functions for Replication in Cell Cultures and Mice

2006 - Resurrection of an ''extinct" SARS-CoV isolate GD03 from late 2003

2006 - Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: Engineering a recombination-resistant genome

2007 - Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists

2007 - A Reverse Genetics System for dsRNA Viruses

2007 - Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

2010 - Transcriptomic Analysis Reveals a Mechanism for a Prefibrotic Phenotype in STAT1 Knockout Mice during Severe Acute Respiratory Syndrome Coronavirus Infection

2010 - Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling

2011 - SARS-CoV and Emergent Coronaviruses: Viral Determinants of Interspecies Transmission

2012 - P115 Pathogenic Influenza A viruses and SARS-Coronaviruses modulate global interferon stimulated gene induction through diverse mechanisms

2012 - Evidence Supporting a Zoonotic Origin of Human Coronavirus Strain NL63

2012 - Emerging Human Coronaviruses - Disease Potential and Preparedness

2013 - Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production

2013 - Protein co-expression network analysis (ProCoNA)

2015 - Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus

2019 - Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry