Tag: P53

The Molecular Bomb

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The Molecular Bomb

Highly recommended stream. Dr Kevin McCairn talks with @DoorlessCarp (Dave) [https://doorlesscarp953.substack.com/ ] and Genervter Burger (Annoyed Citizen) [https://genervter.substack.com/p/der-weg-richtung-himmel-oder-holle  Any missing links can be found on the substack]

The Molecular Bomb: Why Nuking miRNA Signaling With Synthetic mRNA Is A bad Idea (3:00)

 

So RNA is usually protected from being broken down because it is inside exosomes or protected by lipids (fatty compounds) but now we discover RNA on the surface of cells

19 min Extracellular RNAs: A New Awareness of Old Perspectives
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509047/

24 min Human genome-produced RNA discovered on surface of cells.
https://www.drugtargetreview.com/news/70823/human-genome-produced-rna-discovered-on-surface-of-cells/

30 min The impact of BNT162b2 mRNA vaccine on adaptive and innate immune responses https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v2
The vaccine stopped working after six months and changed the immune cells sequences as well as the built -in (inate) interferon immune response (higher IL-1/IL-6 release and decreased production of IFN-α.)

Down-regulating innate AND adaptive immune response when a big fat ball (LNP i.e. PEG) hits your cell surface.

This (see below) was changed in the updated version of the article (lolz):

*specific (viral, fungal and bacterial) stimuli. The response 
of innate immune cells to TLR4 and TLR7/8 ligands was 
lower after BNT162b2 vaccination, while fungi-induced 
cytokine responses were stronger. In conclusion, the 
mRNA BNT162b2 vaccine induces complex functional 
reprogramming of innate immune responses, which 
should be considered in the development and use of this 
new class of vaccines.

Mitogen = cell division
https://en.wikipedia.org/wiki/Mitogen
A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a mitogen is that it triggers signal transduction pathways involving mitogen-activated protein kinase (MAPK), leading to mitosis.

Uncontrolled cell division =cancer (see the Tumor cell)

36 min KRAS -Mutant non-small cell lung cancer: From biology to therapy
https://www.researchgate.net/publication/326517018_KRAS_-Mutant_non-small_cell_lung_cancer_From_biology_to_therapy

37 min BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant
https://www.nature.com/articles/s43856-022-00083-x

Supplementary Data 3
Link: https://static-content.springer.com/esm/art%3A10.1038%2Fs43856-022-00083-x/MediaObjects/43856_2022_83_MOESM5_ESM.xlsx
Interferon up-regulated
He dug into the spreadsheet  RAS over-expressed

P53 tumor expresses up-regulated or down-regulated? More like dysregulated i.o.w out of balance.

In yeast and fungi, the Ras signalling casscade determines gene expression while attenuating growth as well as morphogenetic transformations in response to different environmental conditions.

48 min Regulation of mRNA Translation by Signaling Pathways
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536343/

modulating phosphorylation status = energy =fine tuned and malfunction leads to cancer (but just smack it with a blob on Synthetic lipid that encases mRNA -she’ll be right mate-lolz).
Don’t worry we thought of everything:

51 min Immune modulatory effects of oncogenic KRAS in cancer

https://www.nature.com/articles/s41467-020-19288-6

Some alterations induced by oncogenic KRAS mutations in cancer promote tumour cell proliferation (mitogenic effects), whereas other immune-modulatory effects allow the tumours to evade immune-mediated attack by creating an immunosuppressive microenvironment

55 min Increased PD-L1 surface expression on peripheral blood granulocytes and monocytes after vaccination with Sars-CoV2 Mrna or vector vaccine
https://pubmed.ncbi.nlm.nih.gov/36245120/

PD-L1= Programmed death-ligand 1. A protein that acts as a kind of “brake” to keep the body’s immune responses under control.

Up regulation PD-L1 lowers TCell responses to tumors

57 min Bombshell paper
Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536038/
Both the MRNA and the protein that it expresses can cross the nuclear membrane
therefore nuclear integration.

1:03 min SARS-CoV-2 mRNA vaccine is re-adenylated in vivo, enhancing antigen production and immune response
https://www.biorxiv.org/content/10.1101/2022.12.01.518149v2

Adenylation is an elegant biological process used to chemically activate carboxylate substrates by condensing them with ATP to liberate pyrophosphate.
https://en.wikipedia.org/wiki/Adenylylation

The poly-A tail is a long chain of adenine nucleotides that is added to a messenger RNA (mRNA) molecule during RNA processing to increase the stability of the molecule.
The poly-A tail makes the RNA molecule more stable and prevents its degradation. Additionally, the poly-A tail allows the mature messenger RNA molecule to be exported from the nucleus and translated into a protein by ribosomes in the cytoplasm.
https://www.nature.com/scitable/definition/poly-a-tail-276/

1:07 min MicroRNA video

Biogenesis of MiRNAs and mode of action

Understanding the pathway leading to the formation and function of microRNA
https://youtu.be/j-zTy6vOP3M

All the videos are on the substack

https://genervter.substack.com/p/der-weg-richtung-himmel-oder-holle

1:18 min natural RNa is proof read but the synthetic version is not proofread and can be frameshifted transcription errors misreading which means protein misfolding neurodegenerative disorders.

1:25 min Quantum microRNA Assessment of COVID-19 RNA Vaccine: Hidden Potency of BNT162b2 SASR-CoV-2 Spike RNA as MicroRNA Vaccine

https://crimsonpublishers.com/aics/fulltext/AICS.000552.php

Built into the genetic code of the spike protein are mimickry like microRNAs

There are inverse microRNAs that will cancel each other out (lolz)

1:30 min Inhibition of miR-21 Regulates Mutant KRAS Effector Pathways and Intercepts Pancreatic Ductal Adenocarcinoma Development
https://pubmed.ncbi.nlm.nih.gov/32409593/

What can happen if you over or under express….

An RNA hairpin is an essential secondary structure of RNA. It can guide RNA folding, determine interactions in a ribozyme, protect messenger RNA (mRNA) from degradation, serve as a recognition motif for RNA binding proteins or act as a substrate for enzymatic reactions.
Short hairpin RNAA short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi)Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. https://en.wikipedia.org/wiki/Short_hairpin_RNA

mIRN21 is one of the most frequently up-regulated miRNAs in solid tumors
https://en.wikipedia.org/wiki/MIRN21

1:34 min How do microRNAs regulate gene expression?
https://pubmed.ncbi.nlm.nih.gov/19021530/

1:56 min 

miRNAs (microRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally. They generally bind to the 3'-UTR (untranslated region) of their target mRNAs and repress protein production by destabilizing the mRNA and translational silencing. The exact mechanism of miRNA-mediated translational repression is yet to be fully determined, but recent data from our laboratory have shown that the stage of translation which is inhibited by miRNAs is dependent upon the promoter used for transcribing the target mRNA. This review focuses on understanding how miRNA repression is operating in light of these findings and the questions that still remain.

1:37 min  Circulating extracellular vesicle microRNAs associated with adverse reactions, proinflammatory cytokine, and antibody production after COVID-19 vaccination
https://www.nature.com/articles/s41541-022-00439-3

An in silico pipeline approach uncovers a potentially intricate network involving spike SARS-CoV-2 RNA, RNA vaccines, host RNA-binding proteins (RBPs), and host miRNAs at the cellular level https://pubmed.ncbi.nlm.nih.gov/36066672/

Our in silico analysis could aid in shedding light on the potential effects of exogenous RNA (i.e. viruses and vaccines), thereby improving our understanding of the cellular interactions between virus and host biomolecules. Finally, using the computational approach, it is possible to obtain a safety assessment of RNA-based vaccines as well as indications for use in specific clinical conditions.

miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047241/

1:45 min after 2nd shot of BNT162b2 oncogenic miR-21 is significantly upregulated

The microRNA’s detected in the plasma of pregnant women who had recieved three doses of the Moderna.

1:56 min Lifelong epigenetic changes

KRAS Hijacks the MicroRNA Regulatory Pathway in Cancer
https://pubmed.ncbi.nlm.nih.gov/36946612/

2:00 min miR-16 and miR-21 Expression in the Placenta Is Associated with Fetal Growth
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115987/

They knew:

2:03 min Nucleotide Modification Alters MicroRNA-Dependent Silencing of MicroRNA Switches
https://www.cell.com/molecular-therapy-family/nucleic-acids/fulltext/S2162-2531(18)30322-6

2:06 min Turbo cancer (stabilized miRna21)

Lost three years on the epigenetic clock

2:09 min Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination
https://pubmed.ncbi.nlm.nih.gov/35719387/

2:13 min miR29 dysregulated
Epigenetic Changes Mediated by MicroRNA miR29 Activate Cyclooxygenase 2 and Lambda-1 Interferon Production during Viral Infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255816/

Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic.
https://europepmc.org/article/pmc/pmc9650991

We detected upregulation of miR-29s and miR-142-3p during myeloid differentation in leukemia cell lines and CD34 hematopietic stem/progenitor cells

2:43 min Point of care vaccines – they will spin up a personalized vaccine for you at the pharmacy.

Conclusion

I praise you because I am fearfully and wonderfully made;
    your works are wonderful,
    I know that full well. (Ps 139:14)

Life is far more complex than they think. Fools rush in were angels fear to tread…but this is worse…much worse because it cannot all be put down to incompetence. They knew and they are experimenting on us.

Virus evolution and LNP

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Virus evolution and LNP

The Explosion of Cancer and Latent Disease: The Lipid Nanoparticle Platform Is Asking for Trouble (5 min)

Virus evolution by antibodies + BA 2 Omicron – COVID-19 vaccines update 40 (17 min)

How does the virus evolve inside an infected person – we commence this story with a new demonstration in a vaccinated patient, and relapse to a well-documented history in COVID-19 patients, and how antibodies can be contributing to such viral evolution. This also leads us to a hypothesis as to why evolving variants might show up in wastewater prior to taking over a population. We conclude with how the BA2 variant of the Omicron is different from the BA1 variant, demonstrating continuous uninterrupted evolution of the virus.

Described content: Vaccine patient variants: https://www.sciencedirect.com/science… Variants database: https://cov-lineages.org/lineage_list… Innunocompromised host: https://www.nejm.org/doi/10.1056/NEJM… Cancer host: https://linkinghub.elsevier.com/retri… HIV host: https://www.medrxiv.org/content/10.11… Prolonged infection variants: https://academic.oup.com/ve/article/7… Evolution speed: https://www.clinicalmicrobiologyandin… Immune escape co-evolution: https://www.science.org/doi/10.1126/s… Convalescent plasma host: https://www.nature.com/articles/s4158… GIT variant evolution: https://genomemedicine.biomedcentral…. GIT viral load: https://www.gastrojournal.org/article… Viral load impact: https://academic.oup.com/ve/article/7… BA2 Omicron: https://arxiv.org/abs/2202.05031

Gigaohm Biological Aug 5

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Gigaohm Biological Aug 5

Another good show. I am just placing two links under the video that were of interest to me.

S2 Subunit of SARS-nCoV-2 Interacts with Tumor Suppressor Protein p53 and BRCA: an In Silico Study

With tumor suppressor proteins p53 and BRCA-1/2. In this short communication we report the interaction between S2 subunit proteins with tumor suppressor proteins for the first time. 


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324311/
This is a link to Jessica Malaty Rivera is an infectious disease epidemiologist

The usual suspects...she is with the Rockerfeller Foundation and went  to Georgetown University (the one where Katzwoman is a Professor).

https://www.rockefellerfoundation.org/profile/jessica-malaty-rivera/