mRNAワクチン接種者の体内に発生するフレームシフト突然変異が今後、齎し得る『謎遺伝子疾患』の一例だゾ☆

2023年12月7日木曜日

ｍRNA型接種した勇者はもう全員、欠陥遺伝子組換え人間だゾ☆

https://jyado.blogspot.com/2023/12/rna_7.html

2023年12月7日木曜日

フレームシフトの阻害を利用した新型コロナ治療薬 vs.フレームシフトを誘発するｍRNAワクチン（笑）

https://jyado.blogspot.com/2023/12/vsrna.html

2023年12月7日木曜日

接種したｍRNAの約８％がバグってタンパク質にフレームシフト変異が発生するって事だゾ☆

https://jyado.blogspot.com/2023/12/rna.html 

2023年12月7日木曜日

mRNAワクチンが細胞に作成させるタンパク質の８％はスパイクタンパク以外の『想定外の謎のタンパク質』だゾ☆

https://jyado.blogspot.com/2023/12/mrna.html

Mutant Proteins Gum Up Nucleolus, Cause Rare Genetic Disease
February 8, 2023

 

By studying an extremely rare genetic disease, an international team of scientists has uncovered a molecular mechanism that could explain how a great many diseases develop. The genetic disease is called brachyphalangy, polydactyly, and tibial aplasia/hypoplasia (BPTA) syndrome, and it is characterized by complex and striking malformations of the limbs, the face, and the nervous and bone systems. The team of scientists included specialists in clinical medicine and basic biology from the Charité–Universitätsmedizin Berlin, the Max Planck Institute for Molecular Genetics (MPIMG), and the University Hospital Schleswig-Holstein (UKSH).

At most, 10 people in the world are known to have BPTA. Five of them participated in the current study, and they were found to share virtually the same mutation in the gene for the HMGB1 protein. It was a frameshift mutation, one that caused the final one-third of the protein’s structure to have a positive charge rather than the usual negative one.

The mutation led to a chain of consequences. The disordered protein tails for HMGB1 became improperly disordered, causing the phase transition properties for HMGB1 to become altered, such that HMBG1 more readily became part of protein droplets called condensates. Ultimately, the condensates localized on the nucleolus, compromising its function.

Details about this sequence of events appeared in Nature, in an article titled, “Aberrant phase separation and nucleolar dysfunction in rare genetic diseases.” The paper also describes how researchers searched DNA databases for mutations that could favor condensate formation—and potentially impair brain development or increase the risk of cancer.

“The frameshifts replace the intrinsically disordered acidic tail of HMGB1 with an arginine-rich basic tail,” the article’s authors wrote. “The mutant tail alters HMGB1 phase separation, enhances its partitioning into the nucleolus, and causes nucleolar dysfunction. We built a catalogue of more than 200,000 variants in disordered carboxy-terminal tails and identified more than 600 frameshifts that create arginine-rich basic tails in transcription factors and other proteins. For 12 out of the 13 disease-associated variants tested, the mutation enhanced partitioning into the nucleolus, and several variants altered rRNA biogenesis.”

Thousands of genetic changes are associated with various diseases, disorders, and conditions. But how, exactly, these mutations produce disease is seldom clear. This is because the changes relate to sections of proteins with a disordered three-dimensional structure and a function inside the cell about which little is known so far.

“It’s hard to study what these kinds of protein segments are responsible for doing because in many cases, they have to interact with other molecules before producing their effects,” said one of the study’s first two authors, Martin Mensah of the Institute of Medical and Human Genetics at Charité. “Taking BPTA syndrome as an example, we have now described in detail how changes in disordered areas of proteins can cause a genetic disease.”

In experiments with isolated proteins and cell cultures, the research team showed that the mutated HMGB1 protein, which has a positively charged end section, is improperly drawn toward the nucleolus. And because the extension of the protein has also grown stiffer, the HMGB1 protein also clumps together.Nucleus of a human cell. The HMGB1 protein (green) is normally distributed throughout the nucleus of the cell (dotted line). Pink: nucleolus. [MPIMG/Henri otted line) of a human cell. The HMGB1 protein (green) that is mutated in BPTA syndrome forms a hard layer at the nucleolus (pink), causing the developmental disorder. [MPIMG/Henri Niskanen]“Under a microscope, we were able to see that this causes the nucleolus to lose its own liquid-like properties and become increasingly rigid,” explained Henri Niskanen, PhD, a researcher at MPIMG and the study’s other first author.

This solidification of the nucleolus adversely affects the cells’ vital functioning. More cells with the mutated protein than without the mutation died in the culture. “We showed how mutations in disordered sections of proteins can cause a disease,” said Malte Spielmann, director of the Institute of Human Genetics at UKSH and one of the study’s three senior authors. “When there is a change in the charge, the protein wrongly accumulates in the nucleolus, adversely affecting its vital functioning. This leads to a disorder in the organism’s development.”

Although BPTA syndrome is rare, the basic mechanism behind it does not appear to be rare at all, not according to the current study. “The mechanism that causes BPTA syndrome could be implicated in many other diseases and conditions as well,” said Denise Horn, another of the study’s senior authors. She works at the Institute of Medical and Human Genetics at Charité. “We’ve opened a door that could help to explain many other diseases,” she added. “The real work starts now.”

The newly identified mechanism could also lead to new therapeutic approaches, at least for some diseases. “Tumors are attributable to genetic changes in the affected cells,” explained Denes Hnisz, PhD, the head of a research group at MPIMG and the study’s third senior author. “This means we may be able to prevent cancer from developing in the future by intervening in the cell’s self-organization, which is mediated by disordered sections of proteins.”

https://www.genengnews.com/news/mutant-proteins-gum-up-nucleolus-cause-rare-genetic-disease/

mRNAワクチン接種者の血統はもうダメかもしれんね。

もう繁殖期を過ぎた老人はともかく、複数回異なるｍRNAワクチン接種してしまった若者は完全にアウト。

結構悲惨な状況に陥りそうですな。

一部ででも容姿の変形ミュータント化がはじまったらもう誤魔化し通せなくなるかもね。

、、、（爆ｗｗｗｗｗｗｗｗｗｗｗ