N1-Methylpseudouridine (abbreviated m1Ψ) is a natural archaeal tRNA component[1] as well as a synthetic pyrimidine nucleoside used in biochemistry and molecular biology for in vitro transcription and is found in the SARS-CoV-2 mRNA vaccines tozinameran (Pfizer–BioNTech) and elasomeran (Moderna).[2]: 1 It had previously been tested in vaccines against Zika,[3][4][5] HIV-1,[5] influenza,[5] and Ebola[6] in 2017–2018.[2]: 5
Properties
N1-Methylpseudouridine is the methylated derivative of pseudouridine. It is used in in vitro transcription and for the production of RNA vaccines,[7][8] In vertebrates, it stimulates significantly less activation of the innate immune response compared to uridine.[9] At the same time, the translation is stronger.[10][11] In protein biosynthesis, it is read like uridine and enables comparatively high protein yields.[11][12] In 2016, a protocol for large-scale synthesis of the nucleoside triphosphate from the ribonucleoside was published.[13] The nucleoside itself can be made by chemical methylation of pseudouridine.[14]
While pseudouridine can wobble-pair with bases other than A,[15] potentially leading to mistranslated proteins, it is unclear whether this happens with m1Ψ.[16][2]: 4 [contradictory]
The innate, or nonspecific, immune system [1]is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms (see Beyond vertebrates).[2]
The major functions of the innate immune system are to:
- recruit immune cells to infection sites by producing chemical factors, including chemical mediators called cytokines
- activate the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead cells
- identify and remove foreign substances present in organs, tissues, blood and lymph, by specialized white blood cells
- activate the adaptive immune system through antigen presentation
- act as a physical and chemical barrier to infectious agents; via physical measures such as skin and chemical measures such as clotting factors in blood, which are released following a contusion or other injury that breaks through the first-line physical barrier (not to be confused with a second-line physical or chemical barrier, such as the blood-brain barrier, which protects the nervous system from pathogens that have already gained access to the host).
Inflammation is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells. It establishes a physical barrier against the spread of infection and promotes healing of any damaged tissue following pathogen clearance.[5]
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells, and mast cells. These cells present receptors contained on the surface or within the cell, named pattern recognition receptors (PRRs), which recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRRs recognizes a PAMP) and release inflammatory mediators responsible for the clinical signs of inflammation.
Chemical factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, cause local vasodilation of the blood vessels, and attract phagocytes, especially neutrophils.[5] Neutrophils then trigger other parts of the immune system by releasing factors that summon additional leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF, HMGB1, and IL-1.[6]
The inflammatory response is characterized by the following symptoms:
- redness of the skin, due to locally increased blood circulation;
- heat, either increased local temperature, such as a warm feeling around a localized infection, or a systemic fever;
- swelling of affected tissues, such as the upper throat during the common cold or joints affected by rheumatoid arthritis;
- increased production of mucus, which can cause symptoms like a runny nose or a productive cough;
- pain, either local pain, such as painful joints or a sore throat, or affecting the whole body, such as body aches; and
- possible dysfunction of involved organs/tissues.
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> N1-Methylpseudouridine (abbreviated m1Ψ)
M1-Ψ難グランプリｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗ
uridine・・・
ウリジーン・・・
ｳﾘ Gene ｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗｗ
吠えない番犬
猿轡ならぬ犬轡
やっぱヤマサ(爆
易感染と出血
エボラかー
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