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Mechanistic Target Of Rapamycin
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also been implicated in the control and maintenance of t ...
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Sirolimus
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumor (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin kinase (mTOR) inhibitor that inhibits activation of T cells and B cells by reducing their sensitivity to interleukin-2 (IL-2). It is produced by the bacterium '' Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent immun ...
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Actin Cytoskeleton
Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other proteins in the cell. Microfilaments are usually about 7 nm in diameter and made up of two strands of actin. Microfilament functions include cytokinesis, amoeboid movement, cell motility, changes in cell shape, endocytosis and exocytosis, cell contractility, and mechanical stability. Microfilaments are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces. In inducing cell motility, one end of the actin filament elongates while the other end contracts, presumably by myosin II molecular motors. Additionally, they function as part of actomyosin-driven contractile molecular motors, wherein the thin filaments serve as tensile platforms for myosin's ATP-dep ...
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FK506
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T-cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, as part of the body's learned (or adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in 1987, from the fermentation broth of a Japanese soil sample that contained the bacterium ''Streptomyces tsukubensis''. It is o ...
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Immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into five groups: * glucocorticoids * cytostatics * antibodies * drugs acting on immunophilins * other drugs Glucocorticoids In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Immunosuppressive mechanism Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL- ...
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T-lymphocytes
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or C ...
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G1 Phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 phase ends when the cell moves into the S phase of interphase. Around 30 to 40 percent of cell cycle time is spent in the G1 phase. Overview G1 phase together with the S phase and G2 phase comprise the long growth period of the cell cycle cell division called interphase that takes place before cell division in mitosis (M phase). During G1 phase, the cell grows in size and synthesizes mRNA and protein that are required for DNA synthesis. Once the required proteins and growth are complete, the cell enters the next phase of the cell cycle, S phase. The duration of each phase, including the G1 phase, is different in many different types of cells. In human somatic cells, the cell cycle lasts about 10 hours, and the G1 H ...
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Stuart Schreiber
Stuart L. Schreiber (born 6 February 1956) is a scientist at Harvard University and co-Founder of the Broad Institute. He has been active in chemical biology, especially the use of small molecules as probes of biology and medicine. Small molecules are the molecules of life most associated with dynamic information flow; these work in concert with the macromolecules (DNA, RNA, proteins) that are the basis for inherited information flow. Education and training Schreiber obtained a Bachelor of Science degree in chemistry from the University of Virginia in 1977, after which he entered Harvard University as a graduate student in Chemistry. He joined the research group of Robert B. Woodward and after Woodward's death continued his studies under the supervision of Yoshito Kishi. In 1980, he joined the faculty of Yale University as an assistant professor in Chemistry, and in 1988 he moved to Harvard University as the Morris Loeb Professor. Work in 1980s and 1990s Schreiber started his r ...
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Solomon H
Solomon (; , ),, ; ar, سُلَيْمَان, ', , ; el, Σολομών, ; la, Salomon also called Jedidiah ( Hebrew: , Modern: , Tiberian: ''Yăḏīḏăyāh'', "beloved of Yah"), was a monarch of ancient Israel and the son and successor of David, according to the Hebrew Bible and the Old Testament. He is described as having been the penultimate ruler of an amalgamated Israel and Judah. The hypothesized dates of Solomon's reign are 970–931 BCE. After his death, his son and successor Rehoboam would adopt harsh policy towards the northern tribes, eventually leading to the splitting of the Israelites between the Kingdom of Israel in the north and the Kingdom of Judah in the south. Following the split, his patrilineal descendants ruled over Judah alone. The Bible says Solomon built the First Temple in Jerusalem, dedicating the temple to Yahweh, or God in Judaism. Solomon is portrayed as wealthy, wise and powerful, and as one of the 48 Jewish prophets. He is also the ...
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David M
David (; , "beloved one") (traditional spelling), , ''Dāwūd''; grc-koi, Δαυΐδ, Dauíd; la, Davidus, David; gez , ዳዊት, ''Dawit''; xcl, Դաւիթ, ''Dawitʿ''; cu, Давíдъ, ''Davidŭ''; possibly meaning "beloved one". was, according to the Hebrew Bible, the third king of the United Kingdom of Israel. In the Books of Samuel, he is described as a young shepherd and harpist who gains fame by slaying Goliath, a champion of the Philistines, in southern Canaan. David becomes a favourite of Saul, the first king of Israel; he also forges a notably close friendship with Jonathan, a son of Saul. However, under the paranoia that David is seeking to usurp the throne, Saul attempts to kill David, forcing the latter to go into hiding and effectively operate as a fugitive for several years. After Saul and Jonathan are both killed in battle against the Philistines, a 30-year-old David is anointed king over all of Israel and Judah. Following his rise to power, David ...
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Michael N
Michael may refer to: People * Michael (given name), a given name * Michael (surname), including a list of people with the surname Michael Given name "Michael" * Michael (archangel), ''first'' of God's archangels in the Jewish, Christian and Islamic religions * Michael (bishop elect), English 13th-century Bishop of Hereford elect * Michael (Khoroshy) (1885–1977), cleric of the Ukrainian Orthodox Church of Canada * Michael Donnellan (fashion designer), Michael Donnellan (1915–1985), Irish-born London fashion designer, often referred to simply as "Michael" * Michael (footballer, born 1982), Brazilian footballer * Michael (footballer, born 1983), Brazilian footballer * Michael (footballer, born 1993), Brazilian footballer * Michael (footballer, born February 1996), Brazilian footballer * Michael (footballer, born March 1996), Brazilian footballer * Michael (footballer, born 1999), Brazilian footballer Rulers =Byzantine emperors= *Michael I Rangabe (d. 844), married the d ...
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Joseph Heitman
Joseph Heitman is an American physician-scientist focused on research in genetics, microbiology, and infectious diseases. He is the James B. Duke Professor and Chair of the Department of Molecular Genetics and Microbiology at Duke University School of Medicine. Education and career Joseph Heitman grew up in southwestern Michigan and attended Portage Northern High School. He completed a dual Bachelor of Science–Master of Science program in chemistry and biochemistry at the University of Chicago from 1980 to 1984. There he began his research career, working in the laboratories of organic chemist Josef Fried, biochemist Kan Agarwal, and bacteriologist Malcolm Casadaban. In 1984, he began a dual MD–PhD program at Cornell Medical College and Rockefeller University, working on DNA repair in bacteria with Peter Model and Norton Zinder. In 1989, after receiving his PhD from Rockefeller University, Heitman took a leave of absence from medical school to serve as an EMBO-sponsored long ...
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Streptomyces Hygroscopicus
''Streptomyces hygroscopicus'' is a bacterial species in the genus '' Streptomyces''. It was first described by Hans Laurits Jensen in 1931. Biochemistry Cultures of different strains of ''S. hygroscopicus'' can be used to produce a number of chemical compounds or enzymes. Small molecules Immunosuppressants Sirolimus (also known as rapamycin) is an immunosuppressant that has been isolated from ''S. hygroscopicus'' from soil samples from Easter Island. Ascomycin can be used to treat autoimmune diseases and skin diseases, and can help prevent rejection after an organ transplant. Antibiotics The antibiotics geldanamycin, hygromycin B, nigericin, validamycin, and cyclothiazomycin are found in ''S. hygroscopicus''. Experimental cancer drugs Indolocarbazoles can be found in ''S. hygroscopicus'' . Anthelmintics and insecticides Milbemycin and milbemycin oxime can be found in ''S. hygroscopicus'' cultures. Herbicide ''S. hygroscopicus'' also produces the natural ...
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