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Ras   Listen
noun
ras  n.  The name and genetic symbol for a mutant gene that has been identified as one of those associated with certains types of cancer; it is a form of oncogene. It was first observed in rats, but analogues have been found in humans and other animals. " During the 1960s and 1970s, a great deal of research was done on a class of viruses that affects rodents and birds and causes tumors in those species. The motivation for a lot of this research was the idea that similar viruses might cause tumors in humans, but in fact it's turned out that there are very few viruses that cause tumors in humans. Nevertheless, the study of these rodent viruses has been enormously fruitful in helping us to understand human cancer, and that's the basis of this story. One of the viruses that was studied in those years had two peculiarities. One was that it had lost most of the genes that it needed to reproduce itself. It could only reproduce if a helper virus was present in the same cell to supply the missing functions. The second peculiarity was that in place of the genes that were required for reproduction of the virus was another gene that had actually been picked up at some point in the history of this virus when it went through rats, and it picked up a rat gene and incorporated it into its own genome. At the same time that a lot of work was going on on these viruses, other scientists were studying other aspects of tumor formation, in particular, the action of carcinogenic agents, chemicals and X-rays and ultraviolet light. As you all know, human cells can turn into tumor cells under the influence of such agents. The tumor-like properties of those cells are inherited by all the daughter cells through many generations and, moreover, almost all chemicals that turn out to be carcinogens are also able to cause mutations. Another observation was that in tumor cells, many of the chromosomes seemed to have altered structures. So, all of these observations and others certainly suggested that changes in DNA might be involved in the development of tumor cells. By about 1980, it became possible to test that hypothesis directly. If you have human tumor cells produced in laboratory dishes or isolated from the tumor itself, then perhaps they have a gene or genes in them which is responsible for the fact that they're tumor cells. If you isolate the DNA from the cells and cut it up into more or less gene-sized pieces and then put it on top of mouse cells growing in a dish, the mouse cells can take up pieces of this DNA, and any mouse cell that picks up a piece of DNA that carries on it a gene that can cause a tumor will begin to grow like tumor cells, and its progeny will grow rapidly and form a tight little cluster on the cell. Now it's possible to pick such cells off and isolate the DNA from them and also separate the human DNA sequence that might have caused the tumor-like property from the bulk of the mouse sequences and to clone that DNA. And when you do that and put that DNA, which is now pure sequence, back in mouse cells, many of the cells become tumor-like rather than just a rare few. And such a gene, such a DNA sequence, bears the name of an oncogene. When such DNA segments are cloned, the DNA can also be used to probe, to find out whether matching DNA sequences occur only in tumor cells or whether there are similar DNA sequences in normal cells. And the answer has been for a whole group of oncogenes, that very similar DNA sequences are present in normal cells. To find out just how similar, the sequences of the normal genes were compared with those from the genes that were isolated from these tumor cells. The first such oncogene isolated was from a human bladder tumor, and everyone was surprised by the results. First of all, the gene isolated from the bladder tumor was almost identical to the normal human gene and almost identical to the gene that was present in the tumor virus that infected rodents that I told you about before. This gene has become known as "ras", because it was originally isolated from rats with sarcoma, and it caused sarcomas and it's called that, and it's protein is called that. And the only really significant difference between the normal human gene, the bladder tumor gene, and the rodent virus gene was a change in one codon, Codon XII, and therefore a change in amino acids. So the normal human gene has a sequence GGC, encodes the amino acid glycine, and does not cause tumors. But the bladder tumor gene has GTC; it encodes valine. The rodent virus has AGA; it encodes arginine, and both of these cause tumors. In fact, any change that leads to a loss of the glycine at Codon XII can change this normal gene, ras, into a gene that would cause tumors. So there were two different ways in which the ras gene turned up. First, as a rat gene in a tumor virus and second of all as the gene that could account for the tumor-like properties of the bladder tumor. Well by now, many of the questions that occurred to the scientists working on this have occurred to you. What is the ras protein normally (if anything), and what does the altered ras protein do that differently, and how can a change in one amino acid in a protein change cells from normal to tumor cells? It turns out that the ras gene and the ras protein are important for a lot of things, but more particularly for regulating the growth of cells. Normal cells need to have a good ras gene in order to grow, in order to make new DNA, to time it all right so they don't grow out of control. Moreover, the ras gene occurs in virtually all living things. For example, yeast cells also have two ras genes. If either one of them is knocked out, the yeast cells can still grow very well and multiply. But if both ras genes are knocked out, the yeast cells cannot multiply, and they die. Astonishingly, if a human ras gene is applied to these yeast cells, it completely takes the place of the yeast's own ras genes. So we know from this that the ras gene is very important to all living cells and that it's probably been around for a couple billion years, ever since the very first cells were formed on the planet. So ras does something important and the question is, what does it do? David Golde told you before about receptors that span cell membranes that bind molecules outside the cell and provide a signal inside the cell, and it turns out that what the ras protein does is to help convey that signal from the receptor at the surface down into the cell and into the gene where it results in a change in gene expression. The ras protein itself actually sits right under the cell membrane, very well positioned to do this. Well, how can it do that? To tell you about that I need to tell you a couple of things about the ras protein and what it does. First of all, ras combines two small molecules called GDP and GTP, and they differ only in the presence of one more phosphate, three in GTP and two in GDP. This G is related; it's in fact the same kind of molecule as the G that occurs in DNA. Moreover, ras protein can catalyze the removal of one phosphate, so you go from ras GTP to ras GDP and a phosphate is lost. Furthermore, the ras GDP can lose the GDP and pick up the GTP, and there are extra proteins in the cell that foster either this exchange, back to GTP or this loss of the phosphate to GDP. And the whole trick is the ratio of the GTP to the GDP. So if you have ras GTP, it's active and it stimulates growth, but if you have ras GDP, then it's inactive and you don't stimulate growth. In fact, the change in Codon XII from a glycine results in a change in the amount of ras GTP, so that there's more ras GTP collecting in the cell than the ras GDP, and therefore the cell is constantly under pressure to make DNA and grow and divide. And this is the critical reason for this change, this oncogenic change in those versions of ras that cause tumors or are related to tumor formation as opposed to the natural protein. How can that happen, a small change like that? You've heard a little bit about the importance of shapes of proteins. If one looks closely at the atoms in the proteins then you see that the whole shape of the protein changes as you go from GTP to GDP. Now one ras gene and protein all by itself would be interesting, but it turns out that there's a whole family of ras genes and ras proteins. Two of them are specially similar to the type that I've been describing, and mutations in those genes are associated with a whole variety of human tumors including some that are believed to be the result of the reaction to environmental agents. A mutant in one of those two related genes, which was also first discovered in a tumor virus, is very frequently associated with human tumors of the colon and rectum. And again, it's Codon XII in that similar gene that is altered in the oncogenic form of this kind of ras. Tumors of the colon and rectum are the third most common human malignancy worldwide, and surgical removal of the tumors can actually cure the disease in many cases, but only if the tumor is detected very, very early. Recent work has shown that you can, in fact, detect the change in the gene even by looking at the DNA in the stool of people who are suspected of having the colon tumor. Even though the mutant DNA only occurs in a very small percentage of the cells in the stool, namely the cells that come from the tumor, not from all the normal cells or all the bacterial cells that are there, it is possible to amplify the amount of a possible abnormal ras gene and test directly for it. So, for example in this test, DNA from the stool of patient #1 matched a probe for the normal ras gene, but DNA isolated from the stool of patient #2 matched a probe not only from a normal ras gene but also from a ras gene with a mutation at Codon XII, thereby permitting a very early diagnosis of a colon tumor and thereby providing real hope that such tumors can be detected early, when the tumor is small enough to be removed surgically with a successful cure."






Collaborative International Dictionary of English 0.48








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"Ras" Quotes from Famous Books



... waters of the fountain just named bear a great reputation among the natives in that neighbourhood for their healing qualities, and numerous invalids may always be found there, who come for the cure of their various ailments. At six we encamped near the famous fountain known by the name of "Ras el-'ain," where the ruins of its great aqueduct leading to "El Ma'-shuk" (an isolated hill in the plain) and the ancient Tyre were still to be seen. This fountain and those previously named were considered by ...
— Diaries of Sir Moses and Lady Montefiore, Volume I • Sir Moses Montefiore

... altar was reconstructed, under Dean Stanley's supervision, from such pieces of the old Italian pilasters and frieze as could be found; one was actually discovered at Oxford in the Ashmolean Museum. Upon it stands the cross which was presented by the Ras Makonnen, Envoy from Abyssinia, as a votive offering for the present King's recovery from his sudden illness, when the Coronation was postponed in the summer of 1902. The stalls next claim our attention, and it must be pointed out that only part of these date from the sixteenth century, ...
— Westminster Abbey • Mrs. A. Murray Smith

... got married to Mr. Ras Laird, dey had a big weddin' an' all dey folks come to see 'em married. Den dey went to live in Rankin County an' took me wid 'em. Old Marster had give me to ...
— Slave Narratives: A Folk History of Slavery in the United States From Interviews with Former Slaves - Mississippi Narratives • Works Projects Administration

... first-born. And she, who loved him much, and whom he loved, prevailed upon him to name my brother after her father as well as after himself, the child's father (as is our custom) and so my brother was rightly called Mir Jan Rah-bin-Ras el-Isan Ilderim Dost Mahommed ...
— Driftwood Spars - The Stories of a Man, a Boy, a Woman, and Certain Other People Who - Strangely Met Upon the Sea of Life • Percival Christopher Wren

... and bunked with ye, and watched with ye all three, And better shipmates than ye were I never hope to see. I've seen ye in the wild typhoon beneath a Southern sky, I've seen ye when the Northern gales drove seas to mast-head high, But summer breeze or winter blow, from Hatt'ras to Cape Race, I've yet to see ye with the sign ...
— The Seiners • James B. (James Brendan) Connolly

... Branches reach the Levant seaports of Tripoli, Beirut, and Haifa. Another railway was started from Aleppo to Bagdad shortly before the war, and construction begun at both ends. We have no reliable information as to how far it has progressed, but the presumption is that there is a large gap between Ras-el-ain and Mosul and between ...
— World's War Events, Vol. II • Various

... it. Accordingly wherever he encamped, we meet with these extensive plantations of olive trees, planted by his troops, which are not only a great ornament to the country, but produce abundance of fine oil. The olive plantations at Ras El Wed, near Terodant in Suse, are so extensive, that one 78 may travel from the rising to the setting sun under their shade, without being exposed to the rays of the effulgent ...
— An Account of Timbuctoo and Housa Territories in the Interior of Africa • Abd Salam Shabeeny

... first day at Bagamoyo was Ali bin Salim, a brother of the famous Sayd bin Salim, formerly Ras Kafilah to Burton and Speke, and subsequently to Speke and Grant. His salaams were very profuse, and moreover, his brother was to be my agent in Unyamwezi, so that I did not hesitate to accept his offer of ...
— How I Found Livingstone • Sir Henry M. Stanley

... to the open air custom-house (coffee exchange) in the center of the town, where a ten-percent duty (in coffee) is exacted by the local government, and one Abyssinian dollar (fifty cents) is added for every thirty-seven and a half pounds, this latter being Ras Makonnen's share. As soon as the native dealer has released to him what remains of his shipment, he takes it out of the custom-house enclosure and disposes of it through the native brokers, who have their little "office" booths ...
— All About Coffee • William H. Ukers

... With a cynical frown, On the face of his beautiful bride! He had picked up a cargo Of curious argot While living in Paris the gay; In the slang of that city He cried without pity: "Comme ca tu me fich'ras ...
— Grimm Tales Made Gay • Guy Wetmore Carryl

... Pythag'ras rose at early dawn, By soaring meditation drawn, To breathe the fragrance of the day, Through flowery fields he took his way. In musing contemplation warm, His steps misled him to a farm, Where, on the ladder's topmost round, A ...
— The Poetical Works of Addison; Gay's Fables; and Somerville's Chase • Joseph Addison, John Gay, William Sommerville



Words linked to "Ras" :   rf, Ras Tafari, neural network, neural net, reticular activating system, Ras Tafari Makonnen, reticular formation



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