Rna Quick Quotes

Pharmaceutical companies became very interested in using siRNAs as potential new drugs. Theoretically, siRNA molecules could be used to knock down expression of any protein that was believed to be harmful in a disease. In the same year that Fire and Mello were awarded their Nobel Prize, the giant pharmaceutical company Merck paid over one billion US dollars for a siRNA company in California called Sirna Therapeutics. Other large pharmaceutical companies have also invested heavily. But in 2010 a bit of a chill breeze began to drift through the pharmaceutical industry. Roche, the giant Swiss company, announced that it was stopping its siRNA programmes, despite having spent more than $500 million on them over three years. Its neighbouring Swiss corporation, Novartis, pulled out of a collaboration with a siRNA company called Alnylam in Massachusetts. There are still plenty of other companies who have stayed in this particular game, but it would probably be fair to say there’s a bit more nervousness around this technology than in the past. One of the major problems with using this kind of approach therapeutically may sound rather mundane. Nucleic acids, such as DNA and RNA, are just difficult to turn into good drugs. Most good existing drugs – ibuprofen, Viagra, anti-histamines – have certain characteristics in common. You can swallow them, they get across your gut wall, they get distributed around your body, they don’t get destroyed too quickly by your liver, they get taken up by cells, and they work their effects on the molecules in or on the cells. Those all sound like really simple things, but they’re often the most difficult things to get right when developing a new drug. Companies will spend tens of millions of dollars – at least – getting this bit right, and it is still a surprisingly hit-and-miss process. It’s so much worse when trying to create drugs around nucleic acids. This is partly because of their size. An average siRNA molecule is over 50 times larger than a drug like ibuprofen. When creating drugs (especially ones to be taken orally rather than injected) the general rule is, the smaller the better. The larger a drug is, the greater the problems with getting high enough doses into patients, and keeping them in the body for long enough. This may be why a company like Roche has decided it can spend its money more effectively elsewhere. This doesn’t mean that siRNA won’t ever work in the treatment of illnesses, it’s just quite high risk as a business venture.

RNA viruses mutate relatively quickly, and many, like influenza, are able to undergo a process known as antigenic drift, by which the virus is able to alter the surface antigens that are the targets of our antibodies—thus evading our existing immunity. Some viruses, like measles, cannot change their genomic sequence in ways that substantially alter enough of their surface proteins, so measles remains susceptible to our vaccines or the immunity that we get from prior infection. However, for viruses like influenza, as their surface proteins undergo change, the virus is able to dodge the protective antibodies that we’ve developed from past infection or vaccination

These increases in brain cholesterol and pituitary activity were clues that were rich in their implications, and in the late 1960’s a research team at the University of California at Berkeley began to look for specific differences in the neural structures of gentled and ungentled rats. They found that greater tactile stimulation resulted in the following differences: These animals’ brains were heavier, and in particular they had heavier and thicker cerebral cortexes. This heaviness was not due only to the presence of more cholesterol—that is, more myeline sheaths—but also to the fact that actual neural cell bodies and nuclei were larger. Associated with these larger cells were greater quantities of cholinesterase and acetylcholinesterase, two enzymes that support the chemical activities of nerve cells, and also a higher ratio of RNA to DNA within the cells. Increased amounts of these specific compounds indicates higher metabolic activity. Measurements of the synaptic junctions connecting nerve cells revealed that these junctions were 50% larger in cross-section in the gentled rats than in the isolated ones. The gentled rats’ adrenal glands were also markedly heavier, evidence that the pituitary-adrenal axis—the most important monitor of the body’s hormonal secretions—was indeed more active.34 Many other studies have confirmed and added to these findings. Laboratory animals who are given rich tactile experience in their infancy grow faster, have heavier brains, more highly developed myelin sheaths, bigger nerve cells, more advanced skeletal muscular growth, better coordination, better immunological resistance, more developed pituitary/adrenal activity, earlier puberties, and more active sex lives than their isolated genetic counterparts. Associated with these physiological advantages are a host of emotional and behavioral responses which indicate a stronger and much more successfully adapted organism. The gentled rats are much calmer and less excitable, yet they tend to be more dominant in social and sexual situations. They are more lively, more curious, more active problem solvers. They are more willing to explore new environments (ungentled animals usually withdraw fearfully from novel situations), and advance more quickly in all forms of conditioned learning exercises.35 Moreover, these felicitous changes are not to be observed only in infancy and early maturation; an enriched environment will produce exactly the same increases in brain and adrenal weights and the same behavioral changes in adult animals as well, even though the adults require a longer period of stimulation to show the maximum effect.36

The study of stem cell niches in mammalian systems presents an 'arduous endeavor'; in comparison, the fly germarium is relatively easy to manipulate. In the 1990s, H. Lin, A.C. Spradling, and others used of a number of approaches to study Drosophilia GSCs and their niche, including killing specific cells in the germarium with precisely directed lasers; transplantation of cells from the ovary of one fly to another; and genetic perturbations that included the dialing up or down of Hh pathway signaling. The researchers found that following laser ablation of cells surrounding the GSCs - that is killing the niche cells - all the GSCs went on to form eggs, and the system was quickly depleted of its GSC reserve. Moreover, through genetic analyses the researchers identified specific genes required in the niche cells to maintain GSCs within the niche, as would be deduced for a gene that, when disrupted in niche cells, has the same effect as laser ablation of those cells. These studies are credited with providing the first clear experimental evidence of a stem cell niche, as well as defining what genes - what signaling pathways and other cellular activities - are important to the process. Many of the same pathways relevant in other cell types proved relevant to communication between the niche and GSCs, including the Hh pathway. The genes required for suppression of transposon mobilization by the piRNA system also have relevance to the GSC niche; disruption of the piwi gene, for example, can lead to uncontrolled proliferation of GSCs.

Through RNA editing—swapping out one RNA base for another. They can produce molecular diversity quickly, particularly in their nervous systems. It’s an alternative engine for evolution,