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New tool developed for profiling critical regulatory structures of RNA molecules
A molecular technique that will help the scientific community to analyze-on a scale previously impossible-molecules that play a critical role in regulating gene expression has been developed by a research team led by a chemist and a plant biologist at Penn State University. The scientists developed a method that enables more-accurate prediction of how ribonucleic acid molecules (RNAs) fold within living cells, thus shedding new light on how plants-as well as other living organisms-respond to environmental conditions. A paper by the research team-led by Sarah M. Assmann, Waller Professor of Biology, and Philip Bevilacqua, professor of chemistry-is scheduled for early online publication in the journal Nature on 24 November 2013.
"Scientists have studied a few individual RNA molecules, but now we have data on almost all the RNA molecules in a cell-more than 10,000 different RNAs," Assmann said. "We are the first to determine, on a genome-wide basis, the structures of the RNA molecules in a plant, or in any living organism."
Temperature and drought are among the environmental stress factors that affect the structure of RNA molecules, thereby influencing how genes are "expressed"-how their functions are turned on or turned off. "Climate change is predicted to cause increasingly extreme and unpredictable heat waves and droughts, which would impact our food crops, in part by affecting the structures of their RNA molecules and so influencing their translation into proteins," Bevilacqua said. "The more we understand about how environmental factors affect RNA structure and thereby influence gene expression, the more we may be able to breed-or develop with biotechnological methods-crops that are more resistant to those stresses. Such crops, which could perform better under more-marginal conditions, could help feed the world's growing population."
The scientific achievement of the Penn State research team-postdoctoral scholar Yiliang Ding, graduate students Yin Tang and Chun Kit Kwok, and Professor of Statistics Yu Zhang, along with Assmann and Bevilacqua-involved determining the structures of the varieties of RNA molecules in a plant named Arabidopsis thaliana. This plant is used worldwide as a model species for scientific research.
Arabidopsis thaliana, commonly known as mouse-ear cress, is an ideal organism for RNA studies, the researchers say, because it is the first plant species to have its full genome sequenced and has the greatest number of genetic tools available.
RNA is the intermediate molecule between DNA and proteins in all living things. It is a critical component in the pathway of gene expression, which controls an organism's function. Unlike the double-stranded DNA molecule, which is compressed into cells by twisting and wrapping around proteins, RNA is single stranded, and folds back on itself. The researchers set out to answer the question, How exactly does RNA fold in a cell and how does that folding regulate gene function?
"We needed a tool to answer that question," says Bevilacqua. "That tool involves introducing a chemical into the plant that can modify some segments of the RNA but not others, which then gives a readout of the structure of the RNA. Using this technique we can figure out which classes of genes are associated with certain RNA structural traits. And we can try to understand how these RNA structural changes relate to certain biological functions."
"Previously, researchers would query the structures of individual RNAs in a cell one by one, and it was a tedious process," says Assmann. "You can't abstract rules or generalities about how RNAs are behaving just from knowing the structures of one or a few RNAs-you can't get a pattern. Now that we have genome-wide information for a particular organism, we can start to abstract patterns of how RNA structure influences gene expression and ultimately plant function. Other scientists can query their organisms of interest and ask what rules they can abstract. Are there universal rules that will be true for all organisms for how RNA structure influences gene expression?"
Bevilacqua adds, "Because RNA is so central in its role in gene regulation, the tools we've developed can be transferred to scientists who are working with essentially any biological system."
Long-term potential implications of the methodology include human health-for example, how an infection-induced fever could affect the RNA structures of both humans and pathogens.
Super antibodies almost won HIV
In AIDS patients as there is only one hope - to antiretroviral therapy, which is based on drugs that prevent HIV from reproducing. Genome recorded in the virus RNA and thus enter the cell it with reverse transcriptase enzyme (reverse transcriptase) makes a copy of its own DNA template RNA. Then, this DNA was self proteins cells begin RNA viral clone. If, for example, to suppress the work of the reverse transcriptase of the virus, it can not reproduce.
But even cocktails of antiretroviral drugs only help to translate the acute phase of the disease chronic. Such therapy can not do anything with the virus, which floats in the blood or in the cell is dormant. Therefore, researchers are looking for a way to get rid of the virus, rather than just suppressing its ability to reproduce. (By the way, the usual anti-HIV therapy is theoretically allows to get rid of the virus, but only under special conditions, and such cases are, unfortunately, rare.)
HIV and human lymphocyte
When it comes to completely banish HIV, all agree that the best anti tool to be found here. On the one hand, it's simple: just find the immunoglobulins, which would learn viral envelope protein have been associated with him and would have signaled an immune killer cells that this complex must be destroyed. The problem, however, is that HIV has enormous variability, and antibodies usually catch only a certain proportion of the virus particles, for the same protein they endowed with a number of differences that make antibodies do not see it.
However, our immune system is still able to cope with such a variety of the virus , creating a broad-spectrum antibodies . The fact that the immune system can produce immunoglobulins that recognize more than 90 % of the species of HIV , scientists discovered in 2010, and this discovery , of course, has given all hope that AIDS is about to fall . But over time it became clear that such antibodies are rare and a huge amount of time , then only in response to a real infection - that is to provoke a synthesis of a vaccine of killed pathogen will not work.
Nevertheless, scholars have continued to work with the likes of antibodies. And not so long ago have found universal antibodies that appear much earlier and look simpler than those observed before - however, proved their versatility and low. But be sure to make yourself immune to produce such antibodies? The experiments showed the two research groups - Deaconess Medical Center Beth Israel and the National Institute of Allergy and Infectious Diseases (both - USA) - immunoglobulins broad-spectrum, just introduced into the blood, effectively reduce the level of HIV.
HIV between epithelial cells (bottom) and lymphocyte (top)
Immediately it should be said that the group of Dan Baruch (Dan Barouch) and Malcolm Martin (Malcolm Martin) experimented with monkeys: macaques infected with simian-human hybrid HIV, which multiply in monkeys, but looked like a human virus. He served as a weapon against a broad-spectrum antibodies obtained from patients with AIDS.
Dan Baruch and his colleagues used a cocktail of three types of antibodies, and, as the researchers write in Nature, in the week of the virus level down so that it can not be detected! A similar result was also when used instead of a mixture of immunoglobulins only one of their kind. Once the content of such antibodies in the blood began to decline, the concentration of the virus rose again, but some monkeys it was still indistinguishably low even without the introduction of additional portions of antibodies.
In another study carried out by Malcolm Martin and his colleagues, we are talking about the same thing , but here researchers have used different types of antibodies against HIV. Again, the concentration of the virus in macaques fell for seven days prior to the indiscernible ( again: undetectable !) Level and remained so for 56 days, until the antibodies do not begin to fade. Then it all depended on how much virus was originally in monkeys , if small, following the disappearance of virus antibodies remained under the control of its own immunity of animals , and if it was originally much, the level began to rise.
Thus, as emphasized by the researchers, the virus disappeared from both the blood and other tissues, and no resistance to the administered antibodies, it appeared. (However, there was one exception: when the second study administered only one antibody and experimental monkey was a 3-year experience of cohabitation with the virus, it has a sustained viral strain.)
In both cases, scientists are not too long treated the virus with human antibodies because they were afraid that the immune system begins to resent monkeys against foreign immune proteins , and perhaps that was the reason that in most cases, the virus recovered . That is, it is not clear whether it is possible to make the effect of the " long-playing ". All this is clear only after a clinical trial , and as for the results described above , the enthusiasm of researchers can understand the first time in a living organism could so much lower level of viremia (alas , previous experiments with antibodies that were placed on humans and mice had a very unimpressive results ) .
What's next? The cost of antibodies is much higher than the anti-retroviral drugs, and to treat them more difficult. But the authors of the work suggest that such antibodies should be connected to conventional anti-HIV drugs: it will reduce the cost of treatment, and is likely to increase its efficiency - if antibodies to add substances harmful to reproduction of the virus in the cell.
Like New Again
Reactivating expression of the RNA-binding protein Lin28a in mice leads to improved regrowth of hair follicles, as well as of cartilage, bone, and mesenchyme after ear and digit injuries, according to a study published in Cell Magazine last week (November 7). Harvard Medical School’s George Daley and his colleagues have shown in several models of tissue injury that “Lin28a enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics,” as they wrote in their paper.
“It sounds like science fiction, but Lin28a could be part of a healing cocktail that gives adults the superior tissue repair seen in juveniles,” Daley said in a statement.
However, not every tissue injury model showed improved healing with increased expression of Lin28a. “The fact that it doesn't work sometimes is even more interesting because it raises the question why,” the University of Michigan’s Daniel Goldman, who was not a part of the study, told Nature.
Study coauthor Shyh-Chang Ng added that the perceived renewing effects of Lin28a are particularly interesting because of the RNA-binding protein’s prevalence. “Most biologists would think that you need a special factor to generate the healing pathway, but this is a thing that every cell has,” Ng told Nature.
The deadliest substance in the world is now found
Scientists have discovered the most poisonous substance known to man to date. However, for the first time, the scientific community decided to keep secret the details of his discovery, as yet not found an antidote to the dangerous substance.
According to the experts, the inhalation of substances produced by the bacterium Clostridium botulinum of only 2 billion per gram can kill an adult.
Toxicant blocking acetylcholine release from nerve cells, responsible for the operation of the muscles. If by chance the substance gets into the body with food, and this can happen, because the bacteria often grow in food - Man Gets botulism and die in a short time from paralysis.
Botulism is typically treated by means of antibodies which are produced artificially. They react to seven known type of disease known to experts from A to G. However, scientists from the California Department of Public Health in Sacramento said they found eight toxin type - H. Toxic substance found in the stool of a child in which they observed the characteristic symptoms of the terrible disease. And, unfortunately, currently not found a way to combat the new disease.
The presence of metastasis of melanoma will be detected with a test
A blood test can be used to identify patients in whom skin cancer spreads to other organs, according to a presentation given at a conference at National Cancer Research Institute in the UK.
The presence of metastases of melanoma - the most dangerous and aggressive skin cancer, is one of the biggest challenges in medicine. According to researchers from the University of Dundee measurement of gene TFP12 may be the key to faster diagnosis and a new treatment.
This may be achieved by using a single blood test. If doctors know when the tumor begins to affect other organs, the chances for a cure are much higher, said the head of research - Dr Tim Crook.
Researchers to reach the conclusion that "exclusion" and "inclusion" of certain genes may affect how, where and why spreading melanoma. The next step for researchers to develop a panel of biomarkers such, by means of which will be able to detect those patients who are in need of further treatment in the fight against melanoma.
The research team identified other biomarker - NT5E, which is associated with the spread of aggressive melanoma. Experts believe that based on the findings will be possible to develop a new treatment for the disease.
Eating itself of cancer cells as a new type of treatment
Incitement of tumor cells devours itself would probably be one of the best decision on the treatment of large numbers of tumor diseases.
In a new study, researchers found that a combination of certain medications can cause the cancer cells to "cannibalism", without damaging healthy tissue. This type of treatment has demonstrated efficacy in tumors in the colon, liver, lung, breast, brain and kidneys.
Researchers are trying to determine whether co-administration of drugs sorafenib and regorafenib can be combined with so-called PI3K/AKT inhibitors to achieve better effect.
Andrew Poklepovic who is co-author of this work, says that despite the need for further research, the results so far are promising. Scientists are encouraged by the fact that the drugs used have already been approved by the FDA to treat certain types of tumors or are currently undergoing trials and pending approval.
The medicaments sorafenib and regorafenib influence the growth of tumor cells by blocking the release of enzymes - kinases that play a decisive role in the spread of cancer cells.
Newfound combination drugs enhances this effect, as it adds a new class of kinases inhobitori - PI3K/AKT inhibitors. Thus, many of the tumor cells "starve", limiting tumor growth.
More effective vaccine will fight papilloma virus (HPV)
Experimental vaccine against cancer progression showed a broad protection against the virus that carries the risk of developing tumors. Innovative vaccine is the U.S. pharmaceutical company Merck & Co.
In its report, the vaccine makers explained that the survey results support the company's plan to submit a new vaccine approved in the U.S. by the end of the year. In the event that it is received, the new vaccine can be introduced next year.
Gardasil is the first vaccine company that was developed in 2006 It protects against several strains of the virus: 6, 11, 16 and 18, as the risk for cervical cancer are strains 16 and 18, and 6 and 11 cause the formation of genital warts. The company's new vaccine offers greater protection.
Company Merck & Co has already conducted clinical trials to test the safety and efficacy of the new vaccine, and the results should be presented at a special meeting of doctors in Florence, Italy this week, said the report.
Antibodies produced from seropositive, can form the basis of treatment of HIV
A powerful mixture of antibodies fighting against the AIDS virus attack pulls strong form of the virus in monkeys and then " hold off " weeks , Reuters reported , citing a research team of the U.S. government , led by researchers at Harvard University . Experts have presented findings from two studies in this direction in the journal " Nature "
Researchers found that the rare antibodies produced by 10 to 20 percent of people with HIV, such as to counteract many of the strains of the virus. Such antibodies adhere to those areas of the virus, which are critically important to him, and which are monitored in any strain of HIV. And are attached to the virus , the antibodies do unable to infect other cells.
In the past decade, scientists have tried to develop a vaccine that can cause the body to produce this type of specific antibodies to HIV , but it was quite difficult.
Scientists describe the above antibodies as Ferraris antibody indicates Dr. Dan Baruch , a professor at the Medical College of Harvard University , participated in the research.
For the purpose of both research scientists experienced antibodies on monkeys of the species rhesus infected monkey version of HIV. Rare antibodies were collected from HIV -infected people were then grown in large quantities in the laboratory and were infused in large doses to monkeys. Researchers tested various combinations of antibodies in 35 monkeys. Best working antibody called PGT 121 . Alone or with other antibodies , it gives great results.
Generally antibodies reduced the virus to very low levels in 16 to 18 monkeys within seven days, and this effect was maintained for up to three months. In three animals carry the virus, but in small quantities after treatment he did not reappear.
The effect of the antibodies to be tested on humans. Furthermore, it has not been studied in combination with antiretroviral drugs, which are the standard anti-HIV drugs, used by many thousands of patients in order to control the virus.
According to scientists, however, the combination of antibodies with antiretroviral drugs would make sense because the two treatments have different mechanisms of action. Antiretroviral drugs only attack the mechanism of HIV virus to create copies, while antibodies can directly attack the particles of the virus in blood and in cells that are infected with the virus.
It is not clear whether the antibodies can attack the dormant HIV cells that are hidden in the body and allow the virus to reappear when treatment is discontinued.
Researchers develop more effective drug for hepatitis-C
Medicament for the treatment of hepatitis C, developed by Gilead Sciences, received a positive evaluation by the Administration Food and Drug Administration in the U.S..
A positive response by the administration due to the success that the medicament is accomplished by treatment of the disease - more patients are cured in a shorter period of time compared with other drugs in the market.
Studies have shown that adding the drug to Sofosbuvir other prescribed medication is able to cure 90% of patients within 12 weeks, reports the Associated Press. So far no evidence of side effects associated with taking Sofosbuvir.
Since 1986 suffering from hepatitis C treated with interferon alpha protein. However, it is not suitable for everybody, and the positive outcome of the treatment was observed in less than half of the patients who take it.
On the other hand, side effects include depression, symptoms resemble those of the flu, such as fever, fatigue and headache. In some cases, they may even be exacerbated to the extent that may be necessary to slow or stop the treatment.
In 2011, the Administration has approved two drugs that can be used as an add-on to treat the most common type of hepatitis C. Studies have found that the drugs increase the number of patients cured by 65 - 75% of. Recently, however, pharmaceutical companies insist on medications that do not contain interferon.
Hepatitis C is a blood disorder that causes inflammation of the liver. Around 70-80% of people with hepatitis C do not notice any symptoms.
When they are present include: pain in the right upper abdomen, dark urine, fever, jaundice, nausea and vomiting. People with acute hepatitis C may develop a chronic infection.
Chronic hepatitis C can cause cirrhosis of the liver and is a leading factor in the development of liver cancer cherry.
Protein destroys lymphoma
The key in combating certain types of cancer is probably in the cessation of cell proliferation. Cell proliferation is a process of newly formed cells in the body by division. Researchers try to influence B-cell lymphoma using a similar mechanism.
They reactivate gene that controls the natural process of aging of the cells, and thus prevent their replication. Researchers believe that the discovery could lead to the development of a new medicament for the treatment of tumor diseases.
Scientists say they have discovered a new role of a protein called Smurf2, which is to suppress tumors. It assists in the process of aging of the cells of the subclass of diffuse B-cell lymphoma.
The authors of the study explained that the recovery of Smurf2 expression on the body can bring benefits for the treatment of patients and help treatment in severe cases. This is possible, since it regulates the process of aging of the cells, and stops cell division and proliferation of B-cells.
In people suffering from diffuse large B-cell lymphoma, however, protein Smurf2 is less pronounced.
Diffuse B-cell lymphoma is the most common form of non-Hodgkin's lymphoma, - the group of cancers that begin from the lymph nodes and lymphoid system. Scientists believe that if they could develop a drug that increases the expression of Smurf2 protein in tumor cells, medicine can achieve a more effective treatment of the disease.