Pattern formation is essential in the development of animals and plants. The central problem in the formation of patterns is how to translate the genetic information into a reliable way to get the specific spatial pattern of cell differentiation.
The stripes formed by the French national flag model are a classic example of developmental biology. Cell differentiation, represented by different colors of the French national flag, is caused by a gradient of signal molecules (morphology), i.e., in high, medium and low concentrations of the morphology of the "blue", "white" or "red" gene stripes are activated, respectively. How cellular gene regulatory networks (GRNS) respond to morphogenesis, in a concentration dependent manner, is a key issue in developmental biology. Synthetic biology is a promising new tool to construct the function and performance of the genetic engineering regulatory network (GRNS) from the first principle. This research developed a synthetic biology approach to establish some basic mechanisms behind the formation of the fringes.
In previous studies, and the behaviour of the predefined gene circuit was successfully constructed and model, but most of them on a case by case basis. In this study, published in nature, researchers at the EMBL / CRG systems biology research group, beyond the individual network, and to investigate the computational and synthetic mechanisms of the two sides in a complete set of 3 nodes that form a network of Escherichia coli. The approach combines experimental synthetic biology, led by Mark Isalan, and is now the head of the life sciences department and computational modeling of the, ICREA, Professor of research at the Imperial College London, and the, and in the head of the CRG multicellular systems biology laboratory.
"We have carried out very innovative and ambitious research: we have used a three step approach to effectively explore and create a successful synthetic gene circuit we created a theoretical framework for the detailed study of GRNS" - 2800 of the one hundred thousand version of the network is simulated by computer. Then, we successfully developed a synthetic network engineering system, and finally, we determined all the new experimental data to fit it with a single mathematical model, explained: "the corresponding author James Sharp.
First, Andrea Munteanu, co-author of the study, theory on the screen was found to produce desired behavior (formation of striation morphology gradient) all kinds of design. In this step, she found 4 fundamental - different mechanisms to form the stripes. Then, Yolanda Schaerli, first author of the study and successfully show the four network is the function through establish their in the bacterium Escherichia coli using the tools of synthetic biology. The third step is to validate the different mechanisms by fitting all experimental data to a mathematical model.
The success of this process allows the researchers to take a step to the formation of a deeper level of the design principles. They identified a simple network of 2 nodes - where the Striped gene is directly activated by both activation and inhibition from the morphology of the sensor gene - i.e., replication in its simplest form of stripe formation ability to control. They succeed in building the prototype of a stripe forming network, and eventually find that it can even display an "anti - Striped" phenotype.
"The combination of detailed computational modeling and synthetic biology is more efficient and more powerful than the establishment of a network of networks," said Mark Isalan, author of the. "Our approach provides synthetic biology as a novel and fast diet - a new science discipline that is designed to design a variety of useful biological systems".
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2015年8月17日星期一
Lab grown tissue
Lab grown tissue may one day provide a new therapy for the joints, including the joints, cartilage, tendons and ligaments.
Cartilage, for example, is the cap bone end, and allows the joint to work smoothly and hard materials. Biomedical engineer, University of California at Davis, explores how to work harder to engineer cartilage, and maintain a strong body of nature, in the journal reports on new progress, this week's proceedings of the National Academy of Sciences.
"Is a problem with the tissue engineering, mechanical properties in far different from natural organization," Ailaifusailiao MAKRIS, a postdoctoral fellow in biomedical engineering at the University of California, Davis, and first author on the said. Makris is Professor A. Athanasiou Kyriacos, a professor of Biomedical Engineering and Department of orthopedics surgery for the outstanding teaching, biomedical engineering, and under the supervision of the.
While the engineered cartilage has not been tested or approved for human use, the current approach to the treatment of severe joint problems is associated with the transplantation of natural cartilage. But it is well known that the method is not sufficient for a long-term clinical solution, Makris.
The main component of the cartilage is a collagen, which also provides the strength and flexibility of the organization, including ligaments, tendons, skin and bones. Collagen is produced by the cells and by the long fiber, which can be cross-linked together.
Engineering new cartilage
The Athanasiou group of researchers has been maintained in the laboratory by native cartilage and cartilage cultured cells, cartilage or, produced by engineered cartilage.
"The cells in the engineered tissue produce the initial immature matrix, and the process of maturation makes it more rigid," Makris said.
Knee joints are usually low in oxygen, so researchers are in the role of natural or engineered cartilage in depriving oxygen. In these two cases, low oxygen leads to more cross-linking and strong materials. They also found that the enzyme called ELISA, which is a test of the enzyme, was triggered by a low oxygen level, and promoted the cross-linking and made it stronger.
"The impact of the work presented in the proceedings of the National Academy of Sciences is a huge relative to the use of tissue grafts in surgery, as well as the use of tissue engineering, the principle of the new organization," Athanasiou said. Plants such as dead bodies, tendons, ligaments, or - the infamous loss of stored mechanical properties - are now in the development of the University of California at Davis, which makes them more powerful, full-featured technology, he said.
Athanasiou is also envisaged that many organizational engineering methods are now being changed to enhance the advantages of technology.
Read more:http://about.cusabio.com/m-187.html
Cartilage, for example, is the cap bone end, and allows the joint to work smoothly and hard materials. Biomedical engineer, University of California at Davis, explores how to work harder to engineer cartilage, and maintain a strong body of nature, in the journal reports on new progress, this week's proceedings of the National Academy of Sciences.
"Is a problem with the tissue engineering, mechanical properties in far different from natural organization," Ailaifusailiao MAKRIS, a postdoctoral fellow in biomedical engineering at the University of California, Davis, and first author on the said. Makris is Professor A. Athanasiou Kyriacos, a professor of Biomedical Engineering and Department of orthopedics surgery for the outstanding teaching, biomedical engineering, and under the supervision of the.
While the engineered cartilage has not been tested or approved for human use, the current approach to the treatment of severe joint problems is associated with the transplantation of natural cartilage. But it is well known that the method is not sufficient for a long-term clinical solution, Makris.
The main component of the cartilage is a collagen, which also provides the strength and flexibility of the organization, including ligaments, tendons, skin and bones. Collagen is produced by the cells and by the long fiber, which can be cross-linked together.
Engineering new cartilage
The Athanasiou group of researchers has been maintained in the laboratory by native cartilage and cartilage cultured cells, cartilage or, produced by engineered cartilage.
"The cells in the engineered tissue produce the initial immature matrix, and the process of maturation makes it more rigid," Makris said.
Knee joints are usually low in oxygen, so researchers are in the role of natural or engineered cartilage in depriving oxygen. In these two cases, low oxygen leads to more cross-linking and strong materials. They also found that the enzyme called ELISA, which is a test of the enzyme, was triggered by a low oxygen level, and promoted the cross-linking and made it stronger.
"The impact of the work presented in the proceedings of the National Academy of Sciences is a huge relative to the use of tissue grafts in surgery, as well as the use of tissue engineering, the principle of the new organization," Athanasiou said. Plants such as dead bodies, tendons, ligaments, or - the infamous loss of stored mechanical properties - are now in the development of the University of California at Davis, which makes them more powerful, full-featured technology, he said.
Athanasiou is also envisaged that many organizational engineering methods are now being changed to enhance the advantages of technology.
Read more:http://about.cusabio.com/m-187.html
2015年8月14日星期五
Escape from the yeast can improve the health benefits of wine, reduce headache after
Scientists at the University of Illinois have designed the "escape" of the yeast, which can greatly improve the health benefits of wine, while reducing the toxic byproducts that cause you to have a headache.
"Fermented foods - such as beer, wine and bread - are made with yeast strains, which means that they contain multiple copies of the gene in the genome, and it has been difficult to do so. If you are the one copy in the genome changes a gene, a constant copy will correct has changed one eye, "permanent Sujin, I microbial genomics of associate professor, main research personnel in the energy Biosciences Institute U shape that.
Recently, scientists have developed a "genomic knife" that spans multiple copies of the target gene in the genome of a very precise - until all copies are cut off. Jinyi group has used this enzyme using ELISA test kits and RNA directed cas9 nucleic acid, polyploid precise metabolic engineering of Saccharomyces cerevisiae has is widely used in wine, beer, and industrial fermentation strains.
The possibility of improving the nutritional value of the food is amazing, he said. "Wine, for example, contains a healthy component of resveratrol, along with the engineered yeast, we can increase the amount of Resveratrol by 10 times more than the amount of resveratrol, but it also can be added to the metabolic pathway for the introduction of other foods that are biologically active compounds, e.g.. Such as ginseng, into the wine yeast or we can pull for beer into the pathway of resveratrol production, sour milk, cheese, pickles, pickles or yeast strains - use yeast fermentation production of any food.
Another advantage is that the wine maker can clone enzymes to improve the lactic acid fermentation, the two fermentation process, so that the wine is smooth. To produce toxic byproducts of lactic acid fermentation is not correct, may cause the symptoms of a hangover, he said.
Kim stressed the importance of the genome knife as a tool that allows genetic engineers to make these extremely precise mutations.
"Scientists need to create design mutations to determine the function of a particular gene," he explained. "We have a great taste for wine production, and we want to know why. We removed a gene and then went to a different flavor, and we knew we had isolated the genes responsible for this."
The new technology also makes it less offensive to genetically modified organisms, he said. "In the past, scientists had to use antibiotic markers to indicate the genetic changes in the light spot in organisms, and many people against their use in dangerous food because of developing antibiotic resistance, and as a genomic knife can cut the genome very accurately and efficiently, so we don't have to use antibiotic markers to identify a genetic event".
The study is reported in the recent issue of environmental microbiology.
Read more:http://about.cusabio.com/m-179.html
"Fermented foods - such as beer, wine and bread - are made with yeast strains, which means that they contain multiple copies of the gene in the genome, and it has been difficult to do so. If you are the one copy in the genome changes a gene, a constant copy will correct has changed one eye, "permanent Sujin, I microbial genomics of associate professor, main research personnel in the energy Biosciences Institute U shape that.
Recently, scientists have developed a "genomic knife" that spans multiple copies of the target gene in the genome of a very precise - until all copies are cut off. Jinyi group has used this enzyme using ELISA test kits and RNA directed cas9 nucleic acid, polyploid precise metabolic engineering of Saccharomyces cerevisiae has is widely used in wine, beer, and industrial fermentation strains.
The possibility of improving the nutritional value of the food is amazing, he said. "Wine, for example, contains a healthy component of resveratrol, along with the engineered yeast, we can increase the amount of Resveratrol by 10 times more than the amount of resveratrol, but it also can be added to the metabolic pathway for the introduction of other foods that are biologically active compounds, e.g.. Such as ginseng, into the wine yeast or we can pull for beer into the pathway of resveratrol production, sour milk, cheese, pickles, pickles or yeast strains - use yeast fermentation production of any food.
Another advantage is that the wine maker can clone enzymes to improve the lactic acid fermentation, the two fermentation process, so that the wine is smooth. To produce toxic byproducts of lactic acid fermentation is not correct, may cause the symptoms of a hangover, he said.
Kim stressed the importance of the genome knife as a tool that allows genetic engineers to make these extremely precise mutations.
"Scientists need to create design mutations to determine the function of a particular gene," he explained. "We have a great taste for wine production, and we want to know why. We removed a gene and then went to a different flavor, and we knew we had isolated the genes responsible for this."
The new technology also makes it less offensive to genetically modified organisms, he said. "In the past, scientists had to use antibiotic markers to indicate the genetic changes in the light spot in organisms, and many people against their use in dangerous food because of developing antibiotic resistance, and as a genomic knife can cut the genome very accurately and efficiently, so we don't have to use antibiotic markers to identify a genetic event".
The study is reported in the recent issue of environmental microbiology.
Read more:http://about.cusabio.com/m-179.html
2015年8月13日星期四
Genes may help to reduce pollution
Genetically modified crops of long-term opponents, from the fear of the potential of traditional crops and other plant pollution. Now scientists at the University of Guelph have discovered that a plant gene may help to reduce the risk of farmers' GM contamination, and to quell the argument against the use of genetically modified crops, said Sharif Sharif, a new research paper, the results of the main authors.
This is considered to be the first study ever to find genes involved in altering the normal cross pollination of fruit trees - the need for one plant to another fertilization - into self - pollination, said Sheriff.
The paper was published in the Journal BMC biology.
Sheriff said the researchers may have one day to insert the gene into GM crops, to prevent its pollen from reaching other plants.
Plant a professor of agriculture at the Jay Subramanian, Nawaz Sharif, student mentor and the co-author, said: "there are a lot of global GM crops from creating a 'them to fertilization in wild populations and about the pollen. Super weed. "
Researchers have found that a genetically made protein is naturally a very small number of plants that are self - pollination and fruit. Peach, for example, have been receiving flowers, unlike those in need of pollen of another tree tree fertilization and set the fruit showy flowers of plum and cherry's cousin.
Subramanian study of fruit trees in the vineyard research and innovation center of the vineyard, Ontario province. Sheriff had worked with him on the study of plants to stress, such as drought or disease.
In the paper co authors are at the University of Guelph professor jaideep Mathur, molecular and cell biology department and Gopi Paliyath plants Agiruclture system. With the Islamic El-Sharkawy, had any researcher Arvind Subramanian with; and colleagues at the National University of Singapore.
In addition to helping farmers and food producers, their findings could be a boon for the perfume maker, Subramanian said.
In the use of perennial such as jasmine, the gene may keep off the flowers, let growers to collect more by perfume maker valuable aromatic compounds. "When the peaks of volatile compounds," Subramanian said. "When the flowers bloom, you lose almost 80% of the proportion of volatile substances."
Most plants develop open flowers that attract pollination, but it takes energy to make flowers as well as nectar and pollen. Subramanian said that the closure of flowers and plants - known as the closed flower fertilization, or Greece's "closed marriage" - may be in the development of a lack of pollination media environment or adverse conditions.
"This is the first time that we have known that it has been shown that the use of molecular tools can induce the closure of flowers and plants," he said.
Read more:http://www.cusabio.com/catalog-13-1.html
This is considered to be the first study ever to find genes involved in altering the normal cross pollination of fruit trees - the need for one plant to another fertilization - into self - pollination, said Sheriff.
The paper was published in the Journal BMC biology.
Sheriff said the researchers may have one day to insert the gene into GM crops, to prevent its pollen from reaching other plants.
Plant a professor of agriculture at the Jay Subramanian, Nawaz Sharif, student mentor and the co-author, said: "there are a lot of global GM crops from creating a 'them to fertilization in wild populations and about the pollen. Super weed. "
Researchers have found that a genetically made protein is naturally a very small number of plants that are self - pollination and fruit. Peach, for example, have been receiving flowers, unlike those in need of pollen of another tree tree fertilization and set the fruit showy flowers of plum and cherry's cousin.
Subramanian study of fruit trees in the vineyard research and innovation center of the vineyard, Ontario province. Sheriff had worked with him on the study of plants to stress, such as drought or disease.
In the paper co authors are at the University of Guelph professor jaideep Mathur, molecular and cell biology department and Gopi Paliyath plants Agiruclture system. With the Islamic El-Sharkawy, had any researcher Arvind Subramanian with; and colleagues at the National University of Singapore.
In addition to helping farmers and food producers, their findings could be a boon for the perfume maker, Subramanian said.
In the use of perennial such as jasmine, the gene may keep off the flowers, let growers to collect more by perfume maker valuable aromatic compounds. "When the peaks of volatile compounds," Subramanian said. "When the flowers bloom, you lose almost 80% of the proportion of volatile substances."
Most plants develop open flowers that attract pollination, but it takes energy to make flowers as well as nectar and pollen. Subramanian said that the closure of flowers and plants - known as the closed flower fertilization, or Greece's "closed marriage" - may be in the development of a lack of pollination media environment or adverse conditions.
"This is the first time that we have known that it has been shown that the use of molecular tools can induce the closure of flowers and plants," he said.
Read more:http://www.cusabio.com/catalog-13-1.html
2015年8月12日星期三
Anti HIV new drug development
In the study, scientists from Australia found that three of the HIV fragmentation - 1 reverse transcriptase inhibitors, can effectively inhibit the activity of HIV - 1 reverse transcriptase, for the prevention and treatment of HIV - 1 drug development provides an important information.
In the study of saturation transfer, the researchers used magnetic resonance imaging (MRI), and in the experimental method of in vitro activity, found the viral fragment 1 reverse transcriptase inhibitors (NNRTI) and reverse transcriptase inhibitors (NRTI) compared to the chemical structure and mechanism of action of the fragment is completely different.
Researchers identified three compounds can inhibit HIV RNA and DNA dependent DNA polymerase activity of reverse transcriptase, in micro friction levels of concentration, but still retains the suppression mutation in the reverse transcriptase enzyme, including three mutations in the NNRTI resistant effect: K103N, Y181C and G190A.These synthetic compounds could inhibit mouse Moloney leukemia virus, retroviral activity, but EC on our production: oli DNA polymerase I Klenow fragment no inhibitory effect.
The researchers also analyzed the dynamic balance, the results showed that one of the fragments is the special effect of HIV - 1 reverse transcriptase inhibitors, on the dNTP substrate, and the other is a compound of a competitive inhibitor, DNA template by the special effects of reverse transcription polymerase activity / primer, and so the compound also inhibits RNA activity of H.In, this dNTP competitive reverse transcriptase inhibitor NRTI M184V.In and other anti viral test activity, the study of the template / primer can inhibit HIV - 1 copies.
To sum up, the study found that 1 of the fragments with a combination of three pieces of screening with anti HIV method - the discovery of HIV prevention and treatment of powerful functions.The fragment 1 reverse transcriptase activity - provides a new opportunity for the development of new drugs has a very important significance.
Read more:http://about.cusabio.com/m-179.html
In the study of saturation transfer, the researchers used magnetic resonance imaging (MRI), and in the experimental method of in vitro activity, found the viral fragment 1 reverse transcriptase inhibitors (NNRTI) and reverse transcriptase inhibitors (NRTI) compared to the chemical structure and mechanism of action of the fragment is completely different.
Researchers identified three compounds can inhibit HIV RNA and DNA dependent DNA polymerase activity of reverse transcriptase, in micro friction levels of concentration, but still retains the suppression mutation in the reverse transcriptase enzyme, including three mutations in the NNRTI resistant effect: K103N, Y181C and G190A.These synthetic compounds could inhibit mouse Moloney leukemia virus, retroviral activity, but EC on our production: oli DNA polymerase I Klenow fragment no inhibitory effect.
The researchers also analyzed the dynamic balance, the results showed that one of the fragments is the special effect of HIV - 1 reverse transcriptase inhibitors, on the dNTP substrate, and the other is a compound of a competitive inhibitor, DNA template by the special effects of reverse transcription polymerase activity / primer, and so the compound also inhibits RNA activity of H.In, this dNTP competitive reverse transcriptase inhibitor NRTI M184V.In and other anti viral test activity, the study of the template / primer can inhibit HIV - 1 copies.
To sum up, the study found that 1 of the fragments with a combination of three pieces of screening with anti HIV method - the discovery of HIV prevention and treatment of powerful functions.The fragment 1 reverse transcriptase activity - provides a new opportunity for the development of new drugs has a very important significance.
Read more:http://about.cusabio.com/m-179.html
2015年8月11日星期二
Statins improve the risk of memory decline
But the researchers said the Medical Association, because patients are often associated with medical conditions and drug efficacy, it is convenient for doctors to find their memory loss symptoms, in the use of statins to describe a number of cases and acute memory loss directly related, but the study shows that long-term use of statins to improve individual memory or memory of individuals are not.
The researchers compared the use of statins in two patients and the other 482543 control groups: non lipid lowering drugs (LLDs) 482543 individuals and 26484 non statin drugs, such as the test to the study of the amino acid, chlorine, hydrochloric acid test as the ester, etc.; at the same time, the researchers also conducted a cross study of two cases, the use of diagnostic criteria, personal memory loss related data.
The researchers compared statin users and any personal cholesterol lowering drugs. After 30 days of treatment with statins, the risk of memory decline began, and that any individual cholesterol lowering drugs were not personal, and the researchers found that the drug was associated with an increased risk of memory loss after 30 days.
Finally, the researchers said, the experiment, or all of the drugs will cause acute individual memory loss, which is likely to lead to memory loss, and may be related to the possibility of testing bias, bias and the possibility of testing may be very high, late, of course, the study will be tested in patients with preventive treatment, such as patients taking cholesterol lowering drugs.
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2015年8月10日星期一
Reports: Scientific novel nano drug, specific killer tumor cells!
Recently, a study in the Journal Reports Dalhousie, researchers at Scientific medical school, developed a new way of delivering chemotherapy drugs. Using nano technology, the new drug delivery system is only in tumor cells to release the drug, thereby protecting healthy cells from damage. The research was published in the Journal Reports Scientific.
Dr. Puvvada Naga, a blogger at New Brunswick Dalhousie (DMNB), invented the drug delivery system. He collaborated with Brunt DMNB, Keith, and researchers in the United States and India to develop the new system.
The team has designed a nano particle that can increase the amount of chemotherapy drugs delivered to the tumor cells, and only release chemotherapy drugs within the tumor cells. This reduces the impact of health organizations to a minimum.
Tumor cells produce a high level of acid, which can activate the nanoparticles, thus allowing them to enter the tumor cells, the release of drugs. When nano particles release the drug, its color will change, that is, the light conversion. This light conversion can help researchers understand how many chemotherapy drugs have been released, and identify the presence of a tumor.
"We design originality is fluorescent light conversion potential clinical possibility of transformation, because it helps to detect chemotherapy drug release. "Dr. Puvvada said. "We will still have a lot of work to do before this technology is used in the clinic because the current fluorescence can't be detected by CTs or MRIs. This is our next step. "
Although the study is carried out on human breast cancer cells, the technology has the potential to be used in any solid tumor.
"Although this new drug delivery system is still in its early stages, it is promising to become a method of individual treatment for patients. "Dr. Brunt, assistant professor of pharmacology. "This target to good, and can detect drug release amount of treatment, there is the potential to improve the quality of life of patients with solid tumors, the overall effect of their just around the corner. "
Read more:http://www.cusabio.com/catalog-13-1.html
Dr. Puvvada Naga, a blogger at New Brunswick Dalhousie (DMNB), invented the drug delivery system. He collaborated with Brunt DMNB, Keith, and researchers in the United States and India to develop the new system.
The team has designed a nano particle that can increase the amount of chemotherapy drugs delivered to the tumor cells, and only release chemotherapy drugs within the tumor cells. This reduces the impact of health organizations to a minimum.
Tumor cells produce a high level of acid, which can activate the nanoparticles, thus allowing them to enter the tumor cells, the release of drugs. When nano particles release the drug, its color will change, that is, the light conversion. This light conversion can help researchers understand how many chemotherapy drugs have been released, and identify the presence of a tumor.
"We design originality is fluorescent light conversion potential clinical possibility of transformation, because it helps to detect chemotherapy drug release. "Dr. Puvvada said. "We will still have a lot of work to do before this technology is used in the clinic because the current fluorescence can't be detected by CTs or MRIs. This is our next step. "
Although the study is carried out on human breast cancer cells, the technology has the potential to be used in any solid tumor.
"Although this new drug delivery system is still in its early stages, it is promising to become a method of individual treatment for patients. "Dr. Brunt, assistant professor of pharmacology. "This target to good, and can detect drug release amount of treatment, there is the potential to improve the quality of life of patients with solid tumors, the overall effect of their just around the corner. "
Read more:http://www.cusabio.com/catalog-13-1.html
2015年8月5日星期三
Powerful molecular promoter of colon cancers
Cancer researchers already know of some oncogenes and other factors that
promote the development of colon cancers, but they don't yet have the full
picture of how these cancers originate and spread. Now researchers from the
Perelman School of Medicine at the University of Pennsylvania have illuminated
another powerful factor in this process.
"This work reveals and unravels an additional pathway for the origin of colon cancer," said senior author Anil K. Rustgi, MD, the T. Grier Miller Professor of Medicine and chief of the Gastroenterology division.
Explorations of this pathway could lead to new ways of categorizing and treating colon cancers, which, together with less common rectal cancers, kill about 5,000 Americans every year.
The research, published this week in PLoS Genetics, follows a 2013 study in Genes and Development from Rustgi's group, which found that a protein called LIN28B promotes cancerous growth in intestinal cells by suppressing the Let-7 family of molecules.
LIN28B has attracted keen interest among biologists in recent years. The protein's suppression of Let-7 molecules normally helps keep embryonic stem cells in their stem-like state, not only in humans and other mammals but in evolutionarily distant species too. When Let-7 molecules are allowed to work, cells tend to move out of the stem-like state and mature into specific cell types, with much less capacity for uninhibited growth.
This ancient interaction between LIN28B and Let-7 is clearly important for the normal development of animals to maturity and for other growth-related processes such as tissue regeneration after injury. But as Rustgi and other scientists have been finding, LIN28B's suppression of Let-7 is also abnormally switched on in many cancers.
In the new study, Rustgi's team, including first author Blair B. Madison, PhD, who at the time was a postdoctoral fellow in the Rustgi laboratory and is now an assistant professor of Medicine at Washington University, looked downstream of the LIN28B/Let-7 interaction, to determine how Let-7 molecules normally keep intestinal cells from turning cancerous.
Let-7 molecules are not proteins. They are short stretches of RNA (microRNAs, or miRNAs) that work within cells to regulate the expression of various genes. To understand better what Let-7 miRNAs normally do to prevent cancer, Rustgi's team created transgenic mice that produce no Let-7 miRNAs in the intestinal lining.
The researchers observed that adenomas adenomatous polyps, as well as adenocarcinomas resembling typical human colon tumors, sprouted in the intestines of all these no-Let-7 mice by mid-adulthood, increasing their mortality compared to normal mice. Analyses of the tumors, and of derived "tumoroid" three-dimensional cell clusters cultured in the lab dish, pointed to a protein called Hmga2 as a major factor in the tumors' development.
Hmga2 is normally produced during the fast-growth period of fetal life and is thereafter suppressed by Let-7 miRNAs. Rustgi's team observed that in the intestinal lining of the no-Let-7 mice, as well as in tumors and derived tumoroids, Hmga2's gene was expressed at unusually high levels. Using antibodies to mark Hmga2 proteins, they found it to be particularly abundant in tumors that had begun to spread beyond the intestinal lining.
The researchers also found that experimentally lowering Hmga2's production, introduced by another line of transgenic mice, significantly suppressed tumors induced by Lin28b, and suppression of Let-7. What's more, experimentally lowering Hmga2 production in cultures of intestinal tissue from such mice significantly reduced the cells' tendency to proliferate, whereas increasing Hmga2 levels boosted that proliferation.
Analyses of gene expression in the tumors showed a strong relationship between the elevated expression of Hmga2 and the elevated expression of genes considered classic markers of stem cells. That observation adds to findings in recent years that many cancers, including colon cancers, may be driven in part by cancer cells that are in a stem-like state--which may enable them not only to proliferate more easily, but also to better withstand therapies.
Clearly, other factors were also at work in spurring the development of tumors in the Let-7-suppressed mice. Indeed, the researchers found evidence in the tumors of the overactivation of the Wnt signaling pathway, a known promoter of colon cancer--which in these cases may have become spontaneously switched on in some cells. "We suspect that that's the main dysregulation that occurs after Let-7 suppression to boost tumor progression," said Rustgi.
To check the relevance of these mouse results to humans, Rustgi's group examined several hundred human colorectal cancer samples, and found, among other things, lower-than-normal expression of Let-7 miRNAs, and higher-than-normal expression of HMGA2 (the human version of the mouse Hmga2 protein) as well as stem cell markers. In these human cancer samples, HMGA2 expression was also associated with a more advanced stage of tumor growth and reduced survival.
The findings point to a surge in HMGA2 as one of the key factors that promotes colon cancer in the many cases where Let-7 levels are suppressed. HMGA2 is already being considered as a target for new treatments for other cancer types, and this study suggests that targeting HMGA2--perhaps in concert with Wnt signaling factors--may make a difference in colon cancer too.
"We think that there's an axis of cancer promotion here, from LIN28B to Let-7 to the targets of Let-7, including HMGA2, and if one could disrupt the latter with therapeutics, that might help alleviate colon cancer progression and maybe metastasis as well," said Rustgi.
HMGA2 levels may also have a prognostic value, since in this study high HMGA2 levels correlated with more advanced and invasive tumors and a poorer outcome. "We might consider a different therapeutic approach for such patients," Rustgi noted.
Read more:http://www.cusabio.com/catalog-13-1.html
"This work reveals and unravels an additional pathway for the origin of colon cancer," said senior author Anil K. Rustgi, MD, the T. Grier Miller Professor of Medicine and chief of the Gastroenterology division.
Explorations of this pathway could lead to new ways of categorizing and treating colon cancers, which, together with less common rectal cancers, kill about 5,000 Americans every year.
The research, published this week in PLoS Genetics, follows a 2013 study in Genes and Development from Rustgi's group, which found that a protein called LIN28B promotes cancerous growth in intestinal cells by suppressing the Let-7 family of molecules.
LIN28B has attracted keen interest among biologists in recent years. The protein's suppression of Let-7 molecules normally helps keep embryonic stem cells in their stem-like state, not only in humans and other mammals but in evolutionarily distant species too. When Let-7 molecules are allowed to work, cells tend to move out of the stem-like state and mature into specific cell types, with much less capacity for uninhibited growth.
This ancient interaction between LIN28B and Let-7 is clearly important for the normal development of animals to maturity and for other growth-related processes such as tissue regeneration after injury. But as Rustgi and other scientists have been finding, LIN28B's suppression of Let-7 is also abnormally switched on in many cancers.
In the new study, Rustgi's team, including first author Blair B. Madison, PhD, who at the time was a postdoctoral fellow in the Rustgi laboratory and is now an assistant professor of Medicine at Washington University, looked downstream of the LIN28B/Let-7 interaction, to determine how Let-7 molecules normally keep intestinal cells from turning cancerous.
Let-7 molecules are not proteins. They are short stretches of RNA (microRNAs, or miRNAs) that work within cells to regulate the expression of various genes. To understand better what Let-7 miRNAs normally do to prevent cancer, Rustgi's team created transgenic mice that produce no Let-7 miRNAs in the intestinal lining.
The researchers observed that adenomas adenomatous polyps, as well as adenocarcinomas resembling typical human colon tumors, sprouted in the intestines of all these no-Let-7 mice by mid-adulthood, increasing their mortality compared to normal mice. Analyses of the tumors, and of derived "tumoroid" three-dimensional cell clusters cultured in the lab dish, pointed to a protein called Hmga2 as a major factor in the tumors' development.
Hmga2 is normally produced during the fast-growth period of fetal life and is thereafter suppressed by Let-7 miRNAs. Rustgi's team observed that in the intestinal lining of the no-Let-7 mice, as well as in tumors and derived tumoroids, Hmga2's gene was expressed at unusually high levels. Using antibodies to mark Hmga2 proteins, they found it to be particularly abundant in tumors that had begun to spread beyond the intestinal lining.
The researchers also found that experimentally lowering Hmga2's production, introduced by another line of transgenic mice, significantly suppressed tumors induced by Lin28b, and suppression of Let-7. What's more, experimentally lowering Hmga2 production in cultures of intestinal tissue from such mice significantly reduced the cells' tendency to proliferate, whereas increasing Hmga2 levels boosted that proliferation.
Analyses of gene expression in the tumors showed a strong relationship between the elevated expression of Hmga2 and the elevated expression of genes considered classic markers of stem cells. That observation adds to findings in recent years that many cancers, including colon cancers, may be driven in part by cancer cells that are in a stem-like state--which may enable them not only to proliferate more easily, but also to better withstand therapies.
Clearly, other factors were also at work in spurring the development of tumors in the Let-7-suppressed mice. Indeed, the researchers found evidence in the tumors of the overactivation of the Wnt signaling pathway, a known promoter of colon cancer--which in these cases may have become spontaneously switched on in some cells. "We suspect that that's the main dysregulation that occurs after Let-7 suppression to boost tumor progression," said Rustgi.
To check the relevance of these mouse results to humans, Rustgi's group examined several hundred human colorectal cancer samples, and found, among other things, lower-than-normal expression of Let-7 miRNAs, and higher-than-normal expression of HMGA2 (the human version of the mouse Hmga2 protein) as well as stem cell markers. In these human cancer samples, HMGA2 expression was also associated with a more advanced stage of tumor growth and reduced survival.
The findings point to a surge in HMGA2 as one of the key factors that promotes colon cancer in the many cases where Let-7 levels are suppressed. HMGA2 is already being considered as a target for new treatments for other cancer types, and this study suggests that targeting HMGA2--perhaps in concert with Wnt signaling factors--may make a difference in colon cancer too.
"We think that there's an axis of cancer promotion here, from LIN28B to Let-7 to the targets of Let-7, including HMGA2, and if one could disrupt the latter with therapeutics, that might help alleviate colon cancer progression and maybe metastasis as well," said Rustgi.
HMGA2 levels may also have a prognostic value, since in this study high HMGA2 levels correlated with more advanced and invasive tumors and a poorer outcome. "We might consider a different therapeutic approach for such patients," Rustgi noted.
Read more:http://www.cusabio.com/catalog-13-1.html
2015年8月4日星期二
Team advances therapy preventing addiction relapse by erasing drug-associated memories
Recovering addicts often grapple with the ghosts of their
addiction--memories that tempt them to relapse even after rehabilitation and
months, or even years, of drug-free living. Now, scientists from the Florida
campus of The Scripps Research Institute (TSRI) have made a discovery that
brings them closer to a new therapy based on selectively erasing these dangerous
and tenacious drug-associated memories.
"We now have a viable target and by blocking that target, we can disrupt, and potentially erase, drug memories, leaving other memories intact," said TSRI Associate Professor Courtney Miller. "The hope is that, when combined with traditional rehabilitation and abstinence therapies, we can reduce or eliminate relapse for meth users after a single treatment by taking away the power of an individual's triggers."
The new study, published this week online ahead of print by the journal Molecular Psychiatry, demonstrates the effectiveness of a single injection of an early drug candidate called blebbistatin in preventing relapse in animal models of methamphetamine addiction.
The new study builds on previous work in Miller's lab. In 2013, the team made the surprising discovery that drug-associated memories could be selectively erased by targeting actin, the protein that provides the structural scaffold supporting memories in the brain. However, the therapeutic potential of the finding seemed limited by the problem that actin is critically important throughout the body--taking a pill that generally inhibits actin, even once, would likely be fatal.
In the new study, Miller and her colleagues report a major advance--the discovery of a safe route to selectively targeting brain actin through nonmuscle myosin II (NMII), a molecular motor that supports memory formation. To accomplish this, the researchers used a compound called blebbistatin that acts on this protein.
The results showed that a single injection of blebbistatin successfully disrupted long-term storage of drug-related memories--and blocked relapse for at least a month in animal models of methamphetamine addiction.
"What makes myosin II such an exciting therapeutic target is that a single injection of blebbistatin makes methamphetamine-associated memories go away, along with dendritic spines, the structures in the brain that store memory," said Research Associate Erica Young, a member of the Miller lab and a key author of the new study, along with Research Associates Ashley M. Blouin and Sherri B. Briggs.
Blouin added, "Drugs targeting actin usually have to be delivered directly into the brain. But blebbistatin reaches the brain even when injected into the body's periphery and, importantly, the animals remained healthy."
Moreover, the effect of this novel treatment approach was specific to drug-associated memories (not affecting other memories), and the animals were still able to form new recollections.
"Our results argue for developing small molecule inhibitors of nonmuscle myosin II as potential therapeutics for relapse prevention, and that's exactly what we're doing with our colleagues here at Scripps with expertise in drug development," said Briggs.
Read more:http://www.cusabio.com/catalog-16-1.html
"We now have a viable target and by blocking that target, we can disrupt, and potentially erase, drug memories, leaving other memories intact," said TSRI Associate Professor Courtney Miller. "The hope is that, when combined with traditional rehabilitation and abstinence therapies, we can reduce or eliminate relapse for meth users after a single treatment by taking away the power of an individual's triggers."
The new study, published this week online ahead of print by the journal Molecular Psychiatry, demonstrates the effectiveness of a single injection of an early drug candidate called blebbistatin in preventing relapse in animal models of methamphetamine addiction.
The new study builds on previous work in Miller's lab. In 2013, the team made the surprising discovery that drug-associated memories could be selectively erased by targeting actin, the protein that provides the structural scaffold supporting memories in the brain. However, the therapeutic potential of the finding seemed limited by the problem that actin is critically important throughout the body--taking a pill that generally inhibits actin, even once, would likely be fatal.
In the new study, Miller and her colleagues report a major advance--the discovery of a safe route to selectively targeting brain actin through nonmuscle myosin II (NMII), a molecular motor that supports memory formation. To accomplish this, the researchers used a compound called blebbistatin that acts on this protein.
The results showed that a single injection of blebbistatin successfully disrupted long-term storage of drug-related memories--and blocked relapse for at least a month in animal models of methamphetamine addiction.
"What makes myosin II such an exciting therapeutic target is that a single injection of blebbistatin makes methamphetamine-associated memories go away, along with dendritic spines, the structures in the brain that store memory," said Research Associate Erica Young, a member of the Miller lab and a key author of the new study, along with Research Associates Ashley M. Blouin and Sherri B. Briggs.
Blouin added, "Drugs targeting actin usually have to be delivered directly into the brain. But blebbistatin reaches the brain even when injected into the body's periphery and, importantly, the animals remained healthy."
Moreover, the effect of this novel treatment approach was specific to drug-associated memories (not affecting other memories), and the animals were still able to form new recollections.
"Our results argue for developing small molecule inhibitors of nonmuscle myosin II as potential therapeutics for relapse prevention, and that's exactly what we're doing with our colleagues here at Scripps with expertise in drug development," said Briggs.
Read more:http://www.cusabio.com/catalog-16-1.html
Combination therapy may be more effective against the most common ovarian cancer
High-grade serous ovarian cancer often responds well to the chemotherapy
drug carboplatin, but why it so frequently comes back after treatment has been a
medical mystery.
Now a team of UCLA researchers has discovered that a subset of tumor cells that don't produce the protein CA125, a biomarker used to test for ovarian cancer, has an enhanced ability to repair their DNA and resist programmed cell death -- which allows the cells to evade the drug and live long enough to regrow the original tumor.
It's that regenerative ability and their resistance to carboplatin therapy that make the cells so dangerous, said Deanna Janzen, the study's first author, and a senior scientist in the G.O. Discovery Lab at UCLA.
The study, which appears August 3 in the peer-reviewed journalNature Communications, showed that pairing the chemotherapy with an experimental drug eliminates the deadly population of cells believed to be responsible for repopulating the tumor.
The drug, birinapant, sensitizes the CA125-negative cells to the chemotherapy by restoring apoptosis, or programmed cell death, said Dr. Sanaz Memarzadeh, a senior author of the study and a UCLA gynecologic cancer surgeon.
Combining chemotherapy and birinapant significantly improved disease-free survival in laboratory models of human ovarian cancer compared to using either therapy alone. This suggests that targeting the CA125-negative cells may improve outcomes in these high-grade serous cancers, the most common subtype of ovarian cancer, said Memarzadeh, who also is a UCLA associate professor of obstetrics and gynecology and director of the G.O. Discovery Lab. This is vital, since the cancer recurs in 80 to 85 percent of patients despite standard treatments.
Scientists had previously hypothesized that there was a population of cells that could not be reached using the conventional treatment of surgery followed by chemotherapy, but they had been mostly unable to identify them.
Alarming findings
"We found that these cells were like little time bombs, hiding from the chemotherapy and then later initiating tumor growth," Memarzadeh said. "We think that by isolating the CA125-negative tumor cells we have uncovered this reservoir of carboplatin-resistant high-grade serous ovarian cancer cells."
In the five-year study, the research team first analyzed ovarian tumors gathered from patients at UCLA. Most of the cells that made up the tumors were positive for CA125, but the researchers found a small population that were negative and focused on those, Janzen said. The team wondered if the CA125-negative cells grew the same as those that were CA125-positive. The results were alarming.
"The CA125-negative cells grew 700 times better than CA125-positive cells," Janzen said. "It was very striking that the two cell populations had such different growth potentials. But what was more remarkable was that the CA125-negative cells were clearly resistant to the drugs normally used to treat serous cancers."
Memarzadeh, who also is a member of UCLA's Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, agreed.
"For me, as a physician, this was frightening," she said. "The chemotherapy drug killed the CA125-positive cells and left behind the cells armed with the capacity to regrow the tumor."
The test most widely used to detect recurrences of serous cancer works by measuring CA125 levels. As a result, Memarzadeh said, the test completely overlooks the cells that slowly regrow the tumor, which are CA125-negative.
Once the researchers isolated the CA125-negative cells, they worked with UCLA collaborators to analyze the genes expressed in these cells. They discovered the ability of these cells to quickly repair the DNA damage done by the chemotherapy, and they found the cells' "anti-death" protein. The DNA damage that killed the CA125-positive cells did not work on the CA125-negative cells because of the two protective mechanisms.
"These cells reacted like hair does to chemotherapy," Janzen said. "The treatment damages most of patients' hair cells, causing the hair to fall out. But the cells responsible for hair growth live on, so hair regrows after therapy stops. Similarly, most of the tumor cells die in response to platinum therapy, but the CA125-negative cells survive and serve as a source of tumor re-growth once therapy ceases. The good news is that we found a small molecule drug being tested in cancers that activates apoptosis and we decided to test it in combination therapy."
Planning further study
Going forward, Memarzadeh and her team plan to conduct a clinical trial of the combination therapy in women whose tumors have high levels of the anti-death protein. She estimates that about 50 percent of women with ovarian cancer have tumors with this type of tumor and would qualify for the trial, which needs about $2 million in philanthropic funding before it could begin.
The researchers also are seeking other potential drug targets in the 50 percent of patients who don't have high levels of the anti-death protein, as well as biomarkers in addition to CA125 that could be used to screen for ovarian cancer.
"We do a phenomenal job with surgery, peeling off as much of the tumor as we can see, and then we do standard chemotherapy, but the cancers still recur," Memarzadeh said. "I think our study helps explain why this happens. If this combination of drugs proves effective, we may be able to improve outcomes for this deadly disease. I think it's entirely feasible."
Ovarian cancer accounts for 5 percent of cancer deaths among women, and causes more deaths than any other gynecologic cancer. About 21,000 American women will be diagnosed with ovarian cancer this year, and more than 14,000 will die of the disease.
"This study provides evidence that CA125-negative high-grade serous ovarian cancer cells have stem properties and are inherently platinum resistant. The de novo platinum resistance of this tumor subpopulation can explain why these cancers consistently reappear after first-line platinum-based chemotherapy," the study states. "On the basis of the promising preclinical results here, improving outcomes for this deadly malignancy could be achieved simply by supplementing existing therapies that work well against the majority of tumor cells with agents that sensitize the CA125-negative cells to carboplatin."
Read more:http://www.cusabio.com/catalog-13-1.html
Now a team of UCLA researchers has discovered that a subset of tumor cells that don't produce the protein CA125, a biomarker used to test for ovarian cancer, has an enhanced ability to repair their DNA and resist programmed cell death -- which allows the cells to evade the drug and live long enough to regrow the original tumor.
It's that regenerative ability and their resistance to carboplatin therapy that make the cells so dangerous, said Deanna Janzen, the study's first author, and a senior scientist in the G.O. Discovery Lab at UCLA.
The study, which appears August 3 in the peer-reviewed journalNature Communications, showed that pairing the chemotherapy with an experimental drug eliminates the deadly population of cells believed to be responsible for repopulating the tumor.
The drug, birinapant, sensitizes the CA125-negative cells to the chemotherapy by restoring apoptosis, or programmed cell death, said Dr. Sanaz Memarzadeh, a senior author of the study and a UCLA gynecologic cancer surgeon.
Combining chemotherapy and birinapant significantly improved disease-free survival in laboratory models of human ovarian cancer compared to using either therapy alone. This suggests that targeting the CA125-negative cells may improve outcomes in these high-grade serous cancers, the most common subtype of ovarian cancer, said Memarzadeh, who also is a UCLA associate professor of obstetrics and gynecology and director of the G.O. Discovery Lab. This is vital, since the cancer recurs in 80 to 85 percent of patients despite standard treatments.
Scientists had previously hypothesized that there was a population of cells that could not be reached using the conventional treatment of surgery followed by chemotherapy, but they had been mostly unable to identify them.
Alarming findings
"We found that these cells were like little time bombs, hiding from the chemotherapy and then later initiating tumor growth," Memarzadeh said. "We think that by isolating the CA125-negative tumor cells we have uncovered this reservoir of carboplatin-resistant high-grade serous ovarian cancer cells."
In the five-year study, the research team first analyzed ovarian tumors gathered from patients at UCLA. Most of the cells that made up the tumors were positive for CA125, but the researchers found a small population that were negative and focused on those, Janzen said. The team wondered if the CA125-negative cells grew the same as those that were CA125-positive. The results were alarming.
"The CA125-negative cells grew 700 times better than CA125-positive cells," Janzen said. "It was very striking that the two cell populations had such different growth potentials. But what was more remarkable was that the CA125-negative cells were clearly resistant to the drugs normally used to treat serous cancers."
Memarzadeh, who also is a member of UCLA's Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, agreed.
"For me, as a physician, this was frightening," she said. "The chemotherapy drug killed the CA125-positive cells and left behind the cells armed with the capacity to regrow the tumor."
The test most widely used to detect recurrences of serous cancer works by measuring CA125 levels. As a result, Memarzadeh said, the test completely overlooks the cells that slowly regrow the tumor, which are CA125-negative.
Once the researchers isolated the CA125-negative cells, they worked with UCLA collaborators to analyze the genes expressed in these cells. They discovered the ability of these cells to quickly repair the DNA damage done by the chemotherapy, and they found the cells' "anti-death" protein. The DNA damage that killed the CA125-positive cells did not work on the CA125-negative cells because of the two protective mechanisms.
"These cells reacted like hair does to chemotherapy," Janzen said. "The treatment damages most of patients' hair cells, causing the hair to fall out. But the cells responsible for hair growth live on, so hair regrows after therapy stops. Similarly, most of the tumor cells die in response to platinum therapy, but the CA125-negative cells survive and serve as a source of tumor re-growth once therapy ceases. The good news is that we found a small molecule drug being tested in cancers that activates apoptosis and we decided to test it in combination therapy."
Planning further study
Going forward, Memarzadeh and her team plan to conduct a clinical trial of the combination therapy in women whose tumors have high levels of the anti-death protein. She estimates that about 50 percent of women with ovarian cancer have tumors with this type of tumor and would qualify for the trial, which needs about $2 million in philanthropic funding before it could begin.
The researchers also are seeking other potential drug targets in the 50 percent of patients who don't have high levels of the anti-death protein, as well as biomarkers in addition to CA125 that could be used to screen for ovarian cancer.
"We do a phenomenal job with surgery, peeling off as much of the tumor as we can see, and then we do standard chemotherapy, but the cancers still recur," Memarzadeh said. "I think our study helps explain why this happens. If this combination of drugs proves effective, we may be able to improve outcomes for this deadly disease. I think it's entirely feasible."
Ovarian cancer accounts for 5 percent of cancer deaths among women, and causes more deaths than any other gynecologic cancer. About 21,000 American women will be diagnosed with ovarian cancer this year, and more than 14,000 will die of the disease.
"This study provides evidence that CA125-negative high-grade serous ovarian cancer cells have stem properties and are inherently platinum resistant. The de novo platinum resistance of this tumor subpopulation can explain why these cancers consistently reappear after first-line platinum-based chemotherapy," the study states. "On the basis of the promising preclinical results here, improving outcomes for this deadly malignancy could be achieved simply by supplementing existing therapies that work well against the majority of tumor cells with agents that sensitize the CA125-negative cells to carboplatin."
Read more:http://www.cusabio.com/catalog-13-1.html
2015年8月3日星期一
Discovery about brain protein causes rethink on development of Alzheimer's disease
Researchers at the University of Melbourne have discovered that a protein
involved in the progression of Alzheimer's disease also has properties that
could be helpful for human health.
The discovery helps researchers better understand the complicated brain chemistry behind the development of Alzheimer's disease, a condition that affects hundreds of thousands of Australians.
An international team of researchers, led by Dr Simon Drew at the University of Melbourne and Prof Wojciech Bal at the Polish Academy of Sciences, has revealed that a shorter form of a protein called beta amyloid, may act as a sponge that safely binds a metal that can damage brain tissue when it's in excess.
Researchers have been intensely interested in the role of beta-amyloid in the development of Alzheimer's disease. This is because clumps of the protein are formed in brains of people with the illness.
In the late 1990s, high levels of copper were discovered within these clumps. Copper is essential to health, but too much can produce harmful free radicals. Many scientists began to suspect that this copper might be contributing to the disease. They found that beta-amyloid can bind to copper indiscriminately and allow it to produce these damaging free radicals.
Closer analysis of beta amyloid protein has revealed different sizes. A good proportion of beta amyloid is missing the first three links at the start of the protein's chain-like structure.
"This short form has been overlooked by most researchers since the composition of beta amyloid was first identified 30 years ago," Dr Simon Drew explains.
"We know that the shorter form of beta amyloid is present in the diseased brain, but we now know that it is abundant in healthy brains as well.
"The small change in length makes a huge difference to its copper binding properties. We found that the short form of the protein is capable of binding copper at least 1000 times stronger than the longer forms. It also wraps around the metal in a way that prevents it from producing free radicals.
"Given these properties and its relative abundance, we can speculate this type of beta amyloid is protective. It's very different from the current view of how beta amyloid interacts with biological copper."
So far, therapies aimed at lowering the production of beta amyloid have shown only a modest ability to slow cognitive decline and the number of people affected by the Alzheimer's disease continues to grow.
Dr Drew and the team from Poland are now working to develop a method for identifying the copper-bound form of the short beta amyloid in the body.
This will enable them to screen how much copper it holds in the brain, whether it safely escorts the copper from one place to another, and how this may change in aging and disease.
"If a beneficial role in copper balance can be established, it's still possible to have too much of a good thing," Dr Drew said.
"As the amount of beta amyloid in the brain increases during Alzheimer's disease, the shorter form can also clump together and this may interfere with its normal function. Higher levels of the short form may further enable it to soak up copper from other places where it is needed. It could be a Jekyll and Hyde scenario."
Read more:http://www.cusabio.com/catalog-13-1.html
The discovery helps researchers better understand the complicated brain chemistry behind the development of Alzheimer's disease, a condition that affects hundreds of thousands of Australians.
An international team of researchers, led by Dr Simon Drew at the University of Melbourne and Prof Wojciech Bal at the Polish Academy of Sciences, has revealed that a shorter form of a protein called beta amyloid, may act as a sponge that safely binds a metal that can damage brain tissue when it's in excess.
Researchers have been intensely interested in the role of beta-amyloid in the development of Alzheimer's disease. This is because clumps of the protein are formed in brains of people with the illness.
In the late 1990s, high levels of copper were discovered within these clumps. Copper is essential to health, but too much can produce harmful free radicals. Many scientists began to suspect that this copper might be contributing to the disease. They found that beta-amyloid can bind to copper indiscriminately and allow it to produce these damaging free radicals.
Closer analysis of beta amyloid protein has revealed different sizes. A good proportion of beta amyloid is missing the first three links at the start of the protein's chain-like structure.
"This short form has been overlooked by most researchers since the composition of beta amyloid was first identified 30 years ago," Dr Simon Drew explains.
"We know that the shorter form of beta amyloid is present in the diseased brain, but we now know that it is abundant in healthy brains as well.
"The small change in length makes a huge difference to its copper binding properties. We found that the short form of the protein is capable of binding copper at least 1000 times stronger than the longer forms. It also wraps around the metal in a way that prevents it from producing free radicals.
"Given these properties and its relative abundance, we can speculate this type of beta amyloid is protective. It's very different from the current view of how beta amyloid interacts with biological copper."
So far, therapies aimed at lowering the production of beta amyloid have shown only a modest ability to slow cognitive decline and the number of people affected by the Alzheimer's disease continues to grow.
Dr Drew and the team from Poland are now working to develop a method for identifying the copper-bound form of the short beta amyloid in the body.
This will enable them to screen how much copper it holds in the brain, whether it safely escorts the copper from one place to another, and how this may change in aging and disease.
"If a beneficial role in copper balance can be established, it's still possible to have too much of a good thing," Dr Drew said.
"As the amount of beta amyloid in the brain increases during Alzheimer's disease, the shorter form can also clump together and this may interfere with its normal function. Higher levels of the short form may further enable it to soak up copper from other places where it is needed. It could be a Jekyll and Hyde scenario."
Read more:http://www.cusabio.com/catalog-13-1.html
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