Sirtuin proteins have been shown to promote longevity in many organisms, and increased expression of one sirtuin protein, SIRT3, has been linked to increased human lifespan. New data, generated in mice, by Mahesh Gupta and colleagues, at the University of Chicago, Chicago, has revealed that Sirt3 helps protect the mouse heart.
In the study, the heart of mice lacking Sirt3 was found to show signs of becoming enlarged (a process known as cardiac hypertrophy), at about 8 weeks of age. Further, these mice responded dramatically to conditions that induce cardiac hypertrophy, whereas mice overexpressing Sirt3 were protected from cardiac hypertrophy under the same conditions. Additional analysis revealed the mechanism by which Sirt3 blocks the cardiac hypertrophic response, thereby providing protection to the mouse heart. Specifically, it acts in heart muscle cells via the protein Foxo3a to increase expression of anti-oxidant proteins, thereby reducing levels of damaging oxidants.
TITLE: Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
AUTHOR:
Mahesh P. Gupta
University of Chicago, Chicago, Illinois, USA.
PDF of this article
Source:
Karen Honey
Journal of Clinical Investigation
понедельник, 20 июня 2011 г.
воскресенье, 19 июня 2011 г.
Pathogenic Attacks On Host Plants Have Medicinal Research Implications
Two Kansas State University researchers focusing on rice genetics are providing a better understanding of how pathogens take over a plant's nutrients.
Their research provides insight into ways of reducing crop losses or developing new avenues for medicinal research.
Frank White, professor of plant pathology, and Ginny Antony, postdoctoral fellow in plant pathology, are co-authors, in partnership with researchers at three other institutions, of an article in a recent issue of the journal Nature. The article, "Sugar transporters for intercellular exchange and nutrition of pathogens," was led by Li-Qing Chen from the department of plant biology in the Carnegie Institution for Science at Stanford University.
The project involves the identification a family of sugar transporters, called SWEETS, which transport glucose between plant cells. These transporters are also important because they are targeted by pathogens trying to obtain plant sugar for nutrition.
"It's remarkable," White said. "These bacteria are able to regulate the plant genes directly by inserting proteins into the plant cells. The proteins take over the transcription of the SWEET gene, and the plant, as a consequence, becomes susceptible to bacterial disease."
White and Antony focused specifically on rice bacterial disease and tried to understand what makes rice susceptible and what makes it resistant to specific pathogens. The K-State researchers discovered three resistance genes in rice that can be mutated in order to build the resistance of the rice against a pathogen. One of these resistance genes -- Xa13 -- is included in the Nature article and was discovered by White's lab in 2006.
"We've identified the genes that bacteria can induce to cause the plant to be susceptible," White said. "We've identified them as critical for disease from a pathogen standpoint. For the plant, these genes are involved in normal development. However, once the pathogen takes control of expression, it makes the plant susceptible."
White and Antony also have an article appearing in the December issue of the journal The Plant Cell. They collaborated with researchers from Iowa State University to investigate a second susceptibility gene and its role in the spread of disease.
White's laboratory has been working on such rice research for 15 years, but started collaborating with the Stanford researchers earlier this year.
"We have been trying to understand what the pathogen wants from the host, how the pathogen gets it, and how the host tries to defend itself," Antony said.
Although the research is important in the field of plant genetics, it has broader applications as well. Because researchers have a better understanding of how to control pathogen food supplies, they can use this research to reduce crop diseases and subsequent losses. The plant research may also apply the findings to humans or animals because both use similar sugar transporter genes to transfer glucose, leading to new possibilities for medicine and diabetes research.
Notes:
White and Antony are in the midst of a three-year, $3-million National Science Foundation grant, and have also been funded in their research by the U.S. Department of Agriculture's National Research Initiative program through the Cooperative State Research, Education and Extension Service.
Source:
Frank White
Kansas State University
Their research provides insight into ways of reducing crop losses or developing new avenues for medicinal research.
Frank White, professor of plant pathology, and Ginny Antony, postdoctoral fellow in plant pathology, are co-authors, in partnership with researchers at three other institutions, of an article in a recent issue of the journal Nature. The article, "Sugar transporters for intercellular exchange and nutrition of pathogens," was led by Li-Qing Chen from the department of plant biology in the Carnegie Institution for Science at Stanford University.
The project involves the identification a family of sugar transporters, called SWEETS, which transport glucose between plant cells. These transporters are also important because they are targeted by pathogens trying to obtain plant sugar for nutrition.
"It's remarkable," White said. "These bacteria are able to regulate the plant genes directly by inserting proteins into the plant cells. The proteins take over the transcription of the SWEET gene, and the plant, as a consequence, becomes susceptible to bacterial disease."
White and Antony focused specifically on rice bacterial disease and tried to understand what makes rice susceptible and what makes it resistant to specific pathogens. The K-State researchers discovered three resistance genes in rice that can be mutated in order to build the resistance of the rice against a pathogen. One of these resistance genes -- Xa13 -- is included in the Nature article and was discovered by White's lab in 2006.
"We've identified the genes that bacteria can induce to cause the plant to be susceptible," White said. "We've identified them as critical for disease from a pathogen standpoint. For the plant, these genes are involved in normal development. However, once the pathogen takes control of expression, it makes the plant susceptible."
White and Antony also have an article appearing in the December issue of the journal The Plant Cell. They collaborated with researchers from Iowa State University to investigate a second susceptibility gene and its role in the spread of disease.
White's laboratory has been working on such rice research for 15 years, but started collaborating with the Stanford researchers earlier this year.
"We have been trying to understand what the pathogen wants from the host, how the pathogen gets it, and how the host tries to defend itself," Antony said.
Although the research is important in the field of plant genetics, it has broader applications as well. Because researchers have a better understanding of how to control pathogen food supplies, they can use this research to reduce crop diseases and subsequent losses. The plant research may also apply the findings to humans or animals because both use similar sugar transporter genes to transfer glucose, leading to new possibilities for medicine and diabetes research.
Notes:
White and Antony are in the midst of a three-year, $3-million National Science Foundation grant, and have also been funded in their research by the U.S. Department of Agriculture's National Research Initiative program through the Cooperative State Research, Education and Extension Service.
Source:
Frank White
Kansas State University
суббота, 18 июня 2011 г.
Molecular Prosthesis Against Gout
Researchers from the ETH Zurich's Department of Biosystems Science and Engineering (D-BSSE) have devised a new method for preventing and permanently eradicating the cause of gout. It involves implanting a biological network that regulates the uric acid levels autonomously.
As Paracelsus once stated, the dose makes the poison. This not only goes for chemical substances introduced to the body, but also those produced by it. The uric acid in the blood especially needs to be in the proper dosage. If the level is too high (i.e. above 6.8 mg/dl blood), the uric acid crystallizes out, which can cause kidney stones and gout. However, uric acid is an important part of the human detoxification system, acting as a so-called "scavenger" of free radicals, which cause neurological disorders, brain diseases and tumors. A team of re-searchers headed by Professor Martin Fussenegger from ETH Zurich's D-BSSE in Basle has now succeeded in building a network of genes which permanently keep the uric acid concentration in check. The preliminary trials in mice have been encouraging. The research results will be published on Sunday in the journal Nature Biotechnology.
Self-regulating network
In most mammals, the enzyme urate oxydase controls the uric acid level. As humans evolved from the apes, however, they lost this enzyme, which is why we suffer more from an elevated uric acid concentration. Researchers from ETH Zurich set about finding a way to rectify the defect and restore the subtle control of the uric acid level. With this in mind, they put together a biological network of genes called UREX. The individual components of UREX were "programmed" differently by the researchers: a uric acid sensor constantly gauges and controls the concentration in the blood. If the uric acid level reaches an alarming concen-tration, the sensor relays the information to a genetic circuit. This then makes sure that the third component of the network releases the correct amount of urate oxydase into the blood and that the uric acid level is restored to a healthy balance. The three components of the network thus communicate with each other and work independently and automatically without any external assistance. The uric acid level can therefore be controlled permanently using UREX.
Genes left untouched
The gene network is integrated in a single cell. Around two million of these cells are enclosed in a seaweed gelatine capsule measuring 0.2 mm in diameter to protect the cells against an immune response. Pores in the capsule ensure that the cell receives an optimal supply of nutrients, the uric acid level can be gauged by the sensor and the enzyme can find its way into the blood. However, the organism does not come into contact with the network's modified genes. Even if the method were used in humans, a direct intervention in the patient's genetic make-up would not be necessary. "In the case of diseases resulting from genetic defects, it might make sense to channel genetically modified material directly into the human cells. However, this also raises concerns as the material can no longer be removed", explains Martin Fussenegger. But this is not the case with the new method: the implant can be removed safely at any time and without any after-effects.
For the ETH-Zurich professor, the result is a prime example of what the relatively new research branch of synthetic biology can achieve: "Many medical problems are solved by introducing chemical substances, i.e. medication, into the body from outside. In our method, we repair a defective metabolic pathway and help the body to treat itself in the best possible way." Martin Fussenegger refers to it fondly as a "molecular prosthesis" an artificial aid that compensates for the evolutionary lack of urate oxydase.
Gout: a scourge of mankind
Around 1 % of the population in the industrialized countries suffers from the ex-tremely painful joint disease gout due to elevated uric acid levels. There are many causes for the increase in the uric acid level: a genetic predisposition, environmental influences or an unbalanced diet. Moreover, it can lead to so-called tumor lysis syndrome after chemotherapy. Due to the intervention, tumor cells disintegrate so quickly that too much uric acid finds its way into the blood. This results in metabolic complications and possibly renal failure.
The team of researchers from ETH Zurich has successfully tested the UREX network on mice: as expected, the uric acid concentration in the blood decreased to a stable and healthy level, and the uric acid crystals in the animals' kidneys dissolved. The researchers have already filed a patent application for the network, but the next steps for its medical application are now in the hands of other partners. "We're confident that our network will complete all the necessary series of tests in the not too distant future, but in our experience it takes longer than you might hope for a finished product to reach the market", cautions Fussenegger. Once this one does, however, gout and kidney stones will be a thing of the past.
Source: ETH ZГјrich
As Paracelsus once stated, the dose makes the poison. This not only goes for chemical substances introduced to the body, but also those produced by it. The uric acid in the blood especially needs to be in the proper dosage. If the level is too high (i.e. above 6.8 mg/dl blood), the uric acid crystallizes out, which can cause kidney stones and gout. However, uric acid is an important part of the human detoxification system, acting as a so-called "scavenger" of free radicals, which cause neurological disorders, brain diseases and tumors. A team of re-searchers headed by Professor Martin Fussenegger from ETH Zurich's D-BSSE in Basle has now succeeded in building a network of genes which permanently keep the uric acid concentration in check. The preliminary trials in mice have been encouraging. The research results will be published on Sunday in the journal Nature Biotechnology.
Self-regulating network
In most mammals, the enzyme urate oxydase controls the uric acid level. As humans evolved from the apes, however, they lost this enzyme, which is why we suffer more from an elevated uric acid concentration. Researchers from ETH Zurich set about finding a way to rectify the defect and restore the subtle control of the uric acid level. With this in mind, they put together a biological network of genes called UREX. The individual components of UREX were "programmed" differently by the researchers: a uric acid sensor constantly gauges and controls the concentration in the blood. If the uric acid level reaches an alarming concen-tration, the sensor relays the information to a genetic circuit. This then makes sure that the third component of the network releases the correct amount of urate oxydase into the blood and that the uric acid level is restored to a healthy balance. The three components of the network thus communicate with each other and work independently and automatically without any external assistance. The uric acid level can therefore be controlled permanently using UREX.
Genes left untouched
The gene network is integrated in a single cell. Around two million of these cells are enclosed in a seaweed gelatine capsule measuring 0.2 mm in diameter to protect the cells against an immune response. Pores in the capsule ensure that the cell receives an optimal supply of nutrients, the uric acid level can be gauged by the sensor and the enzyme can find its way into the blood. However, the organism does not come into contact with the network's modified genes. Even if the method were used in humans, a direct intervention in the patient's genetic make-up would not be necessary. "In the case of diseases resulting from genetic defects, it might make sense to channel genetically modified material directly into the human cells. However, this also raises concerns as the material can no longer be removed", explains Martin Fussenegger. But this is not the case with the new method: the implant can be removed safely at any time and without any after-effects.
For the ETH-Zurich professor, the result is a prime example of what the relatively new research branch of synthetic biology can achieve: "Many medical problems are solved by introducing chemical substances, i.e. medication, into the body from outside. In our method, we repair a defective metabolic pathway and help the body to treat itself in the best possible way." Martin Fussenegger refers to it fondly as a "molecular prosthesis" an artificial aid that compensates for the evolutionary lack of urate oxydase.
Gout: a scourge of mankind
Around 1 % of the population in the industrialized countries suffers from the ex-tremely painful joint disease gout due to elevated uric acid levels. There are many causes for the increase in the uric acid level: a genetic predisposition, environmental influences or an unbalanced diet. Moreover, it can lead to so-called tumor lysis syndrome after chemotherapy. Due to the intervention, tumor cells disintegrate so quickly that too much uric acid finds its way into the blood. This results in metabolic complications and possibly renal failure.
The team of researchers from ETH Zurich has successfully tested the UREX network on mice: as expected, the uric acid concentration in the blood decreased to a stable and healthy level, and the uric acid crystals in the animals' kidneys dissolved. The researchers have already filed a patent application for the network, but the next steps for its medical application are now in the hands of other partners. "We're confident that our network will complete all the necessary series of tests in the not too distant future, but in our experience it takes longer than you might hope for a finished product to reach the market", cautions Fussenegger. Once this one does, however, gout and kidney stones will be a thing of the past.
Source: ETH ZГјrich
пятница, 17 июня 2011 г.
Collapse Of The Cellular Protein Network Causes Alzheimer's?
Protein aggregation underlies several neurodegenerative diseases such as Alzheimer's, Huntington's chorea or Parkinson's. Scientists at the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, now discovered a fundamental mechanism which explains how toxic protein aggregation occurs and why it leads to a widespread impairment of essential cellular functions. "Not all proteins are affected by aggregation", says Heidi Olzscha, PhD student at the MPIB. "Especially those proteins are susceptible, which possess specific structural characteristics and are involved in important biological processes."
To fulfill their different functions, proteins have to acquire the correct three-dimensional structure. In other words, polypeptides have to fold first. Molecular chaperones, a diverse group of conserved proteins, have specialized to assist other proteins during their folding. If the chaperones fail, misfolding and aggregation of the newly synthesized and pre-existing proteins might occur. In the worst case, this results then in neurodegenerative diseases, such as Alzheimer's, Huntington's chorea or Parkinson's. Alzheimer's disease, for example, develops because the A-beta and tau proteins aggregate, which leads to neuronal dysfunction and cell death. According to Alzheimer Forschung Initiative e. V., approximately 1.2 million people suffer from this disease only in Germany. The risk to fall ill grows with increasing age.
Scientists in the Department of Cellular Biochemistry at the Max Planck Institute of Biochemistry, headed by F.-Ulrich Hartl, now established a novel experimental model aimed at elucidating cellular protein misfolding and discovered why the misfolding and aggregation are deleterious for cells. They prepared several artificial aggregating proteins without any biological function and introduced them into cells. These model proteins clumped together, coaggregating many natural proteins and, in that way, disturbing their function. By means of quantitative proteomics, the researchers discovered that the affected proteins share certain structural characteristics which predispose them for the co-aggregation: They are large in size, less hydrophobic and show a significant increase of disorder in their structure.
"These are proteins that have not only many, but also very important functions in the cell", explains Martin Vabulas. "For instance, they are responsible for the stability of the cytoskeleton, the organization of the chromatin in nucleus, the transcription of DNA to RNA or the synthesis of proteins. Simultaneous disturbance of several of these essential processes is most probably the reason of the cellular break-down. As a consequence, protein misfolding diseases develop."
Molecular chaperones could possibly prevent this dire scenario. They are able to shield the aggregates, so that the aggregates cannot get in touch with other proteins anymore. The scientists hope that their new insights might help to develop novel therapeutic strategies in the battle against neurodegenerative diseases, especially at the earlier stages, before the irreversible collapse of cellular protein network sets in.
Sources: Max Planck Institute of Biochemistry, AlphaGalileo Foundation.
To fulfill their different functions, proteins have to acquire the correct three-dimensional structure. In other words, polypeptides have to fold first. Molecular chaperones, a diverse group of conserved proteins, have specialized to assist other proteins during their folding. If the chaperones fail, misfolding and aggregation of the newly synthesized and pre-existing proteins might occur. In the worst case, this results then in neurodegenerative diseases, such as Alzheimer's, Huntington's chorea or Parkinson's. Alzheimer's disease, for example, develops because the A-beta and tau proteins aggregate, which leads to neuronal dysfunction and cell death. According to Alzheimer Forschung Initiative e. V., approximately 1.2 million people suffer from this disease only in Germany. The risk to fall ill grows with increasing age.
Scientists in the Department of Cellular Biochemistry at the Max Planck Institute of Biochemistry, headed by F.-Ulrich Hartl, now established a novel experimental model aimed at elucidating cellular protein misfolding and discovered why the misfolding and aggregation are deleterious for cells. They prepared several artificial aggregating proteins without any biological function and introduced them into cells. These model proteins clumped together, coaggregating many natural proteins and, in that way, disturbing their function. By means of quantitative proteomics, the researchers discovered that the affected proteins share certain structural characteristics which predispose them for the co-aggregation: They are large in size, less hydrophobic and show a significant increase of disorder in their structure.
"These are proteins that have not only many, but also very important functions in the cell", explains Martin Vabulas. "For instance, they are responsible for the stability of the cytoskeleton, the organization of the chromatin in nucleus, the transcription of DNA to RNA or the synthesis of proteins. Simultaneous disturbance of several of these essential processes is most probably the reason of the cellular break-down. As a consequence, protein misfolding diseases develop."
Molecular chaperones could possibly prevent this dire scenario. They are able to shield the aggregates, so that the aggregates cannot get in touch with other proteins anymore. The scientists hope that their new insights might help to develop novel therapeutic strategies in the battle against neurodegenerative diseases, especially at the earlier stages, before the irreversible collapse of cellular protein network sets in.
Sources: Max Planck Institute of Biochemistry, AlphaGalileo Foundation.
четверг, 16 июня 2011 г.
Regulating Hematopoietic Stem Cell Homeostasis And Leukemogenesis
In the April 15th issue of G&D, Dr. Richard Flavell (Yale University) and colleagues identify the c-Cbl protein as a critical repressor of hematopoietic stem cell (HSC) self-renewal. In addition to establishing a key role for protein ubiquitylation in HSC development, this finding posits c-Cbl as a potential target in research into stem cell engineering as well as cell-based leukemia treatments.
Dr. Flavell describes the work as elucidating "a novel dimension in our understanding the self-renewal of Hematopoietic stem cells."
Like all stem cell populations, HSC reply upon asymmetric cell division to generate two different daughter cells: one future stem cell, and another cell that will further differentiate into a more specialized cell type. Thus, a balance is struck between the production of new cell types and the renewal of the stem cell pool. However, imbalances between HSC self-renewal and differentiation can lead to hematologic malignancies like leukemia.
Dr. Flavell's group discovered that the E3 ubiquitin ligase, c-Cbl, suppresses HSC self-renewal. The researchers generated transgenic mice deficient in c-Cbl, and demonstrated that these c-Cbl-mutant mice display an increased number of HSCs.
Lead author, Dr. Chozhavendan Rathinam, is confident that "our findings may facilitate the expansion and manipulation of hematopoietic stem cells for tissue engineering and stem cell based therapies."
Source: Heather Cosel-Pieper
Cold Spring Harbor Laboratory
Dr. Flavell describes the work as elucidating "a novel dimension in our understanding the self-renewal of Hematopoietic stem cells."
Like all stem cell populations, HSC reply upon asymmetric cell division to generate two different daughter cells: one future stem cell, and another cell that will further differentiate into a more specialized cell type. Thus, a balance is struck between the production of new cell types and the renewal of the stem cell pool. However, imbalances between HSC self-renewal and differentiation can lead to hematologic malignancies like leukemia.
Dr. Flavell's group discovered that the E3 ubiquitin ligase, c-Cbl, suppresses HSC self-renewal. The researchers generated transgenic mice deficient in c-Cbl, and demonstrated that these c-Cbl-mutant mice display an increased number of HSCs.
Lead author, Dr. Chozhavendan Rathinam, is confident that "our findings may facilitate the expansion and manipulation of hematopoietic stem cells for tissue engineering and stem cell based therapies."
Source: Heather Cosel-Pieper
Cold Spring Harbor Laboratory
среда, 15 июня 2011 г.
Novel Method Of Immunization That Completely Eliminates Malaria Parasites
Singapore scientists report that they have discovered a novel method of immunization that completely eliminates the malaria parasites in both stages of the parasite's development.
The scientists, part of the Singapore Immunology Network (SIgN), attribute the novel method's effectiveness in eliminating the malaria parasites to the fact that it targets common proteins that are found on the parasite in both stages of its sequential development, first, in the liver, and then in the blood.
The malaria research findings, which may serve as a basis for the development of a vaccine, were described in a "report card" about SIgN's first year in its state-of-the-art research facility on the Biopolis biomedical sciences campus of Singapore's Agency of Science, Technology and Research (A*STAR).
SIgN is a research consortium under A*STAR, which aims to make the program an international hub for immunology research.
"Building R&D is a strategic priority for Singapore," said A*STAR Chairman Lim Chuan Poh. "Singapore remains committed to investing in R&D even in this time of global financial crisis."
"The spotlight has increasingly turned on human immunology research over the last few years," said Paola Castagnoli, Ph.D., SIgN's Scientific Director. "There is increasing urgency to devise strategies and methods for translating what is already known in traditional immunology and develop it into something that can be used in the clinics and hospitals.
"SIgN will continue to ramp up its R&D efforts on human immunology as we believe that such an approach can potentially yield direct clinical applications with greater impact for human health," added Castagnoli, who is also Professor of Immunology and Pathology at the University of Milan-Bicocca.
Castagnoli noted that these plans are consistent with the scientific strategy set by SIgN Chairman Philippe Kourilsky, Ph.D., when he initiated the research program. He also is Professor and Chair of Molecular Immunology at the College de France.
During its first year, SIgN has made significant headway in three major areas of human immunity: infection, immuno-regulation and inflammation.
In cancer inflammation, SIgN scientists are using a skin tumour model that can better mimic the course of disease progression in human cancers and thus is more clinically relevant than other models. SIgN scientists found that skin tumours are able to escape detection because of immuno-tolerance, and in their studies to determine how to reverse immuno-tolerance, they have been investigating how some white blood cells (CD 8+ T cells) could play a role in this phenomenon by contributing to disease progression and the body's efforts to control the spread of the tumour.
A*STAR Chairman Lim Chuan Poh said, "Under the very able leadership of Professors Philippe Kourilsky and Paola Castagnoli, SIgN has indeed made significant progress.
They have attracted some very notable scientists and built extensive collaborations both within and outside Singapore. This is truly an anniversary to be celebrated.
"Our steady and sustained investments in R&D will not only differentiate us from the other R&D hubs, but make us very attractive as an R&D partner, and position us as the place to be for international scientific talent. Indeed, as we continue with our research activities, we are developing our capacity and positioning ourselves well for future growth once the global economy recovers."
For more information:
Ms Joyce Pang
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Singapore Immunology Network (SIgN): sign.a-star.sg
SIgN, officially inaugurated on 15 January 2008, is a research consortium under A*STAR's Biomedical Research Council aimed at building on the strengths of the existing immunology research groups at A*STAR, as well as expanding and strengthening the immunology research expertise in Singapore. SIgN's objectives include coordinating basic, translational and clinical research needed to establish immunology as a core capability in Singapore; establishing productive links with local initiatives within Biopolis and across Singapore; obtaining international recognition while establishing relationships with leading institutions in the world; and building up a strong platform in basic human immunology research for better translation of results into medical applications.
In its first year, SIgN also has rapidly expanded its stable of research talent as well as actively engaged industrial and clinical partners to develop and drive innovation in the area of human immunology. To date, 85 scientists have been recruited to SIgN вЂ" an increase of 42% since the program's official inauguration. Among the recent recruits are two notable immunologists whose unique expertise strengthens SIgN's human immunology knowledge base. They are:
Catharina Svanborg, M.D., Ph.D., a clinical immunologist and bacteriologist who came to SIgN from Lund University in Sweden where she was Professor of Clinical Immunology. She is furthering her research on HAMLET, a variant of a protein complex in human milk that has the ability to selectively kill tumour cells while leaving healthy cells unscathed.
Olaf Rotschzke, Ph.D., who came to SIgN from the Max-Delbrueck-Center in Berlin and who has more than 15 years of immunology research experience in studying a group of protective immune cells known as regulatory T cells (T-Regs), which are essential to the suppression of inflammation. Suppressing inflammation is important in treating autoimmune diseases, allergies and graft rejection. His research involves translating scientific results that have been successfully proven in animal models into therapies that can be used in human patients.
Over the past year, SIgN has built up a strong network for the exchange of ideas and expertise with over 40 research centres, hospitals and companies worldwide. It has also established several research collaborations with both local and international partners such as Singapore's Nanyang Technological University, Environmental Health Institute and Novartis Institute for Tropical Diseases; France's Institut National de la SantГ© et de la Recherche MГ©dicale; Humalys SAS; Italy's University of Milano-Bicocca; and Thailand's University of Mahidol.
SIgN is also actively collaborating with other A*STAR research units, leveraging on each other's strengths and capabilities to advance scientific knowledge. Examples of such collaborations include a hepatic disease research programme with the Singapore Institute for Clinical Sciences, joint grant call with the Singapore Bioimaging Consortium, setting up a transcriptional profiling database for immune cells with the Bioinformatics Institute and initiating projects on skin tissues with the Institute of Medical Biology.
Going forward, SIgN plans to collaborate with even more A*STAR research units such as the Experimental Therapeutics Centre (ETC), to which SIgN would bring validated products or targets for further development by ETC to the stage at which they can attract funding by venture capital investors or be out-licensed to industry.
Agency for Science, Technology and Research (A*STAR): a-star.sg
The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore.
A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering. We strongly support Singapore's key economic clusters by providing intellectual, human and industrial capital to our partners in industry and the healthcare sector. A*STAR oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR's research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
The scientists, part of the Singapore Immunology Network (SIgN), attribute the novel method's effectiveness in eliminating the malaria parasites to the fact that it targets common proteins that are found on the parasite in both stages of its sequential development, first, in the liver, and then in the blood.
The malaria research findings, which may serve as a basis for the development of a vaccine, were described in a "report card" about SIgN's first year in its state-of-the-art research facility on the Biopolis biomedical sciences campus of Singapore's Agency of Science, Technology and Research (A*STAR).
SIgN is a research consortium under A*STAR, which aims to make the program an international hub for immunology research.
"Building R&D is a strategic priority for Singapore," said A*STAR Chairman Lim Chuan Poh. "Singapore remains committed to investing in R&D even in this time of global financial crisis."
"The spotlight has increasingly turned on human immunology research over the last few years," said Paola Castagnoli, Ph.D., SIgN's Scientific Director. "There is increasing urgency to devise strategies and methods for translating what is already known in traditional immunology and develop it into something that can be used in the clinics and hospitals.
"SIgN will continue to ramp up its R&D efforts on human immunology as we believe that such an approach can potentially yield direct clinical applications with greater impact for human health," added Castagnoli, who is also Professor of Immunology and Pathology at the University of Milan-Bicocca.
Castagnoli noted that these plans are consistent with the scientific strategy set by SIgN Chairman Philippe Kourilsky, Ph.D., when he initiated the research program. He also is Professor and Chair of Molecular Immunology at the College de France.
During its first year, SIgN has made significant headway in three major areas of human immunity: infection, immuno-regulation and inflammation.
In cancer inflammation, SIgN scientists are using a skin tumour model that can better mimic the course of disease progression in human cancers and thus is more clinically relevant than other models. SIgN scientists found that skin tumours are able to escape detection because of immuno-tolerance, and in their studies to determine how to reverse immuno-tolerance, they have been investigating how some white blood cells (CD 8+ T cells) could play a role in this phenomenon by contributing to disease progression and the body's efforts to control the spread of the tumour.
A*STAR Chairman Lim Chuan Poh said, "Under the very able leadership of Professors Philippe Kourilsky and Paola Castagnoli, SIgN has indeed made significant progress.
They have attracted some very notable scientists and built extensive collaborations both within and outside Singapore. This is truly an anniversary to be celebrated.
"Our steady and sustained investments in R&D will not only differentiate us from the other R&D hubs, but make us very attractive as an R&D partner, and position us as the place to be for international scientific talent. Indeed, as we continue with our research activities, we are developing our capacity and positioning ourselves well for future growth once the global economy recovers."
For more information:
Ms Joyce Pang
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Singapore Immunology Network (SIgN): sign.a-star.sg
SIgN, officially inaugurated on 15 January 2008, is a research consortium under A*STAR's Biomedical Research Council aimed at building on the strengths of the existing immunology research groups at A*STAR, as well as expanding and strengthening the immunology research expertise in Singapore. SIgN's objectives include coordinating basic, translational and clinical research needed to establish immunology as a core capability in Singapore; establishing productive links with local initiatives within Biopolis and across Singapore; obtaining international recognition while establishing relationships with leading institutions in the world; and building up a strong platform in basic human immunology research for better translation of results into medical applications.
In its first year, SIgN also has rapidly expanded its stable of research talent as well as actively engaged industrial and clinical partners to develop and drive innovation in the area of human immunology. To date, 85 scientists have been recruited to SIgN вЂ" an increase of 42% since the program's official inauguration. Among the recent recruits are two notable immunologists whose unique expertise strengthens SIgN's human immunology knowledge base. They are:
Catharina Svanborg, M.D., Ph.D., a clinical immunologist and bacteriologist who came to SIgN from Lund University in Sweden where she was Professor of Clinical Immunology. She is furthering her research on HAMLET, a variant of a protein complex in human milk that has the ability to selectively kill tumour cells while leaving healthy cells unscathed.
Olaf Rotschzke, Ph.D., who came to SIgN from the Max-Delbrueck-Center in Berlin and who has more than 15 years of immunology research experience in studying a group of protective immune cells known as regulatory T cells (T-Regs), which are essential to the suppression of inflammation. Suppressing inflammation is important in treating autoimmune diseases, allergies and graft rejection. His research involves translating scientific results that have been successfully proven in animal models into therapies that can be used in human patients.
Over the past year, SIgN has built up a strong network for the exchange of ideas and expertise with over 40 research centres, hospitals and companies worldwide. It has also established several research collaborations with both local and international partners such as Singapore's Nanyang Technological University, Environmental Health Institute and Novartis Institute for Tropical Diseases; France's Institut National de la SantГ© et de la Recherche MГ©dicale; Humalys SAS; Italy's University of Milano-Bicocca; and Thailand's University of Mahidol.
SIgN is also actively collaborating with other A*STAR research units, leveraging on each other's strengths and capabilities to advance scientific knowledge. Examples of such collaborations include a hepatic disease research programme with the Singapore Institute for Clinical Sciences, joint grant call with the Singapore Bioimaging Consortium, setting up a transcriptional profiling database for immune cells with the Bioinformatics Institute and initiating projects on skin tissues with the Institute of Medical Biology.
Going forward, SIgN plans to collaborate with even more A*STAR research units such as the Experimental Therapeutics Centre (ETC), to which SIgN would bring validated products or targets for further development by ETC to the stage at which they can attract funding by venture capital investors or be out-licensed to industry.
Agency for Science, Technology and Research (A*STAR): a-star.sg
The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore.
A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering. We strongly support Singapore's key economic clusters by providing intellectual, human and industrial capital to our partners in industry and the healthcare sector. A*STAR oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR's research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.
Source: Cathy Yarbrough
Agency for Science, Technology and Research (A*STAR), Singapore
вторник, 14 июня 2011 г.
Key Mechanism For The Proliferation Of Epstein Barr Virus Discovered
Scientists of Helmholtz Zentrum MГјnchen have elucidated a crucial mechanism in the lytic cycle of Epstein-Barr virus. A team of researchers led by Professor Wolfgang Hammerschmidt identified the function of a protein which plays a critical role in the proliferation of the virus. The Epstein-Barr virus can induce cancer. The findings, published in the current issue of the renowned journal PNAS, represent a major step forward in understanding tumor development.
The Epstein-Barr virus (EBV), a virus of the herpes family, has two distinct life phases: After infecting a cell it first goes into a resting phase. Under certain circumstances the virus can become active and then induces tumor growth or promotes its synthesis in the cell. Especially in patients with weakened immune systems, EBV can cause its host cells to divide uncontrollably causing a tumor to develop.
The causes for the transition of EBV from the quiescent phase to an active mode particularly with respect to the responsible factors and to how the molecular mechanisms function have until now remained elusive. With their findings, the scientists at Helmholtz Zentrum MГјnchen have discovered how the virus terminates latency and activates its synthesis in the infected cells.
Professor Wolfgang Hammerschmidt, head of the Department of Gene Vectors at Helmholtz Zentrum MГјnchen, explained: "We have now identified the crucial function of the viral BZLF1 protein: It activates the genes of EBV, which are essential for the proliferation of virus particles." About 70 different genes are switched off during the latent phase because certain DNA segments are chemically modified: Some DNA building blocks carry methyl groups. They are a kind of stop signal for the cell apparatus, so that these genes cannot be converted into protein.
"BZLF1 can detect these methylation patterns in the DNA," said Markus Kalla, lead author of the study. With its DNA binding domain, the protein binds directly to the methylated DNA sequence. A second domain of BZLF1 is responsible for the reactivation of the gene. "Such a mechanism was not known before," Wolfgang Hammerschmidt said. Previous research assumed that the methyl groups had to be removed from the DNA building blocks before the transcription factors could bind to the regulatory DNA sequence and thus activate the gene.
The researchers' findings indicate that BZLF1 avoids this hurdle. Accordingly, BZLF1 appears to be essential for establishing and maintaining latency, but also for escaping from it.
During viral synthesis a large number of new particles are usually formed within the cell. To achieve this, viruses use large portions of the cell apparatus, in particular specific proteins and factors. After progeny synthesis the new viruses are released researchers speak of a lytic cycle. The disadvantage: the viruses thus attract the attention of the immune system, which then fights against the pathogen and destroys the cell supporting viral synthesis.
However, the Epstein-Barr virus uses another strategy. Instead of putting all of its energy into immediate synthesis of progeny in the infected cell, it goes into a resting phase following the infection and thus prevents a reaction of the immune system. The virus infects cells of the immune system - the so-called B cells - first inserting its DNA into their cell nucleus. Whereas most viruses immediately start their lytic proliferation cycle and thus use the cell apparatus to replicate the DNA and to generate important structural proteins from the genes, EBV drives transformation of merely a few genes from the cell into proteins. These so-called latent genes are important for the quiescent phase: They see to it that the DNA of the Epstein-Barr virus remains stable in the cell nucleus while the cell itself proliferates. This seemingly peaceful co-existence ends when the virus goes into the lytic phase or induces tumor growth.
These findings published in PNAS by Wolfgang Hammerschmidt and his colleagues constitute an important step for a better understanding of the role of EBV in tumor growth.
Source: Helmholtz Zentrum Muenchen
The Epstein-Barr virus (EBV), a virus of the herpes family, has two distinct life phases: After infecting a cell it first goes into a resting phase. Under certain circumstances the virus can become active and then induces tumor growth or promotes its synthesis in the cell. Especially in patients with weakened immune systems, EBV can cause its host cells to divide uncontrollably causing a tumor to develop.
The causes for the transition of EBV from the quiescent phase to an active mode particularly with respect to the responsible factors and to how the molecular mechanisms function have until now remained elusive. With their findings, the scientists at Helmholtz Zentrum MГјnchen have discovered how the virus terminates latency and activates its synthesis in the infected cells.
Professor Wolfgang Hammerschmidt, head of the Department of Gene Vectors at Helmholtz Zentrum MГјnchen, explained: "We have now identified the crucial function of the viral BZLF1 protein: It activates the genes of EBV, which are essential for the proliferation of virus particles." About 70 different genes are switched off during the latent phase because certain DNA segments are chemically modified: Some DNA building blocks carry methyl groups. They are a kind of stop signal for the cell apparatus, so that these genes cannot be converted into protein.
"BZLF1 can detect these methylation patterns in the DNA," said Markus Kalla, lead author of the study. With its DNA binding domain, the protein binds directly to the methylated DNA sequence. A second domain of BZLF1 is responsible for the reactivation of the gene. "Such a mechanism was not known before," Wolfgang Hammerschmidt said. Previous research assumed that the methyl groups had to be removed from the DNA building blocks before the transcription factors could bind to the regulatory DNA sequence and thus activate the gene.
The researchers' findings indicate that BZLF1 avoids this hurdle. Accordingly, BZLF1 appears to be essential for establishing and maintaining latency, but also for escaping from it.
During viral synthesis a large number of new particles are usually formed within the cell. To achieve this, viruses use large portions of the cell apparatus, in particular specific proteins and factors. After progeny synthesis the new viruses are released researchers speak of a lytic cycle. The disadvantage: the viruses thus attract the attention of the immune system, which then fights against the pathogen and destroys the cell supporting viral synthesis.
However, the Epstein-Barr virus uses another strategy. Instead of putting all of its energy into immediate synthesis of progeny in the infected cell, it goes into a resting phase following the infection and thus prevents a reaction of the immune system. The virus infects cells of the immune system - the so-called B cells - first inserting its DNA into their cell nucleus. Whereas most viruses immediately start their lytic proliferation cycle and thus use the cell apparatus to replicate the DNA and to generate important structural proteins from the genes, EBV drives transformation of merely a few genes from the cell into proteins. These so-called latent genes are important for the quiescent phase: They see to it that the DNA of the Epstein-Barr virus remains stable in the cell nucleus while the cell itself proliferates. This seemingly peaceful co-existence ends when the virus goes into the lytic phase or induces tumor growth.
These findings published in PNAS by Wolfgang Hammerschmidt and his colleagues constitute an important step for a better understanding of the role of EBV in tumor growth.
Source: Helmholtz Zentrum Muenchen
понедельник, 13 июня 2011 г.
Carbon Nanotube Technology Based On University Research
Some great inventions are birthed at a bar, their futures scribbled on cocktail napkins. Multi-pixel X-ray technology, the first substantial technological change in X-rays in more than a century, was born over a greasy Philly cheesesteak sandwich.
It was 2000. Otto Zhou was the principal investigator on a $6 million grant from the Office of Naval Research to find applications for carbon nanotubes. Zhou and Jianping Lu, both physics professors at the University of North Carolina at Chapel Hill, often brainstormed ideas over lunch. Other scientists across the country were applying the material to flat-panel displays.
"We were at Miami Subs when we thought, 'what about X-ray"'" said Zhou, the Lyle Jones Distinguished Professor of Physics and Materials Sciences in UNC's College of Arts and Sciences.
"We thought, basically, TV is no different from X-rays, and X-rays are one of the most commonly used devises," Lu said. "We started drawing around on a napkin. We have limited medical knowledge but we understand the basic physics of X-rays."
Zhou, Lu and other collaborators grew their napkin diagram and the grant-funded research into Xintek, a small nanotechnology start-up company that licensed technology from UNC and Duke University. Two years ago the company established formal collaborations with Siemens Medical Solutions in Erlangen, Germany.
Siemens and Xintek announced on Sept. 18 a new joint venture company, XinRay Systems, with headquarters in North Carolina's Research Triangle Park, to further develop the technology.
"This agreement with Siemens is a major step for us," said Zhou. "We can be as confident as we want, but it's nice to be confirmed by others willing to take the next steps. That's gratifying.
"As engineers we like to see ideas become something useful, more than just a stack of papers," Zhou said. "We like to see the papers, but we want our work to translate into something useful to society."
Zhou originally thought their technology would first be used in manufacturing settings, inspecting parts for tiny defects. Sept. 11, 2001, changed that. Now, with grants from the U.S. Department of Homeland Security, he said he expected their first products to be airport security screeners. They could enter the field of medical diagnostics within a few years.
X-ray technology has many limitations: it requires heating a filament to 1,000 degrees in order to produce the electrons that make an X-ray image; it requires large and bulky equipment; and it's slow.
Early CT scanners use one x-ray source that rotates around an object. They have limited imaging acquisition speed. Siemens' technology has addressed some of these issues, and the new nanotechnology enabled x-ray sources may improve future generations of CT scanners.
In 2005, UNC and Xintek announced a major advance by placing multiple carbon nanotube sources in an array. In this multi-pixel configuration all the energy sources -- the carbon nanotubes -- can fire at once from different angles, and they can fire repeatedly, in one-millionth of a second, Lu said. Fast enough to clearly capture a beating heart.
Carbon nanotubes are sheets of carbon rolled into a seamless tube about 300 times smaller than the diameter of human hair. They require much less energy to produce electrons which means they can be turned on and off very quickly at low energy. And, unlike conventional filaments, they're microscopic.
In today's digital imaging technology, only the detector, the medium, is digital. Multi-pixel X-rays digitize the source. "This," say Zhou and Lu, "is truly digital."
College campuses are increasingly becoming the site of such discoveries and developments. Zhou, who worked at Bell Labs before coming to UNC in 1996, said industry is taking fewer risks in research and development than it did 20 years ago. "Universities have to take up some of those risks with private funding, venture capital."
At UNC, Zhou has brought to bear on his research expertise from a wide palette of specialties, including biomedical engineers, radiation oncologists, radiologist, chemists and physicists. His students have also pursued interdisciplinary studies and they've found jobs in his lab and with Xintek.
Zhou and Lu also have appointments in UNC's Lineberger Comprehensive Cancer Center. They were instrumental in the center's receiving major National Cancer Institute funding that created the Carolina Center for Cancer Nanotechnology Excellence. That Center, in turn, dovetails with the UNC Roadmap Office, which brings together researchers from a variety of disciplines under a National Institutes of Health program.
UNC's Office of Technology Development, which helps place UNC among the top 10 U.S. universities in patent strength, also assisted Zhou, Lu and other collaborators to obtain patents, create Xintek and license the technology.
"It's not so often," Zhou said, "that you can find a technology that will help so many people -- cancer screening, security -- you can talk with your mom about without getting too technical."
Zhou and Lu can bask, at least momentarily, in their current success. But if history is in the making, curators years from now will bemoan the loss of one key artifact; they didn't save the napkin.
For more on Xintek, visit: xintek/
For more on XinRay Systems, visit: xinraysystems/
For more on Siemens, visit: usa.siemens/medical-pressroom
For more on Zhou's lab, visit: physics.unc/project/zhou/index.php
For more on Lu's lab, visit: physics.unc/~jpl/home.html
For more on UNC's Office of Technology Development, visit: research.unc/
Source: Clinton Colmenares
University of North Carolina at Chapel Hill
It was 2000. Otto Zhou was the principal investigator on a $6 million grant from the Office of Naval Research to find applications for carbon nanotubes. Zhou and Jianping Lu, both physics professors at the University of North Carolina at Chapel Hill, often brainstormed ideas over lunch. Other scientists across the country were applying the material to flat-panel displays.
"We were at Miami Subs when we thought, 'what about X-ray"'" said Zhou, the Lyle Jones Distinguished Professor of Physics and Materials Sciences in UNC's College of Arts and Sciences.
"We thought, basically, TV is no different from X-rays, and X-rays are one of the most commonly used devises," Lu said. "We started drawing around on a napkin. We have limited medical knowledge but we understand the basic physics of X-rays."
Zhou, Lu and other collaborators grew their napkin diagram and the grant-funded research into Xintek, a small nanotechnology start-up company that licensed technology from UNC and Duke University. Two years ago the company established formal collaborations with Siemens Medical Solutions in Erlangen, Germany.
Siemens and Xintek announced on Sept. 18 a new joint venture company, XinRay Systems, with headquarters in North Carolina's Research Triangle Park, to further develop the technology.
"This agreement with Siemens is a major step for us," said Zhou. "We can be as confident as we want, but it's nice to be confirmed by others willing to take the next steps. That's gratifying.
"As engineers we like to see ideas become something useful, more than just a stack of papers," Zhou said. "We like to see the papers, but we want our work to translate into something useful to society."
Zhou originally thought their technology would first be used in manufacturing settings, inspecting parts for tiny defects. Sept. 11, 2001, changed that. Now, with grants from the U.S. Department of Homeland Security, he said he expected their first products to be airport security screeners. They could enter the field of medical diagnostics within a few years.
X-ray technology has many limitations: it requires heating a filament to 1,000 degrees in order to produce the electrons that make an X-ray image; it requires large and bulky equipment; and it's slow.
Early CT scanners use one x-ray source that rotates around an object. They have limited imaging acquisition speed. Siemens' technology has addressed some of these issues, and the new nanotechnology enabled x-ray sources may improve future generations of CT scanners.
In 2005, UNC and Xintek announced a major advance by placing multiple carbon nanotube sources in an array. In this multi-pixel configuration all the energy sources -- the carbon nanotubes -- can fire at once from different angles, and they can fire repeatedly, in one-millionth of a second, Lu said. Fast enough to clearly capture a beating heart.
Carbon nanotubes are sheets of carbon rolled into a seamless tube about 300 times smaller than the diameter of human hair. They require much less energy to produce electrons which means they can be turned on and off very quickly at low energy. And, unlike conventional filaments, they're microscopic.
In today's digital imaging technology, only the detector, the medium, is digital. Multi-pixel X-rays digitize the source. "This," say Zhou and Lu, "is truly digital."
College campuses are increasingly becoming the site of such discoveries and developments. Zhou, who worked at Bell Labs before coming to UNC in 1996, said industry is taking fewer risks in research and development than it did 20 years ago. "Universities have to take up some of those risks with private funding, venture capital."
At UNC, Zhou has brought to bear on his research expertise from a wide palette of specialties, including biomedical engineers, radiation oncologists, radiologist, chemists and physicists. His students have also pursued interdisciplinary studies and they've found jobs in his lab and with Xintek.
Zhou and Lu also have appointments in UNC's Lineberger Comprehensive Cancer Center. They were instrumental in the center's receiving major National Cancer Institute funding that created the Carolina Center for Cancer Nanotechnology Excellence. That Center, in turn, dovetails with the UNC Roadmap Office, which brings together researchers from a variety of disciplines under a National Institutes of Health program.
UNC's Office of Technology Development, which helps place UNC among the top 10 U.S. universities in patent strength, also assisted Zhou, Lu and other collaborators to obtain patents, create Xintek and license the technology.
"It's not so often," Zhou said, "that you can find a technology that will help so many people -- cancer screening, security -- you can talk with your mom about without getting too technical."
Zhou and Lu can bask, at least momentarily, in their current success. But if history is in the making, curators years from now will bemoan the loss of one key artifact; they didn't save the napkin.
For more on Xintek, visit: xintek/
For more on XinRay Systems, visit: xinraysystems/
For more on Siemens, visit: usa.siemens/medical-pressroom
For more on Zhou's lab, visit: physics.unc/project/zhou/index.php
For more on Lu's lab, visit: physics.unc/~jpl/home.html
For more on UNC's Office of Technology Development, visit: research.unc/
Source: Clinton Colmenares
University of North Carolina at Chapel Hill
воскресенье, 12 июня 2011 г.
Scientists Discovered A New Molecular Mechanism Linking Viral Infection To Cancer Susceptibility
Portuguese scientists discovered a new molecular mechanism that allows gamma herpes viruses to chronically infect patients and helps to explain why these patients present an abnormally high incidence of the lymphocyte (or white blood cell) cancer lymphoma, particularly when their immune system is compromised.
The research, just published in the advance online edition of The Embo Journal 1, reveals how these viruses mimic the host molecular machinery to shutdown NF-kB a key regulatory protein complex involved in cell division and death on infected lymphocytes, and how this - probably by disrupting the cells normal regulatory systems creates the conditions for the development of lymphomas. A crucial implication of the discovery if gamma herpes virus-infected patients with lymphomas are confirmed to have their NF-kB shutdown is that drugs to rescue this molecule, which are available in the market, will be able to substantially reduce the chance of lymphomas in these patients.
Gamma herpes viruses specifically infect white blood cells (B or T lymphocytes) often remaining latent in the lymphoid tissues as an asymptomatic chronic infection but, sometimes - particularly in immune compromised individuals such as transplant or AIDS patients can lead to the appearance of lymphomas. Examples of gamma herpes viruses include the Epstein-BarrVirus responsible for mononucleosis or glandular fever and linked to the endemic Burkitt lymphoma, the most common childhood cancer in many parts of Africa and the Kaposi's sarcoma-associated herpes virus, a type of cancer very characteristic of AIDS patients.
This association between the chronic lymphocyte infection and lymphomas a cancer where lymphocytes divide abnormally and without control is not understood as not much is known abut the mechanisms behind the virus/infected lymphocytes interaction. The most logical explanation, however since viruses do not have the means to reproduce themselves and need to hijack the infected cells' molecular machinery in order to divide and spread infection is that the viral manipulation of the host molecular machinery disturbs the cells' normal controls leading to an increased risk of cancer.
To understand these phenomenon better LГ©nia Rodrigues, J Pedro Simas and colleagues at the Institute of Molecular Medicine and the Gulbenkian Institute in Lisbon Portugal and the Weill Medical College of Cornell University, New York, USA decided to look into NF-kB, a known target for many viruses but also a key regulatory molecule of genes involved in cell death and proliferation, which when defective can lead to cancer. Because the establishment of a chronic infection depends on the capacity of the virus to remain latent in the organism, the researchers analysed NF-kB in the host germinal centres, which are the areas of the lymph nodes where B cells divide but also the place where the gamma herpes virus is known to stay latent.
What Rodrigues, Simas and colleagues discovered was a totally new viral "hijacking" mechanism where a protein from gamma herpes viruses - called ORFT3 - mimics a host NF-kB regulator to shutdown NF-kB. In fact, when the cells are resting, NF-kB molecules are maintained in the cell cytoplasm away from the nucleus where the chromosomes - with all the genes that NF-kB regulates are found. When NF-kB needs to be activated - for example when an immune response is necessary - the inhibitory molecules are destroyed and NF-kB can then migrate into the nucleus where it specifically activates its target genes. ORF73 was shown to shutdown NF-kB in the nucleus by destroying a subunit of NF-kB by a similar mechanism to the one used to eliminate the inhibitory molecules.
In a second set of experiments Rodrigues and colleagues showed that gamma herpes viruses with defective ORF73 were incapable of expanding within the infected B cells, or maintain a persistent infection, higlighting the importance of this viral NF-kB shutdown mechanism for the establishment of the chronic infection (and the accompanying tumour susceptibility).
So NF-kB shutdown by OFR73 results in the proliferation of B cells which allows the virus to divide spreading the infection throughout the germinal centres where it could then stay latent. Rodrigues and colleagues believe that during the normal process of B cell differentiation NF-kB needs to be temporarily shutdown - after a prior activation that allows the molecule to migrate into the nucleus - to let the cells divide and it is this period that ORF73 mimics. This explanation agrees with results showing that constant NF-kB inhibition from the most initial stages of viral infection impairs the establishment of latency, as well as with Rodrigues, Simas and colleagues' findings that ORF73 targets NF-kB in the nucleus.
Rodrigues, Simas and colleagues' study has several important implications including a better understanding of how herpes viruses persist in the host and their interactions with the infected system.
But, and most crucially, it shows a new molecular link between viral infections and the appearance of cancer. This can now be further researched and, if confirmed in patients, become an important therapeutic target to prevent the appearance of potentially fatal lymphomas in infected patients.
Source: Ciencia Viva
The research, just published in the advance online edition of The Embo Journal 1, reveals how these viruses mimic the host molecular machinery to shutdown NF-kB a key regulatory protein complex involved in cell division and death on infected lymphocytes, and how this - probably by disrupting the cells normal regulatory systems creates the conditions for the development of lymphomas. A crucial implication of the discovery if gamma herpes virus-infected patients with lymphomas are confirmed to have their NF-kB shutdown is that drugs to rescue this molecule, which are available in the market, will be able to substantially reduce the chance of lymphomas in these patients.
Gamma herpes viruses specifically infect white blood cells (B or T lymphocytes) often remaining latent in the lymphoid tissues as an asymptomatic chronic infection but, sometimes - particularly in immune compromised individuals such as transplant or AIDS patients can lead to the appearance of lymphomas. Examples of gamma herpes viruses include the Epstein-BarrVirus responsible for mononucleosis or glandular fever and linked to the endemic Burkitt lymphoma, the most common childhood cancer in many parts of Africa and the Kaposi's sarcoma-associated herpes virus, a type of cancer very characteristic of AIDS patients.
This association between the chronic lymphocyte infection and lymphomas a cancer where lymphocytes divide abnormally and without control is not understood as not much is known abut the mechanisms behind the virus/infected lymphocytes interaction. The most logical explanation, however since viruses do not have the means to reproduce themselves and need to hijack the infected cells' molecular machinery in order to divide and spread infection is that the viral manipulation of the host molecular machinery disturbs the cells' normal controls leading to an increased risk of cancer.
To understand these phenomenon better LГ©nia Rodrigues, J Pedro Simas and colleagues at the Institute of Molecular Medicine and the Gulbenkian Institute in Lisbon Portugal and the Weill Medical College of Cornell University, New York, USA decided to look into NF-kB, a known target for many viruses but also a key regulatory molecule of genes involved in cell death and proliferation, which when defective can lead to cancer. Because the establishment of a chronic infection depends on the capacity of the virus to remain latent in the organism, the researchers analysed NF-kB in the host germinal centres, which are the areas of the lymph nodes where B cells divide but also the place where the gamma herpes virus is known to stay latent.
What Rodrigues, Simas and colleagues discovered was a totally new viral "hijacking" mechanism where a protein from gamma herpes viruses - called ORFT3 - mimics a host NF-kB regulator to shutdown NF-kB. In fact, when the cells are resting, NF-kB molecules are maintained in the cell cytoplasm away from the nucleus where the chromosomes - with all the genes that NF-kB regulates are found. When NF-kB needs to be activated - for example when an immune response is necessary - the inhibitory molecules are destroyed and NF-kB can then migrate into the nucleus where it specifically activates its target genes. ORF73 was shown to shutdown NF-kB in the nucleus by destroying a subunit of NF-kB by a similar mechanism to the one used to eliminate the inhibitory molecules.
In a second set of experiments Rodrigues and colleagues showed that gamma herpes viruses with defective ORF73 were incapable of expanding within the infected B cells, or maintain a persistent infection, higlighting the importance of this viral NF-kB shutdown mechanism for the establishment of the chronic infection (and the accompanying tumour susceptibility).
So NF-kB shutdown by OFR73 results in the proliferation of B cells which allows the virus to divide spreading the infection throughout the germinal centres where it could then stay latent. Rodrigues and colleagues believe that during the normal process of B cell differentiation NF-kB needs to be temporarily shutdown - after a prior activation that allows the molecule to migrate into the nucleus - to let the cells divide and it is this period that ORF73 mimics. This explanation agrees with results showing that constant NF-kB inhibition from the most initial stages of viral infection impairs the establishment of latency, as well as with Rodrigues, Simas and colleagues' findings that ORF73 targets NF-kB in the nucleus.
Rodrigues, Simas and colleagues' study has several important implications including a better understanding of how herpes viruses persist in the host and their interactions with the infected system.
But, and most crucially, it shows a new molecular link between viral infections and the appearance of cancer. This can now be further researched and, if confirmed in patients, become an important therapeutic target to prevent the appearance of potentially fatal lymphomas in infected patients.
Source: Ciencia Viva
суббота, 11 июня 2011 г.
What Do Fats Do In The Body?
It's common knowledge that too much cholesterol and other fats can lead to disease, and that a healthy diet involves watching how much fatty food we eat. However, our bodies need a certain amount of fat to function and we can't make it from scratch.
Triglycerides, cholesterol and other essential fatty acids the scientific term for fats the body can't make on its own store energy, insulate us and protect our vital organs. They act as messengers, helping proteins do their jobs. They also start chemical reactions that help control growth, immune function, reproduction and other aspects of basic metabolism.
The cycle of making, breaking, storing and mobilizing fats is at the core of how humans and all animals regulate their energy. An imbalance in any step can result in disease, including heart disease and diabetes. For instance, having too many triglycerides in our bloodstream raises our risk of clogged arteries, which can lead to heart attack and stroke.
Fats help the body stockpile certain nutrients as well. The so-called "fat-soluble" vitamins A, D, E and KвЂ"are stored in the liver and in fatty tissues.
Knowing that fats play such an important role in many basic functions in the body, researchers funded by the National Institutes of Health study them in humans and other organisms to learn more about normal and abnormal biology.
Looking to Insects for Insight into Fat Regulation
Despite fat's importance, no one yet understands exactly how humans store it and call it into action. In search of insight, Oklahoma State University biochemist Estela Arrese studies triglyceride metabolism in unexpected places: silkworms, fruit flies and mosquitoes.
The main type of fat we consume, triglycerides are especially suited for energy storage because they pack more than twice as much energy as carbohydrates or proteins.
Once triglycerides have been broken down during digestion, they are shipped out to cells through the bloodstream. Some of the fat gets used for energy right away. The rest is stored inside cells in blobs called lipid droplets.
When we need extra energy for instance, when we run a marathon our bodies use enzymes called lipases to break down the stored triglycerides. The cell's power plants, mitochondria, can then create more of the body's main energy source: adenosine triphosphate, or ATP.
Arrese works to identify, purify and determine the roles of individual proteins involved in triglyceride metabolism. Her lab was the first to purify the main fat regulation protein in insects, TGL, and now she is trying to learn what it does. She also discovered the function of a key lipid droplet protein called Lsd1, and she is investigating its sister, Lsd2.
Arrese's work could teach us more about disorders like diabetes, obesity and heart disease. Plus, by understanding how insects use fat when they metamorphose and lay eggs and by hypothesizing how to disrupt those processes, her discoveries could lead to new ways for farmers to protect their crops from pests and for health officials to combat mosquito-borne diseases like malaria and West Nile virus.
But before any of that can happen, says Arrese, "We need to study a lot and have information at the molecular level."
Cholesterol and Cell Membranes
One of Arrese's challenges is trying to get oily substances like fat to work in lab tests, which tend to be water-based. However, our cells couldn't function without fat and water's mutual dislike.
Cell membranes encase our cells and the organelles inside them. Fat specifically, cholesterol makes these membranes possible. The fatty ends of membrane molecules veer away from the water inside and outside cells, while the non-fatty ends gravitate toward it. The molecules spontaneously line up to form a semi-permeable membrane. The result: flexible protective barriers that, like bouncers at a club, only allow the appropriate molecules to cross into and out of cells.
Chew on that the next time you ponder the fate of the fat in a French fry.
Source: NIH, National Institute of General Medical Sciences (NIGMS)
Triglycerides, cholesterol and other essential fatty acids the scientific term for fats the body can't make on its own store energy, insulate us and protect our vital organs. They act as messengers, helping proteins do their jobs. They also start chemical reactions that help control growth, immune function, reproduction and other aspects of basic metabolism.
The cycle of making, breaking, storing and mobilizing fats is at the core of how humans and all animals regulate their energy. An imbalance in any step can result in disease, including heart disease and diabetes. For instance, having too many triglycerides in our bloodstream raises our risk of clogged arteries, which can lead to heart attack and stroke.
Fats help the body stockpile certain nutrients as well. The so-called "fat-soluble" vitamins A, D, E and KвЂ"are stored in the liver and in fatty tissues.
Knowing that fats play such an important role in many basic functions in the body, researchers funded by the National Institutes of Health study them in humans and other organisms to learn more about normal and abnormal biology.
Looking to Insects for Insight into Fat Regulation
Despite fat's importance, no one yet understands exactly how humans store it and call it into action. In search of insight, Oklahoma State University biochemist Estela Arrese studies triglyceride metabolism in unexpected places: silkworms, fruit flies and mosquitoes.
The main type of fat we consume, triglycerides are especially suited for energy storage because they pack more than twice as much energy as carbohydrates or proteins.
Once triglycerides have been broken down during digestion, they are shipped out to cells through the bloodstream. Some of the fat gets used for energy right away. The rest is stored inside cells in blobs called lipid droplets.
When we need extra energy for instance, when we run a marathon our bodies use enzymes called lipases to break down the stored triglycerides. The cell's power plants, mitochondria, can then create more of the body's main energy source: adenosine triphosphate, or ATP.
Arrese works to identify, purify and determine the roles of individual proteins involved in triglyceride metabolism. Her lab was the first to purify the main fat regulation protein in insects, TGL, and now she is trying to learn what it does. She also discovered the function of a key lipid droplet protein called Lsd1, and she is investigating its sister, Lsd2.
Arrese's work could teach us more about disorders like diabetes, obesity and heart disease. Plus, by understanding how insects use fat when they metamorphose and lay eggs and by hypothesizing how to disrupt those processes, her discoveries could lead to new ways for farmers to protect their crops from pests and for health officials to combat mosquito-borne diseases like malaria and West Nile virus.
But before any of that can happen, says Arrese, "We need to study a lot and have information at the molecular level."
Cholesterol and Cell Membranes
One of Arrese's challenges is trying to get oily substances like fat to work in lab tests, which tend to be water-based. However, our cells couldn't function without fat and water's mutual dislike.
Cell membranes encase our cells and the organelles inside them. Fat specifically, cholesterol makes these membranes possible. The fatty ends of membrane molecules veer away from the water inside and outside cells, while the non-fatty ends gravitate toward it. The molecules spontaneously line up to form a semi-permeable membrane. The result: flexible protective barriers that, like bouncers at a club, only allow the appropriate molecules to cross into and out of cells.
Chew on that the next time you ponder the fate of the fat in a French fry.
Source: NIH, National Institute of General Medical Sciences (NIGMS)
пятница, 10 июня 2011 г.
Are Scientists Making Progress In Being Able To Regenerate Bone Tissue?
In an article in PLoS Medicine, Gert Meijer (University Medical Centre Utrecht, The Netherlands) and colleagues discuss what kind of progress there has been in restoring the function of diseased or damaged bone by bone tissue regeneration.
Until recently, say the authors, the use of bone grafts from a different part of the patient's own body has been the number one choice for attempting to restore function. But there are major problems with such grafts-for example, removing bone from a different part of the body can lead to post-operative pain, infection, and abnormal sensations at the removal site. An alternative is to use bone given by a donor-but such bone grafts from donors are less successful and there is a risk of transmitting viruses from the donor to the recipient.
Given all these problems with bone grafts, scientists have attempted to engineer bone tissue. "Bone tissue engineering using bone marrow stem cells has been suggested as a promising technique for reconstructing bone defects," say Meijer and colleagues. Bone tissue engineering has shown success in animal studies.
In their article the authors review the available data on bone tissue engineering in human studies, including clinical research they themselves have conducted. They also discuss possible new directions that need to be exploited to make bone tissue engineering a clinical success.
Citation: Meijer GJ, de Bruijn JD, Koole R, van Blitterswijk CA (2007) Cell-based bone tissue engineering. PLoS Med 4(2): e9.
About PUBLIC LIBRARY OF SCIENCE
PLoS is a nonprofit organization of scientists whose aim is to make the world's scientific and medical research literature a public resource. We are funded by a grant from the Gordon and Betty Moore Foundation to develop a publishing program based on the Open Access business model, whereby the costs of publication are paid upfront so that anyone with an internet connection can have access to the content, in a free and unrestricted manner. Our immediate goal is to launch two top-tier journals - PLoS Biology (in October, 2003) and PLoS Medicine (in 2004).
PUBLIC LIBRARY OF SCIENCE
European Bioinformatics Institute
Wellcome Trust Genome Campus
CB10 1DS
plos
Until recently, say the authors, the use of bone grafts from a different part of the patient's own body has been the number one choice for attempting to restore function. But there are major problems with such grafts-for example, removing bone from a different part of the body can lead to post-operative pain, infection, and abnormal sensations at the removal site. An alternative is to use bone given by a donor-but such bone grafts from donors are less successful and there is a risk of transmitting viruses from the donor to the recipient.
Given all these problems with bone grafts, scientists have attempted to engineer bone tissue. "Bone tissue engineering using bone marrow stem cells has been suggested as a promising technique for reconstructing bone defects," say Meijer and colleagues. Bone tissue engineering has shown success in animal studies.
In their article the authors review the available data on bone tissue engineering in human studies, including clinical research they themselves have conducted. They also discuss possible new directions that need to be exploited to make bone tissue engineering a clinical success.
Citation: Meijer GJ, de Bruijn JD, Koole R, van Blitterswijk CA (2007) Cell-based bone tissue engineering. PLoS Med 4(2): e9.
About PUBLIC LIBRARY OF SCIENCE
PLoS is a nonprofit organization of scientists whose aim is to make the world's scientific and medical research literature a public resource. We are funded by a grant from the Gordon and Betty Moore Foundation to develop a publishing program based on the Open Access business model, whereby the costs of publication are paid upfront so that anyone with an internet connection can have access to the content, in a free and unrestricted manner. Our immediate goal is to launch two top-tier journals - PLoS Biology (in October, 2003) and PLoS Medicine (in 2004).
PUBLIC LIBRARY OF SCIENCE
European Bioinformatics Institute
Wellcome Trust Genome Campus
CB10 1DS
plos
четверг, 9 июня 2011 г.
The Power Of Networks Lets Scientists Unravel The Complex Control Of Biological Processes
Scientists at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital (Canada), European Molecular Biology Laboratory (Germany), and Massachusetts Institute of Technology (USA) have created a new computational method called NetworKIN. This method uses biological networks to better identify relationships between molecules. In a cover story featured in the June 29, 2007 edition of the journal Cell, the scientists report insights into the regulation of protein networks that will ultimately help to target human disease.
"Thousands of proteins can be changed (via phosphorylation) but until now, it has not been possible to know which protein has made the change," states Dr. Tony Pawson, distinguished investigator at the Lunenfeld.
Proteins are the functional agents that carry out processes in a cell. But they rarely act alone. Instead they accomplish their effects as part of big networks. How proteins interact in these networks often depends on phosphorylation, the addition of a phosphate at specific sites on a protein. Kinases are proteins that bring about the phosphorylation of other proteins and in this way regulate cellular processes.
"By getting a network-wide view, multiple aberrant genes of kinase-controlled processes are more easily targeted," states Dr. Rune Linding, postdoctoral fellow, Samuel Lunenfeld Research Institute. "In the future, the treatment of complex human diseases will be treated by targeting multiple genes." Complex diseases like cancer often contain defects in several processes controlled by kinases.
"It works a bit like getting a recommendation from Amazon," says Dr. Peer Bork, group leader at EMBL. "The fact that certain books have been bought by the same customers tells you that they have something in common. In the same way biological networks tell us about shared features between different proteins. These help us predicting which kinases are likely to act on them."
Samuel Lunenfeld Research Institute
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre, established in 1985, is one of the world's leading centres in biomedical research. 32 principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit mshri.on.ca/
EMBL
The European Molecular Biology Laboratory is a basic research institute funded by public research monies from 19 member states (Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom). Research at EMBL is conducted by approximately 80 independent groups covering the spectrum of molecular biology. The Laboratory has five units: the main Laboratory in Heidelberg, and Outstations in Hinxton (the European Bioinformatics Institute), Grenoble, Hamburg, and Monterotondo near Rome. The cornerstones of EMBL's mission are: to perform basic research in molecular biology; to train scientists, students and visitors at all levels; to offer vital services to scientists in the member states; to develop new instruments and methods in the life sciences and to actively engage in technology transfer activities. EMBL's International PhD Programme has a student body of about 170. The Laboratory also sponsors an active Science and Society programme. Visitors from the press and public are welcome.
Source Article:
Rune Linding*, Lars Juhl Jensen*, Gerard J. Ostheimer*, Marcel A.T.M. van Vugt, Claus JГёrgensen, Ioana M. Miron, Francesca Diella, Karen Colwill, Lorne Taylor, Kelly Elder, Pavel Metalnikov, Vivian Nguyen, Adrian Pasculescu, Jing Jin, Jin Gyoon Park, Leona D. Samson, James R. Woodgett, Robert B. Russell, Peer Bork, Michael B. Yaffe and Tony Pawson. Systematic Discovery of In Vivo Phosphorylation Networks. Cell, 129, 7, June 29, 2007. Linding et al., Systematic
Discovery of In Vivo Phosphorylation Networks, Cell (2007),doi:10.1016/j.cell.2007.05.052
[* These authors contributed equally.]
Contact: Nikki Luscombe
Samuel Lunenfeld Research Institute
"Thousands of proteins can be changed (via phosphorylation) but until now, it has not been possible to know which protein has made the change," states Dr. Tony Pawson, distinguished investigator at the Lunenfeld.
Proteins are the functional agents that carry out processes in a cell. But they rarely act alone. Instead they accomplish their effects as part of big networks. How proteins interact in these networks often depends on phosphorylation, the addition of a phosphate at specific sites on a protein. Kinases are proteins that bring about the phosphorylation of other proteins and in this way regulate cellular processes.
"By getting a network-wide view, multiple aberrant genes of kinase-controlled processes are more easily targeted," states Dr. Rune Linding, postdoctoral fellow, Samuel Lunenfeld Research Institute. "In the future, the treatment of complex human diseases will be treated by targeting multiple genes." Complex diseases like cancer often contain defects in several processes controlled by kinases.
"It works a bit like getting a recommendation from Amazon," says Dr. Peer Bork, group leader at EMBL. "The fact that certain books have been bought by the same customers tells you that they have something in common. In the same way biological networks tell us about shared features between different proteins. These help us predicting which kinases are likely to act on them."
Samuel Lunenfeld Research Institute
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre, established in 1985, is one of the world's leading centres in biomedical research. 32 principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit mshri.on.ca/
EMBL
The European Molecular Biology Laboratory is a basic research institute funded by public research monies from 19 member states (Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Israel, Italy, the Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and the United Kingdom). Research at EMBL is conducted by approximately 80 independent groups covering the spectrum of molecular biology. The Laboratory has five units: the main Laboratory in Heidelberg, and Outstations in Hinxton (the European Bioinformatics Institute), Grenoble, Hamburg, and Monterotondo near Rome. The cornerstones of EMBL's mission are: to perform basic research in molecular biology; to train scientists, students and visitors at all levels; to offer vital services to scientists in the member states; to develop new instruments and methods in the life sciences and to actively engage in technology transfer activities. EMBL's International PhD Programme has a student body of about 170. The Laboratory also sponsors an active Science and Society programme. Visitors from the press and public are welcome.
Source Article:
Rune Linding*, Lars Juhl Jensen*, Gerard J. Ostheimer*, Marcel A.T.M. van Vugt, Claus JГёrgensen, Ioana M. Miron, Francesca Diella, Karen Colwill, Lorne Taylor, Kelly Elder, Pavel Metalnikov, Vivian Nguyen, Adrian Pasculescu, Jing Jin, Jin Gyoon Park, Leona D. Samson, James R. Woodgett, Robert B. Russell, Peer Bork, Michael B. Yaffe and Tony Pawson. Systematic Discovery of In Vivo Phosphorylation Networks. Cell, 129, 7, June 29, 2007. Linding et al., Systematic
Discovery of In Vivo Phosphorylation Networks, Cell (2007),doi:10.1016/j.cell.2007.05.052
[* These authors contributed equally.]
Contact: Nikki Luscombe
Samuel Lunenfeld Research Institute
среда, 8 июня 2011 г.
Texas Center For Cancer Nanomedicine Targets Two Tough Cancers
A $16-million, five-year grant by the National Cancer Institute's nanomedicine initiative blends the expertise of five research institutions to focus an array of innovative nanotechnologies on improving the outcome of patients with ovarian or pancreatic cancers.
The Texas Center for Cancer Nanomedicine, an NCI Center for Nanotechnology Excellence funded by the grant assembles researchers from The University of Texas MD Anderson Cancer Center, The University of Texas Health Science Center at Houston (UTHealth), The Methodist Hospital Research Institute, Rice University and Albert Einstein College of Medicine In New York.
Team members have developed nanoparticles made from a variety of substances that hold potential for medical use, including gold, silicon, tiny balls of fat called nanoliposomes and chitosan, which is derived from crustacean shells. A nanometer is one billionth of a meter. Nanoparticles are engineered materials that are 100 nanometers or less in size the scale where most biological functions occur.
The TCCN anticipates launching clinical trials of its nanomedicine therapies 24 months after the center opens. The grant from the NCI Alliance for Nanotechnology in Cancer will not fund the clinical trials.
"We believe our team of internationally recognized scientists will push the boundaries of cancer therapy and diagnosis, starting with two cancers that are among the hardest to detect and the most difficult to treat," said Anil Sood, M.D., professor in MD Anderson's departments of Gynecologic Oncology and Cancer Biology, one of four principal investigators.
Sood, David Gorenstein, Ph.D., deputy director of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth, Gabriel Lopez-Berestein, M.D., professor of Experimental Therapeutics at MD Anderson, and Mauro Ferrari, Ph.D., president and CEO of The Methodist Hospital Research Institute, are co-principal investigators of the center.
Ovarian cancer is the fourth-leading cause of cancer death among women. The NCI estimates 13,850 will die of the disease in 2010. Pancreatic cancer is the fifth-leading cause of cancer death, with 36,800 expected fatalities this year. There is no early detection strategy for either disease.
"Our understanding of the natural and physical barriers that impede development of drugs guides the advancement of our nanomedicine approaches for the prevention and personalized treatment of cancer," said Lopez-Berestein, who pioneered the field of nanomedicine in 1995 with a version of the antifungal drug amphotericin B encapsulated in a liposomal nanoparticle.
Nanoparticle Platforms
Gold nanoparticles for therapeutic and diagnostic use, Jennifer West, Ph.D., Rice University
Hollow gold nanoparticles, Chun Li, Ph.D., MD Anderson
Mesoporous silicon nanoparticles for multistage carriers and proteomic nanochips, Mauro Ferrari, Ph.D., Methodist Research Institute
Thioaptamer constructs, David Gorenstein, Ph.D., UTHealth
Neutral nanoliposomes, chitosan and rHDL nanoparticles, Anil Sood, M.D., and Gabriel Lopez-Berestein, M.D., MD Anderson
Nanoassemblies and phage display, Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D.
"This is a triumph of the multi-institutional collaborations fostered and developed over several years with the Alliance for NanoHealth in Houston," said Ferrari, who is president of the alliance of Houston-area research institutions. "It's the fifth large center we've been able to fund in the last four years. This unparalleled success speaks volumes about the primacy of Houston-area institutions in both cancer and nanotechnology, and our ability to work together."
In addition to being accomplished developers of nanoparticles, the team also has expertise in research about and treatment of pancreatic and ovarian cancers, drug development, moving ideas from the lab to clinical trials (translational research), as well as entrepreneurial experience forming local spin-off companies and working with existing pharmaceutical and biotech companies to broadly distribute new therapies.
Center researchers have an extensive record of collaboration among themselves and strong connections to other nanotechnology experts.
"We know each other's strengths, we understand each other's roles, we trust each other, we've taken years to form the complete team that can bridge the laboratories to the clinic, and we're unanimously focused on clinical translation," said Gorenstein, who also is associate dean for research at the UTHealth Medical School.
Because all of the TCCN's nanotechnologies are delivery platforms, the impact of the center's research is likely to reach beyond cancer.
Center research is divided into four projects, with scientists from multiple institutions using a variety of nanoparticles in each.
1) Multiple-stage delivery systems that can efficiently put drugs or small interfering RNA in ovarian cancers and the blood vessels that support them. This project also includes development of a sensitive imaging approach and proteomic nanochips to monitor response to treatment.
2) Highly targeted therapeutic nanoparticles designed specifically to hit the blood vessels that support ovarian cancer tumors using novel thioaptamer and peptide targeting agents. Two nanotechnologies will be deployed пїЅ" one that delivers siRNA to silence target genes and another that will permit the burning of blood vessels with near-infrared laser light.
3) Nanoparticles that can penetrate or destroy connective tissues that are abundant in pancreatic cancer tumors and block destruction of cancerous cells. Three types of nanoparticles and two types of targeting agents will be used against the fibrous material. Nanoparticles also will be tested as preventive agents to reverse conditions that nurture cancer formation and as a method of early detection.
4) Multifunctional nanoassemblies capable of treating neuroendocrine pancreatic tumors by homing in on a specific vascular address marking the blood vessels that feed the tumor and then delivering smaller nanoparticles to either treat or image the malignancy.
TCCN also includes four core programs that support the researchers with targeting expertise, biomathematics, nanoengineering and administration.
Jennifer West, Ph.D., professor and chair of Rice University's Department of Bioengineering, Paolo Decuzzi, Ph.D., senior member and co-director of Methodist Research Institute's Department of Nanomedicine, Craig Logsdon, Ph.D., professor in MD Anderson's Department of Cancer Biology, and Wadih Arap, M.D., Ph.D. of MD Anderson's David H. Koch Center serve as project or core leaders of the TCCN. Paolo Decuzzi (Methodist),
Investigators on this project are also affiliated with MD Anderson's Center for RNA Interference and Non-Coding RNAs, the first such center in the United States, which is designed to foster multidisciplinary and multi-institutional collaboration.
Rahul Mitra, director of the molecular markers program in MD Anderson's Department of Gynecologic Oncology, is director of the TCCN.
Source: University of Texas M. D. Anderson Cancer Center
The Texas Center for Cancer Nanomedicine, an NCI Center for Nanotechnology Excellence funded by the grant assembles researchers from The University of Texas MD Anderson Cancer Center, The University of Texas Health Science Center at Houston (UTHealth), The Methodist Hospital Research Institute, Rice University and Albert Einstein College of Medicine In New York.
Team members have developed nanoparticles made from a variety of substances that hold potential for medical use, including gold, silicon, tiny balls of fat called nanoliposomes and chitosan, which is derived from crustacean shells. A nanometer is one billionth of a meter. Nanoparticles are engineered materials that are 100 nanometers or less in size the scale where most biological functions occur.
The TCCN anticipates launching clinical trials of its nanomedicine therapies 24 months after the center opens. The grant from the NCI Alliance for Nanotechnology in Cancer will not fund the clinical trials.
"We believe our team of internationally recognized scientists will push the boundaries of cancer therapy and diagnosis, starting with two cancers that are among the hardest to detect and the most difficult to treat," said Anil Sood, M.D., professor in MD Anderson's departments of Gynecologic Oncology and Cancer Biology, one of four principal investigators.
Sood, David Gorenstein, Ph.D., deputy director of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth, Gabriel Lopez-Berestein, M.D., professor of Experimental Therapeutics at MD Anderson, and Mauro Ferrari, Ph.D., president and CEO of The Methodist Hospital Research Institute, are co-principal investigators of the center.
Ovarian cancer is the fourth-leading cause of cancer death among women. The NCI estimates 13,850 will die of the disease in 2010. Pancreatic cancer is the fifth-leading cause of cancer death, with 36,800 expected fatalities this year. There is no early detection strategy for either disease.
"Our understanding of the natural and physical barriers that impede development of drugs guides the advancement of our nanomedicine approaches for the prevention and personalized treatment of cancer," said Lopez-Berestein, who pioneered the field of nanomedicine in 1995 with a version of the antifungal drug amphotericin B encapsulated in a liposomal nanoparticle.
Nanoparticle Platforms
Gold nanoparticles for therapeutic and diagnostic use, Jennifer West, Ph.D., Rice University
Hollow gold nanoparticles, Chun Li, Ph.D., MD Anderson
Mesoporous silicon nanoparticles for multistage carriers and proteomic nanochips, Mauro Ferrari, Ph.D., Methodist Research Institute
Thioaptamer constructs, David Gorenstein, Ph.D., UTHealth
Neutral nanoliposomes, chitosan and rHDL nanoparticles, Anil Sood, M.D., and Gabriel Lopez-Berestein, M.D., MD Anderson
Nanoassemblies and phage display, Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D.
"This is a triumph of the multi-institutional collaborations fostered and developed over several years with the Alliance for NanoHealth in Houston," said Ferrari, who is president of the alliance of Houston-area research institutions. "It's the fifth large center we've been able to fund in the last four years. This unparalleled success speaks volumes about the primacy of Houston-area institutions in both cancer and nanotechnology, and our ability to work together."
In addition to being accomplished developers of nanoparticles, the team also has expertise in research about and treatment of pancreatic and ovarian cancers, drug development, moving ideas from the lab to clinical trials (translational research), as well as entrepreneurial experience forming local spin-off companies and working with existing pharmaceutical and biotech companies to broadly distribute new therapies.
Center researchers have an extensive record of collaboration among themselves and strong connections to other nanotechnology experts.
"We know each other's strengths, we understand each other's roles, we trust each other, we've taken years to form the complete team that can bridge the laboratories to the clinic, and we're unanimously focused on clinical translation," said Gorenstein, who also is associate dean for research at the UTHealth Medical School.
Because all of the TCCN's nanotechnologies are delivery platforms, the impact of the center's research is likely to reach beyond cancer.
Center research is divided into four projects, with scientists from multiple institutions using a variety of nanoparticles in each.
1) Multiple-stage delivery systems that can efficiently put drugs or small interfering RNA in ovarian cancers and the blood vessels that support them. This project also includes development of a sensitive imaging approach and proteomic nanochips to monitor response to treatment.
2) Highly targeted therapeutic nanoparticles designed specifically to hit the blood vessels that support ovarian cancer tumors using novel thioaptamer and peptide targeting agents. Two nanotechnologies will be deployed пїЅ" one that delivers siRNA to silence target genes and another that will permit the burning of blood vessels with near-infrared laser light.
3) Nanoparticles that can penetrate or destroy connective tissues that are abundant in pancreatic cancer tumors and block destruction of cancerous cells. Three types of nanoparticles and two types of targeting agents will be used against the fibrous material. Nanoparticles also will be tested as preventive agents to reverse conditions that nurture cancer formation and as a method of early detection.
4) Multifunctional nanoassemblies capable of treating neuroendocrine pancreatic tumors by homing in on a specific vascular address marking the blood vessels that feed the tumor and then delivering smaller nanoparticles to either treat or image the malignancy.
TCCN also includes four core programs that support the researchers with targeting expertise, biomathematics, nanoengineering and administration.
Jennifer West, Ph.D., professor and chair of Rice University's Department of Bioengineering, Paolo Decuzzi, Ph.D., senior member and co-director of Methodist Research Institute's Department of Nanomedicine, Craig Logsdon, Ph.D., professor in MD Anderson's Department of Cancer Biology, and Wadih Arap, M.D., Ph.D. of MD Anderson's David H. Koch Center serve as project or core leaders of the TCCN. Paolo Decuzzi (Methodist),
Investigators on this project are also affiliated with MD Anderson's Center for RNA Interference and Non-Coding RNAs, the first such center in the United States, which is designed to foster multidisciplinary and multi-institutional collaboration.
Rahul Mitra, director of the molecular markers program in MD Anderson's Department of Gynecologic Oncology, is director of the TCCN.
Source: University of Texas M. D. Anderson Cancer Center
вторник, 7 июня 2011 г.
Moss-In-Prisons Project Helps Promote Sustainable Living
Nalini Nadkarni of Evergreen State College currently advises a team of researchers who sport shaved heads, tattooed biceps and prison-issued garb rather than the lab coats and khakis typically worn by researchers. Why is Nadkarni's team composed of such apparently iconoclastic researchers? Because all of her researchers are inmates at Cedar Creek Corrections Center, a medium security prison in Littlerock, Washington.
With partial funding from the National Science Foundation (NSF), Nadkarni has guided her unlikely but productive team of researchers since 2004, as they conduct experiments to identify the best ways to cultivate slow-growing mosses. Nadkarni's so-called Moss-in-Prisons project is designed to help ecologists replace large quantities of ecologically important mosses that are regularly illegally stripped from Pacific Northwest forests by horticulturalists.
Why did Nadkarni recruit inmates into her research team? "Because," she explains, "I need help from people who have long periods of time available to observe and measure the growing mosses; access to extensive space to lay out flats of plants; and fresh minds to put forward innovative solutions."
In addition to managing the Moss-in-Prisons research at Cedar Creek, Nadkarni helps the facility's inmates run various projects that promote sustainable living--including an organic garden that produces 15,000 pounds of fresh vegetables every summer, a bee-keeping operation and a composting operation that processes one ton of food per month.
One member of Nadkarni's research team, who was released from Cedar Creek, enrolled in a Ph.D. program in microbiology at the University of Nevada and presented his Cedar Creek research at the annual meeting of the Ecological Society of America in August 2008.
Nadkarni started the Moss-in-Prisons project with a type of NSF award that is specially designed to help scientists reach out to public audiences. More recently, she has received additional funding from the Washington State Department of Corrections.
In addition, Nadkarni has creatively stretched project resources by recruiting other NSF-funded researchers to contribute to a popular lecture series that she started at Cedar Creek. By giving such lectures, these scientists fulfill requirements for conducting public outreach that accompany NSF awards.
A recent TV news report about the Moss-in-Prisons and the sustainability projects at Cedar Creek is posted at kcts9/video/green-prison-reform.
Source: Lily Whiteman
National Science Foundation
With partial funding from the National Science Foundation (NSF), Nadkarni has guided her unlikely but productive team of researchers since 2004, as they conduct experiments to identify the best ways to cultivate slow-growing mosses. Nadkarni's so-called Moss-in-Prisons project is designed to help ecologists replace large quantities of ecologically important mosses that are regularly illegally stripped from Pacific Northwest forests by horticulturalists.
Why did Nadkarni recruit inmates into her research team? "Because," she explains, "I need help from people who have long periods of time available to observe and measure the growing mosses; access to extensive space to lay out flats of plants; and fresh minds to put forward innovative solutions."
In addition to managing the Moss-in-Prisons research at Cedar Creek, Nadkarni helps the facility's inmates run various projects that promote sustainable living--including an organic garden that produces 15,000 pounds of fresh vegetables every summer, a bee-keeping operation and a composting operation that processes one ton of food per month.
One member of Nadkarni's research team, who was released from Cedar Creek, enrolled in a Ph.D. program in microbiology at the University of Nevada and presented his Cedar Creek research at the annual meeting of the Ecological Society of America in August 2008.
Nadkarni started the Moss-in-Prisons project with a type of NSF award that is specially designed to help scientists reach out to public audiences. More recently, she has received additional funding from the Washington State Department of Corrections.
In addition, Nadkarni has creatively stretched project resources by recruiting other NSF-funded researchers to contribute to a popular lecture series that she started at Cedar Creek. By giving such lectures, these scientists fulfill requirements for conducting public outreach that accompany NSF awards.
A recent TV news report about the Moss-in-Prisons and the sustainability projects at Cedar Creek is posted at kcts9/video/green-prison-reform.
Source: Lily Whiteman
National Science Foundation
понедельник, 6 июня 2011 г.
Freshwater Pollution Revealed By Diatoms
Researchers in India have demonstrated that microscopic aquatic creatures could be used as the ecological equivalent of a canary in a coalmine for assessing inland freshwater lakes and ponds. Writing in the World Review of Science, Technology and Sustainable Development the team explains how diatoms respond badly to pollutants and sewage contamination.
Bijaya Kumar Padhi, Jnanendra Rath, and Pratap Kumar Padhy of the Visva-Bharati University, in Santiniketan, India, have looked at the ecological responses of diatoms to pollution and nutrient enrichment, caused by domestic and municipal sewage, in five freshwater ponds. Absent diatom species were present in some heavily polluted lakes, while raised levels of nutrients boost numbers of other species. They suggest that a Biological Index for Diatoms could be used as a simple biological method for monitoring water quality that avoids the need for sophisticated chemical analysis.
Rapid urbanization and economic development have resulted in unfavorable changes in the hydrology and ecology of freshwater systems, which are felt most acutely in the developing world. The researchers explain that the remediation and protection of freshwater ecosystems is increasingly important but water quality management requires reliable long-term data on water quality and how remediation work affects the water. Moreover, information about natural, baseline, conditions in undisturbed ponds, lakes and rivers is needed against which polluted bodies of water undergoing remediation might be gauged.
Natural changes in environmental conditions, such as flow rate, water temperature, dissolved oxygen, and food resources exert direct control on the population dynamics of aquatic organisms, which gives rise to characteristic biological communities within different ecosystems. However, pollution and other human activities also disturb these community profiles significantly and so can provide such a measure.
Diatoms are important contributors to the primary production in aquatic ecosystems, sitting at the bottom of the food chain. They are eukaryotic algae, commonly unicellular, although they do exist as filamentous colonies and are good indicators of the environmental integrity, the researchers explain. They have several advantages over other indicators, the team adds.
First, they are readily dispersed and can invade a variety of habitats. They are relatively easy to sample and such sampling has negligible impact on the ecosystem during collection. Their "response" time to variation in environmental conditions lies between bacteria (change hourly) and bigger invertebrates (change over the course of months). Finally, diatoms are sensitive to very subtle changes in environmental conditions and/or disturbances that may not visibly affect other communities, or may only affect other communities at greater levels of disturbance.
The team's evaluation of diatom monitoring of five freshwater bodies was consistent with more conventional physical and chemical determinations carried out in parallel. Diatoms usually grow better in unpolluted ponds and streams and this preliminary investigation suggests that they could be useful for biological monitoring of pollution levels and ecosystem integrity in the short and potentially in the long-term once seasonal studies confirm the preliminary results.
"Diatoms for assessing the ecological condition of inland freshwater bodies" in World Review of Science, Technology and Sustainable Development, 2010, 7, 352-359
Source:
Pratap Kumar Padhy
Inderscience Publishers
Bijaya Kumar Padhi, Jnanendra Rath, and Pratap Kumar Padhy of the Visva-Bharati University, in Santiniketan, India, have looked at the ecological responses of diatoms to pollution and nutrient enrichment, caused by domestic and municipal sewage, in five freshwater ponds. Absent diatom species were present in some heavily polluted lakes, while raised levels of nutrients boost numbers of other species. They suggest that a Biological Index for Diatoms could be used as a simple biological method for monitoring water quality that avoids the need for sophisticated chemical analysis.
Rapid urbanization and economic development have resulted in unfavorable changes in the hydrology and ecology of freshwater systems, which are felt most acutely in the developing world. The researchers explain that the remediation and protection of freshwater ecosystems is increasingly important but water quality management requires reliable long-term data on water quality and how remediation work affects the water. Moreover, information about natural, baseline, conditions in undisturbed ponds, lakes and rivers is needed against which polluted bodies of water undergoing remediation might be gauged.
Natural changes in environmental conditions, such as flow rate, water temperature, dissolved oxygen, and food resources exert direct control on the population dynamics of aquatic organisms, which gives rise to characteristic biological communities within different ecosystems. However, pollution and other human activities also disturb these community profiles significantly and so can provide such a measure.
Diatoms are important contributors to the primary production in aquatic ecosystems, sitting at the bottom of the food chain. They are eukaryotic algae, commonly unicellular, although they do exist as filamentous colonies and are good indicators of the environmental integrity, the researchers explain. They have several advantages over other indicators, the team adds.
First, they are readily dispersed and can invade a variety of habitats. They are relatively easy to sample and such sampling has negligible impact on the ecosystem during collection. Their "response" time to variation in environmental conditions lies between bacteria (change hourly) and bigger invertebrates (change over the course of months). Finally, diatoms are sensitive to very subtle changes in environmental conditions and/or disturbances that may not visibly affect other communities, or may only affect other communities at greater levels of disturbance.
The team's evaluation of diatom monitoring of five freshwater bodies was consistent with more conventional physical and chemical determinations carried out in parallel. Diatoms usually grow better in unpolluted ponds and streams and this preliminary investigation suggests that they could be useful for biological monitoring of pollution levels and ecosystem integrity in the short and potentially in the long-term once seasonal studies confirm the preliminary results.
"Diatoms for assessing the ecological condition of inland freshwater bodies" in World Review of Science, Technology and Sustainable Development, 2010, 7, 352-359
Source:
Pratap Kumar Padhy
Inderscience Publishers
воскресенье, 5 июня 2011 г.
Atherosclerosis, Weight Gain Could Be Reduced By Lipoic Acid
A new study done with mice has discovered that supplements of lipoic acid can inhibit formation of arterial lesions, lower triglycerides, and reduce blood vessel inflammation and weight gain - all key issues for addressing cardiovascular disease.
Although the results cannot be directly extrapolated beyond the laboratory, researchers report that "they strongly suggest that lipoic acid supplementation may be useful as an inexpensive but effective intervention strategy . . . reducing known risk factors for the development of atherosclerosis and other inflammatory vascular diseases in humans."
The findings were made by scientists from the Linus Pauling Institute and College of Veterinary Medicine at Oregon State University, and the Department of Medicine at the University of Washington. They were just published in Circulation, a journal of the American Heart Association.
Heart disease is the leading cause of death in the United States.
The study found that lipoic acid supplements reduced atherosclerotic lesion formation in two types of mice that are widely used to study cardiovascular disease, by 55 percent and 40 percent, respectively. The supplements were also associated with almost 40 percent less body weight gain, and lower levels of triglycerides in very low-density lipoproteins.
As a result, the authors concluded that "lipoic acid may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases."
"We are excited about these results, particularly since the supplements of lipoic acid appear to provide several different mechanisms to improve cardiovascular health," said Balz Frei, professor and director of the Linus Pauling Institute. "They are helping in a fundamental way to reset and normalize metabolic processes, in ways that could help address one of the most significant health problems in the Western world.
"These findings also reinforce the need for more comprehensive human studies," Frei said. "That will be the next step in our research, in double-blind, randomized, clinical studies during the next five years with Oregon Health and Science University."
Alpha lipoic acid is a naturally occurring nutrient found at low levels in green leafy vegetables, potatoes and meats, especially organ meats such as kidney, heart or liver. The amounts used in this research would not be obtainable by any normal diet, researchers said, and for human consumption might equate to supplements of about 2,000 milligrams per day. Even at low, normal, dietary levels, the compound can play a key role in energy metabolism.
Atherosclerosis, or what used to be called "hardening of the arteries," is a long-term process that is now seen as a chronic inflammatory disease, which begins when certain types of white blood cells called monocytes bind to "adhesion molecules" on the walls of arteries. This in turn allows the monocytes to enter the arterial wall, there they become inflammatory macrophages that, in the presence of low density lipoprotein, or LDL, can transform into lipid-laden foam cells - ultimately, an arterial fat deposit.
This chronic process often begins during adolescence, can continue for a lifetime, and has been linked to obesity, poor diet, lack of exercise, diabetes, high blood pressure, genetic predisposition and other causes. The fatty deposits in arteries can ultimately trigger a heart attack or stroke.
Researchers now believe that high levels of alpha lipoic acid can be particularly useful in preventing this process, by inhibiting the formation of the adhesion molecules. It can also lower triglycerides, another important risk factor for cardiovascular disease. It may also function as an antioxidant, and helps to normalize insulin signaling and glucose metabolism.
"From what we understand, this supplement would be most valuable as a preventive mechanism before people have advanced cardiovascular disease," Frei said. "However, it may help retard the process at any stage, and may also be of value in treating diabetic complications."
Also of considerable interest, Frei said, is the apparent role of lipoic acid supplementation in reducing weight gain. It appears to have this effect both through appetite suppression, an enhanced metabolic rate, and - at least in laboratory animals - has been shown to stimulate higher levels of physical activity, which again would increase caloric expenditure and further reduce weight.
Mice given lipoic acid supplements simply chose to eat less than a control group that did not receive supplements, suggesting a reduced appetite. In another test, mice that received supplements gained less weight than other mice in a control group that were given identical amounts to eat, suggesting a higher metabolic rate and enhanced activity levels.
Weight gain and obesity is a major risk factor for atherosclerosis and heart disease, and lower weight and abdominal fat may be one of the mechanisms by which lipoic acid has beneficial effects, Frei said. The study concluded that "lipoic acid supplementation may be a promising approach to prevent weight gain and to lower cardiovascular disease risk in humans."
Although some of the most compelling research with lipoic acid research has been done in mouse models, scientists say, there should be a reasonable extrapolation to humans, because the lipoprotein profile is similar, as well as the composition of the atherosclerotic lesions. These mouse models are routinely used in studies of human atherosclerosis.
This research was supported by the National Institutes of Health and the National Center for Complementary and Alternative Medicine.
By David Stauth
Source: Balz Frei
Oregon State University
Although the results cannot be directly extrapolated beyond the laboratory, researchers report that "they strongly suggest that lipoic acid supplementation may be useful as an inexpensive but effective intervention strategy . . . reducing known risk factors for the development of atherosclerosis and other inflammatory vascular diseases in humans."
The findings were made by scientists from the Linus Pauling Institute and College of Veterinary Medicine at Oregon State University, and the Department of Medicine at the University of Washington. They were just published in Circulation, a journal of the American Heart Association.
Heart disease is the leading cause of death in the United States.
The study found that lipoic acid supplements reduced atherosclerotic lesion formation in two types of mice that are widely used to study cardiovascular disease, by 55 percent and 40 percent, respectively. The supplements were also associated with almost 40 percent less body weight gain, and lower levels of triglycerides in very low-density lipoproteins.
As a result, the authors concluded that "lipoic acid may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases."
"We are excited about these results, particularly since the supplements of lipoic acid appear to provide several different mechanisms to improve cardiovascular health," said Balz Frei, professor and director of the Linus Pauling Institute. "They are helping in a fundamental way to reset and normalize metabolic processes, in ways that could help address one of the most significant health problems in the Western world.
"These findings also reinforce the need for more comprehensive human studies," Frei said. "That will be the next step in our research, in double-blind, randomized, clinical studies during the next five years with Oregon Health and Science University."
Alpha lipoic acid is a naturally occurring nutrient found at low levels in green leafy vegetables, potatoes and meats, especially organ meats such as kidney, heart or liver. The amounts used in this research would not be obtainable by any normal diet, researchers said, and for human consumption might equate to supplements of about 2,000 milligrams per day. Even at low, normal, dietary levels, the compound can play a key role in energy metabolism.
Atherosclerosis, or what used to be called "hardening of the arteries," is a long-term process that is now seen as a chronic inflammatory disease, which begins when certain types of white blood cells called monocytes bind to "adhesion molecules" on the walls of arteries. This in turn allows the monocytes to enter the arterial wall, there they become inflammatory macrophages that, in the presence of low density lipoprotein, or LDL, can transform into lipid-laden foam cells - ultimately, an arterial fat deposit.
This chronic process often begins during adolescence, can continue for a lifetime, and has been linked to obesity, poor diet, lack of exercise, diabetes, high blood pressure, genetic predisposition and other causes. The fatty deposits in arteries can ultimately trigger a heart attack or stroke.
Researchers now believe that high levels of alpha lipoic acid can be particularly useful in preventing this process, by inhibiting the formation of the adhesion molecules. It can also lower triglycerides, another important risk factor for cardiovascular disease. It may also function as an antioxidant, and helps to normalize insulin signaling and glucose metabolism.
"From what we understand, this supplement would be most valuable as a preventive mechanism before people have advanced cardiovascular disease," Frei said. "However, it may help retard the process at any stage, and may also be of value in treating diabetic complications."
Also of considerable interest, Frei said, is the apparent role of lipoic acid supplementation in reducing weight gain. It appears to have this effect both through appetite suppression, an enhanced metabolic rate, and - at least in laboratory animals - has been shown to stimulate higher levels of physical activity, which again would increase caloric expenditure and further reduce weight.
Mice given lipoic acid supplements simply chose to eat less than a control group that did not receive supplements, suggesting a reduced appetite. In another test, mice that received supplements gained less weight than other mice in a control group that were given identical amounts to eat, suggesting a higher metabolic rate and enhanced activity levels.
Weight gain and obesity is a major risk factor for atherosclerosis and heart disease, and lower weight and abdominal fat may be one of the mechanisms by which lipoic acid has beneficial effects, Frei said. The study concluded that "lipoic acid supplementation may be a promising approach to prevent weight gain and to lower cardiovascular disease risk in humans."
Although some of the most compelling research with lipoic acid research has been done in mouse models, scientists say, there should be a reasonable extrapolation to humans, because the lipoprotein profile is similar, as well as the composition of the atherosclerotic lesions. These mouse models are routinely used in studies of human atherosclerosis.
This research was supported by the National Institutes of Health and the National Center for Complementary and Alternative Medicine.
By David Stauth
Source: Balz Frei
Oregon State University
суббота, 4 июня 2011 г.
Diversification Trajectories And Evolutionary Life-history Traits In Early Sharks And Batoids
The timing of the early diversification of modern sharks and batoids (Neoselachii) is crucial to understand their early evolutionary history.
However, different concepts of this timing exist, which are related to discrepancies in taxonomic and phylogenetic interpretations. Statistic analyses performed in this study show that a burst in neoselachian diversity occurred very early ca.
180 Myr ago representing the first maximum diversification event in their evolutionary history. Reasons for this early and rapid diversification and radiation include small body sizes, short life spans and oviparity enabling faster ecological reorganizations and innovations in body plans for adapting to changing environmental conditions.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
However, different concepts of this timing exist, which are related to discrepancies in taxonomic and phylogenetic interpretations. Statistic analyses performed in this study show that a burst in neoselachian diversity occurred very early ca.
180 Myr ago representing the first maximum diversification event in their evolutionary history. Reasons for this early and rapid diversification and radiation include small body sizes, short life spans and oviparity enabling faster ecological reorganizations and innovations in body plans for adapting to changing environmental conditions.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
пятница, 3 июня 2011 г.
Turning Off Mutated Gene Causes Cancers In Mice To Self-Destruct, Stanford Researchers Find
Killing cancerous tumors isn't easy, as anyone who has suffered through chemotherapy can attest. But a new study in mice shows that switching off a single malfunctioning gene can halt the limitless division of tumor cells and turn them back to the path of their own planned obsolescence.
The surprising possibility that a cell's own natural mechanism for ensuring its mortality could be used to vanquish tumors opens the door to a new approach to developing drugs to treat cancer patients, according to Dean Felsher, MD, PhD, associate professor of medicine (oncology) and of pathology at the Stanford University School of Medicine. Felsher is the senior author of the study published in the advance online version of the Proceedings of the National Academy of Sciences.
"Our research implies that by shutting off a critical cancer gene, tumor cells can realize that they are broken and restore this physiologic fail-safe program," said Felsher.
Cancer can be notoriously resistant to medical treatment. Not only do cancer cells proliferate uncontrollably, they somehow circumvent the mechanism that causes normal cells to die when they get old or malfunction. That makes cancer cells effectively immortal unless doctors manage to squelch them.
The gene Felsher's team studied produces a protein called Myc (pronounced "mick"), which promotes cell division. A mutation of the gene causes cells to overproduce the protein, prompting perpetual cell division and tumor growth. By turning off the mutated gene, the researchers found that not only did uncontrolled cell division cease, but the cells also reactivated a normal physiological mechanism, called senescence, which makes it possible for a cell to eventually die.
"What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all," said Felsher. Cancer researchers had long thought the senescence process had to be irreversibly disrupted for a tumor to develop.
The researchers worked with a series of mice engineered to have Myc-triggered cancers of either the liver, blood or bones, along with a specially constructed version of the Myc gene that they could switch off by feeding the mice antibiotics. When the mice dined on doses of the drugs, invariably, the tumors ceased growing and then diminished, with some disappearing over the course of just a few days.
Although Felsher's lab had previously shown that mouse tumors diminished and disappeared when Myc was switched off, they hadn't been sure how the process actually worked. Historically, most research involving genetic methods of battling cancer cells has focused on reactivating genes called tumor-suppressor genes, which are generally overcome by a proliferating cancer. No one had explored the idea that senescence might play a key role in diminishing tumors.
Felsher described senescence as acting like a fail-safe mechanism to stop cancer. When a cell detects a deleterious mutation, it launches the senescence process, resulting in the permanent loss of the cell's ability to proliferate, thus halting any cancer.
"In order to become tumor cells, those cells have to overcome senescence," said Chi-Hwa Wu, PhD, postdoctoral researcher in Felsher's lab and first author of the study. Wu had the inspiration to explore whether the sudden diminishment they had observed in the tumors might be due to the reactivation of some latent remnant of the trigger for senescence.
Through a series of experiments looking at enzymes associated with the senescence process, as well as some molecular markers, Wu confirmed her suspicion. And not only was senescence occurring in cells that had been thought to be incapable of it, the process was reactivated in all the different tumors they studied.
Consider it a cell version of the Jekyll-and-Hyde transformation. "It's sort of like Mr. Hyde realizing that there's something wrong with him and then being able to put himself back into his normal state as Dr. Jekyll," Felsher said.
In addition to the deepened understanding of how the process of senescence works, Felsher and Wu see a lot of potential for new approaches to treating cancer, beyond the traditional tactic of trying to kill cancer cells directly. "This work implies that maybe part of the strategy should involve figuring out how to get the cancer cells to just be allowed to do what they originally wanted to do anyway, which is to not be proliferating endlessly and growing uncontrolled," said Felsher.
The next step for the team is to see how well the approach works in human cancer cells. "And we're also trying to figure out what the mechanism is," Felsher said. "What are the molecular mechanisms of this, so that we can figure out how to better treat cancer""
Other authors on the research paper are Jan van Riggelen, PhD, postdoctoral researcher; Alper Yetil, graduate student in cancer biology; Alice Fan, MD, instructor in medicine (oncology), and medical student Pavan Bachireddy.
The study was funded by the National Cancer Institute, the National Institutes of Health, the Leukemia and Lymphoma Society, the Burroughs Wellcome Fund, the Damon Runyon Lilly Clinical Investigator Award, the Lymphoma Research Foundation and the Howard Hughes Medical Institute.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford/.
Source: Lou Bergeron
Stanford University Medical Center
The surprising possibility that a cell's own natural mechanism for ensuring its mortality could be used to vanquish tumors opens the door to a new approach to developing drugs to treat cancer patients, according to Dean Felsher, MD, PhD, associate professor of medicine (oncology) and of pathology at the Stanford University School of Medicine. Felsher is the senior author of the study published in the advance online version of the Proceedings of the National Academy of Sciences.
"Our research implies that by shutting off a critical cancer gene, tumor cells can realize that they are broken and restore this physiologic fail-safe program," said Felsher.
Cancer can be notoriously resistant to medical treatment. Not only do cancer cells proliferate uncontrollably, they somehow circumvent the mechanism that causes normal cells to die when they get old or malfunction. That makes cancer cells effectively immortal unless doctors manage to squelch them.
The gene Felsher's team studied produces a protein called Myc (pronounced "mick"), which promotes cell division. A mutation of the gene causes cells to overproduce the protein, prompting perpetual cell division and tumor growth. By turning off the mutated gene, the researchers found that not only did uncontrolled cell division cease, but the cells also reactivated a normal physiological mechanism, called senescence, which makes it possible for a cell to eventually die.
"What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all," said Felsher. Cancer researchers had long thought the senescence process had to be irreversibly disrupted for a tumor to develop.
The researchers worked with a series of mice engineered to have Myc-triggered cancers of either the liver, blood or bones, along with a specially constructed version of the Myc gene that they could switch off by feeding the mice antibiotics. When the mice dined on doses of the drugs, invariably, the tumors ceased growing and then diminished, with some disappearing over the course of just a few days.
Although Felsher's lab had previously shown that mouse tumors diminished and disappeared when Myc was switched off, they hadn't been sure how the process actually worked. Historically, most research involving genetic methods of battling cancer cells has focused on reactivating genes called tumor-suppressor genes, which are generally overcome by a proliferating cancer. No one had explored the idea that senescence might play a key role in diminishing tumors.
Felsher described senescence as acting like a fail-safe mechanism to stop cancer. When a cell detects a deleterious mutation, it launches the senescence process, resulting in the permanent loss of the cell's ability to proliferate, thus halting any cancer.
"In order to become tumor cells, those cells have to overcome senescence," said Chi-Hwa Wu, PhD, postdoctoral researcher in Felsher's lab and first author of the study. Wu had the inspiration to explore whether the sudden diminishment they had observed in the tumors might be due to the reactivation of some latent remnant of the trigger for senescence.
Through a series of experiments looking at enzymes associated with the senescence process, as well as some molecular markers, Wu confirmed her suspicion. And not only was senescence occurring in cells that had been thought to be incapable of it, the process was reactivated in all the different tumors they studied.
Consider it a cell version of the Jekyll-and-Hyde transformation. "It's sort of like Mr. Hyde realizing that there's something wrong with him and then being able to put himself back into his normal state as Dr. Jekyll," Felsher said.
In addition to the deepened understanding of how the process of senescence works, Felsher and Wu see a lot of potential for new approaches to treating cancer, beyond the traditional tactic of trying to kill cancer cells directly. "This work implies that maybe part of the strategy should involve figuring out how to get the cancer cells to just be allowed to do what they originally wanted to do anyway, which is to not be proliferating endlessly and growing uncontrolled," said Felsher.
The next step for the team is to see how well the approach works in human cancer cells. "And we're also trying to figure out what the mechanism is," Felsher said. "What are the molecular mechanisms of this, so that we can figure out how to better treat cancer""
Other authors on the research paper are Jan van Riggelen, PhD, postdoctoral researcher; Alper Yetil, graduate student in cancer biology; Alice Fan, MD, instructor in medicine (oncology), and medical student Pavan Bachireddy.
The study was funded by the National Cancer Institute, the National Institutes of Health, the Leukemia and Lymphoma Society, the Burroughs Wellcome Fund, the Damon Runyon Lilly Clinical Investigator Award, the Lymphoma Research Foundation and the Howard Hughes Medical Institute.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford/.
Source: Lou Bergeron
Stanford University Medical Center
четверг, 2 июня 2011 г.
Identification Of Primary Driver Of Stomach Cancer Development
In a discovery that could lead to the development of new treatments for gastric cancer, scientists at the Melbourne Branch of the international Ludwig Institute for Cancer Research (LICR) have discovered what appears to be the primary driver of tumor development in the stomach. Results published on-line in the Journal of Clinical Investigation show that inhibiting the signaling cascade initiated by the IL-11 protein prevented the development of inflammation, hyperplasia (an abnormal increase in the number of cells) and tumor formation in pre-clinical models of gastric cancer.
Gastric cancer is the second most common cause of cancer-related deaths around the world, and has been shown previously to be correlated with chronic inflammation. Persistent activation of the Stat3 protein, which is known to play roles in inflammation-associated carcinogenesis, is commonly found in gastric and many other types of cancer. Until now, however, the underlying cause of hyperactive Stat3 was unknown. The current study demonstrates that IL-11 promotes chronic inflammation and associated tumorigenesis in the stomach by inducing excessive activation of Stat3. The study used both genetic and pharmacologic inhibitors to show that blocking this signaling pathway prevented or reduced tumorigenesis in a mouse model of inflammation-dependent human gastric cancer.
"Although we made this discovery in a mouse model, we expect it to be highly relevant to the clinic because of the striking similarity in gastric tumour development and appearance between mice and men," says the lead author of the study, Professor Matthias Ernst from the LICR Melbourne Branch. "The clear link between inhibition of IL-11/Stat3 activity and suppression of gastric tumorigenesis that we identified supports the further development of pharmacologic agents that target these molecules for the treatment of gastric and potentially other cancers. We believe that we have a very relevant model in our hand for the preclinical assessment of such compounds as well as for the identification of potential markers that may ultimately help in the early detection of disease.
Source: Sarah L. White, Ph.D.
Ludwig Institute for Cancer Research
Gastric cancer is the second most common cause of cancer-related deaths around the world, and has been shown previously to be correlated with chronic inflammation. Persistent activation of the Stat3 protein, which is known to play roles in inflammation-associated carcinogenesis, is commonly found in gastric and many other types of cancer. Until now, however, the underlying cause of hyperactive Stat3 was unknown. The current study demonstrates that IL-11 promotes chronic inflammation and associated tumorigenesis in the stomach by inducing excessive activation of Stat3. The study used both genetic and pharmacologic inhibitors to show that blocking this signaling pathway prevented or reduced tumorigenesis in a mouse model of inflammation-dependent human gastric cancer.
"Although we made this discovery in a mouse model, we expect it to be highly relevant to the clinic because of the striking similarity in gastric tumour development and appearance between mice and men," says the lead author of the study, Professor Matthias Ernst from the LICR Melbourne Branch. "The clear link between inhibition of IL-11/Stat3 activity and suppression of gastric tumorigenesis that we identified supports the further development of pharmacologic agents that target these molecules for the treatment of gastric and potentially other cancers. We believe that we have a very relevant model in our hand for the preclinical assessment of such compounds as well as for the identification of potential markers that may ultimately help in the early detection of disease.
Source: Sarah L. White, Ph.D.
Ludwig Institute for Cancer Research
среда, 1 июня 2011 г.
Researchers Link Defects In Mitochondria To Abnormal Nuclear Genome Packaging In Cancer Cells
New research by Roswell Park Cancer Institute (RPCI) scientists may help explain how cancer develops. In a study published in the journal Cancer Biology and Therapy*, authors Keshav K. Singh, PhD, and Dominic J. Smiraglia, PhD, of RPCI's Department of Cancer Genetics, analyzed defects in two major cellular mechanisms - dysfunction of mitochondria and abnormal epigenetic changes of the genome - and discovered that these alterations are linked in cancer.
Mitochondria, the power plants that produce energy within each cell, perform multiple functions within cells, including the generation of the basic building blocks of DNA. Mitochondria contain their own DNA (mitochondrial DNA). Changes in mitochondrial DNA copy numbers are associated with development of cancer and poor cancer survival.
Over 1.8 meters of DNA is packed into the nucleus of every cell. Precise packaging of the DNA is essential for this to be possible. Researchers have previously reported that how the genome is packaged is highly dynamic and critical to cellular behavior. This dynamic packaging of the genome is tightly regulated by a set of chemical modifications that occur on the DNA and proteins. The study of these modifications is described as "epigenetics." DNA methylation is one type of epigenetic change which was studied in this research. Methylation changes in the nuclear genome play a key role in human tumorigenesis.
Researchers investigated whether changes in the mitochondrial DNA (mtDNA), which is commonly seen in a number of human tumors, could induce methylation changes in the nucleus. They used the Restriction Landmark Genomic Scanning (RLGS) method to identify genes that acquire changes in DNA methylation in response to the depletion of mtDNA. These studies provide the first direct evidence that mitochondria regulate epigenetic modifications in the nucleus that may contribute to tumorigenesis.
Under the direction of Dr. Singh, researchers eliminated normal mitochondrial function in cell lines, thereby creating what they labeled "rho-zero" cells. The rho-zero cells and normal cells were then both evaluated for the pattern of DNA abnormalities.
The researchers found that mitochondrial impairment induces epigenetic DNA abnormalities in the nuclear genome and that some, but not all, of the changes induced by the depletion of the mitochondrial genome can be reversed by reintroduction of the mitochondria.
This is the first demonstration of how defects in the mitochondria can impact the DNA regulatory epigenetic mechanisms of the cell. These changes can alter the genes expressed in the cell and therefore the behavior of the cell, which in turn can lead to cancer development.
"Our research has shed a novel light on the relationship between the DNA of the cell and the energy source which powers that cell. Further studies may reveal the exact nature of the mitochondrial signal that triggers the epigenetic response and aid in the understanding of the mechanisms associated with tumorigenesis and ultimately impact the treatment of cancer," said Dr. Singh.
Roswell Park Cancer Institute, founded in 1898, is the nation's first cancer research, treatment and education center. The Institute was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation's leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. roswellpark
* Commentary regarding this study was published by Cancer Biology and Therapy and can be accessed here.
Roswell Park Cancer Institute
Mitochondria, the power plants that produce energy within each cell, perform multiple functions within cells, including the generation of the basic building blocks of DNA. Mitochondria contain their own DNA (mitochondrial DNA). Changes in mitochondrial DNA copy numbers are associated with development of cancer and poor cancer survival.
Over 1.8 meters of DNA is packed into the nucleus of every cell. Precise packaging of the DNA is essential for this to be possible. Researchers have previously reported that how the genome is packaged is highly dynamic and critical to cellular behavior. This dynamic packaging of the genome is tightly regulated by a set of chemical modifications that occur on the DNA and proteins. The study of these modifications is described as "epigenetics." DNA methylation is one type of epigenetic change which was studied in this research. Methylation changes in the nuclear genome play a key role in human tumorigenesis.
Researchers investigated whether changes in the mitochondrial DNA (mtDNA), which is commonly seen in a number of human tumors, could induce methylation changes in the nucleus. They used the Restriction Landmark Genomic Scanning (RLGS) method to identify genes that acquire changes in DNA methylation in response to the depletion of mtDNA. These studies provide the first direct evidence that mitochondria regulate epigenetic modifications in the nucleus that may contribute to tumorigenesis.
Under the direction of Dr. Singh, researchers eliminated normal mitochondrial function in cell lines, thereby creating what they labeled "rho-zero" cells. The rho-zero cells and normal cells were then both evaluated for the pattern of DNA abnormalities.
The researchers found that mitochondrial impairment induces epigenetic DNA abnormalities in the nuclear genome and that some, but not all, of the changes induced by the depletion of the mitochondrial genome can be reversed by reintroduction of the mitochondria.
This is the first demonstration of how defects in the mitochondria can impact the DNA regulatory epigenetic mechanisms of the cell. These changes can alter the genes expressed in the cell and therefore the behavior of the cell, which in turn can lead to cancer development.
"Our research has shed a novel light on the relationship between the DNA of the cell and the energy source which powers that cell. Further studies may reveal the exact nature of the mitochondrial signal that triggers the epigenetic response and aid in the understanding of the mechanisms associated with tumorigenesis and ultimately impact the treatment of cancer," said Dr. Singh.
Roswell Park Cancer Institute, founded in 1898, is the nation's first cancer research, treatment and education center. The Institute was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation's leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. roswellpark
* Commentary regarding this study was published by Cancer Biology and Therapy and can be accessed here.
Roswell Park Cancer Institute
вторник, 31 мая 2011 г.
Dark Matter Between Genes Is Not Widespread
The activity of supposed 'dark matter' between the genes seems to be mostly noise from the genes themselves. NWO researcher Harm van Bakel researched RNA transcripts particles of copied DNA the function of which has been a mystery until now. He reached the conclusion that we need not assign any unexplained biological function to them. The results of his research were published by the open access journal PLoS BIOLOGY.
DNA provides instructions for the manufacture of proteins, which in turn make up our bodies. The DNA sends these instruction messages in the form of an RNA transcript. Over recent decades, however, researchers have discovered RNA transcripts that could not be traced back to the known genes and that had no demonstrable function. They compared this phenomenon with the 'dark matter' in the universe: widespread, but with nobody actually knowing its function. Many biologists suspect that the uprooted RNA transcripts have an important biological function, which has simply eluded people until now. Harm van Bakel has shown that this is unlikely.
Two percent of origins unknown
Harm van Bakel combined two measurement methods to find out where the odd RNA transcripts had come from. He used DNA chips and DNA sequence analysis. The latter method allowed Van Bakel to chart the origins of millions of fragments of transcripts. It turned out that 98% of the RNA transcripts actually came from known genes. The majority of the remaining 2% came from the vicinity of a known gene. The 'dark matter transcripts' are not, therefore, new signs of a hitherto hidden universe within the genome, but are probably simply the result of the noise associated with active genetic processes.
The fact that most of the 'dark matter transcripts' are the result of the activity of known genes also provides a new understanding of how the genome operates. It appears that the machinery responsible for gene expression is not as meticulous as it could be. Van Bakel's article can be consulted free of charge on the website of PLoS BIOLOGY.
Rubicon
The young researcher performed his research at the University of Toronto. The Netherlands Organisation for Scientific Research (NWO) financed his two-year residence at the Canadian university. Harm van Bakel was awarded a Rubicon Grant by NWO in 2006. Dutch researchers who have recently gained their doctorates can gain research experience in other countries using Rubicon.
Source: NWO (Netherlands Organization for Scientific Research)
DNA provides instructions for the manufacture of proteins, which in turn make up our bodies. The DNA sends these instruction messages in the form of an RNA transcript. Over recent decades, however, researchers have discovered RNA transcripts that could not be traced back to the known genes and that had no demonstrable function. They compared this phenomenon with the 'dark matter' in the universe: widespread, but with nobody actually knowing its function. Many biologists suspect that the uprooted RNA transcripts have an important biological function, which has simply eluded people until now. Harm van Bakel has shown that this is unlikely.
Two percent of origins unknown
Harm van Bakel combined two measurement methods to find out where the odd RNA transcripts had come from. He used DNA chips and DNA sequence analysis. The latter method allowed Van Bakel to chart the origins of millions of fragments of transcripts. It turned out that 98% of the RNA transcripts actually came from known genes. The majority of the remaining 2% came from the vicinity of a known gene. The 'dark matter transcripts' are not, therefore, new signs of a hitherto hidden universe within the genome, but are probably simply the result of the noise associated with active genetic processes.
The fact that most of the 'dark matter transcripts' are the result of the activity of known genes also provides a new understanding of how the genome operates. It appears that the machinery responsible for gene expression is not as meticulous as it could be. Van Bakel's article can be consulted free of charge on the website of PLoS BIOLOGY.
Rubicon
The young researcher performed his research at the University of Toronto. The Netherlands Organisation for Scientific Research (NWO) financed his two-year residence at the Canadian university. Harm van Bakel was awarded a Rubicon Grant by NWO in 2006. Dutch researchers who have recently gained their doctorates can gain research experience in other countries using Rubicon.
Source: NWO (Netherlands Organization for Scientific Research)
понедельник, 30 мая 2011 г.
New Findings On Mercury Content In Salmon
A new study published in Environmental Toxicology
and Chemistry finds that although mercury levels in both wild
and farmed salmon from British Columbia are substantially below human
health consumption guidelines, the levels found in wild salmon were
three times higher than in farmed salmon.
A large proportion of the farmed salmon consumed in the United States
originates in British Columbia, Canada. Over the years, there have been
health concerns because high levels of methylmercury have been found in
long-lived fish species nearer to the top of the food chain - such as
tuna and salmon. High mercury levels have been associated with an
increase in the risk of cancer, and this has led many people to avoid
consuming certain fishes.
This most recent study has determined that levels of mercury and other
trace metals measured in both farmed and wild salmon were significantly
below
Health Canada's consumption guidelines. Compared to wild salmon, the
researchers found that farmed salmon did not
have significantly higher concentrations of metals such as arsenic,
cobalt, copper, or
cadmium. The threefold higher mercury concentration observed in the
flesh of wild salmon than in farmed salmon is potentially explained by
farmed salmon's low gastrointestinal absorption efficiency, its
negligible transfer of metals to muscle tissue, and its rapid growth
cycles (growth dilution). In farmed fish, there were no differences in
metal levels found between pre- and post-processing.
For comparison to other parts of the human diet, the researchers
indicate that total mercury levels were slightly
higher in wild or farmed salmon than in chicken, beef, or pork and
about the same as in fruit, vegetables, honey, and eggs. Compared to
other foods, salmon contains lower levels of other trace elements. The
average dietary intake of mercury and trace metals from salmon still
remains a paltry 0.05% to 32% compared to the 68% to 99% that is
absorbed from meat, poultry, fruit, and vegetables. Salmon
also contains its own protection against mercury in the form of the
element selenium. The moderate surplus of this metal can counteract
mercury's toxicity.
"Estimates of human dietary exposure indicate that human health risks
associated with trace metal exposure via consumption of farmed and wild
British Columbia salmon are negligible," conclude the authors. "The
current scientific evidence therefore supports the weekly consumption
of oily fish species (including all British Columbia salmon sources) as
recommended by the American Heart Association."
Mercury and Other Trace Elements in Farmed
and Wild Salmon from British Columbia, Canada
Barry C. Kelly, Michael
G. Ikonomou, David A. Higgs, Janice Oakes, and Cory Dubetz
Environmental Toxicology and Chemistry (2008). Vol.
27(6):1361-1370.
Click
here to view paper
Written by: Peter M Crosta
and Chemistry finds that although mercury levels in both wild
and farmed salmon from British Columbia are substantially below human
health consumption guidelines, the levels found in wild salmon were
three times higher than in farmed salmon.
A large proportion of the farmed salmon consumed in the United States
originates in British Columbia, Canada. Over the years, there have been
health concerns because high levels of methylmercury have been found in
long-lived fish species nearer to the top of the food chain - such as
tuna and salmon. High mercury levels have been associated with an
increase in the risk of cancer, and this has led many people to avoid
consuming certain fishes.
This most recent study has determined that levels of mercury and other
trace metals measured in both farmed and wild salmon were significantly
below
Health Canada's consumption guidelines. Compared to wild salmon, the
researchers found that farmed salmon did not
have significantly higher concentrations of metals such as arsenic,
cobalt, copper, or
cadmium. The threefold higher mercury concentration observed in the
flesh of wild salmon than in farmed salmon is potentially explained by
farmed salmon's low gastrointestinal absorption efficiency, its
negligible transfer of metals to muscle tissue, and its rapid growth
cycles (growth dilution). In farmed fish, there were no differences in
metal levels found between pre- and post-processing.
For comparison to other parts of the human diet, the researchers
indicate that total mercury levels were slightly
higher in wild or farmed salmon than in chicken, beef, or pork and
about the same as in fruit, vegetables, honey, and eggs. Compared to
other foods, salmon contains lower levels of other trace elements. The
average dietary intake of mercury and trace metals from salmon still
remains a paltry 0.05% to 32% compared to the 68% to 99% that is
absorbed from meat, poultry, fruit, and vegetables. Salmon
also contains its own protection against mercury in the form of the
element selenium. The moderate surplus of this metal can counteract
mercury's toxicity.
"Estimates of human dietary exposure indicate that human health risks
associated with trace metal exposure via consumption of farmed and wild
British Columbia salmon are negligible," conclude the authors. "The
current scientific evidence therefore supports the weekly consumption
of oily fish species (including all British Columbia salmon sources) as
recommended by the American Heart Association."
Mercury and Other Trace Elements in Farmed
and Wild Salmon from British Columbia, Canada
Barry C. Kelly, Michael
G. Ikonomou, David A. Higgs, Janice Oakes, and Cory Dubetz
Environmental Toxicology and Chemistry (2008). Vol.
27(6):1361-1370.
Click
here to view paper
Written by: Peter M Crosta
воскресенье, 29 мая 2011 г.
Team Finds A Better Way To Watch Bacteria Swim
Researchers have developed a new method for studying bacterial swimming, one that allows them to trap Escherichia coli bacteria and modify the microbes' environment without hindering the way they move.
The new approach, described this month in Nature Methods, uses optical traps, microfluidic chambers and fluorescence to get an improved picture of how E. coli get around.
The microfluidic chambers provide a controlled environment in which the bacteria swim, and allow the researchers to introduce specific stimuli - such as chemical attractants - to see if the microbes change direction in response to that stimulus.
Optical traps use lasers to confine individual cells without impeding their rotation or the movement of their flagella. University of Illinois physics professor Yann Chemla, who co-led the study with physics professor Ido Golding, calls the optical traps "bacterial treadmills."
Movement of the bacterial cell alters the light from the laser, allowing the researchers to track its behavior.
Fluorescent markers enhance visualization of the bacteria and their flagella under a microscope.
Three to six helical flagella emerge from various points along E. coli's rod-shaped body. When they rotate in a counterclockwise fashion (as seen from behind), they gather into what looks like a coordinated bundle that pushes the bacterium forward, causing it to corkscrew through its environment. But when one or more flagella rotate in the opposite direction, they splay apart, reorienting the bacterium.
This "run and tumble" behavior has long been of interest to scientists for two reasons, Golding said. First, the elaborate mechanics of bacterial swimming "tell you a lot about biomechanics," he said. And second, "it serves as a paradigm for the way living cells process information from their environment."
Earlier studies have been unable to follow individual bacterial cells moving in three dimensions for more than about 30 seconds, the researchers said. And it is nearly impossible to determine what cues are spurring a cell to move in a given direction. The new method addresses both of these problems without altering the normal behavior of the bacterium, they found.
"Because the cell is immobilized, what we do is change the environment around it," Chemla said. "We can set up a flow cell that has two different concentrations of some chemical, for example, and see how the bacterium responds. Technically we're moving the swimming pool relative to the swimmer," he said.
The new approach allows the researchers to track a single bacterium as it swims for up to an hour, "which is orders of magnitude above what people could do before," Golding said. This will offer a new look at questions that so far have been unanswerable, he said.
"For example, some people have asked whether E. coli has a nose. Does it have a front and back?" Golding said. The team's observations indicate that while the bacterium can travel in either direction, most E. coli have "a pronounced preference" for one over the other, he said.
The researchers found that after most tumbles, a bacterium usually continued swimming in the same general direction, but that about one in six tumbles caused it to change direction completely. They were also able to quantify other features of bacterial swimming, such as changes in velocity and the time spent running and tumbling. The new technique will allow researchers to address many more questions about this model organism, they said.
"That's the typical way biology moves forward," Golding said. "You develop a new measurement capability and then you can use that to go back and look at fundamental questions that people had been looking at but had no way of answering."
The study is a project of the National Science Foundation's Center for the Physics of Living Cells at the University of Illinois, which promotes collaboration across disciplines, the researchers said.
Source:
Diana Yates
University of Illinois at Urbana-Champaign
The new approach, described this month in Nature Methods, uses optical traps, microfluidic chambers and fluorescence to get an improved picture of how E. coli get around.
The microfluidic chambers provide a controlled environment in which the bacteria swim, and allow the researchers to introduce specific stimuli - such as chemical attractants - to see if the microbes change direction in response to that stimulus.
Optical traps use lasers to confine individual cells without impeding their rotation or the movement of their flagella. University of Illinois physics professor Yann Chemla, who co-led the study with physics professor Ido Golding, calls the optical traps "bacterial treadmills."
Movement of the bacterial cell alters the light from the laser, allowing the researchers to track its behavior.
Fluorescent markers enhance visualization of the bacteria and their flagella under a microscope.
Three to six helical flagella emerge from various points along E. coli's rod-shaped body. When they rotate in a counterclockwise fashion (as seen from behind), they gather into what looks like a coordinated bundle that pushes the bacterium forward, causing it to corkscrew through its environment. But when one or more flagella rotate in the opposite direction, they splay apart, reorienting the bacterium.
This "run and tumble" behavior has long been of interest to scientists for two reasons, Golding said. First, the elaborate mechanics of bacterial swimming "tell you a lot about biomechanics," he said. And second, "it serves as a paradigm for the way living cells process information from their environment."
Earlier studies have been unable to follow individual bacterial cells moving in three dimensions for more than about 30 seconds, the researchers said. And it is nearly impossible to determine what cues are spurring a cell to move in a given direction. The new method addresses both of these problems without altering the normal behavior of the bacterium, they found.
"Because the cell is immobilized, what we do is change the environment around it," Chemla said. "We can set up a flow cell that has two different concentrations of some chemical, for example, and see how the bacterium responds. Technically we're moving the swimming pool relative to the swimmer," he said.
The new approach allows the researchers to track a single bacterium as it swims for up to an hour, "which is orders of magnitude above what people could do before," Golding said. This will offer a new look at questions that so far have been unanswerable, he said.
"For example, some people have asked whether E. coli has a nose. Does it have a front and back?" Golding said. The team's observations indicate that while the bacterium can travel in either direction, most E. coli have "a pronounced preference" for one over the other, he said.
The researchers found that after most tumbles, a bacterium usually continued swimming in the same general direction, but that about one in six tumbles caused it to change direction completely. They were also able to quantify other features of bacterial swimming, such as changes in velocity and the time spent running and tumbling. The new technique will allow researchers to address many more questions about this model organism, they said.
"That's the typical way biology moves forward," Golding said. "You develop a new measurement capability and then you can use that to go back and look at fundamental questions that people had been looking at but had no way of answering."
The study is a project of the National Science Foundation's Center for the Physics of Living Cells at the University of Illinois, which promotes collaboration across disciplines, the researchers said.
Source:
Diana Yates
University of Illinois at Urbana-Champaign
суббота, 28 мая 2011 г.
Update On Jungle Yellow Fever (JYF) In Brazil, Paraguay, And Argentina
Yellow fever is a zoonosis of the tropical regions of South America and Africa, which occurs in two distinct epidemiologic cycles: jungle and urban. In the jungle cycle, the virus spreads among monkeys and humans, who may be infected when they enter the jungle and are bitten by mosquitoes infected with the yellow fever virus. Urban yellow fever has long been eradicated from the Americas, with the last cases occurring in Brazil in 1942.
Since the 1970s, the area where jungle yellow fever (JYF) cases have occurred has been restricted to the northern region of the South American continent. From 1985 to December 2007, 3,837 cases of JYF have been reported, with 2,229 deaths.
In 2007 and the beginning of 2008, Brazil reported an intense and extensive epizootic of Jungle Yellow Fever in an area encompassing 6 states (GoiГЎs, the Federal District, Mato Grosso do Sul, Minas Gerais, Tocantins, and SГЈo Paulo). The State Health Departments have confirmed the epizootic based on laboratory and clinical epidemiological criteria. In the past two months, 26 confirmed human cases were reported in 3 Federal States (GoiГЎs, Mato Grosso do Sul, and the Federal District); 13 of the patients died. The affected areas have high vaccination coverage. Nevertheless, as part of ongoing control measures, health authorities have intensified vaccination for people living in or traveling to affected areas.
On 15 January 2008, the national health authorities of Paraguay reported their first confirmed cases of Jungle Yellow Fever. One of the cases was confirmed using molecular techniques; the other four, by epidemiological nexus. As of 11 February 2008, 4 other suspected cases of JYF have been reported. All the confirmed cases reported by the national health authorities come from a rural area of San Pedro department in the northern part of the country. National health authorities have intensified epidemiological surveillance for the detection and investigation of suspected cases, and yellow fever vaccination for people living in or traveling to the affected area.
On 17 January 2008, the national health authorities of Argentina reported finding dead monkeys in PiГ±alito Park, San Pedro department, Misiones province. On 4 February 2008, yellow fever was confirmed in one of the primates using molecular techniques. Although there is high vaccination coverage in the area, national health authorities have intensified vaccination for people living in or traveling to the affected area with no previous vaccination history.
For many years, jungle yellow fever has caused numerous high-mortality epidemics. The clinical manifestations of infection from the yellow fever virus can vary greatly, from asymptomatic or subclinical forms with non-specific symptoms, to hemorrhagic fever, which develops in 15-25% of infected patients and which presents a case fatality of around 50%.
Currently, the recommended strategy for vaccination against yellow fever is to focus on protecting the population living in or traveling to areas with any risk of transmission, where epizootics or human cases were recently reported, thus avoiding massive vaccination and re-vaccination.
The Pan American Health Organization is providing technical support to these countries through advisors in its Country Offices and at Headquarters in Washington, DC, in accordance with requests from the countries.
The Pan American Health Organization, founded in 1902, works with all the countries of the Americas to improve the health and quality of life of their peoples. It serves as the Regional Office of the World Health Organization (WHO).
World Health Organization
Since the 1970s, the area where jungle yellow fever (JYF) cases have occurred has been restricted to the northern region of the South American continent. From 1985 to December 2007, 3,837 cases of JYF have been reported, with 2,229 deaths.
In 2007 and the beginning of 2008, Brazil reported an intense and extensive epizootic of Jungle Yellow Fever in an area encompassing 6 states (GoiГЎs, the Federal District, Mato Grosso do Sul, Minas Gerais, Tocantins, and SГЈo Paulo). The State Health Departments have confirmed the epizootic based on laboratory and clinical epidemiological criteria. In the past two months, 26 confirmed human cases were reported in 3 Federal States (GoiГЎs, Mato Grosso do Sul, and the Federal District); 13 of the patients died. The affected areas have high vaccination coverage. Nevertheless, as part of ongoing control measures, health authorities have intensified vaccination for people living in or traveling to affected areas.
On 15 January 2008, the national health authorities of Paraguay reported their first confirmed cases of Jungle Yellow Fever. One of the cases was confirmed using molecular techniques; the other four, by epidemiological nexus. As of 11 February 2008, 4 other suspected cases of JYF have been reported. All the confirmed cases reported by the national health authorities come from a rural area of San Pedro department in the northern part of the country. National health authorities have intensified epidemiological surveillance for the detection and investigation of suspected cases, and yellow fever vaccination for people living in or traveling to the affected area.
On 17 January 2008, the national health authorities of Argentina reported finding dead monkeys in PiГ±alito Park, San Pedro department, Misiones province. On 4 February 2008, yellow fever was confirmed in one of the primates using molecular techniques. Although there is high vaccination coverage in the area, national health authorities have intensified vaccination for people living in or traveling to the affected area with no previous vaccination history.
For many years, jungle yellow fever has caused numerous high-mortality epidemics. The clinical manifestations of infection from the yellow fever virus can vary greatly, from asymptomatic or subclinical forms with non-specific symptoms, to hemorrhagic fever, which develops in 15-25% of infected patients and which presents a case fatality of around 50%.
Currently, the recommended strategy for vaccination against yellow fever is to focus on protecting the population living in or traveling to areas with any risk of transmission, where epizootics or human cases were recently reported, thus avoiding massive vaccination and re-vaccination.
The Pan American Health Organization is providing technical support to these countries through advisors in its Country Offices and at Headquarters in Washington, DC, in accordance with requests from the countries.
The Pan American Health Organization, founded in 1902, works with all the countries of the Americas to improve the health and quality of life of their peoples. It serves as the Regional Office of the World Health Organization (WHO).
World Health Organization
пятница, 27 мая 2011 г.
Glycobiology: The Sheer Versatility Of Sugars - Glycobiology Is A Hot New Topic, A Science That Has Arrived And Blossomed In The Last Decade
The latest issue of The Biochemist puts glycobiology in perspective with an authoritative article on its origin by Professor Raymond Dwek and with reports from the cutting edge of this fascinating and vitally important new discipline. Read how it is making significant discoveries in the fields of molecular biology and in the fight against disease.
Also: the discovery of muscle biochemistry, how the structure of immunoglobin was found and what John Prescott is really like.
All this and much more in the latest issue of The Biochemist
Glycobiology at Oxford
By Raymond Dwek
How the study of oligosaccharides became glycobiology and became firmly established as part of mainstream biochemistry.
Recognizing glycans
By Kurt Drickamer and Maureen E. Taylor
Many well-understood examples of glycan-receptor interactions exist, but are there enough receptors to account for the number of glycans that are being identified?
Protein-carbohydrate interactions
By Nathan Sharon
Proteins that possess the ability to bind carbohydrates specifically and reversibly abound in nature, being present in all living organisms, from viruses to humans.
Glycobiology and medicine
By Pauline M. Rudd and Raymond A. Dwek
The bright future for high throughput glycan analysis and disease markers.
Glycobiology and viruses
By Nicole Zitzmann, Joanne M. O'Leary and Raymond Dwek
Most aspects of glycobiology play important roles in the 'life' of viruses, for example in the correct folding of their envelope glycoproteins as well as in immune representation and escape.
Raman optical activity
By Laurence D. Barron
A new light on proteins, carbohydrates and glycoproteins.
Q & A:
Interview with S. V. Perry
Flexing their muscles
By Michael P. Walsh
The Biochemical Journal classic papers of S. V. Perry and co-workers.
In the blood
By Michael A. Kerr
Rodney Porter and the structure of immunoglobulin.
The trap hypothesis
By Guy S. Salvesen
The classic Biochemical Journal paper of Alan Barrett and Phyllis Starkey.
48 Q & A:
Q. Is John Prescott a nice guy to work with?
A. Yes; the image of John given by the press and the media is very unfair.
Our exclusive interview with Phyllis Starkey, MP
Obituary
Helen Muir 1920-2005
By Tim Hardingham
biochemist/bio
Also: the discovery of muscle biochemistry, how the structure of immunoglobin was found and what John Prescott is really like.
All this and much more in the latest issue of The Biochemist
Glycobiology at Oxford
By Raymond Dwek
How the study of oligosaccharides became glycobiology and became firmly established as part of mainstream biochemistry.
Recognizing glycans
By Kurt Drickamer and Maureen E. Taylor
Many well-understood examples of glycan-receptor interactions exist, but are there enough receptors to account for the number of glycans that are being identified?
Protein-carbohydrate interactions
By Nathan Sharon
Proteins that possess the ability to bind carbohydrates specifically and reversibly abound in nature, being present in all living organisms, from viruses to humans.
Glycobiology and medicine
By Pauline M. Rudd and Raymond A. Dwek
The bright future for high throughput glycan analysis and disease markers.
Glycobiology and viruses
By Nicole Zitzmann, Joanne M. O'Leary and Raymond Dwek
Most aspects of glycobiology play important roles in the 'life' of viruses, for example in the correct folding of their envelope glycoproteins as well as in immune representation and escape.
Raman optical activity
By Laurence D. Barron
A new light on proteins, carbohydrates and glycoproteins.
Q & A:
Interview with S. V. Perry
Flexing their muscles
By Michael P. Walsh
The Biochemical Journal classic papers of S. V. Perry and co-workers.
In the blood
By Michael A. Kerr
Rodney Porter and the structure of immunoglobulin.
The trap hypothesis
By Guy S. Salvesen
The classic Biochemical Journal paper of Alan Barrett and Phyllis Starkey.
48 Q & A:
Q. Is John Prescott a nice guy to work with?
A. Yes; the image of John given by the press and the media is very unfair.
Our exclusive interview with Phyllis Starkey, MP
Obituary
Helen Muir 1920-2005
By Tim Hardingham
biochemist/bio
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