Diets and beauty products which claim to have anti-oxidant properties are unlikely to prevent ageing, according to research funded by the Wellcome Trust. Researchers at the Institute of Healthy Ageing at UCL (University College London) say this is because a key fifty year old theory about the causes of ageing is wrong.
"Superoxide" free radicals - oxygen molecules that have an imbalance of electrons to protons - are generated in the body through natural processes such as metabolism. These free radicals can cause oxidation in the body, analogous to rust when iron is exposed to oxygen. Biological systems, such as the human body, are usually able to restrict or repair this damage.
In 1956, Denham Harman proposed the theory that ageing is caused by an accumulation of molecular damage caused by "oxidative stress", the action of reactive forms of oxygen, such as superoxide, on cells. This theory has dominated the field of ageing research for over fifty years. But now, a study published online today in the journal Genes & Development suggests that this theory is probably incorrect and that superoxide is not a major cause of ageing.
"The fact is that we don't understand much about the fundamental mechanisms of ageing," says Dr David Gems from UCL. "The free radical theory of ageing has filled a knowledge vacuum for over fifty years now, but it just doesn't stand up to the evidence."
Dr Gems and colleagues at the Institute of Healthy Ageing studied the action of key genes involved in removing superoxide from the bodies of the nematode worm C. elegans, a commonly-used model for research into ageing. By manipulating these genes, they were able to control the worm's ability to "mop up" surplus superoxide and limit potential damage caused by oxidation.
Contrary to the result predicted by the free radical theory of ageing, the researchers found that the lifespan of the worm was relatively unaffected by its ability to tackle the surplus superoxide. The findings, combined with similar recent findings from the University of Texas using mice, imply that this theory is incorrect.
"One of the hallmarks of ageing is the accumulation of molecular damage, but what causes this damage?" says Dr Gems. "It's clear that if superoxide is involved, it only plays a small part in the story. Oxidative damage is clearly not a universal, major driver of the ageing process. Other factors, such as chemical reactions involving sugars in our body, clearly play a role."
Dr Gems believes the study suggests that anti-ageing products which claim to have anti-oxidant properties are unlikely to have any effect.
"A healthy, balanced diet is very important for reducing the risk of developing many diseases associated with old age, such as cancer, diabetes and osteoporosis," he says. "But there is no clear evidence that dietary antioxidants can slow or prevent ageing. There is even less evidence to support the claims of most anti-ageing products."
The research was welcomed by Dr Alan Schafer, Head of Molecular and Physiological Sciences at the Wellcome Trust.
"With increasing lifespan comes greater exposure and vulnerability to the ageing process," comments Dr Schafer. "Research such as this points to how much we have to learn about ageing, and the importance of understanding the mechanisms behind this process. This new study will encourage researchers to explore new avenues in ageing research."
Source: Craig Brierley
Wellcome Trust
вторник, 10 мая 2011 г.
понедельник, 9 мая 2011 г.
Scientists Discover Trigger That Deploys Geckos' Amazing Grip
Geckos are very adept at climbing through difficult terrain using an intricate adhesive system. Until now it has not been known when and how they switch on their unique system of traction.
Scientists at the University of Calgary and Clemson University in South Carolina have discovered that the geckos' amazing grip is triggered by gravity.
This latest development in gecko adhesive research will be published Aug. 5 by Anthony Russell of the U of C and Tim Higham of Clemson in the online edition of the Proceedings of the Royal Society B.
"Geckos use microscopic, hair-like filaments to attach to surfaces. Only at certain angles do they switch on their traction system, however," says Russell, a biological sciences professor at the U of C. "We are trying to understand this process, which will help in mimicking it for application to robotics."
Geckos have long been known for their remarkable abilities to move on smooth surfaces such as glass. This study adds a new angle to previous research: geckos must be on an incline in order to trigger the deployment of their adhesive system.
"Much has been learned in recent years about the mechanism by which clinging takes place, but little is known about how geckos determine when to use this ability," says Higham, a former U of C student and now an assistant professor of biological sciences at Clemson. "We show that perception of body orientation determines when the adhesive system is switched on."
The scientists discovered that the tipping point which turns on the gecko's adhesive system is 10 degrees. Three of the six geckos studied applied their adhesive system on a 10 degree slope. At 30 degrees all six applied the system. The three that applied the traction at 10 degrees slowed down, the three that didn't were much quicker.
"There are costs, in terms of speed, and benefits, in terms of traction, associated with this switch just as there are for Formula 1 cars when rain tires are employed instead of slicks when circumstances place a premium on grip over outright speed," says Russell.
In the case of the geckos, the intricate way that the toes are used in order to achieve the grip necessary to climb is responsible for slowing them.
Russell and Higham are both evolutionary biologists and study animals in their natural environment as well as in the lab. Insights gained through basic research assist them in designing experiments through an appreciation of how evolution has crafted its own solutions to complex problems.
The goal of Russell's research is to try to understand this complex traction system and to apply this knowledge to the development of commercial applications.
The results could be used in such areas as space exploration, medical procedures, military applications such as bomb disposal, and purposes as simple as hanging pictures on walls.
Source:
Leanne Yohemas
University of Calgary
Scientists at the University of Calgary and Clemson University in South Carolina have discovered that the geckos' amazing grip is triggered by gravity.
This latest development in gecko adhesive research will be published Aug. 5 by Anthony Russell of the U of C and Tim Higham of Clemson in the online edition of the Proceedings of the Royal Society B.
"Geckos use microscopic, hair-like filaments to attach to surfaces. Only at certain angles do they switch on their traction system, however," says Russell, a biological sciences professor at the U of C. "We are trying to understand this process, which will help in mimicking it for application to robotics."
Geckos have long been known for their remarkable abilities to move on smooth surfaces such as glass. This study adds a new angle to previous research: geckos must be on an incline in order to trigger the deployment of their adhesive system.
"Much has been learned in recent years about the mechanism by which clinging takes place, but little is known about how geckos determine when to use this ability," says Higham, a former U of C student and now an assistant professor of biological sciences at Clemson. "We show that perception of body orientation determines when the adhesive system is switched on."
The scientists discovered that the tipping point which turns on the gecko's adhesive system is 10 degrees. Three of the six geckos studied applied their adhesive system on a 10 degree slope. At 30 degrees all six applied the system. The three that applied the traction at 10 degrees slowed down, the three that didn't were much quicker.
"There are costs, in terms of speed, and benefits, in terms of traction, associated with this switch just as there are for Formula 1 cars when rain tires are employed instead of slicks when circumstances place a premium on grip over outright speed," says Russell.
In the case of the geckos, the intricate way that the toes are used in order to achieve the grip necessary to climb is responsible for slowing them.
Russell and Higham are both evolutionary biologists and study animals in their natural environment as well as in the lab. Insights gained through basic research assist them in designing experiments through an appreciation of how evolution has crafted its own solutions to complex problems.
The goal of Russell's research is to try to understand this complex traction system and to apply this knowledge to the development of commercial applications.
The results could be used in such areas as space exploration, medical procedures, military applications such as bomb disposal, and purposes as simple as hanging pictures on walls.
Source:
Leanne Yohemas
University of Calgary
воскресенье, 8 мая 2011 г.
How Ubiquitin Chains Are Added To Cell-Cycle Proteins Could Lead To The Development Of Targeted Cancer Therapies
Researchers from the California Institute of Technology (Caltech) have been able to view in detail, and for the first time, the previously mysterious process by which long chains of a protein called ubiquitin are added by enzymes called ubiquitin ligases to proteins that control the cell cycle. Ubiquitin chains tag target proteins for destruction by protein-degrading complexes in the cell.
"We found that ubiquitin ligases build ubiquitin chains very rapidly by transferring ubiquitins one at a time," says Raymond Deshaies, professor of biology at Caltech and Howard Hughes Medical Institute investigator.
Their findings, and the innovative process by which they were obtained, are described in this week's issue of the journal Nature.
Ubiquitin is one of nature's most unusual proteins. Unlike most of its protein brethren, ubiquitin has to be physically attached to other proteins to do its job.
"As its name implies, ubiquitin is found in essentially every kind of eukaryotic cell," says Caltech graduate student Nathan Pierce, the Nature paper's lead author.
In their Nature paper, the Caltech team looked at the process of ubiquitylation, the method by which ubiquitin and ubiquitin chains are added to target proteins. The target proteins used in the study, cyclin E and ОІ-Catenin, are both involved in controlling the cell cycle.
It was already known, Pierce explains, that the addition of a chain of four or more ubiquitins to a target protein marks that protein for annihilation. The destruction of cyclin E is critical for the accurate replication of DNA, while the degradation of ОІ-Catenin keeps cells from dividing during development at the wrong time. If ОІ-Catenin is not degraded, cells proliferate excessively and become predisposed to tumorigenesis. Meanwhile, cells that don't degrade cyclin E accumulate DNA damage and mutations, which can help fuel the unchecked growth of a tumor.
It was also already known that ubiquitin chains are added to the protein using three different enzymes, dubbed E1, E2, and E3. Simply put, E1 activates ubiquitin for transfer, then passes it over to E2. E3 then gets into the act. A form of E3 called a RING ligase (RING stands for "really interesting new gene") plays a key role in the tagging of cyclin E and ОІ-Catenin; according to Pierce, the RING ligase "simultaneously binds to E2 and the target protein (like cyclin E), and then causes E2 to transfer the ubiquitin to the target protein."
Despite all of this knowledge, one question has remained: is the chain transferred to the protein in an already assembled form, or are the ubiquitins moved over one at a time?
"The process is so complicated and so fast," Pierce notes, "that we weren't able to see how the chain is actually built."
To address that issue, Pierce created a sort of biological stop-motion animation that allowed the Caltech team to watch every step in the transfer of ubiquitin from E2 onto the cyclin E protein substrate.
"We devised methods to take snapshots of ubiquitin ligase reactions at a rate of up to 100 'pictures' every second," says Deshaies. "This enables us to see things that would normally evade detection. "
Previous studies had looked at the reaction on the scale of seconds or minutes, Pierce adds. But through an innovative use of a laboratory tool called a quench-flow machine - a machine that allows for extreme precision in the stopping, or "quenching," of a reaction - the team was able to look at what was going on over intervals of just 10 milliseconds in both yeast and human proteins.
"Prior methods did not have sufficient time resolution to see what was going on," says Deshaies. "It's as if you gave an ice-cream cone to a kid and took pictures every minute. You would see the ice cream disappear from the first photo to the next, but since the pictures are too far apart in time, you would have no idea whether the child ate the ice cream one bite at a time, or swallowed the entire scoop in one gulp."
The new method revealed the biological equivalent of small, single bites of ice cream. "Using our approach," Deshaies says, "we could see that our ubiquitin ligase builds ubiquitin chains one ubiquitin at a time."
"Once we knew what the steps were, we calculated the rates at which they occur," adds Pierce. "And from those rates, we were able to really describe the biology of how this system works."
The quest doesn't stop there, of course. "One thing we have to understand now is, how do ubiquitin ligases achieve the speeds that they do?" asks Deshaies. "What special mechanisms do they have to enable them to build chains rapidly? And the flip side of the coin: What sets the speed limit? Why can't our ubiquitin ligase work even faster?"
A recent paper published in the journal Cell by Gary Kleiger, a postdoctoral scholar in the Deshaies lab, answered some of these speed-related questions. By measuring the rates at which E2 and E3 interacted with one another, Kleiger was able to demonstrate their unusually fast association - faster than predicted for normal proteins. E2 and E3 use oppositely-charged surfaces to attract each other, thereby speeding up the formation of a functional complex of the two proteins. This helps explain how the rapid sequential additions of ubiquitin described in the Nature paper are possible.
Gaining these kinds of insights into the ubiquitin system is important, Deshaies says, because ubiquitin ligases play a critical role in a number of human diseases, including cancer, due to their role in the regulation of the cell cycle.
"Once we understand these aspects of how ubiquitin ligases work, and what limits their speed, we will be in an excellent position to think about how we might develop drugs that attack the ligase's Achilles' heel, to make its slowest step even slower," he says. "If we can slow down ubiquitin ligases enough, they may become too slow to get their job done - to build chains - in the time available to them to do so. Being able to develop drugs to block their function would open up a new frontier in medicine."
"We were able to invent HIV therapeutics because we understand how reverse transcriptase works," adds Pierce. "The same applies here. We need to understand how these enzymes work if we're ever going to be able to target them with therapeutics."
In addition to Pierce and Deshaies, other researchers involved in the study included Kleiger and Shu-ou Shan, assistant professor of chemistry at Caltech.
The work described in the Nature paper, "Detection of Sequential Polyubiquitylation on a Millisecond Time-Scale," was funded by a Gordon Ross Fellowship, National Institutes of Health training and research grants, and the Howard Hughes Medical Institute.
Source: Lori Oliwenstein
California Institute of Technology
"We found that ubiquitin ligases build ubiquitin chains very rapidly by transferring ubiquitins one at a time," says Raymond Deshaies, professor of biology at Caltech and Howard Hughes Medical Institute investigator.
Their findings, and the innovative process by which they were obtained, are described in this week's issue of the journal Nature.
Ubiquitin is one of nature's most unusual proteins. Unlike most of its protein brethren, ubiquitin has to be physically attached to other proteins to do its job.
"As its name implies, ubiquitin is found in essentially every kind of eukaryotic cell," says Caltech graduate student Nathan Pierce, the Nature paper's lead author.
In their Nature paper, the Caltech team looked at the process of ubiquitylation, the method by which ubiquitin and ubiquitin chains are added to target proteins. The target proteins used in the study, cyclin E and ОІ-Catenin, are both involved in controlling the cell cycle.
It was already known, Pierce explains, that the addition of a chain of four or more ubiquitins to a target protein marks that protein for annihilation. The destruction of cyclin E is critical for the accurate replication of DNA, while the degradation of ОІ-Catenin keeps cells from dividing during development at the wrong time. If ОІ-Catenin is not degraded, cells proliferate excessively and become predisposed to tumorigenesis. Meanwhile, cells that don't degrade cyclin E accumulate DNA damage and mutations, which can help fuel the unchecked growth of a tumor.
It was also already known that ubiquitin chains are added to the protein using three different enzymes, dubbed E1, E2, and E3. Simply put, E1 activates ubiquitin for transfer, then passes it over to E2. E3 then gets into the act. A form of E3 called a RING ligase (RING stands for "really interesting new gene") plays a key role in the tagging of cyclin E and ОІ-Catenin; according to Pierce, the RING ligase "simultaneously binds to E2 and the target protein (like cyclin E), and then causes E2 to transfer the ubiquitin to the target protein."
Despite all of this knowledge, one question has remained: is the chain transferred to the protein in an already assembled form, or are the ubiquitins moved over one at a time?
"The process is so complicated and so fast," Pierce notes, "that we weren't able to see how the chain is actually built."
To address that issue, Pierce created a sort of biological stop-motion animation that allowed the Caltech team to watch every step in the transfer of ubiquitin from E2 onto the cyclin E protein substrate.
"We devised methods to take snapshots of ubiquitin ligase reactions at a rate of up to 100 'pictures' every second," says Deshaies. "This enables us to see things that would normally evade detection. "
Previous studies had looked at the reaction on the scale of seconds or minutes, Pierce adds. But through an innovative use of a laboratory tool called a quench-flow machine - a machine that allows for extreme precision in the stopping, or "quenching," of a reaction - the team was able to look at what was going on over intervals of just 10 milliseconds in both yeast and human proteins.
"Prior methods did not have sufficient time resolution to see what was going on," says Deshaies. "It's as if you gave an ice-cream cone to a kid and took pictures every minute. You would see the ice cream disappear from the first photo to the next, but since the pictures are too far apart in time, you would have no idea whether the child ate the ice cream one bite at a time, or swallowed the entire scoop in one gulp."
The new method revealed the biological equivalent of small, single bites of ice cream. "Using our approach," Deshaies says, "we could see that our ubiquitin ligase builds ubiquitin chains one ubiquitin at a time."
"Once we knew what the steps were, we calculated the rates at which they occur," adds Pierce. "And from those rates, we were able to really describe the biology of how this system works."
The quest doesn't stop there, of course. "One thing we have to understand now is, how do ubiquitin ligases achieve the speeds that they do?" asks Deshaies. "What special mechanisms do they have to enable them to build chains rapidly? And the flip side of the coin: What sets the speed limit? Why can't our ubiquitin ligase work even faster?"
A recent paper published in the journal Cell by Gary Kleiger, a postdoctoral scholar in the Deshaies lab, answered some of these speed-related questions. By measuring the rates at which E2 and E3 interacted with one another, Kleiger was able to demonstrate their unusually fast association - faster than predicted for normal proteins. E2 and E3 use oppositely-charged surfaces to attract each other, thereby speeding up the formation of a functional complex of the two proteins. This helps explain how the rapid sequential additions of ubiquitin described in the Nature paper are possible.
Gaining these kinds of insights into the ubiquitin system is important, Deshaies says, because ubiquitin ligases play a critical role in a number of human diseases, including cancer, due to their role in the regulation of the cell cycle.
"Once we understand these aspects of how ubiquitin ligases work, and what limits their speed, we will be in an excellent position to think about how we might develop drugs that attack the ligase's Achilles' heel, to make its slowest step even slower," he says. "If we can slow down ubiquitin ligases enough, they may become too slow to get their job done - to build chains - in the time available to them to do so. Being able to develop drugs to block their function would open up a new frontier in medicine."
"We were able to invent HIV therapeutics because we understand how reverse transcriptase works," adds Pierce. "The same applies here. We need to understand how these enzymes work if we're ever going to be able to target them with therapeutics."
In addition to Pierce and Deshaies, other researchers involved in the study included Kleiger and Shu-ou Shan, assistant professor of chemistry at Caltech.
The work described in the Nature paper, "Detection of Sequential Polyubiquitylation on a Millisecond Time-Scale," was funded by a Gordon Ross Fellowship, National Institutes of Health training and research grants, and the Howard Hughes Medical Institute.
Source: Lori Oliwenstein
California Institute of Technology
суббота, 7 мая 2011 г.
Study Reveals A Reprogrammed Role For The Androgen Receptor In Adndrogen-independent Prostate Cancer
The androgen receptor a protein ignition switch for prostate cancer cell growth and division is a master of adaptability. When drug therapy deprives the receptor of androgen hormones, thereby halting cell proliferation, the receptor manages to find an alternate growth route. A new study by Dana-Farber Cancer Institute and Ohio State University scientists demonstrates how.
The shift from androgen-dependent to androgen-independent cell growth occurs, in part, because the androgen receptor switches on an entirely different set of genes in the latter group than in the former, the researchers report in the July 24 issue of Cell. In contrast to androgen-dependent prostate tumors, androgen-independent ones experience an uptick in the activity of genes that control cell division, or mitosis. One such gene, called UBE2C, which causes cells to ignore a natural pause in the division process, becomes especially active, the researchers report. This pause, or "checkpoint," ensures that cell division progresses normally; without it, daughter cells may grow even more aggressively and be harder to stop.
"The evolution of prostate cancer from an androgen-dependent state to an androgen-independent one is a key step in its progression," says study senior author Myles Brown, MD, of Dana-Farber. "The discovery that the androgen receptor directs a distinct gene pathway in androgen-independent prostate cancers may lead to the identification of genes in that pathway that can be targeted by future therapies."
Prostate cancers whose growth is fed by androgen are commonly treated with androgen-blocking drugs. Such medications can hold the disease in check for a period of time that varies from patient to patient, but the tumor almost invariably gains the ability to grow without external androgen.
One of the ways such cells re-start their growth is by producing their own androgen, scientists have discovered. Another way involves the androgen receptor itself the "keyhole" in the cell nucleus that androgen molecules fit into but the actual mechanism by which it operates hasn't been known.
To find that mechanism, Brown's team, including co-lead authors Qianben Wang, PhD, now of Ohio State, and Wei Li, PhD, now of Baylor College of Medicine, charted the activity levels, or expression, of genes controlled by the androgen receptor in androgen-dependent and androgen-independent prostate cancer cells. In the androgen-independent cells, they found a group of genes with epigenetic markings tiny attachments to DNA that switchs genes on and off that caused them to be especially active. The genes form a completely separate pathway from the one active in androgen-dependent cells.
It's not known what causes those epigenetic changes to occur, but "we are profiling the genome-wide epigenetic landscape of androgen-dependent and -independent cancers, trying both experimental and computational methods to identify additional regulators," says study co-senior author X. Shirley Liu, PhD, of Dana-Farber.
"The androgen receptor clearly works by an entirely different program in androgen-dependent and -independent cancers," says Wang. "Having discovered that program, we'll be in a better position to understand how it operates and how gene-targeted therapies may shut it down."
The study was supported by grants from the National Institutes of Health, the U.S. Department of Defense, and the Prostate Cancer Foundation.
Co-authors of the study include Yong Zhang, PhD, Kexin Xu, PhD, Mathieu Lupien, Meredith Regan, ScD, Clifford Meyer, PhD, Arjun Kumn Manrai, Michelangelo Fiorentino, MD, PhD, Christopher Fiore, Massimo Loda, MD, and Philip Kantoff, MD, Dana-Farber; Rameen Beroukhim, MD, PhD, Dana-Farber and the Broad Institute of Harvard and MIT; Zhong Chen, PhD, Ohio State; Xin Yuan, MD, PhD, Hongyun Wang, PhD, and Steven Balk, MD, PhD, Beth Israel Deaconess Medical Center, Boston; Jindan Yu, PhD, Rohit Mehra, MD, Bo Han, and Arul Chinnaiyan, MD, PhD, University of Michigan; Tao Wu, PhD, Harvard Medical School; Jason Carroll, PhD, Cambridge Research Institute in the United Kingdom; Olli Janne, MD, PhD, University of Helsinki; Mark Rubin, MD, Weill Cornell Medical College; and Lawrence True, MD, University of Washington.
Source: Dana-Farber Cancer Institute
The shift from androgen-dependent to androgen-independent cell growth occurs, in part, because the androgen receptor switches on an entirely different set of genes in the latter group than in the former, the researchers report in the July 24 issue of Cell. In contrast to androgen-dependent prostate tumors, androgen-independent ones experience an uptick in the activity of genes that control cell division, or mitosis. One such gene, called UBE2C, which causes cells to ignore a natural pause in the division process, becomes especially active, the researchers report. This pause, or "checkpoint," ensures that cell division progresses normally; without it, daughter cells may grow even more aggressively and be harder to stop.
"The evolution of prostate cancer from an androgen-dependent state to an androgen-independent one is a key step in its progression," says study senior author Myles Brown, MD, of Dana-Farber. "The discovery that the androgen receptor directs a distinct gene pathway in androgen-independent prostate cancers may lead to the identification of genes in that pathway that can be targeted by future therapies."
Prostate cancers whose growth is fed by androgen are commonly treated with androgen-blocking drugs. Such medications can hold the disease in check for a period of time that varies from patient to patient, but the tumor almost invariably gains the ability to grow without external androgen.
One of the ways such cells re-start their growth is by producing their own androgen, scientists have discovered. Another way involves the androgen receptor itself the "keyhole" in the cell nucleus that androgen molecules fit into but the actual mechanism by which it operates hasn't been known.
To find that mechanism, Brown's team, including co-lead authors Qianben Wang, PhD, now of Ohio State, and Wei Li, PhD, now of Baylor College of Medicine, charted the activity levels, or expression, of genes controlled by the androgen receptor in androgen-dependent and androgen-independent prostate cancer cells. In the androgen-independent cells, they found a group of genes with epigenetic markings tiny attachments to DNA that switchs genes on and off that caused them to be especially active. The genes form a completely separate pathway from the one active in androgen-dependent cells.
It's not known what causes those epigenetic changes to occur, but "we are profiling the genome-wide epigenetic landscape of androgen-dependent and -independent cancers, trying both experimental and computational methods to identify additional regulators," says study co-senior author X. Shirley Liu, PhD, of Dana-Farber.
"The androgen receptor clearly works by an entirely different program in androgen-dependent and -independent cancers," says Wang. "Having discovered that program, we'll be in a better position to understand how it operates and how gene-targeted therapies may shut it down."
The study was supported by grants from the National Institutes of Health, the U.S. Department of Defense, and the Prostate Cancer Foundation.
Co-authors of the study include Yong Zhang, PhD, Kexin Xu, PhD, Mathieu Lupien, Meredith Regan, ScD, Clifford Meyer, PhD, Arjun Kumn Manrai, Michelangelo Fiorentino, MD, PhD, Christopher Fiore, Massimo Loda, MD, and Philip Kantoff, MD, Dana-Farber; Rameen Beroukhim, MD, PhD, Dana-Farber and the Broad Institute of Harvard and MIT; Zhong Chen, PhD, Ohio State; Xin Yuan, MD, PhD, Hongyun Wang, PhD, and Steven Balk, MD, PhD, Beth Israel Deaconess Medical Center, Boston; Jindan Yu, PhD, Rohit Mehra, MD, Bo Han, and Arul Chinnaiyan, MD, PhD, University of Michigan; Tao Wu, PhD, Harvard Medical School; Jason Carroll, PhD, Cambridge Research Institute in the United Kingdom; Olli Janne, MD, PhD, University of Helsinki; Mark Rubin, MD, Weill Cornell Medical College; and Lawrence True, MD, University of Washington.
Source: Dana-Farber Cancer Institute
пятница, 6 мая 2011 г.
Methods To Screen Genomes And Analyze Evolution Featured In Cold Spring Harbor Protocols
Identifying genes that are important in specific tissues or processes in the mouse used to be a monumental task. New technologies and strategies have simplified this search, making it effective for even the smallest laboratories. This month's issue of Cold Spring Harbor Protocols (cshprotocols/TOCs/toc4_08.dtl) highlights a method for screening the mouse genome using ENU mutagenesis. The method, "Mouse Mutagenesis Using N-ethyl-N-nitrosourea (ENU)," was submitted by Monica Justice and colleagues from the Baylor College of Medicine (bcm/db/db_fac-justice.html). In her laboratory, Justice uses this "forward genetics" method to identify genes that may play a role in human disease. In particular, Justice's lab focuses on the process of hematopoiesis, the development of blood cells. Mutations in these genes can lead to leukemias or lymphomas. The method is freely accessible on the website for Cold Spring Harbor Protocols (cshprotocols/cgi/content/full/2008/5/pdb.prot4985).
The second featured protocol for April is a guide for selecting the proper method for analyzing evolutionary relationships between genes. In "Choosing a Method for Phylogenetic Prediction," David Mount from the University of Arizona (bmcb.biology.arizona/mount.html) provides a step by step process to determine which of the major methods one should use for predicting "phylogeny", the relatedness among gene sequences. The method is freely accessible on the website for Cold Spring Harbor Protocols (cshprotocols/cgi/content/full/2008/5/pdb.ip49).
About Cold Spring Harbor Protocols: Cold Spring Harbor Protocols (cshprotocols/) is a monthly peer-reviewed journal of methods used in a wide range of biology laboratories. It is structured to be highly interactive, with each protocol cross-linked to related methods, descriptive information panels, and illustrative material to maximize the total information available to investigators. Each protocol is clearly presented and designed for easy use at the bench - complete with reagents, equipment, and recipe lists. Life science researchers can access the entire collection via institutional site licenses, and can add their suggestions and comments to further refine the techniques.
About Cold Spring Harbor Laboratory Press: Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit cshl/.
Source: David Crotty
Cold Spring Harbor Laboratory
The second featured protocol for April is a guide for selecting the proper method for analyzing evolutionary relationships between genes. In "Choosing a Method for Phylogenetic Prediction," David Mount from the University of Arizona (bmcb.biology.arizona/mount.html) provides a step by step process to determine which of the major methods one should use for predicting "phylogeny", the relatedness among gene sequences. The method is freely accessible on the website for Cold Spring Harbor Protocols (cshprotocols/cgi/content/full/2008/5/pdb.ip49).
About Cold Spring Harbor Protocols: Cold Spring Harbor Protocols (cshprotocols/) is a monthly peer-reviewed journal of methods used in a wide range of biology laboratories. It is structured to be highly interactive, with each protocol cross-linked to related methods, descriptive information panels, and illustrative material to maximize the total information available to investigators. Each protocol is clearly presented and designed for easy use at the bench - complete with reagents, equipment, and recipe lists. Life science researchers can access the entire collection via institutional site licenses, and can add their suggestions and comments to further refine the techniques.
About Cold Spring Harbor Laboratory Press: Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit cshl/.
Source: David Crotty
Cold Spring Harbor Laboratory
четверг, 5 мая 2011 г.
Government Takes Further Action On Substances As Part Of World-Leading Chemicals Management Plan
The Honourable Tony Clement, Minister of Health, and the Honourable John Baird, Minister of the Environment, released preliminary findings for 19 chemical substances identified as high priorities for action under Batch 3 of the Chemicals Management Plan.
"The goal of our world-leading Chemicals Management Plan is to protect the health of Canadians from potentially harmful substances," said Minister Clement. "By identifying four substances that are potentially 'toxic' to human health in this latest batch of substances, the Government is continuing to deliver results for Canadians and meet the commitments we established when the Chemicals Management Plan was launched in 2006."
"Canadians are increasingly concerned about their environmental legacy," said Minister Baird. "This is another example of how our Government, through the Chemicals Management Plan, is taking real action to reduce the presence of harmful chemicals in our environment and protecting it for future generations."
Out of the 19 substances assessed, four are proposed "toxic" to human health. In addition, the Government is also proposing to create a provision for four other substances so that any proposed new use of these substances (which are no longer used or are used in extremely low quantities in Canada) would be subject to notification of the federal government. With this provision the government would be able to set conditions or prohibit the use of these substances if their use would increase exposure to Canadians or environmental organisms.
Following the extensive assessment, the 11 remaining substances are proposed "not toxic."
The notices containing summaries of draft screening assessment reports for all Batch 3 substances will be published in Canada Gazette, Part I on August 23.
Public summaries, which contain information about how all Batch 3 substances are used in Canada are available on the new Chemicals At A Glance Web page. The draft screening assessments as well as risk management scope documents for Batch 3 substances proposed "toxic" can be found on the Chemicals Management Plan Web site. Interested parties can submit comments on these documents until October 23, 2008. Final screening assessments for Batch 3 substances will be published on or before February 21, 2009.
Health Canada
"The goal of our world-leading Chemicals Management Plan is to protect the health of Canadians from potentially harmful substances," said Minister Clement. "By identifying four substances that are potentially 'toxic' to human health in this latest batch of substances, the Government is continuing to deliver results for Canadians and meet the commitments we established when the Chemicals Management Plan was launched in 2006."
"Canadians are increasingly concerned about their environmental legacy," said Minister Baird. "This is another example of how our Government, through the Chemicals Management Plan, is taking real action to reduce the presence of harmful chemicals in our environment and protecting it for future generations."
Out of the 19 substances assessed, four are proposed "toxic" to human health. In addition, the Government is also proposing to create a provision for four other substances so that any proposed new use of these substances (which are no longer used or are used in extremely low quantities in Canada) would be subject to notification of the federal government. With this provision the government would be able to set conditions or prohibit the use of these substances if their use would increase exposure to Canadians or environmental organisms.
Following the extensive assessment, the 11 remaining substances are proposed "not toxic."
The notices containing summaries of draft screening assessment reports for all Batch 3 substances will be published in Canada Gazette, Part I on August 23.
Public summaries, which contain information about how all Batch 3 substances are used in Canada are available on the new Chemicals At A Glance Web page. The draft screening assessments as well as risk management scope documents for Batch 3 substances proposed "toxic" can be found on the Chemicals Management Plan Web site. Interested parties can submit comments on these documents until October 23, 2008. Final screening assessments for Batch 3 substances will be published on or before February 21, 2009.
Health Canada
среда, 4 мая 2011 г.
Human Derived Stem Cells Can Repair Rat Hearts Damaged By Heart Attack
When human heart muscle cells derived from embryonic stem cells are implanted into a rat after a heart attack, they can help rebuild the animal's heart muscle and improve function of the organ, scientists report in the September issue of Nature Biotechnology. The researchers also developed a new process that greatly improves how stem cells are turned into heart muscle cells and then survive after being implanted in the damaged rat heart. The findings suggest that stem-cell-based treatments might one day help people suffering from heart disease, the leading cause of death in most of the world.
The study was conducted by researchers at the University of Washington School of Medicine in Seattle and at Geron Corp. in Menlo Park, Calif. The scientists set out to tackle two of the main challenges to treating damaged hearts with stem cells: the creation of cardiac cells from embryonic stem cells, and the survival of those cells once they are implanted in a damaged heart.
"Past attempts at treating infarcted hearts with stem cells have shown promise, but they have really been hampered by these challenges," explained Dr. Chuck Murry, director of the Center for Cardiovascular Biology in the UW Institute for Stem Cell and Regenerative Medicine, and corresponding author on the study. "This method we developed goes a long way towards solving both of those problems. We got stem cells to differentiate into mostly cardiac muscle cells, and then got those cardiac cells to survive and thrive in the damaged rat heart."
Embryonic stem cells can differentiate, or turn into, any type of cell found in the body. But researchers had struggled to get stem cells to differentiate into just cardiomyocytes, or heart muscle cells -- most previous efforts resulted in cell preparations in which only a fraction of 1 percent of the differentiated cells were cardiac muscle cells. By treating the stem cells with two growth factors, or growth-encouraging proteins, and then purifying the cells, they were able to turn about 90 percent of stem cells into cardiomyocytes.
The researchers dealt with the other big challenge of stem cell death by implanting the cells along with a cocktail of compounds aimed at helping them grow. The cocktail included a growth "matrix"-- a sort of scaffolding for the cells to latch on to as they grow -- and drugs that block processes related to cell death. When using the pro-growth cocktail, the success rate of heart muscle grafts improved drastically: 100 percent of rat hearts showed successful tissue grafts, compared to only 18 percent in grafts without the cocktail.
"The problem of cell death is pretty common in stem-cell treatments," Murry explained. "When we try to regenerate with liquid tissues, like blood or bone marrow, we're pretty good at it, but we haven't been very successful with solid tissues like skeletal muscle, brain tissue, or heart muscle. This is one of the most successful attempts so far using cells to repair solid tissues -- every one of the treated hearts had a well-developed tissue graft."
When the researchers followed up on the stem-cell treatment by taking images of the rat hearts, they found that the grafts helped thicken the walls that normally stretch out after a heart attack and cause the heart to weaken. The thickened walls were also associated with more vigorous contraction.
"We found that the grafts didn't just survive in the rat hearts -- they also helped improve the function of the damaged heart," said Dr. Michael Laflamme, UW assistant professor of pathology and the lead author of the study. "That's very important, because one of the major problems for people suffering a myocardial infarction is that the heart is damaged and doesn't pump blood nearly as well. This sort of treatment could help the heart rebound from an infarction and retain more of its function afterwards."
The next step in studying stem-cell treatments for the heart is to conduct similar experiments in large animals, like pigs or sheep, while further refining the treatment in rats. Early human clinical trials could begin in about two years, Murry said.
University of Washington
The study was conducted by researchers at the University of Washington School of Medicine in Seattle and at Geron Corp. in Menlo Park, Calif. The scientists set out to tackle two of the main challenges to treating damaged hearts with stem cells: the creation of cardiac cells from embryonic stem cells, and the survival of those cells once they are implanted in a damaged heart.
"Past attempts at treating infarcted hearts with stem cells have shown promise, but they have really been hampered by these challenges," explained Dr. Chuck Murry, director of the Center for Cardiovascular Biology in the UW Institute for Stem Cell and Regenerative Medicine, and corresponding author on the study. "This method we developed goes a long way towards solving both of those problems. We got stem cells to differentiate into mostly cardiac muscle cells, and then got those cardiac cells to survive and thrive in the damaged rat heart."
Embryonic stem cells can differentiate, or turn into, any type of cell found in the body. But researchers had struggled to get stem cells to differentiate into just cardiomyocytes, or heart muscle cells -- most previous efforts resulted in cell preparations in which only a fraction of 1 percent of the differentiated cells were cardiac muscle cells. By treating the stem cells with two growth factors, or growth-encouraging proteins, and then purifying the cells, they were able to turn about 90 percent of stem cells into cardiomyocytes.
The researchers dealt with the other big challenge of stem cell death by implanting the cells along with a cocktail of compounds aimed at helping them grow. The cocktail included a growth "matrix"-- a sort of scaffolding for the cells to latch on to as they grow -- and drugs that block processes related to cell death. When using the pro-growth cocktail, the success rate of heart muscle grafts improved drastically: 100 percent of rat hearts showed successful tissue grafts, compared to only 18 percent in grafts without the cocktail.
"The problem of cell death is pretty common in stem-cell treatments," Murry explained. "When we try to regenerate with liquid tissues, like blood or bone marrow, we're pretty good at it, but we haven't been very successful with solid tissues like skeletal muscle, brain tissue, or heart muscle. This is one of the most successful attempts so far using cells to repair solid tissues -- every one of the treated hearts had a well-developed tissue graft."
When the researchers followed up on the stem-cell treatment by taking images of the rat hearts, they found that the grafts helped thicken the walls that normally stretch out after a heart attack and cause the heart to weaken. The thickened walls were also associated with more vigorous contraction.
"We found that the grafts didn't just survive in the rat hearts -- they also helped improve the function of the damaged heart," said Dr. Michael Laflamme, UW assistant professor of pathology and the lead author of the study. "That's very important, because one of the major problems for people suffering a myocardial infarction is that the heart is damaged and doesn't pump blood nearly as well. This sort of treatment could help the heart rebound from an infarction and retain more of its function afterwards."
The next step in studying stem-cell treatments for the heart is to conduct similar experiments in large animals, like pigs or sheep, while further refining the treatment in rats. Early human clinical trials could begin in about two years, Murry said.
University of Washington
Подписаться на:
Сообщения (Atom)