Edinburgh scientists have identified the way a specific cell protein can trigger the spread of cancer. The study by researchers in the Cell Signalling Unit, University of Edinburgh Cancer Research Centre could pave the way for new drugs which limit the protein's ability to turn a normal cell cancerous.
The protein, MDM2, normally functions to control the activity of a key cancer preventing protein called p53. In some of the body's cells, the biochemical ratio between MDM2 and p53 can become unbalanced causing MDM2 to act as a cancer-promoting agent.
The project's lead investigator, Dr Kathryn Ball, a researcher at the University, explains: "One way in which MDM2 controls the p53 protein is by activating its destruction and we are interested in understanding how this happens at a biochemical level.
"In the current study, funded by Cancer Research UK, we have identified protein fragments which can bind to MDM2, inhibiting its activity. These fragments could be a good template for drugs designed to hinder the role of MDM2 in the p53 destruction pathway. We hope our findings may lead to improved treatments for a broad range of cancer types."
Welcoming the findings, Professor John Toy, medical director at Cancer Research UK, said: "p53 is a crucial protein that acts as a guardian of the normal cell. Its failure to do its job properly is associated with many types of cancer. If p53 is being destroyed by another protein in a cancer cell, then it offers an excellent target when designing new anti-cancer drugs. This research suggests MDM2 is just such a target."
The study is published in the current edition of Molecular Cell.
Contact: Linda Menzies
University of Edinburgh
среда, 25 мая 2011 г.
вторник, 24 мая 2011 г.
New Targets For Modification Enzymes Uncovered By Epigenetic Research
Enzymes regulating genetic expression can be just as important as the genome itself, increasing evidence shows. The expanding field of epigenetics focuses on the multiple influences on DNA and surrounding molecules that determine whether genes are turned on or off during development and disease processes.
A consortium of scientists, led by Albert Jeltsch at Jacobs University, Breman, Germany, Yoichi Shinkai at Kyoto University, Japan, and Xiaodong Cheng at Emory University, has now discovered new non-histone targets for one enzyme previously believed to modify only histones--the group of proteins that creates tightly bundled packages of DNA strands. The research is reported online in the journal Nature Chemical Biology.
These modification enzymes, called protein methyltransferases, add methyl groups to lysine amino acids within the histones and change their influence on gene expression. The newly identified non-histone targets add yet another influence on gene expression in addition to the already-known DNA methylation and histone modifications in the epigenome.
The international research team has found that a histone methyltransferase called G9a adds methyl groups to other proteins in addition to histones and changes the behavior of those proteins. The researchers used a peptide array technology called SPOT to identify the new enzyme targets.
"This discovery broadens our view of methyltransferases and tells us that epigenetic regulation in cells is even more complicated than we thought," says principal investigator Xiaodong Cheng, PhD, professor of biochemistry at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar.
"We have known for some time that we had a great deal more to discover about methyltransferases. This is an important piece of the puzzle, and additional research will continue to help us unwind the multiple mechanisms involved in epigenetic gene regulation."
The research was partly supported by the National Institute of General Medical Sciences of the National Institutes of Health.
Source: Holly Korschun
Emory University
A consortium of scientists, led by Albert Jeltsch at Jacobs University, Breman, Germany, Yoichi Shinkai at Kyoto University, Japan, and Xiaodong Cheng at Emory University, has now discovered new non-histone targets for one enzyme previously believed to modify only histones--the group of proteins that creates tightly bundled packages of DNA strands. The research is reported online in the journal Nature Chemical Biology.
These modification enzymes, called protein methyltransferases, add methyl groups to lysine amino acids within the histones and change their influence on gene expression. The newly identified non-histone targets add yet another influence on gene expression in addition to the already-known DNA methylation and histone modifications in the epigenome.
The international research team has found that a histone methyltransferase called G9a adds methyl groups to other proteins in addition to histones and changes the behavior of those proteins. The researchers used a peptide array technology called SPOT to identify the new enzyme targets.
"This discovery broadens our view of methyltransferases and tells us that epigenetic regulation in cells is even more complicated than we thought," says principal investigator Xiaodong Cheng, PhD, professor of biochemistry at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar.
"We have known for some time that we had a great deal more to discover about methyltransferases. This is an important piece of the puzzle, and additional research will continue to help us unwind the multiple mechanisms involved in epigenetic gene regulation."
The research was partly supported by the National Institute of General Medical Sciences of the National Institutes of Health.
Source: Holly Korschun
Emory University
понедельник, 23 мая 2011 г.
The Secret Of Life May Be As Simple As What Happens Between The Sheets--Mica Sheets
That age-old question, "where did life on Earth start?" now has a new answer. If the life between the mica sheets hypothesis is correct, life would have originated between sheets of mica that were layered like the pages in a book.
The so-called "life between the sheets" mica hypothesis was developed by Helen Hansma of the University of California, Santa Barbara, with funding from the National Science Foundation (NSF). This hypothesis was originally introduced by Hansma at the 2007 annual meeting of the American Society for Cell Biology, and is now fully described by Hansma in the September 7, 2010 issue of Journal of Theoretical Biology.
According to the "life between the sheets" mica hypothesis, structured compartments that commonly form between layers of mica--a common mineral that cleaves into smooth sheets--may have sheltered molecules that were the progenitors to cells. Provided with the right physical and chemical environment in the structured compartments to survive and evolve, the molecules eventually reorganized into cells, while still sheltered between mica sheets.
Mica chunks embedded in rocks could have provided the right physical and chemical environment for pre-life molecules and developing cells because:
Mica compartments could have held, protected and sheltered molecules, and thereby promoted their survival. Also, mica could have provided enough isolation for molecules to evolve without being disturbed and still allow molecules to migrate towards one another and eventually bond together to form large organic molecules. And mica compartments may have provided something akin to a template for the production of a life form composed of compartments, which are now known as cells.
Mica sheets are held together by potassium. If high levels of potassium were donated by mica sheets to developing cells, the high levels of potassium found in mica sheets could account for the high levels of potassium currently found in human cells.
Mica chunks embedded in rocks that were sitting in an early ocean would have received an endless supply of energy from waves, the sun, and the occasional sloshing of water into the spaces between the mica sheets. This energy could have pushed the mica sheets into up-and-down motions that could have pushed together molecules sitting between mica sheets, thereby enabling them to bond together.
Because mica surfaces are hospitable to living cells and to all the major classes of large biological molecules, including proteins, nucleic acids, carbohydrates and fats, the "between the sheets" mica hypothesis is consistent with other well-known hypotheses that propose that life originated as RNA, fatty vesicles or primitive metabolisms. Hansma says a "mica world" might have sheltered all the ancient metabolic and fat-vesicle and RNA "worlds."
Hansma also says that mica would provide a better substrate for developing cells than other minerals that have been considered for that role. Why? Because most other minerals would probably have tended to intermittently become either too wet or too dry to support life. By contrast, the spaces between mica sheets would probably have undergone more limited wet/dry cycles that would support life without reaching killing extremes. In addition, many clays that have been considered as potential surfaces for life's origins respond to exposure to water by swelling. By contrast, mica resists swelling and would therefore provide a relatively stable environment for developing cells and biological molecules, even when it did get wet.
Hansma sums up her hypothesis by observing that "mica would provide enough structure and shelter for molecules to evolve but also accommodate the dynamic, ever-changing nature of life."
What's more, Hansma says that "mica is old." Some micas are estimated to be over 4 billion years old. And micas such as biotite have been found in regions containing evidence of the earliest life-forms, which are believed to have existed about 3.8 million years ago.
Hansma's passion for mica evolved gradually--starting when she began conducting pioneering, NSF-funded research in former husband Paul K. Hansma's AFM lab to develop techniques for imaging DNA and other biological molecules in the atomic force microscope (AFM)--a high-resolution imaging technique that allows researchers to observe and manipulate molecular and atomic level features.
Says Helen Hansma, "Mica sheets are atomically flat, so we can see DNA molecules on the mica surface without having to cover the DNA with something that makes it look bigger and easier to see. Sometimes we can even see DNA molecules swimming on the surface of mica, under water, in the AFM. Mica sheets are so thin (one nanometer) that there are a million of them in a millimeter-thick piece of mica."
Hansma's "life between the sheets" hypothesis first struck her a few years ago, after she and family members had collected some mica from a Connecticut mine. When she put water on a piece of the mica under her dissecting microscope, she noticed a greenish organic 'crud' at some step edges in the mica. "It occurred to me that this might be a good place for the origins of life--sheltered within these stacks of sheets that can move up and down in response to flowing water, which could have provided the mechanical energy for making and breaking chemical bonds," says Hansma.
Hansma says that recent advancements in imaging techniques, including the AFM, made possible her recent research, leading to her "between mica sheets" hypothesis. She adds that direct support for her hypothesis might be obtained from additional studies involving mica sheets in an AFM, being subjected its push-and-pull forces while sitting in liquids resembling an early ocean.
Source:
Lily Whiteman
National Science Foundation
The so-called "life between the sheets" mica hypothesis was developed by Helen Hansma of the University of California, Santa Barbara, with funding from the National Science Foundation (NSF). This hypothesis was originally introduced by Hansma at the 2007 annual meeting of the American Society for Cell Biology, and is now fully described by Hansma in the September 7, 2010 issue of Journal of Theoretical Biology.
According to the "life between the sheets" mica hypothesis, structured compartments that commonly form between layers of mica--a common mineral that cleaves into smooth sheets--may have sheltered molecules that were the progenitors to cells. Provided with the right physical and chemical environment in the structured compartments to survive and evolve, the molecules eventually reorganized into cells, while still sheltered between mica sheets.
Mica chunks embedded in rocks could have provided the right physical and chemical environment for pre-life molecules and developing cells because:
Mica compartments could have held, protected and sheltered molecules, and thereby promoted their survival. Also, mica could have provided enough isolation for molecules to evolve without being disturbed and still allow molecules to migrate towards one another and eventually bond together to form large organic molecules. And mica compartments may have provided something akin to a template for the production of a life form composed of compartments, which are now known as cells.
Mica sheets are held together by potassium. If high levels of potassium were donated by mica sheets to developing cells, the high levels of potassium found in mica sheets could account for the high levels of potassium currently found in human cells.
Mica chunks embedded in rocks that were sitting in an early ocean would have received an endless supply of energy from waves, the sun, and the occasional sloshing of water into the spaces between the mica sheets. This energy could have pushed the mica sheets into up-and-down motions that could have pushed together molecules sitting between mica sheets, thereby enabling them to bond together.
Because mica surfaces are hospitable to living cells and to all the major classes of large biological molecules, including proteins, nucleic acids, carbohydrates and fats, the "between the sheets" mica hypothesis is consistent with other well-known hypotheses that propose that life originated as RNA, fatty vesicles or primitive metabolisms. Hansma says a "mica world" might have sheltered all the ancient metabolic and fat-vesicle and RNA "worlds."
Hansma also says that mica would provide a better substrate for developing cells than other minerals that have been considered for that role. Why? Because most other minerals would probably have tended to intermittently become either too wet or too dry to support life. By contrast, the spaces between mica sheets would probably have undergone more limited wet/dry cycles that would support life without reaching killing extremes. In addition, many clays that have been considered as potential surfaces for life's origins respond to exposure to water by swelling. By contrast, mica resists swelling and would therefore provide a relatively stable environment for developing cells and biological molecules, even when it did get wet.
Hansma sums up her hypothesis by observing that "mica would provide enough structure and shelter for molecules to evolve but also accommodate the dynamic, ever-changing nature of life."
What's more, Hansma says that "mica is old." Some micas are estimated to be over 4 billion years old. And micas such as biotite have been found in regions containing evidence of the earliest life-forms, which are believed to have existed about 3.8 million years ago.
Hansma's passion for mica evolved gradually--starting when she began conducting pioneering, NSF-funded research in former husband Paul K. Hansma's AFM lab to develop techniques for imaging DNA and other biological molecules in the atomic force microscope (AFM)--a high-resolution imaging technique that allows researchers to observe and manipulate molecular and atomic level features.
Says Helen Hansma, "Mica sheets are atomically flat, so we can see DNA molecules on the mica surface without having to cover the DNA with something that makes it look bigger and easier to see. Sometimes we can even see DNA molecules swimming on the surface of mica, under water, in the AFM. Mica sheets are so thin (one nanometer) that there are a million of them in a millimeter-thick piece of mica."
Hansma's "life between the sheets" hypothesis first struck her a few years ago, after she and family members had collected some mica from a Connecticut mine. When she put water on a piece of the mica under her dissecting microscope, she noticed a greenish organic 'crud' at some step edges in the mica. "It occurred to me that this might be a good place for the origins of life--sheltered within these stacks of sheets that can move up and down in response to flowing water, which could have provided the mechanical energy for making and breaking chemical bonds," says Hansma.
Hansma says that recent advancements in imaging techniques, including the AFM, made possible her recent research, leading to her "between mica sheets" hypothesis. She adds that direct support for her hypothesis might be obtained from additional studies involving mica sheets in an AFM, being subjected its push-and-pull forces while sitting in liquids resembling an early ocean.
Source:
Lily Whiteman
National Science Foundation
воскресенье, 22 мая 2011 г.
A Method That Captures Cell Growth And Activity Highlighted By Cold Spring Harbor Protocols
This month's issue of Cold Spring Harbor Protocols/ features a cutting-edge method that provides a snapshot of growth and activity patterns in mixed populations of cells. Click here to view the protocol which is freely accessible online.
Written by Ingrid Schmid, a scientist at UCLA (cyto.mednet.ucla/), the protocol involves taking a population of cells and labeling their nucleic acids (DNA and RNA) and cell-surface proteins with specific dyes. Then, using a technique called flow cytometry, scientists can determine the DNA and RNA content of the cells. This allows them to identify the cell-cycle stage of each cell, which provides insight into patterns of cell growth and activity in the population. For example, they can identify which sub-populations of cells are actively dividing and which are not.
Schmid and her colleagues have used the procedure to characterize specific sub-populations of cells in human blood that are involved in the immune response.
This month's issue of Cold Spring Harbor Protocols also includes the related classic technique for the quantification of DNA and RNA in solutions. This essential and routine procedure is used in virtually every laboratory. Click here to view the protocol which is also freely accessible online.
About Cold Spring Harbor Protocols: Cold Spring Harbor Protocols (cshprotocols/) is an online resource 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 cshlpress/.
Source: Maria Smit
Cold Spring Harbor Laboratory
Written by Ingrid Schmid, a scientist at UCLA (cyto.mednet.ucla/), the protocol involves taking a population of cells and labeling their nucleic acids (DNA and RNA) and cell-surface proteins with specific dyes. Then, using a technique called flow cytometry, scientists can determine the DNA and RNA content of the cells. This allows them to identify the cell-cycle stage of each cell, which provides insight into patterns of cell growth and activity in the population. For example, they can identify which sub-populations of cells are actively dividing and which are not.
Schmid and her colleagues have used the procedure to characterize specific sub-populations of cells in human blood that are involved in the immune response.
This month's issue of Cold Spring Harbor Protocols also includes the related classic technique for the quantification of DNA and RNA in solutions. This essential and routine procedure is used in virtually every laboratory. Click here to view the protocol which is also freely accessible online.
About Cold Spring Harbor Protocols: Cold Spring Harbor Protocols (cshprotocols/) is an online resource 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 cshlpress/.
Source: Maria Smit
Cold Spring Harbor Laboratory
суббота, 21 мая 2011 г.
Graphene Could Hold The Key To Speeding Up DNA Sequencing
In a paper published as the cover story of the September 9, 2010 Nature, researchers from Harvard University and MIT have demonstrated that graphene, a surprisingly robust planar sheet of carbon just one-atom thick, can act as an artificial membrane separating two liquid reservoirs.
By drilling a tiny pore just a few-nanometers in diameter, called a nanopore, in the graphene membrane, they were able to measure exchange of ions through the pore and demonstrated that a long DNA molecule can be pulled through the graphene nanopore just as a thread is pulled through the eye of a needle.
"By measuring the flow of ions passing through a nanopore drilled in graphene we have demonstrated that the thickness of graphene immersed in liquid is less then 1 nm thick, or many times thinner than the very thin membrane which separates a single animal or human cell from its surrounding environment," says lead author Slaven Garaj, a Research Associate in the Department of Physics at Harvard. "This makes graphene the thinnest membrane able to separate two liquid compartments from each other. The thickness of the membrane was determined by its interaction with water molecules and ions."
Graphene, the strongest material known, has other advantages. Most importantly, it is electrically conductive.
"Although the membrane prevents ions and water from flowing through it, the graphene membrane can attract different ions and other chemicals to its two atomically close surfaces. This affects graphene's electrical conductivity and could be used for chemical sensing," says co-author Jene Golovchenko, Rumford Professor of Physics and Gordon McKay Professor of Applied Physics at Harvard, whose pioneering work started the field of artificial nanopores in solid-state membranes.
"I believe the atomic thickness of the graphene makes it a novel electrical device that will offer new insights into the physics of surface processes and lead to a wide range of practical application, including chemical sensing and detection of single molecules."
In recent years graphene has astonished the scientific community with its many unique properties and potential applications, ranging from electronics and solar energy research to medical applications.
Jing Kong, also a co-author on the paper, and her colleagues at MIT first developed a method for the large-scale growth of graphene films that was used in the work.
The graphene was stretched over a silicon-based frame, and inserted between two separate liquid reservoirs. An electrical voltage applied between the reservoirs pushed the ions towards graphene membrane. When a nanopore was drilled through the membrane, this voltage channeled the flow of ions through the pore and registered as an electrical current signal.
When the researchers added long DNA chains in the liquid, they were electrically pulled one by one through the graphene nanopore. As the DNA molecule threads the nanopore, it blocks the flow of ions, resulting in a characteristic electrical signal that reflects the size and conformation of the DNA molecule.
Co-author Daniel Branton, Higgins Professor of Biology, Emeritus at Harvard, is one of the researches who, more than a decade ago, initiated the use of nanopores in artificial membranes to detect and characterize single molecules of DNA.
Together with his colleague David Deamer at the University of California, Branton suggested that nanopores might be used to quickly read the genetic code, much as one reads the data from a ticker-tape machine.
As a DNA chain passes through the nanopore, the nucleobases, which are the letters of the genetic code, can be identified. But a nanopore in graphene is the first nanopore short enough to distinguish between two closely neighboring nucleobases.
Several challenges still remain to be overcome before a nanopore can do such reading, including controlling the speed with which DNA threads through the nanopore.
When achieved, nanopore sequencing could lead to very inexpensive and rapid DNA sequencing and has potential to advance personalized health care.
"We were the first to demonstrate DNA translocation through a truly atomically thin membrane. The unique thickness of the graphene might bring the dream of truly inexpensive sequencing closer to reality. The research to come will be very exciting," concludes Branton.
Garaj, Golovchenko, Kong, and Branton's other co-authors on the Nature paper were W. Hubbard in the Harvard School of Engineering and Applied Sciences and A. Reina in the Department of Materials Science and Engineering, MIT. The work was funded by the National Human Genome Research Institute, National Institutes of Health.
Source:
Michael Patrick Rutter
Harvard University
By drilling a tiny pore just a few-nanometers in diameter, called a nanopore, in the graphene membrane, they were able to measure exchange of ions through the pore and demonstrated that a long DNA molecule can be pulled through the graphene nanopore just as a thread is pulled through the eye of a needle.
"By measuring the flow of ions passing through a nanopore drilled in graphene we have demonstrated that the thickness of graphene immersed in liquid is less then 1 nm thick, or many times thinner than the very thin membrane which separates a single animal or human cell from its surrounding environment," says lead author Slaven Garaj, a Research Associate in the Department of Physics at Harvard. "This makes graphene the thinnest membrane able to separate two liquid compartments from each other. The thickness of the membrane was determined by its interaction with water molecules and ions."
Graphene, the strongest material known, has other advantages. Most importantly, it is electrically conductive.
"Although the membrane prevents ions and water from flowing through it, the graphene membrane can attract different ions and other chemicals to its two atomically close surfaces. This affects graphene's electrical conductivity and could be used for chemical sensing," says co-author Jene Golovchenko, Rumford Professor of Physics and Gordon McKay Professor of Applied Physics at Harvard, whose pioneering work started the field of artificial nanopores in solid-state membranes.
"I believe the atomic thickness of the graphene makes it a novel electrical device that will offer new insights into the physics of surface processes and lead to a wide range of practical application, including chemical sensing and detection of single molecules."
In recent years graphene has astonished the scientific community with its many unique properties and potential applications, ranging from electronics and solar energy research to medical applications.
Jing Kong, also a co-author on the paper, and her colleagues at MIT first developed a method for the large-scale growth of graphene films that was used in the work.
The graphene was stretched over a silicon-based frame, and inserted between two separate liquid reservoirs. An electrical voltage applied between the reservoirs pushed the ions towards graphene membrane. When a nanopore was drilled through the membrane, this voltage channeled the flow of ions through the pore and registered as an electrical current signal.
When the researchers added long DNA chains in the liquid, they were electrically pulled one by one through the graphene nanopore. As the DNA molecule threads the nanopore, it blocks the flow of ions, resulting in a characteristic electrical signal that reflects the size and conformation of the DNA molecule.
Co-author Daniel Branton, Higgins Professor of Biology, Emeritus at Harvard, is one of the researches who, more than a decade ago, initiated the use of nanopores in artificial membranes to detect and characterize single molecules of DNA.
Together with his colleague David Deamer at the University of California, Branton suggested that nanopores might be used to quickly read the genetic code, much as one reads the data from a ticker-tape machine.
As a DNA chain passes through the nanopore, the nucleobases, which are the letters of the genetic code, can be identified. But a nanopore in graphene is the first nanopore short enough to distinguish between two closely neighboring nucleobases.
Several challenges still remain to be overcome before a nanopore can do such reading, including controlling the speed with which DNA threads through the nanopore.
When achieved, nanopore sequencing could lead to very inexpensive and rapid DNA sequencing and has potential to advance personalized health care.
"We were the first to demonstrate DNA translocation through a truly atomically thin membrane. The unique thickness of the graphene might bring the dream of truly inexpensive sequencing closer to reality. The research to come will be very exciting," concludes Branton.
Garaj, Golovchenko, Kong, and Branton's other co-authors on the Nature paper were W. Hubbard in the Harvard School of Engineering and Applied Sciences and A. Reina in the Department of Materials Science and Engineering, MIT. The work was funded by the National Human Genome Research Institute, National Institutes of Health.
Source:
Michael Patrick Rutter
Harvard University
пятница, 20 мая 2011 г.
Researchers Pinpoint Neural Nanoblockers In Carbon Nanotubes
Carbon nanotubes hold many exciting possibilities, some of them in the realm of the human nervous system. Recent research has shown that carbon nanotubes may help regrow nerve tissue or ferry drugs used to repair damaged neurons associated with disorders such as epilepsy, Parkinson's disease and perhaps even paralysis.
Yet some studies have shown that carbon nanotubes appear to interfere with a critical signaling transaction in neurons, throwing doubt on the tubes' value in treating neurological disorders. No one knew why the tubes were causing a problem.
Now a team of Brown University researchers has found that it's not the tubes that are to blame. Writing in the journal Biomaterials, the scientists report that the metal catalysts used to form the tubes are the culprits, and that minute amounts of one metal - yttrium - could impede neuronal activity. The findings mean that carbon nanotubes without metal catalysts may be able to treat human neurological disorders, although other possible biological effects still need to be studied.
"We can purify the nanotubes by removing the metals," said Lorin Jakubek, a Ph.D. candidate in biomedical engineering and lead author of the paper, "so, it's a problem we can fix."
Jakubek took single-walled carbon nanotubes to the laboratory of Diane Lipscombe, a Brown neuroscientist. The researchers zeroed in on ion channels located at the end of neurons' axons. These channels are gateways of sorts, driven by changes in the voltage across neurons' membranes. When an electrical signal, known as an action potential, is triggered in neurons, these ion channels "open," each designed to take in a certain ion. One such ion channel passes only calcium, a protein that is critical for transmitter release and thus for neurons to communicate with each other.
In experiments using cloned calcium ion channels in embryonic kidney cells, the scientists discovered that nickel and yttrium, two metal catalysts used to form the single-walled carbon nanotubes, were interfering with the ion channel's ability to absorb the calcium.
Because its ionic radius is nearly identical to calcium's, yttrium in particular "gets stuck and prevents calcium from entering and passing through. It's an ion pore blocker," said Lipscombe, who specializes in neuronal ion channels and is a corresponding author on the paper.
The experiments showed that yttrium in trace amounts - less than 1 microgram per milliliter of water - may disrupt normal calcium signaling in neurons and other electrically active cells, an amount far lower than what had been thought to be safe levels. With nickel, the amount needed to impede calcium signaling was 300 times higher.
"Yttrium is so potent that ... a very low nanotube dose" would be needed to affect neuronal activity, said Robert Hurt, professor of engineering and a corresponding author on the paper.
Jakubek said she was surprised that the metals turned out to be the cause. "Based on the literature, I thought it would be the nanotubes themselves," she said.
Spiro Marangoudakis, Jessica Raingo and Xinyuan Liu contributed to the paper. The National Institutes of Health, the National Science Foundation and the U.S. Environmental Protection Agency funded the research.
Source:
Richard Lewis
Brown University
Yet some studies have shown that carbon nanotubes appear to interfere with a critical signaling transaction in neurons, throwing doubt on the tubes' value in treating neurological disorders. No one knew why the tubes were causing a problem.
Now a team of Brown University researchers has found that it's not the tubes that are to blame. Writing in the journal Biomaterials, the scientists report that the metal catalysts used to form the tubes are the culprits, and that minute amounts of one metal - yttrium - could impede neuronal activity. The findings mean that carbon nanotubes without metal catalysts may be able to treat human neurological disorders, although other possible biological effects still need to be studied.
"We can purify the nanotubes by removing the metals," said Lorin Jakubek, a Ph.D. candidate in biomedical engineering and lead author of the paper, "so, it's a problem we can fix."
Jakubek took single-walled carbon nanotubes to the laboratory of Diane Lipscombe, a Brown neuroscientist. The researchers zeroed in on ion channels located at the end of neurons' axons. These channels are gateways of sorts, driven by changes in the voltage across neurons' membranes. When an electrical signal, known as an action potential, is triggered in neurons, these ion channels "open," each designed to take in a certain ion. One such ion channel passes only calcium, a protein that is critical for transmitter release and thus for neurons to communicate with each other.
In experiments using cloned calcium ion channels in embryonic kidney cells, the scientists discovered that nickel and yttrium, two metal catalysts used to form the single-walled carbon nanotubes, were interfering with the ion channel's ability to absorb the calcium.
Because its ionic radius is nearly identical to calcium's, yttrium in particular "gets stuck and prevents calcium from entering and passing through. It's an ion pore blocker," said Lipscombe, who specializes in neuronal ion channels and is a corresponding author on the paper.
The experiments showed that yttrium in trace amounts - less than 1 microgram per milliliter of water - may disrupt normal calcium signaling in neurons and other electrically active cells, an amount far lower than what had been thought to be safe levels. With nickel, the amount needed to impede calcium signaling was 300 times higher.
"Yttrium is so potent that ... a very low nanotube dose" would be needed to affect neuronal activity, said Robert Hurt, professor of engineering and a corresponding author on the paper.
Jakubek said she was surprised that the metals turned out to be the cause. "Based on the literature, I thought it would be the nanotubes themselves," she said.
Spiro Marangoudakis, Jessica Raingo and Xinyuan Liu contributed to the paper. The National Institutes of Health, the National Science Foundation and the U.S. Environmental Protection Agency funded the research.
Source:
Richard Lewis
Brown University
четверг, 19 мая 2011 г.
How Brain Cells Deal With Mathematical Rules
Intelligent behavior requires strategic processing of numbers and abstract quantity information in accordance with internally maintained goals. For instance, we typically adopt a "less than" strategy when shopping for a product to pay the smallest amount of money. When searching for a job, on the other hand, our plan of action is "greater than", and we strive to earn the largest sum of money. In such pragmatic situations, our decisions on quantities are guided by mathematical rules applied to them. They constitute the foundation of mathematical operations and are thus taught to first-graders. Neurobiologists in the laboratory of Andreas Nieder at the University of TГјbingen now showed for the first time how brain cells process simple mathematical rules. The study is published online in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) (January 18.-24. 2010).
Humans are unrivalled in their understanding of numbers and rules, but the foundations of such high-level skills can already be found in the animal kingdom. To get a glimpse of where and how brain cells master such complex tasks, scientists at the Institute of Neurobiology in TГјbingen trained rhesus monkeys to compare set sizes (numerosities) and to switch flexibly between two abstract mathematical rules. The "greater than" rule required the monkeys to release a lever if the first test display showed more dots than the sample display, whereas the "less than" rule required a lever release if the number of items in the test display was smaller compared to the first test display. The monkeys learned the quantitative "greater than/less than"-rule and were able to choose the smaller or greater set size relative to the sample numerosity, independently of the absolute numerosity of the displays. While the animals were performing this task, neurons recorded in the prefrontal cortex of the frontal lobe exhibited interesting activity. Irrespective of the absolute magnitude of the dot sets, the brain cells exclusively represented the mathematical rule at hand. Approximately one half of these neurons were only active whenever the animal followed the "greater than"-rule, whereas the other half preferred the "less than"-rule.
This new study provides valuable insight into the neurobiological foundations of highly abstract thinking that is necessary for mathematical operations. "First of all we want to understand how neurons process mathematical operations" Andreas Nieder explains. "At the same time, our investigations of the number sense are meaningful for assessing the very complex thinking processes that are necessary, for instance, when dealing with numbers." It is the cerebral cortex at the frontal pole of the brain that constitutes the brain's highest cognitive control center. This region of the brain also gives rise to mental activities that build personality. Damage to the frontal lobe (e.g. after injuries or stroke) disturb goal-directed logical thinking and reasoning. The new study provides important clues to how the healthy brain obeys abstract mathematical rules, which in turn will help to elucidate and treat related mental illnesses.
Source: Universitaet Tuebingen
Humans are unrivalled in their understanding of numbers and rules, but the foundations of such high-level skills can already be found in the animal kingdom. To get a glimpse of where and how brain cells master such complex tasks, scientists at the Institute of Neurobiology in TГјbingen trained rhesus monkeys to compare set sizes (numerosities) and to switch flexibly between two abstract mathematical rules. The "greater than" rule required the monkeys to release a lever if the first test display showed more dots than the sample display, whereas the "less than" rule required a lever release if the number of items in the test display was smaller compared to the first test display. The monkeys learned the quantitative "greater than/less than"-rule and were able to choose the smaller or greater set size relative to the sample numerosity, independently of the absolute numerosity of the displays. While the animals were performing this task, neurons recorded in the prefrontal cortex of the frontal lobe exhibited interesting activity. Irrespective of the absolute magnitude of the dot sets, the brain cells exclusively represented the mathematical rule at hand. Approximately one half of these neurons were only active whenever the animal followed the "greater than"-rule, whereas the other half preferred the "less than"-rule.
This new study provides valuable insight into the neurobiological foundations of highly abstract thinking that is necessary for mathematical operations. "First of all we want to understand how neurons process mathematical operations" Andreas Nieder explains. "At the same time, our investigations of the number sense are meaningful for assessing the very complex thinking processes that are necessary, for instance, when dealing with numbers." It is the cerebral cortex at the frontal pole of the brain that constitutes the brain's highest cognitive control center. This region of the brain also gives rise to mental activities that build personality. Damage to the frontal lobe (e.g. after injuries or stroke) disturb goal-directed logical thinking and reasoning. The new study provides important clues to how the healthy brain obeys abstract mathematical rules, which in turn will help to elucidate and treat related mental illnesses.
Source: Universitaet Tuebingen
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