Do flu vaccines work for the elderly?
Review suggests study is needed on influenza jabs and how they are used.
-Matt Kaplan
How effective are flu vaccines at preventing death in the elderly? A review suggests that there isn't actually much proof that these jabs prevent influenza-related deaths in older people, stirring up controversy over this issue once more. The debate could influence both how the elderly are treated against flu, and how vaccines are distributed to try to prevent epidemics.
Managing influenza epidemics is a huge logistical challenge: there are always going to be more people than there are vaccines, and the vaccines need to be used where they will do the most good. The World Health Organisation endorses targeting vaccination efforts to those with a high risk of a severe outcome from a bout of flu, such as the sick and the elderly.
Many studies of influenza vaccines have analysed elderly populations and concluded that the vaccines reduced mortality during the winter in those aged 65 and older by about 50%1.
But Lone Simonsen, at the National Institute of Allergy and Infectious Diseases, thinks that number cannot be right. Instead, she and her colleagues argue in The Lancet this week2, this apparent benefit is probably due to a mathematical glitch — the real benefit, they argue, is probably smaller. However, they don't know by how much.
"We aren't saying that the elderly should not be vaccinated, we are simply saying we don't have enough evidence at this time to know what benefit is being derived," says co-author Lisa Jackson, from the GroupHealth Center for Health Studies in Seattle, Washington.
The authors suggest that while vaccines continue to be delivered, more work be done to find out how effective they are. And, they add, it might be worth exploring other options for the elderly — such as changing the type of vaccine they receive or upping the dose.
Biased studies
This debate has been long running. In 2005, Simonsen and his colleagues reported in the Archives of Internal Medicine that, although distribution of vaccines to the elderly in America had gone from 15% in 1980 to 65% in 2001, influenza related deaths had not decreased as expected3.
The study also noted that influenza only caused about 5% of winter deaths amongst the elderly — making the 50% reduction in deaths that had previously been reported seem mysterious.
In 2006 an analysis in the International Journal of Epidemiology, led by Jackson, revealed a bias in the original studies4. Jackson noticed that vaccinated seniors had an overall lower risk of death, not just during the winter flu season, but also before and after that. The explanation, she suggested, is that healthier people were more likely to receive the jab, perhaps because they were more likely to make it into the clinic.
Epidemiologist Heath Kelly at the University of Melbourne in Australia says he is "persuaded" that there is some sort of bias in the previous studies. "We need to have a serious look at the effectiveness of the influenza vaccine against laboratory confirmed influenza in the elderly," he says. Meanwhile, epidemiologist and physician Kristin Nichol at the Minneapolis Veterans Affairs Medical Center in Minnesota agrees that "the evidence base is imperfect".
Sensitive subject
No one is suggesting that this means the vaccines should be scrapped. "It is still compelling to support elder vaccination not just to reduce mortality but to prevent hospitalization and the associated cost," adds Nichol.
"The reality is that the vaccine is one of the best available tools that we have, so if it is even marginally helpful to the elderly it should be used," agrees epidemiologist Mark Miller, a co-author of the review at the Fogarty International Center in Bethesda, Maryland.
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The question of whether the old and frail ought to be targeted specially with vaccines is a touchy one. "It is heretical to even suggest that the vaccine may not be effective in the elderly," says Tom Jefferson at Cochrane Vaccines Field in Rome, Italy. This is despite the huge amount of uncertainty and even some bad research in the field, he adds. "The resistance [to such statements] is outright baffling," he says.
Simonsen is of the opinion that the review will lead researchers to explore other options against flu, including creating more potent vaccines for seniors or focusing more on vaccinating school children. "Protecting the elderly indirectly by reducing overall influenza levels in kids, the primary transmitters of the disease, could have real merit," she says.
Saturday, September 29, 2007
Towards a treatment for epilepsy
Japanese neuroscientists from the RIKEN Brain Science Institute have uncovered a mechanism for an epileptic disorder which occurs in infants. “We hope to develop effective therapies for this intractable epilepsy from further work,” says project leader Kazuhiro Yamakawa.
Japanese neuroscientists have clarified the molecular basis of the intractable epileptic disorder known as severe myoclonic epilepsy in infancy (SMEI). In the process they have redefined the position and role of an important protein involved in controlling the firing of nerve impulses in the brain. The work also has generated a mouse model of severe myoclonic epilepsy that the researchers hope to use to study the condition and how to treat it.
More than 200 different mutations of the human SCN1A gene are known to be associated with human epileptic disorders including SMEI. The gene itself encodes an ion-channel protein, Nav1.1, which forms a pore in the plasma membrane that controls the in-flow of electrically-charged sodium ions into nerve cells. This is a significant step in the generation of nerve impulses. There is a homologous gene, Scn1a, in mice.
In a recent paper in The Journal of Neuroscience (1), researchers from the RIKEN Brain Science Institute, Wako, and their colleagues, describe how they produced a ‘knock-in’ mouse, by introducing a disease-causing, nonsense mutation found in SMEI patients into the middle of the Scn1a gene. Mouse pups which inherited copies of the mutant gene from both mother and father were markedly smaller (Fig. 1), developed epilepsy and an unstable gait by the second week after birth, and died within three weeks. Pups with only one copy of the mutant gene began epileptic seizures in the third week, and about 40% had died within three months.
Previous studies suggested that the Nav1.1 protein was distributed rather evenly throughout the brain and could be found in the projections of nerve cells known as dendrites. Using three different antibodies as probes, the RIKEN-based research team corrected this picture. The Nav1.1 proteins are more likely to be found on axons and cell bodies. In particular, they are found on inhibitory nerve cells that express the calcium-binding protein parvalbumin, often in the area known as the axon initial segment where nerve impulses are generated.
By measuring and comparing the output of excitatory and inhibitory neurons in normal and mutant mice, the research team found that the Nav1.1 channel proteins were needed not to initiate firing of the excitatory nerve, but to maintain the inhibitory pulse, thus preventing epileptic seizures.
“We hope to develop effective therapies for this intractable epilepsy from further work,” says project leader Kazuhiro Yamakawa.
Reference
1. Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., Furuichi, T., Hensch, T.K. & Yamakawa, K. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: A circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. The Journal of Neuroscience 27, 5903–5914 (2007).
Japanese neuroscientists from the RIKEN Brain Science Institute have uncovered a mechanism for an epileptic disorder which occurs in infants. “We hope to develop effective therapies for this intractable epilepsy from further work,” says project leader Kazuhiro Yamakawa.
Japanese neuroscientists have clarified the molecular basis of the intractable epileptic disorder known as severe myoclonic epilepsy in infancy (SMEI). In the process they have redefined the position and role of an important protein involved in controlling the firing of nerve impulses in the brain. The work also has generated a mouse model of severe myoclonic epilepsy that the researchers hope to use to study the condition and how to treat it.
More than 200 different mutations of the human SCN1A gene are known to be associated with human epileptic disorders including SMEI. The gene itself encodes an ion-channel protein, Nav1.1, which forms a pore in the plasma membrane that controls the in-flow of electrically-charged sodium ions into nerve cells. This is a significant step in the generation of nerve impulses. There is a homologous gene, Scn1a, in mice.
In a recent paper in The Journal of Neuroscience (1), researchers from the RIKEN Brain Science Institute, Wako, and their colleagues, describe how they produced a ‘knock-in’ mouse, by introducing a disease-causing, nonsense mutation found in SMEI patients into the middle of the Scn1a gene. Mouse pups which inherited copies of the mutant gene from both mother and father were markedly smaller (Fig. 1), developed epilepsy and an unstable gait by the second week after birth, and died within three weeks. Pups with only one copy of the mutant gene began epileptic seizures in the third week, and about 40% had died within three months.
Previous studies suggested that the Nav1.1 protein was distributed rather evenly throughout the brain and could be found in the projections of nerve cells known as dendrites. Using three different antibodies as probes, the RIKEN-based research team corrected this picture. The Nav1.1 proteins are more likely to be found on axons and cell bodies. In particular, they are found on inhibitory nerve cells that express the calcium-binding protein parvalbumin, often in the area known as the axon initial segment where nerve impulses are generated.
By measuring and comparing the output of excitatory and inhibitory neurons in normal and mutant mice, the research team found that the Nav1.1 channel proteins were needed not to initiate firing of the excitatory nerve, but to maintain the inhibitory pulse, thus preventing epileptic seizures.
“We hope to develop effective therapies for this intractable epilepsy from further work,” says project leader Kazuhiro Yamakawa.
Reference
1. Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., Furuichi, T., Hensch, T.K. & Yamakawa, K. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: A circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. The Journal of Neuroscience 27, 5903–5914 (2007).
Fires of creation probed by quarks
Scientists have confirmed that a powerful particle accelerator has recreated the intense conditions that existed just microseconds after the beginning of the universe.
PHENIX detector spots melting particles
Scientists have confirmed that a powerful particle accelerator has recreated the intense conditions that existed just microseconds after the beginning of the universe. The experiments have also revealed a surprise about quarks, the fundamental building blocks of every atomic nucleus.
Quarks are normally held together by gluons, but immediately after the big bang these ingredients existed as a hot quark–gluon plasma (QGP). Understanding how this soup condenses into the discrete particles that make up ordinary matter can help to reveal how the subatomic world works.
To generate quarks of various flavors—known by names such as ‘charm’ or ‘strange’—the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL) in Upton, US, smashes particles together at close to the speed of light.
Scientists working there conducted a series of experiments there in 2004/5 to create and study an unusual particle called J/ψ, made up of a charm quark paired with its opposite number, the anti-charm quark.
The scientists first smashed protons together, and used the PHENIX (Pioneering High Energy Nuclear Interaction eXperiment) detector to spot thousands of J/ψ particle decays1 (Fig. 1).
When they switched protons for gold atoms, the heavier missiles created more intense explosions expected to generate a quark–gluon plasma2. They saw that, as expected, some of the J/ψ particles from the initial explosion were melting in this hot bath, lowering their overall numbers.
“This supports the theoretical prediction that J/ψ will melt in a QGP, and thus provides strong evidence for QGP formation at RHIC,” says Yasuyuki Akiba of RIKEN’s Nishina Center for Accelerator-Based Science, Wako, who is part of the PHENIX team.
Surprisingly, they also found that the central, hotter region of the collision actually hosted more J/ψ particles than the cooler outskirts. This suggests that charm and anti-charm quarks produced at the heart of the collision can recombine into J/ψ. “This is a very intriguing explanation but, at present, the data cannot rule out other possibilities,” adds Akiba.
The team have now just finished collecting a new set of data on gold–gold collisions which will allow them to measure J/ψ much more precisely. They hope they will be able to track the characteristic motion of J/ψ particles produced by recombination of quarks, dubbed ‘elliptic flow’, which would distinguish them from existing J/ψ that failed to melt in the QGP. This would allow them to calculate the balance between melting and recombination effects, revealing more about the primordial QGP.
Reference
1. Adare, A., Afanasiev, S., Aidala, C., Ajitanand, N.N., Akiba, Y., Al-Bataineh, H., Alexander, J., Aoki, K., Aphecetche, L., Armendariz, R. et al. J/ψ production versus transverse momentum and rapidity in p + p collisions at Image Symbol = 200 GeV. Physical Review Letters 98, 232002 (2007).
2. Adare, A., Afanasiev, S., Aidala, C., Ajitanand, N.N., Akiba, Y., Al-Bataineh, H., Alexander, J., Al-Jamel, A., Aoki, K., Aphecetche, L. et al. J/ψ production versus centrality, transverse momentum and rapidity in Au + Au collisions at Image SymbolNN = 200 GeV. Physical Review Letters 98, 232301 (2007).
Scientists have confirmed that a powerful particle accelerator has recreated the intense conditions that existed just microseconds after the beginning of the universe.
PHENIX detector spots melting particles
Scientists have confirmed that a powerful particle accelerator has recreated the intense conditions that existed just microseconds after the beginning of the universe. The experiments have also revealed a surprise about quarks, the fundamental building blocks of every atomic nucleus.
Quarks are normally held together by gluons, but immediately after the big bang these ingredients existed as a hot quark–gluon plasma (QGP). Understanding how this soup condenses into the discrete particles that make up ordinary matter can help to reveal how the subatomic world works.
To generate quarks of various flavors—known by names such as ‘charm’ or ‘strange’—the Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL) in Upton, US, smashes particles together at close to the speed of light.
Scientists working there conducted a series of experiments there in 2004/5 to create and study an unusual particle called J/ψ, made up of a charm quark paired with its opposite number, the anti-charm quark.
The scientists first smashed protons together, and used the PHENIX (Pioneering High Energy Nuclear Interaction eXperiment) detector to spot thousands of J/ψ particle decays1 (Fig. 1).
When they switched protons for gold atoms, the heavier missiles created more intense explosions expected to generate a quark–gluon plasma2. They saw that, as expected, some of the J/ψ particles from the initial explosion were melting in this hot bath, lowering their overall numbers.
“This supports the theoretical prediction that J/ψ will melt in a QGP, and thus provides strong evidence for QGP formation at RHIC,” says Yasuyuki Akiba of RIKEN’s Nishina Center for Accelerator-Based Science, Wako, who is part of the PHENIX team.
Surprisingly, they also found that the central, hotter region of the collision actually hosted more J/ψ particles than the cooler outskirts. This suggests that charm and anti-charm quarks produced at the heart of the collision can recombine into J/ψ. “This is a very intriguing explanation but, at present, the data cannot rule out other possibilities,” adds Akiba.
The team have now just finished collecting a new set of data on gold–gold collisions which will allow them to measure J/ψ much more precisely. They hope they will be able to track the characteristic motion of J/ψ particles produced by recombination of quarks, dubbed ‘elliptic flow’, which would distinguish them from existing J/ψ that failed to melt in the QGP. This would allow them to calculate the balance between melting and recombination effects, revealing more about the primordial QGP.
Reference
1. Adare, A., Afanasiev, S., Aidala, C., Ajitanand, N.N., Akiba, Y., Al-Bataineh, H., Alexander, J., Aoki, K., Aphecetche, L., Armendariz, R. et al. J/ψ production versus transverse momentum and rapidity in p + p collisions at Image Symbol = 200 GeV. Physical Review Letters 98, 232002 (2007).
2. Adare, A., Afanasiev, S., Aidala, C., Ajitanand, N.N., Akiba, Y., Al-Bataineh, H., Alexander, J., Al-Jamel, A., Aoki, K., Aphecetche, L. et al. J/ψ production versus centrality, transverse momentum and rapidity in Au + Au collisions at Image SymbolNN = 200 GeV. Physical Review Letters 98, 232301 (2007).
Getting out of a jam with jellies
One jellyfish can throw a swimmer into a panic, but relentless swarms can disrupt entire economies. Recent, dramatic increases in jellyfish populations—for reasons ranging from overfishing to the impact of global warming on coastal ecosystems—have had equally dramatic effects on human communities.
Several coastal power plants in Japan have been damaged or shut down entirely by the accumulation of tons of jellyfish bodies within their cooling systems, and fishermen in the Sea of Japan now find themselves confronted by nets full of jellyfish—including one particularly massive species (Fig. 1). Removing and disposing of these jellyfish bodies in an economically feasible way represents a major challenge, but a recent discovery by Kiminori Ushida and colleagues at the RIKEN Discovery Research Institute, Wako, and Shinwa Chemical Industries, Kyoto, may offer new hope.
“I know a lot about the economic situation with waste that requires compensation for the cost of collection, transportation and disposal,” Ushida explains. “I felt that figuring out how to make money from jellyfish waste is essential for cleaning up and protecting the environment.” Ushida’s group set about performing a series of extractions on different jellyfish species, and identified a novel protein that consistently appeared in every sample (1). It turned out to be a glycoprotein—a class of proteins naturally linked to sugar molecules—from a family known as mucins.
Mucins are found in many plant and animal species, and are currently used as additives for a number of commercial applications, ranging from cosmetics to medicines. Ushida’s team named their protein ‘qniumucin’, a play on the word ‘kuniumi’; this term from Japanese history refers to the early government that arose to provide stability to a once-disorganized country. “I am worried about the terrible situation of people living in the districts where the ancient Japanese government originated, who are suffering because of these giant jellyfish,” says Ushida, “and I hope that this material will generate new industry in the district, like the ‘rebirth of the countryside’.”
Indeed, qniumucin shows a great deal of promise—its structure is simple and well-understood, making it a candidate for further engineering to enhance particular characteristics. For example, some mucins have proven to be effective as antibiotics. Accordingly, Ushida’s top priority is to make qniumucin extraction as profitable as possible. “We are developing designer mucins to enhance certain functions of our protein,” he says, “and many companies are interested in finding effective commercial uses for qniumucin.”
One jellyfish can throw a swimmer into a panic, but relentless swarms can disrupt entire economies. Recent, dramatic increases in jellyfish populations—for reasons ranging from overfishing to the impact of global warming on coastal ecosystems—have had equally dramatic effects on human communities.
Several coastal power plants in Japan have been damaged or shut down entirely by the accumulation of tons of jellyfish bodies within their cooling systems, and fishermen in the Sea of Japan now find themselves confronted by nets full of jellyfish—including one particularly massive species (Fig. 1). Removing and disposing of these jellyfish bodies in an economically feasible way represents a major challenge, but a recent discovery by Kiminori Ushida and colleagues at the RIKEN Discovery Research Institute, Wako, and Shinwa Chemical Industries, Kyoto, may offer new hope.
“I know a lot about the economic situation with waste that requires compensation for the cost of collection, transportation and disposal,” Ushida explains. “I felt that figuring out how to make money from jellyfish waste is essential for cleaning up and protecting the environment.” Ushida’s group set about performing a series of extractions on different jellyfish species, and identified a novel protein that consistently appeared in every sample (1). It turned out to be a glycoprotein—a class of proteins naturally linked to sugar molecules—from a family known as mucins.
Mucins are found in many plant and animal species, and are currently used as additives for a number of commercial applications, ranging from cosmetics to medicines. Ushida’s team named their protein ‘qniumucin’, a play on the word ‘kuniumi’; this term from Japanese history refers to the early government that arose to provide stability to a once-disorganized country. “I am worried about the terrible situation of people living in the districts where the ancient Japanese government originated, who are suffering because of these giant jellyfish,” says Ushida, “and I hope that this material will generate new industry in the district, like the ‘rebirth of the countryside’.”
Indeed, qniumucin shows a great deal of promise—its structure is simple and well-understood, making it a candidate for further engineering to enhance particular characteristics. For example, some mucins have proven to be effective as antibiotics. Accordingly, Ushida’s top priority is to make qniumucin extraction as profitable as possible. “We are developing designer mucins to enhance certain functions of our protein,” he says, “and many companies are interested in finding effective commercial uses for qniumucin.”
Friday, September 28, 2007
NASA Research Indicates Oxygen on Earth 2.5 Billion Years Ago
NASA-funded astrobiologists have found evidence of oxygen present in Earth's atmosphere earlier than previously known, pushing back the timeline for the rise of
oxygen in the atmosphere. Two teams of researchers report that traces of
oxygen appeared in Earth's atmosphere from 50 to 100 million years before
what is known as the Great Oxidation Event. This event happened between 2.3
and 2.4 billion years ago, when many scientists think atmospheric oxygen
increased significantly from the existing very low levels.
Scientists analyzed a kilometer-long drill core from Western Australia,
representing the time just before the major rise of atmospheric oxygen.
They found evidence that a small but significant amount of oxygen was
present in Earth's oceans and atmosphere 2.5 billion years ago. The
findings appear in a pair of research papers in the Sept. 28 issue of the
journal Science.
"We seem to have captured a piece of time during which the amount of
oxygen was actually changing -- caught in the act, as it were," said Ariel
Anbar, an associate professor at Arizona State University, Tempe, and
leader of one of the research teams.
The goal of both research teams was to learn more about the environment
and life in the oceans leading up to the Great Oxidation Event. The
researchers did not expect to find evidence of oxygen earlier than what was
previously known.
"The core provides a continuous record of environmental conditions,
analogous to a tape recording," explained Anbar. He and his research group
analyzed the amounts of the trace metals molybdenum, rhenium and uranium.
The quantity of these metals in oceans and sediments depend on the amount
of oxygen in the environment. The other research group, led by Alan Kaufman
of the University of Maryland, College Park, Md., analyzed sulfur isotopes.
Its distribution also relies on the abundance of oxygen.
"Studying the dynamics that gave rise to the presence of oxygen in
Earth's atmosphere deepens our appreciation of the complex interaction
between biology and geochemistry," said Carl Pilcher, director of the NASA
Astrobiology Institute at NASA's Ames Research Center, Moffett Field,
Calif., which co- funded the study. "Their results support the idea that
our planet and the life on it evolved together."
One possible explanation for the Great Oxidation Event is the ancient
ancestors of today's plants first began to produce oxygen by
photosynthesis. However, many geoscientists think organisms began to
produce oxygen much earlier, but the oxygen was destroyed in reactions with
volcanic gases and rocks.
"What we have now is new evidence for some oxygen in the environment 50
to 100 million years before the big rise of oxygen," Anbar said. "Our
findings strengthen the notion that organisms learned to produce oxygen
long before the Great Oxidation Event, and that the rise of oxygen in the
atmosphere ultimately was controlled by geological processes."
The international project brought together researchers from Arizona
State University, the University of Maryland, the University of Washington,
the University of California, Riverside, and the University of Alberta. The
project received financial support from the NASA Astrobiology Institute and
the National Science Foundation. The Geological Survey of Western Australia
provided logistical support.
Founded in 1998, the NASA Astrobiology Institute is a partnership
between NASA, 16 U.S. teams and five international consortia to promote,
conduct and lead integrated multidisciplinary astrobiology research and
train a new generation of astrobiology researchers. The institute's
Astrobiology Drilling Program is an international program aimed at
coordinating continental drilling projects of astrobiological significance,
especially those concerning Earth's early atmosphere.
NASA-funded astrobiologists have found evidence of oxygen present in Earth's atmosphere earlier than previously known, pushing back the timeline for the rise of
oxygen in the atmosphere. Two teams of researchers report that traces of
oxygen appeared in Earth's atmosphere from 50 to 100 million years before
what is known as the Great Oxidation Event. This event happened between 2.3
and 2.4 billion years ago, when many scientists think atmospheric oxygen
increased significantly from the existing very low levels.
Scientists analyzed a kilometer-long drill core from Western Australia,
representing the time just before the major rise of atmospheric oxygen.
They found evidence that a small but significant amount of oxygen was
present in Earth's oceans and atmosphere 2.5 billion years ago. The
findings appear in a pair of research papers in the Sept. 28 issue of the
journal Science.
"We seem to have captured a piece of time during which the amount of
oxygen was actually changing -- caught in the act, as it were," said Ariel
Anbar, an associate professor at Arizona State University, Tempe, and
leader of one of the research teams.
The goal of both research teams was to learn more about the environment
and life in the oceans leading up to the Great Oxidation Event. The
researchers did not expect to find evidence of oxygen earlier than what was
previously known.
"The core provides a continuous record of environmental conditions,
analogous to a tape recording," explained Anbar. He and his research group
analyzed the amounts of the trace metals molybdenum, rhenium and uranium.
The quantity of these metals in oceans and sediments depend on the amount
of oxygen in the environment. The other research group, led by Alan Kaufman
of the University of Maryland, College Park, Md., analyzed sulfur isotopes.
Its distribution also relies on the abundance of oxygen.
"Studying the dynamics that gave rise to the presence of oxygen in
Earth's atmosphere deepens our appreciation of the complex interaction
between biology and geochemistry," said Carl Pilcher, director of the NASA
Astrobiology Institute at NASA's Ames Research Center, Moffett Field,
Calif., which co- funded the study. "Their results support the idea that
our planet and the life on it evolved together."
One possible explanation for the Great Oxidation Event is the ancient
ancestors of today's plants first began to produce oxygen by
photosynthesis. However, many geoscientists think organisms began to
produce oxygen much earlier, but the oxygen was destroyed in reactions with
volcanic gases and rocks.
"What we have now is new evidence for some oxygen in the environment 50
to 100 million years before the big rise of oxygen," Anbar said. "Our
findings strengthen the notion that organisms learned to produce oxygen
long before the Great Oxidation Event, and that the rise of oxygen in the
atmosphere ultimately was controlled by geological processes."
The international project brought together researchers from Arizona
State University, the University of Maryland, the University of Washington,
the University of California, Riverside, and the University of Alberta. The
project received financial support from the NASA Astrobiology Institute and
the National Science Foundation. The Geological Survey of Western Australia
provided logistical support.
Founded in 1998, the NASA Astrobiology Institute is a partnership
between NASA, 16 U.S. teams and five international consortia to promote,
conduct and lead integrated multidisciplinary astrobiology research and
train a new generation of astrobiology researchers. The institute's
Astrobiology Drilling Program is an international program aimed at
coordinating continental drilling projects of astrobiological significance,
especially those concerning Earth's early atmosphere.
Monday, September 24, 2007
Finding co-dependent genes in fission yeast
A method for the rapid and large-scale generation of double mutants in a popular yeast strain to determine which genes are functionally dependent on each other.
Yeast is a simple unicellular organism but it comes in many different species that are only very distantly related on an evolutionary scale. The two main species used for research are budding and fission yeast – the former being very popular with geneticists for ease of handling, the latter being of interest because it is more closely related to higher eukaryotes.
Yeast, being a single cell organism, is ideal for the screening of genes that together are essential for survival of the cell. These interaction screens are done in yeast cells with a haploid genome - consisting of only one set of chromosomes – where each cell has mutations in two genes. If the combination of the two genes is required the yeast will die. By generating all possible combinations of gene pairs, a map of genetic interaction can be drawn.
These screens are already widely used in budding yeast, but the difficulty in generating haploid double mutants in fission yeast have prevented their application in this species. Nevan Krogan and colleagues now present a strategy to target genes of interest in fission yeast and select for haploid double-mutant cells. By investigating the pairs of all genes linked to a certain biological process they can draw a comprehensive map of the genes involved in this process.
Comparing the genetic maps in both of these yeast species will shed light on biological pathways that were conserved or diverged during evolution.
Author contact:
Nevan Krogan (University of California, San Francisco)
Tel: +1 415 476 3068; E-mail: krogan@cmp.ucsf.edu
A method for the rapid and large-scale generation of double mutants in a popular yeast strain to determine which genes are functionally dependent on each other.
Yeast is a simple unicellular organism but it comes in many different species that are only very distantly related on an evolutionary scale. The two main species used for research are budding and fission yeast – the former being very popular with geneticists for ease of handling, the latter being of interest because it is more closely related to higher eukaryotes.
Yeast, being a single cell organism, is ideal for the screening of genes that together are essential for survival of the cell. These interaction screens are done in yeast cells with a haploid genome - consisting of only one set of chromosomes – where each cell has mutations in two genes. If the combination of the two genes is required the yeast will die. By generating all possible combinations of gene pairs, a map of genetic interaction can be drawn.
These screens are already widely used in budding yeast, but the difficulty in generating haploid double mutants in fission yeast have prevented their application in this species. Nevan Krogan and colleagues now present a strategy to target genes of interest in fission yeast and select for haploid double-mutant cells. By investigating the pairs of all genes linked to a certain biological process they can draw a comprehensive map of the genes involved in this process.
Comparing the genetic maps in both of these yeast species will shed light on biological pathways that were conserved or diverged during evolution.
Author contact:
Nevan Krogan (University of California, San Francisco)
Tel: +1 415 476 3068; E-mail: krogan@cmp.ucsf.edu
Fountain of youth
Researchers have identified the cells that provide an essential survival factor to newly created immune cells.
White blood cells known as T lymphocytes are born in the thymus and these cells are required to fight off viral and other infections. Upon leaving the thymus these cells prowl throughout the body seeking out potential foreign agents; however, the survival of these cells depends on periodic visits to lymph nodes, where they can ‘recharge’ by receiving a chemical signal called interleukin 7 (IL-7).
It was known for many years that IL-7 provides ‘survival’ signals to these naive T cells, but what actually produced IL-7 proved elusive. Sanjiv Luther and colleagues identify specialized ‘fibroblastic reticular cells’ found in lymph nodes and spleen as the source of IL-7. These cells make chemical signals that direct T cells to them and supply the essential IL-7 that prevents T cells from dying, thereby allowing them to continue to recirculate throughout the body searching for enemies.
Author contact:
Sanjiv Luther (University of Lausanne, Epalinges, Switzerland)
Tel: +41 21 692 5678; E-mail: sanjiv.luther@unil.ch
Researchers have identified the cells that provide an essential survival factor to newly created immune cells.
White blood cells known as T lymphocytes are born in the thymus and these cells are required to fight off viral and other infections. Upon leaving the thymus these cells prowl throughout the body seeking out potential foreign agents; however, the survival of these cells depends on periodic visits to lymph nodes, where they can ‘recharge’ by receiving a chemical signal called interleukin 7 (IL-7).
It was known for many years that IL-7 provides ‘survival’ signals to these naive T cells, but what actually produced IL-7 proved elusive. Sanjiv Luther and colleagues identify specialized ‘fibroblastic reticular cells’ found in lymph nodes and spleen as the source of IL-7. These cells make chemical signals that direct T cells to them and supply the essential IL-7 that prevents T cells from dying, thereby allowing them to continue to recirculate throughout the body searching for enemies.
Author contact:
Sanjiv Luther (University of Lausanne, Epalinges, Switzerland)
Tel: +41 21 692 5678; E-mail: sanjiv.luther@unil.ch
Catching bird flu in a droplet
Detecting bird flu may soon get a whole lot easier.Juergen Pipper and colleagues describe a cheap, fast and effective droplet-based system for detecting the H5N1 virus directly from a throat swab sample in less than 30 minutes. The method could also be adapted to other viruses such as SARS, AIDS and hepatitis B.
In the event of a flu epidemic, its rapid containment would depend on the prompt identification of the first cases. But as routine surveillance may be problematic in countries with limited public health resources, low-cost, easy-to-use detection assays would be are advantageous.
The new system uses droplets that contain particles to automatically isolate, purify and concentrate viral RNA. The method is as sensitive as other available tests, but over one hundred times faster and even cheaper. In addition, it may be applicable not only to the flu virus, but could be adapted to other infectious agents, and to other bodily fluids like blood, urine or saliva.
Author contact:
Juergen Pipper (Institute of Bioengineering and Nanotechnology, Singapore)
Tel: +65 6824 7157; E-mail: jpipper@ibn.a-star.edu.sg
Detecting bird flu may soon get a whole lot easier.Juergen Pipper and colleagues describe a cheap, fast and effective droplet-based system for detecting the H5N1 virus directly from a throat swab sample in less than 30 minutes. The method could also be adapted to other viruses such as SARS, AIDS and hepatitis B.
In the event of a flu epidemic, its rapid containment would depend on the prompt identification of the first cases. But as routine surveillance may be problematic in countries with limited public health resources, low-cost, easy-to-use detection assays would be are advantageous.
The new system uses droplets that contain particles to automatically isolate, purify and concentrate viral RNA. The method is as sensitive as other available tests, but over one hundred times faster and even cheaper. In addition, it may be applicable not only to the flu virus, but could be adapted to other infectious agents, and to other bodily fluids like blood, urine or saliva.
Author contact:
Juergen Pipper (Institute of Bioengineering and Nanotechnology, Singapore)
Tel: +65 6824 7157; E-mail: jpipper@ibn.a-star.edu.sg
In charge of biosensing
A scanning probe microscope capable of detecting changes in the electrical charge on a surface. This technique offers a rapid and sensitive way to sense biological targets, such as DNA and proteins.
Kelvin probe force microscopy (KPFM) is named after Lord Kelvin who investigated how charge is generated when two different materials are brought into close contact. Although KPFM is an established method that has been used to detect biomolecules in microarrays, Angela Belcher and Asher Sinensky have now applied it to measure binding events at the nanoscale. By considering much smaller feature sizes than previously studied, this development has increased both the speed and sensitivity of the technique.
The authors patterned single strands of DNA, which are negatively charged, onto gold substrates and measured their KPFM response. When complementary ‘target’ DNA strands were captured on the surface, the charge density in a given area was doubled and easily detected with KPFM. In this way, Sinensky and Belcher demonstrate the selective sensing of DNA sequences taken from the genes of anthrax and malaria.
Author contact:
Angela Belcher (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 252 1163; E-mail: belcher@mit.edu
Albena Ivanisevic (Purdue University, West Lafayette, IN, USA)
Tel: +1 765 496 3676; E-mail: albena@purdue.edu N&V author
A scanning probe microscope capable of detecting changes in the electrical charge on a surface. This technique offers a rapid and sensitive way to sense biological targets, such as DNA and proteins.
Kelvin probe force microscopy (KPFM) is named after Lord Kelvin who investigated how charge is generated when two different materials are brought into close contact. Although KPFM is an established method that has been used to detect biomolecules in microarrays, Angela Belcher and Asher Sinensky have now applied it to measure binding events at the nanoscale. By considering much smaller feature sizes than previously studied, this development has increased both the speed and sensitivity of the technique.
The authors patterned single strands of DNA, which are negatively charged, onto gold substrates and measured their KPFM response. When complementary ‘target’ DNA strands were captured on the surface, the charge density in a given area was doubled and easily detected with KPFM. In this way, Sinensky and Belcher demonstrate the selective sensing of DNA sequences taken from the genes of anthrax and malaria.
Author contact:
Angela Belcher (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 252 1163; E-mail: belcher@mit.edu
Albena Ivanisevic (Purdue University, West Lafayette, IN, USA)
Tel: +1 765 496 3676; E-mail: albena@purdue.edu N&V author
Saturday, September 22, 2007
Cardiovascular diseases: Periostin regenerates broken heart
By Bethan Hughes
Myocardial infarction, which results in scar formation rather than regeneration of the lost cardiomyocytes responsible for the 'pump' function of the heart, is a major cause of heart failure. Kühn and colleagues, writing in Nature Medicine, now show that following myocardial infarction, cardiomyocytes can be induced to proliferate by a recombinant protein known as periostin, resulting in improved cardiac function. Periostin and the pathway it induces could thus represent a novel therapeutic target for heart failure.
Following observations that cardiomyocytes in the border zone of a myocardial infarction have transiently increased cell-cycle activity, the authors hypothesized that it may be possible to apply extracellular factors to induce cardiomyocyte proliferation. The authors identified periostin — a protein normally expressed during cardiac development but also re-expressed following injury to adult tissue including the myocardium — as a potential factor for inducing proliferation.
In vitro studies showed that periostin induces the full mitotic cell cycle of differentiated mononucleated rat cardiomyocytes. Further examinations showed that periostin requires integrin v and a 1, 3 or 5 subunit to induce cell-cycle re-entry via the phosphatidylinositol-3 kinase (PI3K) pathway. Inhibition of AKT signalling, an important downstream target of PI3K, also reduced periostin-induced cell-cycle re-entry. To confirm these results, adenoviral transduction of the bifunctional phosphatase PTEN, known to regulate the PI3K pathway, abolished periostin-stimulated DNA synthesis in cardiomyocytes. Also, transduction of a constitutively active form of PI3K increased cardiomyocyte DNA synthesis in the absence of periostin, indicating that PI3K signalling is sufficient for cell-cycle re-entry in the absence of periostin.
To determine whether periostin stimulates cardiomyocyte cell-cycle re-entry in vivo, recombinant periostin was injected into the myocardium of rats, resulting in cycling mononucleated cardiomyocytes with periostin-induced DNA synthesis and cytokinesis near the injection site. As it had been previously suggested that sustained cardiomyocyte cell-cycle activity may decrease infarct size following myocardial infarction, Kühn and colleagues developed a long-term delivery system in which periostin is associated with Gelfoam, a biodegradable extracellular matrix.
In a rat model of myocardial infarction, periostin bound to Gelfoam was administered epicardially at the time of heart injury. Twelve weeks later, the periostin-treated rats had improved ventricular remodelling, better myocardial function and reduced infarct size. In periostin-treated hearts, these improvements were attributed to the 100-fold higher proportion of cycling cardiomyocytes compared with apoptotic cardiomyocytes 12 weeks after the myocardial infarction. Also, compared with the control hearts, the periostin-treated hearts had 6 million more cardiomyocyte nuclei. Based on this, the authors concluded that cell-cycle re-entry and division of differentiated cardiomyocytes can account for the periostin-induced functional and structural improvements, which may provide an approach to induce myocardial repair.
ORIGINAL RESEARCH PAPER
Kühn, B. et al. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nature Med. 13, 962–969 (2007)
Wrapping up a cell biology riddle
New research has revealed how protein filaments drive a key cellular process by physically wrapping around and constricting bits of cell membrane
The process of endocytosis, by which a cell internalizes molecules bound to outward-facing receptors, is essential for a wide variety of cellular functions. During the first steps of endocytosis, the cell membrane invaginates, puckering inward to form a pocket that is ultimately pinched off to become a bubble-like vesicle, which can act as a vehicle for delivering encapsulated molecules to various locations within the cell.
This invagination requires the assembly of various proteins into complexes that associate with the membrane and induce deformation and the subsequent formation of membrane ‘tubules’. Tadaomi Takenawa's group at the Kobe University Graduate School of Medicine has focused much of their work on these proteins, and recently identified a protein domain known as EFC/F-BAR that plays a direct role in membrane tubulation1. At the same time, Shigeyuki Yokoyama's research team at the RIKEN Genomic Sciences Center in Yokohama was studying the Cdc42-interacting protein (CIP4), which happens to contain a functional EFC domain. Yokoyama and Takenawa decided to collaborate on an in-depth structural analysis of EFC in an effort to clarify its function.
They found that EFC domains pair off to form crescent-shaped dimers—much like BAR, another known membrane-binding domain, although the curve is far subtler for EFC domains2. “This explains why the EFC domain generates tubular membranes with diameters that are several times larger than those induced by the BAR domain,” says Yokoyama. Surprisingly, the structural data also suggested that these EFC dimers can further assemble into lengthy filaments, which can tightly wrap around—and thereby extend—tubulations in the cell membrane (Fig. 1). Subsequent microscopic analysis of endocytotic cells would demonstrate that this model was accurate. “The physiological function of the EFC filament was predicted by the structure-function analysis of the EFC domain,” says Yokoyama.
Based on these findings, Yokoyama, Takenawa and colleagues were able to develop a more sophisticated model for endocytosis, where EFC proteins like CIP4 drive early stages of invagination through filament formation, then gradually recruit additional proteins like dynamin, which further constrict the tubules before pinching them off to form mature vesicles.
Yokoyama doesn’t think this is the end of the story, however, and his group is continuing to investigate EFC proteins with Takenawa’s team. “We would like to investigate the function of the full-length protein and its interaction partners,” he says, “because we believe that yet unknown, interesting regulatory mechanisms are hidden in this molecule.”
1. Tsujita, K., Suetsugu, S., Sasaki, N., Furutani, M., Oikawa, T. & Takenawa, T. Coordination between actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis. Journal of Cell Biology 172, 269–279 (2006).
2. Shimada, A., Niwa, H., Tsujita, K., Suetsugu, S., Nitta, K., Hanawa-Suetsugu, K., Akasaka, R., Nishino, Y., Toyama, M., Chen, L. et al. Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell 129, 761–772 (2007).
New research has revealed how protein filaments drive a key cellular process by physically wrapping around and constricting bits of cell membrane
The process of endocytosis, by which a cell internalizes molecules bound to outward-facing receptors, is essential for a wide variety of cellular functions. During the first steps of endocytosis, the cell membrane invaginates, puckering inward to form a pocket that is ultimately pinched off to become a bubble-like vesicle, which can act as a vehicle for delivering encapsulated molecules to various locations within the cell.
This invagination requires the assembly of various proteins into complexes that associate with the membrane and induce deformation and the subsequent formation of membrane ‘tubules’. Tadaomi Takenawa's group at the Kobe University Graduate School of Medicine has focused much of their work on these proteins, and recently identified a protein domain known as EFC/F-BAR that plays a direct role in membrane tubulation1. At the same time, Shigeyuki Yokoyama's research team at the RIKEN Genomic Sciences Center in Yokohama was studying the Cdc42-interacting protein (CIP4), which happens to contain a functional EFC domain. Yokoyama and Takenawa decided to collaborate on an in-depth structural analysis of EFC in an effort to clarify its function.
They found that EFC domains pair off to form crescent-shaped dimers—much like BAR, another known membrane-binding domain, although the curve is far subtler for EFC domains2. “This explains why the EFC domain generates tubular membranes with diameters that are several times larger than those induced by the BAR domain,” says Yokoyama. Surprisingly, the structural data also suggested that these EFC dimers can further assemble into lengthy filaments, which can tightly wrap around—and thereby extend—tubulations in the cell membrane (Fig. 1). Subsequent microscopic analysis of endocytotic cells would demonstrate that this model was accurate. “The physiological function of the EFC filament was predicted by the structure-function analysis of the EFC domain,” says Yokoyama.
Based on these findings, Yokoyama, Takenawa and colleagues were able to develop a more sophisticated model for endocytosis, where EFC proteins like CIP4 drive early stages of invagination through filament formation, then gradually recruit additional proteins like dynamin, which further constrict the tubules before pinching them off to form mature vesicles.
Yokoyama doesn’t think this is the end of the story, however, and his group is continuing to investigate EFC proteins with Takenawa’s team. “We would like to investigate the function of the full-length protein and its interaction partners,” he says, “because we believe that yet unknown, interesting regulatory mechanisms are hidden in this molecule.”
1. Tsujita, K., Suetsugu, S., Sasaki, N., Furutani, M., Oikawa, T. & Takenawa, T. Coordination between actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis. Journal of Cell Biology 172, 269–279 (2006).
2. Shimada, A., Niwa, H., Tsujita, K., Suetsugu, S., Nitta, K., Hanawa-Suetsugu, K., Akasaka, R., Nishino, Y., Toyama, M., Chen, L. et al. Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis. Cell 129, 761–772 (2007).
Layering and positioning neurons
Multipolar-to-biopolar neuronal transition is essential during brain development. A team of Japanese scientists have determined that a protein called cyclin-dependent kinase 5 (Cdk5) is required for neurons to develop their proper shape.
A team of Japanese scientists led by Toshio Ohshima, at the RIKEN Brain Science Institute, Wako, has determined that a protein called cyclin-dependent kinase 5 (Cdk5) is required for neurons to develop their proper shape. Morphological defects from a lack of Cdk5 affect the position and function of neurons in many parts of the brain, including the cerebral cortex—or gray matter.
Reporting in the June issue of Development (1), Ohshima and colleagues extend their previous work that demonstrated proper migration of neurons to form the normal six layers of the cortex failed to occur in mice lacking Cdk5.
All cells of the body express Cdk proteins which are necessary for controlling when and how long cells divide. However, Cdk5 is different from other Cdk proteins in that it must be activated by specific ‘accessory’ proteins that are most highly expressed in neurons.
Ohshima and colleagues used several experimental approaches, including introducing a fluorescent ‘tag’ protein into developing brains to follow neuron migration in real-time, to evaluate the function of Cdk5.
As cortical neuron layers develop, the shape of neurons shifts from cells with multiple neuronal projections, or multipolar neurites, to cells with fewer neurites ‘pointing’ in opposite directions (‘bipolar’). The team found that in brains lacking Cdk5, however, the neurons remain multipolar.
This morphological defect was especially pronounced in so-called ‘pyramidal’ neurons (Fig. 1), which are specialized neurons with a single apical (‘top’) dendrite and many basal (‘bottom’) dendrites (hence their bipolar morphology) that represent nearly 80% of the neurons in the cortex.
Commenting on their work Ohshima says that he was initially intrigued with Cdk5 because it regulates proteins associated with devastating diseases such as Alzheimer’s and Amyotrophic Lateral Sclerosis. Serendipitously, however, the team found developmental defects in mice lacking Cdk5, which prompted further experiments.
The team’s new contribution adds to the well-accepted view that Cdk5 function is essential for normal brain development. Of particular note, the team found that pyramidal neurons require Cdk5 for multipolar-to-bipolar transition. But exactly which protein substrates Cdk5 regulates to bring about this transition is still not well understood.
“There are some candidates for Cdk5 substrates, but I have no direct evidence to say which one may be involved in its function,” says Ohshima. Indeed, the next step is to uncover the molecular pathway regulated by Cdk5. Using proteomics approaches—a combination of techniques to understand how proteins interact with one another—is one way Ohshima thinks he and his team can move forward.
Reference
1. Ohshima, T., Hirasawa, M., Tabata, H., Mutoh, T., Adachi, T., Suzuki, H., Saruta, K., Iwasato, T., Itohara, S., Hashimoto, M. et al. Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex. Development 134, 2273–2282 (2007).
Multipolar-to-biopolar neuronal transition is essential during brain development. A team of Japanese scientists have determined that a protein called cyclin-dependent kinase 5 (Cdk5) is required for neurons to develop their proper shape.
A team of Japanese scientists led by Toshio Ohshima, at the RIKEN Brain Science Institute, Wako, has determined that a protein called cyclin-dependent kinase 5 (Cdk5) is required for neurons to develop their proper shape. Morphological defects from a lack of Cdk5 affect the position and function of neurons in many parts of the brain, including the cerebral cortex—or gray matter.
Reporting in the June issue of Development (1), Ohshima and colleagues extend their previous work that demonstrated proper migration of neurons to form the normal six layers of the cortex failed to occur in mice lacking Cdk5.
All cells of the body express Cdk proteins which are necessary for controlling when and how long cells divide. However, Cdk5 is different from other Cdk proteins in that it must be activated by specific ‘accessory’ proteins that are most highly expressed in neurons.
Ohshima and colleagues used several experimental approaches, including introducing a fluorescent ‘tag’ protein into developing brains to follow neuron migration in real-time, to evaluate the function of Cdk5.
As cortical neuron layers develop, the shape of neurons shifts from cells with multiple neuronal projections, or multipolar neurites, to cells with fewer neurites ‘pointing’ in opposite directions (‘bipolar’). The team found that in brains lacking Cdk5, however, the neurons remain multipolar.
This morphological defect was especially pronounced in so-called ‘pyramidal’ neurons (Fig. 1), which are specialized neurons with a single apical (‘top’) dendrite and many basal (‘bottom’) dendrites (hence their bipolar morphology) that represent nearly 80% of the neurons in the cortex.
Commenting on their work Ohshima says that he was initially intrigued with Cdk5 because it regulates proteins associated with devastating diseases such as Alzheimer’s and Amyotrophic Lateral Sclerosis. Serendipitously, however, the team found developmental defects in mice lacking Cdk5, which prompted further experiments.
The team’s new contribution adds to the well-accepted view that Cdk5 function is essential for normal brain development. Of particular note, the team found that pyramidal neurons require Cdk5 for multipolar-to-bipolar transition. But exactly which protein substrates Cdk5 regulates to bring about this transition is still not well understood.
“There are some candidates for Cdk5 substrates, but I have no direct evidence to say which one may be involved in its function,” says Ohshima. Indeed, the next step is to uncover the molecular pathway regulated by Cdk5. Using proteomics approaches—a combination of techniques to understand how proteins interact with one another—is one way Ohshima thinks he and his team can move forward.
Reference
1. Ohshima, T., Hirasawa, M., Tabata, H., Mutoh, T., Adachi, T., Suzuki, H., Saruta, K., Iwasato, T., Itohara, S., Hashimoto, M. et al. Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex. Development 134, 2273–2282 (2007).
Molecules switching position
Collective motion of molecules in a crystal could lead to new electronic devices
Researchers from the RIKEN Discovery Research Institute, Wako, and the Tokyo Institute of Technology have developed a new molecular switch that works by using the collective motion of molecules within a crystal.
Over recent years, many researchers from different backgrounds have focused their attention on developing molecular machines and devices. Molecular switches will play a crucial role in any such machines allowing the tiny devices to be turned on and off. The challenge is to develop a system that allows a reliable connection to be made between the switch and other devices to produce a system or circuit.
With this point in mind, the research group, led by Tatsuo Wada, decided on a new strategy to develop a switch from a supramolecular crystal. This strategy has been reported in Angewandte Chemie1. The benefit of using a crystal is that connection to other devices is straightforward. The crystal is made up of supramolecules known as pseudorotaxanes, which consist of two parts: an axle and a wheel, that form a complex in which the axle is threaded through the wheel.
Using x-ray analysis, Wada and his colleagues could see that all the molecules were aligned in the crystal. Both parts of the molecule contained aromatic groups that were also perfectly aligned, face-to-face, throughout. Surprisingly, upon heating from 30 to 128°C, all the aromatic groups on the axle rotated together through 45° changing their configuration. The groups then moved back to their original orientation on cooling. The molecules could be switched a number of times between both orientations (Fig. 1).
This collective motion was also followed visually. Under polarized light the crystal appeared green then changed to orange when heated. The crystal reverted to green upon cooling. For such a clear color change to be seen, the motion of all the axle molecules must be in the same direction. Free movement of the axle is restricted as a consequence of the position of the wheel.
Masaki Horie, a member of the research group, points out that this project, and the results achieved in developing this thermo-optic switch, would not have been possible without the collaboration of experts from several different fields.
The researchers are now planning to extend this research and create new supramolecular systems that show a variety of controllable motions in the condensed state. They are constructing supramolecular systems that share molecular information and develop collective motion from random motion.
Collective motion of molecules in a crystal could lead to new electronic devices
Researchers from the RIKEN Discovery Research Institute, Wako, and the Tokyo Institute of Technology have developed a new molecular switch that works by using the collective motion of molecules within a crystal.
Over recent years, many researchers from different backgrounds have focused their attention on developing molecular machines and devices. Molecular switches will play a crucial role in any such machines allowing the tiny devices to be turned on and off. The challenge is to develop a system that allows a reliable connection to be made between the switch and other devices to produce a system or circuit.
With this point in mind, the research group, led by Tatsuo Wada, decided on a new strategy to develop a switch from a supramolecular crystal. This strategy has been reported in Angewandte Chemie1. The benefit of using a crystal is that connection to other devices is straightforward. The crystal is made up of supramolecules known as pseudorotaxanes, which consist of two parts: an axle and a wheel, that form a complex in which the axle is threaded through the wheel.
Using x-ray analysis, Wada and his colleagues could see that all the molecules were aligned in the crystal. Both parts of the molecule contained aromatic groups that were also perfectly aligned, face-to-face, throughout. Surprisingly, upon heating from 30 to 128°C, all the aromatic groups on the axle rotated together through 45° changing their configuration. The groups then moved back to their original orientation on cooling. The molecules could be switched a number of times between both orientations (Fig. 1).
This collective motion was also followed visually. Under polarized light the crystal appeared green then changed to orange when heated. The crystal reverted to green upon cooling. For such a clear color change to be seen, the motion of all the axle molecules must be in the same direction. Free movement of the axle is restricted as a consequence of the position of the wheel.
Masaki Horie, a member of the research group, points out that this project, and the results achieved in developing this thermo-optic switch, would not have been possible without the collaboration of experts from several different fields.
The researchers are now planning to extend this research and create new supramolecular systems that show a variety of controllable motions in the condensed state. They are constructing supramolecular systems that share molecular information and develop collective motion from random motion.
Friday, September 21, 2007
Geochemistry: Argon retention in terrestrial planets
The Earth’s mantle may not be as efficient as previously thought at expelling gases, such as argon. The study challenges the assumption that most argon escapes into the atmosphere through partial melting when mantle rocks are brought near the Earth’s surface, and concludes that atmospheric argon may therefore not be such a reliable indicator of the vigour of planetary convection.
Stable noble gases such as xenon, helium and argon are generally used as tracers of mantle degassing. It has generally been thought that the Earth releases a large percentage of the gases contained in rocks during episodes of partial melting in the mantle, followed by ascent of the melt to the surface where the gas can move into the atmosphere. That is, scientists believe that noble gases behave as ‘incompatible’ elements during mantle melting — partitioning into a melt as soon as melting begins.
Bruce Watson and colleagues question this theory with data showing that argon doesn’t actually behave in this way. They find that argon is much more compatible in mantle minerals than previously thought, and that the diffusion of argon through mantle minerals is much slower. They conclude that an alternative to magmatism is needed to explain the abundance of argon in the atmosphere, pointing to the hydration of oceanic crust containing argon-rich minerals as a possible source.
Because the mantles of the other terrestrial planets are dominated by similar minerals, the authors note that their results will affect theories of degassing on Mars and Venus as well as Earth.
CONTACT
Bruce Watson (Rensselaer Polytechnic Institute, Troy, NY, USA)
Tel: +1 518 276 8838; E-mail: watsoe@rpi.edum
Chris J. Ballentine (University of Manchester, UK) N&V author
Tel: +44 161 275 3832; E-mail: chris.ballentine@manchester.ac.uk
The Earth’s mantle may not be as efficient as previously thought at expelling gases, such as argon. The study challenges the assumption that most argon escapes into the atmosphere through partial melting when mantle rocks are brought near the Earth’s surface, and concludes that atmospheric argon may therefore not be such a reliable indicator of the vigour of planetary convection.
Stable noble gases such as xenon, helium and argon are generally used as tracers of mantle degassing. It has generally been thought that the Earth releases a large percentage of the gases contained in rocks during episodes of partial melting in the mantle, followed by ascent of the melt to the surface where the gas can move into the atmosphere. That is, scientists believe that noble gases behave as ‘incompatible’ elements during mantle melting — partitioning into a melt as soon as melting begins.
Bruce Watson and colleagues question this theory with data showing that argon doesn’t actually behave in this way. They find that argon is much more compatible in mantle minerals than previously thought, and that the diffusion of argon through mantle minerals is much slower. They conclude that an alternative to magmatism is needed to explain the abundance of argon in the atmosphere, pointing to the hydration of oceanic crust containing argon-rich minerals as a possible source.
Because the mantles of the other terrestrial planets are dominated by similar minerals, the authors note that their results will affect theories of degassing on Mars and Venus as well as Earth.
CONTACT
Bruce Watson (Rensselaer Polytechnic Institute, Troy, NY, USA)
Tel: +1 518 276 8838; E-mail: watsoe@rpi.edum
Chris J. Ballentine (University of Manchester, UK) N&V author
Tel: +44 161 275 3832; E-mail: chris.ballentine@manchester.ac.uk
Stem cells: Identifying self renewing cells
Large numbers of adult stem cells can be efficiently obtained from testis, thanks to a newly identified molecule on the cell surface that will allow researchers to tell them apart from non-self-renewing cell types.
Shahin Rafii and colleagues report that a newly discovered marker, GPR125, flags rapidly multiplying adult spermatogonial progenitor cells and does not appear on differentiated germ-cell counterparts. They developed a system whereby they can use this marker to generate large numbers of stem cells from mouse testicles. These stem-cell populations formed functioning blood vessels in mice, and it has been demonstrated that they convert to cardiac tissue in culture.
CONTACT
Shahin Rafii (Weill Medical College of Cornell University, New York, NY, USA)
Tel: +1 212 746 2070; E-mail: srafii@med.cornell.edu
Marco Seandel (Memorial Sloan Kettering Cancer Center, Howard Hughes Medical Institute & Weill Cornell Medical Center, New York, NY, USA) Co-author
Tel: +1 212 746 2017; E-mail: SeandelM@MSKCC.ORG
Jonathan Weil (Director of Research Communications, Weill Cornell Medical College, New York, NY, USA)
Tel: +1 212 821 0566; E-mail: jweil@med.cornell.edu
Large numbers of adult stem cells can be efficiently obtained from testis, thanks to a newly identified molecule on the cell surface that will allow researchers to tell them apart from non-self-renewing cell types.
Shahin Rafii and colleagues report that a newly discovered marker, GPR125, flags rapidly multiplying adult spermatogonial progenitor cells and does not appear on differentiated germ-cell counterparts. They developed a system whereby they can use this marker to generate large numbers of stem cells from mouse testicles. These stem-cell populations formed functioning blood vessels in mice, and it has been demonstrated that they convert to cardiac tissue in culture.
CONTACT
Shahin Rafii (Weill Medical College of Cornell University, New York, NY, USA)
Tel: +1 212 746 2070; E-mail: srafii@med.cornell.edu
Marco Seandel (Memorial Sloan Kettering Cancer Center, Howard Hughes Medical Institute & Weill Cornell Medical Center, New York, NY, USA) Co-author
Tel: +1 212 746 2017; E-mail: SeandelM@MSKCC.ORG
Jonathan Weil (Director of Research Communications, Weill Cornell Medical College, New York, NY, USA)
Tel: +1 212 821 0566; E-mail: jweil@med.cornell.edu
Primitive hominins outside Africa
Scientists have uncovered the remains of three adults and one adolescent individual, 1.77 million years old, from the Plio-Pleistocene sight of Dmanisi, Georgia. The remains — early evidence of the genus Homo outside Africa — are remarkably well preserved and the postcranial material displays a mixture of primitive and more advanced features. David Lordkipanidze and colleagues analyse the fossils and discuss their evolutionary context in this week’s Nature.
Over the last few decades the site of Dmanisi has yielded a rich fossil and archaeological record — animal remains, primitive tools, and fossil hominin skulls and jaws have all been unearthed. Scientists’ knowledge of the cranio-facial morphology of these early species is reasonably well developed, but there has been little ‘postcranial’ evidence from a complete skeleton.
The authors now present a partial skeleton of an adolescent individual associated with a skull, and the postcranial remains of three adults. The hominins have relatively small cranial capacities and primitive australopith-like upper limbs. However, their spines and lower limbs seem essentially modern, indicating the capability for long-distance travel.
The authors conclude that the Dmanisi hominins — the first hominin species currently known from outside Africa — did not display a full set of advanced locomotor features apparent in African Homo erectus and later hominins. The fossils therefore fill significant gaps in our knowledge of a critical period in human evolution — the transition from autralopith-like species to more modern human-like morphologies.
CONTACT
David Lordkipanidze (Georgian State Museum, Tbilisi, Republic of Georgia)
Tel: +995 32 99 80 22; E-mail: dlordkipanidze@museum.ge
Daniel Lieberman (Harvard University, Cambridge, MA, USA) N&V author
Tel: +1 617 495 5479; E-mail: danlieb@fas.harvard.edu
Scientists have uncovered the remains of three adults and one adolescent individual, 1.77 million years old, from the Plio-Pleistocene sight of Dmanisi, Georgia. The remains — early evidence of the genus Homo outside Africa — are remarkably well preserved and the postcranial material displays a mixture of primitive and more advanced features. David Lordkipanidze and colleagues analyse the fossils and discuss their evolutionary context in this week’s Nature.
Over the last few decades the site of Dmanisi has yielded a rich fossil and archaeological record — animal remains, primitive tools, and fossil hominin skulls and jaws have all been unearthed. Scientists’ knowledge of the cranio-facial morphology of these early species is reasonably well developed, but there has been little ‘postcranial’ evidence from a complete skeleton.
The authors now present a partial skeleton of an adolescent individual associated with a skull, and the postcranial remains of three adults. The hominins have relatively small cranial capacities and primitive australopith-like upper limbs. However, their spines and lower limbs seem essentially modern, indicating the capability for long-distance travel.
The authors conclude that the Dmanisi hominins — the first hominin species currently known from outside Africa — did not display a full set of advanced locomotor features apparent in African Homo erectus and later hominins. The fossils therefore fill significant gaps in our knowledge of a critical period in human evolution — the transition from autralopith-like species to more modern human-like morphologies.
CONTACT
David Lordkipanidze (Georgian State Museum, Tbilisi, Republic of Georgia)
Tel: +995 32 99 80 22; E-mail: dlordkipanidze@museum.ge
Daniel Lieberman (Harvard University, Cambridge, MA, USA) N&V author
Tel: +1 617 495 5479; E-mail: danlieb@fas.harvard.edu
Neuroscience: Serotonin and the brain
Serotonin is used faster in the winter by people suffering from seasonal depression when compared with a control group, according to research to be published in Neurpsychopharmacology this month. The research also shows that serotonin usage returns to normal both where depression is treated effectively and during the summer months.
In depression, studies have found that the brain has too little of a neurotransmitter known as serotonin. However, why the brains of people with depression have low levels of serotonin is not known. Matthaus Williet and colleagues studied the primary way that the brain removes serotonin, known as the serotonin transporter, using an easily accessible model system: the blood platelets. The researchers tested this for a specific type of depression, known as seasonal depression; a depression that worsens in the winter and improves in the summer. This finding, if replicated, could help identify people at risk for depression and could lead to development of a new line of treatment.
Contact:
Matthaus Willeit (Medical University Vienna, Austria)
Tel: +43 1 40 400 3543; E-mail: matthaeus.willeit@medunivien.ac.at
Serotonin is used faster in the winter by people suffering from seasonal depression when compared with a control group, according to research to be published in Neurpsychopharmacology this month. The research also shows that serotonin usage returns to normal both where depression is treated effectively and during the summer months.
In depression, studies have found that the brain has too little of a neurotransmitter known as serotonin. However, why the brains of people with depression have low levels of serotonin is not known. Matthaus Williet and colleagues studied the primary way that the brain removes serotonin, known as the serotonin transporter, using an easily accessible model system: the blood platelets. The researchers tested this for a specific type of depression, known as seasonal depression; a depression that worsens in the winter and improves in the summer. This finding, if replicated, could help identify people at risk for depression and could lead to development of a new line of treatment.
Contact:
Matthaus Willeit (Medical University Vienna, Austria)
Tel: +43 1 40 400 3543; E-mail: matthaeus.willeit@medunivien.ac.at
Chicken cathelicidin-B1, an antimicrobial guardian
at the mucosal M cell gateway
Ryo Goitsuka*†, Chen-lo H. Chen‡§, Lesley Benyon‡, Yusuke Asano*, Daisuke Kitamura*, and Max D. Cooper‡§¶**††
*Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; ‡Division of Developmental and Clinical Immunology,
University of Alabama at Birmingham, Birmingham, AL 35294-2812 ; and Departments of ¶Medicine, Pediatrics, §Microbiology, and **Pathology, University
of Alabama at Birmingham, Birmingham, AL 35294-3300
Contributed by Max D. Cooper, July 26, 2007 (sent for review May 25, 2007)
Mucosal epithelial M cells provide an efficient portal of entry for
microorganisms. Initially defined by their irregular microvilli and
abundant transcytotic channels in the avian bursa of Fabricius,Mcells
also are found in the lymphoid follicle-associated epithelium of the
mammalian appendix, Peyer’s patches, and other mucosal surfacelymphoid
interfaces. We describe here a previously unrecognized
cathelicidin gene in chickens, chCATH-B1, that is expressed exclusively
in the epithelium of the bursa of Fabricius. Like the mature peptides
of previously identified cathelicidins, the carboxyl-terminal peptide of
chCATH-B1 has broad antimicrobial activity against Gram-positive
and Gram-negative bacteria. chCATH-B1 expression is restricted to
the secretory epithelial cell neighbors of the M cells, whereas its
mature peptide is transported to become concentrated on the fibrillar
network surrounding basolateral surfaces of the M cells that overlie
the bursal lymphoid follicles. We conclude that chCATH-B1 is well
placed to serve a protective antimicrobial role at the M cell gateway.
antimicrobial peptides follicle-associated epithelium innate immunity
bursa of Fabricius
The survival of all multicellular organisms depends on an
effective immune response to microbial pathogens. The first
hurdle to microbial entry is provided by our epithelial surfaces.
Microbial pathogens that mount this barrier encounter innate
immunity elements as a first line of defense. Innate immune
responses also facilitate the ensuing adaptive immune responses
that vertebrates use to clear infectious agents. The mucosal M
cells are an important microbial portal of entry because of their
highly efficient pinocytotic channels. Initially identified as specialized
epithelial cells overlying the lymphoid follicles of the
avian bursa of Fabricius that have irregular microvilli and
efficient transcytotic capability (1),Mcells were also found to be
conserved in the lymphoid follicle-associated epithelium of
mammalian appendix and intestinal Peyer’s patches (1, 2). The
Mcells have since been found in other mucosal lymphoid tissues,
including those of the upper and lower airways, oropharynx,
salivary glands, stomach, colon, and eye (3, 4), where they
provide an efficient conduit for transporting microorganisms
and other antigenic substances into the underlying lymphoid
structures to initiate immune responses (5, 6). Despite the
physiological importance of this entry portal, there is limited
information about the differentiation of the M cells, their
transport mechanism(s), and how the microbes that constantly
enter the body via the M cells are rendered noninvasive.
Antimicrobial peptides are well known as front-line participants
in microbial defense (7–10). Two evolutionary groups of
antimicrobial peptides, the cathelicidins and the defensins, provide
endogenous peptide-based defense against microbial invasion
(11–13). Cathelicidins and defensins are produced by many
cell types and have broad spectrum antimicrobial activity against
bacteria, fungi, and viruses. As one example, the human cathelicidin
LL-37 (also called hCAP-18, FALL-39, and CAMP) is
produced by neutrophils, B cells, T cells, natural killer cells,
monocytes, and macrophages (14–16); it is also found in the
squamous epithelium of the mouth, tongue, and esophagus, as
well as in the colonic and bronchial mucosal epithelium (17).
LL-37 expression is negligible in normal skin, but epidermal cells
are induced to express high levels of LL-37 in inflammatory
conditions, such as psoriasis and contact dermatitis (18). Conversely,
deficiencies in the LL-37 cathelicidin and the HBD-2
defensin may underlie the Staphylococcus aureus skin infections
that plague patients with atopic dermatitis (19). Recent studies
have also indicated the importance of epithelial cathelicidin in
the maintenance of the sterility of the human urinary tract (20).
Remarkably, neither cathelicidins nor defensins have been identified
at the M cell interface, where one might anticipate their
need. We report here an avian cathelicidin that appears to fulfill
this expectation. This peptide was identified during a search for
genes expressed preferentially in the bursa of Fabricius.
Results
Identification of a Bursa-Specific Cathelicidin, chCATH-B1. Our search
for bursa-specific genes began with the cloning of bursal cDNA
subtracted by splenic cDNA and yielded cDNA clones, some of
which have been reported (21). Among these, BFG7 is expressed
exclusively in the bursa of Fabricius as shown by Northern blot
analysis (Fig. 1). Sequence analysis of a full-length BFG7 cDNA did
not yield a match with then-reported genes. However, a BLAST
search of the National Center for Biotechnology Information
protein database revealed aBFG7cathelin domain sequence, which
is a conserved hallmark of the cathelicidin gene family (Fig. 2).
Although conserved cathelin regions of mammalian cathelicidins
share 50% or greater amino acid identity (12), the BFG7 cathelin
region has only 20–30% homology with mammalian cathelicidins.
This is in the ‘‘twilight’’ zone of sequence similarity but is within the
range of identity shared by many avian and mammalian orthologs
(22). Provisionally, we have named this cathelicidin relative
‘‘chicken cathelicidin-B1,’’ or chCATH-B1, in view of its selective
expression in the bursa of Fabricius.
Proteolytic cleavage of mammalian cathelicidin proproteins
yields mature C-terminal peptides with antimicrobial activity. In
this context, a comparative alignment of chCATH-B1 with
mammalian cathelin region sequences predicted a cationic peptide
of 40 C-terminal amino acid residues with a high pI value
(pI 12.2) (Fig. 2).
This peptide sequence appears to belong to
Author contributions: R.G., C.-l.H.C., and M.D.C. designed research; R.G., C.-l.H.C., L.B., and
Y.A. performed research; C.-l.H.C. contributed new reagents/analytic tools; R.G., C.-l.H.C.,
D.K., and M.D.C. analyzed data; and R.G., C.-l.H.C., and M.D.C. wrote the paper.
The authors declare no conflict of interest.
Data deposition: The sequences reported in this paper have been deposited in the DNA
Data Bank of Japan database, www.ddbj.nig.ac.jp (accession nos. AB307733 and AB308318
for chCATH-B1).
†To whom correspondence may be addressed at: Division of Development and Aging, 2669
Yamazaki, Noda, Chiba 278-0022, Japan. E-mail: ryogoi@rs.noda.tus.ac.jp.
††To whom correspondence may be addressed at: University of Alabama at Birmingham,
401 Shelby Research Building, 1825 University Boulevard, Birmingham, AL 35294-2812.
E-mail: max.cooper@ccc.uab.edu.
This article contains supporting information online at www.pnas.org/cgi/content/full/
0707037104/DC1.
© 2007 by The National Academy of Sciences of the USA
at the mucosal M cell gateway
Ryo Goitsuka*†, Chen-lo H. Chen‡§, Lesley Benyon‡, Yusuke Asano*, Daisuke Kitamura*, and Max D. Cooper‡§¶**††
*Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan; ‡Division of Developmental and Clinical Immunology,
University of Alabama at Birmingham, Birmingham, AL 35294-2812 ; and Departments of ¶Medicine, Pediatrics, §Microbiology, and **Pathology, University
of Alabama at Birmingham, Birmingham, AL 35294-3300
Contributed by Max D. Cooper, July 26, 2007 (sent for review May 25, 2007)
Mucosal epithelial M cells provide an efficient portal of entry for
microorganisms. Initially defined by their irregular microvilli and
abundant transcytotic channels in the avian bursa of Fabricius,Mcells
also are found in the lymphoid follicle-associated epithelium of the
mammalian appendix, Peyer’s patches, and other mucosal surfacelymphoid
interfaces. We describe here a previously unrecognized
cathelicidin gene in chickens, chCATH-B1, that is expressed exclusively
in the epithelium of the bursa of Fabricius. Like the mature peptides
of previously identified cathelicidins, the carboxyl-terminal peptide of
chCATH-B1 has broad antimicrobial activity against Gram-positive
and Gram-negative bacteria. chCATH-B1 expression is restricted to
the secretory epithelial cell neighbors of the M cells, whereas its
mature peptide is transported to become concentrated on the fibrillar
network surrounding basolateral surfaces of the M cells that overlie
the bursal lymphoid follicles. We conclude that chCATH-B1 is well
placed to serve a protective antimicrobial role at the M cell gateway.
antimicrobial peptides follicle-associated epithelium innate immunity
bursa of Fabricius
The survival of all multicellular organisms depends on an
effective immune response to microbial pathogens. The first
hurdle to microbial entry is provided by our epithelial surfaces.
Microbial pathogens that mount this barrier encounter innate
immunity elements as a first line of defense. Innate immune
responses also facilitate the ensuing adaptive immune responses
that vertebrates use to clear infectious agents. The mucosal M
cells are an important microbial portal of entry because of their
highly efficient pinocytotic channels. Initially identified as specialized
epithelial cells overlying the lymphoid follicles of the
avian bursa of Fabricius that have irregular microvilli and
efficient transcytotic capability (1),Mcells were also found to be
conserved in the lymphoid follicle-associated epithelium of
mammalian appendix and intestinal Peyer’s patches (1, 2). The
Mcells have since been found in other mucosal lymphoid tissues,
including those of the upper and lower airways, oropharynx,
salivary glands, stomach, colon, and eye (3, 4), where they
provide an efficient conduit for transporting microorganisms
and other antigenic substances into the underlying lymphoid
structures to initiate immune responses (5, 6). Despite the
physiological importance of this entry portal, there is limited
information about the differentiation of the M cells, their
transport mechanism(s), and how the microbes that constantly
enter the body via the M cells are rendered noninvasive.
Antimicrobial peptides are well known as front-line participants
in microbial defense (7–10). Two evolutionary groups of
antimicrobial peptides, the cathelicidins and the defensins, provide
endogenous peptide-based defense against microbial invasion
(11–13). Cathelicidins and defensins are produced by many
cell types and have broad spectrum antimicrobial activity against
bacteria, fungi, and viruses. As one example, the human cathelicidin
LL-37 (also called hCAP-18, FALL-39, and CAMP) is
produced by neutrophils, B cells, T cells, natural killer cells,
monocytes, and macrophages (14–16); it is also found in the
squamous epithelium of the mouth, tongue, and esophagus, as
well as in the colonic and bronchial mucosal epithelium (17).
LL-37 expression is negligible in normal skin, but epidermal cells
are induced to express high levels of LL-37 in inflammatory
conditions, such as psoriasis and contact dermatitis (18). Conversely,
deficiencies in the LL-37 cathelicidin and the HBD-2
defensin may underlie the Staphylococcus aureus skin infections
that plague patients with atopic dermatitis (19). Recent studies
have also indicated the importance of epithelial cathelicidin in
the maintenance of the sterility of the human urinary tract (20).
Remarkably, neither cathelicidins nor defensins have been identified
at the M cell interface, where one might anticipate their
need. We report here an avian cathelicidin that appears to fulfill
this expectation. This peptide was identified during a search for
genes expressed preferentially in the bursa of Fabricius.
Results
Identification of a Bursa-Specific Cathelicidin, chCATH-B1. Our search
for bursa-specific genes began with the cloning of bursal cDNA
subtracted by splenic cDNA and yielded cDNA clones, some of
which have been reported (21). Among these, BFG7 is expressed
exclusively in the bursa of Fabricius as shown by Northern blot
analysis (Fig. 1). Sequence analysis of a full-length BFG7 cDNA did
not yield a match with then-reported genes. However, a BLAST
search of the National Center for Biotechnology Information
protein database revealed aBFG7cathelin domain sequence, which
is a conserved hallmark of the cathelicidin gene family (Fig. 2).
Although conserved cathelin regions of mammalian cathelicidins
share 50% or greater amino acid identity (12), the BFG7 cathelin
region has only 20–30% homology with mammalian cathelicidins.
This is in the ‘‘twilight’’ zone of sequence similarity but is within the
range of identity shared by many avian and mammalian orthologs
(22). Provisionally, we have named this cathelicidin relative
‘‘chicken cathelicidin-B1,’’ or chCATH-B1, in view of its selective
expression in the bursa of Fabricius.
Proteolytic cleavage of mammalian cathelicidin proproteins
yields mature C-terminal peptides with antimicrobial activity. In
this context, a comparative alignment of chCATH-B1 with
mammalian cathelin region sequences predicted a cationic peptide
of 40 C-terminal amino acid residues with a high pI value
(pI 12.2) (Fig. 2).
This peptide sequence appears to belong to
Author contributions: R.G., C.-l.H.C., and M.D.C. designed research; R.G., C.-l.H.C., L.B., and
Y.A. performed research; C.-l.H.C. contributed new reagents/analytic tools; R.G., C.-l.H.C.,
D.K., and M.D.C. analyzed data; and R.G., C.-l.H.C., and M.D.C. wrote the paper.
The authors declare no conflict of interest.
Data deposition: The sequences reported in this paper have been deposited in the DNA
Data Bank of Japan database, www.ddbj.nig.ac.jp (accession nos. AB307733 and AB308318
for chCATH-B1).
†To whom correspondence may be addressed at: Division of Development and Aging, 2669
Yamazaki, Noda, Chiba 278-0022, Japan. E-mail: ryogoi@rs.noda.tus.ac.jp.
††To whom correspondence may be addressed at: University of Alabama at Birmingham,
401 Shelby Research Building, 1825 University Boulevard, Birmingham, AL 35294-2812.
E-mail: max.cooper@ccc.uab.edu.
This article contains supporting information online at www.pnas.org/cgi/content/full/
0707037104/DC1.
© 2007 by The National Academy of Sciences of the USA
Monday, September 17, 2007
Differentiating strains of Gumboro disease
Infectious bursal disease (IBD) also known as Gumboro disease is the second most important poultry disease after Newcastle disease. In this study, we reported for the first time the use of Sybr Green I based real-time PCR to differentiate different strains of IBD virus.
Project Title: IBDReal check
Researchers: Abdul Rahman Omar, Aini Ideris, Mohd Hair Bejo, Hairul Aini Hamzah and Kong Lih Ling
Infectious bursal disease (IBD) also known as Gumboro disease is the second most important poultry disease after Newcastle disease. Economical loses associated with IBD is highly mortality and poor vaccine performances due to immune suppression. Even though, infection with very virulent IBDV associated with distinct pathological lesions, the diagnosis of IBD is complicated due to presence of vaccine-induced immunity. In addition, laboratory detection of field strains of IBDV may facilitate farmers to choose the appropriate vaccines to vaccinate their flocks against very virulent IBDV.
The current routine method to differentiate very virulent and vaccine strains of IBDV is by restriction fragment length polymorphism of VP2 gene. However, this method is time consuming, prone to error and less sensitive. Hence, development of improved laboratory detection method is essential for effective control of clinical and sub-clinical IBDV outbreaks. Rapid advances have been made in the development of real-time PCR techniques in the detection of avian pathogens.
In most of the studies, the detection of viruses was based on real-time PCR assays utilizing probe labeled with TaqMan or FRET technology. Besides fluorescent labeled probe PCR assay, Sybr Green I based real-time PCR assay has been used to detect viruses that affect humans such as dengue viruses and hepatitis viruses. This has also been used to detect genetic polymorphisms or genotyping of genes that are associated with clinical disorders in humans. Studies on the application of Sybr Green I based real-time PCR in differentiating different strains of poultry viruses is lacking.
In this study, we reported for the first time the use of Sybr Green I based real-time PCR to differentiate different strains of IBDV. The developed assays were optimized using novel set of primers and previously characterized field and vaccine strains of IBDV (Malaysian Patent PI 20044610). Based on the optimized PCR procedures, a signatory threshold value (Ct) and melting temperature (Tm) values were established as the basis for the detection and differentiation of IBDV strains. The optimized PCR procedure has been transformed into a prototype kit, IBDReal check. The performances of the kit are currently been tested and validated using both standard and clinical samples.
The kit has 100 % specificity when compared to other established IBD detection tests including sequencing of the VP2 gene. In addition, the kit detects dual infections ie. vvIBDV and vaccine strains from bursa samples obtained from outbreak cases of IBDV and at least as sensitive as the conventional virus isolation in embryonated eggs. Furthermore, compared to fluorescent labeled probe based real-time PCR, the developed kit is more rapid, economical and suitable to be used as routine high throughput assay in diagnosing IBDV in chickens.
For more information, please contact
Dr. Nayan KANWAL
Email: ndeeps@admin.upm.edu.my
Infectious bursal disease (IBD) also known as Gumboro disease is the second most important poultry disease after Newcastle disease. In this study, we reported for the first time the use of Sybr Green I based real-time PCR to differentiate different strains of IBD virus.
Project Title: IBDReal check
Researchers: Abdul Rahman Omar, Aini Ideris, Mohd Hair Bejo, Hairul Aini Hamzah and Kong Lih Ling
Infectious bursal disease (IBD) also known as Gumboro disease is the second most important poultry disease after Newcastle disease. Economical loses associated with IBD is highly mortality and poor vaccine performances due to immune suppression. Even though, infection with very virulent IBDV associated with distinct pathological lesions, the diagnosis of IBD is complicated due to presence of vaccine-induced immunity. In addition, laboratory detection of field strains of IBDV may facilitate farmers to choose the appropriate vaccines to vaccinate their flocks against very virulent IBDV.
The current routine method to differentiate very virulent and vaccine strains of IBDV is by restriction fragment length polymorphism of VP2 gene. However, this method is time consuming, prone to error and less sensitive. Hence, development of improved laboratory detection method is essential for effective control of clinical and sub-clinical IBDV outbreaks. Rapid advances have been made in the development of real-time PCR techniques in the detection of avian pathogens.
In most of the studies, the detection of viruses was based on real-time PCR assays utilizing probe labeled with TaqMan or FRET technology. Besides fluorescent labeled probe PCR assay, Sybr Green I based real-time PCR assay has been used to detect viruses that affect humans such as dengue viruses and hepatitis viruses. This has also been used to detect genetic polymorphisms or genotyping of genes that are associated with clinical disorders in humans. Studies on the application of Sybr Green I based real-time PCR in differentiating different strains of poultry viruses is lacking.
In this study, we reported for the first time the use of Sybr Green I based real-time PCR to differentiate different strains of IBDV. The developed assays were optimized using novel set of primers and previously characterized field and vaccine strains of IBDV (Malaysian Patent PI 20044610). Based on the optimized PCR procedures, a signatory threshold value (Ct) and melting temperature (Tm) values were established as the basis for the detection and differentiation of IBDV strains. The optimized PCR procedure has been transformed into a prototype kit, IBDReal check. The performances of the kit are currently been tested and validated using both standard and clinical samples.
The kit has 100 % specificity when compared to other established IBD detection tests including sequencing of the VP2 gene. In addition, the kit detects dual infections ie. vvIBDV and vaccine strains from bursa samples obtained from outbreak cases of IBDV and at least as sensitive as the conventional virus isolation in embryonated eggs. Furthermore, compared to fluorescent labeled probe based real-time PCR, the developed kit is more rapid, economical and suitable to be used as routine high throughput assay in diagnosing IBDV in chickens.
For more information, please contact
Dr. Nayan KANWAL
Email: ndeeps@admin.upm.edu.my
Sunday, September 16, 2007
Clockwork orange beats time for the body
A RIKEN-led team of researchers from Japan and the US has used an innovative combination of genome survey techniques in live Drosophila fruit flies to reveal a previously unknown master gene involved in setting circadian rhythms.
Researchers find new master gene setting circadian rhythms
It is the tenth of a series of genes which generate proteins that interact in complex interlocking feedback loops to measure day length.
This network of genes, which has been highly conserved during evolution, ensures that the rhythms of organisms—sleep and wakefulness, changes in body temperature, the secretion of hormones—are attuned to daily and seasonal cycles. In humans, such common problems as jet lag and lack of alertness of shift workers arise when the body’s circadian rhythms are not properly adjusted to the external environment. But permanent disruption of the body’s clock can lead to much more serious disorders, such as delayed sleep phase syndrome. It has also been implicated in mental illness. The work could well have relevance to treating these conditions.
In a recent issue of the journal Genes & Development (1), the research group—from RIKEN’s Center for Developmental Biology in Kobe, Kyushu University, Japan’s National Institute of Genetics and two universities in Texas—detailed how they found the new gene, clockwork orange (cwo).
With micro-array technology that shows which genes are switched on, the researchers initially followed the daily activity pattern of all genes in the genome of the head region of the fruit fly. Then, using RNA interference techniques, they blocked the activity of each of the nearly 130 genes which showed regular daily cycles of activity, and looked for dramatic disturbances of overall rhythmic behavior. This happened in only the few cases where they disrupted the core circadian genes which set the body’s clock. Of these, cwo was the gene that had the most pronounced impact.
Using a combination of micro-array technology and antibodies, the group then set out to discover the proteins and genes with which cwo interacts. The genes they found were all known to play a key role in the network which regulates the body’s internal clock.
“The work is still far from complete,” says Hiroki Ueda, the research team leader. “But I feel the discovery of cwo, which has a counterpart in the human genome, represents an important step in deciphering biological clocks. We next want to apply our techniques to the mouse, which is very near to humans compared with the fruit fly.”
Reference
1. Matsumoto, A., Ukai-Tadenuma, M., Yamada, R.G., Houl, J., Uno, K.D., Kasukawa, T., Dauwalder, B., Itoh, T.Q., Takahashi, K., Ueda, R., Hardin, P., Tanimura, T. & Ueda, H.R. A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes & Development 21, 1687–1700 (2007).
A RIKEN-led team of researchers from Japan and the US has used an innovative combination of genome survey techniques in live Drosophila fruit flies to reveal a previously unknown master gene involved in setting circadian rhythms.
Researchers find new master gene setting circadian rhythms
It is the tenth of a series of genes which generate proteins that interact in complex interlocking feedback loops to measure day length.
This network of genes, which has been highly conserved during evolution, ensures that the rhythms of organisms—sleep and wakefulness, changes in body temperature, the secretion of hormones—are attuned to daily and seasonal cycles. In humans, such common problems as jet lag and lack of alertness of shift workers arise when the body’s circadian rhythms are not properly adjusted to the external environment. But permanent disruption of the body’s clock can lead to much more serious disorders, such as delayed sleep phase syndrome. It has also been implicated in mental illness. The work could well have relevance to treating these conditions.
In a recent issue of the journal Genes & Development (1), the research group—from RIKEN’s Center for Developmental Biology in Kobe, Kyushu University, Japan’s National Institute of Genetics and two universities in Texas—detailed how they found the new gene, clockwork orange (cwo).
With micro-array technology that shows which genes are switched on, the researchers initially followed the daily activity pattern of all genes in the genome of the head region of the fruit fly. Then, using RNA interference techniques, they blocked the activity of each of the nearly 130 genes which showed regular daily cycles of activity, and looked for dramatic disturbances of overall rhythmic behavior. This happened in only the few cases where they disrupted the core circadian genes which set the body’s clock. Of these, cwo was the gene that had the most pronounced impact.
Using a combination of micro-array technology and antibodies, the group then set out to discover the proteins and genes with which cwo interacts. The genes they found were all known to play a key role in the network which regulates the body’s internal clock.
“The work is still far from complete,” says Hiroki Ueda, the research team leader. “But I feel the discovery of cwo, which has a counterpart in the human genome, represents an important step in deciphering biological clocks. We next want to apply our techniques to the mouse, which is very near to humans compared with the fruit fly.”
Reference
1. Matsumoto, A., Ukai-Tadenuma, M., Yamada, R.G., Houl, J., Uno, K.D., Kasukawa, T., Dauwalder, B., Itoh, T.Q., Takahashi, K., Ueda, R., Hardin, P., Tanimura, T. & Ueda, H.R. A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes & Development 21, 1687–1700 (2007).
Core structures
Japanese scientists describe crystal structures at the heart of antitumor compound synthesis
Japanese biochemists have brought the design of anticancer compounds a step closer in a study published recently in the Proceedings of the National Academy of Sciences USA1. Shingo Nagano, Yoshitsugu Shiro and their colleagues from the RIKEN SPring-8 Center, the University of Hyogo and Toyama Prefectural University have studied the biosynthesis of a natural product called staurosporine. This molecule is isolated from bacteria of the genus Streptomyces and is of interest because it exhibits antitumor activity. Staurosporine has been identified as a potent inhibitor of enzymes that regulate cell growth and death, known as protein kinases.
Staurosporine is a member of a family of compounds whose biosynthesis involves the formation of a base unit called an indolocarbazole core. Because of their potential as therapeutic agents for cancer and neurodegenerative diseases, indolocarbazole compounds have attracted scientists’ attention.
The formation of the indolocarbazole core in part involves binding a molecule of chromopyrrolic acid with an enzyme known as cytochrome P450 StaP. StaP is a member of the cytochrome P450 family of compounds which includes enzymes involved in steroid hormone biosynthesis, drug metabolism and many other physiologically important reactions.
Nagano and co-workers presents the first report of the precise arrangement of atoms during a key stage in the formation of the core structure. The configuration of atoms they describe is known as its crystal structure and is elucidated using the technology of x-ray crystallography, a method of determining the arrangement of atoms in a molecule by analyzing the reflection patterns of x-rays directed at it.
The study provides high resolution crystal structures of StaP in the presence and absence of the substrate chromopyrrolic acid (Fig. 1). The structure of the complex with the substrate StaP in place provides structural insights into the process of enzyme-substrate recognition and the molecular mechanism of indolocarbazole core formation.
This crystallographic study provides valuable insights into the process of staurosporine biosynthesis, the mechanism of indolocarbazole synthesis, and the diverse chemistry performed by cytochrome P450s.
“The ultimate goal of our project on indolocarbazole is structure-based design of enzymes that produce ‘unnatural’ indolocarbazole which have improved antitumor activity or new bioactivities,” says Nagano. Moving forward, in a study to be published shortly, the group has described the structure of an enzyme involved in another similar reaction. The ultimate aim is to synthesize a variety of indolocarbazole compounds that could have important therapeutic use in the fight against cancer.
Reference
1. Makino, M., Sugimoto, H., Shiro, Y., Asamizu, S., Onaka, H., & Nagano, S. Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton. Proceedings of the National Academy of Sciences USA 104, 11591–11596 (2007).
Japanese scientists describe crystal structures at the heart of antitumor compound synthesis
Japanese biochemists have brought the design of anticancer compounds a step closer in a study published recently in the Proceedings of the National Academy of Sciences USA1. Shingo Nagano, Yoshitsugu Shiro and their colleagues from the RIKEN SPring-8 Center, the University of Hyogo and Toyama Prefectural University have studied the biosynthesis of a natural product called staurosporine. This molecule is isolated from bacteria of the genus Streptomyces and is of interest because it exhibits antitumor activity. Staurosporine has been identified as a potent inhibitor of enzymes that regulate cell growth and death, known as protein kinases.
Staurosporine is a member of a family of compounds whose biosynthesis involves the formation of a base unit called an indolocarbazole core. Because of their potential as therapeutic agents for cancer and neurodegenerative diseases, indolocarbazole compounds have attracted scientists’ attention.
The formation of the indolocarbazole core in part involves binding a molecule of chromopyrrolic acid with an enzyme known as cytochrome P450 StaP. StaP is a member of the cytochrome P450 family of compounds which includes enzymes involved in steroid hormone biosynthesis, drug metabolism and many other physiologically important reactions.
Nagano and co-workers presents the first report of the precise arrangement of atoms during a key stage in the formation of the core structure. The configuration of atoms they describe is known as its crystal structure and is elucidated using the technology of x-ray crystallography, a method of determining the arrangement of atoms in a molecule by analyzing the reflection patterns of x-rays directed at it.
The study provides high resolution crystal structures of StaP in the presence and absence of the substrate chromopyrrolic acid (Fig. 1). The structure of the complex with the substrate StaP in place provides structural insights into the process of enzyme-substrate recognition and the molecular mechanism of indolocarbazole core formation.
This crystallographic study provides valuable insights into the process of staurosporine biosynthesis, the mechanism of indolocarbazole synthesis, and the diverse chemistry performed by cytochrome P450s.
“The ultimate goal of our project on indolocarbazole is structure-based design of enzymes that produce ‘unnatural’ indolocarbazole which have improved antitumor activity or new bioactivities,” says Nagano. Moving forward, in a study to be published shortly, the group has described the structure of an enzyme involved in another similar reaction. The ultimate aim is to synthesize a variety of indolocarbazole compounds that could have important therapeutic use in the fight against cancer.
Reference
1. Makino, M., Sugimoto, H., Shiro, Y., Asamizu, S., Onaka, H., & Nagano, S. Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeleton. Proceedings of the National Academy of Sciences USA 104, 11591–11596 (2007).
Saturday, September 15, 2007
Seminar Report: Multi-national, Multi-institutional Consultation on Biotechnology and Biosafety
"Biotechnology has the potential to produce more food to meet the increasing demand in developing countries, but it must be nutritionally and environmentally safe." Representatives and scientists from 16 countries and three international organizations met in Syria to develop an integrated regional framework on biotechnology and biosafety.
Representatives and scientists from ministries of agriculture and environment from 16 countries and three international organizations participated in the “Regional Consultation on Biotechnology and Biosafety for Agriculture and Environment in the West Asia and North Africa Sub-region,” held at ICARDA, Aleppo, Syria, 8-10 September.
Co-sponsored by FAO, UNEP and ICARDA, the objective of this workshop was to develop, through a participatory approach, a proposal for an integrated regional framework on biotechnology and biosafety involving major stakeholders.
Opening the workshop, Dr Mahmoud Solh, Director General of ICARDA, said that biotechnology offers the potential to deliver a new and more sustainable way of producing more food to meet the increasing demand in developing countries, but it must be nutritionally and environmentally safe. To increase the benefits from biotechnology and to reduce its negative impact, we need to rapidly evolve a clear regulatory biosafety framework through which to bring biotechnology products to the grower and consumer. Biosafety regulation is an integral part of the development of any transgenic variety, he said. Dr Solh expressed hope that the deliberations of the meeting would help develop and strengthen biosafety capacity, and promote the use of agricultural biotechnology in a manner that would pave the way for better environmental sustainability through the implementation of national biosafety frameworks.
Dr Kakoli Ghosh, representing the Food and Agriculture Organization (FAO), said that FAO was seeking to establish linkages between agriculture and environment to deal with the challenges of biosafety. “Biotechnology holds great promise for conservation and sustainable use of plant diversity. In this context biosafety acquires greater meaning. We would like to find a way to handle biosafety in an integrated manner to deal with needs of both agriculture and environment. Action-oriented programs and regional and national initiatives on biosafety are required to ensure that all stakeholders get the best benefit of biotechnology development,” she said.
Dr Fee Chon Chong, Manager of UNEP/GEF Projects on the Implementation of National Biosafety Frameworks, said biosafety should not be seen as an obstacle in the development of biotechnology, which can answer surmountable problems in the field of agriculture and health. Biosafety is necessary to ensure that farmers are not poorer by adopting new technologies, she said. Dr Chong added that this is the first time such a broad-based consultation, involving ministries of agriculture, ministries of environment, multi-institutional and multi-organizational representatives, is taking place.
Dr Michael Baum, ICARDA’s Biotechnologist, made a presentation on regional cooperation on biotechnology and biosafety. “ There is a need for establishing a network that allows formalized and structured cooperation between leading research institutes in the region on biotechnology and biosafety. This would also help avoid duplication of efforts and increase cooperation between research centers,” Dr Baum said.
Some countries in the region have already implemented their national biosafety framework or are in the process of developing it.
From Egypt, Dr Taymour Nasr El-Din, Director, Agricultural Genetic Engineering Research Institute (AGERI), said that the work on developing biosafety regulations had started early in Egypt with assistance from USAID. “Egypt could contribute to the regional biosafety framework through its experience in technical aspects of handling transgenic material. We have trained staff and accumulated knowledge in this field,” he said.
Iran has also established a National Biosafety Council. “We are now focusing on sugar beet, date palm, potato, alfalfa and some other plants. The work on Bt rice is at an advanced stage and it is in the process of getting permission from the National Biosafety Council of Iran for commercial release,’’ Dr Mojtaba Khayam Nekoye, Director, Agriculture Biotechnology Research Institute of Iran (ABRI), said.
It was apparent from the presentations of country representatives that so far no transgenic crop variety has been commercialized in the participating countries. The consultation concluded by forming a follow-up committee representing all stakeholders, to develop a regional project for GEF’s consideration to enhance capacity in biotechnology and biosafety as well as to harmonize biosafety regulations across West Asia and North Africa.
The participants unanimously commended the outcome of the consultation.
For more information: Dr Michael Baum (m.baum@cgiar.org)
About ICARDA: Established in 1977, ICARDA (www.icarda.org) is one of the 15 international research centers supported by the Consultative Group on International Agricultural Research (CGIAR). ICARDA serves the entire developing world for the improvement of barley, lentil, and faba bean; and dry-area developing countries for the on-farm management of water, improvement of nutrition and productivity of small ruminants (sheep and goats), and rehabilitation and management of rangelands. In the Central and West Asia and North Africa (CWANA) region, ICARDA is responsible for the improvement of durum and bread wheats, chickpea, pasture and forage legumes and farming systems; and for the protection and enhancement of the natural resource base of water, land, and biodiversity.
The Consultative Group on International Agricultural Research (CGIAR) (http://www.cgiar.org) is a strategic alliance of countries, international and regional organizations, and private foundations supporting15 international research centers that mobilizes cutting-edge science to promote sustainable development by reducing hunger and poverty, improving human nutrition and health, and protecting the environment.
INTERNATIONAL CENTER FOR AGRICULTURAL RESEARCH IN THE DRY AREAS
P.O. Box 5466, Aleppo, Syria
Phone: (963-21) 2213433, 2213477, 2225112, 2225012
Fax: (963-21) 2213490, 2225105; E-mail: ICARDA@CGIAR.ORG
"Biotechnology has the potential to produce more food to meet the increasing demand in developing countries, but it must be nutritionally and environmentally safe." Representatives and scientists from 16 countries and three international organizations met in Syria to develop an integrated regional framework on biotechnology and biosafety.
Representatives and scientists from ministries of agriculture and environment from 16 countries and three international organizations participated in the “Regional Consultation on Biotechnology and Biosafety for Agriculture and Environment in the West Asia and North Africa Sub-region,” held at ICARDA, Aleppo, Syria, 8-10 September.
Co-sponsored by FAO, UNEP and ICARDA, the objective of this workshop was to develop, through a participatory approach, a proposal for an integrated regional framework on biotechnology and biosafety involving major stakeholders.
Opening the workshop, Dr Mahmoud Solh, Director General of ICARDA, said that biotechnology offers the potential to deliver a new and more sustainable way of producing more food to meet the increasing demand in developing countries, but it must be nutritionally and environmentally safe. To increase the benefits from biotechnology and to reduce its negative impact, we need to rapidly evolve a clear regulatory biosafety framework through which to bring biotechnology products to the grower and consumer. Biosafety regulation is an integral part of the development of any transgenic variety, he said. Dr Solh expressed hope that the deliberations of the meeting would help develop and strengthen biosafety capacity, and promote the use of agricultural biotechnology in a manner that would pave the way for better environmental sustainability through the implementation of national biosafety frameworks.
Dr Kakoli Ghosh, representing the Food and Agriculture Organization (FAO), said that FAO was seeking to establish linkages between agriculture and environment to deal with the challenges of biosafety. “Biotechnology holds great promise for conservation and sustainable use of plant diversity. In this context biosafety acquires greater meaning. We would like to find a way to handle biosafety in an integrated manner to deal with needs of both agriculture and environment. Action-oriented programs and regional and national initiatives on biosafety are required to ensure that all stakeholders get the best benefit of biotechnology development,” she said.
Dr Fee Chon Chong, Manager of UNEP/GEF Projects on the Implementation of National Biosafety Frameworks, said biosafety should not be seen as an obstacle in the development of biotechnology, which can answer surmountable problems in the field of agriculture and health. Biosafety is necessary to ensure that farmers are not poorer by adopting new technologies, she said. Dr Chong added that this is the first time such a broad-based consultation, involving ministries of agriculture, ministries of environment, multi-institutional and multi-organizational representatives, is taking place.
Dr Michael Baum, ICARDA’s Biotechnologist, made a presentation on regional cooperation on biotechnology and biosafety. “ There is a need for establishing a network that allows formalized and structured cooperation between leading research institutes in the region on biotechnology and biosafety. This would also help avoid duplication of efforts and increase cooperation between research centers,” Dr Baum said.
Some countries in the region have already implemented their national biosafety framework or are in the process of developing it.
From Egypt, Dr Taymour Nasr El-Din, Director, Agricultural Genetic Engineering Research Institute (AGERI), said that the work on developing biosafety regulations had started early in Egypt with assistance from USAID. “Egypt could contribute to the regional biosafety framework through its experience in technical aspects of handling transgenic material. We have trained staff and accumulated knowledge in this field,” he said.
Iran has also established a National Biosafety Council. “We are now focusing on sugar beet, date palm, potato, alfalfa and some other plants. The work on Bt rice is at an advanced stage and it is in the process of getting permission from the National Biosafety Council of Iran for commercial release,’’ Dr Mojtaba Khayam Nekoye, Director, Agriculture Biotechnology Research Institute of Iran (ABRI), said.
It was apparent from the presentations of country representatives that so far no transgenic crop variety has been commercialized in the participating countries. The consultation concluded by forming a follow-up committee representing all stakeholders, to develop a regional project for GEF’s consideration to enhance capacity in biotechnology and biosafety as well as to harmonize biosafety regulations across West Asia and North Africa.
The participants unanimously commended the outcome of the consultation.
For more information: Dr Michael Baum (m.baum@cgiar.org)
About ICARDA: Established in 1977, ICARDA (www.icarda.org) is one of the 15 international research centers supported by the Consultative Group on International Agricultural Research (CGIAR). ICARDA serves the entire developing world for the improvement of barley, lentil, and faba bean; and dry-area developing countries for the on-farm management of water, improvement of nutrition and productivity of small ruminants (sheep and goats), and rehabilitation and management of rangelands. In the Central and West Asia and North Africa (CWANA) region, ICARDA is responsible for the improvement of durum and bread wheats, chickpea, pasture and forage legumes and farming systems; and for the protection and enhancement of the natural resource base of water, land, and biodiversity.
The Consultative Group on International Agricultural Research (CGIAR) (http://www.cgiar.org) is a strategic alliance of countries, international and regional organizations, and private foundations supporting15 international research centers that mobilizes cutting-edge science to promote sustainable development by reducing hunger and poverty, improving human nutrition and health, and protecting the environment.
INTERNATIONAL CENTER FOR AGRICULTURAL RESEARCH IN THE DRY AREAS
P.O. Box 5466, Aleppo, Syria
Phone: (963-21) 2213433, 2213477, 2225112, 2225012
Fax: (963-21) 2213490, 2225105; E-mail: ICARDA@CGIAR.ORG
Pinpointing the end of Neanderthals
What caused the demise of Neanderthals in Europe, some time around 28,000 years ago? Was it climate, or the arrival of modern humans? The conundrum exists partly because of problems establishing when events in the past actually happened. Polychronis Tzedakis and colleagues report, a way to relate Neanderthal remains to the palaeoclimate record.
All living things use carbon, mostly in the form of the isotope 12C, but a small proportion of carbon in the environment is the radioactive 14C. When an animal dies, the proportion of 14C is fixed and decays at a fixed rate. By measuring the amount of 14C in a fossil, and comparing it with the proportion thought to exist in the creature when it was alive, researchers can estimate the date the creature died.
The problem is that the proportion of 14C in the environment itself varies, which means that ‘radiocarbon’ years and actual calendar years don't always match. The discrepancy was especially marked at around the time the Neanderthals went extinct, making it hard to work out the chronology of their last days. Tzedakis and colleagues got round the problem by ignoring actual chronology completely. They relate radiocarbon years directly to palaeoclimate through a deep-sea core drilled in the Cariaco Basin, Venezuela, in which records of past climate can be related directly to radiocarbon date.
The team investigate three proposed dates for the end of the Neanderthals and find that the oldest two do not coincide with any extreme climate events. The youngest, and most controversial, occurs just before the final expansion of ice sheets, but this was a several 1000-year long gradual transition rather than an abrupt cold snap that would explain a sudden extinction.
CONTACTS
Polychronis Tzedakis (University of Leeds, UK)
Tel: +44 113 343 3300; E-mail: p.c.tzedakis@leeds.ac.uk
Please note the author is travelling but will be available on his mobile:
Tel: +30 697 221 9198
What caused the demise of Neanderthals in Europe, some time around 28,000 years ago? Was it climate, or the arrival of modern humans? The conundrum exists partly because of problems establishing when events in the past actually happened. Polychronis Tzedakis and colleagues report, a way to relate Neanderthal remains to the palaeoclimate record.
All living things use carbon, mostly in the form of the isotope 12C, but a small proportion of carbon in the environment is the radioactive 14C. When an animal dies, the proportion of 14C is fixed and decays at a fixed rate. By measuring the amount of 14C in a fossil, and comparing it with the proportion thought to exist in the creature when it was alive, researchers can estimate the date the creature died.
The problem is that the proportion of 14C in the environment itself varies, which means that ‘radiocarbon’ years and actual calendar years don't always match. The discrepancy was especially marked at around the time the Neanderthals went extinct, making it hard to work out the chronology of their last days. Tzedakis and colleagues got round the problem by ignoring actual chronology completely. They relate radiocarbon years directly to palaeoclimate through a deep-sea core drilled in the Cariaco Basin, Venezuela, in which records of past climate can be related directly to radiocarbon date.
The team investigate three proposed dates for the end of the Neanderthals and find that the oldest two do not coincide with any extreme climate events. The youngest, and most controversial, occurs just before the final expansion of ice sheets, but this was a several 1000-year long gradual transition rather than an abrupt cold snap that would explain a sudden extinction.
CONTACTS
Polychronis Tzedakis (University of Leeds, UK)
Tel: +44 113 343 3300; E-mail: p.c.tzedakis@leeds.ac.uk
Please note the author is travelling but will be available on his mobile:
Tel: +30 697 221 9198
Planetary science: Two-score ice ages for Mars
The forty major ice ages experienced by Mars over the past five million years can explain the present distribution of subsurface ice.
More so than the Earth, Mars experiences dramatic changes in incident sunlight that can redistribute ice on a global scale. By numerically simulating the retreat and growth of ground ice, Norbert Schorghofer has shown how the subsurface ice sheets would have evolved over the many ice ages that occurred on Mars over the past five million years, to end up in the state we see them today. These processes have given rise to a three-layer sequence of ice at high latitudes, and ice in the pores of rocks at mid-latitudes. Combined, these provide enough ice to be compatible with that predicted from spacecraft observations of Mars.
The dynamic nature of martian ice sheets makes them an ideal system in which to test our knowledge of astronomical climate forcing. Furthermore, a great deal might be learned about terrestrial ice ages from the study of martian ice layering — a longer, cleaner and simpler record than Earth’s.
CONTACT
Norbert Schorghofer (University of Hawaii, Honolulu, HI, USA)
Tel: +1 808 956 9086; E-mail: norbert@hawaii.edu
The forty major ice ages experienced by Mars over the past five million years can explain the present distribution of subsurface ice.
More so than the Earth, Mars experiences dramatic changes in incident sunlight that can redistribute ice on a global scale. By numerically simulating the retreat and growth of ground ice, Norbert Schorghofer has shown how the subsurface ice sheets would have evolved over the many ice ages that occurred on Mars over the past five million years, to end up in the state we see them today. These processes have given rise to a three-layer sequence of ice at high latitudes, and ice in the pores of rocks at mid-latitudes. Combined, these provide enough ice to be compatible with that predicted from spacecraft observations of Mars.
The dynamic nature of martian ice sheets makes them an ideal system in which to test our knowledge of astronomical climate forcing. Furthermore, a great deal might be learned about terrestrial ice ages from the study of martian ice layering — a longer, cleaner and simpler record than Earth’s.
CONTACT
Norbert Schorghofer (University of Hawaii, Honolulu, HI, USA)
Tel: +1 808 956 9086; E-mail: norbert@hawaii.edu
Drug delivery: Wet or dry
By Felix Cheung
AbstractSmart surfaces can be switched between water-loving and water-repelling states in response to temperature, pH and glucose changes
Materials with surfaces that attract (superhydrophilic) and repel (superhydrophobic) water have many applications, especially in drug delivery. Now, Guangzhao Zhang at the University of Science and Technology of China in Hefei, Lei Jiang at the Chinese Academy of Sciences in Beijing and co-workers1 have prepared a 'smart' surface that can switch between these extreme states in response to temperature, pH and glucose changes.
The researchers coated a silicon wafer with a copolymer consisting of a temperature-sensitive block and a block sensitive to changes in pH and glucose. They then studied the contact angle that a water droplet makes on the wafer when one of the standard conditions (26 °C; pH7.4; glucose concentration of 8.6 gram per litre) is varied.
The researchers found that the coating on the wafer becomes hydrophilic at low temperatures and hydrophobic at high temperatures. An increase in the pH or glucose concentration shifts the 'equilibrium temperature' — the temperature of the balance between hydrophilic and hydrophobic properties — to a higher value. Furthermore, the water repellence of the coating can be greatly enhanced by using a rough wafer instead of a flat one.
The coating is durable and its ability to switch remains even after being laid aside without special protection for two months or longer. The technology could find application in glucose-responsive drugs that control the release of insulin to treat diabetes.
By Felix Cheung
AbstractSmart surfaces can be switched between water-loving and water-repelling states in response to temperature, pH and glucose changes
Materials with surfaces that attract (superhydrophilic) and repel (superhydrophobic) water have many applications, especially in drug delivery. Now, Guangzhao Zhang at the University of Science and Technology of China in Hefei, Lei Jiang at the Chinese Academy of Sciences in Beijing and co-workers1 have prepared a 'smart' surface that can switch between these extreme states in response to temperature, pH and glucose changes.
The researchers coated a silicon wafer with a copolymer consisting of a temperature-sensitive block and a block sensitive to changes in pH and glucose. They then studied the contact angle that a water droplet makes on the wafer when one of the standard conditions (26 °C; pH7.4; glucose concentration of 8.6 gram per litre) is varied.
The researchers found that the coating on the wafer becomes hydrophilic at low temperatures and hydrophobic at high temperatures. An increase in the pH or glucose concentration shifts the 'equilibrium temperature' — the temperature of the balance between hydrophilic and hydrophobic properties — to a higher value. Furthermore, the water repellence of the coating can be greatly enhanced by using a rough wafer instead of a flat one.
The coating is durable and its ability to switch remains even after being laid aside without special protection for two months or longer. The technology could find application in glucose-responsive drugs that control the release of insulin to treat diabetes.
Thursday, September 13, 2007
Outlook: Neglected diseases
One-sixth of the world’s population is affected by tropical diseases, yet the drug ‘pipeline’ for these diseases is almost dry. Why this urgent need for development of effective therapies is not being met.
Although the factors hindering drug development are well understood in the developed-world environment, the process becomes significantly more complicated when dealing with diseases that disproportionally afflict poor and marginalized populations. Peter Singer and colleagues investigate what additional problems exist in the developing world. Practical issues are paramount — many areas have no electricity, which means that drugs cannot be stored appropriately. And cultural considerations are vital to encourage uptake of a new treatment or technology — often scientists arrive with plans that do not suit the local populations. Singer presents a model for the future, the result of interviews with 70 key experts from academic, industrial, civil and governmental sectors, which takes into account ethical and practical factors.
Also in the supplement, Declan Butler investigates the role of academia in bridging the gap between basic research and effective therapies for neglected diseases. Benedicte Callan and Iain Gillespie write about the path to new medicines and the need for greater government involvement in this process. And Patricia Danzon argues that subsidies coupled with differential pricing could provide incentives for the development of drugs for diseases that have no market in the developed world.
CONTACT
Peter Singer (McLaughlin–Rotman Centre for Global Health, University of Toronto, Canada)
E-mail: peter.singer@utoronto.ca
One-sixth of the world’s population is affected by tropical diseases, yet the drug ‘pipeline’ for these diseases is almost dry. Why this urgent need for development of effective therapies is not being met.
Although the factors hindering drug development are well understood in the developed-world environment, the process becomes significantly more complicated when dealing with diseases that disproportionally afflict poor and marginalized populations. Peter Singer and colleagues investigate what additional problems exist in the developing world. Practical issues are paramount — many areas have no electricity, which means that drugs cannot be stored appropriately. And cultural considerations are vital to encourage uptake of a new treatment or technology — often scientists arrive with plans that do not suit the local populations. Singer presents a model for the future, the result of interviews with 70 key experts from academic, industrial, civil and governmental sectors, which takes into account ethical and practical factors.
Also in the supplement, Declan Butler investigates the role of academia in bridging the gap between basic research and effective therapies for neglected diseases. Benedicte Callan and Iain Gillespie write about the path to new medicines and the need for greater government involvement in this process. And Patricia Danzon argues that subsidies coupled with differential pricing could provide incentives for the development of drugs for diseases that have no market in the developed world.
CONTACT
Peter Singer (McLaughlin–Rotman Centre for Global Health, University of Toronto, Canada)
E-mail: peter.singer@utoronto.ca
Wednesday, September 12, 2007
Seminar Announcement
International Seminar on Andalusia 1300 years - Call for papers People
Revealing the secret of the glorious Islamic civilization in the West. The theme for this conference is Knowledge Integration Based On Tawhid.
THEME
Knowledge Integration Based On Tawhid
DATE
5 - 6 March 2008
VENUE
Dewan Budaya
Universiti Sains Malaysia
ORGANISED BY
Secretariat of Islamic Philosophy and Science
(SEFSI)
Send abstract and full paper to the following address :
Jawatankuasa Seminar Antarabangsa Andalusia 1300 Tahun
d/a Sekretariat Falsafah dan Sains Islam (SEFSI)
Universiti Sains Malaysia
11800 Pulau Pinang
Tel : 00-604-6533884 / 00-604-6533869
Direct line / Fax : 00-604-6561305
Email : sefsi@usm.my / azlinazubaidi@notes.usm.my / shakirah@usm.my
http://www.usm.my/sefsi
International Seminar on Andalusia 1300 years - Call for papers People
Revealing the secret of the glorious Islamic civilization in the West. The theme for this conference is Knowledge Integration Based On Tawhid.
THEME
Knowledge Integration Based On Tawhid
DATE
5 - 6 March 2008
VENUE
Dewan Budaya
Universiti Sains Malaysia
ORGANISED BY
Secretariat of Islamic Philosophy and Science
(SEFSI)
Send abstract and full paper to the following address :
Jawatankuasa Seminar Antarabangsa Andalusia 1300 Tahun
d/a Sekretariat Falsafah dan Sains Islam (SEFSI)
Universiti Sains Malaysia
11800 Pulau Pinang
Tel : 00-604-6533884 / 00-604-6533869
Direct line / Fax : 00-604-6561305
Email : sefsi@usm.my / azlinazubaidi@notes.usm.my / shakirah@usm.my
http://www.usm.my/sefsi
Nanofiltration Process for Pesticides Removal
Producing food for the increasing human population generally results in increased use of pesticides, which is finding its way into drinking water supplies. This research is proven to filter up to 85 % of dimethoate and more than 95% of atrazine.
Title of project: Modulated Nanofiltration Process for Pesticides Removal: An Agriculture Remediation
Prof. Abdul Latif Ahmad
Dr. Syamsul Rizal Abd. Shukor
Tan Lian See
Producing sufficient agriculture crops for the increasing human population with a limited amount of land results in pesticides being indispensable in agriculture industry and its usage as pest control will not cease. Huge amount of pesticides used in agriculture sector is the emerging contaminants in drinking water supplies. This is because pesticides applied directly to the soil can be washed off by rain into nearby surface water or percolate through the soil to lower soil layers and groundwater. There is a long list of pesticides in guidelines for drinking water by World Health Organization, however, data on effectiveness of dimethoate rejection using membrane has not been found so far.
In order to safeguard people's health especially with the increasingly active agriculture activities emphasized in the Ninth Malaysia Plan, this research applies nanofiltration membrane for retention against dimethoate and atrazine, pesticides which are relevant to our Malaysia agriculture scenario.
This research is the first effort in our country to abate pesticides present in water due to the active agriculture activity as no remedy for pesticides in water has been created in Malaysia so far.
The current research is able to:
Retain approximately 85% of dimethoate and more than 95% retention of atrazine.
Operate at a pressure of 6 bar, a distinctly low operating pressure as compared to the much higher pressure required for reverse osmosis process.
Eliminate frequent regeneration process required for treatment processing using activated carbon.
Thus, this research would provide an easy to operate and reliable method for abating pesticides abundantly used in agriculture sector from reaching people via water. This matter is very urgent and important because pesticides will continue to be used for pest controls, but it is up to us to find ways to avoid many of the pesticides poisonings and contamination that exist today.
Contact with Pro.Abdul Latif Ahmad
Telephone:604 594 1013 or 6045937788 ext 6401
Email:chlatif@eng.usm.my
Producing food for the increasing human population generally results in increased use of pesticides, which is finding its way into drinking water supplies. This research is proven to filter up to 85 % of dimethoate and more than 95% of atrazine.
Title of project: Modulated Nanofiltration Process for Pesticides Removal: An Agriculture Remediation
Prof. Abdul Latif Ahmad
Dr. Syamsul Rizal Abd. Shukor
Tan Lian See
Producing sufficient agriculture crops for the increasing human population with a limited amount of land results in pesticides being indispensable in agriculture industry and its usage as pest control will not cease. Huge amount of pesticides used in agriculture sector is the emerging contaminants in drinking water supplies. This is because pesticides applied directly to the soil can be washed off by rain into nearby surface water or percolate through the soil to lower soil layers and groundwater. There is a long list of pesticides in guidelines for drinking water by World Health Organization, however, data on effectiveness of dimethoate rejection using membrane has not been found so far.
In order to safeguard people's health especially with the increasingly active agriculture activities emphasized in the Ninth Malaysia Plan, this research applies nanofiltration membrane for retention against dimethoate and atrazine, pesticides which are relevant to our Malaysia agriculture scenario.
This research is the first effort in our country to abate pesticides present in water due to the active agriculture activity as no remedy for pesticides in water has been created in Malaysia so far.
The current research is able to:
Retain approximately 85% of dimethoate and more than 95% retention of atrazine.
Operate at a pressure of 6 bar, a distinctly low operating pressure as compared to the much higher pressure required for reverse osmosis process.
Eliminate frequent regeneration process required for treatment processing using activated carbon.
Thus, this research would provide an easy to operate and reliable method for abating pesticides abundantly used in agriculture sector from reaching people via water. This matter is very urgent and important because pesticides will continue to be used for pest controls, but it is up to us to find ways to avoid many of the pesticides poisonings and contamination that exist today.
Contact with Pro.Abdul Latif Ahmad
Telephone:604 594 1013 or 6045937788 ext 6401
Email:chlatif@eng.usm.my
Monday, September 10, 2007
Superconducting cement
Researchers find superconductivity in a material typically used as cement
The metal oxide known as 12CaO∙7Al2O3 (C12A7) is often used to make aluminous cements. Researchers from RIKEN’s Discovery Research Institute in Wako and the Tokyo Institute of Technology have now found superconductivity in the metallic version of C12A7.
The crystal structure of C12A7 consists of a number of cages formed by calcium, aluminum and oxygen atoms (Fig. 1). Typically, such oxides are electrically insulating and of little interest to scientists. This changed recently, when researchers from the Tokyo Institute of Technology demonstrated that C12A7 can be made metallic by the chemical reduction that replaces negatively charged oxygen atoms with electrons. As a result, the conductivity of C12A7 changes by an impressive thirteen orders of magnitude. Such compounds, where electrons are used to achieve metallic conductivity, are called ‘electrides’. Electrides are commonly used in batteries or fuel cells.
Owing to the open crystal structure of the C12A7 electride, the nature of the metallic state is quite different to normal metals. “The conduction of this material is supported by electrons trapped in the nano-scale cages,” explains Kimitoshi Kono from the RIKEN team. Although the actual conductivity depends on the magnitude of this replacement, the absence of oxygen atoms allows the trapped electrons to extend and reach across the voids. The resultant overlap of electron distribution thereby enables the electrons to travel across the structure.
Superconductivity originates in the coupling of free electrons; so many metals are superconductive at low temperatures. The researchers therefore studied the electronic properties of the C12A7 electride and observed superconductivity at about 0.4 K, which is less than 272°C. Their results have been published in the Journal of the American Chemical Society (1).
As the ‘metallization’ of the material was rather unexpected by scientists, the discovery of superconductivity in this mundane material is surprising to many. “Nobody else expected a cement to become superconductive,” says Kono. Further investigations into the properties of these unusual superconductors are expected to follow from these pioneering findings. The design of the caged structure of the C12A7 electride is also rather flexible, so many similar compounds exist or are theoretically possible. Kono says that “there is no reason why we should not expect that some of these materials might show superconductivity.” Cement might hold further unexpected surprises for physicists and chemists.
Researchers find superconductivity in a material typically used as cement
The metal oxide known as 12CaO∙7Al2O3 (C12A7) is often used to make aluminous cements. Researchers from RIKEN’s Discovery Research Institute in Wako and the Tokyo Institute of Technology have now found superconductivity in the metallic version of C12A7.
The crystal structure of C12A7 consists of a number of cages formed by calcium, aluminum and oxygen atoms (Fig. 1). Typically, such oxides are electrically insulating and of little interest to scientists. This changed recently, when researchers from the Tokyo Institute of Technology demonstrated that C12A7 can be made metallic by the chemical reduction that replaces negatively charged oxygen atoms with electrons. As a result, the conductivity of C12A7 changes by an impressive thirteen orders of magnitude. Such compounds, where electrons are used to achieve metallic conductivity, are called ‘electrides’. Electrides are commonly used in batteries or fuel cells.
Owing to the open crystal structure of the C12A7 electride, the nature of the metallic state is quite different to normal metals. “The conduction of this material is supported by electrons trapped in the nano-scale cages,” explains Kimitoshi Kono from the RIKEN team. Although the actual conductivity depends on the magnitude of this replacement, the absence of oxygen atoms allows the trapped electrons to extend and reach across the voids. The resultant overlap of electron distribution thereby enables the electrons to travel across the structure.
Superconductivity originates in the coupling of free electrons; so many metals are superconductive at low temperatures. The researchers therefore studied the electronic properties of the C12A7 electride and observed superconductivity at about 0.4 K, which is less than 272°C. Their results have been published in the Journal of the American Chemical Society (1).
As the ‘metallization’ of the material was rather unexpected by scientists, the discovery of superconductivity in this mundane material is surprising to many. “Nobody else expected a cement to become superconductive,” says Kono. Further investigations into the properties of these unusual superconductors are expected to follow from these pioneering findings. The design of the caged structure of the C12A7 electride is also rather flexible, so many similar compounds exist or are theoretically possible. Kono says that “there is no reason why we should not expect that some of these materials might show superconductivity.” Cement might hold further unexpected surprises for physicists and chemists.
Adding a pinch of sugar
Enzymes can be engineered to decorate small molecules with a wide variety of sugars. The biological activity of many natural products—small molecules that occur naturally and form the basis for many drugs—is influenced by the addition of a sugar molecule. Thus, varying these sugar molecules can be important when looking for new drug leads; however, altering these sugars can be challenging using glycosyltransferases (enzymes that transfer sugars) because they typically only function with a narrow range of sugars and small molecules.
Jon Thorson and colleagues used a process called directed evolution, in which random mutations are introduced at select positions in an enzyme and a large number of mutated enzymes are screened for the desired activity. They were able to engineer a glycosyltransferase that can transfer a wide range of sugar molecules onto a variety of therapeutically important small molecules. These ‘mutant’ enzymes can now be used in the search for new therapeutics.
Author contact:
Jon Thorson (University of Wisconsin, Madison, WI, USA)
Tel: +1 608 262 3829; E-mail: jsthorson@pharmacy.wisc.edu
Watching protein-cutting enzymes in action
The activity of proteases – enzymes that cut other proteins and are important in diseases such as AIDS and cancer - can be imaged in living animals with ‘smart probes’ using a method reported in the October issue of Nature Chemical Biology. Cathepsin proteases are specific protein-cleaving enzymes involved in tumour formation and metastasis, and are important targets for diagnosing and treating cancer.
Using probes that only fluoresce when they react with active proteases, Matthew Bogyo and colleagues have imaged cathepsin activity in the tumours of living mice. Because the probes form a covalent bond (a permanent connection) with cathepsin, in vitro experiments can directly follow in vivo imaging to provide a mechanistic explanation for what is observed. The authors demonstrate that these probes are useful for testing the effectiveness of potential drugs.
Author contact:
Matthew Bogyo (Stanford University, Stanford, CA, USA)
Tel: +1 650 725 4132; E-mail: mbogyo@stanford.edu
Enzymes can be engineered to decorate small molecules with a wide variety of sugars. The biological activity of many natural products—small molecules that occur naturally and form the basis for many drugs—is influenced by the addition of a sugar molecule. Thus, varying these sugar molecules can be important when looking for new drug leads; however, altering these sugars can be challenging using glycosyltransferases (enzymes that transfer sugars) because they typically only function with a narrow range of sugars and small molecules.
Jon Thorson and colleagues used a process called directed evolution, in which random mutations are introduced at select positions in an enzyme and a large number of mutated enzymes are screened for the desired activity. They were able to engineer a glycosyltransferase that can transfer a wide range of sugar molecules onto a variety of therapeutically important small molecules. These ‘mutant’ enzymes can now be used in the search for new therapeutics.
Author contact:
Jon Thorson (University of Wisconsin, Madison, WI, USA)
Tel: +1 608 262 3829; E-mail: jsthorson@pharmacy.wisc.edu
Watching protein-cutting enzymes in action
The activity of proteases – enzymes that cut other proteins and are important in diseases such as AIDS and cancer - can be imaged in living animals with ‘smart probes’ using a method reported in the October issue of Nature Chemical Biology. Cathepsin proteases are specific protein-cleaving enzymes involved in tumour formation and metastasis, and are important targets for diagnosing and treating cancer.
Using probes that only fluoresce when they react with active proteases, Matthew Bogyo and colleagues have imaged cathepsin activity in the tumours of living mice. Because the probes form a covalent bond (a permanent connection) with cathepsin, in vitro experiments can directly follow in vivo imaging to provide a mechanistic explanation for what is observed. The authors demonstrate that these probes are useful for testing the effectiveness of potential drugs.
Author contact:
Matthew Bogyo (Stanford University, Stanford, CA, USA)
Tel: +1 650 725 4132; E-mail: mbogyo@stanford.edu
Diet shapes the human genome
Human populations that have high starch diets have an increase in the number of copies of a gene whose product breaks down starch. Although copy number variation has attracted a lot of recent attention, this is one of the first documented examples of positive selection on gene copy number in humans.
Starch has become a prominent component of the human diet. It is metabolized in part by salivary amylase, and the gene encoding it, AMY1, shows extensive variation in copy number. George Perry and colleagues estimated AMY1 copy number in 50 European Americans and showed that the levels of salivary amylase protein are positively correlated with gene copy number. They went on to show that individuals from three populations with high-starch diets tend to have more copies of AMY1 than individuals from populations with low-starch diets. Finally, the authors compared the extent of variation across the genome between two Asian populations – Japanese (high-starch diet) and Yakut pastoralists (low-starch diet) – and found that variation at AMY1 exceeds that of more than 97% of the other sites in the genome that were assessed.
The authors conclude from this that natural selection favored increased AMY1 copy number in at least some populations with high-starch diets. Interestingly, humans have significantly more copies of AMY1 than chimpanzees, which ingest relatively little starch. Increased AMY1 expression would probably improve the digestion of starchy foods, and possibly maintain energy absorption in the face of intestinal disease.
Author contact:
Nathaniel Dominy (University of California, Santa Cruz, CA, USA)
Tel: +1 831 459 2541; E-mail: njdominy@ucsc.edu
Muscle metabolism and human evolution
A variant of a gene associated with elite athletic performance has been subject to strong, recent positive selection in humans. Experiments on mice suggest that this variant may promote more efficient muscle metabolism.
The gene ACTN3, encoding alpha-actinin-3, is specifically expressed in the fast-twitch muscle fibers that are responsible for generating force at high velocity. ACTN3 exists in a non-functional truncated form in more than a billion people worldwide, and is overrepresented in endurance athletes. By contrast, the functional form is overrepresented in elite sprinters. Kathryn North and colleagues examined the extent of genetic variation in the vicinity of ACTN3 in individuals with the truncated version. They found very little variation, which is consistent with the truncated version of the gene being under positive selection.
To understand better the effect of the truncation on muscle function, the authors generated a line of mice lacking ACTN3, and found that there is a shift in muscle metabolism toward the more efficient aerobic pathway. These mice were also able to run on average 33% further before reaching exhaustion than mice with normal ACTN3 function. The authors conclude that this increased metabolic efficiency could explain the overrepresentation of the truncated form of ACTN3 in endurance athletes.
Author contact:
Kathryn North (Children’s Hospital at Westmead, Sydney, Australia)
Tel: +61 2 9845 3011; E-mail: kathryn@chw.edu.au
Human populations that have high starch diets have an increase in the number of copies of a gene whose product breaks down starch. Although copy number variation has attracted a lot of recent attention, this is one of the first documented examples of positive selection on gene copy number in humans.
Starch has become a prominent component of the human diet. It is metabolized in part by salivary amylase, and the gene encoding it, AMY1, shows extensive variation in copy number. George Perry and colleagues estimated AMY1 copy number in 50 European Americans and showed that the levels of salivary amylase protein are positively correlated with gene copy number. They went on to show that individuals from three populations with high-starch diets tend to have more copies of AMY1 than individuals from populations with low-starch diets. Finally, the authors compared the extent of variation across the genome between two Asian populations – Japanese (high-starch diet) and Yakut pastoralists (low-starch diet) – and found that variation at AMY1 exceeds that of more than 97% of the other sites in the genome that were assessed.
The authors conclude from this that natural selection favored increased AMY1 copy number in at least some populations with high-starch diets. Interestingly, humans have significantly more copies of AMY1 than chimpanzees, which ingest relatively little starch. Increased AMY1 expression would probably improve the digestion of starchy foods, and possibly maintain energy absorption in the face of intestinal disease.
Author contact:
Nathaniel Dominy (University of California, Santa Cruz, CA, USA)
Tel: +1 831 459 2541; E-mail: njdominy@ucsc.edu
Muscle metabolism and human evolution
A variant of a gene associated with elite athletic performance has been subject to strong, recent positive selection in humans. Experiments on mice suggest that this variant may promote more efficient muscle metabolism.
The gene ACTN3, encoding alpha-actinin-3, is specifically expressed in the fast-twitch muscle fibers that are responsible for generating force at high velocity. ACTN3 exists in a non-functional truncated form in more than a billion people worldwide, and is overrepresented in endurance athletes. By contrast, the functional form is overrepresented in elite sprinters. Kathryn North and colleagues examined the extent of genetic variation in the vicinity of ACTN3 in individuals with the truncated version. They found very little variation, which is consistent with the truncated version of the gene being under positive selection.
To understand better the effect of the truncation on muscle function, the authors generated a line of mice lacking ACTN3, and found that there is a shift in muscle metabolism toward the more efficient aerobic pathway. These mice were also able to run on average 33% further before reaching exhaustion than mice with normal ACTN3 function. The authors conclude that this increased metabolic efficiency could explain the overrepresentation of the truncated form of ACTN3 in endurance athletes.
Author contact:
Kathryn North (Children’s Hospital at Westmead, Sydney, Australia)
Tel: +61 2 9845 3011; E-mail: kathryn@chw.edu.au
The political brain
People with a more liberal outlook may have a greater sensitivity to cues signalling the need to change a habitual response. The study shows that self-rated liberalism is associated with a type of brain activity involved in regulating conflict between a habitual tendency and an alternative response.
Previous psychological work found that, on average, conservatives tend to be more persistent in their judgements and decision-making, while liberals are more likely to be open to new experiences. These differences are related to a process known as conflict monitoring, a mechanism for detecting when a habitual response is not appropriate for a new situation.
David Amodio and colleagues recorded electrical activity from the brain using electroencephalograms (EEGs) in people who rated themselves as either conservative or liberal. During these recordings, subjects had to quickly press a button when they saw a cue, which was presented often enough that the button-press became habitual. However, subjects occasionally saw another, infrequent cue signalling them to withhold their habitual button press. When such response inhibition was required, liberals had significantly greater neural activity originating in the anterior cingulate cortex – known to be involved in conflict monitoring. Liberals were also more successful at withholding their habitual response when they saw the infrequent cue. The findings support previous suggestions that political orientation may in part reflect differences in cognitive mechanisms.
Author contact:
David Amodio, (New York University, NY, USA)
Tel: +1 212 998 3875; E-mail: david.amodio@nyu.edu
People with a more liberal outlook may have a greater sensitivity to cues signalling the need to change a habitual response. The study shows that self-rated liberalism is associated with a type of brain activity involved in regulating conflict between a habitual tendency and an alternative response.
Previous psychological work found that, on average, conservatives tend to be more persistent in their judgements and decision-making, while liberals are more likely to be open to new experiences. These differences are related to a process known as conflict monitoring, a mechanism for detecting when a habitual response is not appropriate for a new situation.
David Amodio and colleagues recorded electrical activity from the brain using electroencephalograms (EEGs) in people who rated themselves as either conservative or liberal. During these recordings, subjects had to quickly press a button when they saw a cue, which was presented often enough that the button-press became habitual. However, subjects occasionally saw another, infrequent cue signalling them to withhold their habitual button press. When such response inhibition was required, liberals had significantly greater neural activity originating in the anterior cingulate cortex – known to be involved in conflict monitoring. Liberals were also more successful at withholding their habitual response when they saw the infrequent cue. The findings support previous suggestions that political orientation may in part reflect differences in cognitive mechanisms.
Author contact:
David Amodio, (New York University, NY, USA)
Tel: +1 212 998 3875; E-mail: david.amodio@nyu.edu
Dialling up damage responders
Certain cells of the immune system more readily tolerate damage to their genes than other cells, up to a point. New research shows the protein BCL6, expressed in antibody-producing B cells, senses how much DNA damage is occurring inside these cells and activates repair pathways when damage becomes excessive.
BCL6 is a repressor that blocks expression of DNA repair enzymes in the presence of small amounts of damage. This suppression is beneficial to the B cells as these cells can ‘fine-tune’ their antibody responses by mutating the antibody genes or undergoing what is called ‘class switch recombination’, a genetic rearrangement that allows different types of antibodies to be produced.
Riccardo Dalla-Favera and colleagues show excessive DNA damage in these B cells can be recognized by BCL6. BCL6 acts as a ‘damage-sensitive’ resistor that, once tipped beyond a threshold amount of accumulated DNA breaks, initiates a pathway that leads to its own destruction and turns on repair enzymes. These findings further our understanding of BCL6, which is commonly found to be mutated in forms of B cell cancers, and may thereby be instructive in designing therapies to blunt BCL6 activity in these cancers.
Author contact:
Riccardo Dalla-Favera (Columbia University, New York, NY, USA)
Tel: +1 212 851 5273; E-mail: rd10@columbia.edu
Stem cells have nervous impulses
Blood stem cells become activated in response to signals released by nerve cells according to a research.
Tsvee Lapidot and colleagues report bone marrow stem cells express dopamine receptors. Release of neurotransmitters, as occurs during times of stress, triggers the blood cells to divide and migrate from their protected bone marrow environment. Treatment of mice with dopamine or other neurotransmitters led to increased numbers of these stem cells in bone marrow and in the blood circulation. Neurotransmitter stimulation of human bone marrow cells likewise increased their engraftment potential upon transplantation into ‘humanized mouse’ recipients, whose immune system is reconstituted by the human cells. Such findings might translate to increased efficiency of therapies that require bone marrow transplantation.
Author contact:
Tsvee Lapidot (Weizmann Institute of Science, Rehovot, Israel)
Tel: +972 8 934 2481; E-mail: Tsvee.Lapidot@weizmann.ac.il
Certain cells of the immune system more readily tolerate damage to their genes than other cells, up to a point. New research shows the protein BCL6, expressed in antibody-producing B cells, senses how much DNA damage is occurring inside these cells and activates repair pathways when damage becomes excessive.
BCL6 is a repressor that blocks expression of DNA repair enzymes in the presence of small amounts of damage. This suppression is beneficial to the B cells as these cells can ‘fine-tune’ their antibody responses by mutating the antibody genes or undergoing what is called ‘class switch recombination’, a genetic rearrangement that allows different types of antibodies to be produced.
Riccardo Dalla-Favera and colleagues show excessive DNA damage in these B cells can be recognized by BCL6. BCL6 acts as a ‘damage-sensitive’ resistor that, once tipped beyond a threshold amount of accumulated DNA breaks, initiates a pathway that leads to its own destruction and turns on repair enzymes. These findings further our understanding of BCL6, which is commonly found to be mutated in forms of B cell cancers, and may thereby be instructive in designing therapies to blunt BCL6 activity in these cancers.
Author contact:
Riccardo Dalla-Favera (Columbia University, New York, NY, USA)
Tel: +1 212 851 5273; E-mail: rd10@columbia.edu
Stem cells have nervous impulses
Blood stem cells become activated in response to signals released by nerve cells according to a research.
Tsvee Lapidot and colleagues report bone marrow stem cells express dopamine receptors. Release of neurotransmitters, as occurs during times of stress, triggers the blood cells to divide and migrate from their protected bone marrow environment. Treatment of mice with dopamine or other neurotransmitters led to increased numbers of these stem cells in bone marrow and in the blood circulation. Neurotransmitter stimulation of human bone marrow cells likewise increased their engraftment potential upon transplantation into ‘humanized mouse’ recipients, whose immune system is reconstituted by the human cells. Such findings might translate to increased efficiency of therapies that require bone marrow transplantation.
Author contact:
Tsvee Lapidot (Weizmann Institute of Science, Rehovot, Israel)
Tel: +972 8 934 2481; E-mail: Tsvee.Lapidot@weizmann.ac.il
Putting fluorine in its place
A three-component catalytic system enables the formation of carbon–fluorine bonds at precise positions in organic molecules
Organic molecules produced by living systems are often referred to as ‘natural products’, and are a rich source of biologically active substances that can sometimes be used as drugs themselves or, alternatively, offer a convenient starting point for designing and making others. These compounds generally have hydrocarbon skeletons and contain a small number of atoms of other elements—so-called heteroatoms.
Whereas nitrogen and oxygen, and, to a lesser extent, sulfur and phosphorus, are relatively common heteroatoms found in natural products, many of the other elements that comprise the periodic table rarely feature. A case in point is fluorine, which, points out Mikiko Sodeoka from RIKEN’s Discovery Research Institute in Wako, “is not popular in chemicals produced by organisms.”
Substituting a hydrogen atom with fluorine can, however, often confer beneficial properties on a particular compound, such as a drug, by increasing its stability or making it more easily absorbed in the body. Consequently, as many as 20% of therapeutic pharmaceuticals and 30–40% of agrochemicals, made by the chemical industry, contain a fluorine atom.
Many researchers have, therefore, investigated reactions to make carbon–fluorine bonds in an efficient and selective manner. Sodeoka and co-workers (1) have made many contributions in this area and the most recent describes a new three-component catalytic system that enables the fluorination of a family of molecules known as aryl acetic acids.
After screening a range of reaction conditions, it was found that a cocktail of three different chemicals could be used, in conjunction with a fluorinating agent (N-fluorobenzenesulfonimide (NFSI)), to replace a hydrogen atom with a fluorine atom in a range of aryl acetic acid substrates (Fig. 1). Each component of the ternary mixture has a specific function: an acid activates the NFSI, a metal-ligand complex activates the substrate, and the base removes the hydrogen atom that is being substituted.
In principle, this fluorination reaction can produce two different mirror-image forms (enantiomers) of a given compound. The process developed by Sodeoka and co-workers is particularly powerful, however, because it can be intentionally biased to produce greater amounts of either of these closely related products—simply by choosing which mirror-image form of the metal catalyst is used in the reaction.
The ability to introduce fluorine atoms into molecules that can be made selectively in either left- or right-handed form is a powerful and generic synthetic strategy which Sodeoka hopes could make a significant contribution to the field of medicinal chemistry.
Reference
A three-component catalytic system enables the formation of carbon–fluorine bonds at precise positions in organic molecules
Organic molecules produced by living systems are often referred to as ‘natural products’, and are a rich source of biologically active substances that can sometimes be used as drugs themselves or, alternatively, offer a convenient starting point for designing and making others. These compounds generally have hydrocarbon skeletons and contain a small number of atoms of other elements—so-called heteroatoms.
Whereas nitrogen and oxygen, and, to a lesser extent, sulfur and phosphorus, are relatively common heteroatoms found in natural products, many of the other elements that comprise the periodic table rarely feature. A case in point is fluorine, which, points out Mikiko Sodeoka from RIKEN’s Discovery Research Institute in Wako, “is not popular in chemicals produced by organisms.”
Substituting a hydrogen atom with fluorine can, however, often confer beneficial properties on a particular compound, such as a drug, by increasing its stability or making it more easily absorbed in the body. Consequently, as many as 20% of therapeutic pharmaceuticals and 30–40% of agrochemicals, made by the chemical industry, contain a fluorine atom.
Many researchers have, therefore, investigated reactions to make carbon–fluorine bonds in an efficient and selective manner. Sodeoka and co-workers (1) have made many contributions in this area and the most recent describes a new three-component catalytic system that enables the fluorination of a family of molecules known as aryl acetic acids.
After screening a range of reaction conditions, it was found that a cocktail of three different chemicals could be used, in conjunction with a fluorinating agent (N-fluorobenzenesulfonimide (NFSI)), to replace a hydrogen atom with a fluorine atom in a range of aryl acetic acid substrates (Fig. 1). Each component of the ternary mixture has a specific function: an acid activates the NFSI, a metal-ligand complex activates the substrate, and the base removes the hydrogen atom that is being substituted.
In principle, this fluorination reaction can produce two different mirror-image forms (enantiomers) of a given compound. The process developed by Sodeoka and co-workers is particularly powerful, however, because it can be intentionally biased to produce greater amounts of either of these closely related products—simply by choosing which mirror-image form of the metal catalyst is used in the reaction.
The ability to introduce fluorine atoms into molecules that can be made selectively in either left- or right-handed form is a powerful and generic synthetic strategy which Sodeoka hopes could make a significant contribution to the field of medicinal chemistry.
Reference
X-rays in full color
Two researchers from RIKEN’s SPring-8 Center in Harima have demonstrated the conversion of x-rays into longer wavelengths that preserves some of their useful properties, such as high spatial resolution.
Conversion of x-ray beams into longer wavelengths creates a new spectroscopic tool
X-rays—beams of light with short wavelengths and high energy—are a commonly used diagnostic tool, not only in medicine, but also in materials science.
Normally, image resolution is limited by the wavelength of the light being used. Light with a very short wavelength, such as x-rays, therefore yields higher imaging resolution than, for example, visible light. On the other hand, since x-rays have high energies (equivalent to shorter wavelengths) they are not always suitable to study low energy (or long-wavelength) properties of materials.
Writing in the journal Physical Review Letters1, Kenji Tamasaku and Tetsuya Ishikawa, present an experimental demonstration of how some of the advantages of x-rays can be brought towards other wavelengths. They used an optical effect, known as ‘parametric down-conversion’ that can be realized with high-intensity x-rays. “The important point of x-ray nonlinear optical effects, such as parametric down-conversion, is that one can generate an arbitrary wavelength from the visible to the x-ray region for further study,” says Tamasaku.
In this process, an x-ray beam, the ‘pump’, is split into two beams, the ‘signal’ and ‘idler’, by scattering off a regular crystal such as a diamond (Fig. 1). The wavelength of the signal beam is in the x-ray region, whereas the wavelength of the idler beam is much longer, in the extreme ultraviolet light region. The precise relationship between signal and idler wavelengths is given by physical laws such as the conservation of energy. The idler beam in particular is of interest for high-resolution spectroscopy applications.
In their experiments, Tamasaku and Ishikawa have clearly and successfully demonstrated this effect for the first time. Their achievement is rooted in the very high x-ray intensities that can be achieved with the SPring-8 synchrotron radiation facility—necessary for an efficient conversion of the pump beam.
The extreme ultraviolet wavelength region is of particular interest to probe the nature of atomic bonds. As the creation of the idler is directly related to the local environment of the x-ray pump, a high spatial resolution can be achieved in experiments. Therefore, “it will be possible to obtain information about the bonds between individual atoms,” explains Tamasaku. The parametric down-conversion pioneered by the RIKEN researchers might therefore become an important analytical tool.
Two researchers from RIKEN’s SPring-8 Center in Harima have demonstrated the conversion of x-rays into longer wavelengths that preserves some of their useful properties, such as high spatial resolution.
Conversion of x-ray beams into longer wavelengths creates a new spectroscopic tool
X-rays—beams of light with short wavelengths and high energy—are a commonly used diagnostic tool, not only in medicine, but also in materials science.
Normally, image resolution is limited by the wavelength of the light being used. Light with a very short wavelength, such as x-rays, therefore yields higher imaging resolution than, for example, visible light. On the other hand, since x-rays have high energies (equivalent to shorter wavelengths) they are not always suitable to study low energy (or long-wavelength) properties of materials.
Writing in the journal Physical Review Letters1, Kenji Tamasaku and Tetsuya Ishikawa, present an experimental demonstration of how some of the advantages of x-rays can be brought towards other wavelengths. They used an optical effect, known as ‘parametric down-conversion’ that can be realized with high-intensity x-rays. “The important point of x-ray nonlinear optical effects, such as parametric down-conversion, is that one can generate an arbitrary wavelength from the visible to the x-ray region for further study,” says Tamasaku.
In this process, an x-ray beam, the ‘pump’, is split into two beams, the ‘signal’ and ‘idler’, by scattering off a regular crystal such as a diamond (Fig. 1). The wavelength of the signal beam is in the x-ray region, whereas the wavelength of the idler beam is much longer, in the extreme ultraviolet light region. The precise relationship between signal and idler wavelengths is given by physical laws such as the conservation of energy. The idler beam in particular is of interest for high-resolution spectroscopy applications.
In their experiments, Tamasaku and Ishikawa have clearly and successfully demonstrated this effect for the first time. Their achievement is rooted in the very high x-ray intensities that can be achieved with the SPring-8 synchrotron radiation facility—necessary for an efficient conversion of the pump beam.
The extreme ultraviolet wavelength region is of particular interest to probe the nature of atomic bonds. As the creation of the idler is directly related to the local environment of the x-ray pump, a high spatial resolution can be achieved in experiments. Therefore, “it will be possible to obtain information about the bonds between individual atoms,” explains Tamasaku. The parametric down-conversion pioneered by the RIKEN researchers might therefore become an important analytical tool.
Sunday, September 09, 2007
Geology: Potential tsunami risk in the Bay of Bengal
A potential for giant earthquakes in the Bay of Bengal could expose a large and vulnerable population to a significant tsunami hazard. The study combines recent geological and geodetic data with an account of an historical earthquake in the region to produce a simulation of the tsunami that may have accompanied it.
It is now recognised that another large earthquake is likely to occur off central Sumatra, just east of the 2004 Sumatra–Andaman earthquake location. But there has been little concern about the subduction zone to the north, in the northern Bay of Bengal along the coast of Myanmar and Bangladesh.
Phil R. Cummins reviews observations from GPS and geological data which indicate that, contrary to some previous studies, the plate boundary in this region is probably at sea, hidden below the thick layer of sediments in the Bengal Fan. This means that a subduction-zone earthquake would be likely to generate a tsunami. Evidence of a large earthquake in Arakan in Myanmar in 1762 also indicates an off-shore origin. Local reports at the time describe how the river at Dhaka rose suddenly and drove boats ashore, and there is evidence of 3 to 7 metres of uplift along the coast.
The author’s tsunami simulation for this earthquake depicts the severe impact such an event might have today on this low-lying area that is home to over 60 million people. He concludes that the next giant earthquake may not be as large as in 1762 and may not occur for another 200 years, but a smaller event could occur sooner, threatening this heavily populated region.
CONTACT
Phil R. Cummins (Geoscience Australia, Canberra, Australia)
Please contact the author through:
Chris Thompson (Communications Section, Geoscience Australia, Canberra, Australia)
Tel: +61 2 6249 9642; E-mail: chris.thompson@ga.gov.au
A potential for giant earthquakes in the Bay of Bengal could expose a large and vulnerable population to a significant tsunami hazard. The study combines recent geological and geodetic data with an account of an historical earthquake in the region to produce a simulation of the tsunami that may have accompanied it.
It is now recognised that another large earthquake is likely to occur off central Sumatra, just east of the 2004 Sumatra–Andaman earthquake location. But there has been little concern about the subduction zone to the north, in the northern Bay of Bengal along the coast of Myanmar and Bangladesh.
Phil R. Cummins reviews observations from GPS and geological data which indicate that, contrary to some previous studies, the plate boundary in this region is probably at sea, hidden below the thick layer of sediments in the Bengal Fan. This means that a subduction-zone earthquake would be likely to generate a tsunami. Evidence of a large earthquake in Arakan in Myanmar in 1762 also indicates an off-shore origin. Local reports at the time describe how the river at Dhaka rose suddenly and drove boats ashore, and there is evidence of 3 to 7 metres of uplift along the coast.
The author’s tsunami simulation for this earthquake depicts the severe impact such an event might have today on this low-lying area that is home to over 60 million people. He concludes that the next giant earthquake may not be as large as in 1762 and may not occur for another 200 years, but a smaller event could occur sooner, threatening this heavily populated region.
CONTACT
Phil R. Cummins (Geoscience Australia, Canberra, Australia)
Please contact the author through:
Chris Thompson (Communications Section, Geoscience Australia, Canberra, Australia)
Tel: +61 2 6249 9642; E-mail: chris.thompson@ga.gov.au
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