New Chromosomal Abnormality Identified in Leukemia Associated with Down Syndrome
Study led by St. Jude Children's Research Hospital investigators expands understanding of acute lymphoblastic leukemia in children with Down syndrome, fueling hope for new treatment
Researchers identified a new chromosomal abnormality in acute lymphoblastic leukemia (ALL) that appears to work in concert with another mutation to give rise to cancer. This latest anomaly is particularly common in children with Down syndrome.
The findings have already resulted in new diagnostic tests and potential tools for tracking a patient's response to treatment. The research, led by scientists from St. Jude Children's Research Hospital, also highlights a new potential ALL treatment. Clinicians are already planning trials of an experimental medication targeting one of the altered genes.
"A substantial proportion of children with ALL lack one of the previously identified, common chromosomal abnormalities. Also, children with Down syndrome have an increased risk of ALL, but the reasons why are unclear," said Charles Mullighan, M.D., Ph.D., assistant member in the St. Jude Department of Pathology. Mullighan is senior author of the study, which involved scientists from 10 institutions in the U.S. and Italy. "Our results have provided important data regarding the mechanisms contributing to leukemia in these cases," he said.
Instead of the normal pairs of 23 chromosomes, individuals with Down syndrome inherit an extra copy of one chromosome, in this case chromosome 21. Chromosomes are made of DNA and carry the genes that serve as the assembly and operations manual for life. Down syndrome is associated with a variety of medical and developmental problems, including a 10-to-20--fold increased risk of ALL. But patients with Down syndrome rarely have the genetic and chromosomal alterations commonly associated with childhood ALL. Until recently the genetic basis of the elevated risk for these patients was unknown.
The new gene alteration was identified by St. Jude scientists following up on an earlier observation. They had previously found a recurring deletion in a region of DNA duplicated on the X and Y chromosomes. The region is known as pseudoautosomal region 1 or PAR1.
The PAR1 deletion was found only in patients with a subtype of ALL known as B-progenitor ALL. It was most common in children with both B-progenitor ALL and Down syndrome. In this study, investigators screened almost 400 children with ALL, including 75 patients with Down syndrome. The deletion was present in 7 percent of patients with B-progenitor ALL, but in more than half of the patients with both B progenitor and Down syndrome.
The deletion results in a fusion of two genes, P2RY8 and CRLF2. The fusion puts CRLF2 expression under the control of the P2RY8 promoter. As a result, CRLF2 expression jumps as much as 10 fold.
"CRLF2 over-expression identifies a group of ALL cases which were not previously well characterized, and suggests some novel treatment approaches that may improve patient survival. Patients with Down syndrome are particularly vulnerable to complications from standard chemotherapy, and could therefore benefit from novel therapies," said Karen Rabin, M.D., of Texas Children's Cancer Center and a study co-author. She is a Baylor College of Medicine assistant professor of pediatric hematology/oncology.
The CRLF2 protein normally forms part of a receptor where a small growth factor known as a cytokine binds to white blood cells known as lymphocytes. Both the cytokine, thymic stromal lymphopoietin (TSLP), and CRLF2 are known to play important roles in the development of immune cells known as T lymphocytes as well as in inflammation and allergic disease. They had not previously been linked to leukemia.
CRFL2 is the second gene implicated in development of B-progenitor ALL in patients with Down syndrome. The first, a gene called JAK2, was identified in 2008. JAK2 belongs to a family of genes that produce enzymes called kinases. If permanently switched on, kinases can trigger the uncontrolled cell growth that is a hallmark of cancer.
JAK mutations have also been linked to other cancers. Drugs targeting JAK kinases are already in clinical trials against a variety of blood disorders in adults. Additional trials are being planned against other subtypes of childhood ALL.
In this study, researchers reported a significant association between alterations in both the CRFL2 and JAK2 genes. Almost all JAK mutations were observed in patients with CRLF2 alterations. Almost 28 percent of children with Down syndrome and ALL had changes in both the CRFL2 and JAK genes.
"It has been a mystery as to why the JAK mutations in Down syndrome ALL are different from those seen in other cancers," Mullighan said. "Here we show that the JAK mutations in ALL are almost always observed together with a chromosomal alteration that results in over- expression of CRLF2."
When both the JAK mutation and increased CRLF2 production were introduced into white blood cells growing in the laboratory, those cells were transformed and no longer needed cytokines to grow. Neither genetic alteration on its own produced the same effect. Researchers also reported their impact could be weakened by the addition of drugs that target JAK mutations.
"We showed that the two proteins, CRLF2 and mutant JAK2, physically interact, and together transform white blood cells. This work has identified a new pathway contributing to the development of leukemia," Mullighan said. A next step is to determine if these mutations also interact in mouse models of ALL.
Other authors of this paper include J. Racquel Collins-Underwood, Letha A.A. Phillips, Wei Liu, Jing Ma, Elaine Coustan-Smith, Richard T. Williams, Jinjun Cheng, Ching-Hon Pui, Susana Raimondi and James Downing, all of St. Jude; Michael L. Loudin of Baylor; Jinghui Zhang of the National Cancer Institute (NCI); Richard Harvey and Cheryl Willman, of the University of New Mexico; Fady Mikhail and Andrew Carroll, of the University of Alabama at Birmingham; Nyla Heerema of Ohio State University; Giuseppe Basso, of the University of Padua, Padua, Italy; and Andrea Pession of the University of Bologna, Bologna, Italy.
The work was supported in part by National Cancer Institute, the Bear Necessities Pediatric Research Foundation, the Children's Cancer Research Foundation, the National Institutes of Health and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.
Monday, October 19, 2009
Sunday, August 23, 2009
Neutrinos are coming on Earth from Failed supernovae
spectacular supernovae (Fig. 1). The temperatures and pressures generated in these events are so intense they create a large burst of particles called neutrinos, which eventually reach Earth.
Now, Cecilia Lunardini at Arizona State University and RIKEN BNL Research Center in Upton, USA, has calculated that lots of neutrinos may also reach Earth from ‘failed supernovae’—huge stars that collapse without exploding to produce black holes1.
The neutrino contribution from these failed supernovae could greatly increase the total flux of neutrinos reaching Earth from millions of collapsing stars throughout the universe. Lunardini calls this total the ‘diffuse supernova neutrino flux’.
“In the diffuse flux, the contribution of each supernova is very small, but the total is detectable,” she says. “We only need to reach the right experimental sensitivity to start detecting it.”
Unfortunately, neutrinos are notoriously difficult to detect because they barely interact with other matter. One of the world’s best detectors is the Super-Kamiokande (‘Super-K’) neutrino observatory, situated in a mine beneath Gifu prefecture Japan, and even it requires 50,000 tons of ultra-pure water to scatter the neutrinos.
Lunardini decided to calculate whether a device like Super-K could detect neutrinos from supernovae collapsing into black holes.
“The idea that neutrinos are emitted in black-hole-forming collapses is not new,” she says. “The novelty of my work is in showing that these neutrinos can build up to a significant diffuse flux, thus adding to the flux from successful supernovae.”
In fact, Lunardini calculated that the Earth may receive up to one neutrino per square centimeter per second from failed supernovae. This is even more than the flux from successful supernovae, but probably beyond the detection limit of Super-K.
There is growing support in the scientific community to build larger, more sensitive neutrino detectors containing up to a million tons of water. Once these bigger detectors are built, Lunardini thinks it is only a matter of time before the diffuse neutrino flux can be measured. The results could reveal some fascinating new physics.
“[Failed supernovae] are very difficult to study with telescopes due to the fact that they do not explode but just disappear from the sky without much emission other than neutrinos,” says Lunardini. “The possibility to get information on these objects—even just to test their presence and how many there are in the universe—with neutrinos is exciting.”
Reference
1. Lunardini, C. Diffuse neutrino flux from failed supernovae. Physical Review Letters 102, 231101 (2009).
The corresponding author for this highlight is based at the RIKEN BNL Research Center Theory Group
Wednesday, August 19, 2009
Meningitis Bacteria penetrate the Blood-Brain Barrier
A specific protein on the surface of a common bacterial pathogen allows the bacteria to leave the bloodstream and enter the brain, initiating the deadly infection known as meningitis. The new finding, which may guide development of improved vaccines to protect those most vulnerable, including young infants and the elderly, is now available online in the Journal of Experimental Medicine.
"Streptococcus pneumoniae, commonly known as pneumococcus, is responsible for half the cases of bacterial meningitis in humans," said the study's senior author, Victor Nizet, MD, professor of pediatrics and pharmacy at the University of California, San Diego’s School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. “As many as 30 percent of patients can die from this rapidly progressing infection, while half of survivors may be left with permanent neurological problems including deafness, seizures, intellectual deficits or motor disabilities.”
Meningitis develops when bacteria penetrate the "blood-brain barrier." Comprised of a single layer of highly specialized microvascular endothelial cells, the blood-brain barrier prevents most large molecules from entering into the cerebrospinal fluid, preserving an optimal biochemical environment for brain function.
The UC San Diego team investigated the functions of a protein known as NanA in order to discover how an entire bacterium can breech the blood-brain barrier and gain access to the central nervous system. NanA is produced by all strains of pneumococcus and displayed prominently on the bacteria's outer surface.
Through genetic manipulations, the researchers were able to remove the entire NanA protein, or just specific sections of the molecule, from the pathogen. They found that while normal pneumococci were able to bind, enter and penetrate through human brain microvascular endothelial cells, mutant bacteria lacking the NanA protein –or those expressing only a truncated version of the protein – largely lost these abilities. Conversely, when the full-length pneumococcal NanA protein was cloned and expressed on the surface of a nonpathogenic laboratory strain, the transformed bacteria gained the ability to bind and enter the same endothelial cells.
“Our tissue culture studies showed that the NanA protein was both necessary and sufficient for bacterial penetration of the blood brain barrier endothelial cells,” said Satoshi Uchiyama, MD, a postdoctoral fellow in the Nizet Laboratory and lead author on the study. “After infecting mice intravenously, we also found that far fewer NanA-deficient bacteria left the bloodstream and entered the brain, in comparison to mice infected with the normal pneumococcus.”
NanA is best known as an enzyme that cleaves and releases the sugar molecule known as sialic acid, which is present in abundance on the surface of all human cells. While this enzymatic activity played a small part in promoting NanA-mediated blood-brain barrier interactions, a much stronger role was identified for the outer tip of the protein. This tip seems to directly attach to the brain microvascular endothelial cells and then stimulate them to take in the pneumococcus.
“Antibodies directed against the NanA protein also strongly inhibited the ability of pneumococcus to attach to and invade the blood-brain barrier cells,” said Kelly Doran, PhD, an assistant professor at both UC San Diego School of Medicine and San Diego State University, who jointly supervised the project with Nizet.
Because NanA is expressed on the surface of all pneumococcal strains, it is an attractive candidate to include in a universal protein-based vaccine against pneumococcal infection according to Nizet, who is also on the medical staff of Rady Children's Hospital, San Diego. Currently, infants and the elderly are immunized with vaccines comprised of surface capsule sugars from 7 to 23 of the most common strains of pneumococcus.
“Our immune system generates antibodies more readily against protein rather than sugar vaccine antigens,” said Nizet. “Since at least 80 different pneumococcal capsule types exist, not all strains can be represented in the capsule sugar-based vaccines. An added benefit of an effective NanA vaccine would be to reduce the risk of pneumococcus spreading into the brain to cause meningitis.”
Ongoing research in the Nizet and Doran labs will seek to characterize the receptor on the blood-brain barrier cells to which NanA binds, and to explore whether similar processes contribute to the ability of other meningitis pathogens – such as group B streptococcus – to pass through the blood-brain barrier.
Additional contributors to the project were co-lead author Aaron Carlin, MD, PhD, Arya Khosravi, Shannon Weiman, Darin Quach, and George Hightower of the Department of Pediatrics at UC San Diego School of Medicine; Timothy Mitchell, PhD, of the University of Glasgow; and Anirban Banerjee, PhD, of the Department of Biology at San Diego State University. The research was supported by the National Institutes of Health, the American Heart Association, the Burroughs-Wellcome Fund and the Taylor Thomas Foundation.
A specific protein on the surface of a common bacterial pathogen allows the bacteria to leave the bloodstream and enter the brain, initiating the deadly infection known as meningitis. The new finding, which may guide development of improved vaccines to protect those most vulnerable, including young infants and the elderly, is now available online in the Journal of Experimental Medicine.
"Streptococcus pneumoniae, commonly known as pneumococcus, is responsible for half the cases of bacterial meningitis in humans," said the study's senior author, Victor Nizet, MD, professor of pediatrics and pharmacy at the University of California, San Diego’s School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. “As many as 30 percent of patients can die from this rapidly progressing infection, while half of survivors may be left with permanent neurological problems including deafness, seizures, intellectual deficits or motor disabilities.”
Meningitis develops when bacteria penetrate the "blood-brain barrier." Comprised of a single layer of highly specialized microvascular endothelial cells, the blood-brain barrier prevents most large molecules from entering into the cerebrospinal fluid, preserving an optimal biochemical environment for brain function.
The UC San Diego team investigated the functions of a protein known as NanA in order to discover how an entire bacterium can breech the blood-brain barrier and gain access to the central nervous system. NanA is produced by all strains of pneumococcus and displayed prominently on the bacteria's outer surface.
Through genetic manipulations, the researchers were able to remove the entire NanA protein, or just specific sections of the molecule, from the pathogen. They found that while normal pneumococci were able to bind, enter and penetrate through human brain microvascular endothelial cells, mutant bacteria lacking the NanA protein –or those expressing only a truncated version of the protein – largely lost these abilities. Conversely, when the full-length pneumococcal NanA protein was cloned and expressed on the surface of a nonpathogenic laboratory strain, the transformed bacteria gained the ability to bind and enter the same endothelial cells.
“Our tissue culture studies showed that the NanA protein was both necessary and sufficient for bacterial penetration of the blood brain barrier endothelial cells,” said Satoshi Uchiyama, MD, a postdoctoral fellow in the Nizet Laboratory and lead author on the study. “After infecting mice intravenously, we also found that far fewer NanA-deficient bacteria left the bloodstream and entered the brain, in comparison to mice infected with the normal pneumococcus.”
NanA is best known as an enzyme that cleaves and releases the sugar molecule known as sialic acid, which is present in abundance on the surface of all human cells. While this enzymatic activity played a small part in promoting NanA-mediated blood-brain barrier interactions, a much stronger role was identified for the outer tip of the protein. This tip seems to directly attach to the brain microvascular endothelial cells and then stimulate them to take in the pneumococcus.
“Antibodies directed against the NanA protein also strongly inhibited the ability of pneumococcus to attach to and invade the blood-brain barrier cells,” said Kelly Doran, PhD, an assistant professor at both UC San Diego School of Medicine and San Diego State University, who jointly supervised the project with Nizet.
Because NanA is expressed on the surface of all pneumococcal strains, it is an attractive candidate to include in a universal protein-based vaccine against pneumococcal infection according to Nizet, who is also on the medical staff of Rady Children's Hospital, San Diego. Currently, infants and the elderly are immunized with vaccines comprised of surface capsule sugars from 7 to 23 of the most common strains of pneumococcus.
“Our immune system generates antibodies more readily against protein rather than sugar vaccine antigens,” said Nizet. “Since at least 80 different pneumococcal capsule types exist, not all strains can be represented in the capsule sugar-based vaccines. An added benefit of an effective NanA vaccine would be to reduce the risk of pneumococcus spreading into the brain to cause meningitis.”
Ongoing research in the Nizet and Doran labs will seek to characterize the receptor on the blood-brain barrier cells to which NanA binds, and to explore whether similar processes contribute to the ability of other meningitis pathogens – such as group B streptococcus – to pass through the blood-brain barrier.
Additional contributors to the project were co-lead author Aaron Carlin, MD, PhD, Arya Khosravi, Shannon Weiman, Darin Quach, and George Hightower of the Department of Pediatrics at UC San Diego School of Medicine; Timothy Mitchell, PhD, of the University of Glasgow; and Anirban Banerjee, PhD, of the Department of Biology at San Diego State University. The research was supported by the National Institutes of Health, the American Heart Association, the Burroughs-Wellcome Fund and the Taylor Thomas Foundation.
Friday, August 14, 2009
Oxytocin in Mammals and Mesotocin in Birds
What do flocks of birds have in common with trust, monogamy, and even breast milk? According to a new report in the journal Science, they are regulated by virtually identical neurochemicals in the brain, known as oxytocin in mammals and mesotocin in birds.
Neurobiologists at Indiana University showed that if the actions of mesotocin are blocked in the brains of zebra finches, a highly social songbird, the birds shift their social preferences. They spend significantly less time with familiar individuals and more time with unfamiliar individuals. The birds also become less social, preferring to spend less time with a large group of same-sex birds and more time with a smaller group. Conversely, if birds are administered mesotocin instead of the blocker, the finches become more social and prefer familiar partners.
Perhaps most striking is the fact that none of the treatments affect males -- only females.
According to James Goodson, lead author on the study, the sex differences in birds provide important clues to the evolutionary history of oxytocin functions in humans and other mammals. "Oxytocin is an evolutionarily descendant of mesotocin and has long been associated with female reproductive functions -- things such as pair bonding with males, giving birth, providing maternal care and ejecting milk for infants," said Goodson.
Goodson and colleagues have found hints of similar processes in fish, and he speculates that oxytocin-like neuropeptides have played special roles in female affiliation ever since the peptides first evolved. That was sometime around 450 million years ago, about the same time that jaws evolved.
"The ancient properties of this system appear to be retained in all major vertebrate groups, and date back to our common ancestor with sharks," says co-author Marcy Kingsbury, associate scientist at IU Bloomington.
But if all vertebrates possess similar neuropeptide circuits, why don't they all live in big groups -- flocks, schools or herds? A possible answer to that question is provided in the second part of the Science study. The authors speculated that the behavioral actions of mesotocin may differ across species depending upon the distribution of "receptors" for the chemical in the brain -- that is, places where mesotocin can attach to brain cells and alter their activity.
Using a radioactive compound that attaches to oxytocin-like receptors, the authors mapped the distribution of receptors in three finch species that form flocks and two species that are territorial and highly aggressive. What they found was that the flocking species had many more receptors in a part of the brain known as the lateral septum. And when they blocked those receptors in female zebra finches, the birds became less social.
According to Goodson, these findings suggest that it is actually the concentration and location of receptors that determines whether an individual prefers spending time in large groups. Natural selection could act to increase the number of receptors expressed by certain lateral septum neurons, or by altering the regions where receptor genes are expressed, depending on whether female sociality is favored or not among the individuals of a species.
If Goodson's discovery holds true for other birds and even mammals, the concentration of receptors for mesotocin (and oxytocin) in the lateral septum could accurately predict whether an individual is naturally gregarious.
"The lateral septum is structurally very similar in reptiles, birds and mammals," Goodson said. "To our knowledge, it plays an important role in the social and reproductive behaviors of all land vertebrates."
What might be next for Goodson's research group?
"We still don't understand why mesotocin and oxytocin are so potent in females, but not always in males," Goodson said. "And we also don't fully understand how the lateral septum functions to influence sociality." But he is convinced that his group's ongoing studies of songbirds will soon provide the answers.
IU Bloomington Associate Scientist Marcy Kingsbury, postdoctoral fellow David Kabelik, research associate Sara Schrock and Ph.D. student James Klatt also contributed to this research. It was funded with a grant from the National Institutes of Health (NIMH).
Friday, August 07, 2009
Researchers Make Stem Cells from Developing Sperm
The promise of stem cell therapy may lie in uncovering how adult cells revert back into a primordial, stem cell state, whose fate is yet to be determined. Now, cell scientists at the Johns Hopkins University School of Medicine have identified key molecular players responsible for this reversion in fruit fly sperm cells. Reporting online this week in Cell Stem Cell, researchers show that two proteins are responsible redirecting cells on the way to becoming sperm back to stem cells.
“We knew from our previous work that cells destined to be sperm could revert back to being stem cells, but we didn't know how,” says Erika Matunis, Ph.D., an associate professor of cell biology at the Johns Hopkins University School of Medicine. “Since, dedifferentiation is an interesting phenomenon probably occurring in a lot of different stem cell populations, we wanted to know more about the process.“
Like all stem cells, each of the nine stem cells in the fly testis divides to form two daughter cells: One stays a stem cell and the other differentiates into an adult cell, in this case, a sperm cell. To figure out what might cause sperm cells to revert or dedifferentiate, Matunis’s research team genetically altered the flies so that both cells become sperm, reducing the stem cell population in the testis to nothing.
About a week later, the team examined these fly testes and found that the stem cells had been repopulated.
To figure out how this was happening, the researchers first suspected two proteins—Jak and STAT—known to act together to help stem cells maintain their stem cell-ness. The team genetically altered flies to reduce the activity of Jak and STAT in the testis. Counting the number of cells, they found that the loss of Jak-STAT caused fewer cells to revert to stem cells; only 60 percent of testes regained stem cells compared to 97 percent in normal Jak-STAT-containing testes.
“We now know that in the fly testis, interfering with Jak-STAT signaling interferes with the process of dedifferentiation,” says Matunis.
Next, Matunis would like to figure out how Jak and STAT control dedifferentiation. “We don't know if a cell is just reversing all of the steps to go back to being a stem cell or if it is doing something totally new and different, but we’re eager to find out,” she says.
The promise of stem cell therapy may lie in uncovering how adult cells revert back into a primordial, stem cell state, whose fate is yet to be determined. Now, cell scientists at the Johns Hopkins University School of Medicine have identified key molecular players responsible for this reversion in fruit fly sperm cells. Reporting online this week in Cell Stem Cell, researchers show that two proteins are responsible redirecting cells on the way to becoming sperm back to stem cells.
“We knew from our previous work that cells destined to be sperm could revert back to being stem cells, but we didn't know how,” says Erika Matunis, Ph.D., an associate professor of cell biology at the Johns Hopkins University School of Medicine. “Since, dedifferentiation is an interesting phenomenon probably occurring in a lot of different stem cell populations, we wanted to know more about the process.“
Like all stem cells, each of the nine stem cells in the fly testis divides to form two daughter cells: One stays a stem cell and the other differentiates into an adult cell, in this case, a sperm cell. To figure out what might cause sperm cells to revert or dedifferentiate, Matunis’s research team genetically altered the flies so that both cells become sperm, reducing the stem cell population in the testis to nothing.
About a week later, the team examined these fly testes and found that the stem cells had been repopulated.
To figure out how this was happening, the researchers first suspected two proteins—Jak and STAT—known to act together to help stem cells maintain their stem cell-ness. The team genetically altered flies to reduce the activity of Jak and STAT in the testis. Counting the number of cells, they found that the loss of Jak-STAT caused fewer cells to revert to stem cells; only 60 percent of testes regained stem cells compared to 97 percent in normal Jak-STAT-containing testes.
“We now know that in the fly testis, interfering with Jak-STAT signaling interferes with the process of dedifferentiation,” says Matunis.
Next, Matunis would like to figure out how Jak and STAT control dedifferentiation. “We don't know if a cell is just reversing all of the steps to go back to being a stem cell or if it is doing something totally new and different, but we’re eager to find out,” she says.
Plastics That Convert Light to Electricity Could Have a Big impact
Researchers the world over are striving to develop organic solar cells that can be produced easily and inexpensively as thin films that could be widely used to generate electricity.
But a major obstacle is coaxing these carbon-based materials to reliably form the proper structure at the nanoscale (tinier than 2-millionths of an inch) to be highly efficient in converting light to electricity. The goal is to develop cells made from low-cost plastics that will transform at least 10 percent of the sunlight that they absorb into usable electricity and can be easily manufactured.
A research team headed by David Ginger, a University of Washington associate professor of chemistry, has found a way to make images of tiny bubbles and channels, roughly 10,000 times smaller than a human hair, inside plastic solar cells. These bubbles and channels form within the polymers as they are being created in a baking process, called annealing, that is used to improve the materials' performance.
The researchers are able to measure directly how much current each tiny bubble and channel carries, thus developing an understanding of exactly how a solar cell converts light into electricity. Ginger believes that will lead to a better understanding of which materials created under which conditions are most likely to meet the 10 percent efficiency goal.
As researchers approach that threshold, nanostructured plastic solar cells could be put into use on a broad scale, he said. As a start, they could be incorporated into purses or backpacks to charge cellular phones or mp3 players, but eventually they could make in important contribution to the electrical power supply.
Most researchers make plastic solar cells by blending two materials together in a thin film, then baking them to improve their performance. In the process, bubbles and channels form much as they would in a cake batter. The bubbles and channels affect how well the cell converts light into electricity and how much of the electric current actually gets to the wires leading out of the cell. The number of bubbles and channels and their configuration can be altered by how much heat is applied and for how long.
The exact structure of the bubbles and channels is critical to the solar cell's performance, but the relationship between baking time, bubble size, channel connectivity and efficiency has been difficult to understand. Some models used to guide development of plastic solar cells even ignore the structure issues and assume that blending the two materials into a film for solar cells will produce a smooth and uniform substance. That assumption can make it difficult to understand just how much efficiency can be engineered into a polymer, Ginger said.
For the current research, the scientists worked with a blend of polythiophene and fullerene, model materials considered basic to organic solar cell research because their response to forces such as heating can be readily extrapolated to other materials. The materials were baked together at different temperatures and for different lengths of time.
Ginger is the lead author of a paper documenting the work, published online last month by the American Chemical Society journal Nano Letters and scheduled for a future print edition. Coauthors are Liam Pingree and Obadiah Reid of the UW. The research was funded by the National Science Foundation and the U.S. Department of Energy.
Ginger noted that the polymer tested is not likely to reach the 10 percent efficiency threshold. But the results, he said, will be a useful guide to show which new combinations of materials and at what baking time and temperature could form bubbles and channels in a way that the resulting polymer might meet the standard.
Such testing can be accomplished using a very small tool called an atomic force microscope, which uses a needle similar to the one that plays records on an old-style phonograph to make a nanoscale image of the solar cell. The microscope, developed in Ginger's lab to record photocurrent, comes to a point just 10 to 20 nanometers across (a human hair is about 60,000 nanometers wide). The tip is coated with platinum or gold to conduct electrical current, and it traces back and forth across the solar cell to record the properties.
As the microscope traces back and forth over a solar cell, it records the channels and bubbles that were created as the material was formed. Using the microscope in conjunction with the knowledge gained from the current research, Ginger said, can help scientists determine quickly whether polymers they are working with are ever likely to reach the 10 percent efficiency threshold.
Making solar cells more efficient is crucial to making them cost effective, he said. And if costs can be brought low enough, solar cells could offset the need for more coal-generated electricity in years to come.
"The solution to the energy problem is going to be a mix, but in the long term solar power is going to be the biggest part of that mix," he said.
Researchers the world over are striving to develop organic solar cells that can be produced easily and inexpensively as thin films that could be widely used to generate electricity.
But a major obstacle is coaxing these carbon-based materials to reliably form the proper structure at the nanoscale (tinier than 2-millionths of an inch) to be highly efficient in converting light to electricity. The goal is to develop cells made from low-cost plastics that will transform at least 10 percent of the sunlight that they absorb into usable electricity and can be easily manufactured.
A research team headed by David Ginger, a University of Washington associate professor of chemistry, has found a way to make images of tiny bubbles and channels, roughly 10,000 times smaller than a human hair, inside plastic solar cells. These bubbles and channels form within the polymers as they are being created in a baking process, called annealing, that is used to improve the materials' performance.
The researchers are able to measure directly how much current each tiny bubble and channel carries, thus developing an understanding of exactly how a solar cell converts light into electricity. Ginger believes that will lead to a better understanding of which materials created under which conditions are most likely to meet the 10 percent efficiency goal.
As researchers approach that threshold, nanostructured plastic solar cells could be put into use on a broad scale, he said. As a start, they could be incorporated into purses or backpacks to charge cellular phones or mp3 players, but eventually they could make in important contribution to the electrical power supply.
Most researchers make plastic solar cells by blending two materials together in a thin film, then baking them to improve their performance. In the process, bubbles and channels form much as they would in a cake batter. The bubbles and channels affect how well the cell converts light into electricity and how much of the electric current actually gets to the wires leading out of the cell. The number of bubbles and channels and their configuration can be altered by how much heat is applied and for how long.
The exact structure of the bubbles and channels is critical to the solar cell's performance, but the relationship between baking time, bubble size, channel connectivity and efficiency has been difficult to understand. Some models used to guide development of plastic solar cells even ignore the structure issues and assume that blending the two materials into a film for solar cells will produce a smooth and uniform substance. That assumption can make it difficult to understand just how much efficiency can be engineered into a polymer, Ginger said.
For the current research, the scientists worked with a blend of polythiophene and fullerene, model materials considered basic to organic solar cell research because their response to forces such as heating can be readily extrapolated to other materials. The materials were baked together at different temperatures and for different lengths of time.
Ginger is the lead author of a paper documenting the work, published online last month by the American Chemical Society journal Nano Letters and scheduled for a future print edition. Coauthors are Liam Pingree and Obadiah Reid of the UW. The research was funded by the National Science Foundation and the U.S. Department of Energy.
Ginger noted that the polymer tested is not likely to reach the 10 percent efficiency threshold. But the results, he said, will be a useful guide to show which new combinations of materials and at what baking time and temperature could form bubbles and channels in a way that the resulting polymer might meet the standard.
Such testing can be accomplished using a very small tool called an atomic force microscope, which uses a needle similar to the one that plays records on an old-style phonograph to make a nanoscale image of the solar cell. The microscope, developed in Ginger's lab to record photocurrent, comes to a point just 10 to 20 nanometers across (a human hair is about 60,000 nanometers wide). The tip is coated with platinum or gold to conduct electrical current, and it traces back and forth across the solar cell to record the properties.
As the microscope traces back and forth over a solar cell, it records the channels and bubbles that were created as the material was formed. Using the microscope in conjunction with the knowledge gained from the current research, Ginger said, can help scientists determine quickly whether polymers they are working with are ever likely to reach the 10 percent efficiency threshold.
Making solar cells more efficient is crucial to making them cost effective, he said. And if costs can be brought low enough, solar cells could offset the need for more coal-generated electricity in years to come.
"The solution to the energy problem is going to be a mix, but in the long term solar power is going to be the biggest part of that mix," he said.
Monday, August 03, 2009
Breaking News: Major breakthrough in organ replacement regenerative therapies
Research group headed by Takashi Tsuji demonstrates in regenerating
bioengineered “fully functional organ (tooth)”
Substantial advance in the development of next-generationA research group led by Takashi Tsuji (Professor in the Research Institute for Science
and Technology, Tokyo University of Science, and Director of Organ Technologies Inc.) has
demonstrated in growing new organs in adult mice. Tsuji is a research team member in
“Health Labor Sciences Research Grant: Research on Regenerative Medicine for Clinical
Application (Domain Leader: Professor Akira Yamaguchi of Tokyo Medical and Dental
University)”, and “Priority Domain Research: Bio-engineering (Domain Leader: Professor
Toshio Fukuda of Nagoya University)”. In transplantation experiments using the tooth as a
model, a bioengineered tooth germ develops into a fully functioning bioengineered tooth with
sufficient hardness for mastication and a functional responsiveness to mechanical stress in the
maxillofacial region. The research also provided the results that the nerve fibers that have
re-entered the pulp and periodontal ligament (PDL) tissues of the bioengineered tooth have
proper perceptive potential in response to noxious stimulations such as orthodontic treatment
and pulp stimulation.
This research is expected to substantially advance in the development of “tooth
regenerative therapy”, which have potential as next-generation regenerative therapies for
replacing diseased or damaged teeth with bioengineered teeth. Specifically it will not only
promote “tooth regenerative therapy”, whereby organ germs of bioengineered teeth are
transplanted into the jaw bone to grow “3rd generation tooth”, but is expected to evolve into a
wide variety of organ regenerative technologies for liver, kidney and other organs.
This research outcome was the fruit of joint research with Professor Teruko
Takano-Yamamoto (Division of Orthodontics and Dentofacial Orthopedics, Graduate School
of Dentistry, Tohoku University, Japan) and Professor Shohei Kasugai (Oral and Maxillofacial
Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Graduate School,
Tokyo Medical and Dental University, Japan). It was announced in an Advance Online
Publication of the US scientific journal “Proc. Natl. Acad. Sci. USA.”
“organ replacement regenerative therapies”
Wednesday, July 15, 2009
New Tools For Discovering DNA Variations In Crop Genomes
The study of human genetics has been a successful venture for researchers in recent years. Several million single-nucleotide polymorphisms (SNPs) have been identified from the whole-genome resequencing of multiple individuals, which have served as genetic markers to pinpoint genes controlling common human diseases. In contrast, the genome of a single cultivar or line has yet to be sequenced in its entirety for most crops of economic or societal importance. This slow pace of genomic progress can be mostly explained by the high costs and technical difficulties associated with sequencing crop genomes, which tend to be large in size and complex—containing a high amount of repetitive DNA and duplicated genes that are highly similar in sequence.
With the advent of high-throughput DNA sequencing technologies, it is now possible to cheaply and rapidly sequence hundreds of millions of bases in a matter of hours. A team of scientists at Cornell University (Ithaca, NY), the United States Department of Agriculture-Agriculture Research Service (USDA-ARS), Cold Spring Harbor Laboratory (Cold Spring Harbor, NY), Roche Applied Science Corp. (Indianapolis, IN) and 454 Life Sciences (Branford, CT), have developed molecular and computational tools for the efficient and accurate identification of gene-enriched SNPs in crops. The large, complex genome of maize was used to evaluate these tools.
The study was funded by the National Science Foundation (NSF), Roche Applied Science Corp., and the USDA-ARS. Results from the study were published in the July 2009 issue of The Plant Genome.
In this research collaboration, an existing molecular technique was modified to enable gene-enrichment and resequencing of maize inbred lines B73 and Mo17 with massively parallel pyrosequencing. In addition, a custom computational pipeline was developed to analyze and assemble short reads, identify correctly mapped reads, and call high quality SNPs. With the implementation of these methods, the authors identified 126,683 gene-enriched SNPs between B73 and Mo17 at high accuracy.
“Next-generation sequencing technologies will greatly accelerate the resequencing of multiple to numerous individuals for every major crop species,” says Michael Gore, first co-author of the study. “Such efforts will facilitate the construction of SNP datasets on the order of millions that can be used in whole-genome association studies to assess the contribution of SNPs—common or rare—to complex traits. What we have learned from this pilot study will help us to construct a community SNP resource in maize that is comparable in scale to that of the human haplotype map”.
Although the majority of SNPs do not contribute to phenotypic variation, plant breeders and geneticists alike are interested in using SNPs as genetic markers. As a genetic marker, SNPs can be used for studies of genetic diversity and in the selection of superior plants. The SNPs identified in this study can be used for high-resolution genetic mapping of agronomic traits, which could eventually lead to the development of improved commercial maize hybrids.
The study of human genetics has been a successful venture for researchers in recent years. Several million single-nucleotide polymorphisms (SNPs) have been identified from the whole-genome resequencing of multiple individuals, which have served as genetic markers to pinpoint genes controlling common human diseases. In contrast, the genome of a single cultivar or line has yet to be sequenced in its entirety for most crops of economic or societal importance. This slow pace of genomic progress can be mostly explained by the high costs and technical difficulties associated with sequencing crop genomes, which tend to be large in size and complex—containing a high amount of repetitive DNA and duplicated genes that are highly similar in sequence.
With the advent of high-throughput DNA sequencing technologies, it is now possible to cheaply and rapidly sequence hundreds of millions of bases in a matter of hours. A team of scientists at Cornell University (Ithaca, NY), the United States Department of Agriculture-Agriculture Research Service (USDA-ARS), Cold Spring Harbor Laboratory (Cold Spring Harbor, NY), Roche Applied Science Corp. (Indianapolis, IN) and 454 Life Sciences (Branford, CT), have developed molecular and computational tools for the efficient and accurate identification of gene-enriched SNPs in crops. The large, complex genome of maize was used to evaluate these tools.
The study was funded by the National Science Foundation (NSF), Roche Applied Science Corp., and the USDA-ARS. Results from the study were published in the July 2009 issue of The Plant Genome.
In this research collaboration, an existing molecular technique was modified to enable gene-enrichment and resequencing of maize inbred lines B73 and Mo17 with massively parallel pyrosequencing. In addition, a custom computational pipeline was developed to analyze and assemble short reads, identify correctly mapped reads, and call high quality SNPs. With the implementation of these methods, the authors identified 126,683 gene-enriched SNPs between B73 and Mo17 at high accuracy.
“Next-generation sequencing technologies will greatly accelerate the resequencing of multiple to numerous individuals for every major crop species,” says Michael Gore, first co-author of the study. “Such efforts will facilitate the construction of SNP datasets on the order of millions that can be used in whole-genome association studies to assess the contribution of SNPs—common or rare—to complex traits. What we have learned from this pilot study will help us to construct a community SNP resource in maize that is comparable in scale to that of the human haplotype map”.
Although the majority of SNPs do not contribute to phenotypic variation, plant breeders and geneticists alike are interested in using SNPs as genetic markers. As a genetic marker, SNPs can be used for studies of genetic diversity and in the selection of superior plants. The SNPs identified in this study can be used for high-resolution genetic mapping of agronomic traits, which could eventually lead to the development of improved commercial maize hybrids.
Wood Burning Stoves have been Reevaluated
The stress of rising natural gas prices is leading many consumers to rethink how they heat their homes. For some this means moving towards modern alternative energy options, while others have been turning to a more traditional method for a solution to these rising costs. In Canada and the United States, wood burning stoves have been reevaluated as a potentially viable option for home heating.
The case for modern woodstoves has developed with the improvement of the products on the market, as wood heating technology has substantially advanced in recent years. With the advanced secondary combustion systems on Environmental Protection Agency certified woodstoves, they are now 95% more efficient than their predecessors.
Dr. Paul Grogan, a plant and ecosystem ecologist and Canadian Research Chair (II) at Queen’s University in Kingston, Ontario conducted a case study on the benefits of woodstoves with the help of final-year undergraduate and first year graduate students. He determined that adding a woodstove to the home can help both consumers heating costs as well as the environment.
The environmental sustainability of woodstove use is dependent upon the consumption of wood from sustainably managed woodlots, as the carbon released is reused as the next generation of trees grows. Annual gross CO2 emissions did in fact increase from 12,610 kg (i.e., ~2.5 metric tons CO2/person per year) to 17,330 kg after the installation of the wood stove. But while this gross amount did increase, the net carbon released by the combustion is negligible, the only surplus coming from the harvest and transport. Based on an average growing time of 130 years before harvest for local Ontario tree species, a woodlot or forest 3.5 hectares in size would provide an indefinite supply of wood heat for a household without a net increase in carbon emissions.
In the case study, adding a woodstove to the ground floor of a 3200ft2 home reduced the mean annual gas cost by 60%; from $2260 to $880. The annual cost of the wood fuel for the woodstove amounted to $1330 for 5 full cords (a cord is 8 feet long by 4 feet high by 4 feet wide - 128ft3 ). This was a yearly savings of $50 at market fossil fuel prices of 2005-2007 without taking into account rising fossil fuel prices or the impending carbon tax. Should these variables come into play Dr. Grogan estimated that the domestic heating costs would be reduced by 25%. This translates into a potential savings of $920 in the first 3 years.
The stress of rising natural gas prices is leading many consumers to rethink how they heat their homes. For some this means moving towards modern alternative energy options, while others have been turning to a more traditional method for a solution to these rising costs. In Canada and the United States, wood burning stoves have been reevaluated as a potentially viable option for home heating.
The case for modern woodstoves has developed with the improvement of the products on the market, as wood heating technology has substantially advanced in recent years. With the advanced secondary combustion systems on Environmental Protection Agency certified woodstoves, they are now 95% more efficient than their predecessors.
Dr. Paul Grogan, a plant and ecosystem ecologist and Canadian Research Chair (II) at Queen’s University in Kingston, Ontario conducted a case study on the benefits of woodstoves with the help of final-year undergraduate and first year graduate students. He determined that adding a woodstove to the home can help both consumers heating costs as well as the environment.
The environmental sustainability of woodstove use is dependent upon the consumption of wood from sustainably managed woodlots, as the carbon released is reused as the next generation of trees grows. Annual gross CO2 emissions did in fact increase from 12,610 kg (i.e., ~2.5 metric tons CO2/person per year) to 17,330 kg after the installation of the wood stove. But while this gross amount did increase, the net carbon released by the combustion is negligible, the only surplus coming from the harvest and transport. Based on an average growing time of 130 years before harvest for local Ontario tree species, a woodlot or forest 3.5 hectares in size would provide an indefinite supply of wood heat for a household without a net increase in carbon emissions.
In the case study, adding a woodstove to the ground floor of a 3200ft2 home reduced the mean annual gas cost by 60%; from $2260 to $880. The annual cost of the wood fuel for the woodstove amounted to $1330 for 5 full cords (a cord is 8 feet long by 4 feet high by 4 feet wide - 128ft3 ). This was a yearly savings of $50 at market fossil fuel prices of 2005-2007 without taking into account rising fossil fuel prices or the impending carbon tax. Should these variables come into play Dr. Grogan estimated that the domestic heating costs would be reduced by 25%. This translates into a potential savings of $920 in the first 3 years.
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