Sensing Wind Speed with Kites
Kites have a storied history in meteorological research -- think of Benjamin Franklin and his study of electricity -- including being used to carry aloft sensors that measure wind speed. Previously, however, these sensors, because they were exposed to direct sunlight, were prone to temperature errors that affected their accuracy. Now researchers at the University of Reading in the United Kingdom have developed a way to use a kite itself to measure wind speed.
The researchers, professor of atmospheric physics Giles Harrison and applied meteorologist Kieran Walesby, describe their device in the AIP's Review of Scientific Instruments. The instrument consists of a 2-meter-long and 1-meter-wide Rokkaku-type kite -- a simple-to-construct Japanese kite design with "good stability, reasonable load-carrying capacity, and a low sink rate when the wind speed drops," Harrison says -- attached to a ground-based strain gauge that monitors the tension in the kite's tether line. That line tension, Harrison and Walesby found, is linearly related to wind speed.
"The kite method is portable and cheap, and removes the need for a mast to support an anemometer," Harrison says. "A particular use is to provide measurements above those reached by masts" -- although, he adds, "it will work less well at low levels, or in very turbulent conditions. We expect to refine the kite design to allow operation in a wider range of conditions, and to encourage wider adoption of our approach."
The article, "A thermally stable tension meter for atmospheric soundings using kites" by K. T. Walesbya and R. G. Harrison was published online in the journal Review of Scientific Instruments on July 21, 2010. See: http://rsi.aip.org/rsinak/v81/i7/p076104_s1
Thursday, July 29, 2010
Wednesday, June 30, 2010
More Oil Spills to Come, Says Anthropologist
The Deepwater Horizon oil spill in the Gulf of Mexico is not simply a random accident. There will be more of these spills to come, as the days of easy oil are over, says an anthropologist at Washington University in St. Louis.
“BP and other oil companies have tried to portray this spill as an accident or an aberration, but in fact there are spills on off-shore and on-shore sites around the world, increasingly,” says Bret Gustafson, PhD, associate professor of anthropology in Arts & Sciences. Gustafson teaches a course on “Oil Wars: America and the Cultural Politics of Global Energy.”
A rig sank off the coast of Venezuela in May. Last October, a rig spilled oil for two months into the Timor Sea off of Australia. There are recurring spills in virtually every oil region, such as the Peruvian and Ecuadorian Amazon and Nigeria.
“These environmental and public health catastrophes are almost always accompanied by corruption and violence tied to oil activities,” Gustafson says. In the United States, which is more of a consumer than producer of oil, we are generally ignorant about this reality of oil until something like this comes home to roost.”
“Oil has always been destructive, but it is worsening because the days of easy oil are over,” says Gustafson, who currently is studying Bolivia's natural gas boom and the cultural politics of energy resources in Bolivia and neighboring Brazil, which consumes most of Bolivia's gas.
“In combination with weak regulation and intensifying competition, which explains why companies are willing to cut so many corners, oil is in more difficult places, both environmentally, politically and socially,” Gustafson says. “The point is that it is only going to get worse, and that the message by some commentators and the oil companies that we should just get on with business as usual is, quite frankly, almost criminal.”
Gustafson suggests that along with policies to transition us beyond oil and changes in our culture of consumption, we might also debate whether state control of oil companies, popular in other nations around the world, could work in the United States.
At least that way, Gustafson suggests, benefits would accrue to America’s public needs, rather than to multinational firms like BP. “Right now, the American people are subsidizing Big Oil, not benefitting from it,” he says.
“The press and public are only now debating the benefits or costs of regulation, but in fact the United States is the odd-man out in the world, where regulation goes along with government ownership and control,” Gustafson says. “Nearly all oil-producing countries, and not just third world ones, have government run oil companies, called National Oil Companies (NOCs). In places like Norway and Brazil, these contribute greatly to social benefits. Even the World Bank sees NOCs as a potential contributor to economic development. This is not a radical idea.”
Gustafson finds it curious that “our own culture of oil has largely silenced debate on whether or not having a national oil company would address both the environmental and regulatory concerns, as well as some of our other economic needs. Ideally, public and environmental concerns, rather than profit, would be the motivating logic behind oil operations.”
“The cultural addiction we have to oil contributes to both our relative ignorance about its negative effects and our relative willingness to accept these negative effects when they happen,” Gustafson says. “Despite the fact that most of us distrust big oil companies — we vilify them in our movies, our literature and our daily conversations — we are also generally complacent about what they do. When something like oil is so pervasive, it easily becomes invisible or at least very durable and resistant to cultural reflection and change.”
The one benefit of the spill, despite its catastrophic effects, may be, says Gustafson, that more of these issues are being brought into public discussion.
The Deepwater Horizon oil spill in the Gulf of Mexico is not simply a random accident. There will be more of these spills to come, as the days of easy oil are over, says an anthropologist at Washington University in St. Louis.
“BP and other oil companies have tried to portray this spill as an accident or an aberration, but in fact there are spills on off-shore and on-shore sites around the world, increasingly,” says Bret Gustafson, PhD, associate professor of anthropology in Arts & Sciences. Gustafson teaches a course on “Oil Wars: America and the Cultural Politics of Global Energy.”
A rig sank off the coast of Venezuela in May. Last October, a rig spilled oil for two months into the Timor Sea off of Australia. There are recurring spills in virtually every oil region, such as the Peruvian and Ecuadorian Amazon and Nigeria.
“These environmental and public health catastrophes are almost always accompanied by corruption and violence tied to oil activities,” Gustafson says. In the United States, which is more of a consumer than producer of oil, we are generally ignorant about this reality of oil until something like this comes home to roost.”
“Oil has always been destructive, but it is worsening because the days of easy oil are over,” says Gustafson, who currently is studying Bolivia's natural gas boom and the cultural politics of energy resources in Bolivia and neighboring Brazil, which consumes most of Bolivia's gas.
“In combination with weak regulation and intensifying competition, which explains why companies are willing to cut so many corners, oil is in more difficult places, both environmentally, politically and socially,” Gustafson says. “The point is that it is only going to get worse, and that the message by some commentators and the oil companies that we should just get on with business as usual is, quite frankly, almost criminal.”
Gustafson suggests that along with policies to transition us beyond oil and changes in our culture of consumption, we might also debate whether state control of oil companies, popular in other nations around the world, could work in the United States.
At least that way, Gustafson suggests, benefits would accrue to America’s public needs, rather than to multinational firms like BP. “Right now, the American people are subsidizing Big Oil, not benefitting from it,” he says.
“The press and public are only now debating the benefits or costs of regulation, but in fact the United States is the odd-man out in the world, where regulation goes along with government ownership and control,” Gustafson says. “Nearly all oil-producing countries, and not just third world ones, have government run oil companies, called National Oil Companies (NOCs). In places like Norway and Brazil, these contribute greatly to social benefits. Even the World Bank sees NOCs as a potential contributor to economic development. This is not a radical idea.”
Gustafson finds it curious that “our own culture of oil has largely silenced debate on whether or not having a national oil company would address both the environmental and regulatory concerns, as well as some of our other economic needs. Ideally, public and environmental concerns, rather than profit, would be the motivating logic behind oil operations.”
“The cultural addiction we have to oil contributes to both our relative ignorance about its negative effects and our relative willingness to accept these negative effects when they happen,” Gustafson says. “Despite the fact that most of us distrust big oil companies — we vilify them in our movies, our literature and our daily conversations — we are also generally complacent about what they do. When something like oil is so pervasive, it easily becomes invisible or at least very durable and resistant to cultural reflection and change.”
The one benefit of the spill, despite its catastrophic effects, may be, says Gustafson, that more of these issues are being brought into public discussion.
Wednesday, March 10, 2010
Study Provides a Better Understanding of How Mosquitoes Find a Host
The potentially deadly yellow-fever-transmitting Aedes aegypti mosquito detects the specific chemical structure of a compound called octenol as one way to find a mammalian host for a blood meal, Agricultural Research Service (ARS) scientists report.
Scientists have long known that mosquitoes can detect octenol, but this most recent finding by ARS entomologists Joseph Dickens and Jonathan Bohbot explains in greater detail how Ae. aegypti--and possibly other mosquito species--accomplish this.
Dickens and Bohbot, at the ARS Invasive Insect Biocontrol and Behavior Laboratory in Beltsville, Md., have shown that Ae. aegypti taps into the "right-handed" and "left-handed" structural nature of octenol, which is emitted by people, cattle and other mammals. This ability to detect the "handedness" of molecules has been shown in mammals, but the discovery is the first case of scientists finding out how it works in an insect, according to the researchers.
When they hunt for a blood meal, mosquitoes hone in on a variety of chemicals, including carbon dioxide, lactic acid, ammonia and octenol. Octenol is one of many carbon-based compounds that have a molecular structure that can take on either a "right-handed" or "left-handed" form. Each form is a mirror image of the other, and a form's "handedness" is determined by how its molecular bonds are assembled.
The scientists used frog eggs to help them make their discovery. They injected RNA from Ae. aegypti into the frog eggs, allowing the egg membranes to mimic the mosquito's ability to detect octenol. Then they attached microelectrodes to the frog egg cell membranes, passed octenol over them and recorded the electrical signals stimulated by the odors.
They ran the tests using both the right- and left-handed forms of octenol. The scientists found heightened electrical activity when the membrane was exposed to the right-handed form, and weakened activity when it was exposed to the left-handed form.
There are many natural compounds that can take on either a right-handed or left-handed form. While the effects of those differences on many plants and animals remains a mystery, the report, published in PLoS ONE, shows the effects of octenol's dual structure on the yellow fever mosquito and adds to scientists' understanding of how mosquitoes sense the world around them. It also may open the door to speedier development of better mosquito repellents and traps, according to Dickens.
The team's research is being funded by the Department of Defense Deployed War Fighter Protection Research Program.
ARS is the principal intramural scientific research agency of the U.S. Department of Agriculture.
USDA is an equal opportunity provider, employer and lender. To file a complaint of discrimination, write: USDA, Director, Office of Civil Rights, 1400 Independence Ave., S.W., Washington, D.C. 20250-9410 or call (800) 795-3272 (voice), or (202) 720-6382 (TDD).
The potentially deadly yellow-fever-transmitting Aedes aegypti mosquito detects the specific chemical structure of a compound called octenol as one way to find a mammalian host for a blood meal, Agricultural Research Service (ARS) scientists report.
Scientists have long known that mosquitoes can detect octenol, but this most recent finding by ARS entomologists Joseph Dickens and Jonathan Bohbot explains in greater detail how Ae. aegypti--and possibly other mosquito species--accomplish this.
Dickens and Bohbot, at the ARS Invasive Insect Biocontrol and Behavior Laboratory in Beltsville, Md., have shown that Ae. aegypti taps into the "right-handed" and "left-handed" structural nature of octenol, which is emitted by people, cattle and other mammals. This ability to detect the "handedness" of molecules has been shown in mammals, but the discovery is the first case of scientists finding out how it works in an insect, according to the researchers.
When they hunt for a blood meal, mosquitoes hone in on a variety of chemicals, including carbon dioxide, lactic acid, ammonia and octenol. Octenol is one of many carbon-based compounds that have a molecular structure that can take on either a "right-handed" or "left-handed" form. Each form is a mirror image of the other, and a form's "handedness" is determined by how its molecular bonds are assembled.
The scientists used frog eggs to help them make their discovery. They injected RNA from Ae. aegypti into the frog eggs, allowing the egg membranes to mimic the mosquito's ability to detect octenol. Then they attached microelectrodes to the frog egg cell membranes, passed octenol over them and recorded the electrical signals stimulated by the odors.
They ran the tests using both the right- and left-handed forms of octenol. The scientists found heightened electrical activity when the membrane was exposed to the right-handed form, and weakened activity when it was exposed to the left-handed form.
There are many natural compounds that can take on either a right-handed or left-handed form. While the effects of those differences on many plants and animals remains a mystery, the report, published in PLoS ONE, shows the effects of octenol's dual structure on the yellow fever mosquito and adds to scientists' understanding of how mosquitoes sense the world around them. It also may open the door to speedier development of better mosquito repellents and traps, according to Dickens.
The team's research is being funded by the Department of Defense Deployed War Fighter Protection Research Program.
ARS is the principal intramural scientific research agency of the U.S. Department of Agriculture.
USDA is an equal opportunity provider, employer and lender. To file a complaint of discrimination, write: USDA, Director, Office of Civil Rights, 1400 Independence Ave., S.W., Washington, D.C. 20250-9410 or call (800) 795-3272 (voice), or (202) 720-6382 (TDD).
Friday, January 01, 2010
Nominations Wanted for Jacobson Award for Physician Excellence
The Vascular Disease Foundation is seeking nominations for the 2010 Julius H. Jacobson II Award for Physician Excellence. The deadline for nominations is Friday, January 29, 2010.
The Julius H. Jacobson II MD Award for Physician Excellent is awarded annually by the Vascular Disease Foundation. This prestigious annual award recognizes outstanding contributions to physician education, leadership, or patient care in vascular disease. Dr. Jacobson is a pioneer in microsurgery and was the first physician to bring a microscope into the operating room. His work led to such advances as coronary artery surgery and limb reimplantation. Dr. Jacobson also developed the first microscope that allowed the surgeon and the first assistant to view the operative field simultaneously. This award is endowed through a donation from Dr. Jacobson.
Candidates for the Jacobson Award will be screened by a committee of peers independent of Dr. Jacobson. Nomination criteria are:
• Must be a licensed physician in good standing
• Has made significant contributions that have advanced the science or clinical
practice for the prevention and treatment of vascular disease or who has made exceptional contributions to vascular education programs, either to health professionals or patients.
• Must be a person of recognized personal and professional integrity.
• Must not be a current member of the Board of Directors of the Vascular Disease Foundation.
This year’s recipient was Dr. Jess R. Young. Dr. Young is one of the pioneers of vascular medicine and a premier educator in the field, training an entire generation of vascular medicine fellows. Dr. Young was pivotal in establishing the vascular diagnostic laboratory at the Cleveland Clinic. Perhaps one of the greatest visions by Dr. Young was the establishment of the first multi-specialty vascular intervention programs in the United States in the early 1990s. He also served as primary editor for the first edition of "A Textbook of Peripheral Vascular Disease," which remains one of the finest clinical textbooks of its kind. He has over 100 publications showing his depth of contribution to the field.
The Vascular Disease Foundation is seeking nominations for the 2010 Julius H. Jacobson II Award for Physician Excellence. The deadline for nominations is Friday, January 29, 2010.
The Julius H. Jacobson II MD Award for Physician Excellent is awarded annually by the Vascular Disease Foundation. This prestigious annual award recognizes outstanding contributions to physician education, leadership, or patient care in vascular disease. Dr. Jacobson is a pioneer in microsurgery and was the first physician to bring a microscope into the operating room. His work led to such advances as coronary artery surgery and limb reimplantation. Dr. Jacobson also developed the first microscope that allowed the surgeon and the first assistant to view the operative field simultaneously. This award is endowed through a donation from Dr. Jacobson.
Candidates for the Jacobson Award will be screened by a committee of peers independent of Dr. Jacobson. Nomination criteria are:
• Must be a licensed physician in good standing
• Has made significant contributions that have advanced the science or clinical
practice for the prevention and treatment of vascular disease or who has made exceptional contributions to vascular education programs, either to health professionals or patients.
• Must be a person of recognized personal and professional integrity.
• Must not be a current member of the Board of Directors of the Vascular Disease Foundation.
This year’s recipient was Dr. Jess R. Young. Dr. Young is one of the pioneers of vascular medicine and a premier educator in the field, training an entire generation of vascular medicine fellows. Dr. Young was pivotal in establishing the vascular diagnostic laboratory at the Cleveland Clinic. Perhaps one of the greatest visions by Dr. Young was the establishment of the first multi-specialty vascular intervention programs in the United States in the early 1990s. He also served as primary editor for the first edition of "A Textbook of Peripheral Vascular Disease," which remains one of the finest clinical textbooks of its kind. He has over 100 publications showing his depth of contribution to the field.
Monday, October 19, 2009
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.
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.
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.
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