In a study that could lay the foundation for mass-produced single-molecule sensors, physicists and engineers at Rice University have demonstrated a means of simultaneously making optical and electronic measurements of the same molecule.
The research, which is available online, is slated to appear in an upcoming issue of the journal Nano Letters. The experiments were performed on a nanoelectronic device consisting to two tiny electrodes separated by a molecule-sized gap. Using electric current, the researchers measured conduction through single molecules in the gap. In addition, light-focusing properties of the electrodes allowed the researchers to identify the molecule by a unique optical fingerprint.
"We can mass-produce these in known locations, and they have single-molecule sensitivity at room temperature in open air," said study co-author Douglas Natelson, associate professor of physics and astronomy and co-director of Rice's Quantum Magnetism Laboratory (QML). "In principle, we think the design may allow us to observe chemical reactions at the single-molecule level."
While scientists have used electronic and optical instruments to measure single molecules before, Rice's system is the first that allows both simultaneously -- a process known as "multimodal" sensing -- on a single small molecule.
The research sprang from a collaboration between Natelson's group -- where the electrodes were developed -- and Rice's Laboratory for Nanophotonics (LANP), where the simultaneous electronic and optical testing was performed. In research published last year, the two groups explained how the electrodes focus near-infrared light into the molecule-sized gap, increasing light intensity in the gap by as much as a million times. The increased intensity allows the team to collect unique optical signatures for molecules trapped there via a technique called surface enhanced Raman spectroscopy (SERS).
"Our latest results confirm that we have the sensitivity required to measure single molecules," said LANP Director Naomi Halas, the Stanley C. Moore Professor of Electrical and Computer Engineering and professor of chemistry. "That sensitivity, and the multimodal capabilities of this system, gives us a great tool for fundamental science at the nanoscale."
Daniel Ward, a student in Natelson's research group, built the electrodes from tiny gold wires on silicon wafers and performed the critical measurements. The group specializes in studying the electronic and magnetic properties of nanoscale objects -- particles and devices that are built with atomic precision. The devices are so small they can only be seen with certain types of microscopes, and even those provide unclear pictures at best. Natelson said the new multimodal device gives researchers a much clearer idea of what is going on by combining two different kinds of measurements, electronic and optical.
"Conduction across our electrodes is known to depend on a quantum effect called 'tunneling,'" Natelson said. "The gaps are so small that only one or two molecules contribute to the conduction. So when we get conduction, and we see the optical fingerprint associated with a particular molecule, and they track each other, then we know we're measuring a single molecule and we know what kind of molecule it is. We can even tell when it rotates and changes position."
Study co-authors include Jacob Ciszek, James Tour, Yanpeng Wu and Peter Nordlander, all of Rice. The research was sponsored by the National Science Foundation, the Welch Foundation, the Packard Foundation, the Sloan Foundation, the Research Corp., the Defense Advanced Research Projects Agency and the Air Force Office of Scientific Research.
Source: Jade Boyd
Rice University
суббота, 28 мая 2011 г.
Hormone's Role In Insects Could Give Insight For Cancer Treatment, Malnutrition
Starvation typically has dire consequences for an organism's growth. In the tobacco hawkmoth, tissues starved during the last stage of larval development stop growing because they lack the proper nutrients.
But new research shows that in the caterpillar of the moth, also known as Manduca sexta, tissues called imaginal discs, which give rise to structures such as the legs and eyes, form and grow despite severe starvation unless a substance called juvenile hormone is present. The hormone inhibits signals needed for imaginal discs to form and develop into their specified organs in the adult moth.
"You can almost think of the imaginal discs as acting like tumors," said James Truman, a University of Washington biology professor. "Without juvenile hormone, the discs can form and grow at the expense of the rest of the animal, but in the presence of the hormone their growth is coordinated with that of the entire insect."
The findings could have implications for anti-cancer agents as well as for understanding the basis of long-term effects of early infant malnutrition.
The husband-wife team of Truman and Lynn Riddiford, also a UW biology professor, discovered the phenomenon, which is described in a paper published in the June 2 edition of the journal Science. Other authors of the paper are Kiyoshi Hiruma of Hirosaki University in Japan; David Champlin of the University of Southern Maine; and two of Champlin's undergraduate students, Paul Allee and Steven MacWhinnie.
Typically, juvenile hormone declines in the last larval stage, allowing imaginal discs to form and begin developing into adult legs, eyes and antennae. Starvation normally causes higher levels of juvenile hormone during the last larval stage. But when the researchers removed glands called the corpora allata, which produce juvenile hormone, imaginal discs developed and grew despite the fact the larvae were being starved, though growth was slower than normal.
The research shows that juvenile hormone can work independent of nutrition to repress the growth of imaginal tissues in insects. That could herald a change in how scientists think when dealing with cancer or other growth-related phenomena, Truman said. Researchers typically tend to think in terms of chemical signals that promote growth, "but we find in insects that they also have a potent hormone that inhibits growth of developing tissues."
"Our paper is something of a wakeup call that there are hormones that repress growth, as well as those that stimulate it, and we should keep an eye out for them in other organisms, including ourselves," he said.
The work also raises questions about what permanent consequences early infant malnutrition might have for humans.
"It should raise our awareness that some early growth processes are coupled to nutrition, and if you uncouple them you can raise very serious developmental problems," Truman said.
Typically, the onset of metamorphosis to the adult tobacco hawkmoth is associated with the loss of juvenile hormone. But the researchers determined there is something else at work. They identified what they called a "metamorphosis initiating factor" that is tied to nutrition. In feeding caterpillars, nutritional cues can trigger the metamorphosis initiating factor, which in turn can allow imaginal discs to form and grow even when juvenile hormone is present.
In addition, while feeding seems to negate the effect of juvenile hormone in the last larval stage, the researchers found that some aspects of subsequent disc growth are still sensitive to juvenile hormone. When larvae that had not been starved were treated with juvenile hormone early in the last stage of development, they did not molt or go through metamorphosis and instead grew to abnormally large sizes. Their development of leg and wing discs was normal for the first two days and then declined.
"We saw a permanent redirecting of what the animal becomes," Riddiford said.
The work was supported by grants from the National Science Foundation; the U.S. Department of Agriculture Cooperative State Research, Education and Extension Service; the Bioscience Research Institute of Southern Maine and the Japan Society for the Promotion of Science.
Vince Stricherz
vincesu.washington
University of Washington
uwnews
But new research shows that in the caterpillar of the moth, also known as Manduca sexta, tissues called imaginal discs, which give rise to structures such as the legs and eyes, form and grow despite severe starvation unless a substance called juvenile hormone is present. The hormone inhibits signals needed for imaginal discs to form and develop into their specified organs in the adult moth.
"You can almost think of the imaginal discs as acting like tumors," said James Truman, a University of Washington biology professor. "Without juvenile hormone, the discs can form and grow at the expense of the rest of the animal, but in the presence of the hormone their growth is coordinated with that of the entire insect."
The findings could have implications for anti-cancer agents as well as for understanding the basis of long-term effects of early infant malnutrition.
The husband-wife team of Truman and Lynn Riddiford, also a UW biology professor, discovered the phenomenon, which is described in a paper published in the June 2 edition of the journal Science. Other authors of the paper are Kiyoshi Hiruma of Hirosaki University in Japan; David Champlin of the University of Southern Maine; and two of Champlin's undergraduate students, Paul Allee and Steven MacWhinnie.
Typically, juvenile hormone declines in the last larval stage, allowing imaginal discs to form and begin developing into adult legs, eyes and antennae. Starvation normally causes higher levels of juvenile hormone during the last larval stage. But when the researchers removed glands called the corpora allata, which produce juvenile hormone, imaginal discs developed and grew despite the fact the larvae were being starved, though growth was slower than normal.
The research shows that juvenile hormone can work independent of nutrition to repress the growth of imaginal tissues in insects. That could herald a change in how scientists think when dealing with cancer or other growth-related phenomena, Truman said. Researchers typically tend to think in terms of chemical signals that promote growth, "but we find in insects that they also have a potent hormone that inhibits growth of developing tissues."
"Our paper is something of a wakeup call that there are hormones that repress growth, as well as those that stimulate it, and we should keep an eye out for them in other organisms, including ourselves," he said.
The work also raises questions about what permanent consequences early infant malnutrition might have for humans.
"It should raise our awareness that some early growth processes are coupled to nutrition, and if you uncouple them you can raise very serious developmental problems," Truman said.
Typically, the onset of metamorphosis to the adult tobacco hawkmoth is associated with the loss of juvenile hormone. But the researchers determined there is something else at work. They identified what they called a "metamorphosis initiating factor" that is tied to nutrition. In feeding caterpillars, nutritional cues can trigger the metamorphosis initiating factor, which in turn can allow imaginal discs to form and grow even when juvenile hormone is present.
In addition, while feeding seems to negate the effect of juvenile hormone in the last larval stage, the researchers found that some aspects of subsequent disc growth are still sensitive to juvenile hormone. When larvae that had not been starved were treated with juvenile hormone early in the last stage of development, they did not molt or go through metamorphosis and instead grew to abnormally large sizes. Their development of leg and wing discs was normal for the first two days and then declined.
"We saw a permanent redirecting of what the animal becomes," Riddiford said.
The work was supported by grants from the National Science Foundation; the U.S. Department of Agriculture Cooperative State Research, Education and Extension Service; the Bioscience Research Institute of Southern Maine and the Japan Society for the Promotion of Science.
Vince Stricherz
vincesu.washington
University of Washington
uwnews
Breakthrough Discovery Reveals How Circadian Rhythm-Cell Energy Link Can Lead To New Treatments
UC Irvine researchers have discovered that circadian rhythms - our own body clock - regulate energy levels in cells. The findings have far-reaching implications, from providing greater insights into the bond between the body's day-night patterns and metabolism to creating new ways to treat cancer, diabetes, obesity and a host of related diseases.
In addition, Paolo Sassone-Corsi, Distinguished Professor and Chair of Pharmacology, and his colleagues found that the proteins involved with circadian rhythms and metabolism are intrinsically linked and dependent upon each other. Their study appears online in Science Express.
"Our circadian rhythms and metabolism are closely partnered to ensure that cells function properly and remain healthy," Sassone-Corsi said. "This discovery opens a new window for us to understand how these two fundamental processes work together, and it can have a great impact on new treatments for diseases caused by cell energy deficiencies."
Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms. The circadian clocks are the essential time-tracking systems in our bodies that anticipate environmental changes and adapt to the appropriate time of day. Disruption of these rhythms can profoundly influence human health and has been linked to obesity, diabetes, insomnia, depression, coronary heart diseases and cancer.
Sassone-Corsi already had identified that the enzyme protein CLOCK is an essential molecular gear of the circadian machinery and interacts with a protein, SIRT1, which senses cell energy levels and modulates aging and metabolism.
In this study, he and his colleagues show that CLOCK works in balance with SIRT1 to direct activity in a cell pathway by which metabolic proteins send signals called the NAD+ salvage pathway. In turn, a key protein in that pathway, NAMPT, helps control CLOCK levels, creating a tightly regulated codependency between our circadian clock and metabolism.
"When the balance between these two vital processes is upset, normal cellular function can be disrupted," Sassone-Corsi said. "And this can lead to illness and disease."
The findings suggest that proper sleep and diet may help maintain or rebuild this balance, he said, and also help explain why lack of rest or disruption of normal sleep patterns can increase hunger, leading to obesity-related illnesses and accelerated aging.
The specific interaction between CLOCK and SIRT1 and the NAD+ salvage pathway also presents a starting point for drug development aimed at curbing cell dysfunction and death, thereby helping to solve major medical problems such cancer and diabetes.
Notes:
Yasukazu Nakahata, Milota Kaluzova, Saurabh Sahar and Giuseppe Astarita of UCI participated in the study, which was supported by the Cancer Research Coordinating Committee of the University of California and the National Institutes of Health.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 27,000 undergraduate and graduate students. The top employer in dynamic Orange County, UCI contributes an annual economic impact of $4.2 billion. For more UCI news, visit today.uci.
Source: Tom Vasich
University of California - Irvine
In addition, Paolo Sassone-Corsi, Distinguished Professor and Chair of Pharmacology, and his colleagues found that the proteins involved with circadian rhythms and metabolism are intrinsically linked and dependent upon each other. Their study appears online in Science Express.
"Our circadian rhythms and metabolism are closely partnered to ensure that cells function properly and remain healthy," Sassone-Corsi said. "This discovery opens a new window for us to understand how these two fundamental processes work together, and it can have a great impact on new treatments for diseases caused by cell energy deficiencies."
Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms. The circadian clocks are the essential time-tracking systems in our bodies that anticipate environmental changes and adapt to the appropriate time of day. Disruption of these rhythms can profoundly influence human health and has been linked to obesity, diabetes, insomnia, depression, coronary heart diseases and cancer.
Sassone-Corsi already had identified that the enzyme protein CLOCK is an essential molecular gear of the circadian machinery and interacts with a protein, SIRT1, which senses cell energy levels and modulates aging and metabolism.
In this study, he and his colleagues show that CLOCK works in balance with SIRT1 to direct activity in a cell pathway by which metabolic proteins send signals called the NAD+ salvage pathway. In turn, a key protein in that pathway, NAMPT, helps control CLOCK levels, creating a tightly regulated codependency between our circadian clock and metabolism.
"When the balance between these two vital processes is upset, normal cellular function can be disrupted," Sassone-Corsi said. "And this can lead to illness and disease."
The findings suggest that proper sleep and diet may help maintain or rebuild this balance, he said, and also help explain why lack of rest or disruption of normal sleep patterns can increase hunger, leading to obesity-related illnesses and accelerated aging.
The specific interaction between CLOCK and SIRT1 and the NAD+ salvage pathway also presents a starting point for drug development aimed at curbing cell dysfunction and death, thereby helping to solve major medical problems such cancer and diabetes.
Notes:
Yasukazu Nakahata, Milota Kaluzova, Saurabh Sahar and Giuseppe Astarita of UCI participated in the study, which was supported by the Cancer Research Coordinating Committee of the University of California and the National Institutes of Health.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 27,000 undergraduate and graduate students. The top employer in dynamic Orange County, UCI contributes an annual economic impact of $4.2 billion. For more UCI news, visit today.uci.
Source: Tom Vasich
University of California - Irvine
OSU And OU Microbes Hunt Receives $1.3M NSF Grant
The National Science Foundation has approved a $1.3 million grant for researchers at Oklahoma State University and the University of Oklahoma to discover new kinds of microorganisms in natural habitats. The five-year grant will enable scientists to detect, identify, and isolate unique microorganisms using state-of-the-art molecular biological procedures at a sulfur spring in southwestern Oklahoma.
"During the last two decades, advances in techniques used to identify microorganisms have proven that a large number of unknown communities exist in nature, and Zodletone Spring (30 miles west of Anadarko) has several unique features perfect for this study," said Dr. Mostafa Elshahed, assistant professor in the microbiology and molecular genetics department at Oklahoma State University, and the lead investigator for the grant. "The spring has high sulfide and sulfur concentrations, high levels of gaseous hydrocarbons, and an absence of oxygen that makes it ideal to study and hunt for many of these unique bacteria."
Researchers will use the spring as a microbial observatory to identify and study four different groups of bacteria, their metabolic capabilities, and ecological role in the spring, according to Elshahed. Along with genomic (DNA-based) studies, these groups of bacteria will be cultivated and studied in the laboratory.
"Because these bacteria come from an environment in which oxygen is rare, some sophisticated isolation strategies will be used in the laboratory as we verify their environmental role and avoid the presence of oxygen which can kill them," said Elshahed.
The grant will also fund an educational outreach component that will allow high school students to get involved in the project. They will be asked to participate in a summer laboratory to conduct research and present findings at a symposium through the Junior Science and Humanities Symposia at Oklahoma State University.
"Our team is very happy to be chosen to receive this grant in a program that approves only 10 percent of the grant proposals that are submitted," said Elshahed, who together with Dr. Caroline Beller, assistant professor of education, are the lead researchers for the project at OSU. Dr. Lee Krumholz, associate professor of botany and microbiology, is the lead researcher at the University of Oklahoma. Of the total grant, $800,000 will go to OSU and $500,000 to OU.
Source: Kelly Green
Oklahoma State University
"During the last two decades, advances in techniques used to identify microorganisms have proven that a large number of unknown communities exist in nature, and Zodletone Spring (30 miles west of Anadarko) has several unique features perfect for this study," said Dr. Mostafa Elshahed, assistant professor in the microbiology and molecular genetics department at Oklahoma State University, and the lead investigator for the grant. "The spring has high sulfide and sulfur concentrations, high levels of gaseous hydrocarbons, and an absence of oxygen that makes it ideal to study and hunt for many of these unique bacteria."
Researchers will use the spring as a microbial observatory to identify and study four different groups of bacteria, their metabolic capabilities, and ecological role in the spring, according to Elshahed. Along with genomic (DNA-based) studies, these groups of bacteria will be cultivated and studied in the laboratory.
"Because these bacteria come from an environment in which oxygen is rare, some sophisticated isolation strategies will be used in the laboratory as we verify their environmental role and avoid the presence of oxygen which can kill them," said Elshahed.
The grant will also fund an educational outreach component that will allow high school students to get involved in the project. They will be asked to participate in a summer laboratory to conduct research and present findings at a symposium through the Junior Science and Humanities Symposia at Oklahoma State University.
"Our team is very happy to be chosen to receive this grant in a program that approves only 10 percent of the grant proposals that are submitted," said Elshahed, who together with Dr. Caroline Beller, assistant professor of education, are the lead researchers for the project at OSU. Dr. Lee Krumholz, associate professor of botany and microbiology, is the lead researcher at the University of Oklahoma. Of the total grant, $800,000 will go to OSU and $500,000 to OU.
Source: Kelly Green
Oklahoma State University
News From The American Chemical Society Oct. 15, 2008
LEDs may help reduce skin wrinkles, researchers report
Researchers in Germany are describing a potential alternative to Botox and cosmetic surgery for easing facial wrinkles. Their study, scheduled for the November 5 issue of ACS' Crystal Growth & Design, a bi-monthly journal, reports that high intensity visible light from light emitting diodes (LEDs) applied daily for several weeks resulted in "rejuvenated skin, reduced wrinkle levels, juvenile complexion and lasting resilience." LEDs are the miniature lights used in an array of products, from TV remote controls to traffic lights.
In the study, Andrei P. Sommer and Dan Zhu point out that high-intensity visible light has been used in medicine for more than 40 years to speed healing of wounds. That light actually penetrates into the skin, causing changes in the sub-surface tissue. Until now, however, scientists have not known the physicochemical nature of those changes.
They report identifying how the visible light works - by changing the molecular structure of a glue-like layer of water on elastin, the protein that provides elasticity in skin, blood vessels, heart and other body structures. Figuratively speaking, the light strips away those water molecules that are involved in the immobilization of elastin, gradually restoring its elastic function and thus reducing facial wrinkles. "We are justified in believing that our approach can be easily converted to deep body rejuvenation programs," the researchers state. - AD
"From Microtornadoes to Facial Rejuvenation: Implication of Interfacial Water Layers"
CONTACT:
Andrei P. Sommer, Ph.D.
University of Ulm
Ulm, Germany
Spinning natural proteins into fabrics for new wound-repair products
Scientists in Israel are reporting the first successful spinning of a key natural protein into strong nano-sized fibers about 1/50,000th the width of a human hair. The advance could lead to a new generation of stronger, longer-lasting biocompatible sutures and bandages to treat wounds. The study is scheduled for the November 10 issue of ACS' Biomacromolecules, a monthly journal.
Eyal Zussman and colleagues point out that researchers have tried for years to develop wound repair materials from natural proteins, hoping that such fibers would be more compatible with body tissue than existing materials. Scientists recently focused on producing these fibers through "electrospinning," a high-tech weaving process that uses electrical charges to draw out nano-sized fibers from a liquid. But the approach has achieved poor results until now.
In the new study, the scientists describe a new method for producing electrospun polymers using bovine serum albumin (BSA), a so-called "globular" protein found in cow's blood. BSA is similar to serum albumin, one of the most abundant proteins in the human body. The method involves adding certain chemicals to a solution of BSA to loosen the bonds that hold these highly-folded proteins together. That results in a thinner, more spinnable protein solution. Using electrospinning, the process resulted in strong fibers that are easily spun into suture-like threads or thick mats resembling conventional wound dressings. This approach is being followed by the groups of Zvi Nevo and Abraham Katzir at Tel-Aviv University, the researchers said, noting that the new method also can be applied to other types of natural proteins. - MTS
"Nanofibers Made of Globular Proteins"
CONTACT:
Eyal Zussman, Ph.D.
Technion-Israel Institute of Technology
Haifa, Israel
The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Source: Michael Woods
American Chemical Society
View drug information on Botox Cosmetic.
Researchers in Germany are describing a potential alternative to Botox and cosmetic surgery for easing facial wrinkles. Their study, scheduled for the November 5 issue of ACS' Crystal Growth & Design, a bi-monthly journal, reports that high intensity visible light from light emitting diodes (LEDs) applied daily for several weeks resulted in "rejuvenated skin, reduced wrinkle levels, juvenile complexion and lasting resilience." LEDs are the miniature lights used in an array of products, from TV remote controls to traffic lights.
In the study, Andrei P. Sommer and Dan Zhu point out that high-intensity visible light has been used in medicine for more than 40 years to speed healing of wounds. That light actually penetrates into the skin, causing changes in the sub-surface tissue. Until now, however, scientists have not known the physicochemical nature of those changes.
They report identifying how the visible light works - by changing the molecular structure of a glue-like layer of water on elastin, the protein that provides elasticity in skin, blood vessels, heart and other body structures. Figuratively speaking, the light strips away those water molecules that are involved in the immobilization of elastin, gradually restoring its elastic function and thus reducing facial wrinkles. "We are justified in believing that our approach can be easily converted to deep body rejuvenation programs," the researchers state. - AD
"From Microtornadoes to Facial Rejuvenation: Implication of Interfacial Water Layers"
CONTACT:
Andrei P. Sommer, Ph.D.
University of Ulm
Ulm, Germany
Spinning natural proteins into fabrics for new wound-repair products
Scientists in Israel are reporting the first successful spinning of a key natural protein into strong nano-sized fibers about 1/50,000th the width of a human hair. The advance could lead to a new generation of stronger, longer-lasting biocompatible sutures and bandages to treat wounds. The study is scheduled for the November 10 issue of ACS' Biomacromolecules, a monthly journal.
Eyal Zussman and colleagues point out that researchers have tried for years to develop wound repair materials from natural proteins, hoping that such fibers would be more compatible with body tissue than existing materials. Scientists recently focused on producing these fibers through "electrospinning," a high-tech weaving process that uses electrical charges to draw out nano-sized fibers from a liquid. But the approach has achieved poor results until now.
In the new study, the scientists describe a new method for producing electrospun polymers using bovine serum albumin (BSA), a so-called "globular" protein found in cow's blood. BSA is similar to serum albumin, one of the most abundant proteins in the human body. The method involves adding certain chemicals to a solution of BSA to loosen the bonds that hold these highly-folded proteins together. That results in a thinner, more spinnable protein solution. Using electrospinning, the process resulted in strong fibers that are easily spun into suture-like threads or thick mats resembling conventional wound dressings. This approach is being followed by the groups of Zvi Nevo and Abraham Katzir at Tel-Aviv University, the researchers said, noting that the new method also can be applied to other types of natural proteins. - MTS
"Nanofibers Made of Globular Proteins"
CONTACT:
Eyal Zussman, Ph.D.
Technion-Israel Institute of Technology
Haifa, Israel
The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Source: Michael Woods
American Chemical Society
View drug information on Botox Cosmetic.
A Key To Blood Vessel Growth And Possible Drug Target Revealed By Study
Researchers have identified a molecular pathway that plays a critical role in the growth of blood vessels. The finding not only offers an important insight into the development of the vascular system during embryonic development but suggests a potential target for inhibiting the blood vessels that fuel cancers, diabetic eye complications and atherosclerosis, the researchers say.
The study, published online on Oct. 14 in Nature Genetics was conducted in the zebrafish, the tiny, blue-and-silver striped denizen of India's Ganges River and many an aquarium.
A News and Views commentary on the paper will run in the same issue.
"We expect this finding will offer important insights into blood vessel formation in humans," says lead author Massimo Santoro, PhD, UCSF visiting postdoctoral fellow in the lab of senior author Didier Stainier, PhD, UCSF professor of biochemistry and biophysics. "The zebrafish has proven to be an important model for discovering molecules relevant to human disease."
Angiogenesis, or the growth of blood vessels, is active not only during embryonic development but throughout the life of the body, providing a source of oxygenated blood to tissues damaged by wounds.
However, it is also active in a number of disease processes, including cancer. Without a blood supply, tumors cannot grow beyond the size of a small pea. Cancerous tumors release chemical signals into their environment that stimulate healthy blood vessels to sprout new vessels that then extend into the tumors. During the last decade, scientists have identified several molecules that promote angiogenesis. A drug that inhibits these molecules is now commercially available and others are being studied in clinical trials.
Scientists are also exploring strategies for stimulating the growth of new blood vessels in patients whose clogged arteries prevent a sufficient blood supply to the heart muscle.
In the current study, the UCSF team determined that two well known signaling molecules, birc2 and TNF, are crucial to the survival of endothelial cells -- which line the blood vessels and maintain the integrity of the blood vessel wall during vascular development -- in zebrafish embryos.
"The pathway these molecules make up during vascular development has not been looked at before," says Stainier. "It offers a new target for therapeutic strategies."
The birc2 gene belongs to a family of proteins that control the balance between cell survival and cell death (apoptosis). A cell induces apoptosis when it detects that it is irreparably damaged. The integrity of the blood vessel wall is determined by a dynamic balance between endothelial cell survival and apoptosis.
The scientists started the investigation by examining zebrafish with unusual physical characteristics and working to identify the mutated genes that were responsible for the traits.
"We began with a genetic mutant that displayed vascular hemorrhage associated with vascular defects, and soon proved that the mutant had a defective birc2 gene," says Santoro. "Without the birc2 gene, hemorrhage and blood pooling occurred, resulting in vascular regression and cell death."
Next, through a series of genomic analyses and biochemical studies, the team discovered the critical role of birc2 and TNF in blood vessel health in the zebrafish embryo. They showed that birc2 is needed for the formation of the tumor necrosis factor receptor complex 1, a group of proteins and peptides that activate cell survival by initiating signals. Tumor necrosis factor promotes activation of NF-kB, a protein complex transcription factor involved in the transfer of genetic information. Further tests proved the existence of a genetic link between the birc2/NF-kB pathway, and that it is critical for vascular health and endothelial cell survival.
"Studies on vascular development are important so that we can better understand the molecular basis of how endothelial cell-related pathologies such as cancer, diabetic eye complications, known as retinopathies, atherosclerosis and system lupus develop," Santoro said. "It can also help us design new therapeutic strategies for these diseases."
The team hopes that future researchers will investigate other avenues and alternative pathways. "Because vascular health impacts many different diseases, understanding how to genetically control endothelial cell survival and apoptosis is critical to future work in these areas," Stainier said.
Stainier is a member of the UCSF Institute for Regeneration Medicine, the programs in Genetics and Human Genetics, and the Cardiovascular Research Institute.
Co-authors of the study were Tracy Mitchell, of the UCSF Department of Biophysics and Biochemistry, Programs in Developmental Biology, Genetics and Human Genetics, and Cardiovascular Research Institute; Temesgen Samuel, of the Burnham Institute for Medical Research and John C. Reed of the Burnham Institute.
The study was funded by the National Institutes of Health, American Heart Association, Packard Foundation and Human Frontier Science Program Fellowship.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Source: Jennifer O'Brien
University of California - San Francisco
The study, published online on Oct. 14 in Nature Genetics was conducted in the zebrafish, the tiny, blue-and-silver striped denizen of India's Ganges River and many an aquarium.
A News and Views commentary on the paper will run in the same issue.
"We expect this finding will offer important insights into blood vessel formation in humans," says lead author Massimo Santoro, PhD, UCSF visiting postdoctoral fellow in the lab of senior author Didier Stainier, PhD, UCSF professor of biochemistry and biophysics. "The zebrafish has proven to be an important model for discovering molecules relevant to human disease."
Angiogenesis, or the growth of blood vessels, is active not only during embryonic development but throughout the life of the body, providing a source of oxygenated blood to tissues damaged by wounds.
However, it is also active in a number of disease processes, including cancer. Without a blood supply, tumors cannot grow beyond the size of a small pea. Cancerous tumors release chemical signals into their environment that stimulate healthy blood vessels to sprout new vessels that then extend into the tumors. During the last decade, scientists have identified several molecules that promote angiogenesis. A drug that inhibits these molecules is now commercially available and others are being studied in clinical trials.
Scientists are also exploring strategies for stimulating the growth of new blood vessels in patients whose clogged arteries prevent a sufficient blood supply to the heart muscle.
In the current study, the UCSF team determined that two well known signaling molecules, birc2 and TNF, are crucial to the survival of endothelial cells -- which line the blood vessels and maintain the integrity of the blood vessel wall during vascular development -- in zebrafish embryos.
"The pathway these molecules make up during vascular development has not been looked at before," says Stainier. "It offers a new target for therapeutic strategies."
The birc2 gene belongs to a family of proteins that control the balance between cell survival and cell death (apoptosis). A cell induces apoptosis when it detects that it is irreparably damaged. The integrity of the blood vessel wall is determined by a dynamic balance between endothelial cell survival and apoptosis.
The scientists started the investigation by examining zebrafish with unusual physical characteristics and working to identify the mutated genes that were responsible for the traits.
"We began with a genetic mutant that displayed vascular hemorrhage associated with vascular defects, and soon proved that the mutant had a defective birc2 gene," says Santoro. "Without the birc2 gene, hemorrhage and blood pooling occurred, resulting in vascular regression and cell death."
Next, through a series of genomic analyses and biochemical studies, the team discovered the critical role of birc2 and TNF in blood vessel health in the zebrafish embryo. They showed that birc2 is needed for the formation of the tumor necrosis factor receptor complex 1, a group of proteins and peptides that activate cell survival by initiating signals. Tumor necrosis factor promotes activation of NF-kB, a protein complex transcription factor involved in the transfer of genetic information. Further tests proved the existence of a genetic link between the birc2/NF-kB pathway, and that it is critical for vascular health and endothelial cell survival.
"Studies on vascular development are important so that we can better understand the molecular basis of how endothelial cell-related pathologies such as cancer, diabetic eye complications, known as retinopathies, atherosclerosis and system lupus develop," Santoro said. "It can also help us design new therapeutic strategies for these diseases."
The team hopes that future researchers will investigate other avenues and alternative pathways. "Because vascular health impacts many different diseases, understanding how to genetically control endothelial cell survival and apoptosis is critical to future work in these areas," Stainier said.
Stainier is a member of the UCSF Institute for Regeneration Medicine, the programs in Genetics and Human Genetics, and the Cardiovascular Research Institute.
Co-authors of the study were Tracy Mitchell, of the UCSF Department of Biophysics and Biochemistry, Programs in Developmental Biology, Genetics and Human Genetics, and Cardiovascular Research Institute; Temesgen Samuel, of the Burnham Institute for Medical Research and John C. Reed of the Burnham Institute.
The study was funded by the National Institutes of Health, American Heart Association, Packard Foundation and Human Frontier Science Program Fellowship.
UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.
Source: Jennifer O'Brien
University of California - San Francisco
Woo Suk Hwang, Who Faked Research, Made Spectacular Breakthrough
It has emerged that Woo Suk Hwang, the South Korean scientist who was named and shamed for faking his research, made an amazing breakthrough. According to Cell Stem Cell, he may have managed to create stem cells solely from human eggs, without fertilization with sperm. This breakthrough is possibly much more valuable than his original false claims about his work.
Hwang's work at Seoul National University was famous worldwide - he became a national hero and possibly the most esteemed stem cell scientist in the world. In 2005, his status came crumbling down when it was revealed he had faked much of his claims. He had said that he and his team created cloned human embryos by putting a cell's nucleus into an empty human egg, and then used the stem cells for those embryos. It was later found that the embryos had originated from the eggs of female members of his laboratory team - in other words, not from cloned embryos. He was fired and then charged with fraud and misappropriation of funds (embezzlement).
Recently, researchers from Harvard Stem Cell Institute, led by Dr George Daley, examined his research again and determined that the cells came from a another type of embryo. The scientists say it is well possible that Hwang and team had managed to pull off the world's first human case of parthenogenesis, or 'virgin birth'.
(Parthenogenesis = When an egg is stimulated into becoming an embryo without sperm fertilization taking place.)
Parthenogenesis has been done with animals, but never with humans where the embryo survived long enough to get viable stem cells from it.
Dr George Daley told the BBC "Unfortunately at the time they published their work they did not know what they had done so they had mistakenly isolated these parthenogenic embryonic stem cells, and yet misrepresented them as true clones. In fact they had produced the world's first patient-specific embryonic stem cell, and that is very valuable. Scientists interested in modelling complex diseases would like to be able to move a patient's own cells into a petri dish in their embryonic form."
Discredited Korean embryonic stem cells' true origins revealed
Harvard News Office
Click here to view article online
cellstemcell
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Hwang's work at Seoul National University was famous worldwide - he became a national hero and possibly the most esteemed stem cell scientist in the world. In 2005, his status came crumbling down when it was revealed he had faked much of his claims. He had said that he and his team created cloned human embryos by putting a cell's nucleus into an empty human egg, and then used the stem cells for those embryos. It was later found that the embryos had originated from the eggs of female members of his laboratory team - in other words, not from cloned embryos. He was fired and then charged with fraud and misappropriation of funds (embezzlement).
Recently, researchers from Harvard Stem Cell Institute, led by Dr George Daley, examined his research again and determined that the cells came from a another type of embryo. The scientists say it is well possible that Hwang and team had managed to pull off the world's first human case of parthenogenesis, or 'virgin birth'.
(Parthenogenesis = When an egg is stimulated into becoming an embryo without sperm fertilization taking place.)
Parthenogenesis has been done with animals, but never with humans where the embryo survived long enough to get viable stem cells from it.
Dr George Daley told the BBC "Unfortunately at the time they published their work they did not know what they had done so they had mistakenly isolated these parthenogenic embryonic stem cells, and yet misrepresented them as true clones. In fact they had produced the world's first patient-specific embryonic stem cell, and that is very valuable. Scientists interested in modelling complex diseases would like to be able to move a patient's own cells into a petri dish in their embryonic form."
Discredited Korean embryonic stem cells' true origins revealed
Harvard News Office
Click here to view article online
cellstemcell
Written by:
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