Thousands of scientists and health professionals from the field of medical physics will meet at the 52nd meeting of the American Association of Physicists in Medicine (AAPM) from July 18 - 22, 2010 in Philadelphia, Pennsylvania. They will present the latest technological advances in medical imaging and radiation therapy and discuss the safety and regulatory issues facing the field today.
AAPM is the premier organization in medical physics, a broadly-based scientific and professional discipline encompassing physics principles and applications in medicine and biology. Its membership includes medical physicists who specialize in research that develops cutting-edge technologies and board-certified clinical medical physicists who apply these technologies in community hospitals, clinics, and academic medical centers.
The presentations at the AAPM meeting will cover topics ranging from new ways of imaging the human body to the latest clinical developments on treating cancer with high energy X-rays and electrons from accelerators, brachytherapy with radioactive sources, and protons. Many of the talks and posters are focused on patient safety -- tailoring therapy to the specific needs of people undergoing treatment, such as shaping emissions to conform to tumors, or finding ways to image children safely at lower radiation exposures while maintaining good image quality.
Source:
Jason Bardi
American Institute of Physics
суббота, 28 мая 2011 г.
Microscale Environments Could Be Probed By Super Small Nanoelectrodes
Investigating the composition and behavior of microscale environments, including those within living cells, could become easier and more precise with nanoelectrodes being developed at the University of Illinois.
"The individual nanotube-based probes can be used for electrochemical and biochemical sensing," said Min-Feng Yu, a U. of I. professor of mechanical science and engineering, and a researcher at the university's Beckman Institute. "The position of the nanoelectrodes can be controlled very accurately."
To fabricate the nanoelectrodes, Yu and graduate students Kyungsuk Yum, Jie Hu and Han Na Cho begin by attaching a strong, rigid, boron-nitride nanotube to a much larger, conductive probe. The nanotube will form the insulating core of the nanoelectrode.
The researchers then coat the nanotube with a thin film of gold about 10-50 nanometers thick (a nanometer is 1 billionth of a meter.) The gold layer is then coated with an insulating polymer coating about 10 nanometers thick. Lastly, the researchers use a focused ion beam to slice off the end of the nanotube, exposing a conducting ring of gold sandwiched between an insulating core and an insulating outer ring.
The process yields nanoelectrodes with a diameter of 100 nanometers, and a length of up to 30 microns.
Because the nanotube is attached to a much larger probe, the researchers can manipulate the nanotube like a needle. They can control precisely where the nanotube penetrates a cell, for example, and even pinpoint smaller cell structures, such as the nucleus or mitochondrion.
"Nanoelectrodes offer new opportunities for electrochemical sensing in intracellular environments," said Yu, who will describe the fabrication process and demonstrate the feasibility of nanoelectrodes at the March meeting of the American Physical Society, to be held in Denver, March 5-9. "By functionalizing the active area of the nanoelectrode with an appropriate chemical, we can target the detection of specific chemical species."
The researchers have demonstrated that their nanoelectrode can sense the chemical environment within a droplet 10 microns in diameter. Their next step is to show that the probe can penetrate the cellular membrane of a living cell, without damaging the cell.
The National Science Foundation and the University of Illinois funded the work.
Contact: James E. Kloeppel
University of Illinois at Urbana-Champaign
"The individual nanotube-based probes can be used for electrochemical and biochemical sensing," said Min-Feng Yu, a U. of I. professor of mechanical science and engineering, and a researcher at the university's Beckman Institute. "The position of the nanoelectrodes can be controlled very accurately."
To fabricate the nanoelectrodes, Yu and graduate students Kyungsuk Yum, Jie Hu and Han Na Cho begin by attaching a strong, rigid, boron-nitride nanotube to a much larger, conductive probe. The nanotube will form the insulating core of the nanoelectrode.
The researchers then coat the nanotube with a thin film of gold about 10-50 nanometers thick (a nanometer is 1 billionth of a meter.) The gold layer is then coated with an insulating polymer coating about 10 nanometers thick. Lastly, the researchers use a focused ion beam to slice off the end of the nanotube, exposing a conducting ring of gold sandwiched between an insulating core and an insulating outer ring.
The process yields nanoelectrodes with a diameter of 100 nanometers, and a length of up to 30 microns.
Because the nanotube is attached to a much larger probe, the researchers can manipulate the nanotube like a needle. They can control precisely where the nanotube penetrates a cell, for example, and even pinpoint smaller cell structures, such as the nucleus or mitochondrion.
"Nanoelectrodes offer new opportunities for electrochemical sensing in intracellular environments," said Yu, who will describe the fabrication process and demonstrate the feasibility of nanoelectrodes at the March meeting of the American Physical Society, to be held in Denver, March 5-9. "By functionalizing the active area of the nanoelectrode with an appropriate chemical, we can target the detection of specific chemical species."
The researchers have demonstrated that their nanoelectrode can sense the chemical environment within a droplet 10 microns in diameter. Their next step is to show that the probe can penetrate the cellular membrane of a living cell, without damaging the cell.
The National Science Foundation and the University of Illinois funded the work.
Contact: James E. Kloeppel
University of Illinois at Urbana-Champaign
News From The Journal Of Clinical Investigation: Aug. 25, 2010
BACTERIOLOGY: Antifreeze molecule enhances survival of bacteria-carrying ticks
Ticks can carry and transmit to humans disease-causing bacteria. For example, the black-legged tick, Ixodes scapularis, can transmit several bacteria that cause disease in humans, including Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis, a disease characterized by fever, severe headache, muscle aches, chills, and shaking. If bacteria can in any way enhance the survival of the ticks that transmit them, this increases their likelihood of infecting a human, thereby impacting human health. A team of researchers, led by Erol Fikrig, at Yale University School of Medicine, New Haven, has now determined that Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze molecule that enhances tick survival in the cold. As Ixodes scapularis ticks overwinter in the US in the Northeast and Upper Midwest, this likely increases the number of Anaplasma phagocytophilum available to infect humans. As noted by Stephen Dumler, at The Johns Hopkins University School of Medicine, Baltimore, in an accompanying commentary, these data highlight how important understanding ecology and tick biology can be to unraveling the intricacies of human disease.
Title: Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the cold
Accompanying Commentary Title: Fitness and freezing: vector biology and human health
BACTERIOLOGY: Immune interference, an explanation for vaccine failure?
Infection with Staphylococcus aureus bacteria is a major cause of bloodstream, lower respiratory tract, and skin and soft tissue infections. Given the dramatic increase in the number of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), a Staphylococcus aureus vaccine is much needed. However, vaccines developed thus far have failed to induce protection in clinical trials, and even prior infection with the bacterium fails to engender protection against subsequent infection. A team of researchers, led by Gerald Pier, at Brigham and Women's Hospital, Harvard Medical School, Boston, has now generated data in mice to explain why vaccines and prior infection do not provide individuals with protection from Staphylococcus aureus.
In the study, immune molecules known as antibodies that target the Staphylococcus aureus components CP and PNAG were each shown to indirectly mediate bacterial killing in vitro and to provide protection in mouse models of Staphylococcus aureus infection. However, when mixed together, in vitro killing and in vivo protection were markedly reduced because the antibodies interfered with each other. Further analysis indicated that interference occurred because the parts of the antibodies that bound CP and PNAG interacted with each other in a process known as idiotype-anti-idiotype binding. Similar binding was observed for antibodies isolated from humans with Staphylococcus aureus bloodstream infections. As noted by the authors, and Liise-anne Pirofski, at Albert Einstein College of Medicine, New York, in an accompanying commentary, this identification of a mechanism to explain the inability of humans to mount good protective antibody responses to Staphylococcus aureus should help in the design of future candidate vaccines.
Title: Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice
Accompanying Commentary Title: Why antibodies disobey the Hippocratic Oath and end up doing harm: a new clue
PULMONARY: New cystic fibrosis models teach us about disease
Cystic fibrosis (CF) is caused by genetic mutations that disrupt the function of the protein CFTR. Although many organs are affected in cystic fibrosis, the most life-threatening aspect of the disease is lung disease. To understand this more deeply, animal models of cystic fibrosis that more closely mimic the human disease than do mouse models are needed. To this end, three independent research groups - one led by Kevin Foskett, at the University of Pennsylvania, Philadelphia; one led by John Engelhardt, at the University of Iowa, Iowa City; and one led by Jeffrey Wine, at Stanford University, Stanford - have analyzed pig and ferret models of cystic fibrosis and determined that they represent good models of lung disease in individuals with cystic fibrosis. As concluded by each of the authors and noted by Jonathan Widdicombe, at the University of California Davis, Davis, in an accompanying commentary, these animals will prove valuable models to both further understanding of the mechanisms underlying lung disease in individuals with cystic fibrosis and test potential therapies.
Title: cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways
Accompanying Article: Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs
Accompanying Article Title: Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis
Accompanying Commentary Title: Transgenic animals may resolve a sticky situation in cystic fibrosis
REPRODUCTIVE BIOLOGY: Long standing question in sperm biology answered
Nahum Sonenberg, Bernard Robaire, and colleagues, at McGill University, Montreal, have generated data in mice that provides insight into a long unanswered question in sperm biology. Specifically, how protein expression is regulated in the late stages of sperm development. The importance of these data are outlined in an accompanying commentary by Stephen Liebhaber and colleagues, at the University of Pennsylvania, Philadelphia.
A protein in a cell is made from a template known as an mRNA molecule, which in turn is a copy of the information contained in a gene. About half way through sperm development, mRNA formation ceases so the mRNA templates for proteins needed in the late stages of sperm development must be made early in development and stored. Understanding of the mechanisms that underlie mRNA storage and subsequent activation has been long sought after. In the study, Sonenberg, Robaire, and colleagues find that mice lacking the protein Paip2a and mice lacking Paip2a and Paip2b exhibit male infertility associated with impaired activation of stored mRNAs. Further analysis indicated that aberrant increased expression of the protein Pabp caused the impaired activation of stored mRNAs, leading the authors to conclude that mRNA activation in late sperm development requires an optimal concentration of Pabp, as determined by Paip2a.
Title: The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice
Accompanying Commentary Title: Too much PABP, too little translation
Source:
Karen Honey
Journal of Clinical Investigation
Ticks can carry and transmit to humans disease-causing bacteria. For example, the black-legged tick, Ixodes scapularis, can transmit several bacteria that cause disease in humans, including Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis, a disease characterized by fever, severe headache, muscle aches, chills, and shaking. If bacteria can in any way enhance the survival of the ticks that transmit them, this increases their likelihood of infecting a human, thereby impacting human health. A team of researchers, led by Erol Fikrig, at Yale University School of Medicine, New Haven, has now determined that Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze molecule that enhances tick survival in the cold. As Ixodes scapularis ticks overwinter in the US in the Northeast and Upper Midwest, this likely increases the number of Anaplasma phagocytophilum available to infect humans. As noted by Stephen Dumler, at The Johns Hopkins University School of Medicine, Baltimore, in an accompanying commentary, these data highlight how important understanding ecology and tick biology can be to unraveling the intricacies of human disease.
Title: Anaplasma phagocytophilum induces Ixodes scapularis ticks to express an antifreeze glycoprotein gene that enhances their survival in the cold
Accompanying Commentary Title: Fitness and freezing: vector biology and human health
BACTERIOLOGY: Immune interference, an explanation for vaccine failure?
Infection with Staphylococcus aureus bacteria is a major cause of bloodstream, lower respiratory tract, and skin and soft tissue infections. Given the dramatic increase in the number of infections caused by methicillin-resistant Staphylococcus aureus (MRSA), a Staphylococcus aureus vaccine is much needed. However, vaccines developed thus far have failed to induce protection in clinical trials, and even prior infection with the bacterium fails to engender protection against subsequent infection. A team of researchers, led by Gerald Pier, at Brigham and Women's Hospital, Harvard Medical School, Boston, has now generated data in mice to explain why vaccines and prior infection do not provide individuals with protection from Staphylococcus aureus.
In the study, immune molecules known as antibodies that target the Staphylococcus aureus components CP and PNAG were each shown to indirectly mediate bacterial killing in vitro and to provide protection in mouse models of Staphylococcus aureus infection. However, when mixed together, in vitro killing and in vivo protection were markedly reduced because the antibodies interfered with each other. Further analysis indicated that interference occurred because the parts of the antibodies that bound CP and PNAG interacted with each other in a process known as idiotype-anti-idiotype binding. Similar binding was observed for antibodies isolated from humans with Staphylococcus aureus bloodstream infections. As noted by the authors, and Liise-anne Pirofski, at Albert Einstein College of Medicine, New York, in an accompanying commentary, this identification of a mechanism to explain the inability of humans to mount good protective antibody responses to Staphylococcus aureus should help in the design of future candidate vaccines.
Title: Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice
Accompanying Commentary Title: Why antibodies disobey the Hippocratic Oath and end up doing harm: a new clue
PULMONARY: New cystic fibrosis models teach us about disease
Cystic fibrosis (CF) is caused by genetic mutations that disrupt the function of the protein CFTR. Although many organs are affected in cystic fibrosis, the most life-threatening aspect of the disease is lung disease. To understand this more deeply, animal models of cystic fibrosis that more closely mimic the human disease than do mouse models are needed. To this end, three independent research groups - one led by Kevin Foskett, at the University of Pennsylvania, Philadelphia; one led by John Engelhardt, at the University of Iowa, Iowa City; and one led by Jeffrey Wine, at Stanford University, Stanford - have analyzed pig and ferret models of cystic fibrosis and determined that they represent good models of lung disease in individuals with cystic fibrosis. As concluded by each of the authors and noted by Jonathan Widdicombe, at the University of California Davis, Davis, in an accompanying commentary, these animals will prove valuable models to both further understanding of the mechanisms underlying lung disease in individuals with cystic fibrosis and test potential therapies.
Title: cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways
Accompanying Article: Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs
Accompanying Article Title: Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis
Accompanying Commentary Title: Transgenic animals may resolve a sticky situation in cystic fibrosis
REPRODUCTIVE BIOLOGY: Long standing question in sperm biology answered
Nahum Sonenberg, Bernard Robaire, and colleagues, at McGill University, Montreal, have generated data in mice that provides insight into a long unanswered question in sperm biology. Specifically, how protein expression is regulated in the late stages of sperm development. The importance of these data are outlined in an accompanying commentary by Stephen Liebhaber and colleagues, at the University of Pennsylvania, Philadelphia.
A protein in a cell is made from a template known as an mRNA molecule, which in turn is a copy of the information contained in a gene. About half way through sperm development, mRNA formation ceases so the mRNA templates for proteins needed in the late stages of sperm development must be made early in development and stored. Understanding of the mechanisms that underlie mRNA storage and subsequent activation has been long sought after. In the study, Sonenberg, Robaire, and colleagues find that mice lacking the protein Paip2a and mice lacking Paip2a and Paip2b exhibit male infertility associated with impaired activation of stored mRNAs. Further analysis indicated that aberrant increased expression of the protein Pabp caused the impaired activation of stored mRNAs, leading the authors to conclude that mRNA activation in late sperm development requires an optimal concentration of Pabp, as determined by Paip2a.
Title: The poly(A)-binding protein partner Paip2a controls translation during late spermiogenesis in mice
Accompanying Commentary Title: Too much PABP, too little translation
Source:
Karen Honey
Journal of Clinical Investigation
Discovery Of Access Code For Tick-Borne Encephalitis Virus
Fritz et al. have identified an amino acid switch that flaviviruses flip to gain access to cells.
Flaviviruses such as tick-borne encephalitis virus (TBEV), yellow fever, and dengue are dangerous human pathogens. These membrane-encircled viruses enter cells by being gobbled up into endosomes and fusing their membrane with that of the endosome.
Fusion is triggered by the endosome's acidic environment. Low pH prompts the aptly named fusion protein, on the virus's outer membrane, to change shape and grab hold of the endosome membrane, bringing the two membranes together. In their search for possible pH sensors, researchers have focused on five highly conserved histidine residues in the flavivirus fusion protein. The chemical properties of histidines make them prime candidates - they switch from uncharged to having a double positive charge upon acidification of their environment, such as that in endosomes.
Fritz et al. replaced each of the five histidines of the TBEV fusion protein with alternative residues and observed the virus's fusion ability. Given the conservation of the five histidines, the team was surprised, that mutation of one of the histidines, His323, was sufficient to completely abolish fusion. Individual mutation of three of the others had no effect on fusion whatsoever, and mutation of the fourth led to an untestable ill-formed fusion protein.
The team went on to show that mutation of the crucial His323 interfered with the pH-induced shape change of the fusion protein.
Fritz, R., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200806081.
Source: Sati Motieram
Rockefeller University Press
Flaviviruses such as tick-borne encephalitis virus (TBEV), yellow fever, and dengue are dangerous human pathogens. These membrane-encircled viruses enter cells by being gobbled up into endosomes and fusing their membrane with that of the endosome.
Fusion is triggered by the endosome's acidic environment. Low pH prompts the aptly named fusion protein, on the virus's outer membrane, to change shape and grab hold of the endosome membrane, bringing the two membranes together. In their search for possible pH sensors, researchers have focused on five highly conserved histidine residues in the flavivirus fusion protein. The chemical properties of histidines make them prime candidates - they switch from uncharged to having a double positive charge upon acidification of their environment, such as that in endosomes.
Fritz et al. replaced each of the five histidines of the TBEV fusion protein with alternative residues and observed the virus's fusion ability. Given the conservation of the five histidines, the team was surprised, that mutation of one of the histidines, His323, was sufficient to completely abolish fusion. Individual mutation of three of the others had no effect on fusion whatsoever, and mutation of the fourth led to an untestable ill-formed fusion protein.
The team went on to show that mutation of the crucial His323 interfered with the pH-induced shape change of the fusion protein.
Fritz, R., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200806081.
Source: Sati Motieram
Rockefeller University Press
What Does Testosterone Do For Red Deer Males?
The study shows that testosterone levels during the reproductive season have important effects in the life of male red deer.
Stags with high testosterone had larger testes and high quality sperm, translating into higher reproductive success. They also present stronger antlers, expectedly allowing them to win more male to male combats for females.
These males also have more red blood cells supplying oxygen to the muscles, giving them more stamina and endurance to defeat more males in combat and copulate with more females.
However, testosterone also presents costs, as stags with higher levels have more parasites.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
Stags with high testosterone had larger testes and high quality sperm, translating into higher reproductive success. They also present stronger antlers, expectedly allowing them to win more male to male combats for females.
These males also have more red blood cells supplying oxygen to the muscles, giving them more stamina and endurance to defeat more males in combat and copulate with more females.
However, testosterone also presents costs, as stags with higher levels have more parasites.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
Dopamine's Opposing Effects Separated By A Few Millimeters In The Brain
The chemical dopamine induces both desire and dread, according to new animal research in the July 9 issue of The Journal of Neuroscience. Although dopamine is well known to motivate animals and people to seek positive rewards, the study indicates that it also can promote negative feelings like fear. The finding may help explain why dopamine dysfunction is implicated not only in drug addiction, which involves excessive desire, but in schizophrenia and some phobias, which involve excessive fear.
"This study changes our thinking about what dopamine does," said Howard Fields, MD, PhD, of the University of California, San Francisco, an expert unaffiliated with the study. "There is a huge body of evidence out there to support the idea that dopamine mediates positive effects, like reward, happiness, and pleasure. This study says, it does do that, but it can also promote negative behaviors through actions in an adjacent brain area," Fields said.
Kent Berridge, PhD, and his colleagues at the University of Michigan, identified dopamine's dual effect on the nucleus accumbens, a brain region that motivates people and animals to seek out pleasurable rewards like food, sex, or drugs, but is also involved in fear. They found that inhibiting dopamine's normal function prevented the nucleus accumbens neurons from inducing both rewarding and fearful behaviors, suggesting that dopamine is important in both.
In previous research, Berridge and colleagues showed that a distance of only a few millimeters separated desire and dread functions in the nucleus accumbens (which is only about 5 millimeters long in humans). Because dopamine is an important neurotransmitter in this brain structure, the researchers investigated its role in generating these functions in the current study.
When dopamine was allowed to act normally, injection of a chemical to model normal signaling in the front of the nucleus accumbens caused rats to eat nearly three times as much as they normally do. In contrast, injection of the chemical in the back of the nucleus accumbens caused rats to display fearful behavior normally shown in response to a predator.
"It has always been assumed that discrete neurotransmitters might separate fear from desire, but this report shows that transmitters such as dopamine play a constant role and that the anatomy is providing for emotional discretion," said Peter Kalivas, PhD, at the Medical University of South Carolina, who was unaffiliated with the study.
Berridge speculates that disruption of dopamine neurotransmission in one region of the nucleus accumbens may be a mechanism for pathological excesses of fear in disorders such as schizophrenia, whereas disruptions in dopamine neurotransmission in an adjacent region may be a mechanism for excessive reward-seeking in conditions like addiction.
The research was supported by the National Institute of Mental Health and the National Institute on Drug Abuse.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 38,000 basic scientists and clinicians who study the brain and nervous system.
Source: DeeDee Clendenning
Society for Neuroscience
"This study changes our thinking about what dopamine does," said Howard Fields, MD, PhD, of the University of California, San Francisco, an expert unaffiliated with the study. "There is a huge body of evidence out there to support the idea that dopamine mediates positive effects, like reward, happiness, and pleasure. This study says, it does do that, but it can also promote negative behaviors through actions in an adjacent brain area," Fields said.
Kent Berridge, PhD, and his colleagues at the University of Michigan, identified dopamine's dual effect on the nucleus accumbens, a brain region that motivates people and animals to seek out pleasurable rewards like food, sex, or drugs, but is also involved in fear. They found that inhibiting dopamine's normal function prevented the nucleus accumbens neurons from inducing both rewarding and fearful behaviors, suggesting that dopamine is important in both.
In previous research, Berridge and colleagues showed that a distance of only a few millimeters separated desire and dread functions in the nucleus accumbens (which is only about 5 millimeters long in humans). Because dopamine is an important neurotransmitter in this brain structure, the researchers investigated its role in generating these functions in the current study.
When dopamine was allowed to act normally, injection of a chemical to model normal signaling in the front of the nucleus accumbens caused rats to eat nearly three times as much as they normally do. In contrast, injection of the chemical in the back of the nucleus accumbens caused rats to display fearful behavior normally shown in response to a predator.
"It has always been assumed that discrete neurotransmitters might separate fear from desire, but this report shows that transmitters such as dopamine play a constant role and that the anatomy is providing for emotional discretion," said Peter Kalivas, PhD, at the Medical University of South Carolina, who was unaffiliated with the study.
Berridge speculates that disruption of dopamine neurotransmission in one region of the nucleus accumbens may be a mechanism for pathological excesses of fear in disorders such as schizophrenia, whereas disruptions in dopamine neurotransmission in an adjacent region may be a mechanism for excessive reward-seeking in conditions like addiction.
The research was supported by the National Institute of Mental Health and the National Institute on Drug Abuse.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 38,000 basic scientists and clinicians who study the brain and nervous system.
Source: DeeDee Clendenning
Society for Neuroscience
P[acman]-Generated Fruit Fly Gene 'Library': A New Research Tool
Using a specially adapted tool called P[acman], a collaboration of researchers led by Baylor College of Medicine has established a library of clones that cover most of the genome of Drosophila melanogaster (fruit fly) and should speed the pace of genetic research.
In a report in the current online issue of the journal Nature Methods, Dr. Hugo Bellen, a professor of molecular and human genetics at BCM and a Howard Hughes Medical Institute investigator, and his colleagues describe the new libraries.
P[acman] - developed by Dr. Koen Venken in Bellen's laboratory - allows scientists to study large chunks of DNA in living flies. The vector - officially P/phiC31 artificial chromosome for manipulation - combines different technologies: a specially designed bacterial artificial chromosome (BAC) that allows maintenance of large pieces of DNA in bacteria, recombineering that allows the manipulation of large pieces of DNA in bacteria, and the ability to insert the genomic DNA into the genome of the fly at a specific site using phiC31-mediated transgenesis.
Venken adapted the P[acman] vector to create genomic libraries, so that a researcher can choose a gene and find the corresponding clones in the library that cover that gene. Their collaborators at Lawrence Berkeley National Laboratory, Drs. Roger Hoskins and Joseph Carlson, played a key role in the design, construction, and annotation of the libraries.
"You can insert a single copy of a gene and rescue a mutation, or do a structure/function analysis of the gene," Bellen said. "If you don't know where the gene is expressed, you can tag it, put it back and locate where it is expressed."
The library is available at pacmanfly/.
The report is available at nature/nmeth/index.html
Others who took part in this work include Karen L. Schulze, Hongling Pan and Yuchun He of BCM, Ken Wan (LBNL), Rebecca Spokony and Kevin P. White of the University of Chicago, and Maxim Koriabine and Pieter J. de Jong of Children's Hospital Oakland Research Institute in California.
Funding for this work came from the Howard Hughes Medical Institute, the National Institutes of Health and the BCM Intellectual and Developmental Disabilities Research Center.
Source:
Glenna Picton
Baylor College of Medicine
In a report in the current online issue of the journal Nature Methods, Dr. Hugo Bellen, a professor of molecular and human genetics at BCM and a Howard Hughes Medical Institute investigator, and his colleagues describe the new libraries.
P[acman] - developed by Dr. Koen Venken in Bellen's laboratory - allows scientists to study large chunks of DNA in living flies. The vector - officially P/phiC31 artificial chromosome for manipulation - combines different technologies: a specially designed bacterial artificial chromosome (BAC) that allows maintenance of large pieces of DNA in bacteria, recombineering that allows the manipulation of large pieces of DNA in bacteria, and the ability to insert the genomic DNA into the genome of the fly at a specific site using phiC31-mediated transgenesis.
Venken adapted the P[acman] vector to create genomic libraries, so that a researcher can choose a gene and find the corresponding clones in the library that cover that gene. Their collaborators at Lawrence Berkeley National Laboratory, Drs. Roger Hoskins and Joseph Carlson, played a key role in the design, construction, and annotation of the libraries.
"You can insert a single copy of a gene and rescue a mutation, or do a structure/function analysis of the gene," Bellen said. "If you don't know where the gene is expressed, you can tag it, put it back and locate where it is expressed."
The library is available at pacmanfly/.
The report is available at nature/nmeth/index.html
Others who took part in this work include Karen L. Schulze, Hongling Pan and Yuchun He of BCM, Ken Wan (LBNL), Rebecca Spokony and Kevin P. White of the University of Chicago, and Maxim Koriabine and Pieter J. de Jong of Children's Hospital Oakland Research Institute in California.
Funding for this work came from the Howard Hughes Medical Institute, the National Institutes of Health and the BCM Intellectual and Developmental Disabilities Research Center.
Source:
Glenna Picton
Baylor College of Medicine
How Chemical Markers Prevalent On Cancer And HIV-Infected Cells Can Fool The Body
Researchers from the University of Missouri and Imperial College London have found evidence suggesting why vaccines directed against the virus that causes AIDS and many cancers do not work. This research is being published in the Dec. 14 edition of The Journal of Biological Chemistry.
In research spanning more than a decade, Gary Clark, associate professor of Obstetrics, Gynecology and Women's Health in the MU School of Medicine, and Anne Dell, an investigator at Imperial College London, found that HIV, aggressive cancer cells, H. pylori, and parasitic worms known as schistosomes carry the same carbohydrate sequences as many proteins produced in human sperm.
"It's our major Achilles heel," Clark said. "Reproduction is required for the survival of our species. Therefore we are 'hard-wired' to protect our sperm and eggs as well as our unborn babies from any type of immune response. Unfortunately, our results suggest that many pathogens and tumor cells also have integrated themselves into this protective system, thus enabling them to resist the human immune response."
During the initial stages of life, the body goes through a process where it "self-identifies," determining which cells and proteins belong in the body, so it can detect those that do not. After this time, anything foreign is deemed as dangerous, unless the immune system is specifically told to ignore those cells and proteins. This situation arises primarily during reproduction.
When sperm are made, they specifically label their glycoproteins with Lewis carbohydrate sequences, a specific chain of carbohydrates. When these "foreign" sperm enter the female body, the female's immune system does not recognize them as foreign probably because of these Lewis sequences. Similarly, the unborn baby also could be seen as foreign by the mother's immune system, but she produces other types of glycoproteins that likely block any type of immune response in the womb. These events are required for successful human reproduction.
H. pylori is a bacteria known for causing stomach ulcers. Schistosomes live inside our bodies, resisting many types of immune responses. Aggressive tumor cells also can defeat the immune system; this killed more than half a million people in the United States last year. HIV-infected immune cells cause AIDS. The common thread is that each carries Lewis sequences. Clark said this evidence suggests that vaccines are likely ineffective against these diseases because Lewis sequences shut down the specific immune response that enables vaccines to work.
"If aggressive cancers and pathogens are using the same system of universally recognizable markers to trick the immune system into 'thinking' they're harmless, we need to determine exactly how this interaction works," Dell said. "This is where we're planning to take this research next. Understanding how these markers work at a basic biological and chemical level could lead to new ways to treat or prevent cancers and these other diseases in the future."
"This work is creating an entirely new way of thinking about how we must combat viruses like HIV and aggressive tumor cells," Clark said. "We have literally spent billions of dollars developing vaccines for AIDS and cancer. However, the latest high profile HIV and tumor vaccine trials have been spectacularly unsuccessful, perhaps for some very good reasons. We must become more clever if we are ever going to solve the problems of cancer and AIDS."
Clark's research is funded by grants from the National Institute of Allergy and Infectious Diseases (NIAID), the Breeden-Adams Foundation, and the State of Missouri. Dell is funded by grants from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust.
Source Christian Basi
University of Missouri-Columbia
In research spanning more than a decade, Gary Clark, associate professor of Obstetrics, Gynecology and Women's Health in the MU School of Medicine, and Anne Dell, an investigator at Imperial College London, found that HIV, aggressive cancer cells, H. pylori, and parasitic worms known as schistosomes carry the same carbohydrate sequences as many proteins produced in human sperm.
"It's our major Achilles heel," Clark said. "Reproduction is required for the survival of our species. Therefore we are 'hard-wired' to protect our sperm and eggs as well as our unborn babies from any type of immune response. Unfortunately, our results suggest that many pathogens and tumor cells also have integrated themselves into this protective system, thus enabling them to resist the human immune response."
During the initial stages of life, the body goes through a process where it "self-identifies," determining which cells and proteins belong in the body, so it can detect those that do not. After this time, anything foreign is deemed as dangerous, unless the immune system is specifically told to ignore those cells and proteins. This situation arises primarily during reproduction.
When sperm are made, they specifically label their glycoproteins with Lewis carbohydrate sequences, a specific chain of carbohydrates. When these "foreign" sperm enter the female body, the female's immune system does not recognize them as foreign probably because of these Lewis sequences. Similarly, the unborn baby also could be seen as foreign by the mother's immune system, but she produces other types of glycoproteins that likely block any type of immune response in the womb. These events are required for successful human reproduction.
H. pylori is a bacteria known for causing stomach ulcers. Schistosomes live inside our bodies, resisting many types of immune responses. Aggressive tumor cells also can defeat the immune system; this killed more than half a million people in the United States last year. HIV-infected immune cells cause AIDS. The common thread is that each carries Lewis sequences. Clark said this evidence suggests that vaccines are likely ineffective against these diseases because Lewis sequences shut down the specific immune response that enables vaccines to work.
"If aggressive cancers and pathogens are using the same system of universally recognizable markers to trick the immune system into 'thinking' they're harmless, we need to determine exactly how this interaction works," Dell said. "This is where we're planning to take this research next. Understanding how these markers work at a basic biological and chemical level could lead to new ways to treat or prevent cancers and these other diseases in the future."
"This work is creating an entirely new way of thinking about how we must combat viruses like HIV and aggressive tumor cells," Clark said. "We have literally spent billions of dollars developing vaccines for AIDS and cancer. However, the latest high profile HIV and tumor vaccine trials have been spectacularly unsuccessful, perhaps for some very good reasons. We must become more clever if we are ever going to solve the problems of cancer and AIDS."
Clark's research is funded by grants from the National Institute of Allergy and Infectious Diseases (NIAID), the Breeden-Adams Foundation, and the State of Missouri. Dell is funded by grants from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust.
Source Christian Basi
University of Missouri-Columbia
Between-Group Competition And Human Cooperation
Why do humans often cooperate in groups, even when free-riding on efforts of others is possible? This study shows that between-group competition is important for enhancing within-group cooperation.
Human subjects playing a "public goods" - social dilemma game cooperated at a high level when there was competition between groups, but without group competition cooperation and its associated benefits diminished. Further, between-group competition intensified emotions of anger and guilt associated with violations of the cooperative norm.
The study suggests an important role for group conflict in the evolution of human cooperation and moral emotions
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
Human subjects playing a "public goods" - social dilemma game cooperated at a high level when there was competition between groups, but without group competition cooperation and its associated benefits diminished. Further, between-group competition intensified emotions of anger and guilt associated with violations of the cooperative norm.
The study suggests an important role for group conflict in the evolution of human cooperation and moral emotions
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
How An Old Drug Could Have A New Use For Treating River Blindness
Scientists at The Scripps Research Institute have discovered a potential new use for the drug closantel, currently the standard treatment for sheep and cattle infected with liver fluke. The new research suggests that the drug may be useful in combating river blindness, a tropical disease that is the world's second leading infectious cause of blindness for humans.
The study is scheduled for publication in an advance, online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS) during the week of February 8, 2010.
The new research shows that clostanel has the potential to inhibit the molting process of the parasite that causes the disease.
"We think this finding holds terrific potential for the treatment of river blindness, one of 13 recognized neglected tropical diseases," says Scripps Research postdoctoral fellow Christian Gloeckner, the first author of the study.
Professor Kim Janda, who is director of the Worm Institute for Research and Medicine, Ely R. Callaway Chair in Chemistry, and member of The Skaggs Institute for Chemical Biology at Scripps Research, adds that there is an urgency to fighting the infection that leads to river blindness, which is also known as onchocerciasis. Despite several eradication efforts, the disease affects more than 37 million people in Africa, Central and South America, and Yemen.
"Victims of onchocerciasis suffer severe skin lesions, musculoskeletal pain, and various stages of blindness," says Janda, adding that patients also experience decreased body mass index, decreased work productivity, and social stigmatization.
River blindness is caused by thread-like filarial nematode worms, Onchocerca volvulus, which are transmitted among humans through the bite of a black fly. The nematodes then multiply and spread throughout the body. When they die, they cause a strong immune system response that can destroy surrounding tissue, including that of the eye. Currently, the only drug available for mass treatment of river blindness is ivermectin, and it now appears that resistance to that drug is emerging.
This creates a critical need to identify new drug targets and agents that can effectively treat the disease.
Building on Recent Discoveries
The current study builds on recent research that has implicated chitin metabolism in the larval development of the parasite O. volvulus.
Chitin is the protective outer covering that forms part of O. volvulus's outer cuticle. While knowledge of chitin biosynthesis in nematodes is limited, scientists do know that two classes of enzymes are critical for maintenance of the pathway - chitin synthases and chitinases, digestive enzymes that break down glycosidic bonds in chitin. The dynamic synthesis and degradation of chitin by these enzymes is a prerequisite for the organism's development and therefore a potential drug target.
Researchers in the field had recently identified and characterized one interesting chitinase from O. volvulus, OvCHT1. Although OvCHT1's exact metabolic role is not known, it was found to be expressed only in the infective L3 larvae and to have potential involvement in host transmission, molting, and important developmental processes in the parasite. Immunoelectron microscopy analysis detected chitinase in the pharyngeal glands of O. volvulus, structures that may contain a wide variety of proteins essential for the remodeling processes during molting and the shedding of the old cuticle.
"Therefore, we focused on these enzymes," Gloeckner says, "and reasoned that inhibiting them may eliminate onchocerciasis."
To test these enzyme candidates, Gloeckner, Janda and their colleagues used the Johns Hopkins clinical compound library - which contains 1,514 compounds, of which 1,082 are U.S. Food and Drug Administration (FDA)-approved drugs and 432 are foreign-approved drugs - to screen for active compounds.
"We were looking for a molecule that had a dramatic effect on chitanase specific to O. volvulus," Gloeckner explains. "The chitinase's enzymatic activity was monitored by a fluorescent signal. A library member was scored as a "hit" when a decrease in the signal was observed. Simply stated when a huge decrease in the signal was observed, the enzyme was essentially "knocked-out."
The screening efforts identified four known drugs namely levfloxacin, lomefloxacin, dexketoprofen, and closantel. Of these, only closantel was found to exhibit potent enough inhibition to warrant further investigation.
Cross-Country Collaboration
The next step was to find out if closantel would work in vivo, in the larvae of O. volvulus.
"The molting process is considered a potential new target for chemotherapy against onchocerciasis," Gloeckner explains. "And since chitinases may play a key role in molting, we wanted to determine the effect of closantel on this process." Specifically, the researchers were interested in how clostanel would disrupt molting from the L3 to L4 stage of the larvae, a critical step that occurs within the human host.
That's when the Scripps Research team enlisted the help of Sara Lustigman's laboratory at the Lindsley F. Kimball Research Institute at the New York Blood Center. Lustigman's team cultured L3-stage larvae in the presence of increasing concentrations of closantel, and the number of larvae was determined on day six. The results? Closantel completely prevented molting from the L3 to L4 stage.
Gloeckner was excited by this finding. "Based on its specificity, potency, and ease of synthesis, closantel or one its analogues might represent a promising alternative or adjunct therapy in combination with ivermectin for the treatment of onchocerciasis," he says.
Gloeckner adds that, based on this strong evidence of efficacy, he would like to take closantel into experiments with animal models.
In addition to Gloeckner, Janda, and Lustigman, authors of the article, "Repositioning of an old drug for the neglected tropical disease Onchocerciasis," include Amanda L. Garner, Lisa Eubanks, and Gunnar Kaufmann of Scripps Research, Fana Mersha of New England Biolabs, and Yelena Oksov and Nancy Tricoche of the New York Blood Center.
This research was supported by the Worm Institute for Research and Medicine at Scripps Research.
Source:
Keith McKeown
Scripps Research Institute
The study is scheduled for publication in an advance, online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS) during the week of February 8, 2010.
The new research shows that clostanel has the potential to inhibit the molting process of the parasite that causes the disease.
"We think this finding holds terrific potential for the treatment of river blindness, one of 13 recognized neglected tropical diseases," says Scripps Research postdoctoral fellow Christian Gloeckner, the first author of the study.
Professor Kim Janda, who is director of the Worm Institute for Research and Medicine, Ely R. Callaway Chair in Chemistry, and member of The Skaggs Institute for Chemical Biology at Scripps Research, adds that there is an urgency to fighting the infection that leads to river blindness, which is also known as onchocerciasis. Despite several eradication efforts, the disease affects more than 37 million people in Africa, Central and South America, and Yemen.
"Victims of onchocerciasis suffer severe skin lesions, musculoskeletal pain, and various stages of blindness," says Janda, adding that patients also experience decreased body mass index, decreased work productivity, and social stigmatization.
River blindness is caused by thread-like filarial nematode worms, Onchocerca volvulus, which are transmitted among humans through the bite of a black fly. The nematodes then multiply and spread throughout the body. When they die, they cause a strong immune system response that can destroy surrounding tissue, including that of the eye. Currently, the only drug available for mass treatment of river blindness is ivermectin, and it now appears that resistance to that drug is emerging.
This creates a critical need to identify new drug targets and agents that can effectively treat the disease.
Building on Recent Discoveries
The current study builds on recent research that has implicated chitin metabolism in the larval development of the parasite O. volvulus.
Chitin is the protective outer covering that forms part of O. volvulus's outer cuticle. While knowledge of chitin biosynthesis in nematodes is limited, scientists do know that two classes of enzymes are critical for maintenance of the pathway - chitin synthases and chitinases, digestive enzymes that break down glycosidic bonds in chitin. The dynamic synthesis and degradation of chitin by these enzymes is a prerequisite for the organism's development and therefore a potential drug target.
Researchers in the field had recently identified and characterized one interesting chitinase from O. volvulus, OvCHT1. Although OvCHT1's exact metabolic role is not known, it was found to be expressed only in the infective L3 larvae and to have potential involvement in host transmission, molting, and important developmental processes in the parasite. Immunoelectron microscopy analysis detected chitinase in the pharyngeal glands of O. volvulus, structures that may contain a wide variety of proteins essential for the remodeling processes during molting and the shedding of the old cuticle.
"Therefore, we focused on these enzymes," Gloeckner says, "and reasoned that inhibiting them may eliminate onchocerciasis."
To test these enzyme candidates, Gloeckner, Janda and their colleagues used the Johns Hopkins clinical compound library - which contains 1,514 compounds, of which 1,082 are U.S. Food and Drug Administration (FDA)-approved drugs and 432 are foreign-approved drugs - to screen for active compounds.
"We were looking for a molecule that had a dramatic effect on chitanase specific to O. volvulus," Gloeckner explains. "The chitinase's enzymatic activity was monitored by a fluorescent signal. A library member was scored as a "hit" when a decrease in the signal was observed. Simply stated when a huge decrease in the signal was observed, the enzyme was essentially "knocked-out."
The screening efforts identified four known drugs namely levfloxacin, lomefloxacin, dexketoprofen, and closantel. Of these, only closantel was found to exhibit potent enough inhibition to warrant further investigation.
Cross-Country Collaboration
The next step was to find out if closantel would work in vivo, in the larvae of O. volvulus.
"The molting process is considered a potential new target for chemotherapy against onchocerciasis," Gloeckner explains. "And since chitinases may play a key role in molting, we wanted to determine the effect of closantel on this process." Specifically, the researchers were interested in how clostanel would disrupt molting from the L3 to L4 stage of the larvae, a critical step that occurs within the human host.
That's when the Scripps Research team enlisted the help of Sara Lustigman's laboratory at the Lindsley F. Kimball Research Institute at the New York Blood Center. Lustigman's team cultured L3-stage larvae in the presence of increasing concentrations of closantel, and the number of larvae was determined on day six. The results? Closantel completely prevented molting from the L3 to L4 stage.
Gloeckner was excited by this finding. "Based on its specificity, potency, and ease of synthesis, closantel or one its analogues might represent a promising alternative or adjunct therapy in combination with ivermectin for the treatment of onchocerciasis," he says.
Gloeckner adds that, based on this strong evidence of efficacy, he would like to take closantel into experiments with animal models.
In addition to Gloeckner, Janda, and Lustigman, authors of the article, "Repositioning of an old drug for the neglected tropical disease Onchocerciasis," include Amanda L. Garner, Lisa Eubanks, and Gunnar Kaufmann of Scripps Research, Fana Mersha of New England Biolabs, and Yelena Oksov and Nancy Tricoche of the New York Blood Center.
This research was supported by the Worm Institute for Research and Medicine at Scripps Research.
Source:
Keith McKeown
Scripps Research Institute
Where Did We Come From And How Did We Get To Where We Live Today?
In the first scientific publication from The Genographic Project, a five-year effort to understand the human journey, we see the first attempts to
answer these age-old questions. Reporting their experience of genotyping human mitochondrial DNA from the first 18 months of the project in the
open-access journal PLoS Genetics, Doron Behar and colleagues describe the procedures used to generate, manage and analyze the genetic data from
78,590 public participants. They also provide the first anthropological insights in this unprecedented effort to map humanity's genetic journey
through the ages.
An ongoing debate in the field of human population genetics concerns the accurate classification of genetic lineages into distinct branches on the
human family tree, known as haplogroups. The rigorous genotyping and quality assurance strategies of the work done through The Genographic Project
allow classification of mitochondrial lineages with unprecedented accuracy. This methodology is now being made publicly available along with the
anonymous genetic data itself. As well as making available a periodically-updated database comprising all data donated by participants, the
researchers make available the Nearest Neighbor haplogroup prediction tool.
The Genographic Project was launched in 2005 using genetics as a tool to address anthropological questions on a global scale. At the core of the
project is a consortium of ten scientific teams from around the world united by a uniform ethical and scientific framework who are responsible for
sample collection and analysis in their respective regions. The project allows members of the public to participate in a real-time anthropological
genetics study by purchasing a participation kit from the Genographic website and donating the genetic results to the expanding database:
link here.
Related interview with Spencer Wells:
link here
Related video file: Introductory Video of The Genographic Project
link here (27 MB MOV)
CITATION:
Behar DM, Rosset S, Blue-Smith J, Balanovsky O, Tzur S, et al. (2007)
"The Genographic Project public participation mitochondrial DNA database."
PLoS Genet 3(6): e104. doi:10.1371/journal.pgen.0030104
Link to article.
About PLoS Genetics
PLoS Genetics is a peer reviewed, open-access journal published by the Public Library of Science. PLoS Genetics
reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas
of biology. Everything we publish is freely available online throughout the world for you to read, download, copy, distribute, and use (with
attribution) in any way. The Public Library of Science uses the Creative Commons Attribution License.
plosgenetics
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
answer these age-old questions. Reporting their experience of genotyping human mitochondrial DNA from the first 18 months of the project in the
open-access journal PLoS Genetics, Doron Behar and colleagues describe the procedures used to generate, manage and analyze the genetic data from
78,590 public participants. They also provide the first anthropological insights in this unprecedented effort to map humanity's genetic journey
through the ages.
An ongoing debate in the field of human population genetics concerns the accurate classification of genetic lineages into distinct branches on the
human family tree, known as haplogroups. The rigorous genotyping and quality assurance strategies of the work done through The Genographic Project
allow classification of mitochondrial lineages with unprecedented accuracy. This methodology is now being made publicly available along with the
anonymous genetic data itself. As well as making available a periodically-updated database comprising all data donated by participants, the
researchers make available the Nearest Neighbor haplogroup prediction tool.
The Genographic Project was launched in 2005 using genetics as a tool to address anthropological questions on a global scale. At the core of the
project is a consortium of ten scientific teams from around the world united by a uniform ethical and scientific framework who are responsible for
sample collection and analysis in their respective regions. The project allows members of the public to participate in a real-time anthropological
genetics study by purchasing a participation kit from the Genographic website and donating the genetic results to the expanding database:
link here.
Related interview with Spencer Wells:
link here
Related video file: Introductory Video of The Genographic Project
link here (27 MB MOV)
CITATION:
Behar DM, Rosset S, Blue-Smith J, Balanovsky O, Tzur S, et al. (2007)
"The Genographic Project public participation mitochondrial DNA database."
PLoS Genet 3(6): e104. doi:10.1371/journal.pgen.0030104
Link to article.
About PLoS Genetics
PLoS Genetics is a peer reviewed, open-access journal published by the Public Library of Science. PLoS Genetics
reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas
of biology. Everything we publish is freely available online throughout the world for you to read, download, copy, distribute, and use (with
attribution) in any way. The Public Library of Science uses the Creative Commons Attribution License.
plosgenetics
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
In Pacemaker Cell Function, Researchers Find Novel Role For Calcium Channels
Pacemaker cells in the sinoatrial node control heart rate, but what controls the ticking of these pacemaker cells? New research by Angelo Torrente and his colleagues of the M.E. Mangoni group's, reveals, for the first time, a critical functional interaction between Cav1.3 calcium ion (Ca2+) channels and ryanodine-receptor (RyR) mediated Ca2+ signaling.
The study also sheds light on a long-standing debate regarding the relative contributions of the 'funny current' generated by ion channels and the RyR dependent spontaneous diastolic Ca2+ release theory in determining heart rate.
The investigation by the research team compared pacemaker cells in normal mice with mutants that lacked the L-type Cav1.3 channels to contrast how they handled calcium. They found that the absence of Cav1.3 channels in sinoatrial node (SAN) cells reduced the frequency of Ca2+ transients, which determine the rate of cardiac muscle contraction. The Cav1.3 channels were also found to be important regulators of ryanodine-receptor dependent local calcium release in the diastolic pacemaker phase. Overall, their results show that local calcium release in SAN cells is tightly controlled by the Cav1.3 channels.
Defects in calcium channels controlling heart muscle function are known to cause heart failure, and this study reveals that Cav1.3 mutant mice also suffer from bradycardia and other cardiac arrhythmias.
"Our results clarify the role of Cav1.3 channels in pacemaker generation, and are a step towards using it as a target for drug therapy to treat heart dysfunction related to the sinoatrial node", says A. Torrente of CNRS in Montpellier, France, who was the lead author on the study.
Not only Cav1.3 channels are critical to the heart pacemaker cell function, they appear to be important to several other cellular mechanisms as well. In both humans and mice, Cav1.3 mutations have been linked to sinoatrial node dysfunction and deafness (or SANDD) syndrome. Cav1.3 channels are believed to play a role in pancreatic ОІ-cell stimulation, and they may also serve as pacemaker channels in the central nervous system, playing a pathophysiological role in Parkinson's disease.
"A better understanding of these channels in SAN could help us to comprehend the mechanism of calcium release in many other tissues and disease conditions as well", says Torrente.
Notes:
This project was supported by funding from the European Union Research Programme (CavNet project) and the French National Agency for Research
The presentation: "CAV1.3 L-TYPE CALCIUM CHANNELS-MEDIATED RYANODINE RECEPTOR DEPENDENT CALCIUM RELEASE CONTROLS HEART RATE" March 9, 2011 in Hall C of the Baltimore Convention Center.
Source:
Ellen R. Weiss
American Institute of Physics
The study also sheds light on a long-standing debate regarding the relative contributions of the 'funny current' generated by ion channels and the RyR dependent spontaneous diastolic Ca2+ release theory in determining heart rate.
The investigation by the research team compared pacemaker cells in normal mice with mutants that lacked the L-type Cav1.3 channels to contrast how they handled calcium. They found that the absence of Cav1.3 channels in sinoatrial node (SAN) cells reduced the frequency of Ca2+ transients, which determine the rate of cardiac muscle contraction. The Cav1.3 channels were also found to be important regulators of ryanodine-receptor dependent local calcium release in the diastolic pacemaker phase. Overall, their results show that local calcium release in SAN cells is tightly controlled by the Cav1.3 channels.
Defects in calcium channels controlling heart muscle function are known to cause heart failure, and this study reveals that Cav1.3 mutant mice also suffer from bradycardia and other cardiac arrhythmias.
"Our results clarify the role of Cav1.3 channels in pacemaker generation, and are a step towards using it as a target for drug therapy to treat heart dysfunction related to the sinoatrial node", says A. Torrente of CNRS in Montpellier, France, who was the lead author on the study.
Not only Cav1.3 channels are critical to the heart pacemaker cell function, they appear to be important to several other cellular mechanisms as well. In both humans and mice, Cav1.3 mutations have been linked to sinoatrial node dysfunction and deafness (or SANDD) syndrome. Cav1.3 channels are believed to play a role in pancreatic ОІ-cell stimulation, and they may also serve as pacemaker channels in the central nervous system, playing a pathophysiological role in Parkinson's disease.
"A better understanding of these channels in SAN could help us to comprehend the mechanism of calcium release in many other tissues and disease conditions as well", says Torrente.
Notes:
This project was supported by funding from the European Union Research Programme (CavNet project) and the French National Agency for Research
The presentation: "CAV1.3 L-TYPE CALCIUM CHANNELS-MEDIATED RYANODINE RECEPTOR DEPENDENT CALCIUM RELEASE CONTROLS HEART RATE" March 9, 2011 in Hall C of the Baltimore Convention Center.
Source:
Ellen R. Weiss
American Institute of Physics
The Origin Of The Brain Lies In A Worm
The rise of the central nervous system (CNS) in animal evolution has puzzled scientists for centuries. Vertebrates, insects and worms evolved from the same ancestor, but their CNSs are different and were thought to have evolved only after their lineages had split during evolution. Researchers from the European Molecular Biology Laboratory (EMBL) in Heidelberg now reveal that the vertebrate nervous system is probably much older than expected. The study, which is published in the current issue of Cell, suggests that the last common ancestor of vertebrates, insects and worms already had a centralised nervous system resembling that of vertebrates today.
Many animals have evolved complex nervous systems throughout the course of evolution, but their architectures can differ substantially between species. While vertebrates have a CNS in the shape of a spinal cord running along their backs, insects and annelid worms like the earthworm have a rope-ladder-like chain of nerve cell clusters on their belly side. Other invertebrates on the other hand have their nerve cells distributed diffusely over their body. Yet, all these species descend from a common ancestor called Urbilateria. If this ancestor already possessed a nervous system, what it might have looked like and how it gave rise to the diversity of nervous systems seen in animals today is what Detlev Arendt and his group study at EMBL. To do so, they investigate the nervous system of a marine annelid worm called Platynereis dumerilii.
"Platynereis can be considered a living fossil," says Arendt, "it still lives in the same environment as the last common ancestors used to and has preserved many ancestral features, including a prototype invertebrate CNS."
Arendt and his group investigated how the developing CNS in Platynereis embryos gets subdivided into the regions that later on give rise to the different CNS structures. The regions are defined by the unique combination of regulatory genes expressed, which endow every type of neuron with a specific molecular fingerprint. Comparing the molecular fingerpint of Platynereis nerve cells with what is known about vertebrates revealed surprising similarities.
"Our findings were overwhelming," says Alexandru Denes, who carried out the research in Arendt's lab. "The molecular anatomy of the developing CNS turned out to be virtually the same in vertebrates and Platynereis. Corresponding regions give rise to neuron types with similar molecular fingerprints and these neurons also go on to form the same neural structures in annelid worm and vertebrate."
"Such a complex arrangement caould not have been invented twice throughout evolution, it must be the same system," adds a researcher from Arendt's lab, who contributed essentially to the study. "It looks like Platynereis and vertebrates have inherited the organisation of their CNS from their remote common ancestors."
The findings provide strong evidence for a theory that was first put forward by zoologist Anton Dohrn in 1875. It states that vertebrate and annelid CNS are of common descent and vertebrates have turned themselves upside down throughout the course of evolution.
"This explains perfectly why we find the same centralised CNS on the backside of vertebrates and the bellyside of Platynereis," Arendt says. "How the inversion occurred and how other invertebrates have modified the ancestral CNS throughout evolution are the next exciting questions for evolutionary biologists."
Contact: Anna-Lynn Wegener
European Molecular Biology Laboratory
Many animals have evolved complex nervous systems throughout the course of evolution, but their architectures can differ substantially between species. While vertebrates have a CNS in the shape of a spinal cord running along their backs, insects and annelid worms like the earthworm have a rope-ladder-like chain of nerve cell clusters on their belly side. Other invertebrates on the other hand have their nerve cells distributed diffusely over their body. Yet, all these species descend from a common ancestor called Urbilateria. If this ancestor already possessed a nervous system, what it might have looked like and how it gave rise to the diversity of nervous systems seen in animals today is what Detlev Arendt and his group study at EMBL. To do so, they investigate the nervous system of a marine annelid worm called Platynereis dumerilii.
"Platynereis can be considered a living fossil," says Arendt, "it still lives in the same environment as the last common ancestors used to and has preserved many ancestral features, including a prototype invertebrate CNS."
Arendt and his group investigated how the developing CNS in Platynereis embryos gets subdivided into the regions that later on give rise to the different CNS structures. The regions are defined by the unique combination of regulatory genes expressed, which endow every type of neuron with a specific molecular fingerprint. Comparing the molecular fingerpint of Platynereis nerve cells with what is known about vertebrates revealed surprising similarities.
"Our findings were overwhelming," says Alexandru Denes, who carried out the research in Arendt's lab. "The molecular anatomy of the developing CNS turned out to be virtually the same in vertebrates and Platynereis. Corresponding regions give rise to neuron types with similar molecular fingerprints and these neurons also go on to form the same neural structures in annelid worm and vertebrate."
"Such a complex arrangement caould not have been invented twice throughout evolution, it must be the same system," adds a researcher from Arendt's lab, who contributed essentially to the study. "It looks like Platynereis and vertebrates have inherited the organisation of their CNS from their remote common ancestors."
The findings provide strong evidence for a theory that was first put forward by zoologist Anton Dohrn in 1875. It states that vertebrate and annelid CNS are of common descent and vertebrates have turned themselves upside down throughout the course of evolution.
"This explains perfectly why we find the same centralised CNS on the backside of vertebrates and the bellyside of Platynereis," Arendt says. "How the inversion occurred and how other invertebrates have modified the ancestral CNS throughout evolution are the next exciting questions for evolutionary biologists."
Contact: Anna-Lynn Wegener
European Molecular Biology Laboratory
Drug-Resistant Hospital Bacteria Could Be Inactivated At Their Outset
Most scientists believe that staph infections are caused by many bacterial cells that signal each other to emit toxins. The signaling process is called quorum sensing because many bacteria must be present to start the process.
But the Jeff Brinker research group has determined that the very first stage of staph infection, when bacteria switch from a harmless to a virulent form, occurs in a single cell and that this individual process can be stopped by the application of a simple protein.
The Brinker group's nonantibiotic approach may make it easier to treat staphylococci strains that have become drug resistant like the methicillin-resistant Staphylococcus aureus MRSA. The control of such strains is a formidable problem in hospitals.
"The good news is that by inhibiting the single cell's signaling molecules with a small protein, we were able to suppress any genetic reprogramming into the bacterium's more virulent form," said Brinker. "Our work clearly showed the strategy worked."
Brinker, with appointments at Sandia National Laboratories and the University of New Mexico, wrote about his group's findings in the Nov. 22 issue of Nature Chemical Biology.
In the course of its experiments, the Brinker team achieved three firsts:
They isolated Staphylococcus aureus bacteria in individual, self-assembled nanoscale compartments. Isolation of an individual bacterium previously had been achieved only computationally, leaving open questions of how a physically and chemically isolated bacterium would actually behave.
They demonstrated that it was the release of signaling peptides from a single cell - not a quorum - that acted as a trigger to reprogram that same cell so that it released toxins.
By introducing an inexpensive, very low-density lipoprotein (VLDL) to bind to the messenger peptide, they stopped the single cell from reprogramming itself.
The term "quorum sensing" itself may prove a misnomer, the result of observations made in cell cultures rather than in the body, said Brinker. Because signaling molecules tend to diffuse away, a liquid culture of cells would naturally require many bacteria to produce enough signaling bacteria to begin reprogramming. The situation is otherwise in nature, where even a single cell may be sufficiently isolated that its own manufactured peptides would remain in its vicinity.
"Also, it's hard to believe that one cell's evolution could be based on what a whole bunch of cells do," said Brinker. "When we instead consider that an individual cell will do what's best for it, we can more clearly understand the benefits of that cell's behavior."
A bacterium may live longer by reprogramming itself to produce toxins or enzymes that allow it to access external nutrients, the Brinker group showed.
One aspect of experimental rigor was the team's ability to organize living cells into a nanostructured matrix. "We've already done this with yeast," said Brinker. "We just extended the process to bacteria."
A key question was whether a cell could distinguish between peptides emitted by itself from those sent by other cells. If signaling peptides were chemically the same, what would it matter which bacterium emitted it?
As it turned out, said Brinker, "Peptides could bond to surface receptors on their own [generating] cell. So a single cell's peptide molecules could activate its own genes to express proteins that make staph virulent."
Indicating that the experiment had isolated the actual cause of the transformation, when the number of peptides produced by a cell ultimately came to exceed the number of lippoprotein molecules in solution, a stalled "quorum-sensing" procedure started up again.
When still more signaling molecules were added to the mix, the cell's transformation occurred more rapidly.
Researchers hope to find a mechanism to locate bacteria reprogramming in the body so that the antidote can be delivered in time. The problem could be solved, suggested Brinker, by the insertion of VLDL-bearing nanospheres (another Brinker-group creation) into the bloodstream, linked to a 'searcher' molecule designed to find and link to suspect peptides or cells that produce them.
"Inhibiting this specific signaling molecule from turning on virulence wouldn't inhibit other bacteria," Brinker said.
Targeting is important because the human gastro-intestinal system contains many useful bacteria. These are often decimated by conventional antibiotics but would be spared by the Brinker group's method.
Brinker, a Sandia Fellow and distinguished professor of chemical engineering and molecular genetics and microbiology at UNM, performed this work with Eric Carnes and DeAnna Lopez at the UNM Department of Chemical and Nuclear Engineering (Lopez is now a Sandia technologist), Graham Timmins at the UNM College of Pharmacy, Niles Donegan and Ambrose Cheung at Dartmouth Medical School, and Hattie Gresham at the New Mexico Veterans Administration Health Care System.
The Sandia work is supported by the Basic Energy Sciences / Division of Materials Science and Engineering and Sandia's Laboratory Directed Research and Development (LDRD) program. Other project work is supported by the Air Force Office of Scientific Research, the National Science Foundation, the Defense Threat Reduction Agency and the National Institutes of Health.
Source: Neal Singer
DOE/Sandia National Laboratories
But the Jeff Brinker research group has determined that the very first stage of staph infection, when bacteria switch from a harmless to a virulent form, occurs in a single cell and that this individual process can be stopped by the application of a simple protein.
The Brinker group's nonantibiotic approach may make it easier to treat staphylococci strains that have become drug resistant like the methicillin-resistant Staphylococcus aureus MRSA. The control of such strains is a formidable problem in hospitals.
"The good news is that by inhibiting the single cell's signaling molecules with a small protein, we were able to suppress any genetic reprogramming into the bacterium's more virulent form," said Brinker. "Our work clearly showed the strategy worked."
Brinker, with appointments at Sandia National Laboratories and the University of New Mexico, wrote about his group's findings in the Nov. 22 issue of Nature Chemical Biology.
In the course of its experiments, the Brinker team achieved three firsts:
They isolated Staphylococcus aureus bacteria in individual, self-assembled nanoscale compartments. Isolation of an individual bacterium previously had been achieved only computationally, leaving open questions of how a physically and chemically isolated bacterium would actually behave.
They demonstrated that it was the release of signaling peptides from a single cell - not a quorum - that acted as a trigger to reprogram that same cell so that it released toxins.
By introducing an inexpensive, very low-density lipoprotein (VLDL) to bind to the messenger peptide, they stopped the single cell from reprogramming itself.
The term "quorum sensing" itself may prove a misnomer, the result of observations made in cell cultures rather than in the body, said Brinker. Because signaling molecules tend to diffuse away, a liquid culture of cells would naturally require many bacteria to produce enough signaling bacteria to begin reprogramming. The situation is otherwise in nature, where even a single cell may be sufficiently isolated that its own manufactured peptides would remain in its vicinity.
"Also, it's hard to believe that one cell's evolution could be based on what a whole bunch of cells do," said Brinker. "When we instead consider that an individual cell will do what's best for it, we can more clearly understand the benefits of that cell's behavior."
A bacterium may live longer by reprogramming itself to produce toxins or enzymes that allow it to access external nutrients, the Brinker group showed.
One aspect of experimental rigor was the team's ability to organize living cells into a nanostructured matrix. "We've already done this with yeast," said Brinker. "We just extended the process to bacteria."
A key question was whether a cell could distinguish between peptides emitted by itself from those sent by other cells. If signaling peptides were chemically the same, what would it matter which bacterium emitted it?
As it turned out, said Brinker, "Peptides could bond to surface receptors on their own [generating] cell. So a single cell's peptide molecules could activate its own genes to express proteins that make staph virulent."
Indicating that the experiment had isolated the actual cause of the transformation, when the number of peptides produced by a cell ultimately came to exceed the number of lippoprotein molecules in solution, a stalled "quorum-sensing" procedure started up again.
When still more signaling molecules were added to the mix, the cell's transformation occurred more rapidly.
Researchers hope to find a mechanism to locate bacteria reprogramming in the body so that the antidote can be delivered in time. The problem could be solved, suggested Brinker, by the insertion of VLDL-bearing nanospheres (another Brinker-group creation) into the bloodstream, linked to a 'searcher' molecule designed to find and link to suspect peptides or cells that produce them.
"Inhibiting this specific signaling molecule from turning on virulence wouldn't inhibit other bacteria," Brinker said.
Targeting is important because the human gastro-intestinal system contains many useful bacteria. These are often decimated by conventional antibiotics but would be spared by the Brinker group's method.
Brinker, a Sandia Fellow and distinguished professor of chemical engineering and molecular genetics and microbiology at UNM, performed this work with Eric Carnes and DeAnna Lopez at the UNM Department of Chemical and Nuclear Engineering (Lopez is now a Sandia technologist), Graham Timmins at the UNM College of Pharmacy, Niles Donegan and Ambrose Cheung at Dartmouth Medical School, and Hattie Gresham at the New Mexico Veterans Administration Health Care System.
The Sandia work is supported by the Basic Energy Sciences / Division of Materials Science and Engineering and Sandia's Laboratory Directed Research and Development (LDRD) program. Other project work is supported by the Air Force Office of Scientific Research, the National Science Foundation, the Defense Threat Reduction Agency and the National Institutes of Health.
Source: Neal Singer
DOE/Sandia National Laboratories
Synchrotron Study Shows How Nitric Oxide Kills
Nitric oxide is a toxic pollutant, but the human body also creates it and uses it to attack invading microbes and parasites. A new study by researchers at UC Davis, the Massachusetts Institute of Technology and the Japan Synchrotron Radiation Research Institute (JASRI) shows how nitric oxide attacks an important group of proteins critical to cell survival.
A paper describing the work was published in the Journal of the American Chemical Society.
"This information can be used to learn more about possible treatments for nitric oxide toxicity and to help design new and more powerful antimicrobial agents," said Professor Stephen Cramer of the UC Davis Department of Applied Science. Cramer and Hongxin Wang, a project scientist in the same department, are co-authors on the paper.
Using X-rays from the SPring-8 synchrotron radiation facility at JASRI in Japan, the team studied how nitric oxide attacks Rieske proteins, a group of proteins that contain iron-sulfur clusters. These iron-sulfur clusters transfer electrons through the proteins, a vital process in all living organisms. The researchers found that iron-sulfur clusters can be broken up by nitric oxide, forming products with two irons, not the single iron form as was previously thought.
Understanding the structure of these products is important because it tells us exactly how the iron-sulfur clusters are broken down by nitric oxide. That helps researchers understand more about why it is toxic and could lead to new antimicrobials based on the same mechanism.
The SPring-8 machine produces X-rays that are very bright and extremely monochromatic, or of a very narrow range of wavelengths, Wang said. It is the largest synchrotron radiation facility in the world, but of a similar type to synchrotrons at the Argonne Advanced Photon Source in Illinois and the European Synchrotron Radiation Facility in Grenoble, France.
Notes:
The other co-authors on the paper are: Professor Stephen Lippard, research assistant Christine Tinberg, postdoctoral fellow Zachary Tonzetich, and graduate student Loi Hung Do, all of MIT; and research scientist Yoshitaka Yoda of JASRI.
This work was funded by grants from the National Institute of General Medical Sciences (part of the National Institutes of Health) and the U.S. Department of Energy.
Source:
Andy Fell
University of California - Davis
A paper describing the work was published in the Journal of the American Chemical Society.
"This information can be used to learn more about possible treatments for nitric oxide toxicity and to help design new and more powerful antimicrobial agents," said Professor Stephen Cramer of the UC Davis Department of Applied Science. Cramer and Hongxin Wang, a project scientist in the same department, are co-authors on the paper.
Using X-rays from the SPring-8 synchrotron radiation facility at JASRI in Japan, the team studied how nitric oxide attacks Rieske proteins, a group of proteins that contain iron-sulfur clusters. These iron-sulfur clusters transfer electrons through the proteins, a vital process in all living organisms. The researchers found that iron-sulfur clusters can be broken up by nitric oxide, forming products with two irons, not the single iron form as was previously thought.
Understanding the structure of these products is important because it tells us exactly how the iron-sulfur clusters are broken down by nitric oxide. That helps researchers understand more about why it is toxic and could lead to new antimicrobials based on the same mechanism.
The SPring-8 machine produces X-rays that are very bright and extremely monochromatic, or of a very narrow range of wavelengths, Wang said. It is the largest synchrotron radiation facility in the world, but of a similar type to synchrotrons at the Argonne Advanced Photon Source in Illinois and the European Synchrotron Radiation Facility in Grenoble, France.
Notes:
The other co-authors on the paper are: Professor Stephen Lippard, research assistant Christine Tinberg, postdoctoral fellow Zachary Tonzetich, and graduate student Loi Hung Do, all of MIT; and research scientist Yoshitaka Yoda of JASRI.
This work was funded by grants from the National Institute of General Medical Sciences (part of the National Institutes of Health) and the U.S. Department of Energy.
Source:
Andy Fell
University of California - Davis
Using A Molecular Toolkit To Transform Skin Cells Into Stem Cells
In an effort to sidestep the ethical dilemma involved in using human embryonic stem cells to treat diseases, scientists are developing non-controversial alternatives: In particular, they are looking for drug-like chemical compounds that can transform adult skin cells into the stem cells now obtained from human embryos. That's the topic of a fascinating article in Chemical & Engineering News (C&EN), ACS' weekly newsmagazine.
C&EN Associate Editor Sarah Everts notes that in 2006, researchers in Japan figured out a way to use genetic engineering to coax a skin cell to become a so-called "pluripotent" stem cell - a type of cell that can potentially morph or change into any cell of the human body. The scientists achieved the result by infecting the skin cell with a virus containing certain genes instructing the cell to change.
Now chemists are trying to reproduce this cellular alchemy with drug-like substances because gene therapies have faced trouble getting into the clinic. Scientists are looking for chemical ways to go backward in cell development - to reprogram mature cells into stem cells. Others are trying to identify substances that can morph one cell directly into other cell types - for example, from a skin cell directly into a nerve cell that might treat Parkinson's disease - without the use of stem cells at all. The ultimate goal is to be able to reprogram any cell of the body into another by means of a simple molecular kit, the article notes. But as chemists start putting together toolkits with these drug-like molecules, they face many technical hurdles as well as challenges getting acceptance from the stem cell community.
This story is available at
pubs.acs/cen/science/88/8806sci1.html
Article: "Back to the future with stem cells"
Source:
Michael Bernstein
American Chemical Society
C&EN Associate Editor Sarah Everts notes that in 2006, researchers in Japan figured out a way to use genetic engineering to coax a skin cell to become a so-called "pluripotent" stem cell - a type of cell that can potentially morph or change into any cell of the human body. The scientists achieved the result by infecting the skin cell with a virus containing certain genes instructing the cell to change.
Now chemists are trying to reproduce this cellular alchemy with drug-like substances because gene therapies have faced trouble getting into the clinic. Scientists are looking for chemical ways to go backward in cell development - to reprogram mature cells into stem cells. Others are trying to identify substances that can morph one cell directly into other cell types - for example, from a skin cell directly into a nerve cell that might treat Parkinson's disease - without the use of stem cells at all. The ultimate goal is to be able to reprogram any cell of the body into another by means of a simple molecular kit, the article notes. But as chemists start putting together toolkits with these drug-like molecules, they face many technical hurdles as well as challenges getting acceptance from the stem cell community.
This story is available at
pubs.acs/cen/science/88/8806sci1.html
Article: "Back to the future with stem cells"
Source:
Michael Bernstein
American Chemical Society
MicroRNA Undermines Tumor Suppression
FINDINGS: Scientists at the Whitehead Institute for Biomedical Research and the National University of Singapore have discovered the first microRNA (miRNA) capable of directly tamping down the activity of the well known tumor-suppressor gene, p53, While p53 functions to prevent tumor formation, the p53 gene is thought to malfunction in more than 50% of cancerous tumors.
RELEVANCE: The study reports the first time a miRNA has been shown to directly affect the p53 protein level, although researchers have previously identified other genes and miRNAs that indirectly affect p53's activity.
A small piece of RNA, or microRNA (miRNA), ratchets down the activity of the tumor-suppressor gene p53, according to a study by Whitehead Institute and National University of Singapore researchers.
While p53 functions to suppress tumor formation, the p53 gene is thought to malfunction in more than 50% of cancerous tumors.
The study published online March 17 in Genes and Development reports the first time that a miRNA has been shown to directly affect the p53 gene, although researchers have previously identified other genes and miRNAs that regulate p53's activity indirectly.
"For critical genes like p53, it's important that they are maintained at the right level in the cell," says Beiyan Zhou, a postdoctoral researcher in the lab of Whitehead Member Harvey Lodish and mentor to the paper's first author, Minh Le. "Le's work describes one more layer of regulatory mechanism that balances p53 gene expression."
miRNAs, short snippets of RNA, usually reduce how often a certain gene is translated into a protein. When a miRNA matches with and binds to a given messenger RNA coding for a specific protein, thereby preventing that messenger RNA from acting as a template for protein creation.
To investigate whether any miRNAs directly affect p53, Le, who is a joint graduate student in Lodish's lab and in the lab of Bing Lim at the National University of Singapore, searched the p53 gene for any sites that matched with known miRNAs from two databases. Only miRNA125b potentially has p53 target sites in humans, in zebrafish, and in many other vertebrates, indicating that it was important enough in cellular processes to be conserved through evolution.
Le tested miRNA125b's effects on several types of cells known to express p53, including human neural and lung cells. When Le reduced the amount of miRNA125b in the cells, p53 levels and the number of cells undergoing apoptosis (a type of programmed cell death that can be triggered by p53) both increased, whereas an increase in miRNA125b levels decreased levels of p53 and the number of apoptotic cells.
To confirm that miRNA125b played a similar role in developing organisms, Le changed the miRNA125b levels in zebrafish embryos. When she reduced miRNA125b levels in the embryos, cellular p53 levels and apoptosis both increased.
"Taking all of this data together, the p53 pathway is a major target of miRNA125b," says Lodish, who is also a professor of biology and bioengineering at MIT. "Most miRNAs have multiple targets, but there are a few cases that a miRNA has one major target and this is one of them."
Notes:
This research was funded by the National Institutes of Health and the Singapore-MIT Alliance.
Written by Nicole Giese.
Harvey Lodish's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of bioengineering at Massachusetts Institute of Technology.
Full Citation: "MicroRNA-125b is a novel negative regulator of p53"
Genes & Development, online March 18, 2009
Minh T. N. Le (1,2), Cathleen The (3,7), Ng Shyh-Chang (2,7), Huangming Xie (1,2,4), Beiyan Zhou (4), Vladimir Korzh (3), Harvey F. Lodish (1,4,5), Bing Lim (1,2,6).
Computation and Systems Biology, Singapore-MIT Alliance, 4 Engineering Drive 3, Singapore 117576
Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore 138672
Fish Developmental Biology, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Suite 601, Cambridge, MA 02142, USA
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
CLS 442 Beth Israel Deaconess Medical Center, Harvard Medical School, 300 Brookline Ave, Boston, MA 02215, USA
These authors contributed equally to this paper as co-second authors.
Source: Nicole Giese
Whitehead Institute for Biomedical Research
RELEVANCE: The study reports the first time a miRNA has been shown to directly affect the p53 protein level, although researchers have previously identified other genes and miRNAs that indirectly affect p53's activity.
A small piece of RNA, or microRNA (miRNA), ratchets down the activity of the tumor-suppressor gene p53, according to a study by Whitehead Institute and National University of Singapore researchers.
While p53 functions to suppress tumor formation, the p53 gene is thought to malfunction in more than 50% of cancerous tumors.
The study published online March 17 in Genes and Development reports the first time that a miRNA has been shown to directly affect the p53 gene, although researchers have previously identified other genes and miRNAs that regulate p53's activity indirectly.
"For critical genes like p53, it's important that they are maintained at the right level in the cell," says Beiyan Zhou, a postdoctoral researcher in the lab of Whitehead Member Harvey Lodish and mentor to the paper's first author, Minh Le. "Le's work describes one more layer of regulatory mechanism that balances p53 gene expression."
miRNAs, short snippets of RNA, usually reduce how often a certain gene is translated into a protein. When a miRNA matches with and binds to a given messenger RNA coding for a specific protein, thereby preventing that messenger RNA from acting as a template for protein creation.
To investigate whether any miRNAs directly affect p53, Le, who is a joint graduate student in Lodish's lab and in the lab of Bing Lim at the National University of Singapore, searched the p53 gene for any sites that matched with known miRNAs from two databases. Only miRNA125b potentially has p53 target sites in humans, in zebrafish, and in many other vertebrates, indicating that it was important enough in cellular processes to be conserved through evolution.
Le tested miRNA125b's effects on several types of cells known to express p53, including human neural and lung cells. When Le reduced the amount of miRNA125b in the cells, p53 levels and the number of cells undergoing apoptosis (a type of programmed cell death that can be triggered by p53) both increased, whereas an increase in miRNA125b levels decreased levels of p53 and the number of apoptotic cells.
To confirm that miRNA125b played a similar role in developing organisms, Le changed the miRNA125b levels in zebrafish embryos. When she reduced miRNA125b levels in the embryos, cellular p53 levels and apoptosis both increased.
"Taking all of this data together, the p53 pathway is a major target of miRNA125b," says Lodish, who is also a professor of biology and bioengineering at MIT. "Most miRNAs have multiple targets, but there are a few cases that a miRNA has one major target and this is one of them."
Notes:
This research was funded by the National Institutes of Health and the Singapore-MIT Alliance.
Written by Nicole Giese.
Harvey Lodish's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of bioengineering at Massachusetts Institute of Technology.
Full Citation: "MicroRNA-125b is a novel negative regulator of p53"
Genes & Development, online March 18, 2009
Minh T. N. Le (1,2), Cathleen The (3,7), Ng Shyh-Chang (2,7), Huangming Xie (1,2,4), Beiyan Zhou (4), Vladimir Korzh (3), Harvey F. Lodish (1,4,5), Bing Lim (1,2,6).
Computation and Systems Biology, Singapore-MIT Alliance, 4 Engineering Drive 3, Singapore 117576
Stem Cell and Developmental Biology, Genome Institute of Singapore, 60 Biopolis Street, Genome, Singapore 138672
Fish Developmental Biology, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Suite 601, Cambridge, MA 02142, USA
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
CLS 442 Beth Israel Deaconess Medical Center, Harvard Medical School, 300 Brookline Ave, Boston, MA 02215, USA
These authors contributed equally to this paper as co-second authors.
Source: Nicole Giese
Whitehead Institute for Biomedical Research
Blood Component That Turns Bacteria Virulent Identified By Scripps Research Scientists
Scientists from the Scripps Research Institute have discovered the key chemical that signals Bacillus anthracis, the bacterium that causes anthrax, to become lethal. This finding opens up new avenues of exploration for the development of treatments for bacterial infections.
The study was published in the November 21 edition of the journal PLoS Pathogens.
The Scripps Research scientists identified bicarbonate, a chemical found in all body fluids and organs that plays a major role in maintaining pH balance in cells, as providing the signal for Bacillus anthracis to unleash virulence factors. Without the presence of the bicarbonate transporter in the bloodstream, the scientists found, the bacteria do not become virulent.
Scientists have known for some time that bicarbonate is implicated in many diseases, but controversy has existed about whether bicarbonate, carbon dioxide, or some combination of these two molecules are responsible for triggering bacterial pathogenesis. This study confirms, for the first time, that it is indeed bicarbonate, rather than carbon dioxide, that signals the gram-positive B. anthracis to become virulent. This finding also is significant because other pathogenic bacteria such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera have bicarbonate transport pathways similar to B. anthracis and thus are likely to have similar virulence triggering mechanisms.
Gram-positive bacteria are the major culprits driving the increase of community and hospital acquired bacterial infections. The Centers for Disease Control and Prevention estimates that as many as 10 percent of all patients, or about 2 million people, contract hospital acquired infections each year. These bacteria are often resistant to multiple antibiotics, making the problem a growing public health concern and the need for new antibacterial treatment more urgent. Now, the bicarbonate transporter pathway may be investigated as a potential new target for drug intervention.
"How a bacterium recognizes signals in the host that trigger pathogenesis mechanisms, and the nature of the mechanisms necessary to develop pathogenesis, remain poorly understood," said Scripps Research Associate Professor Marta Perego, Ph.D., who conducted the study with Scripps Research postdoctoral fellow Adam Wilson, Ph.D., and colleagues. "We have identified an essential component for the induction of virulence gene expression in response to host bicarbonate levels and have used this finding to learn more about the extracellular and intracellular signals controlling virulence."
Theory Confirmed
Perego's latest discovery builds on her lab's expertise in the study of bacterial virulence signaling and in the regulatory networks responsible for pathogenicity in other gram-positive bacteria. Her interest in bicarbonate transport pathways as bacteria virulence signaling mechanisms grew out of an early observation that growth of B. anthracis in carbon dioxide and sodium bicarbonate strongly induced toxin production in the laboratory setting. The mechanism behind this observation, however, was never uncovered.
"It was observed that the best medium for toxin production was one that people believed mimicked conditions found in the blood of a human or animal host, where anthrax bacteria would find both carbon dioxide and bicarbonate. But we've never known which of these two molecules was the more important for bacterial pathogenesis, and whether this belief was correct," Perego said. "Now, we know that it is bicarbonate and that the growth in the presence of bicarbonate really mimics the host growth conditions."
In their current study, the Perego lab identified a previously unknown ATP-binding cassette transporter (ABC-transporter) - which is identified by the gene number BAS2714-12 - that was shown to be essential to transporting bicarbonate. As a group, ABC-transporters use the energy of ATP hydrolysis to transport various substrates across cellular membranes. In this case, when the genes that code for the BAS2714-12 ABC transporter were deleted, the rate of bicarbonate uptake inside the cell greatly decreased, induction of toxin gene expression did not occur, and virulence in an animal model of infection was abolished. Elimination of carbon dioxide production within the bacterial cell had no effect on toxin production, suggesting that CO2 activity is not essential to virulence factor induction and that bicarbonate, not CO2, is the signal essential for virulence induction.
"In light of these findings, investigation of bicarbonate regulation and transport should be of much greater significance to a large number of pathogenic organisms," Perego said.
In addition to Perego and Wilson, the other authors of "The bicarbonate transporter is essential for Bacillus anthracis lethality" were Magali Soyer and James Hoch, Ph.D., head of the Division of Cellular Biology and Professor in the Department of Molecular and Experimental Medicine at The Scripps Research Institute.
This study was supported by the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, the National Institutes of Health, and the Stein Beneficial Trust.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is currently in the process of moving from temporary facilities to its permanent campus in Jupiter, Florida. Dedication ceremonies for the new campus will be held in February 2009.
Source: Keith Mckeown
Scripps Research Institute
The study was published in the November 21 edition of the journal PLoS Pathogens.
The Scripps Research scientists identified bicarbonate, a chemical found in all body fluids and organs that plays a major role in maintaining pH balance in cells, as providing the signal for Bacillus anthracis to unleash virulence factors. Without the presence of the bicarbonate transporter in the bloodstream, the scientists found, the bacteria do not become virulent.
Scientists have known for some time that bicarbonate is implicated in many diseases, but controversy has existed about whether bicarbonate, carbon dioxide, or some combination of these two molecules are responsible for triggering bacterial pathogenesis. This study confirms, for the first time, that it is indeed bicarbonate, rather than carbon dioxide, that signals the gram-positive B. anthracis to become virulent. This finding also is significant because other pathogenic bacteria such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera have bicarbonate transport pathways similar to B. anthracis and thus are likely to have similar virulence triggering mechanisms.
Gram-positive bacteria are the major culprits driving the increase of community and hospital acquired bacterial infections. The Centers for Disease Control and Prevention estimates that as many as 10 percent of all patients, or about 2 million people, contract hospital acquired infections each year. These bacteria are often resistant to multiple antibiotics, making the problem a growing public health concern and the need for new antibacterial treatment more urgent. Now, the bicarbonate transporter pathway may be investigated as a potential new target for drug intervention.
"How a bacterium recognizes signals in the host that trigger pathogenesis mechanisms, and the nature of the mechanisms necessary to develop pathogenesis, remain poorly understood," said Scripps Research Associate Professor Marta Perego, Ph.D., who conducted the study with Scripps Research postdoctoral fellow Adam Wilson, Ph.D., and colleagues. "We have identified an essential component for the induction of virulence gene expression in response to host bicarbonate levels and have used this finding to learn more about the extracellular and intracellular signals controlling virulence."
Theory Confirmed
Perego's latest discovery builds on her lab's expertise in the study of bacterial virulence signaling and in the regulatory networks responsible for pathogenicity in other gram-positive bacteria. Her interest in bicarbonate transport pathways as bacteria virulence signaling mechanisms grew out of an early observation that growth of B. anthracis in carbon dioxide and sodium bicarbonate strongly induced toxin production in the laboratory setting. The mechanism behind this observation, however, was never uncovered.
"It was observed that the best medium for toxin production was one that people believed mimicked conditions found in the blood of a human or animal host, where anthrax bacteria would find both carbon dioxide and bicarbonate. But we've never known which of these two molecules was the more important for bacterial pathogenesis, and whether this belief was correct," Perego said. "Now, we know that it is bicarbonate and that the growth in the presence of bicarbonate really mimics the host growth conditions."
In their current study, the Perego lab identified a previously unknown ATP-binding cassette transporter (ABC-transporter) - which is identified by the gene number BAS2714-12 - that was shown to be essential to transporting bicarbonate. As a group, ABC-transporters use the energy of ATP hydrolysis to transport various substrates across cellular membranes. In this case, when the genes that code for the BAS2714-12 ABC transporter were deleted, the rate of bicarbonate uptake inside the cell greatly decreased, induction of toxin gene expression did not occur, and virulence in an animal model of infection was abolished. Elimination of carbon dioxide production within the bacterial cell had no effect on toxin production, suggesting that CO2 activity is not essential to virulence factor induction and that bicarbonate, not CO2, is the signal essential for virulence induction.
"In light of these findings, investigation of bicarbonate regulation and transport should be of much greater significance to a large number of pathogenic organisms," Perego said.
In addition to Perego and Wilson, the other authors of "The bicarbonate transporter is essential for Bacillus anthracis lethality" were Magali Soyer and James Hoch, Ph.D., head of the Division of Cellular Biology and Professor in the Department of Molecular and Experimental Medicine at The Scripps Research Institute.
This study was supported by the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, the National Institutes of Health, and the Stein Beneficial Trust.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is currently in the process of moving from temporary facilities to its permanent campus in Jupiter, Florida. Dedication ceremonies for the new campus will be held in February 2009.
Source: Keith Mckeown
Scripps Research Institute
Method Of DNA Repair Linked To Higher Likelihood Of Genetic Mutation
Accurate transmission of genetic information requires the precise replication of DNA. Errors in DNA replication are common and nature has developed several cellular mechanisms for repairing these mistakes. Mutations, which can be deleterious (development of cancerous cells), or beneficial (evolutionary adaption), arise from uncorrected errors. Researchers from Indiana University-Purdue University Indianapolis (U.S.A) and Umea University (Sweden) report that a method by which cells repair breaks in their DNA, known as Break-induced Replication (BIR), is up to 2,800 times more likely to cause genetic mutation than normal DNA synthesis. When one or many cells repair themselves using the efficient BIR method, accuracy is lost. These findings will publish next week in the online, open access journal PLoS Biology.
"When BIR occurs, instead of using a "band aid" to repair a chromosomal break, the broken piece invades another chromosome and initiates replication which happens at the wrong place and at the wrong time and probably with participation of wrong proteins," said Anna Malkova, Ph.D., Associate Professor of Biology at the School of Science at IUPUI, who led the study.
The researchers used yeast to investigate the level of mutagenesis associated with BIR and found that the process's proclivity to cause mutation was not effected by where in the DNA the repair was made. But why is BIR so inaccurate as compared to normal replication?
"We didn't find a smoking gun," said Malkova, also an adjunct associate professor of medical and molecular genetics at the Indiana University School of Medicine. "We think there are at least four changes to the replication machinery that might occur to create a perfect storm or synergy that make BIR repair so mutagenic."
For example, during BIR, the researchers found a dramatic increase in the concentration of nucleotides - the building blocks used to form DNA.
"Our findings strongly suggest that mutagenesis caused by BIR doesn't happen slowly, it occurs in surges - sudden bursts which may lead to cancer," said Malkova, who is a geneticist. "We plan to continue investigating BIR in the hope of finding clues as to why this means of cell repair is so likely to cause mutations. The ultimate goal, of course, is to prevent those mutations that cause cancer."
Co-authors of the study, "Break-induced Replication is Highly Inaccurate," are Angela Deem, Tiffany Blackgrove, Alexandra Vayl, Barbara Coffey, and Ruchi Mathur of the School of Science at IUPUI and Andrea Keszthelyi and Andrei Chabes of Umea University.
Funding: This work was supported by NIH grant GM084242-01 to AM; and by the Swedish Foundation for Strategic Research; the Swedish Research Council, and the Swedish Cancer Society to A.C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests statement: The authors declare that no competing interests exist.
Citation: Deem A, Keszthelyi A, Blackgrove T, Vayl A, Coffey B, et al. (2011) Break-Induced Replication Is Highly Inaccurate. PLoS Biol 9(2): e1000594. doi:10.1371/journal.pbio.1000594
Source:
PLoS Biology
"When BIR occurs, instead of using a "band aid" to repair a chromosomal break, the broken piece invades another chromosome and initiates replication which happens at the wrong place and at the wrong time and probably with participation of wrong proteins," said Anna Malkova, Ph.D., Associate Professor of Biology at the School of Science at IUPUI, who led the study.
The researchers used yeast to investigate the level of mutagenesis associated with BIR and found that the process's proclivity to cause mutation was not effected by where in the DNA the repair was made. But why is BIR so inaccurate as compared to normal replication?
"We didn't find a smoking gun," said Malkova, also an adjunct associate professor of medical and molecular genetics at the Indiana University School of Medicine. "We think there are at least four changes to the replication machinery that might occur to create a perfect storm or synergy that make BIR repair so mutagenic."
For example, during BIR, the researchers found a dramatic increase in the concentration of nucleotides - the building blocks used to form DNA.
"Our findings strongly suggest that mutagenesis caused by BIR doesn't happen slowly, it occurs in surges - sudden bursts which may lead to cancer," said Malkova, who is a geneticist. "We plan to continue investigating BIR in the hope of finding clues as to why this means of cell repair is so likely to cause mutations. The ultimate goal, of course, is to prevent those mutations that cause cancer."
Co-authors of the study, "Break-induced Replication is Highly Inaccurate," are Angela Deem, Tiffany Blackgrove, Alexandra Vayl, Barbara Coffey, and Ruchi Mathur of the School of Science at IUPUI and Andrea Keszthelyi and Andrei Chabes of Umea University.
Funding: This work was supported by NIH grant GM084242-01 to AM; and by the Swedish Foundation for Strategic Research; the Swedish Research Council, and the Swedish Cancer Society to A.C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests statement: The authors declare that no competing interests exist.
Citation: Deem A, Keszthelyi A, Blackgrove T, Vayl A, Coffey B, et al. (2011) Break-Induced Replication Is Highly Inaccurate. PLoS Biol 9(2): e1000594. doi:10.1371/journal.pbio.1000594
Source:
PLoS Biology
Dawn Rheumatology Software Now Offers Web-Based Version For Biologics Patient Tracking
4S Information Systems Ltd. has made a number of enhancements to its rheumatology patient tracking software, which was developed in 1997. The advanced clinical software package-known as Dawn Rheumatology or Dawn RH-now has a web-browser-based version available for tracking patients on very expensive and potentially hazardous biologic drugs as well as DMARDs.
Additionally, Dawn RH also has expanded its features and capabilities to improve functionality. In the area of management and work flow, for example, the current software offers support for case management, configurable patient lists and a dynamic messaging center. With 10 years on the market, Dawn RH is instrumental in the treatment of thousands of patients in the UK, for example, the software has been used by major health care facilities such as St Mary's Hospital, London; Newcastle General Hospital, Newcastle-upon-Tyne; and Great Western Hospital, Swindon.
Dawn RH software makes the work of clinicians much easier by enabling them to:
- handle more patients with less effort by boosting the productivity of staff
- optimise drug utilisations and recall dates by rapidly assessing disease activity
- generate more revenue by using an automated reminder system to reduce time lost to non-attending patients
- keep patients safer and healthier by standardization of practice and maximise clinical accuracy
- facilitate medical audit, research and general management with a powerful scheduling tool and an easy-to-use report facility
- reduce administration time in tracking laboratory results
Rheumatology is a rapidly-evolving medical specialty relating to the loco-motor system, including joints, muscles, connective tissues, and soft tissues around the joints and bones. Dawn RH is designed to help clinicians stay on top of monitoring and managing patients suffering from rheumatologic disorders. It is a powerful, yet easy-to-use tool that can be integrated with other information systems such as laboratory and patient administration. Rheumatologists can use the robust software to create a safer, more organised method for managing patients and producing better outcomes.
4S Information Systems is a leading manufacturer of clinical software. The company's overriding goal is to help address today's chronic health care issues by offering software that allows physicians to provide better care with less effort. Trading under the name 4S Dawn Clinical Software, 4S Information Systems also produces anticoagulation management, anemia patient tracking and hematology patient tracking software packages. 4S Information Systems, which is headquartered in North West England about an hour from Manchester, holds ISO9001:2000 quality management system certification.
More information about the features and benefits of Dawn Rheumatology is available online at
4s-dawn/dmard.
Additionally, Dawn RH also has expanded its features and capabilities to improve functionality. In the area of management and work flow, for example, the current software offers support for case management, configurable patient lists and a dynamic messaging center. With 10 years on the market, Dawn RH is instrumental in the treatment of thousands of patients in the UK, for example, the software has been used by major health care facilities such as St Mary's Hospital, London; Newcastle General Hospital, Newcastle-upon-Tyne; and Great Western Hospital, Swindon.
Dawn RH software makes the work of clinicians much easier by enabling them to:
- handle more patients with less effort by boosting the productivity of staff
- optimise drug utilisations and recall dates by rapidly assessing disease activity
- generate more revenue by using an automated reminder system to reduce time lost to non-attending patients
- keep patients safer and healthier by standardization of practice and maximise clinical accuracy
- facilitate medical audit, research and general management with a powerful scheduling tool and an easy-to-use report facility
- reduce administration time in tracking laboratory results
Rheumatology is a rapidly-evolving medical specialty relating to the loco-motor system, including joints, muscles, connective tissues, and soft tissues around the joints and bones. Dawn RH is designed to help clinicians stay on top of monitoring and managing patients suffering from rheumatologic disorders. It is a powerful, yet easy-to-use tool that can be integrated with other information systems such as laboratory and patient administration. Rheumatologists can use the robust software to create a safer, more organised method for managing patients and producing better outcomes.
4S Information Systems is a leading manufacturer of clinical software. The company's overriding goal is to help address today's chronic health care issues by offering software that allows physicians to provide better care with less effort. Trading under the name 4S Dawn Clinical Software, 4S Information Systems also produces anticoagulation management, anemia patient tracking and hematology patient tracking software packages. 4S Information Systems, which is headquartered in North West England about an hour from Manchester, holds ISO9001:2000 quality management system certification.
More information about the features and benefits of Dawn Rheumatology is available online at
4s-dawn/dmard.
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