A team of researchers from Washington University in St. Louis and the Israeli Institute of Technology (Technion) in Haifa has developed a technique to detect the ancestry of disease genes in hybrid, or mixed, human populations.
The technique, called expected mutual information (EMI), determines how a set of DNA markers is likely to show the ancestral origin of locations on each chromosome. The team constructed an algorithm for the technique that selects panels of DNA markers in order to render the best picture of ancestral origin of disease genes. They then tested the algorithm to show that it is more powerful and accurate than standard algorithms that are currently used.
The result is easier identification of inherited genes that cause diseases in people of mixed races, which researchers call "population admixture." Nephrologists, for instance, have noted that African-Americans are far more likely than Europeans to die rapidly of end-stage, progressive renal failure due to kidney disease. Many African-Americans, though, have genes that originated in Europe due to ethnic mixing. The technique helps researchers isolate the genetic causes of disease by detecting from which continent the recurrent disease genes originated.
A current research goal is to treat or even prevent kidney disease with gene or drug therapies.
"This technique will allow researchers to analyze which regions of the genome are associated with end-stage, progressive renal failure," said Alan R. Templeton, Ph.D., the Charles Rebstock Professor of Biology. "Once the regions are identified, then you look at the individual genes and ask: Are there genetic factors involved with this, and if so, what are the candidates?"
It's a good bet, Templeton said, that the disease genes are highly likely to have emerged from Africa, as African-Americans have shown the tendency to die more quickly of the disease.
The technique and algorithm apply beyond this particular disease, Templeton added.
"We can look at many different hybrid human populations with this algorithm and use it on a diversity of diseases," he said.
"Our novel approach extends previous methods by incorporating knowledge on population admixture, drawing a more precise picture of the mosaic of ancestries along an individual's genome," said Sivan Bercovici, Templeton's colleague at Technion and primary author of a research paper published in Genome Research.
The researchers analyzed DNA from 575 cases of African-Americans with end-stage progressive renal failure and compared it to controls that did not have the disease. They came up with a panel of approximately 2,000 genetic markers. Enough, Templeton said, "to cover the whole genome."
To tease out the origins of disease-causing genes, researchers use a technique called mapping by admixture linkage disequilibrium (MALD), a powerful approach to identify regions of the genome that have genes associated with disease. It takes advantage of differences in disease prevalence between populations to look for variation patterns that are over-represented in groups with high susceptibility to a certain disorder.
Both EMI and the algorithm make MALD more accurate and efficient.
A paper discussing the technique and algorithm is published in the current issue of Genome Research 18, 661-667.
Written by Tony Fitzpatrick
Washington University in St. Louis
среда, 29 июня 2011 г.
воскресенье, 26 июня 2011 г.
The Identification And Functional Evaluation Of Small, Non Coding RNAs In The Regulation Of Complex Biological Processes
ORLANDO, FL () - In a joint meeting of the SBUR and SUO, Dr. Victoria Robinson discussed that small non-coding RNAs are important in the regulation of complex biological processes. She stated that RNA was probably the first biological molecule, have lots of secondary structure and catalyze reactions and serve critical functions. Only 2% of our DNA codes for protein and the other 85% was felt to be "junk". Yet, now it is felt that half of that is unique DNA and the majority of the human genome is transcribed into RNA. Non-coding RNAs (ncRNAs) are a large family of molecules and very diverse. The ncRNAs are powerful sequence specific post-transcriptional regulators for gene expression. One siRNA targets one miRNA. miRNA are endogenously encoded genes with diverse physiological functions. They bind target mRNAs and suppress translation. In contrast to siRNA, miRNA targets many mRNAs. While siRNA forms intracellular complexes, miRNA are transcribed into hairpin loops that is then unwound and each piece can target different genes.
The first miRNA was described in 1933 and the second one in 2000. In 2001, 3 papers showed that miRNA was conserved in many organisms, including humans. In situ hybridization of miRNA was described in 2007 and now it is a blooming field of research. The name given to miRNA reflects the species and sequence and order of discovery. miRNA is now recognized to be endogenous genes and are an ancient mechanism of gene regulation. There are >700 human miRNAs presently described. Target algorithms predict hundreds of targets for each miRNA. In one study, algorithms to predict the number of targets is variable, thus target validation is required.
miRNAs are tumor suppressor genes and can undergo mutation. For example, p53 undergoes transcriptional activation and miR-34 is expressed and involved in regulation of this pathway. Challenges in the field include better target prediction and databases. Cancer cells in general may use an alternative splicing mechanism to avoid miR regulation. Also, mammalian protein translation is not fully understood and understanding other ncRNA mechanisms such as heterochromatin silencing is under investigation. She concluded that every tumor type has mRNAs and will be developed as tumor targets.
Presented by Victoria Robinson, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.
Reported by Contributing Editor Christopher P. Evans, MD, FACS
- the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from , go to:
Copyright © 2008 -
The first miRNA was described in 1933 and the second one in 2000. In 2001, 3 papers showed that miRNA was conserved in many organisms, including humans. In situ hybridization of miRNA was described in 2007 and now it is a blooming field of research. The name given to miRNA reflects the species and sequence and order of discovery. miRNA is now recognized to be endogenous genes and are an ancient mechanism of gene regulation. There are >700 human miRNAs presently described. Target algorithms predict hundreds of targets for each miRNA. In one study, algorithms to predict the number of targets is variable, thus target validation is required.
miRNAs are tumor suppressor genes and can undergo mutation. For example, p53 undergoes transcriptional activation and miR-34 is expressed and involved in regulation of this pathway. Challenges in the field include better target prediction and databases. Cancer cells in general may use an alternative splicing mechanism to avoid miR regulation. Also, mammalian protein translation is not fully understood and understanding other ncRNA mechanisms such as heterochromatin silencing is under investigation. She concluded that every tumor type has mRNAs and will be developed as tumor targets.
Presented by Victoria Robinson, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.
Reported by Contributing Editor Christopher P. Evans, MD, FACS
- the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from , go to:
Copyright © 2008 -
четверг, 23 июня 2011 г.
Proteomics Technology To Focus On Neurological Complications Of HIV
The National Institute on Drug Abuse of the National Institutes of Health has awarded a three-year, $3-million grant to Albert Einstein College of Medicine of Yeshiva University to establish a research center to study the neurological complications that afflict people infected with HIV, the virus that causes AIDS.
Despite the effectiveness of antiretroviral therapy for HIV, neurological complications associated with HIV infection - including cognitive, behavioral, and motor abnormalities - have become more common as infected individuals live longer.
"More than a quarter of those infected with HIV exhibit some form of cognitive impairment," says Ruth Hogue Angeletti, Ph.D., professor of developmental & molecular biology and of biochemistry at Einstein, who will direct the Einstein Proteomics Research Center for HIV-Associated Neurological Disorders and Substance Abuse. "By the time HIV-infected people have progressed to AIDS, more than half display significant neurological deficits."
This new proteomics center will use powerful mass spectrometers to identify the brain proteins responsible for neurological complications in people infected with HIV - particularly those who are also addicted to drugs. Proteomics is the branch of molecular biology that studies the set of proteins expressed by the genes of an organism.
HIV's neurological complications (commonly referred to as neuro-AIDS) primarily stem from toxic proteins produced by immune cells called monocytes, which recruit HIV into the central nervous system. Neuro-AIDS can lead to AIDS dementia complex, HIV-related encephalitis, and fungal and parasitic infections.
The Einstein Proteomics Research Center will investigate the mechanism by which HIV infection causes neurological deficits and identify biomarkers that signal when these deficits begin and how they progress over time.
"The biomarkers identified by this new center should permit the early detection of neurological disease in HIV-infected individuals," says co-principal investigator Harris Goldstein, M.D., director of the Einstein-Montefiore Center for AIDS Research and professor of pediatrics and of microbiology & immunology at Einstein.
"We have developed a unique transgenic HIV mouse model that displays some features of neuro-AIDS," Dr. Goldstein notes. "By studying this mouse model in the proteomics center, we'll be able to determine how HIV infection influences the proteins expressed in the brain. These results may help us to pinpoint new therapeutic targets for preventing the progression of this devastating consequence of HIV infection."
Several studies of autopsy tissue show that the destructive neuro-AIDS process is worsened by drug abuse, particularly the use of opioids such as heroin. Unfortunately, the combination of HIV infection and drug addiction is all too common. In New York City, for example, more than half of all AIDS cases result directly or indirectly from injection drug use.
"Therefore, the intersection between HIV infection and opioid use represents an especially important area of neuro-AIDS research on which our proteomics center will focus," says Dr. Angeletti.
Each of the center's projects will evaluate the neurological effects of buprenorphine - a new, less-addictive alternative to methadone. Compared with methadone, buprenorphine can be given at higher doses with fewer adverse effects. But it could conceivably contribute to neurological problems when used by drugs addicts who are infected with HIV.
"The blood-brain barrier protects the brain from HIV-infected monocytes and other neuroinflammatory mediators, and we don't yet know how buprenorphine affects this barrier," says co-principal investigator Joan W. Berman, Ph.D., professor in the departments of pathology and microbiology & immunology at Einstein. "We need to understand buprenorphine's neurological impact before use of the drug becomes widespread in this patient population."
On the other hand, the center's research may show that buprenorphine is a better alternative than methadone for people infected with HIV. "Because of its unique pharmacological properties, buprenorphine may provide neuropsychological benefits for HIV-infected people who are addicted to opioids," says Julia H. Arnsten, M.D., M.P.H., the center's other co-principal investigator and professor of medicine, of epidemiology & population health, and of psychiatry and behavioral sciences at Einstein.
As part of the study, Dr. Arnsten will recruit a cohort of HIV-infected patients who are undergoing treatment for drug addiction. These people will be monitored to see whether buprenorphine influences the development of neurological deficits.
Other key investigators for this center are Dr. Louis Weiss in the departments of pathology and of medicine, Dr. Andras Fiser in the departments of systems & computational biology and of biochemistry, Dr. Abdissa Negassa in the department of epidemiology & population health, and Dr. Monica Rivera-Mindt in the department of psychology at Fordham University.
Source:
Deirdre Branley
Albert Einstein College of Medicine
Despite the effectiveness of antiretroviral therapy for HIV, neurological complications associated with HIV infection - including cognitive, behavioral, and motor abnormalities - have become more common as infected individuals live longer.
"More than a quarter of those infected with HIV exhibit some form of cognitive impairment," says Ruth Hogue Angeletti, Ph.D., professor of developmental & molecular biology and of biochemistry at Einstein, who will direct the Einstein Proteomics Research Center for HIV-Associated Neurological Disorders and Substance Abuse. "By the time HIV-infected people have progressed to AIDS, more than half display significant neurological deficits."
This new proteomics center will use powerful mass spectrometers to identify the brain proteins responsible for neurological complications in people infected with HIV - particularly those who are also addicted to drugs. Proteomics is the branch of molecular biology that studies the set of proteins expressed by the genes of an organism.
HIV's neurological complications (commonly referred to as neuro-AIDS) primarily stem from toxic proteins produced by immune cells called monocytes, which recruit HIV into the central nervous system. Neuro-AIDS can lead to AIDS dementia complex, HIV-related encephalitis, and fungal and parasitic infections.
The Einstein Proteomics Research Center will investigate the mechanism by which HIV infection causes neurological deficits and identify biomarkers that signal when these deficits begin and how they progress over time.
"The biomarkers identified by this new center should permit the early detection of neurological disease in HIV-infected individuals," says co-principal investigator Harris Goldstein, M.D., director of the Einstein-Montefiore Center for AIDS Research and professor of pediatrics and of microbiology & immunology at Einstein.
"We have developed a unique transgenic HIV mouse model that displays some features of neuro-AIDS," Dr. Goldstein notes. "By studying this mouse model in the proteomics center, we'll be able to determine how HIV infection influences the proteins expressed in the brain. These results may help us to pinpoint new therapeutic targets for preventing the progression of this devastating consequence of HIV infection."
Several studies of autopsy tissue show that the destructive neuro-AIDS process is worsened by drug abuse, particularly the use of opioids such as heroin. Unfortunately, the combination of HIV infection and drug addiction is all too common. In New York City, for example, more than half of all AIDS cases result directly or indirectly from injection drug use.
"Therefore, the intersection between HIV infection and opioid use represents an especially important area of neuro-AIDS research on which our proteomics center will focus," says Dr. Angeletti.
Each of the center's projects will evaluate the neurological effects of buprenorphine - a new, less-addictive alternative to methadone. Compared with methadone, buprenorphine can be given at higher doses with fewer adverse effects. But it could conceivably contribute to neurological problems when used by drugs addicts who are infected with HIV.
"The blood-brain barrier protects the brain from HIV-infected monocytes and other neuroinflammatory mediators, and we don't yet know how buprenorphine affects this barrier," says co-principal investigator Joan W. Berman, Ph.D., professor in the departments of pathology and microbiology & immunology at Einstein. "We need to understand buprenorphine's neurological impact before use of the drug becomes widespread in this patient population."
On the other hand, the center's research may show that buprenorphine is a better alternative than methadone for people infected with HIV. "Because of its unique pharmacological properties, buprenorphine may provide neuropsychological benefits for HIV-infected people who are addicted to opioids," says Julia H. Arnsten, M.D., M.P.H., the center's other co-principal investigator and professor of medicine, of epidemiology & population health, and of psychiatry and behavioral sciences at Einstein.
As part of the study, Dr. Arnsten will recruit a cohort of HIV-infected patients who are undergoing treatment for drug addiction. These people will be monitored to see whether buprenorphine influences the development of neurological deficits.
Other key investigators for this center are Dr. Louis Weiss in the departments of pathology and of medicine, Dr. Andras Fiser in the departments of systems & computational biology and of biochemistry, Dr. Abdissa Negassa in the department of epidemiology & population health, and Dr. Monica Rivera-Mindt in the department of psychology at Fordham University.
Source:
Deirdre Branley
Albert Einstein College of Medicine
понедельник, 20 июня 2011 г.
Molecules In Plants May Have Beneficial Effect On Alzheimer's Disease
A set of molecules found in certain plants appears to have a beneficial effect in brain tissue associated with Alzheimer's disease, according to a new study conducted in mice. The study was led by researchers at the University of South Florida and Cedars-Sinai Medical Center. An article in the Journal of Cellular and Molecular Medicine is available online.
Terrence Town, Ph.D., one of the senior authors of the study, is available to provide more information about this study. He is a research scientist with the departments of Neurosurgery and Biomedical Sciences at Cedars-Sinai Medical Center, and with the hospital's neurosurgical research center, the Maxine Dunitz Neurosurgical Institute.
Researchers administered molecules called flavonoids, which are found in certain fruits and vegetables, to a mouse model genetically programmed to develop Alzheimer's disease. Using two of these molecules, luteolin and diosmin, they were able to reduce the levels of a protein called amyloid-beta, which forms the sticky deposits that build up in the brains of patients with Alzheimer's. The researchers also determined that these molecules work by targeting a protein called presenilin-1, which has long been linked to Alzheimer's as a genetic cause of this devastating and untreatable illness.
The results may offer a new approach to therapy for patients suffering from this neurodegenerative illness, which is the most common cause of dementia and is estimated to affect more than five million people in the United States.
"These flavonoids are widely available in natural foods and it appears that they may be used in purified form as therapeutic agents. The compounds have few if any side effects and are naturally occurring in citrus fruits. They also can be found as dietary supplements in health food stores," Town said.
Jun Tan, M.D., Ph.D., with the University of South Florida Department of Psychiatry, headed the study. Other authors are: Kavon Rezai-Zadeh (first author), R. Douglas Shytle, Ph.D., Yun Bai, M.D., Ph.D., Jun Tian, M.D., Ph.D., Huayan Hou, M.D., Ph.D., Takashi Mori, D.V.M., Ph.D., Jin Zeng, M.D., and Demian Obregon.
The study was supported by the National Institutes of Health and the Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute.
Citation: Journal of Cellular and Molecular Medicine, "Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer's disease ОІ-amyloid production," published online April 17, 2008
Cedars-Sinai Medical Center
8700 Beverly Blvd., Rm 2429A
Los Angeles, CA 90048
United States
cedars-sinai
Terrence Town, Ph.D., one of the senior authors of the study, is available to provide more information about this study. He is a research scientist with the departments of Neurosurgery and Biomedical Sciences at Cedars-Sinai Medical Center, and with the hospital's neurosurgical research center, the Maxine Dunitz Neurosurgical Institute.
Researchers administered molecules called flavonoids, which are found in certain fruits and vegetables, to a mouse model genetically programmed to develop Alzheimer's disease. Using two of these molecules, luteolin and diosmin, they were able to reduce the levels of a protein called amyloid-beta, which forms the sticky deposits that build up in the brains of patients with Alzheimer's. The researchers also determined that these molecules work by targeting a protein called presenilin-1, which has long been linked to Alzheimer's as a genetic cause of this devastating and untreatable illness.
The results may offer a new approach to therapy for patients suffering from this neurodegenerative illness, which is the most common cause of dementia and is estimated to affect more than five million people in the United States.
"These flavonoids are widely available in natural foods and it appears that they may be used in purified form as therapeutic agents. The compounds have few if any side effects and are naturally occurring in citrus fruits. They also can be found as dietary supplements in health food stores," Town said.
Jun Tan, M.D., Ph.D., with the University of South Florida Department of Psychiatry, headed the study. Other authors are: Kavon Rezai-Zadeh (first author), R. Douglas Shytle, Ph.D., Yun Bai, M.D., Ph.D., Jun Tian, M.D., Ph.D., Huayan Hou, M.D., Ph.D., Takashi Mori, D.V.M., Ph.D., Jin Zeng, M.D., and Demian Obregon.
The study was supported by the National Institutes of Health and the Johnnie B. Byrd Sr. Alzheimer's Center & Research Institute.
Citation: Journal of Cellular and Molecular Medicine, "Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer's disease ОІ-amyloid production," published online April 17, 2008
Cedars-Sinai Medical Center
8700 Beverly Blvd., Rm 2429A
Los Angeles, CA 90048
United States
cedars-sinai
пятница, 17 июня 2011 г.
NRC, UOttawa Scientists First To Watch A Chemical Bond Break Using Molecule's Electrons
Scientists at the National Research Council of Canada (NRC) and the University of Ottawa (uOttawa) enjoyed a bird's eye view of a chemical bond as it breaks.
The making and breaking of chemical bonds underlie the biochemical processes of life itself. A greater understanding of the quantum processes that lead to chemical reactions may lead to new strategies in the design and control of molecules - ultimately leading to scientific breakthroughs in health care and diagnostic medicine, quantum computing, nanotechnology, environmental science and energy.
The NRC-uOttawa team, led by Dr. David Villeneuve, achieved their feat using a technique developed several years ago at NRC in which an image was obtained of a single electron orbiting a molecule. In the current experiment, which is reported in the July 29th edition of Nature, scientists injected bromine gas into a vacuum chamber. There, an ultra brief ultraviolet light pulse caused the bromine molecules to separate into their individual atoms (a bromine molecule is composed of two bromine atoms). A few femtoseconds later, an intense infrared laser pulse caused the molecule to emit an attosecond-duration X-ray burst that contained a snapshot of the atom's position as the molecule fell apart and revealed how the electrons rearranged themselves.
"Due to the strange laws of quantum physics," Dr. Villeneuve explains, "a molecule that is broken apart by an ultraviolet laser pulse is at the same time unaffected by the pulse, a paradox, much like Schrödinger's Cat is both dead and alive."
The interference of the x-rays emitted by the two quantum states of the molecule was used to find the location of the atoms and to watch over a period of only 200 femtoseconds as it progressed from being a molecule to being two separate atoms. The experiment reached a precision below 500 zeptoseconds in clocking the emitted x-ray bursts. "It is exciting to see the quantum transformation as it goes from being a molecule, in which electrons are shared, to individual atoms, says Villeneuve.
According to Professor Paul Corkum, co-author and a pioneer in attosecond physics, "In real life we are most sensitive to motion if there is a fixed background for reference. We have shown that it is the same in the molecular world. Unreacting molecules - usually a nuisance in an experiment - can also form a reference. Against this fixed background we become so sensitive to motion that we can see just few dissociating molecules. The experiment is another important step towards the dream of filming chemical reactions."
The research was conducted at JASLab, the Joint Attosecond Science Laboratory, a shared laser facility between the National Research Council of Canada and the University of Ottawa, with the participation of the Technical University of Vienna. JASLab is one of the top laboratories in the world conducting research on the attosecond timescale.
How Fast is Really Fast?
Femtosecond = A femtosecond is an incredibly short period of time. One femtosecond is one millionth of one billionth of a second or 1 / 1,000,000,000,000,000 seconds
Attosecond = An attosecond is even shorter! One attosecond is to one second as one second is to the age of the universe. One attosecond is one billionth of one billionth of a second or 1 / 1,000,000,000,000,000,000 seconds.
Zeptosecond = A zeptosecond is still a shorter period of time. A spaceship traveling at the speed of light will travel from one side of a hydrogen atom to the other in 500 zeptoseconds. A zeptosecond is 1 / 1,000,000,000,000,000,000,000 seconds.
Source:
Helene Letourneau
National Research Council of Canada
The making and breaking of chemical bonds underlie the biochemical processes of life itself. A greater understanding of the quantum processes that lead to chemical reactions may lead to new strategies in the design and control of molecules - ultimately leading to scientific breakthroughs in health care and diagnostic medicine, quantum computing, nanotechnology, environmental science and energy.
The NRC-uOttawa team, led by Dr. David Villeneuve, achieved their feat using a technique developed several years ago at NRC in which an image was obtained of a single electron orbiting a molecule. In the current experiment, which is reported in the July 29th edition of Nature, scientists injected bromine gas into a vacuum chamber. There, an ultra brief ultraviolet light pulse caused the bromine molecules to separate into their individual atoms (a bromine molecule is composed of two bromine atoms). A few femtoseconds later, an intense infrared laser pulse caused the molecule to emit an attosecond-duration X-ray burst that contained a snapshot of the atom's position as the molecule fell apart and revealed how the electrons rearranged themselves.
"Due to the strange laws of quantum physics," Dr. Villeneuve explains, "a molecule that is broken apart by an ultraviolet laser pulse is at the same time unaffected by the pulse, a paradox, much like Schrödinger's Cat is both dead and alive."
The interference of the x-rays emitted by the two quantum states of the molecule was used to find the location of the atoms and to watch over a period of only 200 femtoseconds as it progressed from being a molecule to being two separate atoms. The experiment reached a precision below 500 zeptoseconds in clocking the emitted x-ray bursts. "It is exciting to see the quantum transformation as it goes from being a molecule, in which electrons are shared, to individual atoms, says Villeneuve.
According to Professor Paul Corkum, co-author and a pioneer in attosecond physics, "In real life we are most sensitive to motion if there is a fixed background for reference. We have shown that it is the same in the molecular world. Unreacting molecules - usually a nuisance in an experiment - can also form a reference. Against this fixed background we become so sensitive to motion that we can see just few dissociating molecules. The experiment is another important step towards the dream of filming chemical reactions."
The research was conducted at JASLab, the Joint Attosecond Science Laboratory, a shared laser facility between the National Research Council of Canada and the University of Ottawa, with the participation of the Technical University of Vienna. JASLab is one of the top laboratories in the world conducting research on the attosecond timescale.
How Fast is Really Fast?
Femtosecond = A femtosecond is an incredibly short period of time. One femtosecond is one millionth of one billionth of a second or 1 / 1,000,000,000,000,000 seconds
Attosecond = An attosecond is even shorter! One attosecond is to one second as one second is to the age of the universe. One attosecond is one billionth of one billionth of a second or 1 / 1,000,000,000,000,000,000 seconds.
Zeptosecond = A zeptosecond is still a shorter period of time. A spaceship traveling at the speed of light will travel from one side of a hydrogen atom to the other in 500 zeptoseconds. A zeptosecond is 1 / 1,000,000,000,000,000,000,000 seconds.
Source:
Helene Letourneau
National Research Council of Canada
вторник, 14 июня 2011 г.
'Surprising Link' Points Toward A New Antibiotic
As the best drugs become increasingly resistant to superbugs, McMaster University researchers have discovered a completely different way of looking for a new antibiotic.
In a paper published May 29 in the journal Chemistry and Biology, with colleagues in Germany and Wilfrid Laurier University, they report on work with the bacteria Staphylococcus aureus bacteria, the leading cause of infections in hospitals and the second most common community-acquired infection. Fewer and fewer antibiotics are effective against this bacteria.
Cell wall-active antibiotics, such as penicillin, kill bacteria by blocking production of the cell wall.
The researchers provide new evidence for genetic connections among three processes in the cell wall - teichoic acid, peptidoglycan and poly-isoprenoid synthesis. "Never before has such a profound link been drawn between these biosynthetic pathways supported by genetic, computational and biochemical evidence," they said in their paper.
"We found a connection that perhaps no one expected in the way the cell wall synthesis is wired," said lead author Eric Brown, professor and chair of the department of biochemistry and biomedical sciences in the Michael G. DeGroote School of Medicine.
"We found they are inextricably linked in their genetics and biochemistry," he said. "Along the way in this study, we have built a system that is ripe for being exploited as a way to search for small molecule drugs that would target these processes."
Potentially, he said, this may lead to the development of a new antibiotic.
Brown said the current arsenal of antibiotics was developed during the golden age of antibiotic drug discovery from 1930 to 1960, and then development stopped.
Research began again in earnest, he said, when troublesome strains of hospital and community-acquired infections began to emerge, such as MRSA (methicillin-resistant Staphylococcus aureus). "Since the 1960s, drug companies have for, the most part, been tweaking existing molecules, such as building better penicillin with minor changes to the original scaffold. But, you are not very far away from resistance when all you do is a little tweak."
The discovery of a "surprising link" between the three processes involved in cell wall synthesis lets researchers build a method of looking for molecules that will disturb the balance between them. "It offers a completely different way of looking for a new antibiotic that would be active against the cell wall," Brown said.
Source:
Veronica McGuire
McMaster University
In a paper published May 29 in the journal Chemistry and Biology, with colleagues in Germany and Wilfrid Laurier University, they report on work with the bacteria Staphylococcus aureus bacteria, the leading cause of infections in hospitals and the second most common community-acquired infection. Fewer and fewer antibiotics are effective against this bacteria.
Cell wall-active antibiotics, such as penicillin, kill bacteria by blocking production of the cell wall.
The researchers provide new evidence for genetic connections among three processes in the cell wall - teichoic acid, peptidoglycan and poly-isoprenoid synthesis. "Never before has such a profound link been drawn between these biosynthetic pathways supported by genetic, computational and biochemical evidence," they said in their paper.
"We found a connection that perhaps no one expected in the way the cell wall synthesis is wired," said lead author Eric Brown, professor and chair of the department of biochemistry and biomedical sciences in the Michael G. DeGroote School of Medicine.
"We found they are inextricably linked in their genetics and biochemistry," he said. "Along the way in this study, we have built a system that is ripe for being exploited as a way to search for small molecule drugs that would target these processes."
Potentially, he said, this may lead to the development of a new antibiotic.
Brown said the current arsenal of antibiotics was developed during the golden age of antibiotic drug discovery from 1930 to 1960, and then development stopped.
Research began again in earnest, he said, when troublesome strains of hospital and community-acquired infections began to emerge, such as MRSA (methicillin-resistant Staphylococcus aureus). "Since the 1960s, drug companies have for, the most part, been tweaking existing molecules, such as building better penicillin with minor changes to the original scaffold. But, you are not very far away from resistance when all you do is a little tweak."
The discovery of a "surprising link" between the three processes involved in cell wall synthesis lets researchers build a method of looking for molecules that will disturb the balance between them. "It offers a completely different way of looking for a new antibiotic that would be active against the cell wall," Brown said.
Source:
Veronica McGuire
McMaster University
суббота, 11 июня 2011 г.
Important Advance In Imaging Of Cell Death
For quite some time, the "Holy Grail" in medical imaging has been the development of an effective method to image cell death as a means to intervene early in diseases and rapidly determine the effectiveness of treatments. A new paper by researchers at the University of Notre Dame and the Washington University School of Medicine describes important progress in using a synthetic probe to target dead and dying cells in mammary and prostate tumors in living animals.
Bradley D. Smith, Emil T. Hofman Professor of Chemistry and Biochemistry at Notre Dame, points out that the group of researchers had previously discovered that synthetic zinc (II)-dipicolylamine (Zn-DPA) coordination complexes can selectively target the outer surfaces of anionic (negatively charged) cell membranes. Furthermore, fluorescent versions of these Zn-DPA complexes act as imaging probes that can distinguish dead and dying mammalian cells from healthy cells in a cell culture and also selectively target bacteria in contaminated samples.
The researchers also recently demonstrated that a fluorescent near-infrared probe referred to as PSS-794 can be used to image bacterial infections in mice, indicating that PSS-794 has a notable ability to selectively target anionic cells in living animals.
In the new paper, the researchers describe a significant expansion of the animal imaging capability of PSS-794 by showing that it can target the anionic dead and dying cells within tumors in rat and mouse models. The research is an important step toward the development of optical imaging probes that could determine, noninvasively, the amount and type of cell death in tumors. Such imaging techniques could help clinicians accurately determine the grade of tumors and the stage of cancers, as well as to measure the effectiveness of treatments.
The researchers also believe that analogous probes can be developed that would allow for deep tissue imaging of cancers in humans.
Smith points out that although the study focused on mammary and prostate tumors, imaging of cell death is broadly useful for treatment of numerous conditions, including cardiovascular disease, neurology, renal disease and even transplant rejection.
The research, described in the Journal of the American Chemical Society, was supported by the National Institutes of Health, Notre Dame's Walther Cancer Center and the Notre Dame Integrated Imaging Facility.
Source:
Bradley Smith
University of Notre Dame
Bradley D. Smith, Emil T. Hofman Professor of Chemistry and Biochemistry at Notre Dame, points out that the group of researchers had previously discovered that synthetic zinc (II)-dipicolylamine (Zn-DPA) coordination complexes can selectively target the outer surfaces of anionic (negatively charged) cell membranes. Furthermore, fluorescent versions of these Zn-DPA complexes act as imaging probes that can distinguish dead and dying mammalian cells from healthy cells in a cell culture and also selectively target bacteria in contaminated samples.
The researchers also recently demonstrated that a fluorescent near-infrared probe referred to as PSS-794 can be used to image bacterial infections in mice, indicating that PSS-794 has a notable ability to selectively target anionic cells in living animals.
In the new paper, the researchers describe a significant expansion of the animal imaging capability of PSS-794 by showing that it can target the anionic dead and dying cells within tumors in rat and mouse models. The research is an important step toward the development of optical imaging probes that could determine, noninvasively, the amount and type of cell death in tumors. Such imaging techniques could help clinicians accurately determine the grade of tumors and the stage of cancers, as well as to measure the effectiveness of treatments.
The researchers also believe that analogous probes can be developed that would allow for deep tissue imaging of cancers in humans.
Smith points out that although the study focused on mammary and prostate tumors, imaging of cell death is broadly useful for treatment of numerous conditions, including cardiovascular disease, neurology, renal disease and even transplant rejection.
The research, described in the Journal of the American Chemical Society, was supported by the National Institutes of Health, Notre Dame's Walther Cancer Center and the Notre Dame Integrated Imaging Facility.
Source:
Bradley Smith
University of Notre Dame
среда, 8 июня 2011 г.
The Association For Molecular Pathology Releases Position Statement On Oversight Of Laboratory Tests
The Association for Molecular Pathology (AMP) has released its new position statement on the oversight of laboratory developed tests (LDTs), a recent focus of debate among policy makers, the laboratory community and other stakeholders. AMP's statement outlines the organization's commitment to providing high quality tests and its recognition of the need for implementation of appropriate oversight mechanisms. The association also met with officials from the United States Food and Drug Administration tasked with reviewing applications for diagnostic devices to inform them of the new position statement and discuss FDA's approach to regulating tests.
In recent years, there has been increased attention on the oversight of LDTs among policy makers, manufacturers, regulators and the laboratory community. While AMP believes that current mechanisms are sufficient in ensuring patient safety and broad access to high quality tests, AMP is taking this opportunity to elucidate its position on the issue.
"We believe that laboratory developed tests are an essential and central component of clinical care," said AMP President Dr. Karen Mann. She continued, "There is no evidence that the current oversight system has been inadequate or that there have been systemic problems."
In its position statement, AMP highlights that laboratories performing molecular tests are subject to the Clinical Laboratory Improvement Amendments and all laboratory directors are extensively trained professionals who adhere to all training requirements, certifications, licensure, and other regulations. Dr. Mann stressed the need to foster innovation, "As policymakers, regulators, and other stakeholders consider modifying the current oversight process, AMP urges them to ensure continued patient access to testing." AMP calls for stakeholders to avoid proposals that would hinder innovation in diagnostics, slow the rapid development and modification of necessary tests and impede the practice of medicine as all specialties rely on diagnostic tests.
AMP's specific recommendations include:
Laboratory directors or medical directors should review and reaffirm their policies and procedures for reviewing and documenting that appropriate validation studies have been performed for all tests developed in their laboratories with due consideration of clinical utility and clinical utilization.
CLIA should reassess utilization of resources and enforcement capabilities in order to meet its current mandate. CLIA should strengthen its enforcement capabilities by hiring more inspectors and improve the training of its inspectors.
To increase transparency, CMS should make information collected from laboratories in the CLIA program available and easily accessible to the public and other regulators.
Proficiency testing is a requirement of certification. When a formal proficiency testing program is not available, laboratories must perform and document alternative assessments as directed by CLIA.
Some tests may require greater scrutiny, such as those with hidden or nontransparent algorithms, and should be subject to additional review by regulators.
All LDTs should be subject to the same oversight mechanisms, and molecular tests should not be unduly scrutinized.
Any changes to the current oversight system should occur after a formal rule making process or statutory change.
Source:
Mary Steele Williams
Association for Molecular Pathology
In recent years, there has been increased attention on the oversight of LDTs among policy makers, manufacturers, regulators and the laboratory community. While AMP believes that current mechanisms are sufficient in ensuring patient safety and broad access to high quality tests, AMP is taking this opportunity to elucidate its position on the issue.
"We believe that laboratory developed tests are an essential and central component of clinical care," said AMP President Dr. Karen Mann. She continued, "There is no evidence that the current oversight system has been inadequate or that there have been systemic problems."
In its position statement, AMP highlights that laboratories performing molecular tests are subject to the Clinical Laboratory Improvement Amendments and all laboratory directors are extensively trained professionals who adhere to all training requirements, certifications, licensure, and other regulations. Dr. Mann stressed the need to foster innovation, "As policymakers, regulators, and other stakeholders consider modifying the current oversight process, AMP urges them to ensure continued patient access to testing." AMP calls for stakeholders to avoid proposals that would hinder innovation in diagnostics, slow the rapid development and modification of necessary tests and impede the practice of medicine as all specialties rely on diagnostic tests.
AMP's specific recommendations include:
Laboratory directors or medical directors should review and reaffirm their policies and procedures for reviewing and documenting that appropriate validation studies have been performed for all tests developed in their laboratories with due consideration of clinical utility and clinical utilization.
CLIA should reassess utilization of resources and enforcement capabilities in order to meet its current mandate. CLIA should strengthen its enforcement capabilities by hiring more inspectors and improve the training of its inspectors.
To increase transparency, CMS should make information collected from laboratories in the CLIA program available and easily accessible to the public and other regulators.
Proficiency testing is a requirement of certification. When a formal proficiency testing program is not available, laboratories must perform and document alternative assessments as directed by CLIA.
Some tests may require greater scrutiny, such as those with hidden or nontransparent algorithms, and should be subject to additional review by regulators.
All LDTs should be subject to the same oversight mechanisms, and molecular tests should not be unduly scrutinized.
Any changes to the current oversight system should occur after a formal rule making process or statutory change.
Source:
Mary Steele Williams
Association for Molecular Pathology
воскресенье, 5 июня 2011 г.
Nerves Under Control
The proper transmission of nerve signals along body nerves requires an insulation layer, named myelin sheath. To be efficient this sheath is designed to have a certain thickness and researchers from the ETH ZГјrich have now discovered that proteins Dlg1 and PTEN interact to control the myelin sheath thickness. Recently published in Science their discovery improves our understanding of Charcot-Marie-Tooth neurodegenerative diseases and open a new avenue in the potential treatment of these incurable and debilitating diseases.
A crucial factor in the transmission of nerve signals is the myelin layer - also known as the myelin sheath - which surrounds the axons. Axons are nerve cell projections through which the signals are relayed; the myelin sheath is formed by the Schwann cells in the peripheral nervous system, i.e. in the nervous system outside the brain and spinal chord. If it is too thick or too thin, the signal transmission slows down; if the myelin sheath becomes too badly damaged, it can cause diseases like Charcot-Marie-Tooth diseases. Patients suffer from an increasing weakness of the hands and feet, which gradually spreads to the arms and legs, sometimes even making them wheelchair-bound for the rest of their lives.
But which molecules regulate the thickness of the myelin sheath? Scientists at ETH Zurich from the research groups around biologists Ueli Suter and Nicolas Tricaud set about finding out. They have now published their findings in an online article in the journal "Science".
The scientists didn't have to start their search entirely from scratch, however, having already developed a mouse model for a sub-type of Charcot-Marie-Tooth disease; the model is based upon a mutation in the gene for the protein MTMR2 and leads to hypermyelination by the Schwann cells. What's more, the researchers already knew from other studies that MTMR2 interacts with Dlg1.
In experiments conducted on cell cultures and the sciatic nerve in mice, the researchers were now able to demonstrate that Dlg1 inhibits myelin growth. For this to work, however, it needs to enlist the help of another signal protein: PTEN. Together, they ensure that the growth of the myelin sheath does not go to excess in the mouse's development. If the brake is "released" by suppressing Dlg1 or PTEN, it results in myelin excess that not only leads to an extra-thick myelin sheath, but also to its degeneration. This process is characteristic of various diseases of the peripheral nervous system and , as it was revealed in the mouse model of Charcot-Marie-Tooth disease the Dlg-PTEN brake no longer works in these diseases. Nicolas Tricaud is convinced that the project helps to understand the basic molecular mechanisms of myelination, as well as offering new opportunities to define how the misdirection of these processes can cause neurodegenerative diseases and how this might be remedied.
Source: ETH ZГјrich
A crucial factor in the transmission of nerve signals is the myelin layer - also known as the myelin sheath - which surrounds the axons. Axons are nerve cell projections through which the signals are relayed; the myelin sheath is formed by the Schwann cells in the peripheral nervous system, i.e. in the nervous system outside the brain and spinal chord. If it is too thick or too thin, the signal transmission slows down; if the myelin sheath becomes too badly damaged, it can cause diseases like Charcot-Marie-Tooth diseases. Patients suffer from an increasing weakness of the hands and feet, which gradually spreads to the arms and legs, sometimes even making them wheelchair-bound for the rest of their lives.
But which molecules regulate the thickness of the myelin sheath? Scientists at ETH Zurich from the research groups around biologists Ueli Suter and Nicolas Tricaud set about finding out. They have now published their findings in an online article in the journal "Science".
The scientists didn't have to start their search entirely from scratch, however, having already developed a mouse model for a sub-type of Charcot-Marie-Tooth disease; the model is based upon a mutation in the gene for the protein MTMR2 and leads to hypermyelination by the Schwann cells. What's more, the researchers already knew from other studies that MTMR2 interacts with Dlg1.
In experiments conducted on cell cultures and the sciatic nerve in mice, the researchers were now able to demonstrate that Dlg1 inhibits myelin growth. For this to work, however, it needs to enlist the help of another signal protein: PTEN. Together, they ensure that the growth of the myelin sheath does not go to excess in the mouse's development. If the brake is "released" by suppressing Dlg1 or PTEN, it results in myelin excess that not only leads to an extra-thick myelin sheath, but also to its degeneration. This process is characteristic of various diseases of the peripheral nervous system and , as it was revealed in the mouse model of Charcot-Marie-Tooth disease the Dlg-PTEN brake no longer works in these diseases. Nicolas Tricaud is convinced that the project helps to understand the basic molecular mechanisms of myelination, as well as offering new opportunities to define how the misdirection of these processes can cause neurodegenerative diseases and how this might be remedied.
Source: ETH ZГјrich
четверг, 2 июня 2011 г.
Fighting Hunger: Norman Borlaug, Rob Horsch To Keynote International Lecture
Nobel Peace Prize recipient Norman Borlaug and Rob Horsch of the Gates Foundation will discuss the challenges of developing agricultural technologies to feed the world to kick off the International Annual Meetings of the American Society of Agronomy (ASA), Crop Science Society of America (CSSA), and Soil Science Society of America (SSSA) in New Orleans. They will speak on Sunday, Nov. 4 from 7 to 8 pm in the Grand Ballroom of the Hilton Riverside.
Horsch will present "New Investments in Crops, Soils, and Small Holder Farmers -- Why the Bill & Melinda Gates Foundation is Supporting Agricultural Development," followed by Borlaug on "Challenges for the Crop Scientist in the 21st Century." Both leaders in agriculture, they have utilized technology to fight hunger issues around the world.
Known as the father of the "Green Revolution," Borlaug has been commended for his contributions to science and his ability to influence political policy for the good of humanity. He is one of only five people in history to be awarded the Nobel Peace Prize (1970), Presidential Medal of Freedom (1977), and Congressional Gold Medal (2007). He also received the National Medal of Science (2005) and countless awards throughout his career.
Borlaug worked for 16 years to solve a series of wheat production problems in Mexico and to help train Mexican scientists for the Cooperative Wheat Research and Production Program, a joint undertaking by the Mexican government and Rockefeller Foundation. His new wheat varieties and improved crop management practices transformed agricultural production in Mexico during the 1940s and 1950s and later in Asia and Latin America, sparking what today is known as the "Green Revolution." Because of his achievements to prevent hunger and famine around the world, it is said that Borlaug has saved more lives than anyone.
Previously employed by Monsanto Company, Horsch worked to develop technologies for low-income countries and farmers to improve crop yields and incomes. He launched programs to transfer and apply technology to developing countries, train and educate scientists around the world, and communicate the benefits and risks of agricultural biotechnology.
Horsch joined the Bill & Melinda Foundation as a senior program officer in the agricultural development program in November 2006. He has served on the editorial boards of several leading plant science journals and as an advisor to the National Science Foundation and U.S. Department of Energy. In 1999, he was awarded the 1998 National Medal of Technology by President Bill Clinton for contributions to agricultural biotechnology.
The ASA-CSSA-SSSA Annual Meetings will be Nov. 4-8 at the Morial Convention Center. More than 4,000 scientists and professionals from around the world will attend research presentations on climate change, urban planning, crop production, hazardous waste, human health, bioenergy and more. For information about the meetings, including the abstracts online, go to acsmeetings/.
The ASA (agronomy/), CSSA (crops/) and SSSA (soils/) are educational organizations helping their 11,000+ members advance the disciplines and practices of agronomy, crop and soil sciences by supporting professional growth and science policy initiatives, and by providing quality, research-based publications and a variety of member services.
Source: Sara Uttech
American Society of Agronomy
Horsch will present "New Investments in Crops, Soils, and Small Holder Farmers -- Why the Bill & Melinda Gates Foundation is Supporting Agricultural Development," followed by Borlaug on "Challenges for the Crop Scientist in the 21st Century." Both leaders in agriculture, they have utilized technology to fight hunger issues around the world.
Known as the father of the "Green Revolution," Borlaug has been commended for his contributions to science and his ability to influence political policy for the good of humanity. He is one of only five people in history to be awarded the Nobel Peace Prize (1970), Presidential Medal of Freedom (1977), and Congressional Gold Medal (2007). He also received the National Medal of Science (2005) and countless awards throughout his career.
Borlaug worked for 16 years to solve a series of wheat production problems in Mexico and to help train Mexican scientists for the Cooperative Wheat Research and Production Program, a joint undertaking by the Mexican government and Rockefeller Foundation. His new wheat varieties and improved crop management practices transformed agricultural production in Mexico during the 1940s and 1950s and later in Asia and Latin America, sparking what today is known as the "Green Revolution." Because of his achievements to prevent hunger and famine around the world, it is said that Borlaug has saved more lives than anyone.
Previously employed by Monsanto Company, Horsch worked to develop technologies for low-income countries and farmers to improve crop yields and incomes. He launched programs to transfer and apply technology to developing countries, train and educate scientists around the world, and communicate the benefits and risks of agricultural biotechnology.
Horsch joined the Bill & Melinda Foundation as a senior program officer in the agricultural development program in November 2006. He has served on the editorial boards of several leading plant science journals and as an advisor to the National Science Foundation and U.S. Department of Energy. In 1999, he was awarded the 1998 National Medal of Technology by President Bill Clinton for contributions to agricultural biotechnology.
The ASA-CSSA-SSSA Annual Meetings will be Nov. 4-8 at the Morial Convention Center. More than 4,000 scientists and professionals from around the world will attend research presentations on climate change, urban planning, crop production, hazardous waste, human health, bioenergy and more. For information about the meetings, including the abstracts online, go to acsmeetings/.
The ASA (agronomy/), CSSA (crops/) and SSSA (soils/) are educational organizations helping their 11,000+ members advance the disciplines and practices of agronomy, crop and soil sciences by supporting professional growth and science policy initiatives, and by providing quality, research-based publications and a variety of member services.
Source: Sara Uttech
American Society of Agronomy
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