A team of scientists at The Scripps Research Institute has discovered a new way to stabilize proteins - the workhorse biological macromolecules found in all organisms. Proteins serve as the functional basis of many types of biologic drugs used to treat everything from arthritis, anemia, and diabetes to cancer.
As described in the journal Science, when the team attached a specific oligomeric array of sugars called a "glycan" to proteins having a defined structure, the proteins were up to 200 times more stable in the test tube. In the body, this stability may translate into longer half-lives for therapies, possibly lowering the overall cost of treatment for certain protein-based drugs and requiring patients to have fewer injections during a course of treatment.
The work may have major implications for the drug industry because there are a large number of protein-based drugs on the market, more in clinical trials, and many more under development worldwide. Nearly all of these protein-based drugs have glycans attached to them and are therefore called "glycoproteins". Glycoprotein-based drugs can be quite expensive to produce and usually need to be administered intravenously.
One of the challenges in producing these drugs has been increasing their stability, which generally extends their half-life in the bloodstream - issues that the new discovery appears to address directly.
"We've now provided engineering guidelines for glycoprotein stability," said Scripps Research Professor Jeffery W. Kelly, who is chair of the Department of Molecular and Experimental Medicine, Lita Annenberg Hazen Professor of Chemistry, and member of The Skaggs Institute for Chemical Biology at Scripps Research. Kelly led the study with Scripps Research Associate Professor Evan Powers and Staff Scientist Sarah R. Hanson, in collaboration with Research Associates Elizabeth K. Culyba, Joshua Price, and colleagues.
In Search of Stability
Making therapeutic proteins more stable by attaching glycans to them is nothing new. Scientists have known for many years that the human body widely modifies proteins in this way after they are made inside cells. By some estimates, as many as a third of all types of proteins in the human body are "glycosylated," the scientific name for the process whereby glycans are attached to proteins. Scientists also know that these modifications can be directly linked to protein stability.
Attaching a glycan to one part of a protein can have a dramatic stabilizing effect, accounting for the difference between it lasting in the bloodstream for a few minutes or a few days. But attaching the same glycan to another part of the same protein can have a distinctly different destabilizing effect, turning it into the microscopic equivalent of a cooked egg - unfolded and worthless as a medicine.
Scientists who work on these sorts of drugs often try to stabilize their therapeutic proteins with glycans, but until now nobody understood the rules that govern the process - nobody even knew for sure if there were general rules governing it. Researchers have always made such modifications through trial-and-error - more of a time-consuming art than an exact science.
But now, predicts Powers, "Having a rational design approach will streamline protein drug optimization quite a bit."
Simple Engineering Rules
The new research shows simple engineering rules do exist for achieving stability of glycoproteins in the test tube. In the new paper, the Scripps Research team showed that scientists could dramatically stabilize proteins by integrating the standard N-glycan into a particular part of the protein - a structure known as a "reverse turn" containing a certain combination of amino acids. Reverse turns are found in the vast majority of proteins, making this methodology broadly applicable.
The scientists tested their ability to increase the stability of proteins by creating glycoproteins from proteins that are not normally glycosylated - leading to increased stabilization in the test tube. These scientists have not yet looked at how long the proteins survive in the bloodstream - that work is currently under way. But the team is confident that the principles they discovered will now give scientists a new way to predictably stabilize proteins by design.
Kelly added that this portable stabilizing structural module called the "enhanced aromatic sequon" also leads to more efficient production of glycoproteins by cells, a result that is potentially very important, since glycoproteins remain difficult to produce and purify.
Notes:
In addition to Kelly, Powers, Hanson, Culyba, and Price, the article, "Protein Native-State Stabilization by Placing Aromatic Side Chains in N-Glycosylated Reverse Turns" is authored by Apratim Dhar, Chi-Huey Wong, and Martin Gruebele.
This work was supported in part by the Skaggs Institute for Chemical Biology and the Lita Annenberg Hazen Foundation, and funded through grants from the National Institutes of Health and the National Science Foundation.
Source:
Mika Ono
Scripps Research Institute
суббота, 30 апреля 2011 г.
пятница, 29 апреля 2011 г.
Poxvirus Potency Uncovered In New Atomic Map
Scientists at the University of Alabama at Birmingham (UAB) and Saint Louis University used X-ray crystallography to uncover new details about the infectious potency of poxviruses, furthering the understanding of how one protein in viral infections can subvert the body's immune system.
Having high-resolution detail of this protein on hand will speed the discovery of new drugs to combat inflammation and immune diseases such as atherosclerosis and rheumatoid arthritis, the researchers said.
The findings are published in the online edition of journal Proceedings of the National Academy of Sciences and will soon appear in a print edition.
"Now we have a visual blueprint to guide our future studies on interferon-gamma binding protein, which one day may be used to prevent inflammatory disease," said Mark R. Walter, Ph.D., an associate professor in the UAB Department of Microbiology and senior author on the study.
Interferon-gamma binding protein (IFN-y) is notorious for the role it plays in helping poxviruses replicate. Normally when a virus enters the bloodstream, the immune system fights back by producing IFN-y, which tells surrounding cells to fight the infection.
Remarkably, somewhere during the evolution of the poxvirus, it captured an IFN-y gene from its host and incorporated some of the protein structure into its own. As a result poxvirus has a very efficient "blocker" of the IFN-y antiviral response, Walter said.
The new study shows this blocking ability through crystallography, the science of mapping the atomic structure of molecules by looking at their interaction with an X-ray beam.
Poxviruses include many classes of the invasive organism such as smallpox, cowpox and monkeypox. Smallpox in particular has played a tragic role in human history: estimates show it caused between 300 million and 500 million deaths in the 20th Century.
Smallpox was declared officially eradicated in 1979, but other poxviruses remain a health threat.
"The damage that the smallpox virus has done to mankind is horrific and enormous, which is why we think it's so important to understand more about the poxviruses and how they operate," said Mark Buller, Ph.D., professor of microbiology and immunology at the Saint Louis University School of Medicine and a study author. "The more knowledge we have, the better we should be able to cope with other major viruses and diseases in the future."
The research was funded by grants from the National Institutes of Health and the American Heart Association.
University of Alabama at Birmingham
701 20th St. S., AB 1320
Birmingham, AL 35294-0113
United States
main.uab
Having high-resolution detail of this protein on hand will speed the discovery of new drugs to combat inflammation and immune diseases such as atherosclerosis and rheumatoid arthritis, the researchers said.
The findings are published in the online edition of journal Proceedings of the National Academy of Sciences and will soon appear in a print edition.
"Now we have a visual blueprint to guide our future studies on interferon-gamma binding protein, which one day may be used to prevent inflammatory disease," said Mark R. Walter, Ph.D., an associate professor in the UAB Department of Microbiology and senior author on the study.
Interferon-gamma binding protein (IFN-y) is notorious for the role it plays in helping poxviruses replicate. Normally when a virus enters the bloodstream, the immune system fights back by producing IFN-y, which tells surrounding cells to fight the infection.
Remarkably, somewhere during the evolution of the poxvirus, it captured an IFN-y gene from its host and incorporated some of the protein structure into its own. As a result poxvirus has a very efficient "blocker" of the IFN-y antiviral response, Walter said.
The new study shows this blocking ability through crystallography, the science of mapping the atomic structure of molecules by looking at their interaction with an X-ray beam.
Poxviruses include many classes of the invasive organism such as smallpox, cowpox and monkeypox. Smallpox in particular has played a tragic role in human history: estimates show it caused between 300 million and 500 million deaths in the 20th Century.
Smallpox was declared officially eradicated in 1979, but other poxviruses remain a health threat.
"The damage that the smallpox virus has done to mankind is horrific and enormous, which is why we think it's so important to understand more about the poxviruses and how they operate," said Mark Buller, Ph.D., professor of microbiology and immunology at the Saint Louis University School of Medicine and a study author. "The more knowledge we have, the better we should be able to cope with other major viruses and diseases in the future."
The research was funded by grants from the National Institutes of Health and the American Heart Association.
University of Alabama at Birmingham
701 20th St. S., AB 1320
Birmingham, AL 35294-0113
United States
main.uab
четверг, 28 апреля 2011 г.
Nitrites Help To Struggle Against Ischemia Retinae
Nitrites dilate vessels in case of hypoxia and protect retina from ischemia. The conclusion has been made by specialists of the Moscow Research Institute for Eye Diseases named after Gelmholtz and the N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences. Their discovery is the outcome of a series of experiments on rabbits. It is premature to talk about its clinical use.
Ischemia is a rather widespread pathology of retina and optic nerve. It is provoked by different reasons, including primary hypertension and insular diabetes. An important role in retina pathology development is played by shortage of nitric oxide, which is synthesized in the organism from arginine. Theoretically speaking, nitrites can turn into nitric oxide under the influence of some enzymes. However, till recently, nobody could prove that such reaction does take place in a living organism. The Moscow researchers succeeded to do that based on the acute ischemia retinae model developed by them.
The rabbit is a favorite object for ophthalmologists' investigations. The animals underwent laser coagulation of eye-ground vessels. The experimentalists have chosen such a place for exposure so that several impulses could capture the maximum number of vessels and if possible not to traumatize surrounding tissues. The laser provokes stable vasospasm and, consequently, ischemia. The outcomes of researchers' action were estimated by the rabbits' eye-ground photographs.
After coagulation, the rabbits' eye vessels become desolate and abruptly reduced in diameter. Right after laser exposure, sodium nitrite in physiological solution was intraperitoneally introduced to the rabbits on the basis of 20 mg per 1 kilogram of live weight. As soon as a quarter of an hour after the injection, the retina vessels directly behind the laser impact zone began to fill with blood and the blood circulation restored in them. At that, the nitrite injection to an animal with normal vessels almost did not provoke their dilation. The researchers assume that nitrite in the organism is able to quickly reduce to nitric oxide, which sharply relaxes vessels, but only in case of oxygen shortage.
In the course of a next series of experiments the researchers clarified if preliminary nitrite injection prevented vessel constriction. For this end, a rabbit was initially injected sodium nitrite, and 15 minutes later the researchers cauterized vessels by laser and observed changes in them. In this case, laser impact provoked only a short-term vasospasm of the vessel, which quickly filled with blood and restored the "flow capacity".
The same results were obtained by the researchers via an independent method when observing changes in photoelectric activity of a rabbit's retina. The electroretinogram analysis has shown that laser coagulation of vessels impairs functional state of retina, which restores within 7 days without outside interference. The sodium nitrite injection right after laser coagulation accelerates the rehabilitation process significantly, and the preparation injection prior to laser exposure virtually fully protects retina from injury. At that, even strong laser impact can not provoke abrupt constriction and desolation of animals' vessels.
Thus, the outcomes obtained by two independent methods prove that nitrites presence in vessels protects the retina from acute ischemia. Mechanism of such action, apparently, consists in the fact that under oxygen shortage in the organism, sodium nitrite can reduce to nitric oxide at concentrations that are sufficient for full vessel relaxation.
INFORMNAUKA (INFORMSCIENCE) AGENCY
informnauka.ru/eng
Ischemia is a rather widespread pathology of retina and optic nerve. It is provoked by different reasons, including primary hypertension and insular diabetes. An important role in retina pathology development is played by shortage of nitric oxide, which is synthesized in the organism from arginine. Theoretically speaking, nitrites can turn into nitric oxide under the influence of some enzymes. However, till recently, nobody could prove that such reaction does take place in a living organism. The Moscow researchers succeeded to do that based on the acute ischemia retinae model developed by them.
The rabbit is a favorite object for ophthalmologists' investigations. The animals underwent laser coagulation of eye-ground vessels. The experimentalists have chosen such a place for exposure so that several impulses could capture the maximum number of vessels and if possible not to traumatize surrounding tissues. The laser provokes stable vasospasm and, consequently, ischemia. The outcomes of researchers' action were estimated by the rabbits' eye-ground photographs.
After coagulation, the rabbits' eye vessels become desolate and abruptly reduced in diameter. Right after laser exposure, sodium nitrite in physiological solution was intraperitoneally introduced to the rabbits on the basis of 20 mg per 1 kilogram of live weight. As soon as a quarter of an hour after the injection, the retina vessels directly behind the laser impact zone began to fill with blood and the blood circulation restored in them. At that, the nitrite injection to an animal with normal vessels almost did not provoke their dilation. The researchers assume that nitrite in the organism is able to quickly reduce to nitric oxide, which sharply relaxes vessels, but only in case of oxygen shortage.
In the course of a next series of experiments the researchers clarified if preliminary nitrite injection prevented vessel constriction. For this end, a rabbit was initially injected sodium nitrite, and 15 minutes later the researchers cauterized vessels by laser and observed changes in them. In this case, laser impact provoked only a short-term vasospasm of the vessel, which quickly filled with blood and restored the "flow capacity".
The same results were obtained by the researchers via an independent method when observing changes in photoelectric activity of a rabbit's retina. The electroretinogram analysis has shown that laser coagulation of vessels impairs functional state of retina, which restores within 7 days without outside interference. The sodium nitrite injection right after laser coagulation accelerates the rehabilitation process significantly, and the preparation injection prior to laser exposure virtually fully protects retina from injury. At that, even strong laser impact can not provoke abrupt constriction and desolation of animals' vessels.
Thus, the outcomes obtained by two independent methods prove that nitrites presence in vessels protects the retina from acute ischemia. Mechanism of such action, apparently, consists in the fact that under oxygen shortage in the organism, sodium nitrite can reduce to nitric oxide at concentrations that are sufficient for full vessel relaxation.
INFORMNAUKA (INFORMSCIENCE) AGENCY
informnauka.ru/eng
среда, 27 апреля 2011 г.
Dividing Cells "Feel" Their Way Out Of Warp
Every moment, millions of a body's cells flawlessly divvy up their genes and pinch perfectly in half to form two identical progeny for the replenishment of tissues and organs - even as they collide, get stuck, and squeeze through infinitesimally small spaces that distort their shapes.
Now Johns Hopkins scientists, working with the simplest of organisms, have discovered the molecular sensor that lets cells not only "feel" changes to their neat shapes, but also to remodel themselves back into ready-to-split symmetry. In a study published September 15 in Current Biology, the researchers show that two force-sensitive proteins accumulate at the sites of cell-shape disturbances and cooperate first to sense the changes and then to resculpt the cells. The proteins - myosin II and cortexillin I - monitor and correct shape changes in order to ensure smooth division.
"What we found is an exquisitely tuned mechanosensory system that keeps the cells shipshape so they can divide properly," says Douglas N. Robinson, Ph.D., an associate professor of Cell Biology, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine.
Faulty cell division can put organisms, including people, on the pathway to diseases such as cancer, Robinson notes, and a better understanding of how cells respond to mechanical stress on their shapes could present new targets for both diagnosing and treating such diseases.
Working with hardy, single-celled protozoa that move and divide similarly to human cells, the scientists watched through microscopes while they deformed the cells' shapes with a tiny instrument that, like a soda straw, sucks in on the cell surface and creates distorted shapes.
"This particular method, based on a very old principle that dates back to Archimedes, enables us to deform cells without killing them, much in the same way that natural processes in the body constantly assault them, Robinson says."
Once the cells were warped, the scientists monitored the movements of fluorescent-tagged myosin II and cortexillin I. Myosin, which normally accumulates in the middles of cells during division to help power that process, collected instead at the sites of disturbances made by the micropipette. Also amassing with myosin was cortexillin I, a so-called actin-crosslinking protein that, like glue, holds the toothpick-like filaments of a cell's housing together.
In the experiments, as soon as the two proteins accumulated to a certain level, the cells contracted, escaping the pipettes and assuming their original shapes. After the cells righted themselves, the proteins realigned along the cells' midlines and pinched to divide symmetrically into two daughter cells.
The researchers repeated the experiment using cells engineered to lack myosin II and then again with cells lacking cortexillin I. They discovered that cortexillin I responded to deformations except when myosin II was removed, and myosin II responded to deformations except when cortexillin I was removed.
"It's clear that the two need each other to operate as a cellular mechanosensor," Robinson says.
The research was funded by grants from the National Institutes of Health, the American Cancer Society and the National Science Foundation.
In addition to Robinson, authors of the paper are Yixin Ren, Janet C. Effler, Pablo A. Iglesias and Tianzhi Luo, all of Johns Hopkins; Melanie Norstrom and Ronald S. Rock, both of the University of Chicago; and Richard A. Firtel, University of California San Diego.
On the Web:
hopkinsmedicine/cellbio/robinson/
cell/current-biology/home
Related Video:
Watch dividing cells "feel" their way out of warp
Source
Johns Hopkins University School of Medicine
Now Johns Hopkins scientists, working with the simplest of organisms, have discovered the molecular sensor that lets cells not only "feel" changes to their neat shapes, but also to remodel themselves back into ready-to-split symmetry. In a study published September 15 in Current Biology, the researchers show that two force-sensitive proteins accumulate at the sites of cell-shape disturbances and cooperate first to sense the changes and then to resculpt the cells. The proteins - myosin II and cortexillin I - monitor and correct shape changes in order to ensure smooth division.
"What we found is an exquisitely tuned mechanosensory system that keeps the cells shipshape so they can divide properly," says Douglas N. Robinson, Ph.D., an associate professor of Cell Biology, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine.
Faulty cell division can put organisms, including people, on the pathway to diseases such as cancer, Robinson notes, and a better understanding of how cells respond to mechanical stress on their shapes could present new targets for both diagnosing and treating such diseases.
Working with hardy, single-celled protozoa that move and divide similarly to human cells, the scientists watched through microscopes while they deformed the cells' shapes with a tiny instrument that, like a soda straw, sucks in on the cell surface and creates distorted shapes.
"This particular method, based on a very old principle that dates back to Archimedes, enables us to deform cells without killing them, much in the same way that natural processes in the body constantly assault them, Robinson says."
Once the cells were warped, the scientists monitored the movements of fluorescent-tagged myosin II and cortexillin I. Myosin, which normally accumulates in the middles of cells during division to help power that process, collected instead at the sites of disturbances made by the micropipette. Also amassing with myosin was cortexillin I, a so-called actin-crosslinking protein that, like glue, holds the toothpick-like filaments of a cell's housing together.
In the experiments, as soon as the two proteins accumulated to a certain level, the cells contracted, escaping the pipettes and assuming their original shapes. After the cells righted themselves, the proteins realigned along the cells' midlines and pinched to divide symmetrically into two daughter cells.
The researchers repeated the experiment using cells engineered to lack myosin II and then again with cells lacking cortexillin I. They discovered that cortexillin I responded to deformations except when myosin II was removed, and myosin II responded to deformations except when cortexillin I was removed.
"It's clear that the two need each other to operate as a cellular mechanosensor," Robinson says.
The research was funded by grants from the National Institutes of Health, the American Cancer Society and the National Science Foundation.
In addition to Robinson, authors of the paper are Yixin Ren, Janet C. Effler, Pablo A. Iglesias and Tianzhi Luo, all of Johns Hopkins; Melanie Norstrom and Ronald S. Rock, both of the University of Chicago; and Richard A. Firtel, University of California San Diego.
On the Web:
hopkinsmedicine/cellbio/robinson/
cell/current-biology/home
Related Video:
Watch dividing cells "feel" their way out of warp
Source
Johns Hopkins University School of Medicine
вторник, 26 апреля 2011 г.
NYU's Center For Comparative Functional Genomics Part Of $57 Million MOD-ENCODE Consortium
New York University biologist Fabio Piano, an associate professor at NYU's Center for Comparative Functional Genomics, was selected by National Human Genome Research Institute (NHGRI) to lead one of the teams charged with decoding the genome. NHGRI is an institute within the National Institutes of Health (NIH).
The award to Piano, a professor in NYU's Biology Department, and the nine other researchers leading genome centers across the nation, will create a consortium of scientists who will collaborate in a four-year, $57 million scientific endeavor to understand every part of the genome needed for organisms to develop and thrive, as announced by NIH.
This four-year, multi-institutional collaborative genome project called "MOD-ENCODE" aims to identify all the functional elements (ENCODE) in the genomes of the model organisms (MOD) fruit fly and round worm Caenorhabditis elegans (C. elegans) as models to understand the functional elements and to shed light on the function of these elements in humans.
The effort will build upon the foundation laid by the ENCyclopedia of DNA Elements (ENCODE) consortium, which is preparing to build a comprehensive catalog, or "parts list," of all elements in the human genome crucial to biological function. In addition to genes that code for proteins, these functional elements include: non-protein-coding genes; regulatory elements involved in the control of gene transcription; and DNA sequences that mediate the structure and dynamics of chromosomes. For more information about NHGRI's ENCODE project, go to genome/ENCODE.
"We are making great strides in identifying functional elements in the human genome, but we still don't know much about their biological relevance," said NHGRI Director Francis S. Collins. "This parallel effort in the fruit fly and worm genomes will provide us with information about the functional landscape of two key model organisms, which should aid our efforts to tackle such questions in humans."
Piano and his research team at NYU's Center for Comparative Functional Genomics will develop an encyclopedia of a specific part of the genome of the round worm C. elegans called the 3'UTR. 3'UTR is a section of all animal genomes where special regulatory genes called microRNAs (miRNA) bind to messenger RNA (mRNA) and regulate whether a gene is to be expressed or not. Thus, the 3'UTR is the area where regulatory sequences act as switches to ultimately turn on or off the production of protein from a specific gene. This level of regulation is especially prevalent in embryogenesis. C. elegans is the first animal species whose genome was completely sequenced and a model organism to study how embryos develop.
Piano's earlier research predicted, using computational analysis, miRNA functions of C. elegans genes. This work was in collaboration with other members of the Center for Comparative Functional Genomics at NYU. The researchers found that one-third of C. elegans miRNAs target gene sets have related functions. That is, it appears that miRNAs can control groups of genes that work in a specific biological process. At least 10 percent of C. elegans genes are predicted miRNA targets.
To confirm the computational predictions, the NYU team developed a new in vivo analysis system comparing the expression of a reporter, green fluorescent protein (GFP) carrying target 3' UTRs with controls that did not carry the target 3'UTRs. The laboratory results confirmed the role of specific 3' UTRs in suppressing gene expression even more widely than predicted by the computational analysis, suggesting that 3' UTRs contain a largely unexplored universe for gene regulation.
New York University, located in the heart of Greenwich Village, was established in 1831 and is one of America's leading research universities and a member of the selective Association of American Universities. It is one of the largest private universities, it is a leader in attracting international students and scholars in the U.S, and it sends more students to study abroad than any other U.S. college or university. Through its 14 schools and colleges, NYU conducts research and provides education in the arts and sciences, law, medicine, business, dentistry, education, nursing, the cinematic and performing arts, music, public administration, social work, and continuing and professional studies, among other areas.
The National Institutes of Health -- "The Nation's Medical Research Agency" -- includes 27 institutes and centers, and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more, visit nih/.
Contact: James Devitt
New York University
The award to Piano, a professor in NYU's Biology Department, and the nine other researchers leading genome centers across the nation, will create a consortium of scientists who will collaborate in a four-year, $57 million scientific endeavor to understand every part of the genome needed for organisms to develop and thrive, as announced by NIH.
This four-year, multi-institutional collaborative genome project called "MOD-ENCODE" aims to identify all the functional elements (ENCODE) in the genomes of the model organisms (MOD) fruit fly and round worm Caenorhabditis elegans (C. elegans) as models to understand the functional elements and to shed light on the function of these elements in humans.
The effort will build upon the foundation laid by the ENCyclopedia of DNA Elements (ENCODE) consortium, which is preparing to build a comprehensive catalog, or "parts list," of all elements in the human genome crucial to biological function. In addition to genes that code for proteins, these functional elements include: non-protein-coding genes; regulatory elements involved in the control of gene transcription; and DNA sequences that mediate the structure and dynamics of chromosomes. For more information about NHGRI's ENCODE project, go to genome/ENCODE.
"We are making great strides in identifying functional elements in the human genome, but we still don't know much about their biological relevance," said NHGRI Director Francis S. Collins. "This parallel effort in the fruit fly and worm genomes will provide us with information about the functional landscape of two key model organisms, which should aid our efforts to tackle such questions in humans."
Piano and his research team at NYU's Center for Comparative Functional Genomics will develop an encyclopedia of a specific part of the genome of the round worm C. elegans called the 3'UTR. 3'UTR is a section of all animal genomes where special regulatory genes called microRNAs (miRNA) bind to messenger RNA (mRNA) and regulate whether a gene is to be expressed or not. Thus, the 3'UTR is the area where regulatory sequences act as switches to ultimately turn on or off the production of protein from a specific gene. This level of regulation is especially prevalent in embryogenesis. C. elegans is the first animal species whose genome was completely sequenced and a model organism to study how embryos develop.
Piano's earlier research predicted, using computational analysis, miRNA functions of C. elegans genes. This work was in collaboration with other members of the Center for Comparative Functional Genomics at NYU. The researchers found that one-third of C. elegans miRNAs target gene sets have related functions. That is, it appears that miRNAs can control groups of genes that work in a specific biological process. At least 10 percent of C. elegans genes are predicted miRNA targets.
To confirm the computational predictions, the NYU team developed a new in vivo analysis system comparing the expression of a reporter, green fluorescent protein (GFP) carrying target 3' UTRs with controls that did not carry the target 3'UTRs. The laboratory results confirmed the role of specific 3' UTRs in suppressing gene expression even more widely than predicted by the computational analysis, suggesting that 3' UTRs contain a largely unexplored universe for gene regulation.
New York University, located in the heart of Greenwich Village, was established in 1831 and is one of America's leading research universities and a member of the selective Association of American Universities. It is one of the largest private universities, it is a leader in attracting international students and scholars in the U.S, and it sends more students to study abroad than any other U.S. college or university. Through its 14 schools and colleges, NYU conducts research and provides education in the arts and sciences, law, medicine, business, dentistry, education, nursing, the cinematic and performing arts, music, public administration, social work, and continuing and professional studies, among other areas.
The National Institutes of Health -- "The Nation's Medical Research Agency" -- includes 27 institutes and centers, and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more, visit nih/.
Contact: James Devitt
New York University
понедельник, 25 апреля 2011 г.
Ingredient In Big Macs And Sodas Can Stabilize
The future of cancer detection and treatment may be in gold nanoparticles - tiny pieces of gold so small they cannot be seen by the naked eye. The potential of gold nanoparticles has been hindered by the difficulty of making them in a stable, nontoxic form that can be injected into a patient. New research at the University of Missouri-Columbia has found that a plant extract can be used to overcome this problem, creating a new type of gold nanoparticle that is stable and nontoxic and can be administered orally or injected.
Because gold nanoparticles have a high surface reactivity and biocompatible properties, they can be used for in vivo (inside the body) molecular imaging and therapeutic applications, including cancer detection and therapy. The promise of nanomedicine comes from the high surface area and size relationships of nanoparticles to cells, making it possible to target individual cells for diagnostic imaging or therapy. Gold nanoparticles could function as in vivo sensors, photoactive agents for optical imaging, drug carriers, contrast enhancers in computer tomography and X-ray absorbers in cancer therapy. Despite their promise, however, scientists have been plagued with problems making nontoxic gold nanoparticle constructs.
Kattesh Katti, professor of radiology and physics in MU's School of Medicine and College of Arts and Science, and director of the University of Missouri Cancer Nanotechnology Platform, worked with other MU scientists in the fields of physics, radiology, chemistry and veterinary medicine. The team tested plant extracts for their ability as nontoxic vehicles to stabilize and deliver nanoparticles for in vivo nanomedicinal applications. The researchers became interested in gum arabic, a substance taken from species of the acacia tree, because it is already used to stabilize everyday foods such as yogurt, Big Macs and soda. Gum arabic has unique structural features, including a highly branched polysaccharide structure consisting of a complex mixture of potassium, calcium and magnesium salts derived from arabic acid. The scientists found that gum arabic could be used to absorb and assimilate metals and create a "coating" that makes gold nanoparticles stable and nontoxic.
Katti and Raghuraman Kannan, assistant professor of radiology, have been collaborating on the development of biocompatible gold and silver nanoparticles for medical applications.
"We found that gum arabic can effectively 'lock' gold nanoparticles to produce nontoxic, nanoparticulate constructs that can be used for potential applications in nanomedicine," Katti said. "We have developed a new class of hybrid gold nanoparticles that are stable and can be administered either orally or through intravenous injection within the biological system."
This finding could lead to the development of readily injectable gold nanoparticles that are nontoxic and stable. Mansoor Amiji, professor of pharmaceutical sciences in the Bouve College of Health Sciences' School of Pharmacy and co-director of the Nanomedicine Education and Research Consortium at Northeastern University in Boston, said this represents a major scientific discovery that will initiate a new generation of biocompatible gold nanoparticles.
"The excellent in vivo stability profiles of such gold nanoconstructs will open up new pathways for the intratumoral delivery of gold nanoparticles in diagnostic imaging and therapeutic applications for cancer," Amiji said.
The new generation of trimeric amino acids peptides discovered by Katti in 1999 (referred to by Amijii as 'Katti Peptides') have provided a solid chemical platform and have become sources of a number of other discoveries. Their applications in the development of drugs for Wilscons' disease; their utility for the generation of a wide spectrum of metallic nanoparticles, including gold and silver; and as amphiphilic building blocks in a variety of drug designs were demonstrated by Katti, in collaboration with Kannan and MU's Stan Casteel.
A paper describing the team's recent findings, "Gum arabic as a Phytochemical Construct for the Stabilization of Gold Nanoparticles: In Vivo Pharmacokinetics and X-ray Contrast-Imaging Studies," was recently published in the February edition of the journal Small. Katti's collaborators on this paper include Casteel, Kannan, David Robertson, Evan Boote, Genevieve M. Fent, Kavita Katti, Vijaya Kattumauri and Meera Chandrasekhar.
This work has been supported with a grant from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program.
Contact: Katherine Kostiuk
University of Missouri-Columbia
Because gold nanoparticles have a high surface reactivity and biocompatible properties, they can be used for in vivo (inside the body) molecular imaging and therapeutic applications, including cancer detection and therapy. The promise of nanomedicine comes from the high surface area and size relationships of nanoparticles to cells, making it possible to target individual cells for diagnostic imaging or therapy. Gold nanoparticles could function as in vivo sensors, photoactive agents for optical imaging, drug carriers, contrast enhancers in computer tomography and X-ray absorbers in cancer therapy. Despite their promise, however, scientists have been plagued with problems making nontoxic gold nanoparticle constructs.
Kattesh Katti, professor of radiology and physics in MU's School of Medicine and College of Arts and Science, and director of the University of Missouri Cancer Nanotechnology Platform, worked with other MU scientists in the fields of physics, radiology, chemistry and veterinary medicine. The team tested plant extracts for their ability as nontoxic vehicles to stabilize and deliver nanoparticles for in vivo nanomedicinal applications. The researchers became interested in gum arabic, a substance taken from species of the acacia tree, because it is already used to stabilize everyday foods such as yogurt, Big Macs and soda. Gum arabic has unique structural features, including a highly branched polysaccharide structure consisting of a complex mixture of potassium, calcium and magnesium salts derived from arabic acid. The scientists found that gum arabic could be used to absorb and assimilate metals and create a "coating" that makes gold nanoparticles stable and nontoxic.
Katti and Raghuraman Kannan, assistant professor of radiology, have been collaborating on the development of biocompatible gold and silver nanoparticles for medical applications.
"We found that gum arabic can effectively 'lock' gold nanoparticles to produce nontoxic, nanoparticulate constructs that can be used for potential applications in nanomedicine," Katti said. "We have developed a new class of hybrid gold nanoparticles that are stable and can be administered either orally or through intravenous injection within the biological system."
This finding could lead to the development of readily injectable gold nanoparticles that are nontoxic and stable. Mansoor Amiji, professor of pharmaceutical sciences in the Bouve College of Health Sciences' School of Pharmacy and co-director of the Nanomedicine Education and Research Consortium at Northeastern University in Boston, said this represents a major scientific discovery that will initiate a new generation of biocompatible gold nanoparticles.
"The excellent in vivo stability profiles of such gold nanoconstructs will open up new pathways for the intratumoral delivery of gold nanoparticles in diagnostic imaging and therapeutic applications for cancer," Amiji said.
The new generation of trimeric amino acids peptides discovered by Katti in 1999 (referred to by Amijii as 'Katti Peptides') have provided a solid chemical platform and have become sources of a number of other discoveries. Their applications in the development of drugs for Wilscons' disease; their utility for the generation of a wide spectrum of metallic nanoparticles, including gold and silver; and as amphiphilic building blocks in a variety of drug designs were demonstrated by Katti, in collaboration with Kannan and MU's Stan Casteel.
A paper describing the team's recent findings, "Gum arabic as a Phytochemical Construct for the Stabilization of Gold Nanoparticles: In Vivo Pharmacokinetics and X-ray Contrast-Imaging Studies," was recently published in the February edition of the journal Small. Katti's collaborators on this paper include Casteel, Kannan, David Robertson, Evan Boote, Genevieve M. Fent, Kavita Katti, Vijaya Kattumauri and Meera Chandrasekhar.
This work has been supported with a grant from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program.
Contact: Katherine Kostiuk
University of Missouri-Columbia
воскресенье, 24 апреля 2011 г.
Successful Islet Cell Transplant Without Immunosuppressive Therapy In Mice With Type 1 Diabetes
Scientists at Weill Cornell Medical College may have reached a breakthrough in the search for a lasting cure for type 1 diabetes.
Reporting in the Feb. 20 issue of the Proceedings of the National Academy of Sciences, the team greatly boosted the number of immune T-cells able to shield transplanted pancreatic islet cells from attack by the immune system. Insulin-producing islet cells are deficient in type 1 diabetes.
"If we can replicate this in humans, we might someday do away with the lifelong use of powerful immunosuppressive drugs that patients must take after islet cell transplant -- drugs that we believe also do harm to islet cells over time," explains the study's senior author Dr. Manikkam Suthanthiran, chief of the Division of Nephrology and Hypertension at Weill Cornell Medical College and chief of the Department of Transplantation Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Type 1 diabetes is an inherited disorder in which the body's immune cells attack islet cells in the pancreas, reducing or eliminating the body's ability to produce the blood-sugar hormone. It is distinct from the much more common type 2 form of diabetes, where obesity and other factors cause a gradual decline in cells' sensitivity to insulin.
Scientists have sought to reverse type 1 diabetes by transplanting new islet cells. The procedure has met with some success -- in fact, Dr. Suthanthiran's team at NewYork-Presbyterian/Weill Cornell performed the first successful islet transplantation in the tri-state area in patients with type 1 diabetes in 2004.
However, problems remain. "To stave off the destruction of transplanted cells, patients must be placed on lifelong immunosuppressive therapy," Dr. Suthanthiran explains. "Besides having powerful side effects, we're learning that these drugs can be toxic to islet cells, too."
Now, an innovative biochemical manipulation of immune cells may get around that problem.
Working in collaboration with researchers at The Rockefeller University, the research team focused on immune system regulatory T-cells (T regs). These cells help the immune system decide which entities are "enemies" and which are "friendly" and should be left alone.
"Specifically, there are a subset of T-cells with cell-surface proteins CD4 and CD25, which are called natural regulatory T-cells," Dr. Suthanthiran explains. "These cells express a key factor called Foxp3, and the CD4+CD25+Foxp3+ regulatory T-cells suppress the runaway immune response to islet cells. Without Foxp3, the suppression of the islet destructive response cannot take place."
Unfortunately, Foxp3-positive T-cells make up a paltry 2 to 5 percent of the total T-cell population, so they have little impact in shielding transplanted islet cells from harm.
However, working with the standard mouse model for type 1 diabetes, the researchers were able to convert the much more common form of CD4+ CD25- T-cells into CD4+CD25+ T-cells that did express protective Foxp3.
"We did so by a two-pronged approach," Dr. Suthanthiran says. On the one hand, the research team exposed the much more common form of CD4+ CD25- T-cells to transforming growth factor-beta (TGF-b), which helps switch the T-cell over to a Foxp3 expressing cell.
But TGF-b on its own is too blunt an instrument.
"If we turn all of these T-cells into random immune suppressors, that could lead to more cancers and other problems," the researcher explains. "So, we used another immune system signaler, the dendritic cell, to target Foxp3 activity much more specifically and shield only the islet cells from immune system attack."
Study co-researcher Dr. Ralph Steinman of The Rockefeller University actually discovered the dendritic cell and its role in immune system signaling, and was instrumental in this research, Dr. Suthanthiran says. Dr. Steinman's group has shown that dendritic cells are highly efficient in turning on natural regulatory cells into islet protective cells.
"When CD4+ CD25- T-cells came into contact with both TGF-b and the specific antigen-presenting dendritic cells, they switched over to the immunosuppressive Foxp3 variety," he says. "The dendritic cells made sure that this protective immunosuppression was targeted to islet cells, specifically."
The result: successful islet transplantation in diabetic mice without any pharmacologic immunosuppression; the transplanted islet cells stayed healthy and produced insulin over the full nine weeks of the study.
And there was a bonus: "We also determined that this approach shields the pancreas' own islet cells from harm," the researcher says. "That's important, because newly diagnosed type 1 diabetes patients often have some percentage of working islet cells remaining. This strategy might protect those cells, as well as the transplanted cells."
According to Dr. Suthanthiran, there's no reason to believe this approach wouldn't also protect other types of transplanted cells or organs, including lung, kidney and hearts transplants.
"It's also important to note that we were treating established diabetes in this mouse model," Dr. Suthanthiran says. "Most of the success so far has been in preventing disease before it sets in, but this is akin to going into a house and putting out the fire after it has already started."
Of course, it remains to be seen if success in mice will translate to success in human type 1 diabetes. But Dr. Suthanthiran says he is optimistic.
"We want to create a transplant situation where we don't have to deliver any outside immunosuppressive drugs," he says. "That would truly be the best kind of cure."
This work was funded by the American Society of Transplantation, the Juvenile Diabetes Research Foundation and the U.S. National Institutes of Health.
Co-researchers include lead author Dr. Xunrong Luo, formerly at Weill Cornell Medical College, now at Northwestern University, Chicago; Dr. Hua Yang and Dr. Ruchuang Ding of Weill Cornell Medical College; Samantha L. Bailey and Kathryn Pothoven of Northwestern University; and Dr. Kristin V. Tarbell (co-lead author) and Dr. Ralph M. Steinman of The Rockefeller University, New York City.
Weill Cornell Medical College
Weill Cornell Medical College -- located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer and psychiatry -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. Weill Cornell Medical College is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., and most recently, the world's first clinical trial for gene therapy for Parkinson's disease. Weill Cornell's Physician Organization includes 650 clinical faculty, who provide the highest quality of care to their patients.
NewYork-Presbyterian Hospital
425 East 61st St., Fl. 7
New York, NY 10021
United States
nyp
Reporting in the Feb. 20 issue of the Proceedings of the National Academy of Sciences, the team greatly boosted the number of immune T-cells able to shield transplanted pancreatic islet cells from attack by the immune system. Insulin-producing islet cells are deficient in type 1 diabetes.
"If we can replicate this in humans, we might someday do away with the lifelong use of powerful immunosuppressive drugs that patients must take after islet cell transplant -- drugs that we believe also do harm to islet cells over time," explains the study's senior author Dr. Manikkam Suthanthiran, chief of the Division of Nephrology and Hypertension at Weill Cornell Medical College and chief of the Department of Transplantation Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.
Type 1 diabetes is an inherited disorder in which the body's immune cells attack islet cells in the pancreas, reducing or eliminating the body's ability to produce the blood-sugar hormone. It is distinct from the much more common type 2 form of diabetes, where obesity and other factors cause a gradual decline in cells' sensitivity to insulin.
Scientists have sought to reverse type 1 diabetes by transplanting new islet cells. The procedure has met with some success -- in fact, Dr. Suthanthiran's team at NewYork-Presbyterian/Weill Cornell performed the first successful islet transplantation in the tri-state area in patients with type 1 diabetes in 2004.
However, problems remain. "To stave off the destruction of transplanted cells, patients must be placed on lifelong immunosuppressive therapy," Dr. Suthanthiran explains. "Besides having powerful side effects, we're learning that these drugs can be toxic to islet cells, too."
Now, an innovative biochemical manipulation of immune cells may get around that problem.
Working in collaboration with researchers at The Rockefeller University, the research team focused on immune system regulatory T-cells (T regs). These cells help the immune system decide which entities are "enemies" and which are "friendly" and should be left alone.
"Specifically, there are a subset of T-cells with cell-surface proteins CD4 and CD25, which are called natural regulatory T-cells," Dr. Suthanthiran explains. "These cells express a key factor called Foxp3, and the CD4+CD25+Foxp3+ regulatory T-cells suppress the runaway immune response to islet cells. Without Foxp3, the suppression of the islet destructive response cannot take place."
Unfortunately, Foxp3-positive T-cells make up a paltry 2 to 5 percent of the total T-cell population, so they have little impact in shielding transplanted islet cells from harm.
However, working with the standard mouse model for type 1 diabetes, the researchers were able to convert the much more common form of CD4+ CD25- T-cells into CD4+CD25+ T-cells that did express protective Foxp3.
"We did so by a two-pronged approach," Dr. Suthanthiran says. On the one hand, the research team exposed the much more common form of CD4+ CD25- T-cells to transforming growth factor-beta (TGF-b), which helps switch the T-cell over to a Foxp3 expressing cell.
But TGF-b on its own is too blunt an instrument.
"If we turn all of these T-cells into random immune suppressors, that could lead to more cancers and other problems," the researcher explains. "So, we used another immune system signaler, the dendritic cell, to target Foxp3 activity much more specifically and shield only the islet cells from immune system attack."
Study co-researcher Dr. Ralph Steinman of The Rockefeller University actually discovered the dendritic cell and its role in immune system signaling, and was instrumental in this research, Dr. Suthanthiran says. Dr. Steinman's group has shown that dendritic cells are highly efficient in turning on natural regulatory cells into islet protective cells.
"When CD4+ CD25- T-cells came into contact with both TGF-b and the specific antigen-presenting dendritic cells, they switched over to the immunosuppressive Foxp3 variety," he says. "The dendritic cells made sure that this protective immunosuppression was targeted to islet cells, specifically."
The result: successful islet transplantation in diabetic mice without any pharmacologic immunosuppression; the transplanted islet cells stayed healthy and produced insulin over the full nine weeks of the study.
And there was a bonus: "We also determined that this approach shields the pancreas' own islet cells from harm," the researcher says. "That's important, because newly diagnosed type 1 diabetes patients often have some percentage of working islet cells remaining. This strategy might protect those cells, as well as the transplanted cells."
According to Dr. Suthanthiran, there's no reason to believe this approach wouldn't also protect other types of transplanted cells or organs, including lung, kidney and hearts transplants.
"It's also important to note that we were treating established diabetes in this mouse model," Dr. Suthanthiran says. "Most of the success so far has been in preventing disease before it sets in, but this is akin to going into a house and putting out the fire after it has already started."
Of course, it remains to be seen if success in mice will translate to success in human type 1 diabetes. But Dr. Suthanthiran says he is optimistic.
"We want to create a transplant situation where we don't have to deliver any outside immunosuppressive drugs," he says. "That would truly be the best kind of cure."
This work was funded by the American Society of Transplantation, the Juvenile Diabetes Research Foundation and the U.S. National Institutes of Health.
Co-researchers include lead author Dr. Xunrong Luo, formerly at Weill Cornell Medical College, now at Northwestern University, Chicago; Dr. Hua Yang and Dr. Ruchuang Ding of Weill Cornell Medical College; Samantha L. Bailey and Kathryn Pothoven of Northwestern University; and Dr. Kristin V. Tarbell (co-lead author) and Dr. Ralph M. Steinman of The Rockefeller University, New York City.
Weill Cornell Medical College
Weill Cornell Medical College -- located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer and psychiatry -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. Weill Cornell Medical College is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., and most recently, the world's first clinical trial for gene therapy for Parkinson's disease. Weill Cornell's Physician Organization includes 650 clinical faculty, who provide the highest quality of care to their patients.
NewYork-Presbyterian Hospital
425 East 61st St., Fl. 7
New York, NY 10021
United States
nyp
OHSU Studies Of Technology For Healthy Aging Get Boost
Oregon Health & Science University, with help from Intel Corp., is moving into the next phase of a research program developing and testing new technologies to address the challenge of aging successfully.
OHSU's Oregon Center for Aging & Technology (ORCATECH) is the first funded under a new program of Intel's Digital Health Group called the Behavioral Assessment and Intervention Commons, or BAIC. The academic-industrial alliance, worth about $1 million over the next year for ORCATECH, is aimed at initiating and accelerating research into behavioral markers of disease, such as changes in walking and performance on computer games, that eventually translate into health-related products and services.
ORCATECH director Jeffrey Kaye, M.D., in the Department of Neurology at the School of Medicine and the Department of Biomedical Engineering at the School of Science and Engineering, said the work with Intel will shore up a new model of evidence-based behavioral assessment that's been under development the last two years through ORCATECH.
ORCATECH, an interdisciplinary center at OHSU supported since 2004 by the National Institute on Aging, National Institutes of Health, focuses on the development and translation of basic social, behavioral and biological knowledge about aging independently using state-of-the-art technology and engineering. Its goal is to use unobtrusive, continuous, scaleable technologies to further evidence-based aging research and assure successful aging by helping elders retain independence, detecting early physical and mental decline, and helping caregivers such as family members provide the best possible, economically feasible care.
"This program is an important complement to our NIH-based studies of aging health outcomes, in that it will allow us to make significant progress in developing continuous assessment and in-home technologies that have clinical relevance," said Tamara Hayes, Ph.D., assistant professor of biomedical engineering, OHSU School of Science and Engineering, and the BAIC project's lead investigator. "Because of our complementary blend of clinical, basic science and engineering researchers, ORCATECH is particularly well poised to lead this field of research."
The BAIC represents not only a novel approach to care and to developing new scientific insights, but also a new form of academic and industry collaboration. It builds upon a seed grant awarded in 2002 by the Intel Research Council to ORCATECH investigator Misha Pavel, Ph.D., professor of biomedical engineering, OHSU School of Science & Engineering.
"Intel researchers have been working with OHSU from the onset to help invent and grow the field of behavioral markers," said Eric Dishman, general manager for Intel Health Research and Innovation. "The result is a unique melding of biomedicine, social science and technology employed in a new suite of innovative devices that will change the way patients are assessed for cognitive function and mobility. Long term, we hope these systems help prevent the loss of independence among seniors."
OHSU President Joseph E. Robertson Jr., M.D., M.B.A., said the work between Intel and the biomedical engineering and neurology faculty at OHSU's schools of Medicine and Science & Engineering reflects the power of coupling engineers with biomedical innovations.
"It offers a new model for OHSU's community partnerships and working with the region's high-technology leaders to improve the quality of care for the people of Oregon and beyond," he said.
The backbone of the BAIC effort is a "living laboratory," where the new monitoring technologies will be tested. This network of 20 to 30 elder-inhabited residences throughout the Portland area will be outfitted with a basic set of devices for continuous, remote assessment of activity and computer use, in which fluctuations can mean problems with cognition and mobility.
OHSU researchers will recruit participants ages 65 and older who live independently, without need for in-home nursing care or help with daily activities. Their homes will be outfitted with a suite of sensors for detecting aspects of daily living such as moving through the home, patterns of disrupted sleep, and regularity of medication-taking. In addition, the elders will carry devices to unobtrusively collect data about how their activity outside the home relates to their activity in the home.
If subjects are computer users, they may be asked to allow a computer monitoring system to collect data on their typing speed, the time they spend in applications, mouse movement activity and performance on research versions of computer games, such as FreeCell.
"Our recent preliminary studies have demonstrated the potential of these approaches to tracking cognitive performance," said Pavel, director of ORCATECH's Point of Care Lab, where many of these devices are developed and tested prior to their deployment in homes. "We foresee that further refinements of these methods will allow us to intervene and help elders maintain their cognitive abilities, much as physical exercise helps to maintain physical condition."
ORCATECH scientists in July presented research showing that a research version of FreeCell, a Solitaire-like computer game, when adapted with cognitive performance assessment algorithms, may distinguish between seniors with memory problems and cognitively healthy seniors. Another National Institute on Aging-funded project found that continuous, unobtrusive monitoring of in-home activity using the motion and door sensors may be a reliable way of assessing changes in motor behaviors that can occur with changes in memory.
"The growing convergence of in-home monitoring technologies, telemedicine and ubiquitous computing provides an opportunity to transform the outpatient model of clinical research such that data may be collected continuously, in real time, in a person's natural environment and securely transferred to investigators and research databases," said Daniel Dorsa, Ph.D., OHSU vice president for research.
Contact: Jonathan Modie
Oregon Health & Science University
OHSU's Oregon Center for Aging & Technology (ORCATECH) is the first funded under a new program of Intel's Digital Health Group called the Behavioral Assessment and Intervention Commons, or BAIC. The academic-industrial alliance, worth about $1 million over the next year for ORCATECH, is aimed at initiating and accelerating research into behavioral markers of disease, such as changes in walking and performance on computer games, that eventually translate into health-related products and services.
ORCATECH director Jeffrey Kaye, M.D., in the Department of Neurology at the School of Medicine and the Department of Biomedical Engineering at the School of Science and Engineering, said the work with Intel will shore up a new model of evidence-based behavioral assessment that's been under development the last two years through ORCATECH.
ORCATECH, an interdisciplinary center at OHSU supported since 2004 by the National Institute on Aging, National Institutes of Health, focuses on the development and translation of basic social, behavioral and biological knowledge about aging independently using state-of-the-art technology and engineering. Its goal is to use unobtrusive, continuous, scaleable technologies to further evidence-based aging research and assure successful aging by helping elders retain independence, detecting early physical and mental decline, and helping caregivers such as family members provide the best possible, economically feasible care.
"This program is an important complement to our NIH-based studies of aging health outcomes, in that it will allow us to make significant progress in developing continuous assessment and in-home technologies that have clinical relevance," said Tamara Hayes, Ph.D., assistant professor of biomedical engineering, OHSU School of Science and Engineering, and the BAIC project's lead investigator. "Because of our complementary blend of clinical, basic science and engineering researchers, ORCATECH is particularly well poised to lead this field of research."
The BAIC represents not only a novel approach to care and to developing new scientific insights, but also a new form of academic and industry collaboration. It builds upon a seed grant awarded in 2002 by the Intel Research Council to ORCATECH investigator Misha Pavel, Ph.D., professor of biomedical engineering, OHSU School of Science & Engineering.
"Intel researchers have been working with OHSU from the onset to help invent and grow the field of behavioral markers," said Eric Dishman, general manager for Intel Health Research and Innovation. "The result is a unique melding of biomedicine, social science and technology employed in a new suite of innovative devices that will change the way patients are assessed for cognitive function and mobility. Long term, we hope these systems help prevent the loss of independence among seniors."
OHSU President Joseph E. Robertson Jr., M.D., M.B.A., said the work between Intel and the biomedical engineering and neurology faculty at OHSU's schools of Medicine and Science & Engineering reflects the power of coupling engineers with biomedical innovations.
"It offers a new model for OHSU's community partnerships and working with the region's high-technology leaders to improve the quality of care for the people of Oregon and beyond," he said.
The backbone of the BAIC effort is a "living laboratory," where the new monitoring technologies will be tested. This network of 20 to 30 elder-inhabited residences throughout the Portland area will be outfitted with a basic set of devices for continuous, remote assessment of activity and computer use, in which fluctuations can mean problems with cognition and mobility.
OHSU researchers will recruit participants ages 65 and older who live independently, without need for in-home nursing care or help with daily activities. Their homes will be outfitted with a suite of sensors for detecting aspects of daily living such as moving through the home, patterns of disrupted sleep, and regularity of medication-taking. In addition, the elders will carry devices to unobtrusively collect data about how their activity outside the home relates to their activity in the home.
If subjects are computer users, they may be asked to allow a computer monitoring system to collect data on their typing speed, the time they spend in applications, mouse movement activity and performance on research versions of computer games, such as FreeCell.
"Our recent preliminary studies have demonstrated the potential of these approaches to tracking cognitive performance," said Pavel, director of ORCATECH's Point of Care Lab, where many of these devices are developed and tested prior to their deployment in homes. "We foresee that further refinements of these methods will allow us to intervene and help elders maintain their cognitive abilities, much as physical exercise helps to maintain physical condition."
ORCATECH scientists in July presented research showing that a research version of FreeCell, a Solitaire-like computer game, when adapted with cognitive performance assessment algorithms, may distinguish between seniors with memory problems and cognitively healthy seniors. Another National Institute on Aging-funded project found that continuous, unobtrusive monitoring of in-home activity using the motion and door sensors may be a reliable way of assessing changes in motor behaviors that can occur with changes in memory.
"The growing convergence of in-home monitoring technologies, telemedicine and ubiquitous computing provides an opportunity to transform the outpatient model of clinical research such that data may be collected continuously, in real time, in a person's natural environment and securely transferred to investigators and research databases," said Daniel Dorsa, Ph.D., OHSU vice president for research.
Contact: Jonathan Modie
Oregon Health & Science University
New Medicines Threatened By Credit Crunch
The global financial crisis could seriously delay the discovery and production of many new life-saving medicines, warns a major international conference today (Monday).
Investment into research for new drugs - which globally runs into the billions - is now seriously at threat as former investors in the drug companies shy away as a result of the economic meltdown.
Professor David Wield, Director of the Economic and Social Research Council's (ESRC) Edinburgh-based Innogen Centre, and chair of the 'Genomics and Society: Reinventing Life?' conference, delivered a stark warning prior to the gathering of over 200 experts at conference in London.
Professor Wield said: "Investing in biotech companies is now seen as risk taking, and will not be for the timid. What will happen to investment in biotech research if finance cannot even be found for relatively everyday expenses which are increasingly becoming more of a struggle?
"Drug discovery depends on long-term finance with high risk of failure - and lots of it. Financing of biotechnology companies hit $50bn in 2007. And overall, these biotechs only made profits for the very first time last year, amounting to $1bn on revenues of $59bn."
According to Professor Wield, in addition to the impact on the basic research performed at biotechnology companies, development of medicines by pharmaceutical companies has also been hit by the credit crunch. "Like many other sectors, the pharmaceutical industry has had tough times recently - there is seemingly no way to speed up and improve the drug discovery pipeline, and heavily increased R&D has not increased the number of new drugs."
"As a result, big companies have been laying-off staff and closing down research units, instead looking to biotechnology start-ups for new ideas," he added.
In recognition of the significant long term and immediate challenges faced by the pharmaceutical sector the UK Research Councils are working to help underpin future development of the sector for example to find new ways of enabling effective drug trials that enjoy public confidence; and building new research partnership with the sector.
This impact of the credit crunch on research into new medicines and treatments will be considered at the conference as part of a debate featuring two eminent economics experts, Professor Gary Pisano of Harvard University, and Professor William Lazonick of the University of Massachusetts Lowell. The session will be chaired by BBC business journalist, Simon Gompertz.
With so much of the life sciences already intertwined with our everyday life, further conference sessions will concentrate on whether society is keeping pace with advances in biology. These include issues surrounding the use and safekeeping of our personal biological information, the development of sustainable biofuels, and the creation - for stem cell research - of human-animal hybrids.
Other topics to be discussed range from the ethical impacts of emerging disciplines such as synthetic biology - which attempts to recreate living systems in the laboratory and may one day produce artificial life-forms - to the likely contributions the life sciences will make to global challenges such as food security and climate change.
The gathering is the annual conference of the ESRC's Genomics Network, and it brings together social and natural scientists with policymakers and commentators, from all over the globe. This year it has been organised by the network's Innogen centre, which is based at the University of Edinburgh and the Open University.
NOTES:
1. Genomics and Society: Reinventing Life? 9am - 5pm 27 October - 28 October: 2 Savoy Place, London WC2R 0BL
2. OUTLINE
(The full programme can be downloaded at genomicsandsociety/)
Monday
Welcome from Professor Charlie Jeffery, Chair of the ESRC Strategic Research Board
Keynote lecture by Professor Paul Rabinow, University of California at Berkeley on the implications of synthetic biology - including its potential to create 'artificial life'.
Sessions include:
safeguarding DNA databases
sustainable biofuel development
the use of human-animal hybrids in research
life sciences in developing countries
innovation in the pharmaceutical industry
synthetic biology
meet the authors: 'Genomes and What to Make of Them'
life sciences and the credit crunch
Tuesday
Keynote lecture from Professor Bartha Maria Knoppers, University of Montreal on the ethics of the use of the human genome.
The Knowledge Exchange - debates on (1) the regulation of stem cell therapies and (2) the importance of life sciences to national economies, job creation and sustainable development within the EU
Genomics Futures Panel - a discussion over the future roles for the life sciences in tackling major issues such as climate change, human diseases and food security.
Closing Keynote lecture from Dr Iain Gillespie, Head of Biotechnology Division, Organisation for Economic Cooperation and Development (OECD) on how policy can ensure genomics serves society.
3. The ESRC Genomics Network Launched in 2002 to examine the social and economic consequences surrounding the development and use of genomics, the Economic and Social Research Council (ESRC) Genomics Network is one of the ESRC's largest social science investments. The Network.consists of: Cesagen (Centre for Economic and Social Aspects of Genomics) a Cardiff-Lancaster collaboration led by Professor Ruth Chadwick; Egenis (ESRC Centre for Genomics in Society) headed by Professor John DuprГ© at Exeter; and Innogen (ESRC Centre for Social and Economic Research on Innovation in Genomics) - collaboration between the University of Edinburgh and the Open University, directed by Professor David Wield; and the ESRC Genomics Policy and Research Forum, led by Professor Steve Yearley, Professor of the Sociology of Scientific Knowledge at University of Edinburgh. genomicsnetwork.ac.uk/
4. The Economic and Social Research Council (ESRC) is the UK's largest funding agency for research and postgraduate training relating to social and economic issues. It supports independent, high quality research which impacts on business, the public sector and the third sector. The ESRC's planned total expenditure in 2008/09 is ВЈ203 million. At any one time the ESRC supports over 4,000 researchers and postgraduate students in academic institutions and research policy institutes. More at esrcsocietytoday.ac.uk/
Source: Kelly Barnett
Economic & Social Research Council
Investment into research for new drugs - which globally runs into the billions - is now seriously at threat as former investors in the drug companies shy away as a result of the economic meltdown.
Professor David Wield, Director of the Economic and Social Research Council's (ESRC) Edinburgh-based Innogen Centre, and chair of the 'Genomics and Society: Reinventing Life?' conference, delivered a stark warning prior to the gathering of over 200 experts at conference in London.
Professor Wield said: "Investing in biotech companies is now seen as risk taking, and will not be for the timid. What will happen to investment in biotech research if finance cannot even be found for relatively everyday expenses which are increasingly becoming more of a struggle?
"Drug discovery depends on long-term finance with high risk of failure - and lots of it. Financing of biotechnology companies hit $50bn in 2007. And overall, these biotechs only made profits for the very first time last year, amounting to $1bn on revenues of $59bn."
According to Professor Wield, in addition to the impact on the basic research performed at biotechnology companies, development of medicines by pharmaceutical companies has also been hit by the credit crunch. "Like many other sectors, the pharmaceutical industry has had tough times recently - there is seemingly no way to speed up and improve the drug discovery pipeline, and heavily increased R&D has not increased the number of new drugs."
"As a result, big companies have been laying-off staff and closing down research units, instead looking to biotechnology start-ups for new ideas," he added.
In recognition of the significant long term and immediate challenges faced by the pharmaceutical sector the UK Research Councils are working to help underpin future development of the sector for example to find new ways of enabling effective drug trials that enjoy public confidence; and building new research partnership with the sector.
This impact of the credit crunch on research into new medicines and treatments will be considered at the conference as part of a debate featuring two eminent economics experts, Professor Gary Pisano of Harvard University, and Professor William Lazonick of the University of Massachusetts Lowell. The session will be chaired by BBC business journalist, Simon Gompertz.
With so much of the life sciences already intertwined with our everyday life, further conference sessions will concentrate on whether society is keeping pace with advances in biology. These include issues surrounding the use and safekeeping of our personal biological information, the development of sustainable biofuels, and the creation - for stem cell research - of human-animal hybrids.
Other topics to be discussed range from the ethical impacts of emerging disciplines such as synthetic biology - which attempts to recreate living systems in the laboratory and may one day produce artificial life-forms - to the likely contributions the life sciences will make to global challenges such as food security and climate change.
The gathering is the annual conference of the ESRC's Genomics Network, and it brings together social and natural scientists with policymakers and commentators, from all over the globe. This year it has been organised by the network's Innogen centre, which is based at the University of Edinburgh and the Open University.
NOTES:
1. Genomics and Society: Reinventing Life? 9am - 5pm 27 October - 28 October: 2 Savoy Place, London WC2R 0BL
2. OUTLINE
(The full programme can be downloaded at genomicsandsociety/)
Monday
Welcome from Professor Charlie Jeffery, Chair of the ESRC Strategic Research Board
Keynote lecture by Professor Paul Rabinow, University of California at Berkeley on the implications of synthetic biology - including its potential to create 'artificial life'.
Sessions include:
safeguarding DNA databases
sustainable biofuel development
the use of human-animal hybrids in research
life sciences in developing countries
innovation in the pharmaceutical industry
synthetic biology
meet the authors: 'Genomes and What to Make of Them'
life sciences and the credit crunch
Tuesday
Keynote lecture from Professor Bartha Maria Knoppers, University of Montreal on the ethics of the use of the human genome.
The Knowledge Exchange - debates on (1) the regulation of stem cell therapies and (2) the importance of life sciences to national economies, job creation and sustainable development within the EU
Genomics Futures Panel - a discussion over the future roles for the life sciences in tackling major issues such as climate change, human diseases and food security.
Closing Keynote lecture from Dr Iain Gillespie, Head of Biotechnology Division, Organisation for Economic Cooperation and Development (OECD) on how policy can ensure genomics serves society.
3. The ESRC Genomics Network Launched in 2002 to examine the social and economic consequences surrounding the development and use of genomics, the Economic and Social Research Council (ESRC) Genomics Network is one of the ESRC's largest social science investments. The Network.consists of: Cesagen (Centre for Economic and Social Aspects of Genomics) a Cardiff-Lancaster collaboration led by Professor Ruth Chadwick; Egenis (ESRC Centre for Genomics in Society) headed by Professor John DuprГ© at Exeter; and Innogen (ESRC Centre for Social and Economic Research on Innovation in Genomics) - collaboration between the University of Edinburgh and the Open University, directed by Professor David Wield; and the ESRC Genomics Policy and Research Forum, led by Professor Steve Yearley, Professor of the Sociology of Scientific Knowledge at University of Edinburgh. genomicsnetwork.ac.uk/
4. The Economic and Social Research Council (ESRC) is the UK's largest funding agency for research and postgraduate training relating to social and economic issues. It supports independent, high quality research which impacts on business, the public sector and the third sector. The ESRC's planned total expenditure in 2008/09 is ВЈ203 million. At any one time the ESRC supports over 4,000 researchers and postgraduate students in academic institutions and research policy institutes. More at esrcsocietytoday.ac.uk/
Source: Kelly Barnett
Economic & Social Research Council
OCAST Funds OSU Projects With Commercial Viability
Three OSU researchers received grants totaling more than $240,000 last week from the Oklahoma Center for the Advancement of Science and Technology under its Oklahoma Applied Research Support program. The OARS program backs projects with the potential for producing a commercially successful product, according to the OCAST Web site. Funding is awarded to Oklahoma businesses, universities and non-profit organizations to accelerate the development of technology.
Hongbing Lu, professor in mechanical and aerospace engineering, received $83,168 for two years. Lu will develop multifunctional composites for the interior panels of aircraft using crosslinked aerogels. Noise reduction will be the primary goal of the project. Lu will also test the composite panels for thermal insulation performance and structural load carrying capabilities.
Aerogels are a super-lightweight, highly porous material that provides excellent thermal and acoustic insulation, Lu said. Chemically, however, aerogels are weakly connected, which makes them very fragile. Crosslinked aerogels, developed in 2002 by researchers at the Missouri University of Science and Technology (formerly the University of Missouri at Rolla), are a stronger, more ductile material with high levels of thermal and acoustic insulation.
Yu Mao, professor in biosystems and agricultural engineering, received $90,000 for two years. Mao is working to develop a biosensor that will detect objects like DNA, nerve agents and pesticides. Mao said this is a fundamental project that will be achieved by transferring chemical functionalities and bio molecules to carbon nanotubes.
Janet Cole, professor of horticulture and landscape architecture, received $66,941 for two years. Cole will investigate the potential of using cottonseed and canola meal, waste products from the production of cooking oils, as organic fertilizers for landscape planting. While the meal is currently used in the production of animal feed, Cole said excess meal could potentially end up in landfills. In addition to reducing this waste, the project could reduce the costs associated with fertilizer production by reducing the amount of petroleum used in fertilizers.
For more information on OSU research, visit vpr.okstate/.
Source: Kelly Green
Oklahoma State University
Hongbing Lu, professor in mechanical and aerospace engineering, received $83,168 for two years. Lu will develop multifunctional composites for the interior panels of aircraft using crosslinked aerogels. Noise reduction will be the primary goal of the project. Lu will also test the composite panels for thermal insulation performance and structural load carrying capabilities.
Aerogels are a super-lightweight, highly porous material that provides excellent thermal and acoustic insulation, Lu said. Chemically, however, aerogels are weakly connected, which makes them very fragile. Crosslinked aerogels, developed in 2002 by researchers at the Missouri University of Science and Technology (formerly the University of Missouri at Rolla), are a stronger, more ductile material with high levels of thermal and acoustic insulation.
Yu Mao, professor in biosystems and agricultural engineering, received $90,000 for two years. Mao is working to develop a biosensor that will detect objects like DNA, nerve agents and pesticides. Mao said this is a fundamental project that will be achieved by transferring chemical functionalities and bio molecules to carbon nanotubes.
Janet Cole, professor of horticulture and landscape architecture, received $66,941 for two years. Cole will investigate the potential of using cottonseed and canola meal, waste products from the production of cooking oils, as organic fertilizers for landscape planting. While the meal is currently used in the production of animal feed, Cole said excess meal could potentially end up in landfills. In addition to reducing this waste, the project could reduce the costs associated with fertilizer production by reducing the amount of petroleum used in fertilizers.
For more information on OSU research, visit vpr.okstate/.
Source: Kelly Green
Oklahoma State University
Learning From Songbird's Strategy For Changing Its Tune May Aid Rehab Efforts
It takes songbirds and baseball pitchers thousands of repetitions - a choreography of many muscle movements - to develop an irresistible trill or a killer slider. Now, scientists have discovered that the male Bengalese finch uses a simple mental computation and an uncanny memory to create its near-perfect mate-catching melody - a finding that could have implications for rehabilitating people with neuromuscular diseases and injuries.
Young male Bengalese finches practice their boisterous mating song hundreds of times a day, comparing their melody to the songs of their tutors. By the time they are adults, they have zeroed in on a "successful" pitch for each note in their song. But throughout life they continuously monitor their tune, working to maintain it in the face of such factors as aging, hormone levels, muscular injuries, and illness.
In their study, the UCSF neuroscientists explored the way in which the songbirds learn to perfect and maintain their song, a model of how one learns - and might relearn - fine motor skills when provided only simple reinforcement signals of success or failure.
In a series of experiments, they exposed the singing birds to a sound they did not like at the precise moment they were uttering a specific note, or syllable. After many exposures, the birds learned to alter the pitch of that syllable to avoid prompting the sound. But it was the way in which they did this that was remarkable.
The finches learned to change the pitch of a single note by computing the average pitch of hundreds of what they perceived as successful performances of that note - when they avoided hearing the unpleasant sound. The mental computation required the birds' brains to remember every slight change in pitch of a single syllable sung perhaps 500 times in a day.
"We were very surprised that the brain can direct so complex a behavioral change with such a simple type of computation," said the lead author of the paper, Jonathan Charlesworth, a UCSF PhD candidate in neuroscience in the lab of senior author Michael Brainard, PhD, associate professor of physiology.
The finding suggests "it might be possible to guide a damaged nervous system to recovery using only a simple automated/computerized system that emits simple instructive signals," said Charlesworth. "Given that the averaging rule was true even for subtle details of song, an automated therapeutic strategy could help people regain the intricate details of fine motor skills like playing the piano, articulating speech, or dancing."
The phenomenon may explain how people learn to produce accents or subtle vocal and facial cues: a tilt of the head when we disagree versus the slight nod when we are in accord, Charlesworth said.
The research is reported as an Advance Online Publication this week (posted January 30, 2011) by the journal Nature Neuroscience and will appear later in the journal's print addition.
For the study, the scientists developed a computer program that recognized the pitch of a single syllable each time a bird sang it. The computer was able to trigger a mildly disruptive short burst of sound at a specific time within that note - with a precision of about 1/100th of a second.
In one set of experiments, the computer program issued the short sound burst whenever the bird sang the target syllable at a pitch below a certain threshold. Over the course of several hundred trials, the birds learned to change their tune enough to avoid the noise about 80 percent of the time. Not every "successful" new pitch was the same; they didn't have to be. They just had to be above the key threshold.
The researchers also presented the singers with another, more difficult task. They programmed the computer to measure the pitch both near the beginning and the end of a single syllable. The computer only triggered white noise after the second measurement, and, critically, only if the bird sang the first part of the syllable below a certain threshold and the second part above a similar threshold.
The scientists found that the birds learned to avoid the noise by making a more pronounced "swoop" of sound - starting lower than normal and ending higher than normal. This showed that the birds were able to keep track of the pitch both at the beginning and the end of a single tenth-of-a-second syllable.
"This precision confirms the view that we learn not only in response to external stimuli, but through the capacity for variation in our actions," Brainard said. The nervous system, he said, is constantly introducing variations into our actions and paying very close attention to the consequences of those variations.
"Even Michael Jordan was unable to shoot a free throw the same way each time, instead exhibiting subtle variation that resulted in many baskets but a few misses," said Charlesworth. "This variation, while causing occasional misses, can be productive by allowing for learning in the case of changes to our body or environment."
The experiments indicate, he said, that "even the very subtle variations that you might have thought were irrelevant, such as our annoying inability to throw a dart or break open a billiards rack the same way each time, can play a crucial role in shaping how we learn."
The development of new behavior is akin to Darwinian evolution, but on a very short time scale, said Brainard. The bird creates a reservoir of varying behaviors - analogous to genetic variation - in response to changes in its environment. The environment then selects for a specific new behavior - the new pitch - from the range of available variation.
As a result of the variation and selection, the bird learns to express a new adaptive behavior. The development of new behavior can have "tag-along" consequences, producing new behavior that has no adaptive benefit, he said. Influential behavioral scientist B.F. Skinner showed decades ago that pigeons randomly rewarded with food learned to associate the reward with whatever they were doing at the time - say fluffing their feathers. They then fluffed their feathers frequently, said Brainard, in hopes of summoning a reward.
Charlesworth and Brainard cited the well-known superstitious behavior of baseball players as an example of this tag-along potential in people. Presumably, a coach's habit of leaving his left shoe untied, or a pitcher always wearing a garnet ring stemmed from winning some key game at a time when they happened to be shoelace-challenged or bejeweled. But don't try to explain to the coach or pitcher that there is no connection between the loose shoelaces or the bling.
The researchers now plan to study the brain regions associated with bird song learning, with hopes of finding how neurons generate variation in behavior and keep precise track of performance, as well as compute the averaging calculation that underlies learning.
Notes:
Co-authors on the paper are Evren Tumer, PhD, a postdoctoral scientist in Brainard's lab at the time of the research; and Timothy Warren, a PhD candidate in the lab.
Funding support for the research came from the National Institutes of Health and the National Science Foundation.
Source:
Jennifer O'Brien
University of California - San Francisco
Young male Bengalese finches practice their boisterous mating song hundreds of times a day, comparing their melody to the songs of their tutors. By the time they are adults, they have zeroed in on a "successful" pitch for each note in their song. But throughout life they continuously monitor their tune, working to maintain it in the face of such factors as aging, hormone levels, muscular injuries, and illness.
In their study, the UCSF neuroscientists explored the way in which the songbirds learn to perfect and maintain their song, a model of how one learns - and might relearn - fine motor skills when provided only simple reinforcement signals of success or failure.
In a series of experiments, they exposed the singing birds to a sound they did not like at the precise moment they were uttering a specific note, or syllable. After many exposures, the birds learned to alter the pitch of that syllable to avoid prompting the sound. But it was the way in which they did this that was remarkable.
The finches learned to change the pitch of a single note by computing the average pitch of hundreds of what they perceived as successful performances of that note - when they avoided hearing the unpleasant sound. The mental computation required the birds' brains to remember every slight change in pitch of a single syllable sung perhaps 500 times in a day.
"We were very surprised that the brain can direct so complex a behavioral change with such a simple type of computation," said the lead author of the paper, Jonathan Charlesworth, a UCSF PhD candidate in neuroscience in the lab of senior author Michael Brainard, PhD, associate professor of physiology.
The finding suggests "it might be possible to guide a damaged nervous system to recovery using only a simple automated/computerized system that emits simple instructive signals," said Charlesworth. "Given that the averaging rule was true even for subtle details of song, an automated therapeutic strategy could help people regain the intricate details of fine motor skills like playing the piano, articulating speech, or dancing."
The phenomenon may explain how people learn to produce accents or subtle vocal and facial cues: a tilt of the head when we disagree versus the slight nod when we are in accord, Charlesworth said.
The research is reported as an Advance Online Publication this week (posted January 30, 2011) by the journal Nature Neuroscience and will appear later in the journal's print addition.
For the study, the scientists developed a computer program that recognized the pitch of a single syllable each time a bird sang it. The computer was able to trigger a mildly disruptive short burst of sound at a specific time within that note - with a precision of about 1/100th of a second.
In one set of experiments, the computer program issued the short sound burst whenever the bird sang the target syllable at a pitch below a certain threshold. Over the course of several hundred trials, the birds learned to change their tune enough to avoid the noise about 80 percent of the time. Not every "successful" new pitch was the same; they didn't have to be. They just had to be above the key threshold.
The researchers also presented the singers with another, more difficult task. They programmed the computer to measure the pitch both near the beginning and the end of a single syllable. The computer only triggered white noise after the second measurement, and, critically, only if the bird sang the first part of the syllable below a certain threshold and the second part above a similar threshold.
The scientists found that the birds learned to avoid the noise by making a more pronounced "swoop" of sound - starting lower than normal and ending higher than normal. This showed that the birds were able to keep track of the pitch both at the beginning and the end of a single tenth-of-a-second syllable.
"This precision confirms the view that we learn not only in response to external stimuli, but through the capacity for variation in our actions," Brainard said. The nervous system, he said, is constantly introducing variations into our actions and paying very close attention to the consequences of those variations.
"Even Michael Jordan was unable to shoot a free throw the same way each time, instead exhibiting subtle variation that resulted in many baskets but a few misses," said Charlesworth. "This variation, while causing occasional misses, can be productive by allowing for learning in the case of changes to our body or environment."
The experiments indicate, he said, that "even the very subtle variations that you might have thought were irrelevant, such as our annoying inability to throw a dart or break open a billiards rack the same way each time, can play a crucial role in shaping how we learn."
The development of new behavior is akin to Darwinian evolution, but on a very short time scale, said Brainard. The bird creates a reservoir of varying behaviors - analogous to genetic variation - in response to changes in its environment. The environment then selects for a specific new behavior - the new pitch - from the range of available variation.
As a result of the variation and selection, the bird learns to express a new adaptive behavior. The development of new behavior can have "tag-along" consequences, producing new behavior that has no adaptive benefit, he said. Influential behavioral scientist B.F. Skinner showed decades ago that pigeons randomly rewarded with food learned to associate the reward with whatever they were doing at the time - say fluffing their feathers. They then fluffed their feathers frequently, said Brainard, in hopes of summoning a reward.
Charlesworth and Brainard cited the well-known superstitious behavior of baseball players as an example of this tag-along potential in people. Presumably, a coach's habit of leaving his left shoe untied, or a pitcher always wearing a garnet ring stemmed from winning some key game at a time when they happened to be shoelace-challenged or bejeweled. But don't try to explain to the coach or pitcher that there is no connection between the loose shoelaces or the bling.
The researchers now plan to study the brain regions associated with bird song learning, with hopes of finding how neurons generate variation in behavior and keep precise track of performance, as well as compute the averaging calculation that underlies learning.
Notes:
Co-authors on the paper are Evren Tumer, PhD, a postdoctoral scientist in Brainard's lab at the time of the research; and Timothy Warren, a PhD candidate in the lab.
Funding support for the research came from the National Institutes of Health and the National Science Foundation.
Source:
Jennifer O'Brien
University of California - San Francisco
Annual Symposium On Science, Technology And Values To Discuss "Topics In Bioethics," April 25-26
The College of Arts and Letters at Stevens Institute of Technology will host an annual symposium that will bring together scholars from around the world to discuss various issues at the intersection of science, technology, and values. It will provide a unique possibility for substantial dialogue between humanists, scientists, engineers, artists and the world of business. This year's conference, which is being organized by the Program in Philosophy and co-sponsored by the Howe School of Technology Management and The Center for Science Writings, will have as its theme "Topics in Bioethics."
The event will take place April 25 -26, 2008 at The Babbio Center, located at 6th and River Streets on the Stevens campus in Hoboken, N.J. The symposium will begin with a keynote panel that includes Robert P. George, McCormick Professor of Jurisprudence at Princeton University and member of the President's Council on Bioethics, and Rosamond Rhodes, Professor of Bio-medical Ethics in the Department of Medical Education at Mt. Sinai Medical Center in New York.
The college is currently accepting paper proposals for the second day of sessions. Submissions are welcome from across disciplines and fields, including, but not limited to: bio-ethics, bio-technology, green engineering, technology and the arts, globalization and technology, risk assessment, values and medicine, etc.
All are welcome. For more information about the program and registration, please visit: stevens/cal
About Stevens Institute of Technology
Founded in 1870, Stevens Institute of Technology is one of the leading technological universities in the world dedicated to learning and research. Through its broad-based curricula, nurturing of creative inventiveness, and cross disciplinary research, the Institute is at the forefront of global challenges in engineering, science, and technology management. Partnerships and collaboration between, and among, business, industry, government and other universities contribute to the enriched environment of the Institute. A new model for technology commercialization in academe, known as Technogenesis®, involves external partners in launching business enterprises to create broad opportunities and shared value. Stevens offers baccalaureates, master's and doctoral degrees in engineering, science, computer science and management, in addition to a baccalaureate degree in the humanities and liberal arts, and in business and technology. The university has a total enrollment of 2,040 undergraduate and 3,085 graduate students, and a worldwide online enrollment of 2,250, with about 250 full-time faculty. Stevens' graduate programs have attracted international participation from China, India, Southeast Asia, Europe and Latin America. Additional information may be obtained from its web page at stevens/.
Source: Patrick A. Berzinski
Stevens Institute of Technology
The event will take place April 25 -26, 2008 at The Babbio Center, located at 6th and River Streets on the Stevens campus in Hoboken, N.J. The symposium will begin with a keynote panel that includes Robert P. George, McCormick Professor of Jurisprudence at Princeton University and member of the President's Council on Bioethics, and Rosamond Rhodes, Professor of Bio-medical Ethics in the Department of Medical Education at Mt. Sinai Medical Center in New York.
The college is currently accepting paper proposals for the second day of sessions. Submissions are welcome from across disciplines and fields, including, but not limited to: bio-ethics, bio-technology, green engineering, technology and the arts, globalization and technology, risk assessment, values and medicine, etc.
All are welcome. For more information about the program and registration, please visit: stevens/cal
About Stevens Institute of Technology
Founded in 1870, Stevens Institute of Technology is one of the leading technological universities in the world dedicated to learning and research. Through its broad-based curricula, nurturing of creative inventiveness, and cross disciplinary research, the Institute is at the forefront of global challenges in engineering, science, and technology management. Partnerships and collaboration between, and among, business, industry, government and other universities contribute to the enriched environment of the Institute. A new model for technology commercialization in academe, known as Technogenesis®, involves external partners in launching business enterprises to create broad opportunities and shared value. Stevens offers baccalaureates, master's and doctoral degrees in engineering, science, computer science and management, in addition to a baccalaureate degree in the humanities and liberal arts, and in business and technology. The university has a total enrollment of 2,040 undergraduate and 3,085 graduate students, and a worldwide online enrollment of 2,250, with about 250 full-time faculty. Stevens' graduate programs have attracted international participation from China, India, Southeast Asia, Europe and Latin America. Additional information may be obtained from its web page at stevens/.
Source: Patrick A. Berzinski
Stevens Institute of Technology
Photosynthesizing Bacteria With A Day-Nght Cycle Contain Rare Chromosome
Researchers sequencing the DNA of blue-green algae found a linear chromosome harboring genes important for producing biofuels. Simultaneously analyzing the complement of proteins revealed more genes on the linear and the typical circular chromosomes then they'd have found with DNA sequencing alone.
The team reported the cyanobacterium Cyanothece 51142's genome the week of September 15 in the Proceedings of the National Academy of Sciences Early Edition. Overlaying protein data let the researchers pinpoint about 16 percent more genes than by DNA sequencing alone. The collaboration included a proteomics team from the Department of Energy's Pacific Northwest National Laboratory, a gene sequencing team from the Washington University Genome Sequencing Center, and researchers from Washington University, Saint Louis University, and Purdue University.
"This is the first time anything like this has been found in photosynthetic bacteria. It's extremely rare for bacteria to have a linear chromosome," said team leader Himadri Pakrasi from WUSTL. "Nearly 100 percent of them do not."
Cyanobacteria are unique among bacteria because they seem part plant-like and part microbe-like. They use the sun's energy to make sugar via photosynthesis like plants do. And like bacteria, Cyanothece 51142 has other key life-sustaining functions, such as doctoring atmospheric nitrogen so other species can use it. This so-called nitrogen fixation is performed by a handful of bacterial species in water and soil. Cyanothece also makes ethanol and hydrogen, activities that drew the attention of the DOE and others looking for new ways to make fuel.
But unlike most bacteria, Cyanothece has a day-night schedule for performing work. It makes sugar in the daylight, but then spends its nights breaking down that sugar to fix nitrogen and to produce different compounds. And bacteria generally store their DNA in circular chromosomes. Linear chromosomes are generally found in more complex creatures such as plants and animals.
Photosynthesis and nitrogen fixation are incompatible, leading this microbe to separate the activities both physically within the cell and temporally, via night and day. While not incompatible, scientists sequencing DNA and those identifying proteins often do their work in separate groups as well.
Proteomics analysis examines almost the whole complement of proteins in a cell, but requires a gene sequence with which to pair up protein shards for identification. On the other hand, DNA sequencing can't always identify potential genes or unmask which of those really function, and could benefit from knowing which proteins the cell actually makes.
Instead of waiting on one analysis to do the other, the collaborators simultaneously sequenced the bacteria's DNA and determined proteins that the microbe produced at different times of its life cycle. They then compared the information to determine which of the DNA sequences that looked like genes actually made proteins. In this way, they could better determine where genes lie along the length of its genome, as well as find ones that might otherwise be missed.
"This was an excellent example of using proteomics to guide initial genomic annotation," said protein chemist Jon Jacobs of PNNL. "We're helping to set a precedent if we can do the proteomics work while they're doing the genomics work."
Overall, Cyanothece 51142 carries one large circular chromosome and four small chromosomes called plasmids, and the linear one. On these, the team found 2,735 genes that looked like genes in other organisms, suggesting they are actual proteins. One important finding was that the unexpected linear chromosome was more than just a pretty face. It contained the only copy of a key protein that lets the bugs produce lactate, called lactate dehydrogenase, during fermentation.
DNA sequencing revealed the linear chromosome to be 430 kilobases long and contain a cluster of nine genes that code for other enzymes involved in pyruvate metabolism. These allow Cyanothece 51142 to make ethanol, hydrogen, acetate, and other compounds. Oddly, the linear chromosome was missing some features that linear chromosomes in complex organisms display. Without obvious protective caps called telomeres, for example, Cyanothece must use an unidentified way to preserve the integrity of its linear chromosomes when it reproduces.
In addition to the 2,700-plus real genes, the DNA sequence contained more than 2,500 would-be genes. These had architectural features common to genes but didn't look like recognized genes from other organisms. The team found about 500 of these that produced proteins, so the researchers re-classified these genes as functioning. Lastly, the scientists also found 38 proteins out of another 12,000 sequences that were gene longshots.
"Using proteomics, we always suspected we'd be able to detect genes not called out in the genome, but it was surprising how many hypothetical genes actually produced proteins," said Jacobs.
For the next round, additional DOE resources will enable the sequencing and analysis of the genomes of six other Cyanothece strains in a quest to find the best one to produce hydrogen.
"The goal is to find the hydrogen-producing workhorse of these seven," Pakrasi said. "Work is ongoing, and I expect in a year or so we will learn a lot more."
Reference: E.A. Welsh, M. Liberton, J. Stöckel, T. Loh, T. Elvitigala, C. Wang, A. Wollam, R.S. Fulton, S.W. Clifton, J.M. Jacobs, R. Aurora, B.K. Ghosh, L.A. Sherman, R.D. Smith, R.K. Wilson and H.B. Pakrasi, The genome of Cyanothece 51142, a unicellular diazotrophic cyanobacterium that is important in the marine nitrogen cycle, Proc Natl Acad Sci U S A, Early Edition online the week of September 15-19, 2008, DOI 10.1073_pnas.0805418105 (pnas/).
This work was supported by the Department of Energy's Basic Energy Sciences, part of the Office of Science, and the Danforth Foundation at Washington University. This work is also part of the Membrane Biology Scientific Grand Challenge project at EMSL.
EMSL, the Environmental Molecular Sciences Laboratory, is a national scientific user facility sponsored by the Department of Energy's Office of Science, Biological and Environmental Research program that is located at Pacific Northwest National Laboratory. EMSL offers an open, collaborative environment for scientific discovery to researchers around the world. EMSL's technical experts and suite of custom and advanced instruments are unmatched. Its integrated computational and experimental capabilities enable researchers to realize fundamental scientific insights and create new technologies.
Pacific Northwest National Laboratory is a Department of Energy Office of Science national laboratory where interdisciplinary teams advance science and technology and deliver solutions to America's most intractable problems in energy, national security and the environment. PNNL employs 4,000 staff, has a $855 million annual budget, and has been managed by Ohio-based Battelle since the lab's inception in 1965.
Source: Mary Beckman
DOE/Pacific Northwest National Laboratory
The team reported the cyanobacterium Cyanothece 51142's genome the week of September 15 in the Proceedings of the National Academy of Sciences Early Edition. Overlaying protein data let the researchers pinpoint about 16 percent more genes than by DNA sequencing alone. The collaboration included a proteomics team from the Department of Energy's Pacific Northwest National Laboratory, a gene sequencing team from the Washington University Genome Sequencing Center, and researchers from Washington University, Saint Louis University, and Purdue University.
"This is the first time anything like this has been found in photosynthetic bacteria. It's extremely rare for bacteria to have a linear chromosome," said team leader Himadri Pakrasi from WUSTL. "Nearly 100 percent of them do not."
Cyanobacteria are unique among bacteria because they seem part plant-like and part microbe-like. They use the sun's energy to make sugar via photosynthesis like plants do. And like bacteria, Cyanothece 51142 has other key life-sustaining functions, such as doctoring atmospheric nitrogen so other species can use it. This so-called nitrogen fixation is performed by a handful of bacterial species in water and soil. Cyanothece also makes ethanol and hydrogen, activities that drew the attention of the DOE and others looking for new ways to make fuel.
But unlike most bacteria, Cyanothece has a day-night schedule for performing work. It makes sugar in the daylight, but then spends its nights breaking down that sugar to fix nitrogen and to produce different compounds. And bacteria generally store their DNA in circular chromosomes. Linear chromosomes are generally found in more complex creatures such as plants and animals.
Photosynthesis and nitrogen fixation are incompatible, leading this microbe to separate the activities both physically within the cell and temporally, via night and day. While not incompatible, scientists sequencing DNA and those identifying proteins often do their work in separate groups as well.
Proteomics analysis examines almost the whole complement of proteins in a cell, but requires a gene sequence with which to pair up protein shards for identification. On the other hand, DNA sequencing can't always identify potential genes or unmask which of those really function, and could benefit from knowing which proteins the cell actually makes.
Instead of waiting on one analysis to do the other, the collaborators simultaneously sequenced the bacteria's DNA and determined proteins that the microbe produced at different times of its life cycle. They then compared the information to determine which of the DNA sequences that looked like genes actually made proteins. In this way, they could better determine where genes lie along the length of its genome, as well as find ones that might otherwise be missed.
"This was an excellent example of using proteomics to guide initial genomic annotation," said protein chemist Jon Jacobs of PNNL. "We're helping to set a precedent if we can do the proteomics work while they're doing the genomics work."
Overall, Cyanothece 51142 carries one large circular chromosome and four small chromosomes called plasmids, and the linear one. On these, the team found 2,735 genes that looked like genes in other organisms, suggesting they are actual proteins. One important finding was that the unexpected linear chromosome was more than just a pretty face. It contained the only copy of a key protein that lets the bugs produce lactate, called lactate dehydrogenase, during fermentation.
DNA sequencing revealed the linear chromosome to be 430 kilobases long and contain a cluster of nine genes that code for other enzymes involved in pyruvate metabolism. These allow Cyanothece 51142 to make ethanol, hydrogen, acetate, and other compounds. Oddly, the linear chromosome was missing some features that linear chromosomes in complex organisms display. Without obvious protective caps called telomeres, for example, Cyanothece must use an unidentified way to preserve the integrity of its linear chromosomes when it reproduces.
In addition to the 2,700-plus real genes, the DNA sequence contained more than 2,500 would-be genes. These had architectural features common to genes but didn't look like recognized genes from other organisms. The team found about 500 of these that produced proteins, so the researchers re-classified these genes as functioning. Lastly, the scientists also found 38 proteins out of another 12,000 sequences that were gene longshots.
"Using proteomics, we always suspected we'd be able to detect genes not called out in the genome, but it was surprising how many hypothetical genes actually produced proteins," said Jacobs.
For the next round, additional DOE resources will enable the sequencing and analysis of the genomes of six other Cyanothece strains in a quest to find the best one to produce hydrogen.
"The goal is to find the hydrogen-producing workhorse of these seven," Pakrasi said. "Work is ongoing, and I expect in a year or so we will learn a lot more."
Reference: E.A. Welsh, M. Liberton, J. Stöckel, T. Loh, T. Elvitigala, C. Wang, A. Wollam, R.S. Fulton, S.W. Clifton, J.M. Jacobs, R. Aurora, B.K. Ghosh, L.A. Sherman, R.D. Smith, R.K. Wilson and H.B. Pakrasi, The genome of Cyanothece 51142, a unicellular diazotrophic cyanobacterium that is important in the marine nitrogen cycle, Proc Natl Acad Sci U S A, Early Edition online the week of September 15-19, 2008, DOI 10.1073_pnas.0805418105 (pnas/).
This work was supported by the Department of Energy's Basic Energy Sciences, part of the Office of Science, and the Danforth Foundation at Washington University. This work is also part of the Membrane Biology Scientific Grand Challenge project at EMSL.
EMSL, the Environmental Molecular Sciences Laboratory, is a national scientific user facility sponsored by the Department of Energy's Office of Science, Biological and Environmental Research program that is located at Pacific Northwest National Laboratory. EMSL offers an open, collaborative environment for scientific discovery to researchers around the world. EMSL's technical experts and suite of custom and advanced instruments are unmatched. Its integrated computational and experimental capabilities enable researchers to realize fundamental scientific insights and create new technologies.
Pacific Northwest National Laboratory is a Department of Energy Office of Science national laboratory where interdisciplinary teams advance science and technology and deliver solutions to America's most intractable problems in energy, national security and the environment. PNNL employs 4,000 staff, has a $855 million annual budget, and has been managed by Ohio-based Battelle since the lab's inception in 1965.
Source: Mary Beckman
DOE/Pacific Northwest National Laboratory
Schepens scientists regenerate optic nerve for the first time
For the first time, scientists have regenerated a damaged optic nerve -- from the eye to the brain. This achievement, which occurred in laboratory mice and is described in the March 1, 2005 issue of the Journal of Cell Science, holds great promise for victims of diseases that destroy the optic nerve, and for sufferers of central nervous system injuries. "For us, this is a dream becoming reality," says Dr. Dong Feng Chen, lead author of the study, assistant scientist at Schepens Eye Research Institute and an assistant professor of ophthalmology at Harvard Medical School. "This is the closest science has come to regenerating so many nerve fibers over a long distance to reach their targets and to repair a nerve previously considered irreparably damaged."
This research, which has been supported in part by grants from the National Institutes of Health, the Department of Defense and the Massachusetts Lions Club, has always been a priority of the institute, but in recent times, urgency around it has increased, according to Dr. Michael Gilmore, director of research at Schepens Eye Research Institute and professor of ophthalmology at Harvard Medical School. In addition to the thousands of Americans blinded by glaucoma and injuries that destroy the optic nerve, and hundreds of thousands disabled by spinal cord injuries, "we were hearing stories of soldiers in the Middle East whose lives were saved by body armor, but who were returning with severe damage to limbs and eyes," he says. "At the same time, we learned of the untimely death of Christopher Reeves. It was, therefore, a priority for us to redouble our efforts to find ways to restore damaged nerves."
According to Senator John Kerry, who supported funding of this important work, "Schepens is doing cutting-edge research that can make a real difference for a new generation of troops returning home with nerve damage. We need to support our troops in actions, not just words, and I am glad that we have been able to get funding for this important work." Adds Congressman Lynch, "Last month, I visited the Walter Reed Army Medical Center in Washington and met with dozens of service men and women who could benefit directly from the good work of the people at Schepens. Their vital research will not only enhance the lives of our soldiers but also gives hope to every American who suffers from diseases of the central nervous system."
Many tissues in the body continually renew themselves if injured. However, this is not true for nerve cells or their fibers (axons) in the Central Nervous System (CNS). The CNS consists of the brain (of which the eye and optic nerve are part) and the spinal cord. For all mammals, including human beings, CNS nerves lose their ability to regenerate after injury at the point in their development when they are fully formed. For example, the optic nerve loses this ability shortly before birth. So for those afflicted by glaucoma, which destroys the optic nerve through excessive internal pressure, or with injuries that sever the optic nerve after that developmental milestone, destruction can be permanent and blinding.
Chen and her research team have dedicated themselves to learning the reasons why CNS tissue stops regenerating and to finding ways to reverse that process, using the optic nerve as their research model. The optic nerve, which connects the eye to the brain, consists of millions of nerve cells, which, when uninjured, transmit visual information from the retina to the brain for interpretation
In earlier research, Chen's team discovered several processes that they believed "locked up" the optic nerve's ability to regenerate. The first lock, they found, was the turning off of a specific gene - BCL-2 - which, when turned on, activates growth and regeneration. The second lock, they theorized, was a scar on the brain created shortly after birth by "glial" cells. (glial cells have many functions in the brain, one of which is to create this kind of scar tissue). The researchers believed that the scar puts up a physical as well as molecular barrier to regeneration. Although there may be other "locks" to the regeneration door, Chen and her colleagues believed these two were the most important.
In the current research, Dr. Kin-Sang Cho, research associate in Chen's laboratory and the first author of the paper, tested two keys to unlock regeneration. The first key involved the development of a mouse model in which the BCL-2 gene is always turned on (or is overexpressing). The second key was the use of a mouse line carrying mutations of "glial specific genes" that lead to the reduced "glial scar" formation.
By unlocking the regeneration with the first key, for the first time, they observed robust optic nerve regeneration in postnatal mice, which nerves grew rapidly and reached from the eye to the brain in four days. But the regeneration happens only in the younger mice whose brains had not yet formed a "glial scar." In the mice that were slightly older and had developed the "glial scar," regeneration failed again.
Dr. Cho then added the second key by combining BCL-2 overexpresser with the "glial gene" mutation to prevent the development of the "glial scar" in the older transgenic mice. He found that the combination of the turned-on BCL-2 and the mutation of "glial specific genes" caused the optic nerves to return to an embryonic state and stimulated rapid, robust regeneration of the optic nerve--again, as with the younger mice - within only a few days.
"We could see that at least 40 percent of the optic nerve had been restored," says Chen, "but we believe that an even higher percentage actually regenerated."
The next step for Chen and her colleagues is to determine if the regenerated optic nerves were functional. In other words, did they cause the mice to see again?
Chen also believes that this combination BCL-2 and scar prevention technique could work to regenerate other Central Nervous System tissue, increasing the possibility that spinal cord patients could walk or move again.
This work has important implications. "The possibility of restoring sight following optic nerve injuries is tremendous. Fifteen percent of all wartime injuries include the eye and those with optic nerve trauma are the most grave. Today's medicine has little effective treatment to offer and blindness is often the end result," says Retired Lieutenant Colonel Robert C. Read of the Clinical Applications Division at the Department of Defense's Telemedicine and Advanced Technology Research Center.
"This outstanding breakthrough by Schepens scientists offers new hope to those who suffer from blinding diseases and injuries, including our returning soldiers. The potential application of this discovery to treatments for other central nervous system injuries is yet another reason why I have been proud to support the Department of Defense's funding of the Center for Excellence in Military Low Vision Research," stated Congressman Mike Capuano.
Adds Congressman Stephen F. Lynch, "This extraordinary breakthrough demonstrates what we can achieve when we support public and private partnerships between the Defense Department and the best researchers and scientists in the field. Because of the decades of work and progress by Dr. Gilmore and Dr. Chen and the entire team at the Schepens Eye Research Institute, the search for a way to repair nerve damage in the human body has taken a giant leap forward."
"I'm so pleased with the work going on at Schepens," Rep. Jim McGovern says. "They are on the frontiers of research that will dramatically improve people's lives. And the Federal Government must continue to be a partner in this vital effort."
---------------------
To obtain a copy of the study, "Reestablishing the Regenerative Potential of the Central Nervous System Axons in Postnatal Mice," email pjacobs12comcast.
Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the world.
Contact: Patti Jacobs
pjacobs12comcast
Schepens Eye Research Institute
This research, which has been supported in part by grants from the National Institutes of Health, the Department of Defense and the Massachusetts Lions Club, has always been a priority of the institute, but in recent times, urgency around it has increased, according to Dr. Michael Gilmore, director of research at Schepens Eye Research Institute and professor of ophthalmology at Harvard Medical School. In addition to the thousands of Americans blinded by glaucoma and injuries that destroy the optic nerve, and hundreds of thousands disabled by spinal cord injuries, "we were hearing stories of soldiers in the Middle East whose lives were saved by body armor, but who were returning with severe damage to limbs and eyes," he says. "At the same time, we learned of the untimely death of Christopher Reeves. It was, therefore, a priority for us to redouble our efforts to find ways to restore damaged nerves."
According to Senator John Kerry, who supported funding of this important work, "Schepens is doing cutting-edge research that can make a real difference for a new generation of troops returning home with nerve damage. We need to support our troops in actions, not just words, and I am glad that we have been able to get funding for this important work." Adds Congressman Lynch, "Last month, I visited the Walter Reed Army Medical Center in Washington and met with dozens of service men and women who could benefit directly from the good work of the people at Schepens. Their vital research will not only enhance the lives of our soldiers but also gives hope to every American who suffers from diseases of the central nervous system."
Many tissues in the body continually renew themselves if injured. However, this is not true for nerve cells or their fibers (axons) in the Central Nervous System (CNS). The CNS consists of the brain (of which the eye and optic nerve are part) and the spinal cord. For all mammals, including human beings, CNS nerves lose their ability to regenerate after injury at the point in their development when they are fully formed. For example, the optic nerve loses this ability shortly before birth. So for those afflicted by glaucoma, which destroys the optic nerve through excessive internal pressure, or with injuries that sever the optic nerve after that developmental milestone, destruction can be permanent and blinding.
Chen and her research team have dedicated themselves to learning the reasons why CNS tissue stops regenerating and to finding ways to reverse that process, using the optic nerve as their research model. The optic nerve, which connects the eye to the brain, consists of millions of nerve cells, which, when uninjured, transmit visual information from the retina to the brain for interpretation
In earlier research, Chen's team discovered several processes that they believed "locked up" the optic nerve's ability to regenerate. The first lock, they found, was the turning off of a specific gene - BCL-2 - which, when turned on, activates growth and regeneration. The second lock, they theorized, was a scar on the brain created shortly after birth by "glial" cells. (glial cells have many functions in the brain, one of which is to create this kind of scar tissue). The researchers believed that the scar puts up a physical as well as molecular barrier to regeneration. Although there may be other "locks" to the regeneration door, Chen and her colleagues believed these two were the most important.
In the current research, Dr. Kin-Sang Cho, research associate in Chen's laboratory and the first author of the paper, tested two keys to unlock regeneration. The first key involved the development of a mouse model in which the BCL-2 gene is always turned on (or is overexpressing). The second key was the use of a mouse line carrying mutations of "glial specific genes" that lead to the reduced "glial scar" formation.
By unlocking the regeneration with the first key, for the first time, they observed robust optic nerve regeneration in postnatal mice, which nerves grew rapidly and reached from the eye to the brain in four days. But the regeneration happens only in the younger mice whose brains had not yet formed a "glial scar." In the mice that were slightly older and had developed the "glial scar," regeneration failed again.
Dr. Cho then added the second key by combining BCL-2 overexpresser with the "glial gene" mutation to prevent the development of the "glial scar" in the older transgenic mice. He found that the combination of the turned-on BCL-2 and the mutation of "glial specific genes" caused the optic nerves to return to an embryonic state and stimulated rapid, robust regeneration of the optic nerve--again, as with the younger mice - within only a few days.
"We could see that at least 40 percent of the optic nerve had been restored," says Chen, "but we believe that an even higher percentage actually regenerated."
The next step for Chen and her colleagues is to determine if the regenerated optic nerves were functional. In other words, did they cause the mice to see again?
Chen also believes that this combination BCL-2 and scar prevention technique could work to regenerate other Central Nervous System tissue, increasing the possibility that spinal cord patients could walk or move again.
This work has important implications. "The possibility of restoring sight following optic nerve injuries is tremendous. Fifteen percent of all wartime injuries include the eye and those with optic nerve trauma are the most grave. Today's medicine has little effective treatment to offer and blindness is often the end result," says Retired Lieutenant Colonel Robert C. Read of the Clinical Applications Division at the Department of Defense's Telemedicine and Advanced Technology Research Center.
"This outstanding breakthrough by Schepens scientists offers new hope to those who suffer from blinding diseases and injuries, including our returning soldiers. The potential application of this discovery to treatments for other central nervous system injuries is yet another reason why I have been proud to support the Department of Defense's funding of the Center for Excellence in Military Low Vision Research," stated Congressman Mike Capuano.
Adds Congressman Stephen F. Lynch, "This extraordinary breakthrough demonstrates what we can achieve when we support public and private partnerships between the Defense Department and the best researchers and scientists in the field. Because of the decades of work and progress by Dr. Gilmore and Dr. Chen and the entire team at the Schepens Eye Research Institute, the search for a way to repair nerve damage in the human body has taken a giant leap forward."
"I'm so pleased with the work going on at Schepens," Rep. Jim McGovern says. "They are on the frontiers of research that will dramatically improve people's lives. And the Federal Government must continue to be a partner in this vital effort."
---------------------
To obtain a copy of the study, "Reestablishing the Regenerative Potential of the Central Nervous System Axons in Postnatal Mice," email pjacobs12comcast.
Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the world.
Contact: Patti Jacobs
pjacobs12comcast
Schepens Eye Research Institute
Scientists Trick Bacteria With Small Molecules
A team of Yale University scientists has engineered the cell wall of the Staphylococcus aureus bacteria, tricking it into incorporating foreign small molecules and embedding them within the cell wall.
The finding, described online in the journal ACS Chemical Biology, represents the first time scientists have engineered the cell wall of a pathogenic "Gram-positive" bacteria - organisms responsible not only for Staph infections but also pneumonia, strep throat and many others. The discovery could pave the way for new methods of combating the bacteria responsible for many of the most infectious diseases.
The team engineered one end of their small molecules to contain a peptide sequence that would be recognized by the bacteria. In Staphylococcus aureus, an enzyme called sortase A is responsible for attaching proteins to the cell wall.
"We sort of tricked the bacteria into incorporating something into its cell wall that it didn't actually make," said David Spiegel, a Yale chemist who led the study. "It's as if the cell thought the molecules were its own proteins rather than recognizing them as something foreign."
The scientists focused specifically on the cell wall because it contains many of the components the cell uses to relate to its environment, Spiegel said. "By being able to manipulate the cell wall, we can in theory perturb the bacteria's ability to interact with human tissues and host cells."
The team used three different small molecules in their experiment - including biotin, fluorescein and azide - but the technique could be used with other molecules, Spiegel said, as well as with other types of bacteria. Another advantage to the new technique is that the scientists did not have to first genetically modify the bacteria in any way in order for them to incorporate the small molecules, meaning the method should work on naturally occurring bacteria in the human body.
Staph infections, such as the drug-resistant MRSA, have plagued hospitals in recent years. More Americans die each year from Staphylococcus aureus infections alone than from HIV/AIDS, Parkinson's disease or emphysema.
Being able to engineer the cell walls of not only Staphylococcus aureus but a whole family of bacteria could have widespread use in combating these illnesses, Spiegel said, adding that any number of small molecules could be used with their technique. "For example, if we tag these bacteria with small fluorescent tracer molecules, we could watch the progression of disease in the human body in real time." The molecules could also be used to help recruit antibodies that occur naturally in the bloodstream, boosting the body's own immune response to diseases that tend to go undetected, such as HIV/AIDS or cancer.
"This technique has the potential to help illuminate basic biological processes as well as lead to novel therapeutics from some of the most common and deadly diseases affecting us today," Spiegel said.
Other authors of the paper include James Nelson, Alexander Chamessian, Patrick McEnaney, Ryan Murelli and Barbara Kazmiercak (all of Yale University). DOI: 10.1021/cb100195d
Source:
Yale University
The finding, described online in the journal ACS Chemical Biology, represents the first time scientists have engineered the cell wall of a pathogenic "Gram-positive" bacteria - organisms responsible not only for Staph infections but also pneumonia, strep throat and many others. The discovery could pave the way for new methods of combating the bacteria responsible for many of the most infectious diseases.
The team engineered one end of their small molecules to contain a peptide sequence that would be recognized by the bacteria. In Staphylococcus aureus, an enzyme called sortase A is responsible for attaching proteins to the cell wall.
"We sort of tricked the bacteria into incorporating something into its cell wall that it didn't actually make," said David Spiegel, a Yale chemist who led the study. "It's as if the cell thought the molecules were its own proteins rather than recognizing them as something foreign."
The scientists focused specifically on the cell wall because it contains many of the components the cell uses to relate to its environment, Spiegel said. "By being able to manipulate the cell wall, we can in theory perturb the bacteria's ability to interact with human tissues and host cells."
The team used three different small molecules in their experiment - including biotin, fluorescein and azide - but the technique could be used with other molecules, Spiegel said, as well as with other types of bacteria. Another advantage to the new technique is that the scientists did not have to first genetically modify the bacteria in any way in order for them to incorporate the small molecules, meaning the method should work on naturally occurring bacteria in the human body.
Staph infections, such as the drug-resistant MRSA, have plagued hospitals in recent years. More Americans die each year from Staphylococcus aureus infections alone than from HIV/AIDS, Parkinson's disease or emphysema.
Being able to engineer the cell walls of not only Staphylococcus aureus but a whole family of bacteria could have widespread use in combating these illnesses, Spiegel said, adding that any number of small molecules could be used with their technique. "For example, if we tag these bacteria with small fluorescent tracer molecules, we could watch the progression of disease in the human body in real time." The molecules could also be used to help recruit antibodies that occur naturally in the bloodstream, boosting the body's own immune response to diseases that tend to go undetected, such as HIV/AIDS or cancer.
"This technique has the potential to help illuminate basic biological processes as well as lead to novel therapeutics from some of the most common and deadly diseases affecting us today," Spiegel said.
Other authors of the paper include James Nelson, Alexander Chamessian, Patrick McEnaney, Ryan Murelli and Barbara Kazmiercak (all of Yale University). DOI: 10.1021/cb100195d
Source:
Yale University
Breakthrough In Screening For Alzheimer's Disease
CSIRO scientists have developed a new system to screen for compounds that can inhibit one of the processes that takes place during the progression of Alzheimer's disease.
In a paper published in the latest edition of the Journal of Alzheimer's Disease, folate is shown to be beneficial in the screening system.
Lead author, CSIRO's Dr Ian Macreadie says folate is already well known to have a protective effect against Alzheimer's disease which is believed to be caused by the loss of neurons in the brain due to a process whereby toxic multimers of a small protein called AОІ are formed.
"However, a team of scientists working within CSIRO's Preventative Health Flagship has discovered a rapid screening system to identify inhibitors of this process. Compounds that inhibit the formation of the toxic multimers may lead to the prevention or delay of the disease," Dr Macreadie says.
"Although many other research groups and drug companies around the world are trying to find compounds that act in the same way, the advance by the Flagship team involves using live yeast with the AОІ protein fused to a green fluorescent protein that comes from jellyfish.
"The significance of this development is that the yeast trial we developed could lead to the discovery of new agents which may prove useful in preventing or delaying the onset of Alzheimer's disease."
Currently Alzheimer's disease is an incurable illness and the fourth leading cause of death in people aged 65 years and over.
Although folate is abundant in foods like leafy green vegetables, pulses and liver, CSIRO studies have shown that many Australians do not consume enough folate to benefit from its ability to prevent cell damage. Folate levels can, however, be readily restored by dietary folate supplementation.
National Research Flagships
CSIRO initiated the National Research Flagships to provide science-based solutions in response to Australia's major research challenges and opportunities. The nine Flagships form multidisciplinary teams with industry and the research community to deliver impact and benefits for Australia.
Source: Ms Sarah Nolan
CSIRO Australia
In a paper published in the latest edition of the Journal of Alzheimer's Disease, folate is shown to be beneficial in the screening system.
Lead author, CSIRO's Dr Ian Macreadie says folate is already well known to have a protective effect against Alzheimer's disease which is believed to be caused by the loss of neurons in the brain due to a process whereby toxic multimers of a small protein called AОІ are formed.
"However, a team of scientists working within CSIRO's Preventative Health Flagship has discovered a rapid screening system to identify inhibitors of this process. Compounds that inhibit the formation of the toxic multimers may lead to the prevention or delay of the disease," Dr Macreadie says.
"Although many other research groups and drug companies around the world are trying to find compounds that act in the same way, the advance by the Flagship team involves using live yeast with the AОІ protein fused to a green fluorescent protein that comes from jellyfish.
"The significance of this development is that the yeast trial we developed could lead to the discovery of new agents which may prove useful in preventing or delaying the onset of Alzheimer's disease."
Currently Alzheimer's disease is an incurable illness and the fourth leading cause of death in people aged 65 years and over.
Although folate is abundant in foods like leafy green vegetables, pulses and liver, CSIRO studies have shown that many Australians do not consume enough folate to benefit from its ability to prevent cell damage. Folate levels can, however, be readily restored by dietary folate supplementation.
National Research Flagships
CSIRO initiated the National Research Flagships to provide science-based solutions in response to Australia's major research challenges and opportunities. The nine Flagships form multidisciplinary teams with industry and the research community to deliver impact and benefits for Australia.
Source: Ms Sarah Nolan
CSIRO Australia
Going Beyond Histology: Synchrotron UCT A Methodology For Biological Tissue Characterization - From Tissue Morphology To Individual Cells
Histological techniques allow us to represent physiological or pathophysiological conditions in two dimensions - usually by light microscopic investigation of thin tissue slices.
To go beyond this imposed limitation of conventional histology, micro computed tomography offers an extension into three dimensional tissue characterization.
The authors were able to link conventional histological techniques, including scanning electron microscopy, to synchrotron radiation based micro computed tomography (SR-ВµCT). SR-ВµCT allowed characterizing the morphology of an articular cartilage tissue sample in three dimensions and was able to resolve individual cells, with the possibility to quantify cell number and orientation.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category. The journal also incorporates Interface Focus , a peer-reviewed, themed supplement, each issue of which concentrates on a specific cross-disciplinary subject.
rsif.royalsocietypublishing
To go beyond this imposed limitation of conventional histology, micro computed tomography offers an extension into three dimensional tissue characterization.
The authors were able to link conventional histological techniques, including scanning electron microscopy, to synchrotron radiation based micro computed tomography (SR-ВµCT). SR-ВµCT allowed characterizing the morphology of an articular cartilage tissue sample in three dimensions and was able to resolve individual cells, with the possibility to quantify cell number and orientation.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category. The journal also incorporates Interface Focus , a peer-reviewed, themed supplement, each issue of which concentrates on a specific cross-disciplinary subject.
rsif.royalsocietypublishing
Mathematical Models Of Energy Homeostasis
To tackle diabetes and obesity, clinicians are now turning to mechanism-based mathematical models to reach quantitative diagnoses of insulin resistance, glucose intolerance and obesity, and to predict the likely outcomes of therapeutic interventions.
A massive range of such models is available, which renders a judicious choice difficult. To better inform this choice, we here present the most important models published to date in a uniform format, discussing similarities and differences in terms of the decisions faced by modellers.
We review models for glucostasis, based on the glucose-insulin feedback control loop, and consider extensions to long-term energy balance, dislipidemia and obesity.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category.
Journal of the Royal Society Interface
A massive range of such models is available, which renders a judicious choice difficult. To better inform this choice, we here present the most important models published to date in a uniform format, discussing similarities and differences in terms of the decisions faced by modellers.
We review models for glucostasis, based on the glucose-insulin feedback control loop, and consider extensions to long-term energy balance, dislipidemia and obesity.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category.
Journal of the Royal Society Interface
Use Of Animal Serum-free Media For Growing Live Cells Urged By New Journal Article
WASHINGTON--In the March issue of Trends in Biotechnology, scientists and doctors with the Physicians Committee for Responsible Medicine (PCRM) recommend using only animal serum-free media to grow live cells in the laboratory. At issue is the use of fetal calf serum, which is obtained by puncturing the heart of a fetal calf without anesthesia. Recent breakthroughs permit the growth of human cells in a medium free of animal serum, enabling scientists and researchers to make cell culture safer and more humane.
"Scientists have access to humane and scientifically superior alternatives, so now is the time to completely eliminate the use of fetal calf serum in the laboratory," says Megha Shah Even, M.S., a staff scientist at PCRM and lead author of the paper. Live cells grown in the laboratory are used for many purposes including the manufacture of drugs and diagnostic kits.
Trends in Biotechnology, based in the United Kingdom, invited Mrs. Even to submit a paper after learning that she spearheaded the development of the world's first animal serum-free insulin assay. In addition to humane concerns, the article emphasizes the scientific advantages of serum-free cell culture. Growing cells without animal serum ensures that fewer variables are introduced into experiments, meaning that results are easily reproducible by different laboratories.
For a copy of the new article published in Trends in Biotechnology, "Serum-free hybridoma culture: Ethical, scientific and safety considerations," or an interview with lead author Megha Shah Even, M.S., please contact Jeanne S. McVey at 202-686-2210, ext. 316, or jeannempcrm.
Founded in 1985, the Physicians Committee for Responsible Medicine is a nonprofit health organization that promotes preventive medicine, especially good nutrition. PCRM also conducts clinical research studies, opposes unethical human experimentation, and promotes alternatives to animal research.
Jeanne Stuart McVey
Senior Media Relations Specialist
Physicians Committee for Responsible Medicine
5100 Wisconsin Ave., N.W., Suite 400
Washington, D.C., 20016
jeannempcrm
pcrm/
Contact: Jeanne S. McVey
jeannempcrm
Physicians Committee for Responsible Medicine
"Scientists have access to humane and scientifically superior alternatives, so now is the time to completely eliminate the use of fetal calf serum in the laboratory," says Megha Shah Even, M.S., a staff scientist at PCRM and lead author of the paper. Live cells grown in the laboratory are used for many purposes including the manufacture of drugs and diagnostic kits.
Trends in Biotechnology, based in the United Kingdom, invited Mrs. Even to submit a paper after learning that she spearheaded the development of the world's first animal serum-free insulin assay. In addition to humane concerns, the article emphasizes the scientific advantages of serum-free cell culture. Growing cells without animal serum ensures that fewer variables are introduced into experiments, meaning that results are easily reproducible by different laboratories.
For a copy of the new article published in Trends in Biotechnology, "Serum-free hybridoma culture: Ethical, scientific and safety considerations," or an interview with lead author Megha Shah Even, M.S., please contact Jeanne S. McVey at 202-686-2210, ext. 316, or jeannempcrm.
Founded in 1985, the Physicians Committee for Responsible Medicine is a nonprofit health organization that promotes preventive medicine, especially good nutrition. PCRM also conducts clinical research studies, opposes unethical human experimentation, and promotes alternatives to animal research.
Jeanne Stuart McVey
Senior Media Relations Specialist
Physicians Committee for Responsible Medicine
5100 Wisconsin Ave., N.W., Suite 400
Washington, D.C., 20016
jeannempcrm
pcrm/
Contact: Jeanne S. McVey
jeannempcrm
Physicians Committee for Responsible Medicine
New Method May Rapidly And Effectively Detect Significant Food-Borne Pathogen
Researchers from Sweden and Finland have developed a rapid and specific method that may detect the bacterium Yersinia enterocolitica, a common cause of gastric illness, in food. They report their findings in the October 2008 issue of the journal Applied and Environmental Microbiology.
Y. enterocolitica is the causative agent of yersiniosis, an internal infection resulting in diarrhea, fever, abdominal pain, and vomiting. Predominantly considered a food-borne pathogen, most cases sporadically occur worldwide and the source of infection is often unknown. Pigs are believed to be a main reservoir for Y. enterocolitica with pork being the most likely vehicle of transmission to humans. The ability of Y. enterocolitica to multiply in foods at low temperatures as well as in vacuum-packed containment is cause for major food safety concern and current detection methods available are time consuming and inefficient.
In the study researchers developed and evaluated a TaqMan probe-based real-time PCR method for detecting Y. enterocolitica in food in one to two days. Following overnight synthetic enrichment of samples of milk, minced beef, cold-smoked sausage, fish and carrots with Y. enterocolitica, results of the TaqMan PCR test showed high levels of sensitivity, robustness, precision and efficiency in detecting the bacterium.
"A rapid and specific real-time PCR method for the detection of pathogenic Y. enterocolitica bacteria in food, as presented here, provides a superior alternative to the currently available detection methods and makes it possible to identify the foods at risk for Y. enterocolitica contamination," say the researchers.
(S. Thisted Lambertz, C. Nilsson, S. Hallanvuo, M. Lindblad. 2008. Real-time PCR method for detection of pathogenic Yersinia enterocolitica in food. Applied and Environmental Microbiology, 74. 19: 6060-6067.)
Source:
Carrie Slijepcevic
American Society for Microbiology
Y. enterocolitica is the causative agent of yersiniosis, an internal infection resulting in diarrhea, fever, abdominal pain, and vomiting. Predominantly considered a food-borne pathogen, most cases sporadically occur worldwide and the source of infection is often unknown. Pigs are believed to be a main reservoir for Y. enterocolitica with pork being the most likely vehicle of transmission to humans. The ability of Y. enterocolitica to multiply in foods at low temperatures as well as in vacuum-packed containment is cause for major food safety concern and current detection methods available are time consuming and inefficient.
In the study researchers developed and evaluated a TaqMan probe-based real-time PCR method for detecting Y. enterocolitica in food in one to two days. Following overnight synthetic enrichment of samples of milk, minced beef, cold-smoked sausage, fish and carrots with Y. enterocolitica, results of the TaqMan PCR test showed high levels of sensitivity, robustness, precision and efficiency in detecting the bacterium.
"A rapid and specific real-time PCR method for the detection of pathogenic Y. enterocolitica bacteria in food, as presented here, provides a superior alternative to the currently available detection methods and makes it possible to identify the foods at risk for Y. enterocolitica contamination," say the researchers.
(S. Thisted Lambertz, C. Nilsson, S. Hallanvuo, M. Lindblad. 2008. Real-time PCR method for detection of pathogenic Yersinia enterocolitica in food. Applied and Environmental Microbiology, 74. 19: 6060-6067.)
Source:
Carrie Slijepcevic
American Society for Microbiology
Gene Regulation Determines Individuality, Study
A team of US and German scientists has found that we differ from each more because of the way our genes are regulated, such as which are
switched on and which are switched off, than because of the differences among the genes themselves: furthermore there appears to be as much
variation among humans as between humans and chimpanzees when it comes to gene regulation.
Researchers from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and Yale and Stanford Universities in the USA wrote
about their findings in a paper that was published online in Science on 18 March.
After the human genome was sequenced and published nearly ten years ago, scientists have been searching for the genes that make individual humans
unique.
The process is now so technologically advanced that scientists can obtain the genome of several people in a fraction of the time and cost it took for the
first human genome, and we are now beginning to understand a lot more about how genes work.
But as we get to know more about how genes and DNA works, we realize that perhaps the picture is more complex than we imagined.
The team on this study, led by Jan Korbel at EMBL and Michael Snyder initially at Yale and now in Stanford, wrote that it is becoming increasingly
apparent that:
"Differences in gene expression may play a major role in speciation and phenotypic diversity."
So they decided to investigate genome-wide differences in a key component of gene expression called transcription factor (TF) binding.
While each of us inherits genes from our biological parents, those genes are effectively "switched off" in our DNA until they are transcribed into
mRNA, the process that switches them on and thereby allows them to express control over the production of proteins.
However, the transcription of genes from DNA to mRNA is itself regulated by TF proteins, and a key part of how they work is they have special DNA-binding domains (DBDs) that attach to areas of DNA that lie next to the genes they are transcribing.
In a very crude sense it is like a TF protein has to "dock" next to the gene before it can start transcribing it. These "docking" area sections of DNA are
not like genes: they don't hold instructions for coding proteins, but they can vary from person to person and in this way influence whether genes are
switched on or off.
As Korbel explained to the media:
"We developed a new approach which enabled us to identify cases where a protein's ability to turn a gene on or off can be affected by interactions with
another protein anchored to a nearby area of the genome."
"With it, we can begin to understand where such interactions happen, without having to study every single regulatory protein out there," said
Korbel.
The team found that up to a quarter of all human genes are regulated differently in different people: this is more than the genetic variation among
genes themselves.
Thus even if different people have exactly the same copy of a gene, for instance ORMDL3, thought to influence the development of asthma in children,
the way their cells regulate the gene can vary among them.
They discovered that many of the differences are due to how TF proteins behave because of DNA sequencing differences in the "docking" areas
between the genes: some of the differences comprising only a single-letter change in the DNA code.
They also found variations they could not explain, and proposed these might be used by TF proteins acting together in some way.
Finally, they compared the information they obtained on humans with that of a chimpanzee, and found that gene regulation seems to vary almost as
much among humans as it does between humans and chimpanzees.
They concluded that:
"Our results indicate that many differences in individuals and species occur at the level of TF binding and provide insight into the genetic events
responsible for these differences."
Snyder said these discoveries may change the way we think about ourselves and diseases:
"As well as looking for disease genes, we could start looking at how genes are regulated, and how individual variations in gene regulation could
affect patients' reactions."
"Variation in Transcription Factor Binding Among Humans."
Kasowski M, Grubert F, Heffelfinger C, Hariharan M, Asabere A, Waszak SM, Habegger L, Rozowsky J, Shi M, Urban AE, Hong MY, Karczewski
KJ, Huber W, Weissman SM, Gerstein MB, Korbel JO, Snyder M.
Science, 18 March
2010 (Epub ahead of print).
DOI: 10.1126/science.1183621
Source: European Molecular Biology Laboratory.
Written by: Catharine Paddock, PhD
switched on and which are switched off, than because of the differences among the genes themselves: furthermore there appears to be as much
variation among humans as between humans and chimpanzees when it comes to gene regulation.
Researchers from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and Yale and Stanford Universities in the USA wrote
about their findings in a paper that was published online in Science on 18 March.
After the human genome was sequenced and published nearly ten years ago, scientists have been searching for the genes that make individual humans
unique.
The process is now so technologically advanced that scientists can obtain the genome of several people in a fraction of the time and cost it took for the
first human genome, and we are now beginning to understand a lot more about how genes work.
But as we get to know more about how genes and DNA works, we realize that perhaps the picture is more complex than we imagined.
The team on this study, led by Jan Korbel at EMBL and Michael Snyder initially at Yale and now in Stanford, wrote that it is becoming increasingly
apparent that:
"Differences in gene expression may play a major role in speciation and phenotypic diversity."
So they decided to investigate genome-wide differences in a key component of gene expression called transcription factor (TF) binding.
While each of us inherits genes from our biological parents, those genes are effectively "switched off" in our DNA until they are transcribed into
mRNA, the process that switches them on and thereby allows them to express control over the production of proteins.
However, the transcription of genes from DNA to mRNA is itself regulated by TF proteins, and a key part of how they work is they have special DNA-binding domains (DBDs) that attach to areas of DNA that lie next to the genes they are transcribing.
In a very crude sense it is like a TF protein has to "dock" next to the gene before it can start transcribing it. These "docking" area sections of DNA are
not like genes: they don't hold instructions for coding proteins, but they can vary from person to person and in this way influence whether genes are
switched on or off.
As Korbel explained to the media:
"We developed a new approach which enabled us to identify cases where a protein's ability to turn a gene on or off can be affected by interactions with
another protein anchored to a nearby area of the genome."
"With it, we can begin to understand where such interactions happen, without having to study every single regulatory protein out there," said
Korbel.
The team found that up to a quarter of all human genes are regulated differently in different people: this is more than the genetic variation among
genes themselves.
Thus even if different people have exactly the same copy of a gene, for instance ORMDL3, thought to influence the development of asthma in children,
the way their cells regulate the gene can vary among them.
They discovered that many of the differences are due to how TF proteins behave because of DNA sequencing differences in the "docking" areas
between the genes: some of the differences comprising only a single-letter change in the DNA code.
They also found variations they could not explain, and proposed these might be used by TF proteins acting together in some way.
Finally, they compared the information they obtained on humans with that of a chimpanzee, and found that gene regulation seems to vary almost as
much among humans as it does between humans and chimpanzees.
They concluded that:
"Our results indicate that many differences in individuals and species occur at the level of TF binding and provide insight into the genetic events
responsible for these differences."
Snyder said these discoveries may change the way we think about ourselves and diseases:
"As well as looking for disease genes, we could start looking at how genes are regulated, and how individual variations in gene regulation could
affect patients' reactions."
"Variation in Transcription Factor Binding Among Humans."
Kasowski M, Grubert F, Heffelfinger C, Hariharan M, Asabere A, Waszak SM, Habegger L, Rozowsky J, Shi M, Urban AE, Hong MY, Karczewski
KJ, Huber W, Weissman SM, Gerstein MB, Korbel JO, Snyder M.
Science, 18 March
2010 (Epub ahead of print).
DOI: 10.1126/science.1183621
Source: European Molecular Biology Laboratory.
Written by: Catharine Paddock, PhD
Henry Ford Hospital Study May Hold Promise For Future Disease Therapies
Linking genetic material microRNAs with cells that regulate the immune system could one day lead to new therapies for treating cancer, infections and autoimmune diseases, according to a Henry Ford Hospital study.
Qing-Sheng Mi, M.D., Ph.D., the study's senior author and director of Henry Ford's Immunology Program, says their findings are important because it shows for the first time an association between microRNAs and a key subset of immune regulatory cells in the body, natural killer T cells (NKT), which are known to lead to autoimmune diseases and cancer.
The study was published June 1 in the Proceedings of the National Academy of Sciences.
"While further studies are needed, we believe this provides important insight about how microRNAs can regulate NKT cells, and signals a major step forward in biology science for looking at new therapies for treating some chronic immune disease," Dr. Mi says.
MicroRNAs are short strands of genetic material that researchers believe perform a vital role in healthy development by turning off gene activity. NKT cells potent regulators of diverse immune responses in the body.
By genetically modifying mice with specific deletion microRNAs in hematopoietic stem cells, Henry Ford researchers showed that the lack of microRNAs can block the development and function of normal NKT cells.
If researchers are successful at identifying unique microRNA that specifically regulate NKT cells, Dr. Mi, it could lead to new treatment therapies for some chronic disease.
Source:
David Olejarz
Henry Ford Health System
Qing-Sheng Mi, M.D., Ph.D., the study's senior author and director of Henry Ford's Immunology Program, says their findings are important because it shows for the first time an association between microRNAs and a key subset of immune regulatory cells in the body, natural killer T cells (NKT), which are known to lead to autoimmune diseases and cancer.
The study was published June 1 in the Proceedings of the National Academy of Sciences.
"While further studies are needed, we believe this provides important insight about how microRNAs can regulate NKT cells, and signals a major step forward in biology science for looking at new therapies for treating some chronic immune disease," Dr. Mi says.
MicroRNAs are short strands of genetic material that researchers believe perform a vital role in healthy development by turning off gene activity. NKT cells potent regulators of diverse immune responses in the body.
By genetically modifying mice with specific deletion microRNAs in hematopoietic stem cells, Henry Ford researchers showed that the lack of microRNAs can block the development and function of normal NKT cells.
If researchers are successful at identifying unique microRNA that specifically regulate NKT cells, Dr. Mi, it could lead to new treatment therapies for some chronic disease.
Source:
David Olejarz
Henry Ford Health System
Thermo Fisher Scientific Announces Its 2008 North American Informatics Conference
Thermo Fisher Scientific Inc., the world leader in serving science, has
scheduled its annual North American laboratory Informatics user group
meeting, Thermo Informatics World (TIW), from October 6-9, 2008 in Las
Vegas, Nevada. The conference will not only profile the company's strategic
and product roadmaps, but also demonstrate its latest informatics offerings
that address the growing data management and instrument integration
challenges of today's laboratories.
TIW North America 2008 will provide users with enhanced knowledge, tools and
capabilities for integrating Thermo Scientific LIMS (laboratory information
management systems) and CDS (chromatography data systems) across laboratory
instruments and the enterprise, increasing collaboration and facilitating
more informed decision making. This year's theme is "where your solution is
a sure thing." Thermo Scientific LIMS and CDS are utilized in laboratories
around the world and in diverse industries including chemicals,
environmental, food and beverage, forensics, metals and mining,
pharmaceuticals and bioanalytical, environmental and wastewater.
The management of data is a key factor influencing the overall productivity
and performance of laboratories in all major industries. Demonstrating its
proven expertise in the development of innovative laboratory software
solutions at TIW 2008, Thermo Fisher Scientific will showcase its complete
range of LIMS, CDS, pharmacokinetic-pharmacodynamic software systems, and
spectroscopy software systems.
The North American TIW annual user conference provides industry
professionals with a unique opportunity to share cross-sector perspectives
and become informed on changing business requirements that drive the
enhancements and future direction of Thermo Scientific informatics
solutions. Designed to encourage customer involvement, TIW features product
breakout sessions, including in-depth customer presentations, product
updates and onsite training provided by the Thermo Fisher Scientific team of
informatics experts.
TIW North America 2008 will take place at the JW Marriott Hotel in Las
Vegas. Early bird registration is available until September, 5, 2008 and
offers a savings of $300. Group discounts are also available. In addition,
customers are invited to present on a range of topics from sharing tips for
navigating the software to highlighting a successful implementation.
Presenters will receive a waiver of the registration fee.
Thermo Scientific is part of Thermo Fisher Scientific, the world leader in
serving science.
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving
science, enabling our customers to make the world healthier, cleaner and
safer. With annual revenues of $10 billion, we have more than 30,000
employees and serve over 350,000 customers within pharmaceutical and biotech
companies, hospitals and clinical diagnostic labs, universities, research
institutions and government agencies, as well as environmental and
industrial process control settings. Serving customers through two premier
brands, Thermo Scientific and Fisher Scientific, we help solve analytical
challenges from routine testing to complex research and discovery. Thermo
Scientific offers customers a complete range of high-end analytical
instruments as well as laboratory equipment, software, services, consumables
and reagents to enable integrated laboratory workflow solutions. Fisher
Scientific provides a complete portfolio of laboratory equipment, chemicals,
supplies and services used in healthcare, scientific research, safety and
education. Together, we offer the most convenient purchasing options to
customers and continuously advance our technologies to accelerate the pace
of scientific discovery, enhance value for customers and fuel growth for
shareholders and employees alike.
Thermo Fisher Scientific
scheduled its annual North American laboratory Informatics user group
meeting, Thermo Informatics World (TIW), from October 6-9, 2008 in Las
Vegas, Nevada. The conference will not only profile the company's strategic
and product roadmaps, but also demonstrate its latest informatics offerings
that address the growing data management and instrument integration
challenges of today's laboratories.
TIW North America 2008 will provide users with enhanced knowledge, tools and
capabilities for integrating Thermo Scientific LIMS (laboratory information
management systems) and CDS (chromatography data systems) across laboratory
instruments and the enterprise, increasing collaboration and facilitating
more informed decision making. This year's theme is "where your solution is
a sure thing." Thermo Scientific LIMS and CDS are utilized in laboratories
around the world and in diverse industries including chemicals,
environmental, food and beverage, forensics, metals and mining,
pharmaceuticals and bioanalytical, environmental and wastewater.
The management of data is a key factor influencing the overall productivity
and performance of laboratories in all major industries. Demonstrating its
proven expertise in the development of innovative laboratory software
solutions at TIW 2008, Thermo Fisher Scientific will showcase its complete
range of LIMS, CDS, pharmacokinetic-pharmacodynamic software systems, and
spectroscopy software systems.
The North American TIW annual user conference provides industry
professionals with a unique opportunity to share cross-sector perspectives
and become informed on changing business requirements that drive the
enhancements and future direction of Thermo Scientific informatics
solutions. Designed to encourage customer involvement, TIW features product
breakout sessions, including in-depth customer presentations, product
updates and onsite training provided by the Thermo Fisher Scientific team of
informatics experts.
TIW North America 2008 will take place at the JW Marriott Hotel in Las
Vegas. Early bird registration is available until September, 5, 2008 and
offers a savings of $300. Group discounts are also available. In addition,
customers are invited to present on a range of topics from sharing tips for
navigating the software to highlighting a successful implementation.
Presenters will receive a waiver of the registration fee.
Thermo Scientific is part of Thermo Fisher Scientific, the world leader in
serving science.
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving
science, enabling our customers to make the world healthier, cleaner and
safer. With annual revenues of $10 billion, we have more than 30,000
employees and serve over 350,000 customers within pharmaceutical and biotech
companies, hospitals and clinical diagnostic labs, universities, research
institutions and government agencies, as well as environmental and
industrial process control settings. Serving customers through two premier
brands, Thermo Scientific and Fisher Scientific, we help solve analytical
challenges from routine testing to complex research and discovery. Thermo
Scientific offers customers a complete range of high-end analytical
instruments as well as laboratory equipment, software, services, consumables
and reagents to enable integrated laboratory workflow solutions. Fisher
Scientific provides a complete portfolio of laboratory equipment, chemicals,
supplies and services used in healthcare, scientific research, safety and
education. Together, we offer the most convenient purchasing options to
customers and continuously advance our technologies to accelerate the pace
of scientific discovery, enhance value for customers and fuel growth for
shareholders and employees alike.
Thermo Fisher Scientific
Подписаться на:
Комментарии (Atom)