Discovery by Hebrew University of Jerusalem researchers of a new communication factor that enables bacteria to "talk to each other" and causes their death could have significant consequences leading to development of a new class of antibiotic medications.
Bacteria are traditionally considered unicellular organisms. However, increasing experimental evidence indicates that bacteria seldom behave as isolated organisms. Instead, they are members of a community in which the isolated organisms communicate among themselves, thereby manifesting some multi-cellular behaviors.
In an article published in the journal Science, the Hebrew University scientists describe the new communication factor they have discovered that is produced by the intestinal bacteria Escherichia coli. The new factor is secreted by the bacteria and serves as a communication signal between single bacterial cells.
The research was carried out by a group headed by Prof. Hanna Engelberg-Kulka of the Department of Molecular Biology at the Hebrew University -- Hadassah Medical School. It includes Ph.D. student Ilana Kolodkin-Gal , and a previous Ph.D. student, Dr Ronen Hazan. In addition, the research included Dr Ariel Gaathon from the Facilities Unit of the Medical School.
The communication factor formed by Escherichia coli enables the activation of a built-in "suicide module" which is located on the bacterial chromosome and is esponsible for bacterial cell death under stressful conditions. Therefore, the new factor has been designated EDF (Extra-cellular Death Factor).
While suicidal cell death is counterproductive for the individual bacterial cell, it becomes effective for the bacterial community as a whole by the simultaneous action of a group of cells that are signaled by EDF. Under stressful conditions in which the EDF is activated, a major sub-population within the bacterial culture dies, allowing the survival of the population as a whole.
Understanding how the EDF functions may provide a lead for a new and more efficient class of antibiotics that specifically trigger bacterial cell death in the intestine bacteria Escherichia coli and probably in many other bacteria, including those pathogens that also carry the "suicide module."
The discovered communication factor is a novel biological molecule, noted Prof Engelberg-Kulka. It is a peptide (a very small protein) that is produced by the bacteria. The chemical characterization of the new communication factor was particularly difficult for the researchers because of two main reasons: it is present in the bacterial culture in minute amounts, and the factor decomposes under the conditions that are routinely used during standard chemical characterization methods. Therefore, it was necessary to develop a new specific method. The research has also identified several bacterial genes that are involved in the generation of the communication factor, said Prof. Engelberg-Kulka. .
The research on this project was supported by the Israel Science Foundation (ISF), the U.S.-Israel Binational Science Foundation (BSF), and the American National Institutes of Health (NIH).
Source: Jerry Barach
The Hebrew University of Jerusalem
вторник, 26 апреля 2011 г.
Molecules With Potential To Treat Breast Cancer Found
Hamilton College
researchers have identified molecules that have been shown to be effective
in the fight against breast cancer. The Hamilton researchers used
state-of-the- art computational techniques in a novel way to design
molecules that they predicted would be effective lead compounds for breast
cancer research. Scientists from the Albany Medical College subsequently
synthesized the predicted molecules and showed that they were indeed
potential anti-breast cancer compounds in animal systems
A paper detailing the research, "Computational Design and Experimental
Discovery of an Anti-estrogenic Peptide Derived from Alpha-Fetoprotein,"
will be published in the May 16 issue of the Journal of American Chemical
Society.
Winslow Professor of Chemistry George Shields and co-director of the
Center for Molecular Design Karl Kirschner led the Hamilton research team
with undergraduate students Katrina Lexa '05, Amanda Salisburg '08,
Katherine Alser '09. The Albany team consisted of Leroy Joseph, Thomas
Andersen, James Bennett, and Herbert Jacobsen of Albany Medical College.
Breast cancer is the most common cancer among women and tamoxifen is
the preferred drug for estrogen receptor-positive breast cancer treatment.
Many of these cancers are intrinsically resistant to tamoxifen or acquire
resistance during treatment. Consequently, there is an ongoing need for
breast cancer drugs that have different molecular targets.
Previous work by the Albany Medical College researchers had shown that
8- mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat
models, interacting with an unsolved receptor, while peptides smaller than
eight amino acids did not.
The Hamilton researchers used advanced computational methods to predict
the structure and dynamics of active peptides, leading to discovery of
smaller peptides with full biological activity. The results were used to
identify smaller peptides with the three dimensional structure of the
larger peptides. These peptides were synthesized and shown to inhibit
estrogen-dependent cell growth in a mouse uterine growth assay, a test
showing reliable correlation with human breast cancer inhibition.
This work was funded by the National Institutes of Health, the New York
State Breast Cancer Research and Education fund, the Department of
Defense's Breast Cancer program, and the National Science Foundation.
Founded in 1879, the Journal of the American Chemical Society is the
flagship journal of the American Chemical Society and the premier medium
for the worldwide publication of fundamental research in all areas of the
chemical sciences. It is the most highly cited chemistry journal.
The results reported in the published article were first presented by
Professor Shields at the 2006 International Symposium on Theory and
Computations in Molecular and Materials Sciences, Biology and Pharmacology,
on February 26, 2006, St. Simon's Island, Ga.
The project was sponsored in part by the Department of the Army under
contract # W81XWH-05-1-0441. The U.S. Army Medical Research Acquisition
Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding
and administering acquisition office. The content of the information does
not necessarily reflect the position or the policy of the Government, and
no official endorsement should be inferred.
It was supported by the New York State Breast Cancer Research and
Education Fund through Department of Health Contract # C017922. Opinions
expressed are solely those of the author and do not necessarily reflect
those of the Health Research Science Board, the New York Department of
Health, of the State of New York.
This material is based upon work supported by the National Science
Foundation under Grant No. (CHE-0457275). Any opinions, findings, and
conclusions or recommendations expressed in this material are those of the
author(s) and do not necessarily reflect the views of the National Science
Foundation.
Part of the Federal support came from the National Institutes of
Health/National Cancer Institute. Federal money represents $475,870 or 82%
of total project costs; non-federal funds equal $100,000 or 18% of total
project costs.
Hamilton College
hamilton
researchers have identified molecules that have been shown to be effective
in the fight against breast cancer. The Hamilton researchers used
state-of-the- art computational techniques in a novel way to design
molecules that they predicted would be effective lead compounds for breast
cancer research. Scientists from the Albany Medical College subsequently
synthesized the predicted molecules and showed that they were indeed
potential anti-breast cancer compounds in animal systems
A paper detailing the research, "Computational Design and Experimental
Discovery of an Anti-estrogenic Peptide Derived from Alpha-Fetoprotein,"
will be published in the May 16 issue of the Journal of American Chemical
Society.
Winslow Professor of Chemistry George Shields and co-director of the
Center for Molecular Design Karl Kirschner led the Hamilton research team
with undergraduate students Katrina Lexa '05, Amanda Salisburg '08,
Katherine Alser '09. The Albany team consisted of Leroy Joseph, Thomas
Andersen, James Bennett, and Herbert Jacobsen of Albany Medical College.
Breast cancer is the most common cancer among women and tamoxifen is
the preferred drug for estrogen receptor-positive breast cancer treatment.
Many of these cancers are intrinsically resistant to tamoxifen or acquire
resistance during treatment. Consequently, there is an ongoing need for
breast cancer drugs that have different molecular targets.
Previous work by the Albany Medical College researchers had shown that
8- mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat
models, interacting with an unsolved receptor, while peptides smaller than
eight amino acids did not.
The Hamilton researchers used advanced computational methods to predict
the structure and dynamics of active peptides, leading to discovery of
smaller peptides with full biological activity. The results were used to
identify smaller peptides with the three dimensional structure of the
larger peptides. These peptides were synthesized and shown to inhibit
estrogen-dependent cell growth in a mouse uterine growth assay, a test
showing reliable correlation with human breast cancer inhibition.
This work was funded by the National Institutes of Health, the New York
State Breast Cancer Research and Education fund, the Department of
Defense's Breast Cancer program, and the National Science Foundation.
Founded in 1879, the Journal of the American Chemical Society is the
flagship journal of the American Chemical Society and the premier medium
for the worldwide publication of fundamental research in all areas of the
chemical sciences. It is the most highly cited chemistry journal.
The results reported in the published article were first presented by
Professor Shields at the 2006 International Symposium on Theory and
Computations in Molecular and Materials Sciences, Biology and Pharmacology,
on February 26, 2006, St. Simon's Island, Ga.
The project was sponsored in part by the Department of the Army under
contract # W81XWH-05-1-0441. The U.S. Army Medical Research Acquisition
Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding
and administering acquisition office. The content of the information does
not necessarily reflect the position or the policy of the Government, and
no official endorsement should be inferred.
It was supported by the New York State Breast Cancer Research and
Education Fund through Department of Health Contract # C017922. Opinions
expressed are solely those of the author and do not necessarily reflect
those of the Health Research Science Board, the New York Department of
Health, of the State of New York.
This material is based upon work supported by the National Science
Foundation under Grant No. (CHE-0457275). Any opinions, findings, and
conclusions or recommendations expressed in this material are those of the
author(s) and do not necessarily reflect the views of the National Science
Foundation.
Part of the Federal support came from the National Institutes of
Health/National Cancer Institute. Federal money represents $475,870 or 82%
of total project costs; non-federal funds equal $100,000 or 18% of total
project costs.
Hamilton College
hamilton
Multiple Sclerosis: Tracking Down The Causes
Over 100,000 people suffer from multiple sclerosis in Germany alone. Despite intensive research, the factors that trigger the disease and influence its progress remain unclear. Scientists from the Max Planck Institute of Neurobiology in Martinsried and an international research team have succeeded in attaining three important new insights into the disease. It would appear that B cells play an unexpected role in the spontaneous development of multiple sclerosis and that particularly aggressive T cells are activated by different proteins. Furthermore, a new animal model is helping the scientists to understand the emergence of the most common form of the disease in Germany. (Nature Medicine, May 31, 2009 & Journal of Experimental Medicine, June 1, 2009)
Multiple Sclerosis (MS) poses enormous problems for both patients and doctors: it is the most common inflammatory disease of the central nervous system in our part of the world and often strikes patients at a relatively young age. In some patients it leads to severe disability. Moreover, despite decades of research on MS, the causes and course of the disease are still largely unclear.
There is much evidence to support the fact that MS is triggered by an autoimmune reaction: immune cells that should actually protect the body against threats like viruses, bacteria and tumours, attack the body's own brain tissue. New treatments now available can attenuate the harmful immune reaction and thus delay the progress of the disease. However, the more effective the treatment, the more serious its side effects. Therefore, it is a matter of extreme urgency that new forms of treatment be developed which can differentiate in a targeted way between the immune cells that cause the disease and those that should be protected. A better understanding of the disease is required in order to achieve this.
Entirely new possibilities
The research of multiple sclerosis has proven particularly difficult. This is due, not least, to the fact that the focus of the disease is embedded in the sensitive brain tissue and is, therefore, inaccessible. More than other branches of medicine, MS research is dependent, therefore, on animal models in its study of the disease. Working in collaboration with an international team, scientists at the Max Planck Institute of Neurobiology have succeeded in developing a very effective animal model. The specially bred mice spontaneously develop a disease pattern that is practically identical to the course of the human form of MS most common in our part of the world. Because the disease also develops spontaneously in humans, the new model is superior to all of the previous models which only develop MS symptoms following injection with brain tissue. Moreover, the research using the new model has already prompted a rather sensational discovery: the emergence of the disease requires significantly more immune cells than previously assumed.
Unrecognised significance
Up to now, MS research has worked on the assumption that the disease mainly arises as a result of attacks on a group of white blood cells known as T cells. These immune-system cells provide a kind of 'immediate response' to pathogens - they recognise the pathogens, activate the immune response and thus trigger the destruction of the harmful cells. In addition to T cells, the immune system also has B cells. These also react to the presence of a pathogen, are activated and start to divide rapidly. Thousands of cells are created which produce a pathogen-specific antibody. An invasion of pathogens can be overcome quickly and effectively through the targeted interaction of T and B cells.
Unlike the T cells, the B cells have hitherto only been assigned a subordinate role in the emergence of multiple sclerosis - erroneously, as the new model now shows. Previous experimentally-generated models of the disease had simply failed to reveal the true role of the B cells.
In the new mouse model, T cells also attack the body's own brain tissue. However, this is not sufficient to trigger the disease, as when the scientists remove the B cells, the animals remain healthy. "This observation surprised us all because it contradicted the prevailing doctrine," notes Gurumoorthy Krishnamoorthy. The new model shows that there most be some kind of interaction between the T and B cells, that the resulting army of B cells triggers the full-blown form disease through its antibody attacks.
More aggressive than others
Even if B cells play a far more significant role than was previously believed, the fact remains that T cells can cause extensive damage to nerve cells in the context of multiple sclerosis. Basically, they can misinterpret any component of the nervous system as a foreign body and launch an attack. However, it is well known that some of the autoreactive T cells are significantly more aggressive than others. One group of these 'special' T cells recognises and attacks the protein MOG, which is found on the surface of brain cells. To the amazement of the neuroimmunologists, however, these cells also attack mice that lack MOG. "This finding was completely unexpected, since the T cells should not really attack anything in the absence of MOG", says Krishnamoorthy. The solution to this puzzle was provided by a broad-based biochemical study: T cells that identify MOG as a foreign body also react to a second, completely different protein in the brain.
New understanding - possible treatments
"Such doubly or even triply activated T cells could be the reason for the significantly greater aggressiveness of these cells", suggests Hartmut Wekerle, the head of the study. And, of course, he is already thinking one step ahead: "We must now find a way of identifying these special T cells in the patient." Based on this, treatments could be developed that specifically suppress the activity of these particularly aggressive T cells or remove them from the tissue. Such a treatment should have considerably fewer side effects than the previous, rather unspecific approaches.
The new animal model, which provides a far better simulation of the human form of the disease, has prompted surprising insights into the role of the B cells in the spontaneous development of MS. This and the astonishing finding that particularly aggressive T cells are activated by different proteins both represent considerable advances in the research of multiple sclerosis. All of these insights could provide the basis for the development of new approaches to the treatment of the disease.
Original work:
1:Gurumoorthy Krishnamoorthy, Amit Saxena, Lennart T. Mars, Helena S. Domingues, Reinhard Mentele, Avraham Ben-Nun, Hans Lassmann, Klaus Dornmair, Florian C. Kurschus, Roland Liblau & Hartmut Wekerle
Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
Nature Medicine, May 31st, 2009
2: Bernadette Pöllinger, Gurumoorthy Krishnamoorthy, Kerstin Berer, Hans Lassmann, Michael R. Bösl, Robert Dunn, Helena S. Domingues, Andreas Holz, Florian C.Kurschus and Hartmut Wekerle
Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOGreactive transgenic T cells recruit endogenous MOG-specific B cells
Journal of Experimental Medicine, June 1st, 2009
Source:
Dr. Stefanie Merker
Max-Planck-Gesellschaft
Multiple Sclerosis (MS) poses enormous problems for both patients and doctors: it is the most common inflammatory disease of the central nervous system in our part of the world and often strikes patients at a relatively young age. In some patients it leads to severe disability. Moreover, despite decades of research on MS, the causes and course of the disease are still largely unclear.
There is much evidence to support the fact that MS is triggered by an autoimmune reaction: immune cells that should actually protect the body against threats like viruses, bacteria and tumours, attack the body's own brain tissue. New treatments now available can attenuate the harmful immune reaction and thus delay the progress of the disease. However, the more effective the treatment, the more serious its side effects. Therefore, it is a matter of extreme urgency that new forms of treatment be developed which can differentiate in a targeted way between the immune cells that cause the disease and those that should be protected. A better understanding of the disease is required in order to achieve this.
Entirely new possibilities
The research of multiple sclerosis has proven particularly difficult. This is due, not least, to the fact that the focus of the disease is embedded in the sensitive brain tissue and is, therefore, inaccessible. More than other branches of medicine, MS research is dependent, therefore, on animal models in its study of the disease. Working in collaboration with an international team, scientists at the Max Planck Institute of Neurobiology have succeeded in developing a very effective animal model. The specially bred mice spontaneously develop a disease pattern that is practically identical to the course of the human form of MS most common in our part of the world. Because the disease also develops spontaneously in humans, the new model is superior to all of the previous models which only develop MS symptoms following injection with brain tissue. Moreover, the research using the new model has already prompted a rather sensational discovery: the emergence of the disease requires significantly more immune cells than previously assumed.
Unrecognised significance
Up to now, MS research has worked on the assumption that the disease mainly arises as a result of attacks on a group of white blood cells known as T cells. These immune-system cells provide a kind of 'immediate response' to pathogens - they recognise the pathogens, activate the immune response and thus trigger the destruction of the harmful cells. In addition to T cells, the immune system also has B cells. These also react to the presence of a pathogen, are activated and start to divide rapidly. Thousands of cells are created which produce a pathogen-specific antibody. An invasion of pathogens can be overcome quickly and effectively through the targeted interaction of T and B cells.
Unlike the T cells, the B cells have hitherto only been assigned a subordinate role in the emergence of multiple sclerosis - erroneously, as the new model now shows. Previous experimentally-generated models of the disease had simply failed to reveal the true role of the B cells.
In the new mouse model, T cells also attack the body's own brain tissue. However, this is not sufficient to trigger the disease, as when the scientists remove the B cells, the animals remain healthy. "This observation surprised us all because it contradicted the prevailing doctrine," notes Gurumoorthy Krishnamoorthy. The new model shows that there most be some kind of interaction between the T and B cells, that the resulting army of B cells triggers the full-blown form disease through its antibody attacks.
More aggressive than others
Even if B cells play a far more significant role than was previously believed, the fact remains that T cells can cause extensive damage to nerve cells in the context of multiple sclerosis. Basically, they can misinterpret any component of the nervous system as a foreign body and launch an attack. However, it is well known that some of the autoreactive T cells are significantly more aggressive than others. One group of these 'special' T cells recognises and attacks the protein MOG, which is found on the surface of brain cells. To the amazement of the neuroimmunologists, however, these cells also attack mice that lack MOG. "This finding was completely unexpected, since the T cells should not really attack anything in the absence of MOG", says Krishnamoorthy. The solution to this puzzle was provided by a broad-based biochemical study: T cells that identify MOG as a foreign body also react to a second, completely different protein in the brain.
New understanding - possible treatments
"Such doubly or even triply activated T cells could be the reason for the significantly greater aggressiveness of these cells", suggests Hartmut Wekerle, the head of the study. And, of course, he is already thinking one step ahead: "We must now find a way of identifying these special T cells in the patient." Based on this, treatments could be developed that specifically suppress the activity of these particularly aggressive T cells or remove them from the tissue. Such a treatment should have considerably fewer side effects than the previous, rather unspecific approaches.
The new animal model, which provides a far better simulation of the human form of the disease, has prompted surprising insights into the role of the B cells in the spontaneous development of MS. This and the astonishing finding that particularly aggressive T cells are activated by different proteins both represent considerable advances in the research of multiple sclerosis. All of these insights could provide the basis for the development of new approaches to the treatment of the disease.
Original work:
1:Gurumoorthy Krishnamoorthy, Amit Saxena, Lennart T. Mars, Helena S. Domingues, Reinhard Mentele, Avraham Ben-Nun, Hans Lassmann, Klaus Dornmair, Florian C. Kurschus, Roland Liblau & Hartmut Wekerle
Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
Nature Medicine, May 31st, 2009
2: Bernadette Pöllinger, Gurumoorthy Krishnamoorthy, Kerstin Berer, Hans Lassmann, Michael R. Bösl, Robert Dunn, Helena S. Domingues, Andreas Holz, Florian C.Kurschus and Hartmut Wekerle
Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOGreactive transgenic T cells recruit endogenous MOG-specific B cells
Journal of Experimental Medicine, June 1st, 2009
Source:
Dr. Stefanie Merker
Max-Planck-Gesellschaft
Potential Treatments From Cryptic Genes
Big pharma gave up on soil bacteria as a source of antibiotics too soon, according to research published in the June issue of Microbiology. Scientists have been mining microbial genomes for new natural products that may have applications in the treatment of MRSA and cancer and have made some exciting discoveries.
"Over the last eight years we have been looking for new natural products in the DNA sequence of the antibiotic-producing bacterium Streptomyces coelicolor," said Professor Gregory Challis from the University of Warwick. "In the last 15 years it became accepted that no new natural products remained to be discovered from these bacteria. Our work shows this widely-held view to be incorrect."
In 1928 Alexander Fleming discovered penicillin, which was subsequently developed into a medicine by Florey and Chain in the 1940s. The antibiotic was hailed as a 'miracle cure' and a golden age of drug discovery followed. However, frequent rediscovery of known natural products and technical challenges forced pharmaceutical companies to retreat and stop looking for new molecules.
Currently the complete genetic sequences of more than 580 microbes are known. It is possible to identify pathways that produce new compounds by looking at the DNA sequences and many gene clusters likely to encode natural products have been analysed. 'Genome mining' has become a dynamic and rapidly advancing field.
Professor Challis and his colleagues have discovered the products of two cryptic gene clusters. One of the clusters was found to produce several compounds that inhibit the proliferation of certain bacteria. Three of these compounds were new ones, named isogermicidin A, B and C. "This discovery was quite unexpected," said Professor Challis. "Our research provides important new methodology for the discovery of new natural products with applications in medicine, such as combating MRSA infections."
The other product they discovered is called coelichelin. Iron is essential for the growth of nearly all micro-organisms. Although it is the fourth most abundant element in the Earth's crust it often exists in a ferric form, which microbes are unable to use. "The gene cluster that directs production of coelicehlin was not known to be involved in the production of any known products," said Professor Challis. "Our research suggests that coelichelin helps S. coelicolor take up iron."
Many researchers have followed Professor Challis and his colleagues into the exciting field of genome mining. "In the near future, compounds with useful biological activities will be patented and progressed into clinical or agricultural trials, depending on their applications" said Professor Challis.
Source: Lucy Goodchild
Society for General Microbiology
"Over the last eight years we have been looking for new natural products in the DNA sequence of the antibiotic-producing bacterium Streptomyces coelicolor," said Professor Gregory Challis from the University of Warwick. "In the last 15 years it became accepted that no new natural products remained to be discovered from these bacteria. Our work shows this widely-held view to be incorrect."
In 1928 Alexander Fleming discovered penicillin, which was subsequently developed into a medicine by Florey and Chain in the 1940s. The antibiotic was hailed as a 'miracle cure' and a golden age of drug discovery followed. However, frequent rediscovery of known natural products and technical challenges forced pharmaceutical companies to retreat and stop looking for new molecules.
Currently the complete genetic sequences of more than 580 microbes are known. It is possible to identify pathways that produce new compounds by looking at the DNA sequences and many gene clusters likely to encode natural products have been analysed. 'Genome mining' has become a dynamic and rapidly advancing field.
Professor Challis and his colleagues have discovered the products of two cryptic gene clusters. One of the clusters was found to produce several compounds that inhibit the proliferation of certain bacteria. Three of these compounds were new ones, named isogermicidin A, B and C. "This discovery was quite unexpected," said Professor Challis. "Our research provides important new methodology for the discovery of new natural products with applications in medicine, such as combating MRSA infections."
The other product they discovered is called coelichelin. Iron is essential for the growth of nearly all micro-organisms. Although it is the fourth most abundant element in the Earth's crust it often exists in a ferric form, which microbes are unable to use. "The gene cluster that directs production of coelicehlin was not known to be involved in the production of any known products," said Professor Challis. "Our research suggests that coelichelin helps S. coelicolor take up iron."
Many researchers have followed Professor Challis and his colleagues into the exciting field of genome mining. "In the near future, compounds with useful biological activities will be patented and progressed into clinical or agricultural trials, depending on their applications" said Professor Challis.
Source: Lucy Goodchild
Society for General Microbiology
Insights Into Human Genetic Makeup Provided By Mixed Population
Genetic diseases and genetically mixed populations can help researchers understand human diversity and human origins according to a Penn State physical anthropologist.
"We wanted to get to a strategy to predict what a face will look like," said Mark D. Shriver, associate professor of biological anthropology. "We want to understand the path of evolution that leads to that part of the selection process."
To pinpoint genes that influence the shape of the human face and head, Shriver began with an online database of genes linked to disease -- Online Mendelian Inheritance of Man. If the symptoms of the disease involved the face or skull the gene implicated in the disease became a candidate for those facial traits.
This approach works because although Shriver looked at genes implicated in disease, those same genes in a healthy person may also influence the same physical trait -- length, width, shape, size -- but within the range normal for healthy individuals. Facial traits vary among humans, but do tend to group by population. For example, in general, West Africans have wider faces than Europeans and Europeans have longer faces than West Africans.
"There is a strong relationship between genetic ancestry and facial traits," said Shriver. "Using individuals of combined ancestry, European and African, we can see how the target genes alter facial traits," he told attendees at the 2009 Annual Meeting of the American Association for the Advancement of Science.
The researchers looked at a combined sample of African Americans with West African and European ancestry whose genetic makeup was known through DNA testing. To make it simpler, anyone with Native American ancestry was eliminated so that only two genetic pools were represented -- West African and European. The researchers reported on a sample of 254 individuals using three-dimensional imaging and measured the distances between specific portions of the face. Each individual had provided a DNA sample.
"We started with 22 landmarks on the faces that could be accurately located in all the images," said Shriver.
These landmarks might be the tip of the nose, the tip of the chin, the outer corner of the eye or other repeatable locations. They then recorded the distances between all the points in all directions, so they had a distance map of each of the faces.
From their DNA profiles, Shriver could determine the admixture percentages of each individual, how much of their genetic make up came from each group. He could then compare the genetically determined admixture to the facial feature differences and determine the relative differences from the parental populations.
"This type of study, done on admixed populations shows that each person is a composite of their ancestors and that the range of facial features is a continuum," says Shriver.
Shriver found that there was a very strong statistical correlation between the amounts of admixture and the facial traits.
"We chose to look at African Americans because they were a large enough and available admixed population," said Shriver. "We are trying to solidify our understanding of the origins of humans and the evolutionary processes. Looking at admixed populations shows us the influence genes have and how they relate to physical features."
Source: A'ndrea Elyse Messer
Penn State
"We wanted to get to a strategy to predict what a face will look like," said Mark D. Shriver, associate professor of biological anthropology. "We want to understand the path of evolution that leads to that part of the selection process."
To pinpoint genes that influence the shape of the human face and head, Shriver began with an online database of genes linked to disease -- Online Mendelian Inheritance of Man. If the symptoms of the disease involved the face or skull the gene implicated in the disease became a candidate for those facial traits.
This approach works because although Shriver looked at genes implicated in disease, those same genes in a healthy person may also influence the same physical trait -- length, width, shape, size -- but within the range normal for healthy individuals. Facial traits vary among humans, but do tend to group by population. For example, in general, West Africans have wider faces than Europeans and Europeans have longer faces than West Africans.
"There is a strong relationship between genetic ancestry and facial traits," said Shriver. "Using individuals of combined ancestry, European and African, we can see how the target genes alter facial traits," he told attendees at the 2009 Annual Meeting of the American Association for the Advancement of Science.
The researchers looked at a combined sample of African Americans with West African and European ancestry whose genetic makeup was known through DNA testing. To make it simpler, anyone with Native American ancestry was eliminated so that only two genetic pools were represented -- West African and European. The researchers reported on a sample of 254 individuals using three-dimensional imaging and measured the distances between specific portions of the face. Each individual had provided a DNA sample.
"We started with 22 landmarks on the faces that could be accurately located in all the images," said Shriver.
These landmarks might be the tip of the nose, the tip of the chin, the outer corner of the eye or other repeatable locations. They then recorded the distances between all the points in all directions, so they had a distance map of each of the faces.
From their DNA profiles, Shriver could determine the admixture percentages of each individual, how much of their genetic make up came from each group. He could then compare the genetically determined admixture to the facial feature differences and determine the relative differences from the parental populations.
"This type of study, done on admixed populations shows that each person is a composite of their ancestors and that the range of facial features is a continuum," says Shriver.
Shriver found that there was a very strong statistical correlation between the amounts of admixture and the facial traits.
"We chose to look at African Americans because they were a large enough and available admixed population," said Shriver. "We are trying to solidify our understanding of the origins of humans and the evolutionary processes. Looking at admixed populations shows us the influence genes have and how they relate to physical features."
Source: A'ndrea Elyse Messer
Penn State
A Step Closer To Unravelling The Mystery Of How Cells Control The Number Of Centrosomes
In the 13th January print edition of the journal Current Biology, Instituto Gubenkian de Ciencia researchers provide insight into an old mystery in cell biology, and offer up new clues to understanding cancer. InГЄs Cunha Ferreira and MГіnica Bettencourt Dias, working with researchers at the universities of Cambridge, UK, and Siena, Italy, unravelled the mystery of how cells count the number of centrosomes, the structure that regulates the cell's skeleton, controls the multiplication of cells, and is often transformed in cancer.
This research addresses an ancient question: how does a cell know how many centrosomes it has? It is equally an important question, since both an excess or absence of centrosomes are associated with disease, from infertility to cancer.
Each cell has, at most, two centrosomes. Whenever a cell divides, each centrosome gives rise to a single daughter centrosome, inherited by one of the daughter cells. Thus, there is strict control on progeny! By using the fruit fly, the IGC researchers identified the molecule that is responsible for this 'birth control policy' of the cell - a molecule called Slimb. In the absence of Slimb, each mother centrosome can give rise to several daughters in one go, leading to an excess of centrosomes in the cell.
In recent years, Monica's group has produced several important findings relating to centrosome control: they identified another molecule, SAK, as the trigger for the formation of centrosomes. When SAK is absent, there are no centrosomes, whereas if SAK is overproduced, the cell has too many centrosomes. These results were published in the prestigious journals Current Biology and Science, in 2005 and 2007. Now, the group has discovered the player in the next level up: Slimb mediates the destruction of SAK, and in so doing, ultimately controls the number of centrosomes in a cell.
Monica explains, 'We carried out these studies in the fruit fly, but we know that the same mechanism acts in mice and even in humans. Knowing that Slimb is altered in several cancers opens up new avenues of research into the mechanisms underlying the change in the number of centrosomes seen in many tumours'.
MГіnica first became interested in centrosomes and in SAK when she was an Associate Researcher at Cambridge University, UK, and has pursued this interest at the IGC, where she has been group leader of the Cell Cycle Regulation laboratory since 2006. InГЄs Cunha Ferreira travelled with Monica from Cambridge, and is now in her second year of the in-house PhD programme. Two other PhD students in the lab also contributed to this research, Ana Rodrigues Martins and InГЄs Bento.
Source: Ana Godinho
Instituto Gulbenkian de Ciencia
This research addresses an ancient question: how does a cell know how many centrosomes it has? It is equally an important question, since both an excess or absence of centrosomes are associated with disease, from infertility to cancer.
Each cell has, at most, two centrosomes. Whenever a cell divides, each centrosome gives rise to a single daughter centrosome, inherited by one of the daughter cells. Thus, there is strict control on progeny! By using the fruit fly, the IGC researchers identified the molecule that is responsible for this 'birth control policy' of the cell - a molecule called Slimb. In the absence of Slimb, each mother centrosome can give rise to several daughters in one go, leading to an excess of centrosomes in the cell.
In recent years, Monica's group has produced several important findings relating to centrosome control: they identified another molecule, SAK, as the trigger for the formation of centrosomes. When SAK is absent, there are no centrosomes, whereas if SAK is overproduced, the cell has too many centrosomes. These results were published in the prestigious journals Current Biology and Science, in 2005 and 2007. Now, the group has discovered the player in the next level up: Slimb mediates the destruction of SAK, and in so doing, ultimately controls the number of centrosomes in a cell.
Monica explains, 'We carried out these studies in the fruit fly, but we know that the same mechanism acts in mice and even in humans. Knowing that Slimb is altered in several cancers opens up new avenues of research into the mechanisms underlying the change in the number of centrosomes seen in many tumours'.
MГіnica first became interested in centrosomes and in SAK when she was an Associate Researcher at Cambridge University, UK, and has pursued this interest at the IGC, where she has been group leader of the Cell Cycle Regulation laboratory since 2006. InГЄs Cunha Ferreira travelled with Monica from Cambridge, and is now in her second year of the in-house PhD programme. Two other PhD students in the lab also contributed to this research, Ana Rodrigues Martins and InГЄs Bento.
Source: Ana Godinho
Instituto Gulbenkian de Ciencia
Cell Insight Could Lead To New Approach To Medicines
A surprising discovery about the complex make-up of our cells could lead to the development of new types of medicines, a study suggests.
Scientists studying interactions between cell proteins - which enable the cells in our bodies to function - have shown that proteins communicate not by a series of simple one-to-one communications, but by a complex network of chemical messages.
The findings suggest that medicines would be more effective if they were designed differently. Drugs could have a greater effect on cell function by targeting groups of proteins working together, rather than individual proteins.
Results were obtained by studying yeast, which has many corresponding proteins in human cells. Researchers, including scientists from the University of Edinburgh, used advanced technology to identify hundreds of different proteins, and then used statistical analysis to identify the more important links between them, mapping almost 2000 connections in all.
Scientists expected to find simple links between individual proteins but were surprised to find that proteins were inter-connected in a complex web.
Dr Victor Neduva, of the University of Edinburgh, who took part in the study, said: "Our studies have revealed an intricate network of proteins within cells that is much more complex than we previously thought. This suggests that drugs should be more complex to treat illnesses effectively.
Professor Mike Tyers, who led the study, said: "Medicines could work better if they targeted networks of proteins rather than sole proteins associated with particular illnesses."
The research, published in Science, carried out in collaboration with Mount Sinai Hospital, Ontario and the Universities of Michigan and Toronto, was supported by the Royal Society and the Scottish Universities Life Sciences Alliance.
Source:
Catriona Kelly
University of Edinburgh
Scientists studying interactions between cell proteins - which enable the cells in our bodies to function - have shown that proteins communicate not by a series of simple one-to-one communications, but by a complex network of chemical messages.
The findings suggest that medicines would be more effective if they were designed differently. Drugs could have a greater effect on cell function by targeting groups of proteins working together, rather than individual proteins.
Results were obtained by studying yeast, which has many corresponding proteins in human cells. Researchers, including scientists from the University of Edinburgh, used advanced technology to identify hundreds of different proteins, and then used statistical analysis to identify the more important links between them, mapping almost 2000 connections in all.
Scientists expected to find simple links between individual proteins but were surprised to find that proteins were inter-connected in a complex web.
Dr Victor Neduva, of the University of Edinburgh, who took part in the study, said: "Our studies have revealed an intricate network of proteins within cells that is much more complex than we previously thought. This suggests that drugs should be more complex to treat illnesses effectively.
Professor Mike Tyers, who led the study, said: "Medicines could work better if they targeted networks of proteins rather than sole proteins associated with particular illnesses."
The research, published in Science, carried out in collaboration with Mount Sinai Hospital, Ontario and the Universities of Michigan and Toronto, was supported by the Royal Society and the Scottish Universities Life Sciences Alliance.
Source:
Catriona Kelly
University of Edinburgh
U.S. House passes resolution recognizing National Chemistry Week, Oct. 16-22
The U.S. House of Representatives on Oct. 17 passed a resolution, H.Res.457, recognizing the week of Oct. 16-22 as National Chemistry Week (NCW). Through the resolution, the House recognized "that the important contributions of chemical scientists and engineers to technological progress and the health of many industries have created new jobs, boosted economic growth, and improved the nation's health and standard of living."
The resolution was sponsored by Reps. Rush Holt (D-N.J.) and Vern Ehlers (R-Mich.), the two Ph.D. scientists currently serving in the House of Representatives. Reps. Judy Biggert (R-Ill.), Phil Gingrey (R-Ga.), John Olver (D-Mass.) and 12 other members cosponsored the bill, including House Science Committee Chairman Sherwood Boehlert (R-N.Y.) and Ranking Democratic Member Bart Gordon (D-Tenn.).
American Chemical Society President William F. Carroll, Jr. said, "The American Chemical Society thanks our friends, Representatives Rush Holt and Vern Ehlers and their cosponsors, for their work to recognize the week of October 16, 2005, as National Chemistry Week. They have helped to highlight the excitement of science to children throughout the country. We are pleased to work regularly with them to strengthen science education and research as a foundation for a better future."
National Chemistry Week, an annual community-based educational event sponsored by the ACS, features activities and events organized by local ACS members, businesses and schools. These events give kids the opportunity to learn about chemistry through fun, hands-on activities and demonstrations. This year's theme, "The Joy of Toys," is designed to capture kids' imaginations by showing them something familiar and fun (e.g. Silly Putty or an Etch-a-Sketch) and encouraging them to ask "why?" and "how?"
Carroll is visiting 15 cities in 10 days in what the Society is calling the "Extreme National Chemistry Week Tour." During the tour, Carroll is meeting with students across the country at schools, science fairs and other community events to highlight the importance of science education and remind students that chemistry is essential to modern life.
Rep. Holt said, "Toys spark imagination, imagination fuels innovation. It is in the best interest of our Nation to create both a curiosity and a desire to understand our world and to fuel a technologically and scientifically literate, critical thinking population to carry us forward in the 21st century."
Rep. Ehlers added, "At a time when our workforce is in great need of increased scientific and mathematic literacy, it is important to stimulate children's interest in the chemical sciences so that they will consider careers in these fields and potentially discover the innovations of the future. What better way to stimulate interest than with something fun like National Chemistry Week and 'The Joy of Toys'?"
The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 158,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.
For more information on National Chemistry Week, visit the ACS Web site: chemistry.
Michael Bernstein
m_bernsteinacs
American Chemical Society
acs
The resolution was sponsored by Reps. Rush Holt (D-N.J.) and Vern Ehlers (R-Mich.), the two Ph.D. scientists currently serving in the House of Representatives. Reps. Judy Biggert (R-Ill.), Phil Gingrey (R-Ga.), John Olver (D-Mass.) and 12 other members cosponsored the bill, including House Science Committee Chairman Sherwood Boehlert (R-N.Y.) and Ranking Democratic Member Bart Gordon (D-Tenn.).
American Chemical Society President William F. Carroll, Jr. said, "The American Chemical Society thanks our friends, Representatives Rush Holt and Vern Ehlers and their cosponsors, for their work to recognize the week of October 16, 2005, as National Chemistry Week. They have helped to highlight the excitement of science to children throughout the country. We are pleased to work regularly with them to strengthen science education and research as a foundation for a better future."
National Chemistry Week, an annual community-based educational event sponsored by the ACS, features activities and events organized by local ACS members, businesses and schools. These events give kids the opportunity to learn about chemistry through fun, hands-on activities and demonstrations. This year's theme, "The Joy of Toys," is designed to capture kids' imaginations by showing them something familiar and fun (e.g. Silly Putty or an Etch-a-Sketch) and encouraging them to ask "why?" and "how?"
Carroll is visiting 15 cities in 10 days in what the Society is calling the "Extreme National Chemistry Week Tour." During the tour, Carroll is meeting with students across the country at schools, science fairs and other community events to highlight the importance of science education and remind students that chemistry is essential to modern life.
Rep. Holt said, "Toys spark imagination, imagination fuels innovation. It is in the best interest of our Nation to create both a curiosity and a desire to understand our world and to fuel a technologically and scientifically literate, critical thinking population to carry us forward in the 21st century."
Rep. Ehlers added, "At a time when our workforce is in great need of increased scientific and mathematic literacy, it is important to stimulate children's interest in the chemical sciences so that they will consider careers in these fields and potentially discover the innovations of the future. What better way to stimulate interest than with something fun like National Chemistry Week and 'The Joy of Toys'?"
The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 158,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.
For more information on National Chemistry Week, visit the ACS Web site: chemistry.
Michael Bernstein
m_bernsteinacs
American Chemical Society
acs
Chemicals' Study Pinpoints Threat To Workers' Lungs
Tiny particles used in a range of everyday products from computers to shampoo can adversely affect the lungs in very different ways, a study has shown.
Research by the University of Edinburgh suggests that industrial manufacturers using nanoparticles should be aware of the risks that different types of nanoparticles pose to workers who handle them.
Nanoparticles - which can be 10,000 times smaller than the width of a human hair - are potentially hazardous to workers handling the chemicals used to make products as they may be at risk of inhaling them.
The particles are not, however, thought to pose any substantial risk once they are incorporated in consumer goods used by the public.
The study, published in Environmental Health Perspectives, showed that four different types of nanoparticles produced distinct patterns of lung injury in rats, some involving the immune system.
Researchers found that some nanoparticles were more likely to trigger an asthmatic-style reaction while others led to a worsening severe lung injury.
The study highlights the need for animal models until there are improved cell-based tests to predict the effects of nanoparticles, since the use of cell cultures alone would not be able to pick up the extent of different diseases the nanoparticles are likely to cause.
Ken Donaldson, Professor of Respiratory Toxicology at the University of Edinburgh, said: "Nanoparticles are becoming more important in industry and are being used in ever-increasing amounts. This study shows that different types of nanoparticles may produce different diseases in those exposed to them in industry.
"Therefore each kind of nanoparticle needs to be assessed and appropriate care taken to minimise exposure consistent with the risk they pose. This will ensure better health and safety for those working with these new materials."
Source:
University of Edinburgh
Research by the University of Edinburgh suggests that industrial manufacturers using nanoparticles should be aware of the risks that different types of nanoparticles pose to workers who handle them.
Nanoparticles - which can be 10,000 times smaller than the width of a human hair - are potentially hazardous to workers handling the chemicals used to make products as they may be at risk of inhaling them.
The particles are not, however, thought to pose any substantial risk once they are incorporated in consumer goods used by the public.
The study, published in Environmental Health Perspectives, showed that four different types of nanoparticles produced distinct patterns of lung injury in rats, some involving the immune system.
Researchers found that some nanoparticles were more likely to trigger an asthmatic-style reaction while others led to a worsening severe lung injury.
The study highlights the need for animal models until there are improved cell-based tests to predict the effects of nanoparticles, since the use of cell cultures alone would not be able to pick up the extent of different diseases the nanoparticles are likely to cause.
Ken Donaldson, Professor of Respiratory Toxicology at the University of Edinburgh, said: "Nanoparticles are becoming more important in industry and are being used in ever-increasing amounts. This study shows that different types of nanoparticles may produce different diseases in those exposed to them in industry.
"Therefore each kind of nanoparticle needs to be assessed and appropriate care taken to minimise exposure consistent with the risk they pose. This will ensure better health and safety for those working with these new materials."
Source:
University of Edinburgh
New Research Shows Immune Cells Use Bungee Of Death To Kill Dangerous Cells
Immune cells ensnare dangerous cells that are on the run with a bungee-like nanotube, according to research published in the Proceedings of the National Academy of Sciences. The study, by researchers from Imperial College London, shows that natural killer (NK) cells use this bungee to destroy cells that could otherwise escape them.
NK cells are our first line of defence against dangerous cells, such as tumour cells and cells infected with bacteria and viruses. Researchers are keen to understand how NK cells work because they help the body to fight infection and stop tumours from growing. It is thought that it may ultimately be possible to design drugs that harness the cells' ability to fight disease.
Prior to today's study, it was already known that NK cells can kill their target cells by attaching onto them, forming a connection called an immune synapse, which they use to pass toxic molecules into their target. However, sometimes the target cells move away from the NK cells to escape being killed.
Today's study, which was funded by the Medical Research Council and the Association pour la recherche sur le cancer (ARC), shows that NK cells can keep hold of their target cells by snaring them with a bungee-like tube, called a membrane nanotube. The cells then either recoil the target cells back into direct contact to be killed, or kill them from a distance.
Professor Daniel Davis, corresponding author of the study from the Division of Cell & Molecular Biology at Imperial College London said: "Natural Killer cells are cells that are really good at killing tumours and virus-infected cells. It was thought they kill these diseased cells only by sticking to them tightly for several minutes. These new movies show that in fact they also tether cells with long membrane connections and can pull diseased cells back into contact. We think they may also use these nanotubes to kill them from a distance.
"The movies show the process vividly but the next step is difficult because we have to know where and when these processes are important in your body, and the technology to see such thin nanotubes in the body hasn't been invented yet! It's a very new research area and we need to learn how the process works precisely so that we can then think about ways to design drugs that help immune cells kill," added Professor Davis.
Their next step will be to find out exactly how the bungee tubes help immune cells kill their target cells. The researchers hope that a better understanding of the process may help others in the future to develop drugs to improve the function of NK cells.
The researchers looked at the membrane nanotubes by staining cells with a dye that reveals membranes in microscope images. They found membrane nanotubes connecting NK cells with other NK cells, tumour cells, cells infected with viruses and cancer cells.
The researchers took video footage of the cells, showing the target cells moving away and being pulled back towards the NK cells. When a target cell moves away from an NK cell, it normally moves 'head' first, at around eight micrometres per minute. However, today's research shows that when the NK cell pulls its target cell back using the nanotube bungee it moves much faster, at around 14 micrometres per minute, and the cell is pulled backwards.
Membrane nanotubes increase an NK cell's chance of killing its target cell from a distance dramatically. In today's study, NK cells killed their target cells from a distance in 12 out of 16 cases (75 per cent) if they were connected by a membrane nanotube, compared to four out of 18 (25 per cent) if the nanotube was cut.
"Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells" PNAS, Monday 8 March 2010.
Source:
Lucy Goodchild
Imperial College London
NK cells are our first line of defence against dangerous cells, such as tumour cells and cells infected with bacteria and viruses. Researchers are keen to understand how NK cells work because they help the body to fight infection and stop tumours from growing. It is thought that it may ultimately be possible to design drugs that harness the cells' ability to fight disease.
Prior to today's study, it was already known that NK cells can kill their target cells by attaching onto them, forming a connection called an immune synapse, which they use to pass toxic molecules into their target. However, sometimes the target cells move away from the NK cells to escape being killed.
Today's study, which was funded by the Medical Research Council and the Association pour la recherche sur le cancer (ARC), shows that NK cells can keep hold of their target cells by snaring them with a bungee-like tube, called a membrane nanotube. The cells then either recoil the target cells back into direct contact to be killed, or kill them from a distance.
Professor Daniel Davis, corresponding author of the study from the Division of Cell & Molecular Biology at Imperial College London said: "Natural Killer cells are cells that are really good at killing tumours and virus-infected cells. It was thought they kill these diseased cells only by sticking to them tightly for several minutes. These new movies show that in fact they also tether cells with long membrane connections and can pull diseased cells back into contact. We think they may also use these nanotubes to kill them from a distance.
"The movies show the process vividly but the next step is difficult because we have to know where and when these processes are important in your body, and the technology to see such thin nanotubes in the body hasn't been invented yet! It's a very new research area and we need to learn how the process works precisely so that we can then think about ways to design drugs that help immune cells kill," added Professor Davis.
Their next step will be to find out exactly how the bungee tubes help immune cells kill their target cells. The researchers hope that a better understanding of the process may help others in the future to develop drugs to improve the function of NK cells.
The researchers looked at the membrane nanotubes by staining cells with a dye that reveals membranes in microscope images. They found membrane nanotubes connecting NK cells with other NK cells, tumour cells, cells infected with viruses and cancer cells.
The researchers took video footage of the cells, showing the target cells moving away and being pulled back towards the NK cells. When a target cell moves away from an NK cell, it normally moves 'head' first, at around eight micrometres per minute. However, today's research shows that when the NK cell pulls its target cell back using the nanotube bungee it moves much faster, at around 14 micrometres per minute, and the cell is pulled backwards.
Membrane nanotubes increase an NK cell's chance of killing its target cell from a distance dramatically. In today's study, NK cells killed their target cells from a distance in 12 out of 16 cases (75 per cent) if they were connected by a membrane nanotube, compared to four out of 18 (25 per cent) if the nanotube was cut.
"Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells" PNAS, Monday 8 March 2010.
Source:
Lucy Goodchild
Imperial College London
Prestigious NIH Director's Pioneer And New Innovator Awards Received By Penn Researchers
James Eberwine, PhD, the Elmer Holmes Bobst Professor of Pharmacology and co-director of the Penn Genome Frontiers Institute, has been awarded the National Institutes of Health Pioneer Award, which provides $2.5 million over the next five years. Aaron Gitler, PhD, Assistant Professor of Cell and Developmental Biology, has been awarded the NIH New Innovator Award, which provides $1.5 million over the same timeframe. Eberwine investigates how single neurons work in the context of surrounding cells and how this relates to the emerging field of RNA-based therapeutics and Gitler studies yeast cells to define mechanisms of neurodegenerative diseases and screen for new treatment targets.
"These programs are central elements of NIH efforts to encourage and fund especially novel investigator-initiated research, even if it might carry a greater-than-usual degree of risk of not succeeding," comments NIH Director Elias A. Zerhouni, M.D. on the aim of the Pioneer and Innovator awards. "The awards also reflect our goal of supporting more investigators in the early stages of their careers."
"The Pioneer award will enable us to try many different -- some risky-- approaches to understanding how a cell's individual biochemical characteristics, or phenotype, develops and is regulated," says Eberwine. "One can think of this pursuit as a complex maze with many false passages and the funding will enable us to move much more rapidly through this scientific maze."
"The Innovator award will allow me to take risks and expand my research program in new directions without worrying about funding for a while," says Gitler. "It will be great to be able to focus all of my attention on research and continue to do the work I am most excited about."
Eberwine proposes that by transferring the catalogue of RNA molecules from one cell to another in a way that makes the recipient cells' survival dependent on the donor RNA, the recipient cell's phenotype will mimic the donor cell phenotype. Having the ability to transfer phenotypes between cells would provide important new insights into mechanisms controlling cell differentiation and function. Preliminary data show that donor cell RNA populations carry "memory functions" in which donor RNA can induce long-term changes in the genome of host cells to effectively match the inner workings of the donor cell. The ability to selectively and rationally create cellular phenotypes may yield novel individualized therapeutics.
Gitler studies the mechanisms that cause proteins to misfold and aggregate by identifying genes and cellular pathways that are affected by misfolded human disease proteins. By harnessing baker's yeast as a model system to study the mechanisms underpinning protein-misfolding diseases such as Alzheimer's and Parkinson's, the Gitler lab aims to perform high-throughput, genome-wide screens to elucidate the basic cellular mechanisms of toxicity. These yeast models will provide the Gitler lab with a unique opportunity to observe and understand protein folding and misfolding in real time as it occurs in a living cell. The innovative aspect of Gitler's approach is not just that they are working in yeast, but that they are using this system as a tool to discover new drug targets.
For both programs, NIH selects recipients through special application and evaluation processes. Distinguished outside experts identify the most highly competitive applicants. The Advisory Committee to the Director, NIH, performs the second level of review and Zerhouni makes final decisions based on the outside evaluations and programmatic considerations.
More information on the Pioneer Award
More information on the New Innovator Award
Details on the research plans of the new recipients
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's top 10 "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Karen Kreeger
University of Pennsylvania School of Medicine
"These programs are central elements of NIH efforts to encourage and fund especially novel investigator-initiated research, even if it might carry a greater-than-usual degree of risk of not succeeding," comments NIH Director Elias A. Zerhouni, M.D. on the aim of the Pioneer and Innovator awards. "The awards also reflect our goal of supporting more investigators in the early stages of their careers."
"The Pioneer award will enable us to try many different -- some risky-- approaches to understanding how a cell's individual biochemical characteristics, or phenotype, develops and is regulated," says Eberwine. "One can think of this pursuit as a complex maze with many false passages and the funding will enable us to move much more rapidly through this scientific maze."
"The Innovator award will allow me to take risks and expand my research program in new directions without worrying about funding for a while," says Gitler. "It will be great to be able to focus all of my attention on research and continue to do the work I am most excited about."
Eberwine proposes that by transferring the catalogue of RNA molecules from one cell to another in a way that makes the recipient cells' survival dependent on the donor RNA, the recipient cell's phenotype will mimic the donor cell phenotype. Having the ability to transfer phenotypes between cells would provide important new insights into mechanisms controlling cell differentiation and function. Preliminary data show that donor cell RNA populations carry "memory functions" in which donor RNA can induce long-term changes in the genome of host cells to effectively match the inner workings of the donor cell. The ability to selectively and rationally create cellular phenotypes may yield novel individualized therapeutics.
Gitler studies the mechanisms that cause proteins to misfold and aggregate by identifying genes and cellular pathways that are affected by misfolded human disease proteins. By harnessing baker's yeast as a model system to study the mechanisms underpinning protein-misfolding diseases such as Alzheimer's and Parkinson's, the Gitler lab aims to perform high-throughput, genome-wide screens to elucidate the basic cellular mechanisms of toxicity. These yeast models will provide the Gitler lab with a unique opportunity to observe and understand protein folding and misfolding in real time as it occurs in a living cell. The innovative aspect of Gitler's approach is not just that they are working in yeast, but that they are using this system as a tool to discover new drug targets.
For both programs, NIH selects recipients through special application and evaluation processes. Distinguished outside experts identify the most highly competitive applicants. The Advisory Committee to the Director, NIH, performs the second level of review and Zerhouni makes final decisions based on the outside evaluations and programmatic considerations.
More information on the Pioneer Award
More information on the New Innovator Award
Details on the research plans of the new recipients
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's top 10 "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Karen Kreeger
University of Pennsylvania School of Medicine
Study Shows Competition Not Climate Change Led To Neanderthal Extinction
In a recently conducted study, a multidisciplinary French-American research team with expertise in archaeology, past climates, and ecology reported
that Neanderthal extinction was principally a result of competition with Cro-Magnon populations, rather than the consequences of climate change.
The study, reported in the online, open-access journal PLoS ONE on December 24, figures in the ongoing debate on the reasons behind the eventual
disappearance of Neanderthal populations, which occupied Europe prior to the arrival of human populations like us around 40,000 years ago. Led by Dr
William E. Banks, the authors, who belong to the French Centre National de la Recherche Scientifique, l'Ecole Pratique d'Hautes Etudes, and the
University of Kansas, reached their conclusion by reconstructing climatic conditions during this period and analyzing the distribution of
archaeological sites associated with the last Neanderthals and the first modern human populations with an approach typically used to study the impact
of climate change on biodiversity.
This method uses geographic locations of archaeological sites dated by radiocarbon, in conjunction with high-resolution simulations of past climates
for specific periods, and employs an algorithm to analyze relationships between the two datasets to reconstruct potential areas occupied by each human
population and to determine if and how climatic conditions played a role in shaping these areas. In other words, by integrating archaeological and
paleoenvironmental datasets, this predictive method can reconstruct the regions that a past population could potentially have occupied. By repeating
the modeling process hundreds of times and evaluating where the errors occur, this machine-learning algorithm is able to provide robust predictions of
regions that could have been occupied by specific human cultures.
This modeling approach also allows the projection of the ecological footprint of one culture onto the environmental conditions of a later climatic
phase-by comparing this projected prediction to the known archaeological sites dated to this later period, it is possible to determine if the
ecological niche exploited by this human population remained the same, or if it contracted or expanded during that period of time.
Comparing these reconstructed areas for Neanderthals and anatomically modern humans during each of the climatic phases concerned, and by projecting
each niche onto the subsequent climatic phases, Banks and colleagues determined that Neanderthals had the possibility to maintain their range across
Europe during a period of less severe climatic conditions called Greenland Interstadial 8 (GI8).
However, the archaeological record shows that this did not occur, and Neanderthal disappearance occurs at a point when we see the geographic expansion
of the ecological niche occupied by modern humans during GI8. The researchers' models predict the southern limit of the modern human territory to be
near the Ebro River Valley in northern Spain during the preceding cold period called Heinrich Event 4 (H4), and that this southern boundary moved to
the south during the more temperate phase GI8.
The researchers conclude that the Neanderthal populations that occupied what is now southern Spain were the last to survive because they were able to
avoid direct competition with modern humans since the two populations exploited distinct territories during the cold climatic conditions of H4. They
also point out that during this population event contact between Neanderthals and modern humans may have permitted cultural and genetic exchanges.
Citation:
"Neanderthal Extinction by Competitive Exclusion."
Banks WE, d'Errico F, Peterson AT, Kageyama M, Sima A, et al. (2008)
PLoS ONE 3(12): e3972. doi:10.1371/journal.pone.0003972
Click here to view article online
About PLoS ONE
PLoS ONE is the first journal of primary research from all areas of science to employ a combination of peer review and post-publication rating and
commenting, to maximize the impact of every report it publishes. PLoS ONE is published by the Public Library of Science (PLoS), the open-access
publisher whose goal is to make the world's scientific and medical literature a public resource.
PLoS ONE
that Neanderthal extinction was principally a result of competition with Cro-Magnon populations, rather than the consequences of climate change.
The study, reported in the online, open-access journal PLoS ONE on December 24, figures in the ongoing debate on the reasons behind the eventual
disappearance of Neanderthal populations, which occupied Europe prior to the arrival of human populations like us around 40,000 years ago. Led by Dr
William E. Banks, the authors, who belong to the French Centre National de la Recherche Scientifique, l'Ecole Pratique d'Hautes Etudes, and the
University of Kansas, reached their conclusion by reconstructing climatic conditions during this period and analyzing the distribution of
archaeological sites associated with the last Neanderthals and the first modern human populations with an approach typically used to study the impact
of climate change on biodiversity.
This method uses geographic locations of archaeological sites dated by radiocarbon, in conjunction with high-resolution simulations of past climates
for specific periods, and employs an algorithm to analyze relationships between the two datasets to reconstruct potential areas occupied by each human
population and to determine if and how climatic conditions played a role in shaping these areas. In other words, by integrating archaeological and
paleoenvironmental datasets, this predictive method can reconstruct the regions that a past population could potentially have occupied. By repeating
the modeling process hundreds of times and evaluating where the errors occur, this machine-learning algorithm is able to provide robust predictions of
regions that could have been occupied by specific human cultures.
This modeling approach also allows the projection of the ecological footprint of one culture onto the environmental conditions of a later climatic
phase-by comparing this projected prediction to the known archaeological sites dated to this later period, it is possible to determine if the
ecological niche exploited by this human population remained the same, or if it contracted or expanded during that period of time.
Comparing these reconstructed areas for Neanderthals and anatomically modern humans during each of the climatic phases concerned, and by projecting
each niche onto the subsequent climatic phases, Banks and colleagues determined that Neanderthals had the possibility to maintain their range across
Europe during a period of less severe climatic conditions called Greenland Interstadial 8 (GI8).
However, the archaeological record shows that this did not occur, and Neanderthal disappearance occurs at a point when we see the geographic expansion
of the ecological niche occupied by modern humans during GI8. The researchers' models predict the southern limit of the modern human territory to be
near the Ebro River Valley in northern Spain during the preceding cold period called Heinrich Event 4 (H4), and that this southern boundary moved to
the south during the more temperate phase GI8.
The researchers conclude that the Neanderthal populations that occupied what is now southern Spain were the last to survive because they were able to
avoid direct competition with modern humans since the two populations exploited distinct territories during the cold climatic conditions of H4. They
also point out that during this population event contact between Neanderthals and modern humans may have permitted cultural and genetic exchanges.
Citation:
"Neanderthal Extinction by Competitive Exclusion."
Banks WE, d'Errico F, Peterson AT, Kageyama M, Sima A, et al. (2008)
PLoS ONE 3(12): e3972. doi:10.1371/journal.pone.0003972
Click here to view article online
About PLoS ONE
PLoS ONE is the first journal of primary research from all areas of science to employ a combination of peer review and post-publication rating and
commenting, to maximize the impact of every report it publishes. PLoS ONE is published by the Public Library of Science (PLoS), the open-access
publisher whose goal is to make the world's scientific and medical literature a public resource.
PLoS ONE
Critical Protein Complex In Formation Of Cell Cilia Identified By NYU Scientists
An international team led by NYU Cancer Institute have identified a protein complex that regulates the formation of cilia, which are found on virtually all mature human cells and are essential to normal cell function.
The new report, published this week by Developmental Cell and selected as the featured publication of the open-access online edition, describes how three proteins work together to regulate the formation of primary cilia. The study led by Brian Dynlacht, Ph.D., professor of pathology and director of NYU Cancer Institute Genomics Facility, investigates these antenna-like structures, once thought to be vestigial remnants of cell evolution, which have recently emerged as a focal point of research in developmental cell biology.
"We are trying to understand the regulation of processes that are fundamental to normal cell development and health in humans," said William Y. Tsang, Ph.D., of the NYU School of Medicine and Cancer Institute, and first author of the paper. "Defective cilia are implicated in a wide range of serious illnesses such as polycystic kidney disease, retinal degeneration, and neurological disorders. Inappropriate activation of signaling molecules that normally reside at the primary cilium, may lead to certain cancers."
At the center of the process lies the protein CEP290, which normally promotes primary cilia formation in mature cells. Dr. Tsang and his colleagues discovered that a second protein, CP110, normally suppresses the function of CEP290 until cells are fully mature. At that point, CP110 is destroyed, freeing CEP290 to interact with a third protein, Rab8a, to promote cilia formation on the surface of the mature cell.
The team's findings may help to identify potential targets for future drug design.
"Ciliogenesis is a fundamental process. These structures are found in almost every type of human cell you can imagine," Dr. Tsang said. "If we can ever design drugs that will restore the formation and function of cilia even in the presence of CEP290 mutations, then that would be one way to cure the defects that lead to ciliary diseases."
Research so far has been using in vitro human cell lines. However, team members from the University of Michigan and National Eye Institute have developed a mouse model with a CEP290 mutation implicated in retinal degeneration, and the NYU group is planning a study of human CEP290 mutations to see if they can correlate genotypes to their expression in specific ciliary diseases.
The authors of this study are NYU Cancer Institute scientists William Y. Tsang and Brian David Dynlacht; Carine Bossard (Centre for Genomic Regulation, Barcelona); Hemant Khanna (Department of Ophthalmology and Visual Sciences, University of Michigan); Johan Peränen (Institute of Biotechnology, Program in Cellular Biotechnology, University of Helsinki), Anand Swaroop (Department of Ophthalmology and Visual Sciences, University of Michigan / National Eye Institute, Neurobiology Neurodegeneration & Repair Laboratory, Bethesda, MD); and Vivek Malhotra (Centre for Genomic Regulation, Barcelona).
Click here to access the complete article.
Source: Jennifer Berman
NYU Langone Medical Center / New York University School of Medicine
The new report, published this week by Developmental Cell and selected as the featured publication of the open-access online edition, describes how three proteins work together to regulate the formation of primary cilia. The study led by Brian Dynlacht, Ph.D., professor of pathology and director of NYU Cancer Institute Genomics Facility, investigates these antenna-like structures, once thought to be vestigial remnants of cell evolution, which have recently emerged as a focal point of research in developmental cell biology.
"We are trying to understand the regulation of processes that are fundamental to normal cell development and health in humans," said William Y. Tsang, Ph.D., of the NYU School of Medicine and Cancer Institute, and first author of the paper. "Defective cilia are implicated in a wide range of serious illnesses such as polycystic kidney disease, retinal degeneration, and neurological disorders. Inappropriate activation of signaling molecules that normally reside at the primary cilium, may lead to certain cancers."
At the center of the process lies the protein CEP290, which normally promotes primary cilia formation in mature cells. Dr. Tsang and his colleagues discovered that a second protein, CP110, normally suppresses the function of CEP290 until cells are fully mature. At that point, CP110 is destroyed, freeing CEP290 to interact with a third protein, Rab8a, to promote cilia formation on the surface of the mature cell.
The team's findings may help to identify potential targets for future drug design.
"Ciliogenesis is a fundamental process. These structures are found in almost every type of human cell you can imagine," Dr. Tsang said. "If we can ever design drugs that will restore the formation and function of cilia even in the presence of CEP290 mutations, then that would be one way to cure the defects that lead to ciliary diseases."
Research so far has been using in vitro human cell lines. However, team members from the University of Michigan and National Eye Institute have developed a mouse model with a CEP290 mutation implicated in retinal degeneration, and the NYU group is planning a study of human CEP290 mutations to see if they can correlate genotypes to their expression in specific ciliary diseases.
The authors of this study are NYU Cancer Institute scientists William Y. Tsang and Brian David Dynlacht; Carine Bossard (Centre for Genomic Regulation, Barcelona); Hemant Khanna (Department of Ophthalmology and Visual Sciences, University of Michigan); Johan Peränen (Institute of Biotechnology, Program in Cellular Biotechnology, University of Helsinki), Anand Swaroop (Department of Ophthalmology and Visual Sciences, University of Michigan / National Eye Institute, Neurobiology Neurodegeneration & Repair Laboratory, Bethesda, MD); and Vivek Malhotra (Centre for Genomic Regulation, Barcelona).
Click here to access the complete article.
Source: Jennifer Berman
NYU Langone Medical Center / New York University School of Medicine
News From The Journals Of The American Society For Microbiology
New Alcohol-Based Hand Sanitizer May Minimize Viral Transmission, Including Norovirus
A newly developed ethanol-based hand sanitizer may significantly impact public health by minimizing the transmission of multiple viruses, including norovirus, from food handlers and care providers. The researchers from the University of Ottawa, Ontario, Canada, and North Carolina State University, Raleigh report their findings in the August 2008 issue of the journal Applied and Environmental Microbiology.
The annual number of food-related infections in the U.S. is an estimated 76 million, with norovirus accounting for up to 59% of the viral cases. Contamination of ready-to-eat items by food handlers largely attributes to the high rate of infections, emphasizing the importance of proper hand hygiene. In addition to washing with soap and water some organizations such as the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend the use of alcohol-based hand sanitizers citing such advantages as faster and greater microbial kill, ease of use and time savings, as well as independence from sinks and running water.
In the study the researchers formed a synergistic blend of ethanol, polyquaternium polymer and organic acid and tested its capability to inhibit human and animal viruses. When compared with a benchmark alcohol-based hand sanitizer, results showed higher levels of reduced infectivity of human rotavirus, adenovirus type 5, poliovirus type 1, and norovirus, as well as feline calicivirus and murine norovirus type 1 from the new ethanol-based sanitizer.
"Based on these results, we conclude that this new ethanol-based hand sanitizer is a promising option for reducing the transmission of enteric viruses, including norovirus, by food handlers and care providers," say the researchers.
(D.R. Macinga, S.A. Sattar, L. Jaykus, J.W. Arbogast. 2008. Improved inactivation of nonenveloped enteric viruses and their surrogates by a novel alcohol-based hand sanitizer. Applied and Environmental Microbiology, 74. 16: 5047-5052.)
New Oral Vaccine May Protect Against Bubonic Plague
Researchers from the Institut Pasteur in Paris, France used a less virulent ancestor to the highly infectious bubonic plague to develop a potentially safe, efficient and inexpensive live oral vaccine. They report their findings in the August 2008 issue of the journal Infection and Immunity.
Transmitted by infected fleas, Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. Both highly contagious, the bubonic form of the disease is the most common in the world and can be treated; however, pneumonic plague is almost always fatal within 3 days of infection. Pneumonic plague can also be generated into aerosols and transmitted from human to human placing it at serious risk for use as weapon of bioterrorism.
Yersinia pseudotuberculosis shares a genetic identity rate of 95% with Y. pestis, but is much less virulent and rarely attributed to disease-related fatalities. In the study 41 strains of Y. pseudotuberculosis were screened for low pathogenicity. Researchers identified one strain (IP32680) which was then tested and found to persist in the mouse intestine for 2 months following intragastric and subcutaneous inoculation without any clinical signs of disease. The previously inoculated mice were then challenged intravenously with Y. pestis following which low levels of the bacteria were found in the organs and blood. Finally, IP32680 was administered orally and results showed that one dose protected 75% of mice, while two doses protected 88%.
"We report that oral inoculation with a Y. pseudotuberculosis strain, selected for its very low virulence, induces an efficient immunity against bubonic plague without causing adverse reactions," say the researchers. "This demonstrates that a live attenuated Y. pseudotuberculosis can be a promising vaccine against bubonic plague."
(T. Blisnick, P. Ave, M. Huerre, E. Carniel, C.E. Demeure. 2008. Oral vaccination against bubonic plague using a live avirulent Yersinia pseudotuberculosis strain. Infection and Immunity, 76. 8: 3808-3816.)
Oral Administration of Lactobacillus from Breast Milk May Treat Common Infection in Lactating Mothers
Oral administration of lactobacillus strains found in breast milk may provide an alternative method to antibiotics for effectively treating mastitis, a common infection that occurs in lactating mothers say researchers from Spain. They report their findings in the August 2008 issue of the journal Applied and Environmental Microbiology.
Mastitis, inflammation of one or more lobules of the mammary gland, occurs in anywhere from 3 to 33% of lactating mothers and of those incidences 75 to 95% are diagnosed within the first twelve weeks postpartum. While Staphylococcus aureus and Staphylococcus epidermidis are considered to be the main infectious agents associated with mastitis, increased multi-drug resistance to antibiotics are making such infections difficult to treat, therefore prompting researchers to explore alternative treatment options.
In prior studies researchers collected lactobacillus strains from the breast milk of healthy mothers and found the probiotic potential of Lactobacillus gasseri and Lactobacillus salivarious to be comparable to strains currently used in commercial probiotic products. Here the researchers randomly divided twenty women diagnosed with staphylococcal mastitis into two groups, a probiotic group and a control. The probiotic group received the same daily dosage of L. salivarius and L. gasseri for four weeks, both of which were originally isolated from breast milk. Results showed that on day zero staphylococcal counts in both groups were similar. At day fourteen women in the probiotic group were displaying no clinical signs of mastitis, but infection in the control group persisted. Finally, on day thirty the staphylococcal count was lower in the probiotic group and L. salivarius and L. gasseri were detected in milk samples from six of the ten women.
"In conclusion, L. salivarius CECT5713 and L. gasseri CECT5714 appear to be an efficient alternative for the treatment of lactational infectious mastitis during lactation," say the researchers.
(E. Jimenez, L. Fernandez, A. Maldonado, R. Martin, M. Olivares, J. Xaus, J.M. Rodriguez. 2008. Oral administration of Lactobacillus strains isolated from breast milk as an alternative for the treatment of infectious mastitis during lactation.Applied and Environmental Microbiology, 74. 15: 4650-4655.)
Source: Carrie Slijepcevic
American Society for Microbiology
A newly developed ethanol-based hand sanitizer may significantly impact public health by minimizing the transmission of multiple viruses, including norovirus, from food handlers and care providers. The researchers from the University of Ottawa, Ontario, Canada, and North Carolina State University, Raleigh report their findings in the August 2008 issue of the journal Applied and Environmental Microbiology.
The annual number of food-related infections in the U.S. is an estimated 76 million, with norovirus accounting for up to 59% of the viral cases. Contamination of ready-to-eat items by food handlers largely attributes to the high rate of infections, emphasizing the importance of proper hand hygiene. In addition to washing with soap and water some organizations such as the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend the use of alcohol-based hand sanitizers citing such advantages as faster and greater microbial kill, ease of use and time savings, as well as independence from sinks and running water.
In the study the researchers formed a synergistic blend of ethanol, polyquaternium polymer and organic acid and tested its capability to inhibit human and animal viruses. When compared with a benchmark alcohol-based hand sanitizer, results showed higher levels of reduced infectivity of human rotavirus, adenovirus type 5, poliovirus type 1, and norovirus, as well as feline calicivirus and murine norovirus type 1 from the new ethanol-based sanitizer.
"Based on these results, we conclude that this new ethanol-based hand sanitizer is a promising option for reducing the transmission of enteric viruses, including norovirus, by food handlers and care providers," say the researchers.
(D.R. Macinga, S.A. Sattar, L. Jaykus, J.W. Arbogast. 2008. Improved inactivation of nonenveloped enteric viruses and their surrogates by a novel alcohol-based hand sanitizer. Applied and Environmental Microbiology, 74. 16: 5047-5052.)
New Oral Vaccine May Protect Against Bubonic Plague
Researchers from the Institut Pasteur in Paris, France used a less virulent ancestor to the highly infectious bubonic plague to develop a potentially safe, efficient and inexpensive live oral vaccine. They report their findings in the August 2008 issue of the journal Infection and Immunity.
Transmitted by infected fleas, Yersinia pestis is the causative agent responsible for bubonic and pneumonic plague. Both highly contagious, the bubonic form of the disease is the most common in the world and can be treated; however, pneumonic plague is almost always fatal within 3 days of infection. Pneumonic plague can also be generated into aerosols and transmitted from human to human placing it at serious risk for use as weapon of bioterrorism.
Yersinia pseudotuberculosis shares a genetic identity rate of 95% with Y. pestis, but is much less virulent and rarely attributed to disease-related fatalities. In the study 41 strains of Y. pseudotuberculosis were screened for low pathogenicity. Researchers identified one strain (IP32680) which was then tested and found to persist in the mouse intestine for 2 months following intragastric and subcutaneous inoculation without any clinical signs of disease. The previously inoculated mice were then challenged intravenously with Y. pestis following which low levels of the bacteria were found in the organs and blood. Finally, IP32680 was administered orally and results showed that one dose protected 75% of mice, while two doses protected 88%.
"We report that oral inoculation with a Y. pseudotuberculosis strain, selected for its very low virulence, induces an efficient immunity against bubonic plague without causing adverse reactions," say the researchers. "This demonstrates that a live attenuated Y. pseudotuberculosis can be a promising vaccine against bubonic plague."
(T. Blisnick, P. Ave, M. Huerre, E. Carniel, C.E. Demeure. 2008. Oral vaccination against bubonic plague using a live avirulent Yersinia pseudotuberculosis strain. Infection and Immunity, 76. 8: 3808-3816.)
Oral Administration of Lactobacillus from Breast Milk May Treat Common Infection in Lactating Mothers
Oral administration of lactobacillus strains found in breast milk may provide an alternative method to antibiotics for effectively treating mastitis, a common infection that occurs in lactating mothers say researchers from Spain. They report their findings in the August 2008 issue of the journal Applied and Environmental Microbiology.
Mastitis, inflammation of one or more lobules of the mammary gland, occurs in anywhere from 3 to 33% of lactating mothers and of those incidences 75 to 95% are diagnosed within the first twelve weeks postpartum. While Staphylococcus aureus and Staphylococcus epidermidis are considered to be the main infectious agents associated with mastitis, increased multi-drug resistance to antibiotics are making such infections difficult to treat, therefore prompting researchers to explore alternative treatment options.
In prior studies researchers collected lactobacillus strains from the breast milk of healthy mothers and found the probiotic potential of Lactobacillus gasseri and Lactobacillus salivarious to be comparable to strains currently used in commercial probiotic products. Here the researchers randomly divided twenty women diagnosed with staphylococcal mastitis into two groups, a probiotic group and a control. The probiotic group received the same daily dosage of L. salivarius and L. gasseri for four weeks, both of which were originally isolated from breast milk. Results showed that on day zero staphylococcal counts in both groups were similar. At day fourteen women in the probiotic group were displaying no clinical signs of mastitis, but infection in the control group persisted. Finally, on day thirty the staphylococcal count was lower in the probiotic group and L. salivarius and L. gasseri were detected in milk samples from six of the ten women.
"In conclusion, L. salivarius CECT5713 and L. gasseri CECT5714 appear to be an efficient alternative for the treatment of lactational infectious mastitis during lactation," say the researchers.
(E. Jimenez, L. Fernandez, A. Maldonado, R. Martin, M. Olivares, J. Xaus, J.M. Rodriguez. 2008. Oral administration of Lactobacillus strains isolated from breast milk as an alternative for the treatment of infectious mastitis during lactation.Applied and Environmental Microbiology, 74. 15: 4650-4655.)
Source: Carrie Slijepcevic
American Society for Microbiology
Improvement Seen in Mouse Model Of ALS Following Umbilical Cord Blood Cell Transplant
A study at the University of South Florida has shown that transplants of mononuclear human umbilical cord blood (MNChUCB) cells may help patients suffering from Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease. A disease in which the motor neurons in the spinal cord and brain degenerate, ALS leaves its victims with progressive muscle weakness, paralysis and, finally, respiratory failure three to five years after diagnosis.
In this study, USF researchers transplanted human umbilical cord blood (HUCB) cells into mouse models with ALS. Cells were transplanted at three different dose strength levels -- low, moderate and high -- to determine the degree to which dose levels of transplanted cells might delay disease symptom progression and increase lifespan. In results published online at PloS ONE (Public Library of Science), researchers determined that the moderate-strength dose of HUCB cells was most effective in increasing lifespan and reducing disease progression.
"Our results demonstrate that treatment for ALS with an appropriate dose of MNC hUBC cells may provide a neuroprotective effect for motor neurons through active involvement of these cells in modulating the host immune inflammatory system response," said the study's lead author Svitlana Garbuzova-Davis, PhD, DSc, of the Center of Excellence for Aging and Brain Repair at USF.
According to the research team, modulating immune and inflammatory effectors with HUCB cells could have a protective effect on dying motor neurons. The team had previously shown that hUBC cell transplants reduced inflammation and provided neuroprotection in models of stroke and Alzheimer's disease.
"This preclinical study indicates that MNC hUBC cells may protect motor neurons by inhibiting an immune inflammatory response by decreasing pro-inflammatory cytokines, signaling proteins in the brain and spinal cord that play a role in immune response," Garbuzova-Davis and colleagues wrote. "Proinflammatory cytokines may be indirect mediators for glial cells' contribution to motoneuron death and the decrease in these cytokines might be due to a reduction of activated microglia, the cells that form active immune defense in the central nervous system."
The research team noted, however, that the mechanism underlying the beneficial effect of hUBC cells for repairing diseased motor neurons in ALS still needs more clarification.
Suggesting that 'more is not better,' it was the moderate, not the high, dose of hUBC cells that proved most effective. Researchers speculated that the high dose may have been less effective because it induced an immunological conflict within the mouse model.
"Future studies should look at multiple injections of smaller doses over time, in order to help translate this research to clinical trials," according to co-author Paul R. Sanberg, PhD, DSc, director of the Center.
"Developing an effective treatment for ALS is complicated by the diffuse nature of motor neuron death," concluded Garbuzova-Davis. "However, cell therapy may offer a promising new treatment."
The other co-authors of the study were Cyndy Davis Sanberg and Nicole Kuzmin-Nichols of Saneron CCELL Therapeutics, Inc., and Alison E. Willing, Carmelina Gemma, Paula C. Bickford, Christina Miller, and Robert Rossi from USF.
Source: Anne DeLotto Baier
University of South Florida Health
In this study, USF researchers transplanted human umbilical cord blood (HUCB) cells into mouse models with ALS. Cells were transplanted at three different dose strength levels -- low, moderate and high -- to determine the degree to which dose levels of transplanted cells might delay disease symptom progression and increase lifespan. In results published online at PloS ONE (Public Library of Science), researchers determined that the moderate-strength dose of HUCB cells was most effective in increasing lifespan and reducing disease progression.
"Our results demonstrate that treatment for ALS with an appropriate dose of MNC hUBC cells may provide a neuroprotective effect for motor neurons through active involvement of these cells in modulating the host immune inflammatory system response," said the study's lead author Svitlana Garbuzova-Davis, PhD, DSc, of the Center of Excellence for Aging and Brain Repair at USF.
According to the research team, modulating immune and inflammatory effectors with HUCB cells could have a protective effect on dying motor neurons. The team had previously shown that hUBC cell transplants reduced inflammation and provided neuroprotection in models of stroke and Alzheimer's disease.
"This preclinical study indicates that MNC hUBC cells may protect motor neurons by inhibiting an immune inflammatory response by decreasing pro-inflammatory cytokines, signaling proteins in the brain and spinal cord that play a role in immune response," Garbuzova-Davis and colleagues wrote. "Proinflammatory cytokines may be indirect mediators for glial cells' contribution to motoneuron death and the decrease in these cytokines might be due to a reduction of activated microglia, the cells that form active immune defense in the central nervous system."
The research team noted, however, that the mechanism underlying the beneficial effect of hUBC cells for repairing diseased motor neurons in ALS still needs more clarification.
Suggesting that 'more is not better,' it was the moderate, not the high, dose of hUBC cells that proved most effective. Researchers speculated that the high dose may have been less effective because it induced an immunological conflict within the mouse model.
"Future studies should look at multiple injections of smaller doses over time, in order to help translate this research to clinical trials," according to co-author Paul R. Sanberg, PhD, DSc, director of the Center.
"Developing an effective treatment for ALS is complicated by the diffuse nature of motor neuron death," concluded Garbuzova-Davis. "However, cell therapy may offer a promising new treatment."
The other co-authors of the study were Cyndy Davis Sanberg and Nicole Kuzmin-Nichols of Saneron CCELL Therapeutics, Inc., and Alison E. Willing, Carmelina Gemma, Paula C. Bickford, Christina Miller, and Robert Rossi from USF.
Source: Anne DeLotto Baier
University of South Florida Health
Evidence Of 'Memory' In Cells And Molecules Shown By Researchers
Research reported October 29 in the journal Proceedings of the National Academy of Sciences (PNAS) provides evidence that some molecular interactions on cell surfaces may have a "memory" that affects their future interactions. The report could lead to a re-examination of results from certain single-molecule research.
Researchers who use sequentially repeated tests to obtain statistical samples of molecular properties usually assume that each test is identical to -- and independent of -- any other tests in the sequence. In their article, however, researchers at the Georgia Institute of Technology provide examples of test sequences that may not be composed of independent and identically-distributed (i.i.d.) random variables.
"If you are probing a cell to get a bit of information, how do you know that the cell is not going to respond by changing the information it reveals the next time you probe it?" asked Cheng Zhu, a Regents' Professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "If you are probing a molecule, can you assume that the molecule will return to its original configuration before you test it the next time? We didn't think about this until we had been doing these kinds of experiments for more than ten years."
Supported by the National Institutes of Health, the research demonstrates that certain cells can "remember" their earlier encounters through specific receptor-ligand interactions. That would mean that some sequential measurements may not have been truly independent, and could therefore prompt re-examination of some research that obtained data under the i.i.d. assumption.
"People doing research in this area ought to look at what we have found to see if their systems also have memories that may have affected their conclusions," Zhu said. "They may discover new aspects that may have been overlooked."
Using a micropipette adhesion frequency assay, Zhu's research team studied a number of receptor-ligand interactions. The sequence data analysis conducted by Veronika Zarnitsyna, a research scientist in the Coulter Department, revealed examples in which an interaction observed in one test affected the outcome of a future test. Depending on the biological system, the effect could either increase or decrease the likelihood of a future interaction.
For instance, interaction between T cell receptors and an antigen bound to major histocompatibility molecules showed positive correlation, with one interaction increasing the likelihood of a future interaction. Interaction between C-adherins exhibited the opposite behavior, with one interaction reducing the likelihood of a future interaction. In a third system the researchers studied, the events appeared to be truly independent, with one interaction not affecting a future one. "The i.i.d. assumption in single-molecule experiments was something that people usually took for granted," Zarnitsyna said.
The research reported in PNAS began when Jun Huang, a graduate student in the Zhu lab, examined T cell test data and noted a distinct difference: interactions appeared consecutively in long strings and then disappeared for a long while. Huang asked Zhu about the pattern. Zhu then shared his concerns about the independence of the tests with Zarnitsyna, a biophysicist.
Zarnitsyna analyzed data generated by Huang and Fang Zhang -- another graduate student in the Zhu lab -- and additional data obtained in the lab by Yuan-Hung Chien, a student from the laboratory of Deborah Leckband at the University of Illinois at Urbana-Champaign.
"Positive memory increases the likelihood of having two interactions in a row, which generates long strings of interactions," said Zarnitsyna. "The negative memory, conversely, decreases the likelihood of having consecutive interactions, which results in more solitary interactions in the sequence."
Zhu compares the negative correlation to the effects of strong light on the eyes. "If you go from the dark to the bright, time is required before you can see well again," he noted. "Exposure to strong light temporarily inhibits the eyes' response to the next input."
Zhu's research team studies single-molecule mechanics using sensitive force techniques, such as atomic force microscopes and biomembrane force probes, to put cells and molecules together and then measure the forces or times required to pull them apart. Ideas developed for the adhesion frequency assay may also be applicable to this research because the i.i.d. assumption is violated if the force or time depends on where in a test sequence it was measured.
As a next step, Zhu would like to further characterize the memory effect to determine how long it lasts. "It seems reasonable that if you prolong the cycle time -- the period between trials -- the cell or molecule would gradually forget," he said.
He would also like to study the biological mechanisms of the memory effects.
"We believe this phenomenon may be biologically important, though we don't yet know the implications for it," Zhu said. "This may represent a way for cells to regulate their adhesion and signaling. For T cells, the ability to 'remember' even a brief interaction with a pathogen may be related to their ability to tell an intruder from "self" molecules, which is crucial to the body's defense in the immune system."
Source: John Toon
Georgia Institute of Technology Research News
Researchers who use sequentially repeated tests to obtain statistical samples of molecular properties usually assume that each test is identical to -- and independent of -- any other tests in the sequence. In their article, however, researchers at the Georgia Institute of Technology provide examples of test sequences that may not be composed of independent and identically-distributed (i.i.d.) random variables.
"If you are probing a cell to get a bit of information, how do you know that the cell is not going to respond by changing the information it reveals the next time you probe it?" asked Cheng Zhu, a Regents' Professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "If you are probing a molecule, can you assume that the molecule will return to its original configuration before you test it the next time? We didn't think about this until we had been doing these kinds of experiments for more than ten years."
Supported by the National Institutes of Health, the research demonstrates that certain cells can "remember" their earlier encounters through specific receptor-ligand interactions. That would mean that some sequential measurements may not have been truly independent, and could therefore prompt re-examination of some research that obtained data under the i.i.d. assumption.
"People doing research in this area ought to look at what we have found to see if their systems also have memories that may have affected their conclusions," Zhu said. "They may discover new aspects that may have been overlooked."
Using a micropipette adhesion frequency assay, Zhu's research team studied a number of receptor-ligand interactions. The sequence data analysis conducted by Veronika Zarnitsyna, a research scientist in the Coulter Department, revealed examples in which an interaction observed in one test affected the outcome of a future test. Depending on the biological system, the effect could either increase or decrease the likelihood of a future interaction.
For instance, interaction between T cell receptors and an antigen bound to major histocompatibility molecules showed positive correlation, with one interaction increasing the likelihood of a future interaction. Interaction between C-adherins exhibited the opposite behavior, with one interaction reducing the likelihood of a future interaction. In a third system the researchers studied, the events appeared to be truly independent, with one interaction not affecting a future one. "The i.i.d. assumption in single-molecule experiments was something that people usually took for granted," Zarnitsyna said.
The research reported in PNAS began when Jun Huang, a graduate student in the Zhu lab, examined T cell test data and noted a distinct difference: interactions appeared consecutively in long strings and then disappeared for a long while. Huang asked Zhu about the pattern. Zhu then shared his concerns about the independence of the tests with Zarnitsyna, a biophysicist.
Zarnitsyna analyzed data generated by Huang and Fang Zhang -- another graduate student in the Zhu lab -- and additional data obtained in the lab by Yuan-Hung Chien, a student from the laboratory of Deborah Leckband at the University of Illinois at Urbana-Champaign.
"Positive memory increases the likelihood of having two interactions in a row, which generates long strings of interactions," said Zarnitsyna. "The negative memory, conversely, decreases the likelihood of having consecutive interactions, which results in more solitary interactions in the sequence."
Zhu compares the negative correlation to the effects of strong light on the eyes. "If you go from the dark to the bright, time is required before you can see well again," he noted. "Exposure to strong light temporarily inhibits the eyes' response to the next input."
Zhu's research team studies single-molecule mechanics using sensitive force techniques, such as atomic force microscopes and biomembrane force probes, to put cells and molecules together and then measure the forces or times required to pull them apart. Ideas developed for the adhesion frequency assay may also be applicable to this research because the i.i.d. assumption is violated if the force or time depends on where in a test sequence it was measured.
As a next step, Zhu would like to further characterize the memory effect to determine how long it lasts. "It seems reasonable that if you prolong the cycle time -- the period between trials -- the cell or molecule would gradually forget," he said.
He would also like to study the biological mechanisms of the memory effects.
"We believe this phenomenon may be biologically important, though we don't yet know the implications for it," Zhu said. "This may represent a way for cells to regulate their adhesion and signaling. For T cells, the ability to 'remember' even a brief interaction with a pathogen may be related to their ability to tell an intruder from "self" molecules, which is crucial to the body's defense in the immune system."
Source: John Toon
Georgia Institute of Technology Research News
To Eat Or Not To Eat? New Study On Appetite Stimulants For Hibernating Marmots Could Help Understand Obesity
A nutrient that's common to all living things can make hibernating marmots hungry - a breakthrough that could help scientists understand human obesity and eating disorders, according to a new study by a Colorado State University biologist.
The study appears in the current issue of the Journal of Experimental Biology. The full paper is available at jeb.biologists/cgi/reprint/213/12/2031.
Professor Greg Florant discovered he could slowly release a molecule called AICAR into yellow-bellied marmots that activates a neurological pathway driving food intake and stimulates appetite. The pathway, which shuts down during hibernation, relies on an important balance between two energy molecules - ATP and AMP. The lower the ratio between the two cellular molecules, the lower the energy in the cell and the more the appetite is stimulated.
Without this artificial stimulation, awake, hibernating marmots do not eat - even when researchers place food in front of them.
"The experimental group started to feed because they thought they had this energy deficit," Florant said. "Then when the pumps dispensing the molecule finally stopped, the animals went right back into hibernation. That suggests to us that the animals are still sensing energy levels within cells during the hibernation period."
Tissue samples taken from marmots in Florant's lab allow researchers to identify biochemical processes and genes that are active during hibernation - as opposed to genes that are active when they're feeding or engaging in other behaviors.
The American Physiological Society has called hibernators such as marmots, bears, woodchucks, hedgehogs and lemurs "medical marvels" because they can turn off their appetites and slow their breathing to a point that would be lethal to other animals.
Marmots typically hibernate for as many as six or seven months.
"You can't eat if you're asleep," Florant said. "We've discovered that perhaps nutrients within the brain, such as fatty acids, can alter the food intake pathway, which normally shuts down when marmots hibernate. The perceived drop in energy nutrients (i.e. low ATP) makes the animals think they've got an energy deficit and want to eat."
Florant said he'll conduct additional research this summer to determine whether the reverse is true: Can he stop the animals from eating when they're not hibernating?
His team will also identify neurons in the particular areas of the hypothalamus that are involved in food intake in animals. The hypothalamus is one of the master regulator areas of the brain and controls such activities as food intake, sex and temperature regulation.
"We know which neurons are driving this process," he said. "We're just trying to identify them within the marmot and distinguish what's different about the neurons in a marmot compared to a rat or other animal that does not go into hibernation."
Source:
Emily Wilmsen
Colorado State University
The study appears in the current issue of the Journal of Experimental Biology. The full paper is available at jeb.biologists/cgi/reprint/213/12/2031.
Professor Greg Florant discovered he could slowly release a molecule called AICAR into yellow-bellied marmots that activates a neurological pathway driving food intake and stimulates appetite. The pathway, which shuts down during hibernation, relies on an important balance between two energy molecules - ATP and AMP. The lower the ratio between the two cellular molecules, the lower the energy in the cell and the more the appetite is stimulated.
Without this artificial stimulation, awake, hibernating marmots do not eat - even when researchers place food in front of them.
"The experimental group started to feed because they thought they had this energy deficit," Florant said. "Then when the pumps dispensing the molecule finally stopped, the animals went right back into hibernation. That suggests to us that the animals are still sensing energy levels within cells during the hibernation period."
Tissue samples taken from marmots in Florant's lab allow researchers to identify biochemical processes and genes that are active during hibernation - as opposed to genes that are active when they're feeding or engaging in other behaviors.
The American Physiological Society has called hibernators such as marmots, bears, woodchucks, hedgehogs and lemurs "medical marvels" because they can turn off their appetites and slow their breathing to a point that would be lethal to other animals.
Marmots typically hibernate for as many as six or seven months.
"You can't eat if you're asleep," Florant said. "We've discovered that perhaps nutrients within the brain, such as fatty acids, can alter the food intake pathway, which normally shuts down when marmots hibernate. The perceived drop in energy nutrients (i.e. low ATP) makes the animals think they've got an energy deficit and want to eat."
Florant said he'll conduct additional research this summer to determine whether the reverse is true: Can he stop the animals from eating when they're not hibernating?
His team will also identify neurons in the particular areas of the hypothalamus that are involved in food intake in animals. The hypothalamus is one of the master regulator areas of the brain and controls such activities as food intake, sex and temperature regulation.
"We know which neurons are driving this process," he said. "We're just trying to identify them within the marmot and distinguish what's different about the neurons in a marmot compared to a rat or other animal that does not go into hibernation."
Source:
Emily Wilmsen
Colorado State University
Osteotech Receives FDA Clearance For First Product Under Its Plexus Technology Platform
Osteotech, Inc.
(Nasdaq: OSTE) announced today that the Food and Drug Administration
("FDA") has cleared its 510(k) submission for an osteoconductive,
bone/polymer biocomposite, which will be the first commercial product
manufactured under Osteotech's proprietary Plexus Technology Platform. This
new product, which will be marketed under the trade name Plexur(TM) P, is a
porous, resorbable scaffold that can be used to fill bony voids of the
pelvis and extremities.
Sam Owusu-Akyaw, Osteotech's President and Chief Executive Officer,
stated, "We are very pleased to be able to introduce the Plexur(TM) P. Our
internal team has done an excellent job developing this product and with
this approval we expect to introduce additional products utilizing the
Plexus Technology in the future."
Plexur(TM) P is an osteoconductive biocomposite of cortical mineralized
bone fibers suspended in a resorbable porous polymer scaffold that has
demonstrated controlled remodeling and resorption characteristics.
Plexur(TM) P incorporates overlapping bone fibers with interconnected
pores, which simulate bone structure, facilitate absorption of blood and
allowing multiple pathways for bone forming cells to begin the remodeling
process. Plexur(TM) P will initially be available as granules and
cylindrical plugs, but ultimately, will be available in multiple forms
including blocks, wedges and sheets. Plexur(TM) P uses proprietary
processing steps that have been shown to inactivate viruses. Plexur(TM) P
is also terminally sterilized.
Mr. Owusu-Akyaw concluded, "Plexur(TM) P will be officially introduced
at the American Academy of Orthopedic Surgeons 2007 Annual Meeting,
February 14 through 16, 2007, in San Diego, California. Plexur(TM) P will
be positioned to compete against osteoconductive synthetic bone void
fillers. We expect to begin distributing Plexur(TM) P in March 2007 at key
centers of excellence to allow for the gathering of human clinical
information before a worldwide launch of the product in the third quarter
of 2007. This is in line with our strategy to use science to market
osteo-biologic products."
The Plexus Technology is designed to utilize bone tissue for procedure-
specific surgical applications in combination with a wide variety of
polymers. On a worldwide basis, Osteotech controls over 17 patents and over
68 pending patent applications covering the Plexus Technology for human and
xenograft bone tissue.
Certain statements made throughout this press release that are not
historical facts contain forward-looking statements (as such are defined in
the Private Securities Litigation Reform Act of 1995) regarding the
Company's future plans, objectives and expected performance. Any such
forward-looking statements are based on assumptions that the Company
believes are reasonable, but are subject to a wide range of risks and
uncertainties and, therefore, there can be no assurance that actual results
may not differ materially from those expressed or implied by such
forward-looking statements. Factors that could cause actual results to
differ materially include, but are not limited to, the inability to obtain
required regulatory approvals for products on a timely basis or at all,
differences in anticipated and actual product and service introduction
dates, the ultimate success of those products in the market place, the
continued acceptance and growth of current products and services, the
impact of competitive products and services, the availability of sufficient
quantities of suitable donated tissue and the success of cost control and
margin improvement efforts. Certain of these factors are detailed from time
to time in the Company's periodic reports filed with the Securities and
Exchange Commission. All information in this press release is as of
February 8, 2007 and the Company undertakes no duty to update this
information.
Osteotech, Inc., headquartered in Eatontown, New Jersey, is a leading
provider of human bone and bone connective tissue for transplantation and
an innovator in the development and marketing of biomaterial and implant
products for musculoskeletal surgery. For further information regarding
Osteotech or this press release, please go to Osteotech's website at
osteotech.
Osteotech, Inc.
osteotech
(Nasdaq: OSTE) announced today that the Food and Drug Administration
("FDA") has cleared its 510(k) submission for an osteoconductive,
bone/polymer biocomposite, which will be the first commercial product
manufactured under Osteotech's proprietary Plexus Technology Platform. This
new product, which will be marketed under the trade name Plexur(TM) P, is a
porous, resorbable scaffold that can be used to fill bony voids of the
pelvis and extremities.
Sam Owusu-Akyaw, Osteotech's President and Chief Executive Officer,
stated, "We are very pleased to be able to introduce the Plexur(TM) P. Our
internal team has done an excellent job developing this product and with
this approval we expect to introduce additional products utilizing the
Plexus Technology in the future."
Plexur(TM) P is an osteoconductive biocomposite of cortical mineralized
bone fibers suspended in a resorbable porous polymer scaffold that has
demonstrated controlled remodeling and resorption characteristics.
Plexur(TM) P incorporates overlapping bone fibers with interconnected
pores, which simulate bone structure, facilitate absorption of blood and
allowing multiple pathways for bone forming cells to begin the remodeling
process. Plexur(TM) P will initially be available as granules and
cylindrical plugs, but ultimately, will be available in multiple forms
including blocks, wedges and sheets. Plexur(TM) P uses proprietary
processing steps that have been shown to inactivate viruses. Plexur(TM) P
is also terminally sterilized.
Mr. Owusu-Akyaw concluded, "Plexur(TM) P will be officially introduced
at the American Academy of Orthopedic Surgeons 2007 Annual Meeting,
February 14 through 16, 2007, in San Diego, California. Plexur(TM) P will
be positioned to compete against osteoconductive synthetic bone void
fillers. We expect to begin distributing Plexur(TM) P in March 2007 at key
centers of excellence to allow for the gathering of human clinical
information before a worldwide launch of the product in the third quarter
of 2007. This is in line with our strategy to use science to market
osteo-biologic products."
The Plexus Technology is designed to utilize bone tissue for procedure-
specific surgical applications in combination with a wide variety of
polymers. On a worldwide basis, Osteotech controls over 17 patents and over
68 pending patent applications covering the Plexus Technology for human and
xenograft bone tissue.
Certain statements made throughout this press release that are not
historical facts contain forward-looking statements (as such are defined in
the Private Securities Litigation Reform Act of 1995) regarding the
Company's future plans, objectives and expected performance. Any such
forward-looking statements are based on assumptions that the Company
believes are reasonable, but are subject to a wide range of risks and
uncertainties and, therefore, there can be no assurance that actual results
may not differ materially from those expressed or implied by such
forward-looking statements. Factors that could cause actual results to
differ materially include, but are not limited to, the inability to obtain
required regulatory approvals for products on a timely basis or at all,
differences in anticipated and actual product and service introduction
dates, the ultimate success of those products in the market place, the
continued acceptance and growth of current products and services, the
impact of competitive products and services, the availability of sufficient
quantities of suitable donated tissue and the success of cost control and
margin improvement efforts. Certain of these factors are detailed from time
to time in the Company's periodic reports filed with the Securities and
Exchange Commission. All information in this press release is as of
February 8, 2007 and the Company undertakes no duty to update this
information.
Osteotech, Inc., headquartered in Eatontown, New Jersey, is a leading
provider of human bone and bone connective tissue for transplantation and
an innovator in the development and marketing of biomaterial and implant
products for musculoskeletal surgery. For further information regarding
Osteotech or this press release, please go to Osteotech's website at
osteotech.
Osteotech, Inc.
osteotech
Loss Of A Universal TRNA Feature Reported
Scientists at the Virginia Bioinformatics Institute (VBI) report in the Journal of Bacteriology that two alphaproteobacteria lack the universal extra guanylate nucleotide typically found in the transfer RNA molecule tRNAHis. tRNAs are the molecules responsible for decoding sequence information specified by messenger RNA molecules, information which is ultimately encoded by the DNA template.
tRNAHis is the specific tRNA that assists in incorporating the amino acid histidine into new proteins. Histidine residues make essential contributions to protein structure as well as the catalytic mechanisms of enzymes and must be reliably incorporated during the process of translation.
Until now, bacterial, archaeal, and eukaryotic tRNAs have always been found with an extra guanylate residue at the 5' end of the tRNA molecule. The scientists, led by Kelly Williams of VBI, have shown that tRNAs carrying the amino acid histidine in the alphaproteobacteria Sinorhizobium meliloti and Caulobacter crescentus apparently lack the universal guanylate residue.
Kelly Williams, research investigator at VBI, remarked: "The loss of a universal and apparently ancient tRNA feature in two members of the alphaproteobacteria was particularly surprising as it represents a radical departure from previously known identity rules for the histidine-carrying tRNAs." He added: "This result implies that tRNA recognition by the enzyme adding histidine to tRNA differs considerably from similar enzymes in other organisms. We have indeed been able to detect an impact on particular regions of the histidyl-tRNA synthetase that are critical for recognizing tRNA."
The researchers used bioinformatic tools such as a computer script - specifically written by the group - to probe the tRNA genes in the alphaproteobacteria group. Examination of the corrected tRNAHis sequences revealed that a group of alphaproteobacteria fails to encode a G (guanylate) at the -1 position of the tRNA as all other bacteria do. Amplification and tRNA sequencing approaches were used to confirm the findings.
Sinorhizobium meliloti and Caulobacter crescentus are members of the alphaproteobacteria, a group of diverse organisms whose members have successfully adopted different lifestyle and energy-yielding strategies in the course of evolution. The organisms are members of a specific group of alphaproteobacteria that comprises the Rhizobiales, Rhodobacterales, Caulobacterales, Parvularculales and Pelagibacter.
Dieter S'll, Sterling Professor of Molecular Biophysics and Biochemistry in the Department of Molecular Biophysics and Biochemistry at Yale University, commented: "The observed absence of the extra guanylate in tRNAHis is a unique case of divergence from a highly conserved ancient tRNA recognition mechanism by an aminoacyl-tRNA synthetase. It will be of special interest to examine if the loss of this tRNA feature has resulted from the presence of an RNase P enzyme that is no longer capable of catalyzing abnormal cleavage at the -1 position in the tRNAHis precursor. It will also be revealing to see how different aminoacyl-tRNA synthetases have adapted to discriminate between their cognate or related substrates and the now less distinctive tRNAHis."
The research is available on line in the Journal of Bacteriology (doi:10.1128/JB.01203-06) and is scheduled to appear in the March issue of the journal.
Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the "disease triangle" of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today's key challenges in the biomedical, environmental and plant sciences.
Contact: Barry Whyte
Virginia Tech
tRNAHis is the specific tRNA that assists in incorporating the amino acid histidine into new proteins. Histidine residues make essential contributions to protein structure as well as the catalytic mechanisms of enzymes and must be reliably incorporated during the process of translation.
Until now, bacterial, archaeal, and eukaryotic tRNAs have always been found with an extra guanylate residue at the 5' end of the tRNA molecule. The scientists, led by Kelly Williams of VBI, have shown that tRNAs carrying the amino acid histidine in the alphaproteobacteria Sinorhizobium meliloti and Caulobacter crescentus apparently lack the universal guanylate residue.
Kelly Williams, research investigator at VBI, remarked: "The loss of a universal and apparently ancient tRNA feature in two members of the alphaproteobacteria was particularly surprising as it represents a radical departure from previously known identity rules for the histidine-carrying tRNAs." He added: "This result implies that tRNA recognition by the enzyme adding histidine to tRNA differs considerably from similar enzymes in other organisms. We have indeed been able to detect an impact on particular regions of the histidyl-tRNA synthetase that are critical for recognizing tRNA."
The researchers used bioinformatic tools such as a computer script - specifically written by the group - to probe the tRNA genes in the alphaproteobacteria group. Examination of the corrected tRNAHis sequences revealed that a group of alphaproteobacteria fails to encode a G (guanylate) at the -1 position of the tRNA as all other bacteria do. Amplification and tRNA sequencing approaches were used to confirm the findings.
Sinorhizobium meliloti and Caulobacter crescentus are members of the alphaproteobacteria, a group of diverse organisms whose members have successfully adopted different lifestyle and energy-yielding strategies in the course of evolution. The organisms are members of a specific group of alphaproteobacteria that comprises the Rhizobiales, Rhodobacterales, Caulobacterales, Parvularculales and Pelagibacter.
Dieter S'll, Sterling Professor of Molecular Biophysics and Biochemistry in the Department of Molecular Biophysics and Biochemistry at Yale University, commented: "The observed absence of the extra guanylate in tRNAHis is a unique case of divergence from a highly conserved ancient tRNA recognition mechanism by an aminoacyl-tRNA synthetase. It will be of special interest to examine if the loss of this tRNA feature has resulted from the presence of an RNase P enzyme that is no longer capable of catalyzing abnormal cleavage at the -1 position in the tRNAHis precursor. It will also be revealing to see how different aminoacyl-tRNA synthetases have adapted to discriminate between their cognate or related substrates and the now less distinctive tRNAHis."
The research is available on line in the Journal of Bacteriology (doi:10.1128/JB.01203-06) and is scheduled to appear in the March issue of the journal.
Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the "disease triangle" of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today's key challenges in the biomedical, environmental and plant sciences.
Contact: Barry Whyte
Virginia Tech
Bioengineers Develop A Microfabricated Device To Measure Cellular Forces During Tissue Development
A University of Pennsylvania-collaboration of bioengineers studying the physical forces generated by individual cells has created a tiny micron-sized device that allows researchers to measure and manipulate cellular forces as assemblies of living cells reorganize themselves into tissues.
The new micro-tool created in the study allows researchers to gauge how cells' minute mechanical forces affect cellular behavior, protein deposition and cell differentiation in a 3-dimensional, in vivo-like environment that mimics how tissue actually forms in a living organism. The finding also has implications for the testing of irregular or diseased tissue, such as beating cardiac tissue, which can be modeled and studied.
The findings were published in the June issue of the Proceedings of the National Academy of Sciences.
The push-and-pull of cellular forces drives the buckling, extension and contraction of cells that occur during tissue development. These processes that ultimately shape the architecture of tissues play an important role in coordinating cell signaling, gene expression and behavior, and they are essential for wound healing and tissue homeostasis in adult organisms.
Yet a detailed picture of how tissue mechanics link to morphogenetic phenomena has been hindered by a lack of model systems in which both mechanics and remodeling can be simultaneously examined.
The Penn study highlights a complex and dynamic relationship between cellular forces, visualizes the remodeling of a matrix by living cells and demonstrates a system to study and apply this relationship within engineered 3-D microtissue.
Chris Chen, professor of bioengineering in the School of Engineering and Applied Science at Penn, developed the tool with colleagues at the University of California, Santa Barbara, and the University of Cambridge.
The system was created using photolithography, the same technology used to craft semiconductors. Scientists fabricated an array of tiny divots within a mold and immersed the mold in a culture of cells and collagen. Researchers then placed raised microcantilever posts on either side of the mold and - much like draping a volleyball net across two metal poles - observed the formation of a cell and collagen web of living tissue anchored to the cantilevers. These microcantilevers were used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process.
The cantilever posts allowed the team to observe and measure the retraction and extension of the cells as they remodeled the adjacent matrix into a coherent band of tissue. Varying the mechanical stiffness of the cantilevers and collagen matrix demonstrated that the cellular forces increased with boundary or matrix rigidity, whereas the levels of proteins in the cytoskeleton and extracellular matrix also increased with levels of mechanical stress. By mapping these relationships between cellular and matrix mechanics, cellular forces and protein expression onto a bio-chemo-mechanical model of microtissue contractility, the team demonstrated how intratissue gradients of mechanical stress can emerge from collective cellular contractility and, finally, how such gradients can be used to engineer protein composition and organization within a 3-D tissue.
"Just as we build muscle in the gym, these same mechanical forces are translated down to the cellular level and build the complex arrangement of different tissues in the body," co-author Wesley Legant said. "By varying the properties of our model system, we can study how these mechanical factors are distributed throughout a tissue and how this can, in turn, effect cellular function."
"With this system, we also see the potential for high-throughput drug testing, as researchers will be able to test new pharmaceuticals against a vast array of these small tissue samples, perhaps identifying new ways to increase the contractility of cardiac muscle, or to relax arteries to treat hypertension," said Chen, the study's lead author.
Working with colleagues, the team also created a mathematical model of the entire process that accurately predicted the experimental results.
"With this model, we can extend our findings to more complex and realistic model tissues which might be difficult to study experimentally in the lab" Legant said.
Notes:
The study was conducted by Chen, Legant and Michael T. Yang of the Department of Bioengineering at Penn; Amit Pathak and Robert M. McMeeking of the Department of Mechanical Engineering at UCSB; and Vikram S. Deshpande of the Department of Engineering at Cambridge.
The research was funded by grants from the National Institutes of Health, an Army Research Office Multidisciplinary University Research Initiative, the Material Research Science and Engineering Center and Center for Engineering Cells and Regeneration at Penn, the U.S Department of Education's Graduate Assistance in Areas of National Need and the National Science Foundation's Graduate Research Fellowship.
Source:
Jordan Reese
University of Pennsylvania
The new micro-tool created in the study allows researchers to gauge how cells' minute mechanical forces affect cellular behavior, protein deposition and cell differentiation in a 3-dimensional, in vivo-like environment that mimics how tissue actually forms in a living organism. The finding also has implications for the testing of irregular or diseased tissue, such as beating cardiac tissue, which can be modeled and studied.
The findings were published in the June issue of the Proceedings of the National Academy of Sciences.
The push-and-pull of cellular forces drives the buckling, extension and contraction of cells that occur during tissue development. These processes that ultimately shape the architecture of tissues play an important role in coordinating cell signaling, gene expression and behavior, and they are essential for wound healing and tissue homeostasis in adult organisms.
Yet a detailed picture of how tissue mechanics link to morphogenetic phenomena has been hindered by a lack of model systems in which both mechanics and remodeling can be simultaneously examined.
The Penn study highlights a complex and dynamic relationship between cellular forces, visualizes the remodeling of a matrix by living cells and demonstrates a system to study and apply this relationship within engineered 3-D microtissue.
Chris Chen, professor of bioengineering in the School of Engineering and Applied Science at Penn, developed the tool with colleagues at the University of California, Santa Barbara, and the University of Cambridge.
The system was created using photolithography, the same technology used to craft semiconductors. Scientists fabricated an array of tiny divots within a mold and immersed the mold in a culture of cells and collagen. Researchers then placed raised microcantilever posts on either side of the mold and - much like draping a volleyball net across two metal poles - observed the formation of a cell and collagen web of living tissue anchored to the cantilevers. These microcantilevers were used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process.
The cantilever posts allowed the team to observe and measure the retraction and extension of the cells as they remodeled the adjacent matrix into a coherent band of tissue. Varying the mechanical stiffness of the cantilevers and collagen matrix demonstrated that the cellular forces increased with boundary or matrix rigidity, whereas the levels of proteins in the cytoskeleton and extracellular matrix also increased with levels of mechanical stress. By mapping these relationships between cellular and matrix mechanics, cellular forces and protein expression onto a bio-chemo-mechanical model of microtissue contractility, the team demonstrated how intratissue gradients of mechanical stress can emerge from collective cellular contractility and, finally, how such gradients can be used to engineer protein composition and organization within a 3-D tissue.
"Just as we build muscle in the gym, these same mechanical forces are translated down to the cellular level and build the complex arrangement of different tissues in the body," co-author Wesley Legant said. "By varying the properties of our model system, we can study how these mechanical factors are distributed throughout a tissue and how this can, in turn, effect cellular function."
"With this system, we also see the potential for high-throughput drug testing, as researchers will be able to test new pharmaceuticals against a vast array of these small tissue samples, perhaps identifying new ways to increase the contractility of cardiac muscle, or to relax arteries to treat hypertension," said Chen, the study's lead author.
Working with colleagues, the team also created a mathematical model of the entire process that accurately predicted the experimental results.
"With this model, we can extend our findings to more complex and realistic model tissues which might be difficult to study experimentally in the lab" Legant said.
Notes:
The study was conducted by Chen, Legant and Michael T. Yang of the Department of Bioengineering at Penn; Amit Pathak and Robert M. McMeeking of the Department of Mechanical Engineering at UCSB; and Vikram S. Deshpande of the Department of Engineering at Cambridge.
The research was funded by grants from the National Institutes of Health, an Army Research Office Multidisciplinary University Research Initiative, the Material Research Science and Engineering Center and Center for Engineering Cells and Regeneration at Penn, the U.S Department of Education's Graduate Assistance in Areas of National Need and the National Science Foundation's Graduate Research Fellowship.
Source:
Jordan Reese
University of Pennsylvania
Obesity Drug Helps Unlock Clues About Cancer
An approved drug for fighting obesity is helping scientists at Wake Forest University School of Medicine uncover clues about how to stop the growth of cancerous tumors.
"Our discovery makes an exciting treatment target because theoretically you don't have to worry about harming nearby healthy tissue," said senior researcher Steven J. Kridel, Ph.D., an assistant professor in the Department of Cancer Biology.
In the current issue of Cancer Research, Kridel and colleagues are the first to report that a tubular network within cells, known as the endoplasmic reticulum (ER), is regulated by an enzyme that is tightly linked to tumor growth and development.
"When the ER cannot do its job properly, there's a series of events that gets turned on that can lead to cell suicide or death," said Kridel.
The research showed that an enzyme known as fatty acid synthase is vital for the ER to do its job. Blocking this enzyme, which makes fat in cells, has been shown to prevent tumor cell growth and to promote cell death.
"No one had made connection before between fatty acid synthase and the function of the ER in tumor cells," said Kridel. "This is the first to show that fatty acid synthesis is important in maintaining ER function and keeping tumor cells alive."
The researchers started the work five years ago when they analyzed prostate cancer cells to see which proteins and enzymes were expressed at high levels. Their hope was that treatments that reduced those levels could also stop tumor growth.
"We found that fatty acid synthase is expressed at high levels in tumor cells, but is fairly absent in normal cells," said Kridel. "Other researchers had made similar findings in other types of cancer cells, so we decided to follow up because it looked promising.
"We then made the surprising finding that OrlistatTM, a drug approved by the FDA to treat obesity, can block the function of fatty acid synthase, prevent tumor cell growth and promote tumor cell death."
Finding out exactly how the drug worked was the next step, so that better treatments could be developed. While effective in mice, Olistat's current formulation cannot be given to humans as a cancer treatment because it acts only in the digestive tract.
In the current study, Kridel and colleagues treated prostate, colon and cervical cancer cells in the laboratory with Olistat and two other agents to understand why blocking fatty acid synthase induces cell death.
"Our goal was to understand how fatty acid synthase contributes to tumor growth," said Kridel. "This might provide an explanation for why this enzyme is expressed at high levels."
Now that the scientists understand that the ER is involved -- and that inhibiting fatty acid synthase can impair its function -- they are working to develop new treatments for cancer therapy.
They are exploring the possibility of using existing FDA-approved drugs, as well as developing new drugs. They've already determined that the structure of Orlistat bound to fatty acid synthase, which is the first step in developing similar agents that could be used in humans.
"Our latest findings that connect fatty acid synthase and ER function gives us a better understanding about how the drug kills tumor cells and give us clues to make better drugs," said Kridel. "For any drugs we develop, we'll need to show that they impair the function of the ER."
The study was supported by the Department of Defense Prostate Cancer Research Program.
Co-researchers were graduate student Joy Little, B.S. , lead author, Frances Wheeler, B.S., and Daine Fels, B.S., all with Wake Forest, and Constantinos Koumenis, Ph.D., who was at Wake Forest at the time of the study and is now at the University of Pennsylvania School of Medicine.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.
Contact: Karen Richardson
Wake Forest University Baptist Medical Center
"Our discovery makes an exciting treatment target because theoretically you don't have to worry about harming nearby healthy tissue," said senior researcher Steven J. Kridel, Ph.D., an assistant professor in the Department of Cancer Biology.
In the current issue of Cancer Research, Kridel and colleagues are the first to report that a tubular network within cells, known as the endoplasmic reticulum (ER), is regulated by an enzyme that is tightly linked to tumor growth and development.
"When the ER cannot do its job properly, there's a series of events that gets turned on that can lead to cell suicide or death," said Kridel.
The research showed that an enzyme known as fatty acid synthase is vital for the ER to do its job. Blocking this enzyme, which makes fat in cells, has been shown to prevent tumor cell growth and to promote cell death.
"No one had made connection before between fatty acid synthase and the function of the ER in tumor cells," said Kridel. "This is the first to show that fatty acid synthesis is important in maintaining ER function and keeping tumor cells alive."
The researchers started the work five years ago when they analyzed prostate cancer cells to see which proteins and enzymes were expressed at high levels. Their hope was that treatments that reduced those levels could also stop tumor growth.
"We found that fatty acid synthase is expressed at high levels in tumor cells, but is fairly absent in normal cells," said Kridel. "Other researchers had made similar findings in other types of cancer cells, so we decided to follow up because it looked promising.
"We then made the surprising finding that OrlistatTM, a drug approved by the FDA to treat obesity, can block the function of fatty acid synthase, prevent tumor cell growth and promote tumor cell death."
Finding out exactly how the drug worked was the next step, so that better treatments could be developed. While effective in mice, Olistat's current formulation cannot be given to humans as a cancer treatment because it acts only in the digestive tract.
In the current study, Kridel and colleagues treated prostate, colon and cervical cancer cells in the laboratory with Olistat and two other agents to understand why blocking fatty acid synthase induces cell death.
"Our goal was to understand how fatty acid synthase contributes to tumor growth," said Kridel. "This might provide an explanation for why this enzyme is expressed at high levels."
Now that the scientists understand that the ER is involved -- and that inhibiting fatty acid synthase can impair its function -- they are working to develop new treatments for cancer therapy.
They are exploring the possibility of using existing FDA-approved drugs, as well as developing new drugs. They've already determined that the structure of Orlistat bound to fatty acid synthase, which is the first step in developing similar agents that could be used in humans.
"Our latest findings that connect fatty acid synthase and ER function gives us a better understanding about how the drug kills tumor cells and give us clues to make better drugs," said Kridel. "For any drugs we develop, we'll need to show that they impair the function of the ER."
The study was supported by the Department of Defense Prostate Cancer Research Program.
Co-researchers were graduate student Joy Little, B.S. , lead author, Frances Wheeler, B.S., and Daine Fels, B.S., all with Wake Forest, and Constantinos Koumenis, Ph.D., who was at Wake Forest at the time of the study and is now at the University of Pennsylvania School of Medicine.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.
Contact: Karen Richardson
Wake Forest University Baptist Medical Center
Mast Cells Play Dual Role in Triggering Symptoms In Allergy Attacks But Also Limiting the Damage
A blood cell known as a troublemaker for triggering the itch and inflammation in allergy attacks, the mast cell, can also calm down the flare-ups, researchers from Stanford University School of Medicine have found.
The findings, published in the online version of Nature Immunology, reveal that, in mice, mast cells help decrease skin damage over time from sun exposure or from poison oak.
"These reactions are much worse if mast cells aren't present," said senior author Stephen Galli, MD, professor and chair of pathology. He noted the insight may open new possibilities for the treatment of these problems.
The findings contradict mast cells' reputation for being the trigger-happy gunslinger in an allergic reaction. Located just beneath the skin and in the loose connective tissue throughout the body, mast cells lie in wait for intruders. Packed with granules containing inflammation-inciting molecules such as histamine, they sometimes also react to non-threatening trespassers, such as pollens or plant oils. These confrontations cause allergic reactions and, in extreme cases, the life-threatening overreaction of anaphylaxis seen in bee-sting or peanut allergies.
Mast cells also affect the severity of eczema and asthma, giving rise to some therapies that focus on counteracting their activity. "Some people say, 'Let's get rid of them,'" said Galli, who also holds the Mary Hewitt Loveless Professorship in the School of Medicine. "But we did not evolve mast cells just so we could eat a peanut and die."
Rather than characterize the mast cell as an agitator, Galli said it would be more aptly described by the title of a Clint Eastwood western. "The mast cell would have its good, bad and ugly sides - it would depend on the circumstance," he said. "In the end, I think you would be convinced it was mostly a good guy."
Galli's lab has shown mast cells can help corral rather than unleash distress. His team's previous research in 2006 found that mast cells help break down snake venom poison, and a study in 2004 revealed the cells helped mice survive severe bacterial infection.
The new research is the first to investigate long-term reactions by mast cells to poison oak and sun exposure. His team exposed the ears of mice to either cycles of ultraviolet radiation or urushiol, the irritating oil of poison oak. About a week later, mice genetically lacking mast cells showed much more inflammation than normal mice, and developed skin ulcers. Injections of mast cells helped reduce the ear swelling and prevent the ulceration. "All you have to do to cure the mice of this problem is put the mast cells back in," Galli said.
The discovery originated from an unintended observation by Michelle Grimbaldeston, PhD, first author and postdoctoral scholar in pathology. While similar studies have stopped following mouse reactions past the first 48 hours, she kept records for two weeks. "Just by chance I looked a bit farther along," said Grimbaldeston, who is also a C.J. Martin overseas biomedical fellow of the Australian National Health and Medical Research Council.
After just five days, she noticed the ears of mice lacking mast cells were surprisingly thicker than were the ears of normal mice, suggesting an accumulation of white blood cells. By injecting mast cells back into the deficient mice, Grimbaldeston found the immune-suppressing molecule the cells secrete to limit ear swelling: interleukin-10. She also identified which antibodies activated the mast cell receptors to trigger IL-10's release.
Trial injections of IL-10 have reduced inflammation in patients suffering from rheumatoid arthritis and psoriasis, with mixed results. Yet given the manufacturing cost of producing IL-10, Galli thinks it an unlikely practical treatment for poison oak or sun exposure.
The next studies will look into whether mast cells reduce the development of skin tumors, such as melanoma or carcinomas, from longer term ultraviolet exposure. The group will also investigate what other molecules contribute to suppressing the inflammation. "You can't explain all of the anti-inflammatory aspects of mast cells with IL-10," Galli said.
"The fact that one sees the mast cell playing a role in resolving inflammation is surprising," said Juan Rivera, PhD, chief of the molecular inflammation section of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study. Research has focused on how quickly mast cells unleash inflammation, Rivera said, rather than how they might mitigate it. "I think it is a very intriguing finding that the mast cell plays this dual role," he said.
The National Institutes of Health funded the study. Other authors include postdoctoral fellow Susumu Nakae, PhD; research associate Janet Kalesnikoff, PhD; and senior research scientist Mindy Tsai, DMSc.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford/.
Source: Brian Lee
Stanford University Medical Center
The findings, published in the online version of Nature Immunology, reveal that, in mice, mast cells help decrease skin damage over time from sun exposure or from poison oak.
"These reactions are much worse if mast cells aren't present," said senior author Stephen Galli, MD, professor and chair of pathology. He noted the insight may open new possibilities for the treatment of these problems.
The findings contradict mast cells' reputation for being the trigger-happy gunslinger in an allergic reaction. Located just beneath the skin and in the loose connective tissue throughout the body, mast cells lie in wait for intruders. Packed with granules containing inflammation-inciting molecules such as histamine, they sometimes also react to non-threatening trespassers, such as pollens or plant oils. These confrontations cause allergic reactions and, in extreme cases, the life-threatening overreaction of anaphylaxis seen in bee-sting or peanut allergies.
Mast cells also affect the severity of eczema and asthma, giving rise to some therapies that focus on counteracting their activity. "Some people say, 'Let's get rid of them,'" said Galli, who also holds the Mary Hewitt Loveless Professorship in the School of Medicine. "But we did not evolve mast cells just so we could eat a peanut and die."
Rather than characterize the mast cell as an agitator, Galli said it would be more aptly described by the title of a Clint Eastwood western. "The mast cell would have its good, bad and ugly sides - it would depend on the circumstance," he said. "In the end, I think you would be convinced it was mostly a good guy."
Galli's lab has shown mast cells can help corral rather than unleash distress. His team's previous research in 2006 found that mast cells help break down snake venom poison, and a study in 2004 revealed the cells helped mice survive severe bacterial infection.
The new research is the first to investigate long-term reactions by mast cells to poison oak and sun exposure. His team exposed the ears of mice to either cycles of ultraviolet radiation or urushiol, the irritating oil of poison oak. About a week later, mice genetically lacking mast cells showed much more inflammation than normal mice, and developed skin ulcers. Injections of mast cells helped reduce the ear swelling and prevent the ulceration. "All you have to do to cure the mice of this problem is put the mast cells back in," Galli said.
The discovery originated from an unintended observation by Michelle Grimbaldeston, PhD, first author and postdoctoral scholar in pathology. While similar studies have stopped following mouse reactions past the first 48 hours, she kept records for two weeks. "Just by chance I looked a bit farther along," said Grimbaldeston, who is also a C.J. Martin overseas biomedical fellow of the Australian National Health and Medical Research Council.
After just five days, she noticed the ears of mice lacking mast cells were surprisingly thicker than were the ears of normal mice, suggesting an accumulation of white blood cells. By injecting mast cells back into the deficient mice, Grimbaldeston found the immune-suppressing molecule the cells secrete to limit ear swelling: interleukin-10. She also identified which antibodies activated the mast cell receptors to trigger IL-10's release.
Trial injections of IL-10 have reduced inflammation in patients suffering from rheumatoid arthritis and psoriasis, with mixed results. Yet given the manufacturing cost of producing IL-10, Galli thinks it an unlikely practical treatment for poison oak or sun exposure.
The next studies will look into whether mast cells reduce the development of skin tumors, such as melanoma or carcinomas, from longer term ultraviolet exposure. The group will also investigate what other molecules contribute to suppressing the inflammation. "You can't explain all of the anti-inflammatory aspects of mast cells with IL-10," Galli said.
"The fact that one sees the mast cell playing a role in resolving inflammation is surprising," said Juan Rivera, PhD, chief of the molecular inflammation section of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, who was not involved in the study. Research has focused on how quickly mast cells unleash inflammation, Rivera said, rather than how they might mitigate it. "I think it is a very intriguing finding that the mast cell plays this dual role," he said.
The National Institutes of Health funded the study. Other authors include postdoctoral fellow Susumu Nakae, PhD; research associate Janet Kalesnikoff, PhD; and senior research scientist Mindy Tsai, DMSc.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford/.
Source: Brian Lee
Stanford University Medical Center
"New" Human Adenovirus May Not Make For Good Vaccines, After All AdHu26 Demonstrates Same Fault As Previously Studied Vaccine Vectors
In recent years, scientists have studied the possibility of using engineered human adenoviruses as vaccines against diseases such as HIV, tuberculosis, and malaria. In this approach, adenoviruses, which commonly cause respiratory-tract infections, are rendered relatively harmless before they are used as vectors to deliver genes from pathogens, which in turn stimulate the body to generate a protective immune response.
In a new study of four adenovirus vectors, researchers from The Wistar Institute show that a reportedly rare human adenovirus, called AdHu26, is not so rare, after all, and would thus be unlikely to be optimal as a vaccine carrier for mass vaccination. As previous research has shown, a viral vector may be ineffective if the virus it is based on is common in a given population. According to the Wistar scientists, their study also supports the use of chimpanzee adenoviruses as vaccine vectors, since humans have little exposure to these viruses. Their findings were published online, ahead of print, in the Journal of Virology.
"Despite previous reports to the contrary, we find that AdHu26 commonly infects people, particularly those in Sub-Saharan Africa, the very people for whom the need for novel vaccine strategies is most dire," said senior author Hildegund C. J. Ertl, M.D., Wistar professor and director of The Wistar Institute's Vaccine Center. "HIV, malaria, and other infectious diseases take a tremendous toll in the developing world, especially in Sub-Saharan Africa, and a vaccine platform that could be used in those regions could save the lives of millions."
Scientists believe that prior immunity to human adenoviruses is what led, in part, to the failure in 2007 of the STEP trial, a large vaccine trial in the US and other countries that used an adenovirus vector as the basis for an HIV vaccine.
In the current study, Ertl and her colleagues analyzed blood samples collected from people at seven sites around the world, including Thailand, the United States, and five sub-Saharan African nations. They tested the samples to see if they contained neutralizing antibodies and responsive immune cells when exposed to AdHu26 and AdHu5, the virus used in the STEP trial. Surprisingly, neutralizing antibodies to AdHu26 were very prevalent in blood.
According to Ertl, adenoviruses are still good vaccine vectors, just not necessarily human adenoviruses. In addition to testing AdHu5 and AdHu26, the Wistar scientists also tested two adenoviruses that originated in chimpanzees, called AdC6 and AdC7. As expected, neutralizing antibodies were far less likely to be detected in human samples. Mouse studies of all four vectors demonstrated that that were similar in their ability to generate cellular immune responses.
"This study also confirms our current line of research that suggests engineered chimpanzee adenovirus vectors could be superior to related, native human adenoviruses," Ertl said. "Both human and chimpanzee adenoviruses function in similar ways, but the simple benefit is that humans are rarely exposed to adenoviruses of chimpanzee origin."
The Ertl laboratory is currently developing an HIV vaccine utilizing chimpanzee adenoviruses.
Along with senior author Ertl, co-authors from the Ertl laboratory include senior staff scientists Zhi Quan Xiang, M.D., and Xiang Zhou, M.D.; staff scientist Dongming Zhou, M.D., Ph.D.; research technician Yan Li; research assistant Ang Bian; and visiting scientists Heng Chen and Raj Kurupati, Ph.D. Co-authors also include Michael Betts, Ph.D.; Natalie Hutnick; Sally Yuan, Ph.D.; and Clive Gray, Ph.D.; of the University of Pennsylvania School of Medicine's Department of Microbiology; Jennifer Serwanga, Ph.D., of the National Institute for Communicable Diseases in South Africa; and Betty Auma, Ph.D.; and Pontiano Kaleebu, Ph.D.; of the Uganda Research Unit on AIDS in Uganda.
Funding for this study was provided through grants from the National Institutes of Health.
Source: Wistar Institute
In a new study of four adenovirus vectors, researchers from The Wistar Institute show that a reportedly rare human adenovirus, called AdHu26, is not so rare, after all, and would thus be unlikely to be optimal as a vaccine carrier for mass vaccination. As previous research has shown, a viral vector may be ineffective if the virus it is based on is common in a given population. According to the Wistar scientists, their study also supports the use of chimpanzee adenoviruses as vaccine vectors, since humans have little exposure to these viruses. Their findings were published online, ahead of print, in the Journal of Virology.
"Despite previous reports to the contrary, we find that AdHu26 commonly infects people, particularly those in Sub-Saharan Africa, the very people for whom the need for novel vaccine strategies is most dire," said senior author Hildegund C. J. Ertl, M.D., Wistar professor and director of The Wistar Institute's Vaccine Center. "HIV, malaria, and other infectious diseases take a tremendous toll in the developing world, especially in Sub-Saharan Africa, and a vaccine platform that could be used in those regions could save the lives of millions."
Scientists believe that prior immunity to human adenoviruses is what led, in part, to the failure in 2007 of the STEP trial, a large vaccine trial in the US and other countries that used an adenovirus vector as the basis for an HIV vaccine.
In the current study, Ertl and her colleagues analyzed blood samples collected from people at seven sites around the world, including Thailand, the United States, and five sub-Saharan African nations. They tested the samples to see if they contained neutralizing antibodies and responsive immune cells when exposed to AdHu26 and AdHu5, the virus used in the STEP trial. Surprisingly, neutralizing antibodies to AdHu26 were very prevalent in blood.
According to Ertl, adenoviruses are still good vaccine vectors, just not necessarily human adenoviruses. In addition to testing AdHu5 and AdHu26, the Wistar scientists also tested two adenoviruses that originated in chimpanzees, called AdC6 and AdC7. As expected, neutralizing antibodies were far less likely to be detected in human samples. Mouse studies of all four vectors demonstrated that that were similar in their ability to generate cellular immune responses.
"This study also confirms our current line of research that suggests engineered chimpanzee adenovirus vectors could be superior to related, native human adenoviruses," Ertl said. "Both human and chimpanzee adenoviruses function in similar ways, but the simple benefit is that humans are rarely exposed to adenoviruses of chimpanzee origin."
The Ertl laboratory is currently developing an HIV vaccine utilizing chimpanzee adenoviruses.
Along with senior author Ertl, co-authors from the Ertl laboratory include senior staff scientists Zhi Quan Xiang, M.D., and Xiang Zhou, M.D.; staff scientist Dongming Zhou, M.D., Ph.D.; research technician Yan Li; research assistant Ang Bian; and visiting scientists Heng Chen and Raj Kurupati, Ph.D. Co-authors also include Michael Betts, Ph.D.; Natalie Hutnick; Sally Yuan, Ph.D.; and Clive Gray, Ph.D.; of the University of Pennsylvania School of Medicine's Department of Microbiology; Jennifer Serwanga, Ph.D., of the National Institute for Communicable Diseases in South Africa; and Betty Auma, Ph.D.; and Pontiano Kaleebu, Ph.D.; of the Uganda Research Unit on AIDS in Uganda.
Funding for this study was provided through grants from the National Institutes of Health.
Source: Wistar Institute
The Therapeutic Effect Of Worm-Derived Proteins On Experimental Colitis
Patients with inflammatory bowel disease (IBD) suffer from chronic inflammation of the gut leading to gastrointestinal motility alterations with symptoms such as abdominal pain, cramps and diarrhea that profoundly affect their quality of life. The lack of exposure to worm infections, as a result of improved living standards and medical conditions, might have contributed to the increased incidence of IBD in the Western world. Epidemiological, experimental and clinical data support the idea that worm infection provides protection against IBD. However, treatment of patients with living worms may have serious drawbacks such as infection and/or invasion of the parasite to other tissues. Therefore, therapy with worm-derived proteins might provide a more acceptable form of treatment.
A research article published in the World Journal of Gastroenterology addresses this problem. The research team led by Professor Pelckmans from the University of Antwerp used a mouse model of experimental colitis to study the beneficial therapeutic effect of worm-derived proteins on inflammation and gastrointestinal motility disturbances. This paper further enlightens the therapeutic effect of worm proteins on colitis by investigating the effect on the inflammatory process and on the motility disturbances. The results agree with previous studies showing a beneficial effect of worm infection on intestinal inflammation and of worm proteins in experimental animal models of asthma and type 1 diabetes.
The induction of colitis in mice causes severe gastrointestinal motility alterations such as increased intestinal transit time and abrogation of colonic peristaltic activity, as seen in IBD patients. This paper describes that treatment with worm proteins causes normalization of intestinal transit time and amelioration of colonic peristaltic activity in mice with colitis. Treatment of control animals with worm proteins did not influence gastrointestinal motility. Furthermore, attenuation of inflammation and amelioration of motility disturbances after treatment with worm proteins both appear at the same time. This raises the question whether the beneficial effect of worm proteins on gastrointestinal motility is directly or indirectly related to amelioration of inflammation.
In addition, the paper also reports a shift in the balance between different T lymphocyte subsets (Th1, Th2, Th17 and Treg) after the induction of colitis and treatment with worm proteins. The therapeutic effect of worm proteins appears to be mediated by an immunological pathway involving Th1, Th17 and Treg cells. Unraveling the interaction between the immune system and the nervous system will expand our knowledge on how worm proteins affect gastrointestinal motility. More research on this topic is eagerly awaited.
This study shows that treatment with worm proteins attenuates intestinal inflammation and normalizes gastrointestinal motility disturbances in mice with colitis. These results demonstrate that worm proteins, by influencing intestinal inflammation and the related symptoms during colitis, may provide an attractive option in the management of gastrointestinal inflammation in IBD patients.
Reference: Ruyssers NE, De Winter BY, De Man JG, Ruyssers ND, Van Gils AJ, Loukas A, Pearson MS, Weinstock JV, Pelckmans PA, Moreels TG. Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice. World J Gastroenterol 2010; 16(6): 703-712
wjgnet/1007-9327/16/703.asp
Correspondence to: Tom G Moreels, Professor, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium.
Source:
Jin-Lei Wang
World Journal of Gastroenterology
A research article published in the World Journal of Gastroenterology addresses this problem. The research team led by Professor Pelckmans from the University of Antwerp used a mouse model of experimental colitis to study the beneficial therapeutic effect of worm-derived proteins on inflammation and gastrointestinal motility disturbances. This paper further enlightens the therapeutic effect of worm proteins on colitis by investigating the effect on the inflammatory process and on the motility disturbances. The results agree with previous studies showing a beneficial effect of worm infection on intestinal inflammation and of worm proteins in experimental animal models of asthma and type 1 diabetes.
The induction of colitis in mice causes severe gastrointestinal motility alterations such as increased intestinal transit time and abrogation of colonic peristaltic activity, as seen in IBD patients. This paper describes that treatment with worm proteins causes normalization of intestinal transit time and amelioration of colonic peristaltic activity in mice with colitis. Treatment of control animals with worm proteins did not influence gastrointestinal motility. Furthermore, attenuation of inflammation and amelioration of motility disturbances after treatment with worm proteins both appear at the same time. This raises the question whether the beneficial effect of worm proteins on gastrointestinal motility is directly or indirectly related to amelioration of inflammation.
In addition, the paper also reports a shift in the balance between different T lymphocyte subsets (Th1, Th2, Th17 and Treg) after the induction of colitis and treatment with worm proteins. The therapeutic effect of worm proteins appears to be mediated by an immunological pathway involving Th1, Th17 and Treg cells. Unraveling the interaction between the immune system and the nervous system will expand our knowledge on how worm proteins affect gastrointestinal motility. More research on this topic is eagerly awaited.
This study shows that treatment with worm proteins attenuates intestinal inflammation and normalizes gastrointestinal motility disturbances in mice with colitis. These results demonstrate that worm proteins, by influencing intestinal inflammation and the related symptoms during colitis, may provide an attractive option in the management of gastrointestinal inflammation in IBD patients.
Reference: Ruyssers NE, De Winter BY, De Man JG, Ruyssers ND, Van Gils AJ, Loukas A, Pearson MS, Weinstock JV, Pelckmans PA, Moreels TG. Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice. World J Gastroenterol 2010; 16(6): 703-712
wjgnet/1007-9327/16/703.asp
Correspondence to: Tom G Moreels, Professor, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium.
Source:
Jin-Lei Wang
World Journal of Gastroenterology
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