Medical College of Georgia researchers are seeking to refine cancer treatment with an anti-inflammatory plant derivative long used in Chinese medicine.
Celastrol, derived from trees and shrubs called celastracaea, has been used for centuries in China to treat symptoms such as fever, chills, joint pain and inflammation. The MCG researchers think it may also play a role in cancer treatment by inactivating a protein required for cancer growth.
That protein, P23, is one of many proteins helping the heat shock protein 90. Scientists are just beginning to realize the potential of controlling inflammation-related diseases, including cancer, by inhibiting HSP90.
"Cancer cells need HSP90 more than normal cells because cancer cells have thousands of mutations," said Dr. Ahmed Chadli, biochemist in the MCG Center for Molecular Chaperones/Radiobiology and Cancer Virology. "They need chaperones all the time to keep their mutated proteins active. By taking heat shock proteins away from cells, the stabilization is taken away and cell death occurs."
But most HSP90 inhibitors lack selectivity, disabling the functions of all proteins activated by HSP90 rather than only the ones implicated in a specific tumor. Those proteins vary from one tumor to another.
Dr. Chadli and colleagues at the Mayo Clinic believe celastrol holds the key to specificity, targeting the HSP90-activated protein required for folding steroid receptors.
"The celastrol induces the protein to form fibrils and clusters it together, which inactivates it," said Dr. Chadli, whose research was published in the January edition of The Journal of Biological Chemistry. "When they are clustered, they're not available for other functions that help cancer grow."
The research was funded by a seed grant from the MCG Cardiovascular Discovery Institute and a Scientist Development Grant from The American Heart Association.
Dr. Chadli envisions future studies on cancer patients using even more potent derivatives of celastrol.
"They can hopefully be used in combination with other therapeutic agents to reduce the probability of cancer resistance," he said.
Source:
Jennifer Hilliard
Medical College of Georgia
четверг, 20 октября 2011 г.
понедельник, 17 октября 2011 г.
Material Created To Repel Liquids
Sculpting a surface composed of tightly packed nanostructures that resemble tiny nails, University of Wisconsin-Madison engineers and their colleagues from Bell Laboratories have created a material that can repel almost any liquid.
Add a jolt of electricity, and the liquid on the surface slips past the heads of the nanonails and spreads out between their shanks, wetting the surface completely.
The new material, which was reported this month in Langmuir, a journal of the American Chemical Society, could find use in biomedical applications such as "lab-on-a- chip" technology, the manufacture of self-cleaning surfaces, and could help extend the working life of batteries as a way to turn them off when not in use.
UW-Madison mechanical engineers Tom Krupenkin and J. Ashley Taylor and their team etched a silicon wafer to create a forest of conductive silicon shanks and non-conducting silicon oxide heads. Intriguingly, the ability of the surface of the structure to repel water, oil, and solvents rests on the nanonail geometry.
"It turns out that what's important is not the chemistry of the surface, but the topography of the surface," Krupenkin explains, noting that the overhang of the nail head is what gives his novel surface its dual personality.
A surface of posts, he notes, creates a platform so rough at the nanoscale that "liquid only touches the surface at the extreme ends of the posts. It's almost like sitting on a layer of air."
Source: Tom Krupenkin
University of Wisconsin-Madison
Add a jolt of electricity, and the liquid on the surface slips past the heads of the nanonails and spreads out between their shanks, wetting the surface completely.
The new material, which was reported this month in Langmuir, a journal of the American Chemical Society, could find use in biomedical applications such as "lab-on-a- chip" technology, the manufacture of self-cleaning surfaces, and could help extend the working life of batteries as a way to turn them off when not in use.
UW-Madison mechanical engineers Tom Krupenkin and J. Ashley Taylor and their team etched a silicon wafer to create a forest of conductive silicon shanks and non-conducting silicon oxide heads. Intriguingly, the ability of the surface of the structure to repel water, oil, and solvents rests on the nanonail geometry.
"It turns out that what's important is not the chemistry of the surface, but the topography of the surface," Krupenkin explains, noting that the overhang of the nail head is what gives his novel surface its dual personality.
A surface of posts, he notes, creates a platform so rough at the nanoscale that "liquid only touches the surface at the extreme ends of the posts. It's almost like sitting on a layer of air."
Source: Tom Krupenkin
University of Wisconsin-Madison
пятница, 14 октября 2011 г.
Journal Of Clinical Investigation Online Early Table Of Contents: June 2, 2008
Molecular changes in brain fluid give insight into brain-damaging disease
Soon after an individual becomes infected with HIV the virus infects cells in the brain and spinal cord (the central nervous system [CNS]). Although this causes no immediate problems, during the late-stages of disease it can cause dementia and encephalitis (acute inflammation of the brain that can cause death). Monkeys infected with a relative of HIV (SIV) also sometimes develop CNS damage and provide a good model of CNS disease in individuals infected with HIV. Insight into the mechanisms of CNS damage in SIV-infected monkeys has now been provided by a team of researchers at The Scripps Research Institute, La Jolla, who developed an approach to identify molecular changes in the fluid bathing the CNS (the CSF). The researchers, who were led by Howard Fox and Gary Siuzdak, hope that similar approaches could be used to provide new information about other neurodegenerative and neuropsychiatric disorders.
In the study, an approach known as global metabolomics was used to assess the levels of molecules known as metabolites in the CSF before and after SIV-induced encephalitis was manifest. The level of a number of metabolites, including some known as fatty acids and phospholipids, was observed to increase during infection. Consistent with this, a protein known to be important in the generation of fatty acids was found to be increased in the brain of monkeys with SIV-induced encephalitis. Further studies will be required to determine the precise role of the increased level of each metabolite, but it should be noted that many of them are known to induce receptor signaling and thereby might be able to further modulate CNS function.
TITLE: Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques
AUTHOR CONTACT:
Howard S. Fox
The Scripps Research Institute, La Jolla, California, USA.
Gary Siuzdak
The Scripps Research Institute, La Jolla, California, USA.
It's not a level playing field, your genes determine your levels of glucose
In individuals with type 2 diabetes, the way the level of glucose (the sugar molecule that is our main source of energy) in the body while not eating (fasting glucose level) is regulated fails and fasting glucose levels increase dramatically. New insight into genetic variations that have an impact on the fasting glucose levels of nondiabetic individuals has now been provided by a team of researchers from the Istituto Nazionale Ricovero E Cura Anziari, Italy, and the University of Southern California. Specifically, an association between one defined genetic variation and increased fasting glucose levels was observed in nondiabetic individuals. This variation was located between two genes known as G6PC2 and ABCB11. As G6PC2 carries the information for making a protein expressed by the cells that become dysfunctional in individuals with type 2 diabetes, the authors suggest that the genetic variation probably affects fasting glucose levels by altering the expression of this gene.
TITLE: Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels
AUTHOR CONTACT:
Angelo Scuteri
Istituto Nazionale Ricovero E Cura Anziari, Rome, Italy.
Richard M. Watanabe
Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Pinning down a cause of disease in a model of psoriasis
Psoriasis is a chronic skin disease that affects approximately 2-3% of individuals in the Western world. New data, generated by Karin Scharffetter-Kochanek and colleagues, at the University of Ulm, Germany, have indicated that a subset of immune cells known as Tregs (which act to prevent other immune cells from responding inappropriately) are dysfunctional in a mouse model of psoriasis and that this dysfunction contributes substantially to the development of disease.
Mice that express a reduced amount of the protein CD18 (Cd18hypo mice) develop a skin disease that resembles the symptoms of individuals with psoriasis. In the study, Tregs isolated from Cd18hypo mice failed to suppress the proliferation of disease-causing immune cells because they secreted lower levels of the soluble factor TGF-beta than normal Tregs. This was also important for their inability to control disease in vivo, as transplantation of normal Tregs into Cd18hypo mice resulted in a substantial improvement in the psoriasis-like disease, whereas if these cells were transplanted in the presence of antibodies that neutralized TGF-beta there was no improvement in disease. The authors therefore conclude that psoriasis-like disease in Cd18hypo mice is caused mainly by a defect in Treg function and suggest that maintaining CD18 levels is important for ensuring that Tregs function optimally.
TITLE: TGF-beta-dependent suppressive function of Tregs requires wild-type levels of CD18 in a mouse model of psoriasis
AUTHOR CONTACT:
Karin Scharffetter-Kochanek
University of Ulm, Ulm, Germany.
HSN2 mutations lose touch with pain and heat perception
Hereditary sensory and autonomic neuropathy type II, abbreviated to HSANII, is a poorly understood genetic disorder wherein affected patients lose the ability to feel touch, pain, and heat. Although it has been shown to be caused by mutations in a region of DNA known as HSN2, it was not known exactly what this region of DNA was for. In a new study, Guy Roulaeu and colleagues, at the University of Montreal, Canada, have discovered that HSN2 is part of the gene WNK1, but it is only used to generate a protein in the nervous system; in other parts of the body, the gene WNK1 does not use the information in the HSN2 region of DNA to make protein. Further analysis showed that the protein made using information contained in the HSN2 region of DNA (WNK1/HSN2) was found in mouse nerve cells that are vital for relaying sensory inputs such as touch and pain to the brain. Future studies will focus on determining the molecular mechanisms by which WNK1/HSN2 is important for sensing touch, pain, and heat, the very senses lost in individuals with HSANII.
TITLE: Mutations in the nervous system-specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II
AUTHOR CONTACT:
Guy A. Rouleau
University of Montreal, Montreal, Quebec, Canada.
Linking genes to decreased survival in lung cancer patients
New data, generated by Hongbing Shen and colleagues, at the Cancer Center of Nanjing Medical University, People's Republic of China, has identified a genetic variation that seems to help predict survival in individuals with non-small cell lung cancer (NSCLC).
A systematic screen of the DNA carrying the information for generating regulatory RNA molecules known as a microRNAs identified a specific genetic variant that was associated with decreased survival in individuals with NSCLC. The specific genetic variation resulted in increased levels of expression of the functional miRNA molecule. This was not because more of the miRNA was made but because more of the precursor form of the functional molecule was processed to become functional. The functional miRNA molecule generated by the genetic variation also had different functional properties. The authors hope that further characterization of genetic variations that modify miRNA expression and/or function will uncover other indicators of survival and opportunities for developing new therapeutics.
TITLE: Genetic variants of miRNA sequences and non-small cell lung cancer survival
AUTHOR CONTACT:
Hongbing Shen
Cancer Center of Nanjing Medical University, Nanjing, People's Republic of China.
Blood vessel growth kept under control by the protein LIF
Uncontrolled blood vessel growth is a key feature of many pathological conditions, including the degenerative diabetic eye disease known as diabetic retinopathy. Understanding the factors involved in the process is vital to developing treatments for the disease. In a new study, a team of researchers at Keio University, Japan, has revealed a role for the protein LIF in blood vessel growth in mice.
Specifically, mice lacking LIF were observed to have increased blood vessel growth in many regions of the body, but as this study was focused on the eye, the authors homed in on the increased blood vessel growth in the retina of the eye. Further analysis showed that mice lacking LIF developed more aberrant blood vessels in a model of retinopathy. Mechanistically, LIF was found to inhibit the proliferation of brain cells known as astrocytes as well as inhibit their production of a factor known to promote blood vessel growth, VEGF. It therefore seems that LIF is an important part of the communication between tissues and developing blood vessels, meaning that LIF and the signaling pathway it triggers might serve as a target for new treatment approaches for preventing diabetic retinopathy and other diseases that are associated with uncontrolled blood vessel growth, such as cancer.
TITLE: Leukemia inhibitory factor regulates microvessel density by modulating oxygen-dependent VEGF expression in mice
AUTHOR CONTACT:
Yoshiaki Kubota
Keio University, Tokyo, Japan.
Toshio Suda
Keio University, Tokyo, Japan.
Repairing the damage to DNA from chronic inflammation protects against cancer
Individuals who have health conditions associated with chronic inflammation are often at increased risk of developing cancer at the site of the chronic inflammation. For example, individuals with inflammatory bowel disease and those who are chronically infected with the bacterium Helicobacter pylori are at increased risk of colon cancer and stomach cancer, respectively. New insight into the mechanisms by which chronic inflammation can contribute to the development cancer has been generated in mice by Leona Samson and colleagues, at Massachusetts Institute of Technology, Boston.
Using mice lacking the protein Aag, which is involved in the repair of DNA damaged by inflammation-associated molecules known as reactive oxygen and nitrogen species (RONS), it was shown that Aag-mediated DNA repair limits cell damage in a mouse model of episodic inflammatory bowel disease and reduces the severity of the colon cancer that develops in the mice experiencing episodic bowel inflammation. In addition, in a mouse model of Helicobacter pylori infection, Aag-deficient mice were found to exhibit more severe cell damage and the damaged area of the stomach resembled that observed prior to the development of stomach cancer. The authors therefore conclude that repair of DNA damage caused by RONS seems to be important for protection against chronic inflammation-induced cancer.
TITLE: DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice
AUTHOR CONTACT:
Leona D. Samson
Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Source: Karen Honey
Journal of Clinical Investigation
Soon after an individual becomes infected with HIV the virus infects cells in the brain and spinal cord (the central nervous system [CNS]). Although this causes no immediate problems, during the late-stages of disease it can cause dementia and encephalitis (acute inflammation of the brain that can cause death). Monkeys infected with a relative of HIV (SIV) also sometimes develop CNS damage and provide a good model of CNS disease in individuals infected with HIV. Insight into the mechanisms of CNS damage in SIV-infected monkeys has now been provided by a team of researchers at The Scripps Research Institute, La Jolla, who developed an approach to identify molecular changes in the fluid bathing the CNS (the CSF). The researchers, who were led by Howard Fox and Gary Siuzdak, hope that similar approaches could be used to provide new information about other neurodegenerative and neuropsychiatric disorders.
In the study, an approach known as global metabolomics was used to assess the levels of molecules known as metabolites in the CSF before and after SIV-induced encephalitis was manifest. The level of a number of metabolites, including some known as fatty acids and phospholipids, was observed to increase during infection. Consistent with this, a protein known to be important in the generation of fatty acids was found to be increased in the brain of monkeys with SIV-induced encephalitis. Further studies will be required to determine the precise role of the increased level of each metabolite, but it should be noted that many of them are known to induce receptor signaling and thereby might be able to further modulate CNS function.
TITLE: Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques
AUTHOR CONTACT:
Howard S. Fox
The Scripps Research Institute, La Jolla, California, USA.
Gary Siuzdak
The Scripps Research Institute, La Jolla, California, USA.
It's not a level playing field, your genes determine your levels of glucose
In individuals with type 2 diabetes, the way the level of glucose (the sugar molecule that is our main source of energy) in the body while not eating (fasting glucose level) is regulated fails and fasting glucose levels increase dramatically. New insight into genetic variations that have an impact on the fasting glucose levels of nondiabetic individuals has now been provided by a team of researchers from the Istituto Nazionale Ricovero E Cura Anziari, Italy, and the University of Southern California. Specifically, an association between one defined genetic variation and increased fasting glucose levels was observed in nondiabetic individuals. This variation was located between two genes known as G6PC2 and ABCB11. As G6PC2 carries the information for making a protein expressed by the cells that become dysfunctional in individuals with type 2 diabetes, the authors suggest that the genetic variation probably affects fasting glucose levels by altering the expression of this gene.
TITLE: Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels
AUTHOR CONTACT:
Angelo Scuteri
Istituto Nazionale Ricovero E Cura Anziari, Rome, Italy.
Richard M. Watanabe
Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Pinning down a cause of disease in a model of psoriasis
Psoriasis is a chronic skin disease that affects approximately 2-3% of individuals in the Western world. New data, generated by Karin Scharffetter-Kochanek and colleagues, at the University of Ulm, Germany, have indicated that a subset of immune cells known as Tregs (which act to prevent other immune cells from responding inappropriately) are dysfunctional in a mouse model of psoriasis and that this dysfunction contributes substantially to the development of disease.
Mice that express a reduced amount of the protein CD18 (Cd18hypo mice) develop a skin disease that resembles the symptoms of individuals with psoriasis. In the study, Tregs isolated from Cd18hypo mice failed to suppress the proliferation of disease-causing immune cells because they secreted lower levels of the soluble factor TGF-beta than normal Tregs. This was also important for their inability to control disease in vivo, as transplantation of normal Tregs into Cd18hypo mice resulted in a substantial improvement in the psoriasis-like disease, whereas if these cells were transplanted in the presence of antibodies that neutralized TGF-beta there was no improvement in disease. The authors therefore conclude that psoriasis-like disease in Cd18hypo mice is caused mainly by a defect in Treg function and suggest that maintaining CD18 levels is important for ensuring that Tregs function optimally.
TITLE: TGF-beta-dependent suppressive function of Tregs requires wild-type levels of CD18 in a mouse model of psoriasis
AUTHOR CONTACT:
Karin Scharffetter-Kochanek
University of Ulm, Ulm, Germany.
HSN2 mutations lose touch with pain and heat perception
Hereditary sensory and autonomic neuropathy type II, abbreviated to HSANII, is a poorly understood genetic disorder wherein affected patients lose the ability to feel touch, pain, and heat. Although it has been shown to be caused by mutations in a region of DNA known as HSN2, it was not known exactly what this region of DNA was for. In a new study, Guy Roulaeu and colleagues, at the University of Montreal, Canada, have discovered that HSN2 is part of the gene WNK1, but it is only used to generate a protein in the nervous system; in other parts of the body, the gene WNK1 does not use the information in the HSN2 region of DNA to make protein. Further analysis showed that the protein made using information contained in the HSN2 region of DNA (WNK1/HSN2) was found in mouse nerve cells that are vital for relaying sensory inputs such as touch and pain to the brain. Future studies will focus on determining the molecular mechanisms by which WNK1/HSN2 is important for sensing touch, pain, and heat, the very senses lost in individuals with HSANII.
TITLE: Mutations in the nervous system-specific HSN2 exon of WNK1 cause hereditary sensory neuropathy type II
AUTHOR CONTACT:
Guy A. Rouleau
University of Montreal, Montreal, Quebec, Canada.
Linking genes to decreased survival in lung cancer patients
New data, generated by Hongbing Shen and colleagues, at the Cancer Center of Nanjing Medical University, People's Republic of China, has identified a genetic variation that seems to help predict survival in individuals with non-small cell lung cancer (NSCLC).
A systematic screen of the DNA carrying the information for generating regulatory RNA molecules known as a microRNAs identified a specific genetic variant that was associated with decreased survival in individuals with NSCLC. The specific genetic variation resulted in increased levels of expression of the functional miRNA molecule. This was not because more of the miRNA was made but because more of the precursor form of the functional molecule was processed to become functional. The functional miRNA molecule generated by the genetic variation also had different functional properties. The authors hope that further characterization of genetic variations that modify miRNA expression and/or function will uncover other indicators of survival and opportunities for developing new therapeutics.
TITLE: Genetic variants of miRNA sequences and non-small cell lung cancer survival
AUTHOR CONTACT:
Hongbing Shen
Cancer Center of Nanjing Medical University, Nanjing, People's Republic of China.
Blood vessel growth kept under control by the protein LIF
Uncontrolled blood vessel growth is a key feature of many pathological conditions, including the degenerative diabetic eye disease known as diabetic retinopathy. Understanding the factors involved in the process is vital to developing treatments for the disease. In a new study, a team of researchers at Keio University, Japan, has revealed a role for the protein LIF in blood vessel growth in mice.
Specifically, mice lacking LIF were observed to have increased blood vessel growth in many regions of the body, but as this study was focused on the eye, the authors homed in on the increased blood vessel growth in the retina of the eye. Further analysis showed that mice lacking LIF developed more aberrant blood vessels in a model of retinopathy. Mechanistically, LIF was found to inhibit the proliferation of brain cells known as astrocytes as well as inhibit their production of a factor known to promote blood vessel growth, VEGF. It therefore seems that LIF is an important part of the communication between tissues and developing blood vessels, meaning that LIF and the signaling pathway it triggers might serve as a target for new treatment approaches for preventing diabetic retinopathy and other diseases that are associated with uncontrolled blood vessel growth, such as cancer.
TITLE: Leukemia inhibitory factor regulates microvessel density by modulating oxygen-dependent VEGF expression in mice
AUTHOR CONTACT:
Yoshiaki Kubota
Keio University, Tokyo, Japan.
Toshio Suda
Keio University, Tokyo, Japan.
Repairing the damage to DNA from chronic inflammation protects against cancer
Individuals who have health conditions associated with chronic inflammation are often at increased risk of developing cancer at the site of the chronic inflammation. For example, individuals with inflammatory bowel disease and those who are chronically infected with the bacterium Helicobacter pylori are at increased risk of colon cancer and stomach cancer, respectively. New insight into the mechanisms by which chronic inflammation can contribute to the development cancer has been generated in mice by Leona Samson and colleagues, at Massachusetts Institute of Technology, Boston.
Using mice lacking the protein Aag, which is involved in the repair of DNA damaged by inflammation-associated molecules known as reactive oxygen and nitrogen species (RONS), it was shown that Aag-mediated DNA repair limits cell damage in a mouse model of episodic inflammatory bowel disease and reduces the severity of the colon cancer that develops in the mice experiencing episodic bowel inflammation. In addition, in a mouse model of Helicobacter pylori infection, Aag-deficient mice were found to exhibit more severe cell damage and the damaged area of the stomach resembled that observed prior to the development of stomach cancer. The authors therefore conclude that repair of DNA damage caused by RONS seems to be important for protection against chronic inflammation-induced cancer.
TITLE: DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice
AUTHOR CONTACT:
Leona D. Samson
Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Source: Karen Honey
Journal of Clinical Investigation
вторник, 11 октября 2011 г.
Biologist Andrew Hendry And Psychologist Karim Nader Take Two Of Six National Canadian Fellowships
Two McGill researchers have been named as 2009 recipients of E.W.R. Steacie Memorial Fellowships. Dr. Andrew P. Hendry an associate professor with McGill's Department of Biology and the Redpath Museum, and Dr. Karim Nader, an associate professor and Willam Dawson Chair in the Department of Psychology, will both receive the prestigious fellowships from the Natural Sciences and Engineering Research Council of Canada (NSERC).
It is somehow appropriate that as we mark in 2009 the 150th anniversary of the publication of Charles Darwin's The Origin of the Species and the 200th anniversary of Darwin's birth, that an evolutionary expert like Andrew Hendry is recognized. Dr. Hendry heads McGill's Hendry Lab in Eco-Evolutionary Dynamics and is a leading investigator into the interface between ecological and evolutionary processes and their influence on biodiversity. Most recently, he co-authored a much-cited study about a rarely seen pattern of "disruptive natural selection" leading to the creation of new species among the famous finches of the Galapagos Islands, originally studied by Darwin.
Karim Nader's research group specializes in the esoteric area of memory and trauma. His research has focused on victims of violence, rape and abuse who suffer from post-traumatic stress disorder (PTSD), which can force them to relive their ordeals over and over again, with debilitating consequences. Dr. Nader's experiments suggest that damaging memories can be stripped of their potency by a common blood pressure medication, propranolol. News headlines around the world about this research have often made reference to the fictional Eternal Sunshine of the Spotless Mind.
"McGill is extremely proud of these two outstanding researchers," said Vice-Principal (Research and International Relations) Denis ThГ©rien. "Their work has produced important results on crucial matters related to both the human experience and the natural world. We are grateful to NSERC for recognizing the value of this top-level research."
The NSERC Steacie Fellowships honour the memory of Dr. Edgar William Richard Steacie, an outstanding chemist and research leader who made significant contributions to the development of science in Canada during, and immediately following, World War II. Dr. Steacie believed young researchers are great national assets and should be given every opportunity to develop their own ideas. Through his philosophy, summarized below, he nurtured Canadian talent and drew many promising scientists to Canada.
Every year, NSERC awards up to six Steacie Fellowships that are held for a two-year period. Successful Fellows are relieved of teaching and administrative duties, so they can devote all their time and energy to research. The Fellowships are held at a Canadian university or affiliated research institution.
The Fellowship normally includes a contribution to the university in the amount of $90,000 per year toward the Fellow's salary. As part of the Fellowship agreement, the university is expected to fund a replacement for the Fellow's teaching and administrative responsibilities or to enhance the research environment of the Fellow's department.
Notes:
NSERC is a federal agency whose vision is to help make Canada a country of discoverers and innovators for the benefit of all Canadians. The agency supports some 26,500 university students and postdoctoral fellows in their advanced studies. NSERC promotes discovery by funding more than 11,800 university professors every year and fosters innovation by encouraging more than 1,400 Canadian companies to participate and invest in postsecondary research projects.
ABOUT McGILL UNIVERSITY
McGill University, founded in Montreal, Que., in 1821, is Canada's leading post-secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 34,000 students. McGill attracts students from more than 160 countries around the world. Almost half of McGill students claim a first language other than English - including 6,000 francophones - with more than 6,400 international students making up almost 20 per cent of the student body.
This release is available in French.
Source: Mark Shainblum
McGill University
It is somehow appropriate that as we mark in 2009 the 150th anniversary of the publication of Charles Darwin's The Origin of the Species and the 200th anniversary of Darwin's birth, that an evolutionary expert like Andrew Hendry is recognized. Dr. Hendry heads McGill's Hendry Lab in Eco-Evolutionary Dynamics and is a leading investigator into the interface between ecological and evolutionary processes and their influence on biodiversity. Most recently, he co-authored a much-cited study about a rarely seen pattern of "disruptive natural selection" leading to the creation of new species among the famous finches of the Galapagos Islands, originally studied by Darwin.
Karim Nader's research group specializes in the esoteric area of memory and trauma. His research has focused on victims of violence, rape and abuse who suffer from post-traumatic stress disorder (PTSD), which can force them to relive their ordeals over and over again, with debilitating consequences. Dr. Nader's experiments suggest that damaging memories can be stripped of their potency by a common blood pressure medication, propranolol. News headlines around the world about this research have often made reference to the fictional Eternal Sunshine of the Spotless Mind.
"McGill is extremely proud of these two outstanding researchers," said Vice-Principal (Research and International Relations) Denis ThГ©rien. "Their work has produced important results on crucial matters related to both the human experience and the natural world. We are grateful to NSERC for recognizing the value of this top-level research."
The NSERC Steacie Fellowships honour the memory of Dr. Edgar William Richard Steacie, an outstanding chemist and research leader who made significant contributions to the development of science in Canada during, and immediately following, World War II. Dr. Steacie believed young researchers are great national assets and should be given every opportunity to develop their own ideas. Through his philosophy, summarized below, he nurtured Canadian talent and drew many promising scientists to Canada.
Every year, NSERC awards up to six Steacie Fellowships that are held for a two-year period. Successful Fellows are relieved of teaching and administrative duties, so they can devote all their time and energy to research. The Fellowships are held at a Canadian university or affiliated research institution.
The Fellowship normally includes a contribution to the university in the amount of $90,000 per year toward the Fellow's salary. As part of the Fellowship agreement, the university is expected to fund a replacement for the Fellow's teaching and administrative responsibilities or to enhance the research environment of the Fellow's department.
Notes:
NSERC is a federal agency whose vision is to help make Canada a country of discoverers and innovators for the benefit of all Canadians. The agency supports some 26,500 university students and postdoctoral fellows in their advanced studies. NSERC promotes discovery by funding more than 11,800 university professors every year and fosters innovation by encouraging more than 1,400 Canadian companies to participate and invest in postsecondary research projects.
ABOUT McGILL UNIVERSITY
McGill University, founded in Montreal, Que., in 1821, is Canada's leading post-secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 34,000 students. McGill attracts students from more than 160 countries around the world. Almost half of McGill students claim a first language other than English - including 6,000 francophones - with more than 6,400 international students making up almost 20 per cent of the student body.
This release is available in French.
Source: Mark Shainblum
McGill University
суббота, 8 октября 2011 г.
Replacement Drug For Treating Cocaine Addiction Has Positive Finding In Animal Model
New research in monkeys suggests the feasibility of treating cocaine addiction with a "replacement" drug that mimics the effects of cocaine but has less potential for abuse - similar to the way nicotine and heroin addictions are treated.
Reporting at the annual meeting of the American Society of Pharmacology and Experimental Therapeutics in San Diego, Calif., scientists from Wake Forest University School of Medicine said treating monkeys with amphetamine significantly reduced their self-administration of cocaine for up to a month.
"This suggests the possibility of developing an amphetamine-like drug for treating cocaine addiction," said Paul Czoty, Ph.D., lead author and assistant professor of physiology and pharmacology. "The research also demonstrates the usefulness for conducting studies in monkeys to test potential treatments."
Czoty said the quest to develop a treatment for cocaine addiction has been ongoing for decades with little success. "While we have medications for heroin and tobacco abuse, there is no FDA-approved treatment for cocaine," he said.
With both heroin and tobacco, there are treatments to replace the addictive drug with a drug that has similar effects on the body, but with less potential for abuse.
"With this strategy in mind, clinical researchers have turned to drugs currently available, including amphetamines," said Czoty. "While it's unlikely that amphetamine itself will turn out to be the best treatment, these drugs allow us to prove the concept of using a replacement drug to combat cocaine addiction."
Amphetamines have been used in clinical studies with some success, said Czoty. His research in monkeys may help identify the best dose and schedule for administering a replacement drug - as well as evaluate potential treatment candidates and estimate potential side effects.
For the study, a monkey was taught to press levers multiple times to obtain food or a cocaine injection. With each injection, the number of required lever presses increased so that the animal had to work harder for the cocaine.
"This procedure measures the strength of the reinforcing effects of drugs," said Czoty. "Each injection requires more and more work and eventually it gets to the point where it's not worth it to the monkey because more than 1,000 presses are required."
Access to cocaine was then removed and the monkey was treated intravenously with an amphetamine 24 hours per day. When re-exposed to cocaine one week later, a dramatic decrease in responding for cocaine was observed. They tested three different doses of amphetamine and found that a moderate dose was most effective. Although the treatment also decreased lever-pressing for food - which could be predictive of side effects in humans - this effect disappeared within one week while the effect on responding for cocaine injections persisted for up to one month.
"This was a very positive finding - exactly what we had hoped to see," said Czoty. "Cocaine use was significantly reduced - by about 60 percent."
The researchers are currently repeating the study in additional animals. They hope it could eventually lead to identifying a slightly different drug that will obtain the same results as amphetamines.
Czoty said the study is significant because it and other similar studies in monkeys duplicate what has been found in small studies in humans, which suggests that the animal model can be used to test other treatments. The researchers, for example, plan to test topiramate (Topamax®), an anti-convulsant drug that is sometimes used to treat epilepsy and may be effective in treating alcoholism.
"We have found a model we can use to test new drugs and have an idea of what positive or negative effects would look like," said Czoty.
The research was funded by the National Institute on Drug Abuse and was part of Wake Forest's Center for the Neurobiological Investigation of Drug Abuse. Co-researchers were graduate student Jenn Martelle, and Professor Mike Nader, Ph.D., both in the Department of Physiology and Pharmacology.
Wake Forest University Baptist Medical Center (wfubmc/) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Karen Richardson
Wake Forest University Baptist Medical Center
View drug information on Topamax.
Reporting at the annual meeting of the American Society of Pharmacology and Experimental Therapeutics in San Diego, Calif., scientists from Wake Forest University School of Medicine said treating monkeys with amphetamine significantly reduced their self-administration of cocaine for up to a month.
"This suggests the possibility of developing an amphetamine-like drug for treating cocaine addiction," said Paul Czoty, Ph.D., lead author and assistant professor of physiology and pharmacology. "The research also demonstrates the usefulness for conducting studies in monkeys to test potential treatments."
Czoty said the quest to develop a treatment for cocaine addiction has been ongoing for decades with little success. "While we have medications for heroin and tobacco abuse, there is no FDA-approved treatment for cocaine," he said.
With both heroin and tobacco, there are treatments to replace the addictive drug with a drug that has similar effects on the body, but with less potential for abuse.
"With this strategy in mind, clinical researchers have turned to drugs currently available, including amphetamines," said Czoty. "While it's unlikely that amphetamine itself will turn out to be the best treatment, these drugs allow us to prove the concept of using a replacement drug to combat cocaine addiction."
Amphetamines have been used in clinical studies with some success, said Czoty. His research in monkeys may help identify the best dose and schedule for administering a replacement drug - as well as evaluate potential treatment candidates and estimate potential side effects.
For the study, a monkey was taught to press levers multiple times to obtain food or a cocaine injection. With each injection, the number of required lever presses increased so that the animal had to work harder for the cocaine.
"This procedure measures the strength of the reinforcing effects of drugs," said Czoty. "Each injection requires more and more work and eventually it gets to the point where it's not worth it to the monkey because more than 1,000 presses are required."
Access to cocaine was then removed and the monkey was treated intravenously with an amphetamine 24 hours per day. When re-exposed to cocaine one week later, a dramatic decrease in responding for cocaine was observed. They tested three different doses of amphetamine and found that a moderate dose was most effective. Although the treatment also decreased lever-pressing for food - which could be predictive of side effects in humans - this effect disappeared within one week while the effect on responding for cocaine injections persisted for up to one month.
"This was a very positive finding - exactly what we had hoped to see," said Czoty. "Cocaine use was significantly reduced - by about 60 percent."
The researchers are currently repeating the study in additional animals. They hope it could eventually lead to identifying a slightly different drug that will obtain the same results as amphetamines.
Czoty said the study is significant because it and other similar studies in monkeys duplicate what has been found in small studies in humans, which suggests that the animal model can be used to test other treatments. The researchers, for example, plan to test topiramate (Topamax®), an anti-convulsant drug that is sometimes used to treat epilepsy and may be effective in treating alcoholism.
"We have found a model we can use to test new drugs and have an idea of what positive or negative effects would look like," said Czoty.
The research was funded by the National Institute on Drug Abuse and was part of Wake Forest's Center for the Neurobiological Investigation of Drug Abuse. Co-researchers were graduate student Jenn Martelle, and Professor Mike Nader, Ph.D., both in the Department of Physiology and Pharmacology.
Wake Forest University Baptist Medical Center (wfubmc/) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Karen Richardson
Wake Forest University Baptist Medical Center
View drug information on Topamax.
среда, 5 октября 2011 г.
Long-Distance Brain Waves Focus Attention
Just as our world buzzes with distractions - from phone calls to e-mails to tweets - the neurons in our brain are bombarded with messages. Research has shown that when we pay attention, some of these neurons begin firing in unison, like a chorus rising above the noise. Now, a study in the May 29 issue of Science reveals the likely brain center that serves as the conductor of this neural chorus.
MIT neuroscientists found that neurons in the prefrontal cortex - the brain's planning center - fire in unison and send signals to the visual cortex to do the same, generating high-frequency waves that oscillate between these distant brain regions like a vibrating spring. These waves, also known as gamma oscillations, have long been associated with cognitive states like attention, learning, and consciousness.
"We are especially interested in gamma oscillations in the prefrontal cortex because it provides top-down influences over other parts of the brain," explains senior author Robert Desimone, director of the McGovern Institute for Brain Research and the Doris and Don Berkey Professor of Neuroscience at MIT. "We know that the prefrontal cortex is affected in people with schizophrenia, ADHD and many other brain disorders, and that gamma oscillations are also altered in these conditions. Our results suggest that altered neural synchrony in the prefrontal cortex could disrupt communication between this region and other areas of the brain, leading to altered perceptions, thoughts, and emotions."
To explain neural synchrony, Desimone uses the analogy of a crowded party with people talking in different rooms. If individuals raise their voices at random, the noise just becomes louder. But if a group of individuals in one room chant together in unison, the next room is more likely to hear the message. And if people in the next room chant in response, the two rooms can communicate.
In the Science study, Desimone looked for patterns of neural synchrony in two "rooms" of the brain associated with attention - the frontal eye field (FEF) within the prefrontal cortex and the V4 region of the visual cortex. Lead authors Georgia Gregoriou, a postdoctoral associate in the Desimone lab, and Stephen Gotts of the National Institute of Mental Health, trained two macaque monkeys to watch a monitor displaying multiple objects, and to concentrate on one of the objects when cued. They monitored neural activity from the FEF and the V4 regions of the brain when the monkeys were either paying attention to the object or ignoring it.
When the monkeys first paid attention to the appropriate object, neurons in both areas showed strong increases in activity. Then, as if connected by a spring, the oscillations in each area began to synchronize with one another. Desimone's team analyzed the timing of the neural activity and found that the prefrontal cortex became engaged by attention first, followed by the visual cortex - as if the prefrontal cortex commanded the visual region to snap to attention. The delay between neural activity in these areas during each wave cycle reflected the speed at which signals travel from one region to the other - indicating that the two brain regions were talking to one another.
Desimone suspects this pattern of oscillation is not just specific to attention, but could also represent a more general mechanism for communication between different parts of the brain. These findings support speculation that gamma synchrony enables far-flung regions of the brain to rapidly communicate with each other - which has important implications for understanding and treating disorders ranging from schizophrenia to impaired vision and attention. "This helps us think about how to approach studying and treating these disorders by finding ways to restore gamma rhythms in the affected brain regions."
Huihui Zhou, a research scientist in the Desimone lab, contributed to this study. The NIH/National Eye Institute and National Institute of Mental Health supported this research.
Source:
Elizabeth Thomson
McGovern Institute for Brain Research
MIT neuroscientists found that neurons in the prefrontal cortex - the brain's planning center - fire in unison and send signals to the visual cortex to do the same, generating high-frequency waves that oscillate between these distant brain regions like a vibrating spring. These waves, also known as gamma oscillations, have long been associated with cognitive states like attention, learning, and consciousness.
"We are especially interested in gamma oscillations in the prefrontal cortex because it provides top-down influences over other parts of the brain," explains senior author Robert Desimone, director of the McGovern Institute for Brain Research and the Doris and Don Berkey Professor of Neuroscience at MIT. "We know that the prefrontal cortex is affected in people with schizophrenia, ADHD and many other brain disorders, and that gamma oscillations are also altered in these conditions. Our results suggest that altered neural synchrony in the prefrontal cortex could disrupt communication between this region and other areas of the brain, leading to altered perceptions, thoughts, and emotions."
To explain neural synchrony, Desimone uses the analogy of a crowded party with people talking in different rooms. If individuals raise their voices at random, the noise just becomes louder. But if a group of individuals in one room chant together in unison, the next room is more likely to hear the message. And if people in the next room chant in response, the two rooms can communicate.
In the Science study, Desimone looked for patterns of neural synchrony in two "rooms" of the brain associated with attention - the frontal eye field (FEF) within the prefrontal cortex and the V4 region of the visual cortex. Lead authors Georgia Gregoriou, a postdoctoral associate in the Desimone lab, and Stephen Gotts of the National Institute of Mental Health, trained two macaque monkeys to watch a monitor displaying multiple objects, and to concentrate on one of the objects when cued. They monitored neural activity from the FEF and the V4 regions of the brain when the monkeys were either paying attention to the object or ignoring it.
When the monkeys first paid attention to the appropriate object, neurons in both areas showed strong increases in activity. Then, as if connected by a spring, the oscillations in each area began to synchronize with one another. Desimone's team analyzed the timing of the neural activity and found that the prefrontal cortex became engaged by attention first, followed by the visual cortex - as if the prefrontal cortex commanded the visual region to snap to attention. The delay between neural activity in these areas during each wave cycle reflected the speed at which signals travel from one region to the other - indicating that the two brain regions were talking to one another.
Desimone suspects this pattern of oscillation is not just specific to attention, but could also represent a more general mechanism for communication between different parts of the brain. These findings support speculation that gamma synchrony enables far-flung regions of the brain to rapidly communicate with each other - which has important implications for understanding and treating disorders ranging from schizophrenia to impaired vision and attention. "This helps us think about how to approach studying and treating these disorders by finding ways to restore gamma rhythms in the affected brain regions."
Huihui Zhou, a research scientist in the Desimone lab, contributed to this study. The NIH/National Eye Institute and National Institute of Mental Health supported this research.
Source:
Elizabeth Thomson
McGovern Institute for Brain Research
воскресенье, 2 октября 2011 г.
A Better Way To Battle Mosquitoes
Protecting ourselves from backyard mosquito bites may come down to leaving the vacuuming for later, a study from York University shows.
Rather than vacuuming the grass clippings out of catch basins before adding treatments to control mosquitoes, municipalities should leave the organic waste in place, the research found.
"Catch basins are a permanent source of mosquitoes on every street. By putting S-methoprene in cleaned catch basins we saw an average of 20 per cent of the mosquito larvae make it to the adult stage over the duration of the study. But that number was reduced to less than 3 per cent just by leaving the organic debris in the catch basins until the fall, when mosquito season is over," says Norman Yan, a professor in York University's Department of Biology.
Yan and former York master's student Stacey Baker co-authored a study published in the current issue of the Journal of the American Mosquito Control Association. They were surprised by the results of the research, conducted by Baker in 2005 on residential streets in the Greater Toronto Area.
"We predicted that S-methoprene would work better in the catch basins that had been cleaned. We found the opposite - that S-methoprene binds to organic material, which holds it in the catch basins longer so that mosquito larvae are exposed to it for longer," says Baker.
The research may have implications not only for our comfort levels, but for disease control, says Yan. The human West Nile Virus rate and the number of positive mosquito pools have been lower in the past two years in Ontario, but it remains a problem in some areas of the United States, and warmer temperatures and a wet season could increase the risk in Ontario. The West Nile Virus is not carried by all mosquitoes but it can lead to severe symptoms and even death.
Public health units in Ontario determine if and when they will larvicide based on their surveillance of the level of risk. S-methoprene, which is used in Canada only for control of West Nile Virus, is still being used in hundreds of thousands of catch basins in the GTA, but there has been no thought given to the cleaning schedule, according to the authors. The study demonstrates that scheduling both the application of S-methoprene and the removal of debris makes sense, they said, and it may be worthwhile to clean the catch basins every two years instead of annually.
"Accumulated Organic Debris in Catch Basins Improves the Efficacy of S-methoprene against Mosquitoes in Toronto, Ontario, Canada" appears in the Journal of the American Mosquito Control Association. York University's Knowledge Mobilization Unit, which seeks to maximize the impact of academic research on public policy and professional practice, has sent a summary of the research findings to Ontario's public health units.
Source:
Janice Walls
York University
Rather than vacuuming the grass clippings out of catch basins before adding treatments to control mosquitoes, municipalities should leave the organic waste in place, the research found.
"Catch basins are a permanent source of mosquitoes on every street. By putting S-methoprene in cleaned catch basins we saw an average of 20 per cent of the mosquito larvae make it to the adult stage over the duration of the study. But that number was reduced to less than 3 per cent just by leaving the organic debris in the catch basins until the fall, when mosquito season is over," says Norman Yan, a professor in York University's Department of Biology.
Yan and former York master's student Stacey Baker co-authored a study published in the current issue of the Journal of the American Mosquito Control Association. They were surprised by the results of the research, conducted by Baker in 2005 on residential streets in the Greater Toronto Area.
"We predicted that S-methoprene would work better in the catch basins that had been cleaned. We found the opposite - that S-methoprene binds to organic material, which holds it in the catch basins longer so that mosquito larvae are exposed to it for longer," says Baker.
The research may have implications not only for our comfort levels, but for disease control, says Yan. The human West Nile Virus rate and the number of positive mosquito pools have been lower in the past two years in Ontario, but it remains a problem in some areas of the United States, and warmer temperatures and a wet season could increase the risk in Ontario. The West Nile Virus is not carried by all mosquitoes but it can lead to severe symptoms and even death.
Public health units in Ontario determine if and when they will larvicide based on their surveillance of the level of risk. S-methoprene, which is used in Canada only for control of West Nile Virus, is still being used in hundreds of thousands of catch basins in the GTA, but there has been no thought given to the cleaning schedule, according to the authors. The study demonstrates that scheduling both the application of S-methoprene and the removal of debris makes sense, they said, and it may be worthwhile to clean the catch basins every two years instead of annually.
"Accumulated Organic Debris in Catch Basins Improves the Efficacy of S-methoprene against Mosquitoes in Toronto, Ontario, Canada" appears in the Journal of the American Mosquito Control Association. York University's Knowledge Mobilization Unit, which seeks to maximize the impact of academic research on public policy and professional practice, has sent a summary of the research findings to Ontario's public health units.
Source:
Janice Walls
York University
четверг, 29 сентября 2011 г.
Multiple Detection Of Pathogens May Be Possible With New Magnetic Separation Technique
A magnetic separation technique developed by researchers at Duke University's Pratt School of Engineering and Purdue University makes it relatively simple to sort through beads hundreds of times smaller than the period at the end of this sentence.
The method could lead to new technologies for medical or environmental testing, according to the researchers. For example, specially coated magnetic particles designed to attract particular viruses or bacteria might be used in tailored combinations to simultaneously test for multiple infectious pathogens in a blood or water sample.
Benjamin Yellen, assistant professor of mechanical engineering and materials science at Duke, and Gil Lee, associate professor of chemical engineering at Purdue, report their findings in the December issue of the journal Lab on a Chip.
"If there were five viruses that a patient might have been exposed to, you could potentially develop a technique to look for those five viruses all at the same time," Yellen said. In principle, such a test could be done with just a single drop of blood, as long as there was virus in the sample.
As an initial demonstration of the concept, the researchers attached two "model pathogens," a baker's yeast and a soil bacterium, to magnetic beads, and used their technique to selectively isolate them.
The magnetic separation method, which the researchers call magnetophoresis, uses a rotating magnetic field and a microchip containing an array of miniature magnets to separate tiny magnetic beads based on their size within a matter of minutes.
The physics behind the technique is as interesting as its potential applications, Yellen added. "The method causes certain particles to become essentially immobile -- just jittering back and forth -- while others move off the chip where they can be isolated. It implies that we could achieve effectively infinite separation between particle types. We thought our technique would work well for bioseparation, but we hadn't predicted it would be this good."
While the researchers know how to precisely control which particles move and which stay put, by varying the frequency of the magnetic field they apply, the underlying physics responsible for the behavior remains partly unexplained and will be the subject of future investigation, Yellen said.
Micrometer and nanometer sized "superparamagnetic" beads already are used widely to magnetically separate biological molecules and cells from complex fluid mixtures, Yellen said. Superparamagnetism is a form of magnetic behavior which occurs primarily in materials composed of very small magnetic grains. Such materials are commonly used for drug delivery and imaging applications and in biomedical devices because they become magnetized only in the presence of an externally applied magnetic field, which helps prevent clumping.
Over the past few decades, however, there have been few new developments in the field of magnetic separation, according to the researchers, with most of the efforts focused on using stronger and stronger magnetic fields and field gradients.
"Now, we've demonstrated a fundamentally new and different approach to magnetic separation, which can dramatically increase the separation efficiency, not by exploiting stronger fields and field gradients, but rather by precisely tuning the mobility of beads and exploiting the non-linear dynamics of particles moving in a traveling wave," Yellen said.
Collaborators on the study include Duke graduate students Randall Erb and Hui Son; Rodward Hewlin, Jr., an undergraduate at the North Carolina Agricultural and Technical State University who worked in Yellen's laboratory; and Hao Shang, a postdoctoral fellow at Purdue. The work was funded by the National Science Foundation and the NASA Institute for Nanoelectronics and Computing at Purdue.
Source: Kendall Morgan
Duke University
The method could lead to new technologies for medical or environmental testing, according to the researchers. For example, specially coated magnetic particles designed to attract particular viruses or bacteria might be used in tailored combinations to simultaneously test for multiple infectious pathogens in a blood or water sample.
Benjamin Yellen, assistant professor of mechanical engineering and materials science at Duke, and Gil Lee, associate professor of chemical engineering at Purdue, report their findings in the December issue of the journal Lab on a Chip.
"If there were five viruses that a patient might have been exposed to, you could potentially develop a technique to look for those five viruses all at the same time," Yellen said. In principle, such a test could be done with just a single drop of blood, as long as there was virus in the sample.
As an initial demonstration of the concept, the researchers attached two "model pathogens," a baker's yeast and a soil bacterium, to magnetic beads, and used their technique to selectively isolate them.
The magnetic separation method, which the researchers call magnetophoresis, uses a rotating magnetic field and a microchip containing an array of miniature magnets to separate tiny magnetic beads based on their size within a matter of minutes.
The physics behind the technique is as interesting as its potential applications, Yellen added. "The method causes certain particles to become essentially immobile -- just jittering back and forth -- while others move off the chip where they can be isolated. It implies that we could achieve effectively infinite separation between particle types. We thought our technique would work well for bioseparation, but we hadn't predicted it would be this good."
While the researchers know how to precisely control which particles move and which stay put, by varying the frequency of the magnetic field they apply, the underlying physics responsible for the behavior remains partly unexplained and will be the subject of future investigation, Yellen said.
Micrometer and nanometer sized "superparamagnetic" beads already are used widely to magnetically separate biological molecules and cells from complex fluid mixtures, Yellen said. Superparamagnetism is a form of magnetic behavior which occurs primarily in materials composed of very small magnetic grains. Such materials are commonly used for drug delivery and imaging applications and in biomedical devices because they become magnetized only in the presence of an externally applied magnetic field, which helps prevent clumping.
Over the past few decades, however, there have been few new developments in the field of magnetic separation, according to the researchers, with most of the efforts focused on using stronger and stronger magnetic fields and field gradients.
"Now, we've demonstrated a fundamentally new and different approach to magnetic separation, which can dramatically increase the separation efficiency, not by exploiting stronger fields and field gradients, but rather by precisely tuning the mobility of beads and exploiting the non-linear dynamics of particles moving in a traveling wave," Yellen said.
Collaborators on the study include Duke graduate students Randall Erb and Hui Son; Rodward Hewlin, Jr., an undergraduate at the North Carolina Agricultural and Technical State University who worked in Yellen's laboratory; and Hao Shang, a postdoctoral fellow at Purdue. The work was funded by the National Science Foundation and the NASA Institute for Nanoelectronics and Computing at Purdue.
Source: Kendall Morgan
Duke University
понедельник, 26 сентября 2011 г.
T-Ray Breakthrough Could Make Detecting Disease Far Easier
A breakthrough in the harnessing of 'T-rays' - electromagnetic terahertz waves - which could dramatically improve the detecting and sensing of objects as varied as biological cell abnormalities and explosives has been announced.
Researchers at the University of Bath, UK, and in Spain have said they have found a way to control the flow of terahertz radiation down a metal wire. Their findings are set out in a letter published in the current journal Physical Review Letters.
Terahertz radiation, whose frequency is around one thousand billion cycles a second, bridges the gap between the microwave and infrared parts of the electromagnetic spectrum.
Materials interact with radiation at T-ray frequencies in different ways than with radiation in other parts of the spectrum, making T-rays potentially important in detecting and analysing chemicals by analysing how they absorb T-rays fired at them.
This would allow quality control of prescribed drugs and detection of explosives to be carried out more easily, as many complex molecules have distinctive signatures in this part of the electromagnetic spectrum.
T-ray applications are presently limited by the relatively poor ability to focus the rays, which is achieved using the conventional means of lenses and mirrors to focus the radiation. This limits the spot size of focused T-rays to a substantial fraction of a millimetre and this has made studies of small objects such as biological cells with high resolution are virtually impossible.
But in their work the researchers found that although ordinary metal wire would not guide T-rays very well, if a series of tiny grooves was cut into the wire, it would do so much more effectively. If such a corrugated metal wire is then tapered to a point it becomes possible to very efficiently transport radiation to a point as small as a few millionths of a metre across.
This might, for example, lead to breakthroughs in examining very small objects such as the interior of biological cells where it might be possible to detect diseases or abnormalities. T-rays could also be directed to the interior of objects which could be useful in applications like endoscopic probing for cancerous cells or explosive detection.
"This is a significant development that would allow unprecedented accuracy in studying tiny objects and sensing chemicals using T-rays" said Dr Stefan Maier, of the University of Bath's Department of Physics, who leads the research.
"Metal wire ordinarily has a limited ability to allow T-rays to flow along it, but our idea was to overcome this by corrugating its surface with a series of grooves, in effect creating an artificial material or 'metamaterial' as far as the T-rays are concerned."
"In this way, the T-rays can be focused to the tip of the wire and guided into confined spaces or used to detect small objects, with important implications for disease detection or finding explosive that are hidden."
Dr Maier is working with Dr Steve Andrews at Bath, and with Professor Francisco GarcAa-Vidal, of the Universidad AutAnoma de Madrid, and Luis MartAn-Moreno, of the Universidad de Zaragoza-CSIC.
The project, which is funded by the Royal Society in the UK, the EU and the US Airforce, is one year into its three-year term. The researchers hope to produce a working model within a year.
Contact: Tony Trueman
University of Bath
Researchers at the University of Bath, UK, and in Spain have said they have found a way to control the flow of terahertz radiation down a metal wire. Their findings are set out in a letter published in the current journal Physical Review Letters.
Terahertz radiation, whose frequency is around one thousand billion cycles a second, bridges the gap between the microwave and infrared parts of the electromagnetic spectrum.
Materials interact with radiation at T-ray frequencies in different ways than with radiation in other parts of the spectrum, making T-rays potentially important in detecting and analysing chemicals by analysing how they absorb T-rays fired at them.
This would allow quality control of prescribed drugs and detection of explosives to be carried out more easily, as many complex molecules have distinctive signatures in this part of the electromagnetic spectrum.
T-ray applications are presently limited by the relatively poor ability to focus the rays, which is achieved using the conventional means of lenses and mirrors to focus the radiation. This limits the spot size of focused T-rays to a substantial fraction of a millimetre and this has made studies of small objects such as biological cells with high resolution are virtually impossible.
But in their work the researchers found that although ordinary metal wire would not guide T-rays very well, if a series of tiny grooves was cut into the wire, it would do so much more effectively. If such a corrugated metal wire is then tapered to a point it becomes possible to very efficiently transport radiation to a point as small as a few millionths of a metre across.
This might, for example, lead to breakthroughs in examining very small objects such as the interior of biological cells where it might be possible to detect diseases or abnormalities. T-rays could also be directed to the interior of objects which could be useful in applications like endoscopic probing for cancerous cells or explosive detection.
"This is a significant development that would allow unprecedented accuracy in studying tiny objects and sensing chemicals using T-rays" said Dr Stefan Maier, of the University of Bath's Department of Physics, who leads the research.
"Metal wire ordinarily has a limited ability to allow T-rays to flow along it, but our idea was to overcome this by corrugating its surface with a series of grooves, in effect creating an artificial material or 'metamaterial' as far as the T-rays are concerned."
"In this way, the T-rays can be focused to the tip of the wire and guided into confined spaces or used to detect small objects, with important implications for disease detection or finding explosive that are hidden."
Dr Maier is working with Dr Steve Andrews at Bath, and with Professor Francisco GarcAa-Vidal, of the Universidad AutAnoma de Madrid, and Luis MartAn-Moreno, of the Universidad de Zaragoza-CSIC.
The project, which is funded by the Royal Society in the UK, the EU and the US Airforce, is one year into its three-year term. The researchers hope to produce a working model within a year.
Contact: Tony Trueman
University of Bath
пятница, 23 сентября 2011 г.
'Marathon Mice' Elucidate Little-Known Muscle Type
Researchers report in the January issue of the journal Cell Metabolism, published by Cell Press, the discovery of a genetic "switch" that drives the formation of a poorly understood type of muscle. Moreover, they found, animals whose muscles were full of the so-called IIX fibers were able to run farther and at higher work loads than normal mice could.
The findings could ultimately lead to novel drugs designed to change the composition of muscle, the researchers said. Such treatments might have the potential to boost physical strength and endurance in patients with a variety of muscle wasting conditions.
The research team, led by Bruce Spiegelman of Harvard Medical School, found that increasing activity of the gene known as PGC-1Гў in the skeletal muscles of mice caused them to become crowded with IIX muscle fibers, which are normally much less prevalent.
"One reason why less is known about IIX fibers is that no one muscle group is packed with them," Spiegelman said. "For the first time, we have a mouse model very enriched in IIX fibers. These mice show a greatly increased capacity to sustain physical activity."
Skeletal muscle converts chemical energy into motion and force, ranging from rapid and sudden bursts of intense activity to continuous low-intensity work, the researchers said. At one functional extreme, muscles such as the soleus--a broad, flat muscle found in the calf of the leg--perform slow but steady activities such as maintaining posture. At the other extreme, muscles such as the quadriceps typically perform intense and rapid activities.
To fulfill these varied roles, muscles vary in their proportion of "slow-twitch" muscle fibers (types I and IIA), ideal for slow and constant roles, and "fast-twitch" fibers (type IIB), better suited to rapid and sudden activity of shorter duration. The fiber types are defined by which "myosin heavy chains" (MHCs) they contain and by their metabolic capacity, a feature largely determined by the number of energy-producing mitochondria they house. Myosins are motor proteins that consist of both "heavy" and "light" amino acid chains.
While most muscles in mammals contain a mixture of slow- and fast-twitch fiber types, some muscle beds are enriched for one type or the other, Spiegelman said. However, adult skeletal muscles also contain fibers with an abundance of a fourth MHC, type IIX, about which much less is known.
IIX fibers seem to have the oxidative metabolism of slow-twitch fibers mixed with the biophysical properties of fast-twitch fibers. Oxidative metabolism is by far the most efficient way of generating energy, Spiegelman said.
In the current study, the researchers produced mice with higher than normal levels of the transcriptional coactivator PGC-1Гў in their skeletal muscles. Transcriptional coactivators work with other cellular factors and machinery to control the activity of other genes. While earlier studies had found that the related coactivator PGC-1Гў plays a role in determining muscle type, the role of PGC-1Гў wasn't known.
"The muscle from the PGC-1Гў transgenic mice was strikingly redder in appearance than wild-type controls," indicative of their increased mitochondrial content, the researchers now report. Upon further examination, the researchers were surprised to find that the fibers showed a reduction in I, IIA, and IIB MHCs and as much as a 5-fold increase in IIX MHC.
Nearly 100% of muscle fibers in the transgenic animals contained abundant MHC IIX mRNA and protein, they found, as compared to only 15%-20% in normal animals. PGC-1Гў also changed the muscles' metabolic characteristics by driving the activity of genes that spark proliferation of mitochondria.
The PGC-1Гў animals with more IIX muscle fibers showed a greater capacity for aerobic exercise, they found. Transgenic mice were able to run, on average, for 32.5 min to exhaustion, compared to 26 min for their normal littermates, Spiegelman's group reported.
"These data have potential importance for the therapy of a number of muscular and neuromuscular diseases in humans," Spiegelman's group concluded.
"Many conditions accompanied by loss of physical mobility, including paraplegia, prolonged bed rest, and muscular dystrophies, involve a loss of oxidative fibers and their replacement with glycolytic fibers. This, in turn, results in a further loss of resistance to fatigue, exacerbating the patient's condition in a downward spiral. The identification of PGC-1Гў as a potential mediator of the development of oxidative type IIX fibers suggests new ways to modulate muscle fiber type in health and disease."
The researchers include Zoltan Arany, Eric Smith, Wenli Yang, Yanhong Ma, Sherry Chin, and Bruce M. Spiegelman of Dana-Farber Cancer Institute and Harvard Medical School in Boston, MA; Nathan Lebrasseur and Carl Morris of Boston University School of Medicine in Boston, MA
This work was supported by NIH grants HL079172 to Z.A. and DK54477 and DK61562 to B.M.S.
Arany et al.: "The Transcriptional Coactivator PGC-1b Drives the Formation of Oxidative Type IIX Fibers in Skeletal Muscle." Publishing in Cell Metabolism 5, 35-46, January 2007 DOI 10.1016/j.cmet.2006.12.003 cellmetabolism/
Contact: Erin Doonan
Cell Press
The findings could ultimately lead to novel drugs designed to change the composition of muscle, the researchers said. Such treatments might have the potential to boost physical strength and endurance in patients with a variety of muscle wasting conditions.
The research team, led by Bruce Spiegelman of Harvard Medical School, found that increasing activity of the gene known as PGC-1Гў in the skeletal muscles of mice caused them to become crowded with IIX muscle fibers, which are normally much less prevalent.
"One reason why less is known about IIX fibers is that no one muscle group is packed with them," Spiegelman said. "For the first time, we have a mouse model very enriched in IIX fibers. These mice show a greatly increased capacity to sustain physical activity."
Skeletal muscle converts chemical energy into motion and force, ranging from rapid and sudden bursts of intense activity to continuous low-intensity work, the researchers said. At one functional extreme, muscles such as the soleus--a broad, flat muscle found in the calf of the leg--perform slow but steady activities such as maintaining posture. At the other extreme, muscles such as the quadriceps typically perform intense and rapid activities.
To fulfill these varied roles, muscles vary in their proportion of "slow-twitch" muscle fibers (types I and IIA), ideal for slow and constant roles, and "fast-twitch" fibers (type IIB), better suited to rapid and sudden activity of shorter duration. The fiber types are defined by which "myosin heavy chains" (MHCs) they contain and by their metabolic capacity, a feature largely determined by the number of energy-producing mitochondria they house. Myosins are motor proteins that consist of both "heavy" and "light" amino acid chains.
While most muscles in mammals contain a mixture of slow- and fast-twitch fiber types, some muscle beds are enriched for one type or the other, Spiegelman said. However, adult skeletal muscles also contain fibers with an abundance of a fourth MHC, type IIX, about which much less is known.
IIX fibers seem to have the oxidative metabolism of slow-twitch fibers mixed with the biophysical properties of fast-twitch fibers. Oxidative metabolism is by far the most efficient way of generating energy, Spiegelman said.
In the current study, the researchers produced mice with higher than normal levels of the transcriptional coactivator PGC-1Гў in their skeletal muscles. Transcriptional coactivators work with other cellular factors and machinery to control the activity of other genes. While earlier studies had found that the related coactivator PGC-1Гў plays a role in determining muscle type, the role of PGC-1Гў wasn't known.
"The muscle from the PGC-1Гў transgenic mice was strikingly redder in appearance than wild-type controls," indicative of their increased mitochondrial content, the researchers now report. Upon further examination, the researchers were surprised to find that the fibers showed a reduction in I, IIA, and IIB MHCs and as much as a 5-fold increase in IIX MHC.
Nearly 100% of muscle fibers in the transgenic animals contained abundant MHC IIX mRNA and protein, they found, as compared to only 15%-20% in normal animals. PGC-1Гў also changed the muscles' metabolic characteristics by driving the activity of genes that spark proliferation of mitochondria.
The PGC-1Гў animals with more IIX muscle fibers showed a greater capacity for aerobic exercise, they found. Transgenic mice were able to run, on average, for 32.5 min to exhaustion, compared to 26 min for their normal littermates, Spiegelman's group reported.
"These data have potential importance for the therapy of a number of muscular and neuromuscular diseases in humans," Spiegelman's group concluded.
"Many conditions accompanied by loss of physical mobility, including paraplegia, prolonged bed rest, and muscular dystrophies, involve a loss of oxidative fibers and their replacement with glycolytic fibers. This, in turn, results in a further loss of resistance to fatigue, exacerbating the patient's condition in a downward spiral. The identification of PGC-1Гў as a potential mediator of the development of oxidative type IIX fibers suggests new ways to modulate muscle fiber type in health and disease."
The researchers include Zoltan Arany, Eric Smith, Wenli Yang, Yanhong Ma, Sherry Chin, and Bruce M. Spiegelman of Dana-Farber Cancer Institute and Harvard Medical School in Boston, MA; Nathan Lebrasseur and Carl Morris of Boston University School of Medicine in Boston, MA
This work was supported by NIH grants HL079172 to Z.A. and DK54477 and DK61562 to B.M.S.
Arany et al.: "The Transcriptional Coactivator PGC-1b Drives the Formation of Oxidative Type IIX Fibers in Skeletal Muscle." Publishing in Cell Metabolism 5, 35-46, January 2007 DOI 10.1016/j.cmet.2006.12.003 cellmetabolism/
Contact: Erin Doonan
Cell Press
вторник, 20 сентября 2011 г.
Blood Pressure Drug May Help Stall Parkinson's
Gloria E. Meredith, Ph.D., collaborated with D. James Surmeier, Ph.D. and other scientists at Northwestern University to study the drug, Isradipine, and its possible effects on Parkinson's disease. The findings of this study were published this week in an article in Nature. Dr. Meredith, Professor and Chair of the Department of Cellular and Molecular Pharmacology at Rosalind Franklin University of Medicine and Science, and an expert in Parkinson's disease, co-authored the article. She commented, "Parkinson's disease is a motor disorder caused by the death of dopamine-producing nerve cells in our brains. There is a big race to protect these neurons from dying. Currently available drugs only treat the symptoms."
Dr. Meredith, who studies a chronic mouse model that mimics the signs and symptoms of Parkinson's disease, said, "Isradipine is a common drug used to treat hypertension and stroke. Dr. Surmeier had developed the idea that this drug, a calcium channel blocker, may help protect dopamine neurons in humans. He also designed the basic study. We joined together to see if the drug could stop cells from dying in the mouse model. Our findings indicated that isradipine slowed the disease process and destruction of the dopamine-producing neurons. Results from the mouse model indicate that if the drug works in humans, then it could be used as a means to prevent the onset of this disease or slow its progression."
The next phase will be to develop clinical trials in humans. Dr. Meredith said, "It's exciting to think that if we can protect the dopamine neurons from dying, we may prevent the disease, and improve the quality of life for patients."
Dr. Meredith has been studying Parkinson's disease for over 15 years. Her research is currently funded by the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH), and the Department of Defense.
Rosalind Franklin University of Medicine and Science educates medical doctors, health professionals and biomedical scientists in a personalized atmosphere. The University is located at 3333 Green Bay Road, North Chicago, IL 60064 and encompasses Chicago Medical School, College of Health professions, Dr. William M. Scholl College of Podiatric Medicine, and the School of Graduate and Postdoctoral Studies. Visit at rosalindfranklin/ and lifeindiscovery/.
Contact: Priscilla Khoury
Rosalind Franklin University of Medicine and Science
Dr. Meredith, who studies a chronic mouse model that mimics the signs and symptoms of Parkinson's disease, said, "Isradipine is a common drug used to treat hypertension and stroke. Dr. Surmeier had developed the idea that this drug, a calcium channel blocker, may help protect dopamine neurons in humans. He also designed the basic study. We joined together to see if the drug could stop cells from dying in the mouse model. Our findings indicated that isradipine slowed the disease process and destruction of the dopamine-producing neurons. Results from the mouse model indicate that if the drug works in humans, then it could be used as a means to prevent the onset of this disease or slow its progression."
The next phase will be to develop clinical trials in humans. Dr. Meredith said, "It's exciting to think that if we can protect the dopamine neurons from dying, we may prevent the disease, and improve the quality of life for patients."
Dr. Meredith has been studying Parkinson's disease for over 15 years. Her research is currently funded by the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH), and the Department of Defense.
Rosalind Franklin University of Medicine and Science educates medical doctors, health professionals and biomedical scientists in a personalized atmosphere. The University is located at 3333 Green Bay Road, North Chicago, IL 60064 and encompasses Chicago Medical School, College of Health professions, Dr. William M. Scholl College of Podiatric Medicine, and the School of Graduate and Postdoctoral Studies. Visit at rosalindfranklin/ and lifeindiscovery/.
Contact: Priscilla Khoury
Rosalind Franklin University of Medicine and Science
суббота, 17 сентября 2011 г.
The Vasculature Emerges As A Potential Therapeutic Target In Treating ADPKD Liver Cysts
As part of an effort to develop effective medical therapies that block the progression of liver cyst growth in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD), researchers at the University of Colorado Anschutz Medical Center have found that the liver cyst walls develop and maintain a vasculature as they grow out from the body of the liver and that factors released by epithelial cells that line the liver cyst wall lumen can drive the proliferation and development of vascular endothelial cells.
The findings, which appear in the October 2009 issue of Experimental Biology and Medicine, are the result of a multi-disciplinary team assembled by Dr. Brian Doctor. Dr. Nick Barry, a biophysicist, and Dr. Ryan McWilliams, a medical resident, employed complimentary imaging techniques to visualize and characterize the vasculature within native liver cyst walls of human ADPKD patients and pkd2(WS25/-) mice, an orthologous mouse model of ADPKD. Kelley Brodsky, a senior research associate, and Dr. Claudia Amura, a cell biologist, then used in vitro assays of endothelial cell proliferation and vascular development to demonstrate that human liver cyst fluids, which contain a variety of cytokines and growth factors secreted by the liver cyst lining epithelium, are capable of driving the angiogenic phenotype of endothelial cells. Further, inhibition of VEGF receptor signaling dramatically impeded this angiogenic phenotype. Dr. Doctor noted that "by establishing the presence of the vasculature within the enlarging liver cyst walls and defining the putative signaling pathways that induce angiogenesis within them, this study opens up an exciting new direction in the quest to develop medical therapies that can block the often devastating growth of liver cysts in patients with ADPKD".
In summary, while there are differences in their vascular density and distribution, both human ADPKD and pkd2(WS25/-) mouse liver cyst walls develop vascular structures as they grow out from the liver. In vitro studies demonstrate that angiogenic factors secreted by the liver cyst wall epithelium, including VEGF-A and IL-8, can drive angiogenic development of human endothelial cells. This development is blocked by inhibition of VEGF receptor signaling. Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "The article by Brodsky and colleagues provides the important insight that the liver cyst walls maintain a vasculature as they grow out from the liver and that VEGF receptor signaling plays a key role in inducing angiogenesis. These multidisciplinary studies lay a framework for the development of new therapies aimed at preventing the growth of liver cysts in patients with ADPKD".
Notes:
Dr. R. Brian Doctor
Society for Experimental Biology and Medicine
The findings, which appear in the October 2009 issue of Experimental Biology and Medicine, are the result of a multi-disciplinary team assembled by Dr. Brian Doctor. Dr. Nick Barry, a biophysicist, and Dr. Ryan McWilliams, a medical resident, employed complimentary imaging techniques to visualize and characterize the vasculature within native liver cyst walls of human ADPKD patients and pkd2(WS25/-) mice, an orthologous mouse model of ADPKD. Kelley Brodsky, a senior research associate, and Dr. Claudia Amura, a cell biologist, then used in vitro assays of endothelial cell proliferation and vascular development to demonstrate that human liver cyst fluids, which contain a variety of cytokines and growth factors secreted by the liver cyst lining epithelium, are capable of driving the angiogenic phenotype of endothelial cells. Further, inhibition of VEGF receptor signaling dramatically impeded this angiogenic phenotype. Dr. Doctor noted that "by establishing the presence of the vasculature within the enlarging liver cyst walls and defining the putative signaling pathways that induce angiogenesis within them, this study opens up an exciting new direction in the quest to develop medical therapies that can block the often devastating growth of liver cysts in patients with ADPKD".
In summary, while there are differences in their vascular density and distribution, both human ADPKD and pkd2(WS25/-) mouse liver cyst walls develop vascular structures as they grow out from the liver. In vitro studies demonstrate that angiogenic factors secreted by the liver cyst wall epithelium, including VEGF-A and IL-8, can drive angiogenic development of human endothelial cells. This development is blocked by inhibition of VEGF receptor signaling. Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "The article by Brodsky and colleagues provides the important insight that the liver cyst walls maintain a vasculature as they grow out from the liver and that VEGF receptor signaling plays a key role in inducing angiogenesis. These multidisciplinary studies lay a framework for the development of new therapies aimed at preventing the growth of liver cysts in patients with ADPKD".
Notes:
Dr. R. Brian Doctor
Society for Experimental Biology and Medicine
среда, 14 сентября 2011 г.
Protein Center's Success Nets $5.4 Million More
The University of Arkansas Center for Protein Structure and Function will receive more than $5.4 million over the next five years from the National Institutes of Health to continue the biomedical research it has established during the last decade.
The new funds will help expand the five already established core facilities within the center that support biomedical research. The money also will provide start-up funds to scientists with innovative ideas for new research projects.
"These grants will allow researchers to get some experimental evidence for their ideas so that they can write a major grant proposal," said Frank Millett, Distinguished Professor of chemistry and biochemistry and director of the center. "You have to have significant preliminary results to get funding from NIH these days."
Center projects emphasize developing a detailed understanding of the structure and function of proteins that could lead to improved treatments of human disease. Center scientists study proteins involved in cancer, heart disease, osteoporosis, the flu and other diseases and conditions.
The researchers examining these proteins use five core facilities to do their work. These include the nuclear magnetic resonance spectroscopy facility directed by James Hinton; the X-ray crystallography facility headed by Joshua Sakon; the mass spectrometry facility headed by Jackson Lay and Alan Tackett; the chemical synthesis facility headed by Robert Gawley; and the large-scale protein production facility directed by Ralph Henry. Scientists often use many or all of these facilities as they progress through different stages of a research project.
"These facilities have helped everyone involved in biomedical research on campus become competitive in getting research grants," Millett said. Researchers in the center have brought in more than $60 million in grant support since it was founded in 2000.
In addition to building the core facilities, the university has hired 12 new tenure-track faculty members since 2000, in chemistry and biochemistry and in biological sciences as well as at the University of Arkansas for Medical Sciences. The university provided substantial start-up funds for these faculty members, which helped the center succeed and get continued funding.
"The reviewers noted very positively the university commitment here," Millett said. "It was a major factor in getting all of these grants."
Millett himself is no stranger to NIH funding: He has had continuous support from the organization for the past 36 years for his research into how energy is produced in animals at the molecular level. Defects in the process of energy production lead to degenerative processes, including aging, as well as problems linked to heart disease and other medical conditions.
The Center's original senior investigators include: center director Millett, program coordinator Roger Koeppe, Bill Durham, James Hinton, Peter Pulay, Jackson Lay, Lothar Schafer and Charles Wilkins in chemistry and biochemistry. New senior investigators brought in as part of the NIH funding include Robert Gawley, Distinguished Professor of chemistry and biochemistry and Julie Stenken, professor and Twenty-First Century Chair in chemistry and biochemistry.
Mid-career investigators who started out as junior investigators include Denise Greathouse, T.K.S. Kumar, Matt McIntosh, Joshua Sakon and Wesley Stites in chemistry and biochemistry; Robyn Goforth, Ralph Henry, Michael Lehmann and Kathryn Curtin in biological sciences; and Paul Grover Miller, Kevin D. Raney and Alan Tackett in biochemistry and molecular biology at the University of Arkansas for Medical Sciences. These scientists "graduated" and got their own major research funding after receiving support from the center.
Current junior investigators include Paul Adams, Colin Heyes, Daniel Lessner and Nan Zheng in chemistry and biochemistry and Yu-Chun Du in biological sciences. All junior investigators have reduced teaching loads and can devote at least half of their time to research.
"To get faculty who are competitive for national grants, you need to be able to give them support for the first few years," Millett said. The NIH funding for major instrumentation and the university commitment to start-up funds for laboratories created an environment where these junior researchers and the entire center could succeed, he said.
The grant is funded by the Centers of Biomedical Research Excellence program of the National Center for Research Resources, a part of the National Institutes of Health.
Source: University of Arkansas
The new funds will help expand the five already established core facilities within the center that support biomedical research. The money also will provide start-up funds to scientists with innovative ideas for new research projects.
"These grants will allow researchers to get some experimental evidence for their ideas so that they can write a major grant proposal," said Frank Millett, Distinguished Professor of chemistry and biochemistry and director of the center. "You have to have significant preliminary results to get funding from NIH these days."
Center projects emphasize developing a detailed understanding of the structure and function of proteins that could lead to improved treatments of human disease. Center scientists study proteins involved in cancer, heart disease, osteoporosis, the flu and other diseases and conditions.
The researchers examining these proteins use five core facilities to do their work. These include the nuclear magnetic resonance spectroscopy facility directed by James Hinton; the X-ray crystallography facility headed by Joshua Sakon; the mass spectrometry facility headed by Jackson Lay and Alan Tackett; the chemical synthesis facility headed by Robert Gawley; and the large-scale protein production facility directed by Ralph Henry. Scientists often use many or all of these facilities as they progress through different stages of a research project.
"These facilities have helped everyone involved in biomedical research on campus become competitive in getting research grants," Millett said. Researchers in the center have brought in more than $60 million in grant support since it was founded in 2000.
In addition to building the core facilities, the university has hired 12 new tenure-track faculty members since 2000, in chemistry and biochemistry and in biological sciences as well as at the University of Arkansas for Medical Sciences. The university provided substantial start-up funds for these faculty members, which helped the center succeed and get continued funding.
"The reviewers noted very positively the university commitment here," Millett said. "It was a major factor in getting all of these grants."
Millett himself is no stranger to NIH funding: He has had continuous support from the organization for the past 36 years for his research into how energy is produced in animals at the molecular level. Defects in the process of energy production lead to degenerative processes, including aging, as well as problems linked to heart disease and other medical conditions.
The Center's original senior investigators include: center director Millett, program coordinator Roger Koeppe, Bill Durham, James Hinton, Peter Pulay, Jackson Lay, Lothar Schafer and Charles Wilkins in chemistry and biochemistry. New senior investigators brought in as part of the NIH funding include Robert Gawley, Distinguished Professor of chemistry and biochemistry and Julie Stenken, professor and Twenty-First Century Chair in chemistry and biochemistry.
Mid-career investigators who started out as junior investigators include Denise Greathouse, T.K.S. Kumar, Matt McIntosh, Joshua Sakon and Wesley Stites in chemistry and biochemistry; Robyn Goforth, Ralph Henry, Michael Lehmann and Kathryn Curtin in biological sciences; and Paul Grover Miller, Kevin D. Raney and Alan Tackett in biochemistry and molecular biology at the University of Arkansas for Medical Sciences. These scientists "graduated" and got their own major research funding after receiving support from the center.
Current junior investigators include Paul Adams, Colin Heyes, Daniel Lessner and Nan Zheng in chemistry and biochemistry and Yu-Chun Du in biological sciences. All junior investigators have reduced teaching loads and can devote at least half of their time to research.
"To get faculty who are competitive for national grants, you need to be able to give them support for the first few years," Millett said. The NIH funding for major instrumentation and the university commitment to start-up funds for laboratories created an environment where these junior researchers and the entire center could succeed, he said.
The grant is funded by the Centers of Biomedical Research Excellence program of the National Center for Research Resources, a part of the National Institutes of Health.
Source: University of Arkansas
воскресенье, 11 сентября 2011 г.
Supposed Help Against Tumors - How Glioblastoma Tumor Cells Use The Body's Protection
Glioblastoma is one of the most common but also most aggressive brain tumors, almost invariably leading to death in a short time. It consists of different cell types and their precursors, complicating successful treatment. To fight the driving force of the tumor - the tumor stem cells - scientists have been trying to initiate apoptosis in these cells. However, Dr. Ana Martin-Villalba (German Cancer Research Center, DKFZ, Heidelberg, Germany) suspects that the activated apoptosis program accelerates the progress of the disease. "The tumor growth declines when apoptosis is blocked," she reported at the conference "Brain Tumor 2008" at the Max DelbrГјck Center for Molecular Medicine (MDC) Berlin-Buch, Germany.
Glioblastomas grow like corals and form filigran branches into nearby, healthy brain tissue. For that reason it is very difficult for neurosurgeons to remove the tumor entirely because the risk of damaging healthy tissue is too high. Moreover, glioblastomas are resistant to conventional therapies which normally activate the body's apoptosis program.
This programmed cell death is a vital process. It plays an important role during development but also in the adult organism. Together with its partner CD95L, the molecular switch CD95 ensures that sick or abnormal cells are removed. Once activated, CD95 triggers a chain of different signals which in the end lead to the death of the damaged cell. Until recently, scientists were convinced that triggering apoptosis in brain tumors was a useful tool for not only killing the tumor but also the cells of its origin - the tumor stem cells.
The scientist from Heidelberg could show that CD95 as well as its partner CD95L is active in the tumor cells. However, the cells do not die. "Instead, the signal stimulates the tumor cells to migrate into neighboring, healthy brain regions," Dr. Martin-Villalba explained. For instance, it activates the protein MMP which "drills" its way into the brain tissue. "Contrary to our expectations," the neuroscientist said, "what we find when we activate apoptosis in the tumor cells is that we help them spread into healthy nerve tissue."
In experiments with mice, the researchers could already show that the tumor proliferates less aggressively when they block CD95L with an antibody, thus inhibiting the activation of programmed cell death. "With this changed perspective, we hope to develop new ideas for tumor therapy in the future," Dr. Martin-Villalba said.
Altogether, about 180 scientists and clinicians from Europe and the USA came to the two-day conference, which ended this Friday afternoon. The organizers were the MDC, the Charité - Universitätsmedizin Berlin, and HELIOS Kliniken GmbH, Berlin, a private clinic in Berlin-Buch.
Barbara Bachtler
Press and Public Affairs
Max DelbrГјck Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
mdc-berlin
Further information:
dkfz-heidelberg/en/molekulare-neurobiologie/index.html
cell/cancer-cell/retrieve/pii/S1535610808000433
Glioblastomas grow like corals and form filigran branches into nearby, healthy brain tissue. For that reason it is very difficult for neurosurgeons to remove the tumor entirely because the risk of damaging healthy tissue is too high. Moreover, glioblastomas are resistant to conventional therapies which normally activate the body's apoptosis program.
This programmed cell death is a vital process. It plays an important role during development but also in the adult organism. Together with its partner CD95L, the molecular switch CD95 ensures that sick or abnormal cells are removed. Once activated, CD95 triggers a chain of different signals which in the end lead to the death of the damaged cell. Until recently, scientists were convinced that triggering apoptosis in brain tumors was a useful tool for not only killing the tumor but also the cells of its origin - the tumor stem cells.
The scientist from Heidelberg could show that CD95 as well as its partner CD95L is active in the tumor cells. However, the cells do not die. "Instead, the signal stimulates the tumor cells to migrate into neighboring, healthy brain regions," Dr. Martin-Villalba explained. For instance, it activates the protein MMP which "drills" its way into the brain tissue. "Contrary to our expectations," the neuroscientist said, "what we find when we activate apoptosis in the tumor cells is that we help them spread into healthy nerve tissue."
In experiments with mice, the researchers could already show that the tumor proliferates less aggressively when they block CD95L with an antibody, thus inhibiting the activation of programmed cell death. "With this changed perspective, we hope to develop new ideas for tumor therapy in the future," Dr. Martin-Villalba said.
Altogether, about 180 scientists and clinicians from Europe and the USA came to the two-day conference, which ended this Friday afternoon. The organizers were the MDC, the Charité - Universitätsmedizin Berlin, and HELIOS Kliniken GmbH, Berlin, a private clinic in Berlin-Buch.
Barbara Bachtler
Press and Public Affairs
Max DelbrГјck Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
mdc-berlin
Further information:
dkfz-heidelberg/en/molekulare-neurobiologie/index.html
cell/cancer-cell/retrieve/pii/S1535610808000433
четверг, 8 сентября 2011 г.
Molecular Clues To Wilson Disease Discovered By Rice Lab
Using a combination of computer simulations and cutting-edge lab experiments, physical biochemists at Rice University have discovered how a small genetic mutation -- which is known to cause Wilson disease -- subtly changes the structure of a large, complex protein that the body uses to keep copper from building up to toxic levels.
"The protein we study is like a big puzzle," said lead author Agustina Rodriguez-Granillo, the Rice doctoral student in biochemistry and cell biology who carried out the mathematical simulations and laboratory research. "The mutation that causes most cases of Wilson disease is well-known, but our study looks at the overall puzzle to see how such a small mutation can alter the shape and function of such a large and complex protein."
The protein in question is called ATP7B, which is a multidomain protein that sits in an internal membrane and regulates the movement of copper atoms inside human cells. Though large quantities of copper can be toxic, our bodies need a small amount for key enzymes involved in, for example, respiration and brain functions. ATP7B acts something like a warehouse manager, locking up bulk quantities of copper and handing it out for use in these proteins.
Wilson disease is a genetic disorder that alters the ATP7B protein's ability to work, causing copper to build up to toxic levels in the liver, brain, eyes and other organs. Over time the disease can cause life-threatening organ damage. Wilson disease affects as many as 150,000 people worldwide.
The new study is available online from the Journal of Molecular Biology. It focused on the genetic flaw that causes most cases of Wilson disease. That flaw, known as H1069Q, is caused when just one out of the more than 1,400 amino acids in ATP7B is changed. That amino acid is a histidine located at position 1069. In the disease-causing form of the protein, this histidine is replaced with a glutamic acid.
"This mutation occurs at a crucial location where the protein typically binds with a molecule called ATP that provides the energy the protein needs to move copper from place to place," said study co-author Pernilla Wittung-Stafshede, an adjunct professor of biochemistry and cell biology at Rice and Rodriguez-Granillo's adviser. Wittung-Stafshede, professor in chemistry at Umea University in Sweden, said, "Past studies have compared the behavior of the mutant protein with that of the nonmutant and found very little difference, so it was unclear how this small change led to the devastating effects that are seen in Wilson disease."
Using a combination of experimental data and computer simulations that looked specifically at a portion of the protein called the N-domain, where the H1069Q mutation occurs, Wittung-Stafshede, Rodriguez-Granillo and postdoctoral researcher Erik Sedlak (now at the University of Texas at San Antonio) confirmed that ATP's function was significantly reduced in the mutant form of the protein. They also found that the mutation caused structural changes in other sections of the protein that were far away from the mutation site. For example, the healthy form of the protein is capped with a large, flexible loop. The purpose of the loop is unknown, but its shape is altered and more compact in the diseased form of the protein.
"This implies that the loop has some importance, perhaps in regulation of ATP7B's activities, and we intend to follow up on this in our future studies," Rodriguez-Granillo said.
The research was supported by the Robert A. Welch Foundation.
Source: Jade Boyd
Rice University
"The protein we study is like a big puzzle," said lead author Agustina Rodriguez-Granillo, the Rice doctoral student in biochemistry and cell biology who carried out the mathematical simulations and laboratory research. "The mutation that causes most cases of Wilson disease is well-known, but our study looks at the overall puzzle to see how such a small mutation can alter the shape and function of such a large and complex protein."
The protein in question is called ATP7B, which is a multidomain protein that sits in an internal membrane and regulates the movement of copper atoms inside human cells. Though large quantities of copper can be toxic, our bodies need a small amount for key enzymes involved in, for example, respiration and brain functions. ATP7B acts something like a warehouse manager, locking up bulk quantities of copper and handing it out for use in these proteins.
Wilson disease is a genetic disorder that alters the ATP7B protein's ability to work, causing copper to build up to toxic levels in the liver, brain, eyes and other organs. Over time the disease can cause life-threatening organ damage. Wilson disease affects as many as 150,000 people worldwide.
The new study is available online from the Journal of Molecular Biology. It focused on the genetic flaw that causes most cases of Wilson disease. That flaw, known as H1069Q, is caused when just one out of the more than 1,400 amino acids in ATP7B is changed. That amino acid is a histidine located at position 1069. In the disease-causing form of the protein, this histidine is replaced with a glutamic acid.
"This mutation occurs at a crucial location where the protein typically binds with a molecule called ATP that provides the energy the protein needs to move copper from place to place," said study co-author Pernilla Wittung-Stafshede, an adjunct professor of biochemistry and cell biology at Rice and Rodriguez-Granillo's adviser. Wittung-Stafshede, professor in chemistry at Umea University in Sweden, said, "Past studies have compared the behavior of the mutant protein with that of the nonmutant and found very little difference, so it was unclear how this small change led to the devastating effects that are seen in Wilson disease."
Using a combination of experimental data and computer simulations that looked specifically at a portion of the protein called the N-domain, where the H1069Q mutation occurs, Wittung-Stafshede, Rodriguez-Granillo and postdoctoral researcher Erik Sedlak (now at the University of Texas at San Antonio) confirmed that ATP's function was significantly reduced in the mutant form of the protein. They also found that the mutation caused structural changes in other sections of the protein that were far away from the mutation site. For example, the healthy form of the protein is capped with a large, flexible loop. The purpose of the loop is unknown, but its shape is altered and more compact in the diseased form of the protein.
"This implies that the loop has some importance, perhaps in regulation of ATP7B's activities, and we intend to follow up on this in our future studies," Rodriguez-Granillo said.
The research was supported by the Robert A. Welch Foundation.
Source: Jade Boyd
Rice University
понедельник, 5 сентября 2011 г.
Kinexus Announces The Launch Of A New Protein Kinase Microarray
Kinexus Bioinformatics Corporation announced the commercial release of its novel Protein Kinase Microarray with 200 recombinant human protein kinases for screening. The microarray has wide utility including applications for drug target counter screening, to identify novel kinase substrates, establish kinase antibody specificities, and for the discovery and testing of protein kinase-protein and protein kinase-compound interactions.
With these new and unique kinase microarray services, clients can now inexpensively assay the abilities of their lead compounds to inhibit any of the 200 different protein kinases for as low as $1.65 per kinase with triplicate measurements. Industry standards for these types of measurements typically cost $4-5 per kinase tracked. This counter screening of kinases can be used to establish the specificity of promising therapeutic inhibitors or target kinases in much more cost effective manner than previously available. All compounds can be further validated for direct activity effects in vitro with the Kinase-Inhibitor Profiling Services offered by Kinexus. This complements the Kinex(TM) 800 Antibody Microarray Services, in which endogenous physiological substrates of target kinases can also be defined to measure the effects of drug leads in vivo in cultured cells and tissues from treated animals. The specificity of suspected protein kinase-protein interactions can also be investigated with the new kinase microarray.
"Protein kinases are well recognized by the pharmaceutical and biotech industry as highly productive targets for drugs with the potentially treat over 400 human diseases, commented Dr. Steven Pelech, President and Chief Scientific Officer of Kinexus. "With 516 human protein kinases and only about 75 that have been seriously targeted by the pharmaceutical industry so far, there are exciting possibilities for the identification of new kinase drug targets and new applications for existing drugs with this type of technology".
Source: Kinexus Bioinformatics Corporation
With these new and unique kinase microarray services, clients can now inexpensively assay the abilities of their lead compounds to inhibit any of the 200 different protein kinases for as low as $1.65 per kinase with triplicate measurements. Industry standards for these types of measurements typically cost $4-5 per kinase tracked. This counter screening of kinases can be used to establish the specificity of promising therapeutic inhibitors or target kinases in much more cost effective manner than previously available. All compounds can be further validated for direct activity effects in vitro with the Kinase-Inhibitor Profiling Services offered by Kinexus. This complements the Kinex(TM) 800 Antibody Microarray Services, in which endogenous physiological substrates of target kinases can also be defined to measure the effects of drug leads in vivo in cultured cells and tissues from treated animals. The specificity of suspected protein kinase-protein interactions can also be investigated with the new kinase microarray.
"Protein kinases are well recognized by the pharmaceutical and biotech industry as highly productive targets for drugs with the potentially treat over 400 human diseases, commented Dr. Steven Pelech, President and Chief Scientific Officer of Kinexus. "With 516 human protein kinases and only about 75 that have been seriously targeted by the pharmaceutical industry so far, there are exciting possibilities for the identification of new kinase drug targets and new applications for existing drugs with this type of technology".
Source: Kinexus Bioinformatics Corporation
пятница, 2 сентября 2011 г.
Researchers Hot On The Trail Of Brain Cell Degeneration
A research team headed by Academy Research Fellow Michael Courtney has identified a new molecular pathway in neurons. The pathway is a factor in the degeneration of brain cells, which in turn plays an important role in neurological conditions and diseases, such as Alzheimer's disease, epilepsy and stroke. Courtney and his team, based at the A. I. Virtanen Institute of the University of Kuopio, joined forces with Docent Eleanor Coffey's team at the Turku Centre for Biotechnology to carry out the study as part of a series of successful collaborations between the two teams. The results of their study are published in the latest issue of Nature Neuroscience.
In a number of neurodegenerative diseases, neurons in the brain are over-stimulated, which triggers programmed cell death, or apoptosis. The study shows that the Rho protein, which has long been recognised as an important player in cancer formation, also plays a key role in the destruction of neurons in disease.
"These surprising findings add an entire pathway to the map of neurodegenerative signalling processes," says Courtney. "This area of investigation could therefore offer novel therapeutic strategies for neurodegenerative diseases".
Targeting molecular signals
How neurons actually die has been unclear. It is likely that it is associated with a variety of different mechanisms. Research has shown that the destruction of cells be over-stimulation depends on excess entry of calcium into the cells. Researchers have long been trying to map how cells generate destruction signals in response to the calcium, in the hope of finding new targets for drug design.
The object of the study, the Rho protein, belongs to a family of proteins able to influence signals that had been linked to cell degeneration. The two teams' analysis demonstrated that over-stimulation causes activation of Rho as well as cell destruction signals. Blocking Rho activity by genetic modification keeps the protein in an inactive state, and the nerve cells thus survive a previously toxic level of over-stimulation.
The study identifies a new factor provoking cell degeneration. It is more than likely that future research will uncover more such factors interacting with each other. Investigating these will benefit new forms of treatment and advance research that aims to alleviate symptoms. The researchers behind the study hope that the results can be used in planning new targets for drugs to reduce the cell destruction signals caused by calcium entry. Finding new targets for medicine development is also significant in terms of the economy, owing to the costly treatment of these diseases, both in Finland and globally.
Cooperation between biocentres gets research going
The teams' study is a perfect example of the cooperation between biocentres in Finland (Biocenter Finland) and international networking. The research was funded mainly by the Academy of Finland and the European Union. The two research teams are part of a Europe-wide consortium, STRESSPROTECT, within the EU Sixth Framework Programme. The consortium aims at generating the basis for novel neuroprotective drugs for neurodegenerative conditions involving over-stimulation of neurons (neuroprotect.eu).
SUOMEN AKATEMIA (ACADEMY OF FINLAND)
Vilhonvuorenkatu 6
PO Box 99
00 501 Helsinki
aka.fi/
In a number of neurodegenerative diseases, neurons in the brain are over-stimulated, which triggers programmed cell death, or apoptosis. The study shows that the Rho protein, which has long been recognised as an important player in cancer formation, also plays a key role in the destruction of neurons in disease.
"These surprising findings add an entire pathway to the map of neurodegenerative signalling processes," says Courtney. "This area of investigation could therefore offer novel therapeutic strategies for neurodegenerative diseases".
Targeting molecular signals
How neurons actually die has been unclear. It is likely that it is associated with a variety of different mechanisms. Research has shown that the destruction of cells be over-stimulation depends on excess entry of calcium into the cells. Researchers have long been trying to map how cells generate destruction signals in response to the calcium, in the hope of finding new targets for drug design.
The object of the study, the Rho protein, belongs to a family of proteins able to influence signals that had been linked to cell degeneration. The two teams' analysis demonstrated that over-stimulation causes activation of Rho as well as cell destruction signals. Blocking Rho activity by genetic modification keeps the protein in an inactive state, and the nerve cells thus survive a previously toxic level of over-stimulation.
The study identifies a new factor provoking cell degeneration. It is more than likely that future research will uncover more such factors interacting with each other. Investigating these will benefit new forms of treatment and advance research that aims to alleviate symptoms. The researchers behind the study hope that the results can be used in planning new targets for drugs to reduce the cell destruction signals caused by calcium entry. Finding new targets for medicine development is also significant in terms of the economy, owing to the costly treatment of these diseases, both in Finland and globally.
Cooperation between biocentres gets research going
The teams' study is a perfect example of the cooperation between biocentres in Finland (Biocenter Finland) and international networking. The research was funded mainly by the Academy of Finland and the European Union. The two research teams are part of a Europe-wide consortium, STRESSPROTECT, within the EU Sixth Framework Programme. The consortium aims at generating the basis for novel neuroprotective drugs for neurodegenerative conditions involving over-stimulation of neurons (neuroprotect.eu).
SUOMEN AKATEMIA (ACADEMY OF FINLAND)
Vilhonvuorenkatu 6
PO Box 99
00 501 Helsinki
aka.fi/
вторник, 30 августа 2011 г.
Extinction Most Likely For Rare Trees In The Amazon Rainforest
Common tree species in the Amazon will survive even grim scenarios of deforestation and road-building, but rare trees could suffer extinction rates of up to 50 percent, predict Smithsonian scientists and colleagues in the Aug. 12 issue of the journal Proceedings of the National Academy of Science.
How resilient will natural systems prove to be as they weather the next several decades of severe, human-induced global change? The debate is on between proponents of models that maximize and minimize extinction rates.
The Amazon basin contains about 40 percent of the world's remaining rainforest. One of the fundamental characteristics of tropical forests is the presence of very rare tree species. Competing models of relative species abundance, one based on Fisher's alpha statistic and the other based on Preston's lognormal curve, yield different proportions of rare trees in the forest.
Thirty years ago Stephen P. Hubbell, senior scientist at the Center for Tropical Forest Science of the Smithsonian Tropical Research Institute and distinguished professor in the Department of Ecology and Evolution at the University of California, Los Angeles, and his colleague Robin Foster, now at the Field Museum in Chicago, set up a unique experiment to monitor the growth, birth and death of more than 250,000 tropical trees on Panama's Barro Colorado Island. This large "forest dynamics plot" would generate the data needed to build good models that include rare species.
Today the Center for Tropical Forest Science coordinates a Global Earth Observatory-a network of 20 such forest study sites in 17 countries, which maintains "actuarial tables" for more than 3 million trees.
Hubbell works with data from the network to develop and test his neutral theory of biodiversity-an attempt to find a unified explanation of large, complex biological systems that accurately predicts the outcome of major ecological and evolutionary forces of change.
In this offering, the authors use the neutral theory to predict the number of tree species and to test predictions of the Millenium Ecosystems Assessment that forecasts major tree extinctions in the Amazon over the next several decades. First, they estimate that the Brazilian Amazon has (or had) 11,210 large tree species, and, of these, 5,308 species are classified as rare.
Based on optimistic and non-optimistic scenarios for road construction in the Amazon published by the Smithsonian's William Laurance and colleagues in the journal Science in 2004, they predict that the rare species will suffer between 37 and 50 percent extinction, whereas the extinction rate for all trees could be from 20 to 33 percent overall.
Would a simpler Amazon forest lacking many of its rarer trees function? Will the extinction of species other than trees-pollinators, seed predators, carnivores-contribute significantly to the lost of rainforest resilience? This and other biological quandaries remain. The authors exhort: "Although it is an old scientific chestnut, we must once again emphasize how important it is to support continuing basic science on tropical forests."
The Smithsonian Tropical Research Institute, headquartered in Panama City, Panama, is a unit of the Smithsonian Institution. The institute furthers the understanding of tropical nature and its importance to human welfare, trains students to conduct research in the tropics and promotes conservation by increasing public awareness of the beauty and importance of tropical ecosystems. For more information, visit stri.
Ref: Stephen P. Hubbell, Fangliang He, Richard Condit, Luis Borda-de-Agua, and Hans ter Steege. 2008. How many tree species are there in the Amazon and how many of them will go extinct? Proceedings of the National Academy of Science, August 12 early online edition.
Smithsonian Tropical Research Institute
How resilient will natural systems prove to be as they weather the next several decades of severe, human-induced global change? The debate is on between proponents of models that maximize and minimize extinction rates.
The Amazon basin contains about 40 percent of the world's remaining rainforest. One of the fundamental characteristics of tropical forests is the presence of very rare tree species. Competing models of relative species abundance, one based on Fisher's alpha statistic and the other based on Preston's lognormal curve, yield different proportions of rare trees in the forest.
Thirty years ago Stephen P. Hubbell, senior scientist at the Center for Tropical Forest Science of the Smithsonian Tropical Research Institute and distinguished professor in the Department of Ecology and Evolution at the University of California, Los Angeles, and his colleague Robin Foster, now at the Field Museum in Chicago, set up a unique experiment to monitor the growth, birth and death of more than 250,000 tropical trees on Panama's Barro Colorado Island. This large "forest dynamics plot" would generate the data needed to build good models that include rare species.
Today the Center for Tropical Forest Science coordinates a Global Earth Observatory-a network of 20 such forest study sites in 17 countries, which maintains "actuarial tables" for more than 3 million trees.
Hubbell works with data from the network to develop and test his neutral theory of biodiversity-an attempt to find a unified explanation of large, complex biological systems that accurately predicts the outcome of major ecological and evolutionary forces of change.
In this offering, the authors use the neutral theory to predict the number of tree species and to test predictions of the Millenium Ecosystems Assessment that forecasts major tree extinctions in the Amazon over the next several decades. First, they estimate that the Brazilian Amazon has (or had) 11,210 large tree species, and, of these, 5,308 species are classified as rare.
Based on optimistic and non-optimistic scenarios for road construction in the Amazon published by the Smithsonian's William Laurance and colleagues in the journal Science in 2004, they predict that the rare species will suffer between 37 and 50 percent extinction, whereas the extinction rate for all trees could be from 20 to 33 percent overall.
Would a simpler Amazon forest lacking many of its rarer trees function? Will the extinction of species other than trees-pollinators, seed predators, carnivores-contribute significantly to the lost of rainforest resilience? This and other biological quandaries remain. The authors exhort: "Although it is an old scientific chestnut, we must once again emphasize how important it is to support continuing basic science on tropical forests."
The Smithsonian Tropical Research Institute, headquartered in Panama City, Panama, is a unit of the Smithsonian Institution. The institute furthers the understanding of tropical nature and its importance to human welfare, trains students to conduct research in the tropics and promotes conservation by increasing public awareness of the beauty and importance of tropical ecosystems. For more information, visit stri.
Ref: Stephen P. Hubbell, Fangliang He, Richard Condit, Luis Borda-de-Agua, and Hans ter Steege. 2008. How many tree species are there in the Amazon and how many of them will go extinct? Proceedings of the National Academy of Science, August 12 early online edition.
Smithsonian Tropical Research Institute
суббота, 27 августа 2011 г.
A Step Forward In Virology - Trojan Horse Of Viruses Revealed
Viruses use various tricks and disguises to invade
cells. ETH Zurich researchers have now discovered yet another strategy
used by viruses: the vaccinia virus disguises itself as cell waste, triggers
the formation of evaginations in cells and is suspected to enter the cell
interior before the immune defense even notices. The research results
have been published in Science.
The vaccinia virus has a problem: it is a giant among viruses and needs a
special
strategy in order to infiltrate a cell and reproduce. Professor Ari Helenius
and Postdoc Jason Mercer from ETH Zurich's Institute for Biochemistry have
now discovered what this strategy is. In the process, they stumbled upon new
and surprising findings.
The invasion strategy
In order to infiltrate a cell, the vaccinia virus exploits the cellular
waste disposal
mechanism. When a cell dies, other cells in the vicinity ingest the remains,
without
needing waste disposal experts such as macrophages. The cells recognize
the waste via a special molecule, phosphatidylserine, which sits on the
inner
surface of the double membrane of cells. This special molecule is pushed out
as
soon as the cell dies and is broken into parts. The vaccinia virus itself
also carries
this official waste tag on its surface. "The substance accumulates on the
shell of vaccinia viruses", Jason Mercer explained. The pathogen disguises
itself
as waste material and tricks cells into digesting it, just as they normally
would
with the remains of dead cells. As the immune response is simultaneously
suppressed,
the virus can be ingested as waste without being noticed.
The uptake into the cell itself is via macropinocytosis. The ETH Zurich
researchers
have demonstrated that the vaccinia virus moves along actin-rich
filamentous extensions towards the cell. As soon as they impinge upon the
cell
membrane, an evagination forms, a bleb. The virus itself is the trigger for
the
formation of the evagination. Using a messenger substance to "knock on the
door", the virus triggers a signaling chain reaction inside the cell so that
the bleb
forms, catches the virus and smuggles it into the cell.
Proteins as unsuspecting allies
"The viruses are the Trojan horses that want to enter Troy; the Trojans are
the
many proteins that transmit the signals and open the 'city gates' to the
unwelcome
guest", Ari Helenius said. Aided by Professor Lukas Pelkmans' team, Jason
Mercer examined over 7000 different proteins in order to find out not only
which Trojans let the virus in, but which as well are chiefly involved in
the supply
chain. Using definitive methods, the researchers de-activated each one of
the
suspected proteins to examine their function,and narrowed the vast number of
proteins down to 140 potential culprits. The enzyme kinase PAK1 turned out
to
be an especially "helpful" citizen of Troy. Without PAK1, the pathogen's
trick did
not work and the cell did not form any evaginations.
Until now, very little has been known about the mechanism vaccinia viruses
use
to infiltrate a cell. Professor Helenius, whose research objective is to
find out
what methods and strategies various different viruses employ to invade
somatic
cells, clarified "This strategy is a new one". Other viruses, such as
herpes,
adeno and H1 viruses use macropinocytosis. However the vaccinia virus is the
first one identified that uses apoptotic mimicry as an entry strategy.
Knowledge of the virus strategies and the signal proteins involved in the
ingestion
of a virus by a cell is crucial to finding and developing new agents against
the pathogens. Until now, antiviral medication has targeted the virus
itself. Ari
Helenius, however, is looking for substances that interrupt the signaling
chain
and halt the communication between the virus and the cell. If the cell does
not
ingest a virus, the virus cannot reproduce and is quickly eliminated by the
immune
system. This process also has another big advantage: "Viruses cannot
adapt to the obstruction of the signal chain all that quickly", he said.
Smallpox: a bioterrorist attack?
The vaccinia virus belongs to a family of particularly dangerous viruses,
namely the pox
viruses. The most infamous member, Variola, the casitive agent of smallpox
constituted
a global pandemic disease in the Middle Ages, causing the deaths of millions
of people,
especially among the indigenous population of North America who became
infected by
European settlers. Pox was the first viral disease against which a
vaccination was developed.
In 1771, the first rudimentary vaccine was produced from cowpox viruses,
which protected people from the sequelae of the disease. Since 1978, the
disease has
been classed as eradicated and officially is preserved in only two
laboratories; one in
Atlanta, the other in Novosibirsk. US authorities, however, fear
bioterrorist attacks with
pox viruses. Research on these dangerous pathogens is thus encouraged.
ETH Zurich (Swiss Federal Institute of Technology Zurich) has a student body
of nearly fourteen
thousand students from 80 nations. About 360 professors teach mainly in
engineering
sciences and architecture, system-oriented sciences, mathematics and natural
sciences, as
well as carry out research that is highly valued worldwide. Distinguished by
the successes of
21 Nobel laureates, ETH Zurich is committed to providing its students with
unparalleled education
and outstanding leadership skills.
ETH Zurich
cells. ETH Zurich researchers have now discovered yet another strategy
used by viruses: the vaccinia virus disguises itself as cell waste, triggers
the formation of evaginations in cells and is suspected to enter the cell
interior before the immune defense even notices. The research results
have been published in Science.
The vaccinia virus has a problem: it is a giant among viruses and needs a
special
strategy in order to infiltrate a cell and reproduce. Professor Ari Helenius
and Postdoc Jason Mercer from ETH Zurich's Institute for Biochemistry have
now discovered what this strategy is. In the process, they stumbled upon new
and surprising findings.
The invasion strategy
In order to infiltrate a cell, the vaccinia virus exploits the cellular
waste disposal
mechanism. When a cell dies, other cells in the vicinity ingest the remains,
without
needing waste disposal experts such as macrophages. The cells recognize
the waste via a special molecule, phosphatidylserine, which sits on the
inner
surface of the double membrane of cells. This special molecule is pushed out
as
soon as the cell dies and is broken into parts. The vaccinia virus itself
also carries
this official waste tag on its surface. "The substance accumulates on the
shell of vaccinia viruses", Jason Mercer explained. The pathogen disguises
itself
as waste material and tricks cells into digesting it, just as they normally
would
with the remains of dead cells. As the immune response is simultaneously
suppressed,
the virus can be ingested as waste without being noticed.
The uptake into the cell itself is via macropinocytosis. The ETH Zurich
researchers
have demonstrated that the vaccinia virus moves along actin-rich
filamentous extensions towards the cell. As soon as they impinge upon the
cell
membrane, an evagination forms, a bleb. The virus itself is the trigger for
the
formation of the evagination. Using a messenger substance to "knock on the
door", the virus triggers a signaling chain reaction inside the cell so that
the bleb
forms, catches the virus and smuggles it into the cell.
Proteins as unsuspecting allies
"The viruses are the Trojan horses that want to enter Troy; the Trojans are
the
many proteins that transmit the signals and open the 'city gates' to the
unwelcome
guest", Ari Helenius said. Aided by Professor Lukas Pelkmans' team, Jason
Mercer examined over 7000 different proteins in order to find out not only
which Trojans let the virus in, but which as well are chiefly involved in
the supply
chain. Using definitive methods, the researchers de-activated each one of
the
suspected proteins to examine their function,and narrowed the vast number of
proteins down to 140 potential culprits. The enzyme kinase PAK1 turned out
to
be an especially "helpful" citizen of Troy. Without PAK1, the pathogen's
trick did
not work and the cell did not form any evaginations.
Until now, very little has been known about the mechanism vaccinia viruses
use
to infiltrate a cell. Professor Helenius, whose research objective is to
find out
what methods and strategies various different viruses employ to invade
somatic
cells, clarified "This strategy is a new one". Other viruses, such as
herpes,
adeno and H1 viruses use macropinocytosis. However the vaccinia virus is the
first one identified that uses apoptotic mimicry as an entry strategy.
Knowledge of the virus strategies and the signal proteins involved in the
ingestion
of a virus by a cell is crucial to finding and developing new agents against
the pathogens. Until now, antiviral medication has targeted the virus
itself. Ari
Helenius, however, is looking for substances that interrupt the signaling
chain
and halt the communication between the virus and the cell. If the cell does
not
ingest a virus, the virus cannot reproduce and is quickly eliminated by the
immune
system. This process also has another big advantage: "Viruses cannot
adapt to the obstruction of the signal chain all that quickly", he said.
Smallpox: a bioterrorist attack?
The vaccinia virus belongs to a family of particularly dangerous viruses,
namely the pox
viruses. The most infamous member, Variola, the casitive agent of smallpox
constituted
a global pandemic disease in the Middle Ages, causing the deaths of millions
of people,
especially among the indigenous population of North America who became
infected by
European settlers. Pox was the first viral disease against which a
vaccination was developed.
In 1771, the first rudimentary vaccine was produced from cowpox viruses,
which protected people from the sequelae of the disease. Since 1978, the
disease has
been classed as eradicated and officially is preserved in only two
laboratories; one in
Atlanta, the other in Novosibirsk. US authorities, however, fear
bioterrorist attacks with
pox viruses. Research on these dangerous pathogens is thus encouraged.
ETH Zurich (Swiss Federal Institute of Technology Zurich) has a student body
of nearly fourteen
thousand students from 80 nations. About 360 professors teach mainly in
engineering
sciences and architecture, system-oriented sciences, mathematics and natural
sciences, as
well as carry out research that is highly valued worldwide. Distinguished by
the successes of
21 Nobel laureates, ETH Zurich is committed to providing its students with
unparalleled education
and outstanding leadership skills.
ETH Zurich
среда, 24 августа 2011 г.
Researchers Discover How Compounds Found In Red Wine Thwart Alzheimer's Disease In Mice
Scientists call it the "French paradox" - a society that, despite consuming food high in cholesterol and saturated fats, has long had low death rates from heart disease. Research has suggested it is the red wine consumed with all that fatty food that may be beneficial - and not only for cardiovascular health but in warding off certain tumors and even Alzheimer's disease.
Now, Alzheimer's researchers at UCLA, in collaboration with Mt. Sinai School of Medicine in New York, have discovered how red wine may reduce the incidence of the disease. Reporting in the Nov. 21 issue of the Journal of Biological Chemistry, David Teplow, a UCLA professor of neurology, and colleagues show how naturally occurring compounds in red wine called polyphenols block the formation of proteins that build the toxic plaques thought to destroy brain cells, and further, how they reduce the toxicity of existing plaques, thus reducing cognitive deterioration.
Polyphenols comprise a chemical class with more than 8,000 members, many of which are found in high concentrations in wine, tea, nuts, berries, cocoa and various plants. Past research has suggested that such polyphenols may inhibit or prevent the buildup of toxic fibers composed primarily of two proteins - AГџ40 and AГџ42 - that deposit in the brain and form the plaques which have long been associated with Alzheimer's. Until now, however, no one understood the mechanics of how polyphenols worked.
Teplow's lab has been studying how amyloid beta (AГџ) is involved in causing Alzheimer's. In this work, researchers monitored how AГџ40 and AГџ42 proteins folded up and stuck to each other to produce aggregates that killed nerve cells in mice. They then treated the proteins with a polyphenol compound extracted from grape seeds. They discovered that polyphenols carried a one-two punch: They blocked the formation of the toxic aggregates of AГџ and also decreased toxicity when they were combined with AГџ before it was added to brain cells.
"What we found is pretty straightforward," Teplow said. "If the AГџ proteins can't assemble, toxic aggregates can't form, and thus there is no toxicity. Our work in the laboratory, and Mt. Sinai's Dr. Giulio Pasinetti's work in mice, suggest that administration of the compound to Alzheimer's patients might block the development of these toxic aggregates, prevent disease development and also ameliorate existing disease."
Human clinical trials are next.
"No disease-modifying treatments of Alzheimer's now exist, and initial clinical trials of a number of different candidate drugs have been disappointing," Teplow said. "So we believe that this is an important next step."
This work was supported by the National Institutes of Health; the Department of Veterans Affairs; the James J. Peters Veterans Affairs Medical Center Geriatric Research Education Clinical Center Program, Polyphenolics (to Giulio Pasinetti); grants from the Japan Human Science Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research; grants from the Alzheimer's Association; and the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA (to David Teplow). Teplow reports no conflict of interests.
The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks first among its peers nationwide in National Institutes of Health funding. For more information, visit neurology.medsch.ucla.
Source: Mark Wheeler
University of California - Los Angeles
Now, Alzheimer's researchers at UCLA, in collaboration with Mt. Sinai School of Medicine in New York, have discovered how red wine may reduce the incidence of the disease. Reporting in the Nov. 21 issue of the Journal of Biological Chemistry, David Teplow, a UCLA professor of neurology, and colleagues show how naturally occurring compounds in red wine called polyphenols block the formation of proteins that build the toxic plaques thought to destroy brain cells, and further, how they reduce the toxicity of existing plaques, thus reducing cognitive deterioration.
Polyphenols comprise a chemical class with more than 8,000 members, many of which are found in high concentrations in wine, tea, nuts, berries, cocoa and various plants. Past research has suggested that such polyphenols may inhibit or prevent the buildup of toxic fibers composed primarily of two proteins - AГџ40 and AГџ42 - that deposit in the brain and form the plaques which have long been associated with Alzheimer's. Until now, however, no one understood the mechanics of how polyphenols worked.
Teplow's lab has been studying how amyloid beta (AГџ) is involved in causing Alzheimer's. In this work, researchers monitored how AГџ40 and AГџ42 proteins folded up and stuck to each other to produce aggregates that killed nerve cells in mice. They then treated the proteins with a polyphenol compound extracted from grape seeds. They discovered that polyphenols carried a one-two punch: They blocked the formation of the toxic aggregates of AГџ and also decreased toxicity when they were combined with AГџ before it was added to brain cells.
"What we found is pretty straightforward," Teplow said. "If the AГџ proteins can't assemble, toxic aggregates can't form, and thus there is no toxicity. Our work in the laboratory, and Mt. Sinai's Dr. Giulio Pasinetti's work in mice, suggest that administration of the compound to Alzheimer's patients might block the development of these toxic aggregates, prevent disease development and also ameliorate existing disease."
Human clinical trials are next.
"No disease-modifying treatments of Alzheimer's now exist, and initial clinical trials of a number of different candidate drugs have been disappointing," Teplow said. "So we believe that this is an important next step."
This work was supported by the National Institutes of Health; the Department of Veterans Affairs; the James J. Peters Veterans Affairs Medical Center Geriatric Research Education Clinical Center Program, Polyphenolics (to Giulio Pasinetti); grants from the Japan Human Science Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research; grants from the Alzheimer's Association; and the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA (to David Teplow). Teplow reports no conflict of interests.
The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks first among its peers nationwide in National Institutes of Health funding. For more information, visit neurology.medsch.ucla.
Source: Mark Wheeler
University of California - Los Angeles
воскресенье, 21 августа 2011 г.
Less Expensive Alternative To Therapeutic Antibodies May Be Synthetic Molecules
Researchers at UT Southwestern Medical Center have developed a simple and inexpensive method to screen small synthetic molecules and pull out a handful that might treat cancer and other diseases less expensively than current methods.
In one screen of more than 300,000 such molecules, called peptoids, the new technique quickly singled out five promising candidates that mimicked an antibody already on the market for treating cancer. One of the compounds blocked the growth of human tumors in a mouse model.
Antibodies are molecules produced by the body to help ward off infection. Natural and manmade antibodies work by latching onto very specific targets such as receptors on the surface of cells.
"Many new drugs being made today are antibodies, but they are extremely expensive to make. Financially, the U.S. health care system is going to have a difficult time accommodating the next 500 drugs being antibodies," said Dr. Thomas Kodadek, chief of translational research at UT Southwestern and senior author of the study, which appears online and in an upcoming issue of the Journal of the American Chemical Society.
"Our results show that a peptoid can attack a harmful receptor in the body with the same precision as an antibody, but would cost much less to develop," said Dr. Kodadek.
Peptoids are designed in the laboratory to resemble chains of natural molecules called peptides. Some peptides are used as medications, such as insulin or antibodies used to treat some cancers, but because the stomach digests them, most can't be taken by mouth and must be injected.
By contrast, peptoids are resistant to the stomach enzymes that degrade natural peptides, so it is possible that they could be swallowed as a pill. Peptoids are much less expensive and easier to manufacture than antibodies, Dr. Kodadek said. They are also much smaller than antibodies, so they might be better at penetrating tumors or other disease sites, he said.
"Our technique is simple and fast, works with existing chemicals and needs no high-tech instrumentation, except for a microscope to detect the fluorescent colors we use to sort the compounds," said Dr. D. Gomika Udugamasooriya, postdoctoral researcher in internal medicine and lead author of the study.
The new technique also has major advantages over traditional screening techniques that are commonly used to discover biologically active compounds from large collections. These screens, which require extensive automation, generally cost $40,000 or more; the new method can be conducted for less than $1,000.
The researchers screened about 300,000 peptoids to see which ones would interact with VEGFR2, a type of molecule on the surface of human cells. VEGFR2 is essential in creating new blood vessels through interaction with the hormone VEGF, which is normally a helpful process but is harmful to the body when the new blood vessels are nourishing a growing tumor.
A commercially produced antibody is used to treat some cancers by blocking the VEGF-VEGFR2 interaction and thus starving the tumor, but it costs a patient about $20,000 a year, Dr. Kodadek said.
The new screening technology involves hundreds of thousands of peptoids, bound to tiny plastic beads. In the study, the cells with VEGFR2 were labeled to fluoresce red and those lacking VEGFR2 were labeled to fluoresce green. After exposing the beads to the mixture of cells, the beads were examined under a fluorescent microscope. Those bound to red cells - the ones with VEGFR2 - were collected.
This screen, which took a couple of days, isolated five peptoids out of approximately 300,000 screened, showing that the process was an effective way to quickly narrow down a search, Dr. Kodadek said.
The researchers further tested one of the five peptoids that bound most tightly to VEGFR2 and found that it blocked VEGFR2's action in cultured cells. When they gave it in low doses to mice with implanted human bone- and soft-tissue cancer, the peptoid slowed the growth of the tumors and reduced the density of blood vessels leading to them.
"This new technique of rapidly isolating biologically active peptoids offers a way to hasten the drug-discovery process and may ultimately benefit patients by providing them with new therapies at a fraction of the cost of current drugs," Dr. Kodadek said.
Other UT Southwestern researchers who participated in the study were general surgery resident Dr. Sean Dineen and Dr. Rolf Brekken, assistant professor of surgery.
The work was supported by the National Heart, Lung and Blood Institute and The Welch Foundation.
Source: Aline McKenzie
UT Southwestern Medical Center
In one screen of more than 300,000 such molecules, called peptoids, the new technique quickly singled out five promising candidates that mimicked an antibody already on the market for treating cancer. One of the compounds blocked the growth of human tumors in a mouse model.
Antibodies are molecules produced by the body to help ward off infection. Natural and manmade antibodies work by latching onto very specific targets such as receptors on the surface of cells.
"Many new drugs being made today are antibodies, but they are extremely expensive to make. Financially, the U.S. health care system is going to have a difficult time accommodating the next 500 drugs being antibodies," said Dr. Thomas Kodadek, chief of translational research at UT Southwestern and senior author of the study, which appears online and in an upcoming issue of the Journal of the American Chemical Society.
"Our results show that a peptoid can attack a harmful receptor in the body with the same precision as an antibody, but would cost much less to develop," said Dr. Kodadek.
Peptoids are designed in the laboratory to resemble chains of natural molecules called peptides. Some peptides are used as medications, such as insulin or antibodies used to treat some cancers, but because the stomach digests them, most can't be taken by mouth and must be injected.
By contrast, peptoids are resistant to the stomach enzymes that degrade natural peptides, so it is possible that they could be swallowed as a pill. Peptoids are much less expensive and easier to manufacture than antibodies, Dr. Kodadek said. They are also much smaller than antibodies, so they might be better at penetrating tumors or other disease sites, he said.
"Our technique is simple and fast, works with existing chemicals and needs no high-tech instrumentation, except for a microscope to detect the fluorescent colors we use to sort the compounds," said Dr. D. Gomika Udugamasooriya, postdoctoral researcher in internal medicine and lead author of the study.
The new technique also has major advantages over traditional screening techniques that are commonly used to discover biologically active compounds from large collections. These screens, which require extensive automation, generally cost $40,000 or more; the new method can be conducted for less than $1,000.
The researchers screened about 300,000 peptoids to see which ones would interact with VEGFR2, a type of molecule on the surface of human cells. VEGFR2 is essential in creating new blood vessels through interaction with the hormone VEGF, which is normally a helpful process but is harmful to the body when the new blood vessels are nourishing a growing tumor.
A commercially produced antibody is used to treat some cancers by blocking the VEGF-VEGFR2 interaction and thus starving the tumor, but it costs a patient about $20,000 a year, Dr. Kodadek said.
The new screening technology involves hundreds of thousands of peptoids, bound to tiny plastic beads. In the study, the cells with VEGFR2 were labeled to fluoresce red and those lacking VEGFR2 were labeled to fluoresce green. After exposing the beads to the mixture of cells, the beads were examined under a fluorescent microscope. Those bound to red cells - the ones with VEGFR2 - were collected.
This screen, which took a couple of days, isolated five peptoids out of approximately 300,000 screened, showing that the process was an effective way to quickly narrow down a search, Dr. Kodadek said.
The researchers further tested one of the five peptoids that bound most tightly to VEGFR2 and found that it blocked VEGFR2's action in cultured cells. When they gave it in low doses to mice with implanted human bone- and soft-tissue cancer, the peptoid slowed the growth of the tumors and reduced the density of blood vessels leading to them.
"This new technique of rapidly isolating biologically active peptoids offers a way to hasten the drug-discovery process and may ultimately benefit patients by providing them with new therapies at a fraction of the cost of current drugs," Dr. Kodadek said.
Other UT Southwestern researchers who participated in the study were general surgery resident Dr. Sean Dineen and Dr. Rolf Brekken, assistant professor of surgery.
The work was supported by the National Heart, Lung and Blood Institute and The Welch Foundation.
Source: Aline McKenzie
UT Southwestern Medical Center
четверг, 18 августа 2011 г.
A Mechanism To Explain Biological "Cross Talk" Between 24 Hour Body Cycle And Metabolism
It's well known that the body's energy levels cycle on a 24 hour, or circadian, schedule, and that this metabolic process is fueled by oxygen. Now, researchers at the University of Pennsylvania School of Medicine have found that a protein called Rev erb coordinates the daily cycles of oxygen carrying heme molecules to maintain the body's correct metabolism.
The research appears online this week in Science Express in advance of print publication in Science.
Many studies, including this one, point to a link between the human internal clock and such metabolic disorders as obesity and diabetes. Proteins such as Rev erb are the gears of the clock and understanding their role is important for fighting these diseases.
"This is the next chapter on Rev erb, a member of a family of cell nucleus proteins that includes receptors for anti diabetic drugs," explains senior author Mitchell A. Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn. About two years ago Lazar's group discovered that Rev erb was a critical component of the circadian clock. In this paper, they found that the activity of Rev erb is controlled by heme.
Heme represents the body's most important way of transporting and using oxygen, which would simply bubble away in the body without being bound to heme. "In a molecular baton hand off, oxygen is transferred from heme in the bloodstream to the heme molecules found inside a cell," says Lazar, of how oxygen reaches cells to run their metabolic needs. One of the most important roles of heme inside cells is to facilitate the use of oxygen to generate energy in the process known as cellular respiration.
The findings further tie together the 24-hour cycle of the body with metabolic function. "Circadian rhythms are our sleep wake cycle and metabolism is how we process food, so it makes sense that there would be biological cross talk between the body's 24 hour rhythm and metabolic function," says Lazar. Indeed, scientists already recognize that getting too much or too little sleep increases the risk of diabetes. The newly discovered circadian/metabolic link could be the focus of a new generation of diabetes treatments.
The Penn group worked with scientists at GlaxoSmithKline, who demonstrated that the Rev erb protein can physically bind to heme in the test tube. The Penn scientists then found that heme, by regulating the activity of Rev erb, reduces the amount of glucose produced by liver cells.
"What's exciting about this is that it puts heme in a central role in the metabolic regulation of the cell," says Lazar. "Not only is it a key component in making energy, but also in the pathway for turning off glucose production." Excessive glucose production by the liver is a major cause of high blood sugar in diabetes.
This work was funded by the National Institute of Diabetes and Digestive and Kidney Disease. Co-authors are first author Lei Yin, Joshua C. Curtin, Mohammed Qatananai, and Nava R. Szwergold, all from Penn and Robert A. Reid, Gregory M. Waitt, Derek J. Parks, Kenneth H. Pearce, and G. Bruce Wisely, from GlaxoSmithKline, Research Triangle Park, NC.
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 #3 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 "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.
University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn
The research appears online this week in Science Express in advance of print publication in Science.
Many studies, including this one, point to a link between the human internal clock and such metabolic disorders as obesity and diabetes. Proteins such as Rev erb are the gears of the clock and understanding their role is important for fighting these diseases.
"This is the next chapter on Rev erb, a member of a family of cell nucleus proteins that includes receptors for anti diabetic drugs," explains senior author Mitchell A. Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn. About two years ago Lazar's group discovered that Rev erb was a critical component of the circadian clock. In this paper, they found that the activity of Rev erb is controlled by heme.
Heme represents the body's most important way of transporting and using oxygen, which would simply bubble away in the body without being bound to heme. "In a molecular baton hand off, oxygen is transferred from heme in the bloodstream to the heme molecules found inside a cell," says Lazar, of how oxygen reaches cells to run their metabolic needs. One of the most important roles of heme inside cells is to facilitate the use of oxygen to generate energy in the process known as cellular respiration.
The findings further tie together the 24-hour cycle of the body with metabolic function. "Circadian rhythms are our sleep wake cycle and metabolism is how we process food, so it makes sense that there would be biological cross talk between the body's 24 hour rhythm and metabolic function," says Lazar. Indeed, scientists already recognize that getting too much or too little sleep increases the risk of diabetes. The newly discovered circadian/metabolic link could be the focus of a new generation of diabetes treatments.
The Penn group worked with scientists at GlaxoSmithKline, who demonstrated that the Rev erb protein can physically bind to heme in the test tube. The Penn scientists then found that heme, by regulating the activity of Rev erb, reduces the amount of glucose produced by liver cells.
"What's exciting about this is that it puts heme in a central role in the metabolic regulation of the cell," says Lazar. "Not only is it a key component in making energy, but also in the pathway for turning off glucose production." Excessive glucose production by the liver is a major cause of high blood sugar in diabetes.
This work was funded by the National Institute of Diabetes and Digestive and Kidney Disease. Co-authors are first author Lei Yin, Joshua C. Curtin, Mohammed Qatananai, and Nava R. Szwergold, all from Penn and Robert A. Reid, Gregory M. Waitt, Derek J. Parks, Kenneth H. Pearce, and G. Bruce Wisely, from GlaxoSmithKline, Research Triangle Park, NC.
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 #3 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 "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.
University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn
понедельник, 15 августа 2011 г.
Powerful Integration Of Lipid Metabolic Profiling With Gene Expression Analysis
A recently published research article in the Journal of Proteome Research, authored by researchers from the Nestle Reserarch Center, Genomatix Software GmbH, Rosetta Inpharmatics LLC, CXR Biosciences Ltd, the Cancer Research UK Molecular Pharmacology Unit demonstrates the synergisms and enhanced analytic power of the combination of thorough metabolic profiling with the unique and proprietary microarray analysis methods of Genomatix Software GmbH.
The study elucidated the effects on Mouse lipid metabolism by the disruption of hepatic Cytochrome P450 reductase (POR) in a POR deficient knock-out mouse model. It clearly could demonstrate that though gene expression and lipid metabolism in extrahepatic tissues being sensitive to hepatic POR functionality, the lipidome in general is only minimally affected. Analysis of regulatory pathways and networks, observed expression changes and lipid profiling led to the conclusion that POR can be considered an enzyme critical for the proper functioning of lipid mobilization and metabolism predominantly within the mouse liver with only minor effects on lipid metabolism in the biological system at large.
The concordance between the two analytical platforms (Genomatix transcriptomic vs lipidomic) in the liver was excellent, and serves as a demonstration for the valid approach for generating novel hypГјotheses to unravel protein function that cannot be accomplished with as much confiodence using either platform individually.
"I am very excited about the possibility to overlay metabolic profiles with expression data and pathway information. We see the strategies applied in this study as a prototype for further analyzes bringing together metabolomics and expression analysis in a multiple lines of evidence manner. " says Dr. Martin Seifert, co-author of the study and Vice President Microarray Business and Collaborative Research at Genomatix.
Citation:
Mutch DM, Klocke B, Morrison P, Murray CA, Henderson CJ, Seifert M, Williamson G (2007)
The Disruption of Hepatic Cytochrome P450 Reductase Alters Mouse Lipid Metabolism.
J Proteome Res. 6, 3976-3984
[PUBMED: 17722906]
About Genomatix:
Genomatix is a pioneer and leader in the analysis and understanding of eukaryotic gene regulation. Core competences at Genomatix are annotation driven microarray analysis, ChIP on chip, regulatory network and pathway mining, and promoter analysis on sequence level. Genomatix has published more than 170 peer reviewed scientific papers that have been cited in more than 4,000 papers. Over 35,000 researchers worldwide currently apply Genomatix tools and databases. More information is available from genomatix/.
Source: Klaus May
Genomatix Software GmbH
The study elucidated the effects on Mouse lipid metabolism by the disruption of hepatic Cytochrome P450 reductase (POR) in a POR deficient knock-out mouse model. It clearly could demonstrate that though gene expression and lipid metabolism in extrahepatic tissues being sensitive to hepatic POR functionality, the lipidome in general is only minimally affected. Analysis of regulatory pathways and networks, observed expression changes and lipid profiling led to the conclusion that POR can be considered an enzyme critical for the proper functioning of lipid mobilization and metabolism predominantly within the mouse liver with only minor effects on lipid metabolism in the biological system at large.
The concordance between the two analytical platforms (Genomatix transcriptomic vs lipidomic) in the liver was excellent, and serves as a demonstration for the valid approach for generating novel hypГјotheses to unravel protein function that cannot be accomplished with as much confiodence using either platform individually.
"I am very excited about the possibility to overlay metabolic profiles with expression data and pathway information. We see the strategies applied in this study as a prototype for further analyzes bringing together metabolomics and expression analysis in a multiple lines of evidence manner. " says Dr. Martin Seifert, co-author of the study and Vice President Microarray Business and Collaborative Research at Genomatix.
Citation:
Mutch DM, Klocke B, Morrison P, Murray CA, Henderson CJ, Seifert M, Williamson G (2007)
The Disruption of Hepatic Cytochrome P450 Reductase Alters Mouse Lipid Metabolism.
J Proteome Res. 6, 3976-3984
[PUBMED: 17722906]
About Genomatix:
Genomatix is a pioneer and leader in the analysis and understanding of eukaryotic gene regulation. Core competences at Genomatix are annotation driven microarray analysis, ChIP on chip, regulatory network and pathway mining, and promoter analysis on sequence level. Genomatix has published more than 170 peer reviewed scientific papers that have been cited in more than 4,000 papers. Over 35,000 researchers worldwide currently apply Genomatix tools and databases. More information is available from genomatix/.
Source: Klaus May
Genomatix Software GmbH
пятница, 12 августа 2011 г.
Fluorescence Microscopy Reveals Why Some Antifreeze Proteins Inhibit Ice Growth Better Than Others
Finding could have medical, commercial applications
Antifreeze or "ice structuring" proteins - found in some fish, insects, plants, fungi and bacteria - attach to the surface of ice crystals to inhibit their growth and keep the host organism from freezing to death. Scientists have been puzzled, however, about why some ice structuring proteins, such as those found in the spruce budworm, are more active than others.
Fluorescence microscopy now has shown how those aggressive proteins protect the cells of the insect, which is native to U.S. and Canadian forests.
The finding could have future applications in medical, agricultural and commercial food industries, according to a team of scientists led by Ido Braslavsky, an assistant professor of physics and astronomy at Ohio University, and Peter Davies, a professor of biochemistry and biology at Queen's University in Canada. They presented the work at the March meeting of the American Physical Society in Denver, Colo.
In the recent study, Davies' lab combined spruce budworm and fish antifreeze proteins with a fluorescent tag. Using a fluorescent microscope, Braslavsky and postdoctoral fellow Natalya Pertaya could observe how the proteins interacted with the surfaces of ice crystals. They found that the hyperactive antifreeze protein from the spruce budworm stops ice crystals from growing in particular directions. The antifreeze proteins from fish are less effective.
Antifreeze proteins, especially the hyperactive type found in the spruce budworm and other organisms, have various potential applications, according to Braslavsky. They could be used to preserve organs and tissues for medical applications such as transplants, and also could prevent frostbite. They also can inhibit crystal growth in ice cream - an application already in use by at least one commercial food manufacturer - as well as protect against agricultural frost damage.
The research was funded by Ohio University's NanoBioTechnology Initiative and the Canadian Institutes of Health Research.
Contacts:
Ido Braslavsky
In collaboration with John Wettlaufer, a professor of physics and geophysics from Yale University, the team also has published a related paper on antifreeze protein research in Biophysical Journal. The paper is available online at biophysj/cgi/rapidpdf/biophysj.106.096297v1.
Note: Images can be downloaded here.
Contact: Andrea Gibson
Ohio University
Antifreeze or "ice structuring" proteins - found in some fish, insects, plants, fungi and bacteria - attach to the surface of ice crystals to inhibit their growth and keep the host organism from freezing to death. Scientists have been puzzled, however, about why some ice structuring proteins, such as those found in the spruce budworm, are more active than others.
Fluorescence microscopy now has shown how those aggressive proteins protect the cells of the insect, which is native to U.S. and Canadian forests.
The finding could have future applications in medical, agricultural and commercial food industries, according to a team of scientists led by Ido Braslavsky, an assistant professor of physics and astronomy at Ohio University, and Peter Davies, a professor of biochemistry and biology at Queen's University in Canada. They presented the work at the March meeting of the American Physical Society in Denver, Colo.
In the recent study, Davies' lab combined spruce budworm and fish antifreeze proteins with a fluorescent tag. Using a fluorescent microscope, Braslavsky and postdoctoral fellow Natalya Pertaya could observe how the proteins interacted with the surfaces of ice crystals. They found that the hyperactive antifreeze protein from the spruce budworm stops ice crystals from growing in particular directions. The antifreeze proteins from fish are less effective.
Antifreeze proteins, especially the hyperactive type found in the spruce budworm and other organisms, have various potential applications, according to Braslavsky. They could be used to preserve organs and tissues for medical applications such as transplants, and also could prevent frostbite. They also can inhibit crystal growth in ice cream - an application already in use by at least one commercial food manufacturer - as well as protect against agricultural frost damage.
The research was funded by Ohio University's NanoBioTechnology Initiative and the Canadian Institutes of Health Research.
Contacts:
Ido Braslavsky
In collaboration with John Wettlaufer, a professor of physics and geophysics from Yale University, the team also has published a related paper on antifreeze protein research in Biophysical Journal. The paper is available online at biophysj/cgi/rapidpdf/biophysj.106.096297v1.
Note: Images can be downloaded here.
Contact: Andrea Gibson
Ohio University
вторник, 9 августа 2011 г.
Access Pharmaceuticals Initiates Program Applying Cobalamin Platform To SiRNA Drug Delivery
ACCESS PHARMACEUTICALS, INC. (OTC Bulletin Board: ACCP) announced that it initiated an internal pre-licensing program to confirm the utility of its proprietary Cobalamin (vitamin B12) platform technology for targeted delivery of siRNA therapies. The program is considered important because, despite the widely publicized potential of RNA therapy, researchers up to now have been stymied in their efforts to design a pharmaceutical product that efficiently transports siRNA therapeutics into the cells they are designed to inhibit or kill.
Access has multiple programs ongoing around use of its Cobalamin technology to facilitate oral absorption of pharmaceuticals, including previously announced collaborations with potential pharma and biotech partners. To date, its successful Cobalamin product development program has focused on the oral delivery of insulin and human growth hormone, two peptides that currently can only be given by injection. Because these two molecules share some of the same physical characteristics as RNA's active components, Access believes its Cobalamin technology could effectively deliver RNA therapy in an oral tablet instead of by injection.
But a more compelling feature of the Cobalamin technology may be its ability to overcome the cellular transport obstacles that have held back fuller development of RNA therapy. The large size and high negative charge of RNA molecules prevents their absorption by target cells. Using the 'Trojan Horse' principle, the Cobalamin nanoparticle technology can encapsulate small fragments of RNA (siRNA) and utilize the Colalamin's vitamin B12 uptake mechanism to transport them into target cells, allowing release of the active drug to initiate the therapeutic effect. Cobalamin's vitamin B12 uptake mechanism offers the potential for targeted delivery of siRNA because most human cells have a requirement for vitamin B12. This is served by cell surface receptors, which facilitate absorption of this vitamin. In many diseases, the demand for vitamin B12 is increased, with a corresponding upregulation of the receptor.
"Access scientists and collaborators have so far demonstrated in preclinical models that Cobalamin formulations are effective in achieving good oral drug delivery of charged peptides such as insulin and human growth hormone," commented David P. Nowotnik, Senior Vice President, Research and Development. "These successes with molecules which share some of the same physical characteristics as siRNA would indicate that we should now be able to generate effective formulations of Cobalamin nanoparticles for delivery of siRNA. We know already from previous work that we can make cancer drugs more effective using the Cobalamin approach, and so we have a sound scientific basis for the future development of Cobalamin RNAi therapeutics."
Cobalamin is Access' proprietary technology based upon the use of vitamin B12 for targeted delivery of drugs to disease sites and for oral drug delivery of drugs that otherwise have poor oral bioavailability. Access has focused its Cobalamin product development program on the oral delivery of insulin and human growth hormone, two peptides that currently can only be given by injection. Since presenting promising results at a major conference in mid-2008, Access has made substantial improvements to the formulation technology. A new Cobalamin-coated insulin-containing nanoparticle formulation delivered orally provided a pharmacological response (lowering of blood glucose levels in an animal model of diabetes) equivalent to greater than 80% of that achieved by insulin delivered subcutaneously. This represents a substantial oral bioavailability, indicating that this formulation has potential for clinical development and ultimate commercialization. Adaptation of this technology has provided a Cobalamin human growth hormone formulation that has demonstrated good efficacy, represented by more than 25% improvement in weight gain, when given orally in an established animal model. Access continues to move both products towards clinical development, and plans to submit an additional patent application to protect the improvements to the technology.
About Access:
Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access' products include ProLindac™ currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard™ for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin™-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism and Thiarabine, a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers.
This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements include those relating to: our cash burn rate, clinical trial plans and timelines and clinical results for ProLindac, MuGard, Thiarabine and Cobalamin and other product candidates, our ability to achieve clinical and commercial success and our ability to successfully develop marketed products. These statements are subject to numerous risks, including but not limited Access' need to obtain additional financing in order to continue the clinical trial and operations and to the risks detailed in Access' Annual Reports on Form 10-K and other reports filed by Access with the Securities and Exchange Commission.
Source: Access Pharmaceuticals, Inc
Access has multiple programs ongoing around use of its Cobalamin technology to facilitate oral absorption of pharmaceuticals, including previously announced collaborations with potential pharma and biotech partners. To date, its successful Cobalamin product development program has focused on the oral delivery of insulin and human growth hormone, two peptides that currently can only be given by injection. Because these two molecules share some of the same physical characteristics as RNA's active components, Access believes its Cobalamin technology could effectively deliver RNA therapy in an oral tablet instead of by injection.
But a more compelling feature of the Cobalamin technology may be its ability to overcome the cellular transport obstacles that have held back fuller development of RNA therapy. The large size and high negative charge of RNA molecules prevents their absorption by target cells. Using the 'Trojan Horse' principle, the Cobalamin nanoparticle technology can encapsulate small fragments of RNA (siRNA) and utilize the Colalamin's vitamin B12 uptake mechanism to transport them into target cells, allowing release of the active drug to initiate the therapeutic effect. Cobalamin's vitamin B12 uptake mechanism offers the potential for targeted delivery of siRNA because most human cells have a requirement for vitamin B12. This is served by cell surface receptors, which facilitate absorption of this vitamin. In many diseases, the demand for vitamin B12 is increased, with a corresponding upregulation of the receptor.
"Access scientists and collaborators have so far demonstrated in preclinical models that Cobalamin formulations are effective in achieving good oral drug delivery of charged peptides such as insulin and human growth hormone," commented David P. Nowotnik, Senior Vice President, Research and Development. "These successes with molecules which share some of the same physical characteristics as siRNA would indicate that we should now be able to generate effective formulations of Cobalamin nanoparticles for delivery of siRNA. We know already from previous work that we can make cancer drugs more effective using the Cobalamin approach, and so we have a sound scientific basis for the future development of Cobalamin RNAi therapeutics."
Cobalamin is Access' proprietary technology based upon the use of vitamin B12 for targeted delivery of drugs to disease sites and for oral drug delivery of drugs that otherwise have poor oral bioavailability. Access has focused its Cobalamin product development program on the oral delivery of insulin and human growth hormone, two peptides that currently can only be given by injection. Since presenting promising results at a major conference in mid-2008, Access has made substantial improvements to the formulation technology. A new Cobalamin-coated insulin-containing nanoparticle formulation delivered orally provided a pharmacological response (lowering of blood glucose levels in an animal model of diabetes) equivalent to greater than 80% of that achieved by insulin delivered subcutaneously. This represents a substantial oral bioavailability, indicating that this formulation has potential for clinical development and ultimate commercialization. Adaptation of this technology has provided a Cobalamin human growth hormone formulation that has demonstrated good efficacy, represented by more than 25% improvement in weight gain, when given orally in an established animal model. Access continues to move both products towards clinical development, and plans to submit an additional patent application to protect the improvements to the technology.
About Access:
Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access' products include ProLindac™ currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard™ for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin™-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism and Thiarabine, a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers.
This press release contains certain statements that are forward-looking within the meaning of Section 27a of the Securities Act of 1933, as amended, and that involve risks and uncertainties. These statements include those relating to: our cash burn rate, clinical trial plans and timelines and clinical results for ProLindac, MuGard, Thiarabine and Cobalamin and other product candidates, our ability to achieve clinical and commercial success and our ability to successfully develop marketed products. These statements are subject to numerous risks, including but not limited Access' need to obtain additional financing in order to continue the clinical trial and operations and to the risks detailed in Access' Annual Reports on Form 10-K and other reports filed by Access with the Securities and Exchange Commission.
Source: Access Pharmaceuticals, Inc
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