An area of the brain involved in the planning and production of spoken and signed language in humans plays a similar role in chimpanzee communication, researchers report online on February 28th in the journal Current Biology, a publication of Cell Press.
"Chimpanzee communicative behavior shares many characteristics with human language," said Jared Taglialatela of the Yerkes National Primate Research Center. "The results from this study suggest that these similarities extend to the way in which our brains produce and process communicative signals."
The results also suggest that the "neurobiological foundations" of human language may have been present in the common ancestor of modern humans and chimpanzees, he said.
Scientists had identified Broca's area, located in part of the human brain known as the inferior frontal gyrus (IFG), as one of several critical regions that light up with activity when people plan to say something and when they actually talk or sign. Anatomically, Broca's area is most often larger on the left side of the brain, and imaging studies in humans had shown left-leaning patterns of brain activation during language-related tasks, the researchers said.
"We didn't know if or to what extent other primates, and particularly humans' closest ancestor, the chimpanzees, possess a comparable region involved in the production of their own communicative signals," Taglialatela said.
In the new study, the researchers non-invasively scanned the brains of three chimpanzees as they gestured and called to a person in request for food that was out of their reach. Those chimps showed activation in the brain region corresponding to Broca's area and in other areas involved in complex motor planning and action in humans, the researchers found.
The findings might be interpreted in one of two ways, Taglialatela said.
"One interpretation of our results is that chimpanzees have, in essence, a 'language-ready brain,' " he said. "By this, we are suggesting that apes are born with and use the brain areas identified here when producing signals that are part of their communicative repertoire.
"Alternatively, one might argue that, because our apes were captive-born and producing communicative signals not seen often in the wild, the specific learning and use of these signals 'induced' the pattern of brain activation we saw. This would suggest that there is tremendous plasticity in the chimpanzee brain, as there is in the human brain, and that the development of certain kinds of communicative signals might directly influence the structure and function of the brain."
The researchers include Jared P. Taglialatela, Yerkes National Primate Research Center, Atlanta, GA, Department of Natural Sciences, Clayton State University, Morrow, GA; Jamie L. Russell, Yerkes National Primate Research Center, Atlanta, GA; Jennifer A. Schaeffer, Yerkes National Primate Research Center, Atlanta, GA; and William D. Hopkins, Yerkes National Primate Research Center, Atlanta, GA, Department of Psychology, Agnes Scott College, Decatur, GA.
Source: Cathleen Genova
Cell Press
среда, 1 июня 2011 г.
Hair Cells Act As Biological Wound Dressing
A new study in Artificial Organs tested the effects of a wound dressing created with hair follicular cells. The findings reveal that skin substitutes using living hair cells can increase wound healing.
Researchers applied the technique to wound surfaces on mice. Subjects that were administered this biological dressing produced two times better wound closure than the control set.
The technique not only provides the proper environment for cell attachment and growth, but also serves as an effective biodressing to keep wounds moist and maintain structural strength during healing. "This technique shows promise as a biological dressing that is not only efficient and strong but also can be produced with less time and effort," says Jung Chul Kim, lead author of the study.
The use of skin substitutes for wound healing has suffered setbacks in recent years due to the expensive price. However, this method of wound dressing improves early-stage wound healing and reduces the time between preparation and patient use.
This study is published in the November 2007 issue of Artificial Organs.
Dr. Jung Chul Kim is affiliated with Kyungpook National University in Daegu, Korea.
Since 1977, Artificial Organs has been publishing original articles featuring the studies of design, performance, and evaluation of the biomaterials and devices for the international medical, scientific, and engineering communities involved in the research and clinical application of artificial organ development.
Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley's Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit blackwellpublishing/ or interscience.wiley/.
Source: Amy Molnar
Blackwell Publishing Ltd.
Researchers applied the technique to wound surfaces on mice. Subjects that were administered this biological dressing produced two times better wound closure than the control set.
The technique not only provides the proper environment for cell attachment and growth, but also serves as an effective biodressing to keep wounds moist and maintain structural strength during healing. "This technique shows promise as a biological dressing that is not only efficient and strong but also can be produced with less time and effort," says Jung Chul Kim, lead author of the study.
The use of skin substitutes for wound healing has suffered setbacks in recent years due to the expensive price. However, this method of wound dressing improves early-stage wound healing and reduces the time between preparation and patient use.
This study is published in the November 2007 issue of Artificial Organs.
Dr. Jung Chul Kim is affiliated with Kyungpook National University in Daegu, Korea.
Since 1977, Artificial Organs has been publishing original articles featuring the studies of design, performance, and evaluation of the biomaterials and devices for the international medical, scientific, and engineering communities involved in the research and clinical application of artificial organ development.
Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley's Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit blackwellpublishing/ or interscience.wiley/.
Source: Amy Molnar
Blackwell Publishing Ltd.
The Complexity Of Disease Phenotypes
Animal models have been invaluable in understanding how gene mutations physically affect a complex organism. However, as vividly illustrated in a new research study examining mice with a metabolic disease, the same mutation in the same species can produce wildly variable results.
Niemann-Pick type C (NPC) disease is a rare genetic condition brought on by a mutation in one protein, NPC1, which helps shuttle cholesterol out of a cell compartment called the lysosome. As a result, cholesterol accumulates in virtually every tissue in the body, causing widespread organ dysfunction and death.
John Dietschy and colleagues evaluated how factors like genetic background, additional mutations, and environmental influences affected the lifespan of a mouse model of NBC. Overall, the lifespan of different npc1-/- mice ranged from 50-130 days, and even simple differences such as the host colony (same strain, just different location of breeding), or slight alterations in diet affected the average lifespan.
These studies highlight just how complex a 'simple' genetic disease really is, and that such variability should be carefully considered when designing animal experiments or interpreting results. It is particularly important, Dietschy and colleagues note, to use these animal models to carefully differentiate the non-specific environmental and genetic effects on lifespan from treatments that have a direct effect on the genetic abnormality present in the disease and thus may promote survival.
The Journal of Lipid research
Corresponding Author: John M. Dietschy, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
Niemann-Pick type C (NPC) disease is a rare genetic condition brought on by a mutation in one protein, NPC1, which helps shuttle cholesterol out of a cell compartment called the lysosome. As a result, cholesterol accumulates in virtually every tissue in the body, causing widespread organ dysfunction and death.
John Dietschy and colleagues evaluated how factors like genetic background, additional mutations, and environmental influences affected the lifespan of a mouse model of NBC. Overall, the lifespan of different npc1-/- mice ranged from 50-130 days, and even simple differences such as the host colony (same strain, just different location of breeding), or slight alterations in diet affected the average lifespan.
These studies highlight just how complex a 'simple' genetic disease really is, and that such variability should be carefully considered when designing animal experiments or interpreting results. It is particularly important, Dietschy and colleagues note, to use these animal models to carefully differentiate the non-specific environmental and genetic effects on lifespan from treatments that have a direct effect on the genetic abnormality present in the disease and thus may promote survival.
The Journal of Lipid research
Corresponding Author: John M. Dietschy, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
New Method To Overcome Multiple Drug Resistant Diseases Developed By Stanford Researchers
Many drugs once considered Charles Atlases of the pharmaceutical realm have been reduced to the therapeutic equivalent of 97-pound weaklings as the diseases they once dispatched with ease have developed resistance to them.
The problem is well documented for antibiotics, although not confined to them. Chemotherapy drugs that were once highly effective when first used against a particular cancer now are often rendered near powerless when a patient's cancer resurges.
Even more devastating, when an organism develops resistance to one drug, it often becomes resistant to other drugs (known as multi-drug resistance), rendering not just one medication but a whole class of therapeutics useless against it.
But researchers at Stanford University have developed a method to get around one of the most common forms of resistance, thereby opening up some if not many resistant diseases to the reinvigorated fury of the medications that once laid them low. To do it, they took a tip from nature.
"Nature has developed all of this firepower for getting things into cells, and one of the ways is to create entities that are arginine-rich," said Paul Wender, the Bergstrom Professor of Chemistry at Stanford University. Arginine is an amino acid, the building block of proteins, and as such is found in virtually every cell in the human body, as well as other mammalian bodies.
Using such a common transporter to ferry a potent medication inside a resistant cell is a bit like recruiting your grandmother to cart a load of switchblade knives through customs. Indeed, Wender said, "Arginine-rich sequences appear to figure in the mechanisms by which many pathogens invade cells." Wender's team used a necklace of eight arginine molecules to surround the medication they worked with.
Wender and his colleagues figured out that a particular molecular subunit within arginine, called a guanidinium group, was what nature actually exploits to get foreign substances through cell membranes. Working with Taxol(r), a widely used chemotherapeutic agent, they attached a series of arginines with their associated guanidinium groups and tried it out against Taxol-resistant ovarian cancer cells implanted in mice. It worked.
"It's an exciting result to be able to take a drug known to work against cancer, but stymied by resistant cells, and restore it to effectiveness using an arginine transporter," Wender said. "This bodes well for use with other drugs that succumb to resistance."
A paper describing the work is scheduled to be published next week in the online Early Edition of the Proceedings of the National Academy of Sciences. Wender's group collaborated with that of Chris Contag, a professor of pediatrics and of microbiology and immunology at Stanford's School of Medicine, who is a co-author on the paper.
"Overcoming Taxol resistance is big. It's huge," said Nelson Teng, professor of obstetrics and gynecology at the Medical School. "In essence, the technology can be used to overcome one of the most challenging types of problems of drug resistance."
The type of drug resistance that Wender's work has overcome develops when pumps located in the membrane that encloses a cell become sensitized to a medication. It is one of the most common ways in which resistance manifests. The pumps, which normally capture and eject foreign material from a cell, are produced at higher levels in certain resistant cells and, because of their increased number, become more effective at tossing the drug molecules out.
"It is kind of like a bouncer," Wender said. "If you're not recognized as being part of the club, then you're kicked out." Resistant cells also create a lot more of the pumps than a normal cell would have.
Some researchers have tried dealing with this situation by adding another molecule to the mix to inhibit the pump, keeping it busy so the medication can slip in while the pumps are occupied with the decoy molecule. But if any of the molecules make their way into healthy cells, they can gum up the proper functioning of the pumps in those cells, too, adding to the litany of undesirable side effects that generally accompany chemotherapy.
Wender's group decided to see if they could take drugs to which diseases had become resistant and, by combining them with what they call "molecular transporters," get them in around the pump.
"If we think of the pump as being a bouncer for the cellular club, then effectively what we're doing is disguising one of these therapeutic agents to get it in through the back door or the side door," Wender said. "We're not even going to deal with the bouncer."
Therein lies what may be the greatest value of the work. The basic approach of bonding a medication to an arginine-rich transporter to slip it past the cellular sentries could, in theory, be used to get any of a host of medications into any cell that has developed the type of resistance involving increased numbers of export pumps.
"This could potentially be used with any drug which is effective but has a delivery problem," Teng said. "Not just Taxol."
That could include medications for diseases caused by antibiotic resistant bacteria, such as multi-drug resistant tuberculosis, or by drug resistant parasites such as malaria, as well as other types of cancer.
The arginine transporter manages to avoid ejection by slipping through the membrane of the cell in between the pumps. The key is the ability of arginine to form weak, temporary bonds with some of the molecules that reside in the membrane.
"As the transporter, with all these arginine guanidinium groups, approaches the cell, it basically does a handshake using hydrogen bonds with cell surface constituents that are in the membrane," Wender said. "In essence, it changes its physical properties by shaking hands with all these cell membrane components."
That change in physical properties effectively cloaks the arginine-Taxol complex, allowing it to slip past the sentries and into the cell. As it passes into the cell, the weak bonds it formed with the membrane components break and the transporter, with its therapeutic load, is free to roam inside the cell.
But after getting into the cell, the arginine-Taxol complex still has to break apart for the Taxol to do its job against the cancer cell. Wender's group achieved this by taking advantage of the presence of a molecule called glutathione, which is generally abundant inside cells and which in cancer cells tends to be present in higher levels than usual.
Glutathione is predisposed to attacking sulphur-sulphur bonds, so that is the bond the researchers used to hold the arginine and Taxol together. Once the arginine-Taxol complex is inside the cell, the glutathione can get to work hacking away at the sulphur bonds, and in the process, unwittingly release the compound that will spell its doom.
Because glutathione is relatively scarce outside of cells, the arginine transporter is effectively inert in that environment, so there are no side effects from having the arginine-Taxol complex moving through the patient's body. This is in stark contrast to the present situation, as many patients are extremely sensitive to the molecular vehicle that is currently used to administer ferried Taxol to the cancer cells.
The researchers achieved another breakthrough by tinkering with the form of the arginine used in their transporter. By altering certain aspects of the arginine, the researchers were able to control the rate at which glutathione slices and dices the arginine-Taxol complex.
This gives them an unprecedented ability to regulate the amount of medication that is active inside the patient at any point in time. To date, doctors have had to be content with injecting as high a dose of medication as patients can tolerate and then waiting as the effective amount in the patients slowly dwindled until they could safely inject more. This approach results in a repeated pattern of rapid spikes in the amount of medication in the system, followed by slow declines until the next spike. Ideally, doctors would like the patient to be continually experiencing the maximum tolerable dosage to keep the pressure on the cancer cells, killing them off as quickly and as thoroughly as possible. The arginine transporter makes this possible.
Ovarian cancer was chosen as the subject cancer for this study in part because it commonly develops resistance to Taxol, but also because of a low long-term success rate in treating it. The American Cancer Society estimates that in the United States alone there will be 21,650 diagnoses of ovarian cancer this year and 15,500 deaths from it.
"Ovarian cancer has a drug [Taxol] that works pretty well in the beginning. Seventy or eighty percent of the patients have a response," Teng said. "But it fails at the end because drug resistance develops."
Further studies need to be done to demonstrate the safety of arginine transporters before they can be used in this application in humans, Wender and Teng said. But the researchers already have positive safety data from tests of arginine-transporter technology in another application, one that does not involve drug resistance, so they are optimistic. The discovery of effective arginine transporters could be the key to treating ovarian cancer, as well as other diseases that develop drug resistance, more effectively.
Other co-authors of the paper in PNAS are Elena Dubikovskaya, a graduate student at the time this work was done and now a postdoctoral fellow at University of California-Berkeley; Steve Thorne, a postdoctoral fellow at the time this work was done and now on a faculty member at the University of Pittsburgh; and Thomas Pillow, a graduate student in chemistry.
Teng is working with Wender on other projects stemming from the work with Taxol but was not involved in the research described in this paper.
Source: Louis Bergeron
Stanford University
View drug information on Taxol.
The problem is well documented for antibiotics, although not confined to them. Chemotherapy drugs that were once highly effective when first used against a particular cancer now are often rendered near powerless when a patient's cancer resurges.
Even more devastating, when an organism develops resistance to one drug, it often becomes resistant to other drugs (known as multi-drug resistance), rendering not just one medication but a whole class of therapeutics useless against it.
But researchers at Stanford University have developed a method to get around one of the most common forms of resistance, thereby opening up some if not many resistant diseases to the reinvigorated fury of the medications that once laid them low. To do it, they took a tip from nature.
"Nature has developed all of this firepower for getting things into cells, and one of the ways is to create entities that are arginine-rich," said Paul Wender, the Bergstrom Professor of Chemistry at Stanford University. Arginine is an amino acid, the building block of proteins, and as such is found in virtually every cell in the human body, as well as other mammalian bodies.
Using such a common transporter to ferry a potent medication inside a resistant cell is a bit like recruiting your grandmother to cart a load of switchblade knives through customs. Indeed, Wender said, "Arginine-rich sequences appear to figure in the mechanisms by which many pathogens invade cells." Wender's team used a necklace of eight arginine molecules to surround the medication they worked with.
Wender and his colleagues figured out that a particular molecular subunit within arginine, called a guanidinium group, was what nature actually exploits to get foreign substances through cell membranes. Working with Taxol(r), a widely used chemotherapeutic agent, they attached a series of arginines with their associated guanidinium groups and tried it out against Taxol-resistant ovarian cancer cells implanted in mice. It worked.
"It's an exciting result to be able to take a drug known to work against cancer, but stymied by resistant cells, and restore it to effectiveness using an arginine transporter," Wender said. "This bodes well for use with other drugs that succumb to resistance."
A paper describing the work is scheduled to be published next week in the online Early Edition of the Proceedings of the National Academy of Sciences. Wender's group collaborated with that of Chris Contag, a professor of pediatrics and of microbiology and immunology at Stanford's School of Medicine, who is a co-author on the paper.
"Overcoming Taxol resistance is big. It's huge," said Nelson Teng, professor of obstetrics and gynecology at the Medical School. "In essence, the technology can be used to overcome one of the most challenging types of problems of drug resistance."
The type of drug resistance that Wender's work has overcome develops when pumps located in the membrane that encloses a cell become sensitized to a medication. It is one of the most common ways in which resistance manifests. The pumps, which normally capture and eject foreign material from a cell, are produced at higher levels in certain resistant cells and, because of their increased number, become more effective at tossing the drug molecules out.
"It is kind of like a bouncer," Wender said. "If you're not recognized as being part of the club, then you're kicked out." Resistant cells also create a lot more of the pumps than a normal cell would have.
Some researchers have tried dealing with this situation by adding another molecule to the mix to inhibit the pump, keeping it busy so the medication can slip in while the pumps are occupied with the decoy molecule. But if any of the molecules make their way into healthy cells, they can gum up the proper functioning of the pumps in those cells, too, adding to the litany of undesirable side effects that generally accompany chemotherapy.
Wender's group decided to see if they could take drugs to which diseases had become resistant and, by combining them with what they call "molecular transporters," get them in around the pump.
"If we think of the pump as being a bouncer for the cellular club, then effectively what we're doing is disguising one of these therapeutic agents to get it in through the back door or the side door," Wender said. "We're not even going to deal with the bouncer."
Therein lies what may be the greatest value of the work. The basic approach of bonding a medication to an arginine-rich transporter to slip it past the cellular sentries could, in theory, be used to get any of a host of medications into any cell that has developed the type of resistance involving increased numbers of export pumps.
"This could potentially be used with any drug which is effective but has a delivery problem," Teng said. "Not just Taxol."
That could include medications for diseases caused by antibiotic resistant bacteria, such as multi-drug resistant tuberculosis, or by drug resistant parasites such as malaria, as well as other types of cancer.
The arginine transporter manages to avoid ejection by slipping through the membrane of the cell in between the pumps. The key is the ability of arginine to form weak, temporary bonds with some of the molecules that reside in the membrane.
"As the transporter, with all these arginine guanidinium groups, approaches the cell, it basically does a handshake using hydrogen bonds with cell surface constituents that are in the membrane," Wender said. "In essence, it changes its physical properties by shaking hands with all these cell membrane components."
That change in physical properties effectively cloaks the arginine-Taxol complex, allowing it to slip past the sentries and into the cell. As it passes into the cell, the weak bonds it formed with the membrane components break and the transporter, with its therapeutic load, is free to roam inside the cell.
But after getting into the cell, the arginine-Taxol complex still has to break apart for the Taxol to do its job against the cancer cell. Wender's group achieved this by taking advantage of the presence of a molecule called glutathione, which is generally abundant inside cells and which in cancer cells tends to be present in higher levels than usual.
Glutathione is predisposed to attacking sulphur-sulphur bonds, so that is the bond the researchers used to hold the arginine and Taxol together. Once the arginine-Taxol complex is inside the cell, the glutathione can get to work hacking away at the sulphur bonds, and in the process, unwittingly release the compound that will spell its doom.
Because glutathione is relatively scarce outside of cells, the arginine transporter is effectively inert in that environment, so there are no side effects from having the arginine-Taxol complex moving through the patient's body. This is in stark contrast to the present situation, as many patients are extremely sensitive to the molecular vehicle that is currently used to administer ferried Taxol to the cancer cells.
The researchers achieved another breakthrough by tinkering with the form of the arginine used in their transporter. By altering certain aspects of the arginine, the researchers were able to control the rate at which glutathione slices and dices the arginine-Taxol complex.
This gives them an unprecedented ability to regulate the amount of medication that is active inside the patient at any point in time. To date, doctors have had to be content with injecting as high a dose of medication as patients can tolerate and then waiting as the effective amount in the patients slowly dwindled until they could safely inject more. This approach results in a repeated pattern of rapid spikes in the amount of medication in the system, followed by slow declines until the next spike. Ideally, doctors would like the patient to be continually experiencing the maximum tolerable dosage to keep the pressure on the cancer cells, killing them off as quickly and as thoroughly as possible. The arginine transporter makes this possible.
Ovarian cancer was chosen as the subject cancer for this study in part because it commonly develops resistance to Taxol, but also because of a low long-term success rate in treating it. The American Cancer Society estimates that in the United States alone there will be 21,650 diagnoses of ovarian cancer this year and 15,500 deaths from it.
"Ovarian cancer has a drug [Taxol] that works pretty well in the beginning. Seventy or eighty percent of the patients have a response," Teng said. "But it fails at the end because drug resistance develops."
Further studies need to be done to demonstrate the safety of arginine transporters before they can be used in this application in humans, Wender and Teng said. But the researchers already have positive safety data from tests of arginine-transporter technology in another application, one that does not involve drug resistance, so they are optimistic. The discovery of effective arginine transporters could be the key to treating ovarian cancer, as well as other diseases that develop drug resistance, more effectively.
Other co-authors of the paper in PNAS are Elena Dubikovskaya, a graduate student at the time this work was done and now a postdoctoral fellow at University of California-Berkeley; Steve Thorne, a postdoctoral fellow at the time this work was done and now on a faculty member at the University of Pittsburgh; and Thomas Pillow, a graduate student in chemistry.
Teng is working with Wender on other projects stemming from the work with Taxol but was not involved in the research described in this paper.
Source: Louis Bergeron
Stanford University
View drug information on Taxol.
The Tongue Is The Start Of The Route To Obesity
Obesity gradually numbs the taste sensation of rats to sweet foods and drives them to consume larger and ever-sweeter meals, according to neuroscientists. Findings from the Penn State study could uncover a critical link between taste and body weight, and reveal how flab hooks the brain on sugary food.
"When you have a reduced sensitivity to palatable foods, you tend to consume it in higher amounts," said Andras Hajnal, associate professor of neural and behavioral sciences at Penn State College of Medicine. "It is a vicious circle."
Previous studies have suggested that obese persons are less sensitive to sweet taste and crave sweet foods more than lean people. However, little is known about the specific differences between obese and lean individuals in their sense of taste and the pleasure they derive from sweet foods.
Hajnal and his Penn State colleague Peter Kovacs, a post-doctoral fellow, investigated these differences by studying the taste responses of two strains -- OLETF and LETO rats.
Compared to the lean and healthy LETO rats, the taste responses in OLETF rats mirror those in obese humans. These rats have normal body weight at first, but they tend to chronically overeat due to a missing satiety signal, become obese and develop diabetes. The obese rats also show an increased preference for sweet foods and also are willing to work harder to obtain sweet solutions as a reward for their learning.
"When you have excess body weight, the brain is supposed to tell you not to eat more, or not choose high caloric meals" said Hajnal. "But this control apparently fails and thus the obesity epidemic is rising, and we want to find out how the sense of taste drives up food intake."
The researchers implanted electrodes in the rodents' brains to record the firing of nerve cells when the rats' tongues were exposed to various tastes -- salt, citric acid, plain water and six different concentrations of sucrose.
Hajnal and Kovacs specifically looked at differences in processing taste in the pontine parabrachial nucleus (PBN), a part of the brain that uses nerve cells to relay information from the surface of the tongue to the brain.
"We found that compared to the LETO rats, the OLETF rats had about 50 percent fewer neurons firing when their tongues were exposed to sucrose, suggesting that obese rats are overall less sensitive to sucrose," explained Hajnal, whose findings appeared in a recent issue of the Journal of Neurophysiology. The response to salt was the same for both strains.
However, when the obese rats were fed a stronger concentration of sucrose, their nerve cells fired more vigorously than in the lean rats. In other words, obese rats have a weaker response to weak concentrations and a stronger response to strong concentrations.
"These findings tell us that there is a difference in activation of neurons between lean and obese rats when they are exposed varying concentrations of sucrose," noted Hajnal. "If you sense sweetness less, you may be inclined to eat sweeter foods."
The Penn State researchers believe that the increased consumption of sweet foods over time could be influencing the brain's reward center by relaying progressively weaker nerve signals, which affects the perception of taste of the meals through the PBN.
In obese humans, an increase in the weight-height ratio is usually accompanied by a decrease in dopamine, which is a neurotransmitter associated with the brain's pleasure system.
"In these obese rats, like in humans, the dopamine system is suppressed and it is very possible that the obese rats are seeking a hedonistic experience or reward by eating larger meals and when they have a chance they also eat more sweets," Hajnal added.
The findings linking taste responses and obesity could hold an important message for a condition that affects more than 60 percent of adult Americans.
For instance, Hajnal points to an ever-increasing amount of fat and sugar in processed foods. The enhanced taste of these foods, he says, stimulates our taste and food reward neurons on a chronic basis, making them less sensitive over time. And what do we do when this happens?
"Instead of eating less, we seek out higher palatability," Hajnal explained. "We simply start putting an extra spoonful of sugar in our coffee."
Source: Amitabh Avasthi
Penn State
"When you have a reduced sensitivity to palatable foods, you tend to consume it in higher amounts," said Andras Hajnal, associate professor of neural and behavioral sciences at Penn State College of Medicine. "It is a vicious circle."
Previous studies have suggested that obese persons are less sensitive to sweet taste and crave sweet foods more than lean people. However, little is known about the specific differences between obese and lean individuals in their sense of taste and the pleasure they derive from sweet foods.
Hajnal and his Penn State colleague Peter Kovacs, a post-doctoral fellow, investigated these differences by studying the taste responses of two strains -- OLETF and LETO rats.
Compared to the lean and healthy LETO rats, the taste responses in OLETF rats mirror those in obese humans. These rats have normal body weight at first, but they tend to chronically overeat due to a missing satiety signal, become obese and develop diabetes. The obese rats also show an increased preference for sweet foods and also are willing to work harder to obtain sweet solutions as a reward for their learning.
"When you have excess body weight, the brain is supposed to tell you not to eat more, or not choose high caloric meals" said Hajnal. "But this control apparently fails and thus the obesity epidemic is rising, and we want to find out how the sense of taste drives up food intake."
The researchers implanted electrodes in the rodents' brains to record the firing of nerve cells when the rats' tongues were exposed to various tastes -- salt, citric acid, plain water and six different concentrations of sucrose.
Hajnal and Kovacs specifically looked at differences in processing taste in the pontine parabrachial nucleus (PBN), a part of the brain that uses nerve cells to relay information from the surface of the tongue to the brain.
"We found that compared to the LETO rats, the OLETF rats had about 50 percent fewer neurons firing when their tongues were exposed to sucrose, suggesting that obese rats are overall less sensitive to sucrose," explained Hajnal, whose findings appeared in a recent issue of the Journal of Neurophysiology. The response to salt was the same for both strains.
However, when the obese rats were fed a stronger concentration of sucrose, their nerve cells fired more vigorously than in the lean rats. In other words, obese rats have a weaker response to weak concentrations and a stronger response to strong concentrations.
"These findings tell us that there is a difference in activation of neurons between lean and obese rats when they are exposed varying concentrations of sucrose," noted Hajnal. "If you sense sweetness less, you may be inclined to eat sweeter foods."
The Penn State researchers believe that the increased consumption of sweet foods over time could be influencing the brain's reward center by relaying progressively weaker nerve signals, which affects the perception of taste of the meals through the PBN.
In obese humans, an increase in the weight-height ratio is usually accompanied by a decrease in dopamine, which is a neurotransmitter associated with the brain's pleasure system.
"In these obese rats, like in humans, the dopamine system is suppressed and it is very possible that the obese rats are seeking a hedonistic experience or reward by eating larger meals and when they have a chance they also eat more sweets," Hajnal added.
The findings linking taste responses and obesity could hold an important message for a condition that affects more than 60 percent of adult Americans.
For instance, Hajnal points to an ever-increasing amount of fat and sugar in processed foods. The enhanced taste of these foods, he says, stimulates our taste and food reward neurons on a chronic basis, making them less sensitive over time. And what do we do when this happens?
"Instead of eating less, we seek out higher palatability," Hajnal explained. "We simply start putting an extra spoonful of sugar in our coffee."
Source: Amitabh Avasthi
Penn State
'Fusion' Protein Found By Johns Hopkins Researchers - Without It, Muscle Cells 'refuse To Fuse'
Working with fruit flies, scientists at Johns Hopkins have discovered a protein required for two neighboring cells to fuse and become one "super cell."
Most cells enjoy their singular existence, but the strength and flexibility of muscles relies on hundreds or even thousands of super cells that make large-scale motion smooth and coordinated, such as flexion of a bicep.
The newly discovered protein, dubbed Solitary, coordinates the movement of tiny molecular delivery trucks to a cell's surface. Cells that lack Solitary stay, well, solitary. "They refuse to fuse," says Hopkins assistant professor of molecular biology and genetics Elizabeth Chen, Ph.D., whose report on the work is online this week in Developmental Cell.
Chen and her team studied fruit fly embryo muscles to find the molecular signals that tell two neighboring cells to join as one, plucking out for further study those embryos containing cells that refused to fuse.
They then compared the genetic sequences from healthy embryos with sequences from defective embryos to locate differences and identify the genes responsible for unfused muscle cells. In the process, they identified Solitary.
Chen's team next made a tool to see the Solitary protein, enabling them to track its localization under a fluorescent microscope. At each future fusion point between cells that they examined in the fly muscles, they saw concentrations of glowing clumps of Solitary protein.
"As we uncover more of the players in cell fusion, we get closer to manipulating fusion for our benefit," Chen adds. Muscular dystrophy, for example, might be treated by injecting into patients healthy muscle cells that are designed to fuse efficiently with the diseased muscles, saving the diseased cells from deteriorating.
They also discovered that Solitary protein is attached to the cell's skeleton. "It was so bizarre to see Solitary - something meant to regulate the cell's internal structure - to be involved in the external events of cell fusion," says Chen.
But in addition to structural support, the cell's "skeleton" provides an internal railway of sorts, along which other proteins and molecules can move. Indeed, the researchers saw that while normal cells were able to shuttle tiny storage compartments within the cell - presumably holding important molecular tools needed for cell fusion - to the fusion site, these storage compartments were scattered haphazardly, seemingly lost in the cellular wilderness, in cells lacking Solitary.
When two neighboring cells fuse, they need to break down the barrier between them, explains Chen. It turns out that the Solitary protein marks where that break is happening and subsequently tells the cell where to build its skeleton railway. "In this role, Solitary acts not like the delivery truck, but more like a construction site foreman," says Chen. "It's told where the cell barrier needs to be broken, then directs the building of a delivery road so that the molecular supplies can be brought to the fusion site."
The research was funded by the National Institutes of Health, the American Heart Association, the Edward Mallinckrodt Jr. Foundation, March of Dimes, Packard Foundation and Searle Scholars Program.
Authors on the paper are Sangjoon Kim, Khurts Shilagardi, Shiliang Zhang, Sabrina Hong, Kristen Sens, Jinyan Bo, Guillermo Gonzalez and Elizabeth Chen, all of Johns Hopkins.
On the Web:
developmentalcell/
mbg.jhmi/
Contact: Audrey Huang
Johns Hopkins Medical Institutions
Most cells enjoy their singular existence, but the strength and flexibility of muscles relies on hundreds or even thousands of super cells that make large-scale motion smooth and coordinated, such as flexion of a bicep.
The newly discovered protein, dubbed Solitary, coordinates the movement of tiny molecular delivery trucks to a cell's surface. Cells that lack Solitary stay, well, solitary. "They refuse to fuse," says Hopkins assistant professor of molecular biology and genetics Elizabeth Chen, Ph.D., whose report on the work is online this week in Developmental Cell.
Chen and her team studied fruit fly embryo muscles to find the molecular signals that tell two neighboring cells to join as one, plucking out for further study those embryos containing cells that refused to fuse.
They then compared the genetic sequences from healthy embryos with sequences from defective embryos to locate differences and identify the genes responsible for unfused muscle cells. In the process, they identified Solitary.
Chen's team next made a tool to see the Solitary protein, enabling them to track its localization under a fluorescent microscope. At each future fusion point between cells that they examined in the fly muscles, they saw concentrations of glowing clumps of Solitary protein.
"As we uncover more of the players in cell fusion, we get closer to manipulating fusion for our benefit," Chen adds. Muscular dystrophy, for example, might be treated by injecting into patients healthy muscle cells that are designed to fuse efficiently with the diseased muscles, saving the diseased cells from deteriorating.
They also discovered that Solitary protein is attached to the cell's skeleton. "It was so bizarre to see Solitary - something meant to regulate the cell's internal structure - to be involved in the external events of cell fusion," says Chen.
But in addition to structural support, the cell's "skeleton" provides an internal railway of sorts, along which other proteins and molecules can move. Indeed, the researchers saw that while normal cells were able to shuttle tiny storage compartments within the cell - presumably holding important molecular tools needed for cell fusion - to the fusion site, these storage compartments were scattered haphazardly, seemingly lost in the cellular wilderness, in cells lacking Solitary.
When two neighboring cells fuse, they need to break down the barrier between them, explains Chen. It turns out that the Solitary protein marks where that break is happening and subsequently tells the cell where to build its skeleton railway. "In this role, Solitary acts not like the delivery truck, but more like a construction site foreman," says Chen. "It's told where the cell barrier needs to be broken, then directs the building of a delivery road so that the molecular supplies can be brought to the fusion site."
The research was funded by the National Institutes of Health, the American Heart Association, the Edward Mallinckrodt Jr. Foundation, March of Dimes, Packard Foundation and Searle Scholars Program.
Authors on the paper are Sangjoon Kim, Khurts Shilagardi, Shiliang Zhang, Sabrina Hong, Kristen Sens, Jinyan Bo, Guillermo Gonzalez and Elizabeth Chen, all of Johns Hopkins.
On the Web:
developmentalcell/
mbg.jhmi/
Contact: Audrey Huang
Johns Hopkins Medical Institutions
Industry Teams Receive Awards From Michael J. Fox Foundation
As part of its ongoing efforts to do whatever it takes to speed delivery of transformative treatments and a cure for Parkinson's disease, The Michael J. Fox Foundation for Parkinson's Research has awarded up to $3 million in total funding to four industry teams seeking to push potential new PD treatments closer to the clinic. The awards were granted under MJFF's Therapeutics Development Initiative (TDI) program. Open exclusively to industry researchers, TDI is the cornerstone of the Foundation's efforts to expand industry investment in PD drug development. Through TDI, the Foundation shares the risk of drug development, thus helping to speed companies abilities to reach critical decision points for Parkinson's disease projects. Each of the four TDI grant awardees listed below will undertake research aimed at solving critical gaps in the development of new PD treatments.
"While industry plays a vital role in shepherding new therapeutics through the development process toward clinical trials and patients, competitive pressures and tough allocation decisions too often get in the way of making the kinds of 'big bets' necessary for breakthrough developments" said Katie Hood, CEO of The Michael J. Fox Foundation. "By funding industry partners directly, TDI seeks to advance promising treatments that might otherwise get stuck at the pre-clinical stage. Our capital may be comparatively modest, but it can serve as a 'carrot' to leverage companies expertise and infrastructure and speed the development of therapeutics that could have an immense impact on patients' quality of life."
While the Foundation has funded industry researchers since its inception, the Therapeutics Development Initiative was launched in 2006 as part of a larger initiative to capture the attention and imagination of company decision-makers and encourage them to allocate resources to Parkinson's projects. To date, of the approximately $21 million the Foundation has committed in total funding to industry, almost a third (nearly $8 million) has gone to 14 projects under TDI. The current round of awardees will focus on developing and optimizing new treatments targeting alpha-synuclein toxicity; chronic inflammation; trophic factors; and mitochondrial dysfunction.
Christine Bulawa, PhD, of FoldRx Pharmaceuticals Inc., will work to develop a disease-modifying drug that could block the toxicity associated with clumping of the protein alpha-synuclein, a hallmark of PD pathology. Dr. BulawaВЎ's team has identified chemical compounds that protect neurons from alpha-synuclein toxicity and will now work with the compounds in a rodent model of Parkinson's. The researchers hope to identify promising small molecules that, with further optimization, can be developed into drug candidates to be tested in PD patients in clinical trials.
Chronic inflammation plays a role in the death of the dopamine-producing neurons that are lost in Parkinson's disease. Patrick Flood, PhD, of TheraLogics, Inc., and his group will test compounds that specifically target the inflammatory pathway in a PD animal model to determine whether certain drugs can protect against this neuronal loss. The team will assess whether blocking inflammation reverses destruction of dopamine-producing neurons, and actually leads to regeneration of these cells within the brain, to determine the most effective dose and timing for therapeutic intervention.
The blood-brain barrier is a thin layer of tightly packed cells separating the central nervous system from the body's bloodstream. This layer is crucial to protecting the brain from foreign substances, but also poses a major challenge in delivering potentially therapeutic treatments via orally administered drugs. Antonia Orsi, PhD, and her team from Phytopharm have developed a small orally active molecule that crosses the blood-brain barrier. In vivo and in vitro, the molecule increases levels of trophic factors, specialized proteins that potently promote survival of neurons. The team has already demonstrated that the compound can increase the number of dopaminergic neurons in a mouse model of PD. The goal now is to gain greater understanding of the neurorestorative properties of this compound in mice and, if successful, test the compound in a primate model of Parkinson's disease.
Mitochondria are the "energy factories" of body cells. It is believed that mitochondrial function is decreased in people with Parkinson's disease and that mitochondrial toxins induce parkinsonian symptoms in animal models. Rebecca Pruss, PhD, and her colleagues at Trophos are developing unique compounds that improve mitochondrial function and that are currently being evaluated in patients for the treatment of ALS and diabetic neuropathy. Dr. Pruss will test whether these compounds are neuroprotective in an animal model of Parkinson's disease.
Grant abstracts and researcher bios for all projects are available on the Foundation's Web site, michaeljfox/.
About The Michael J. Fox Foundation
The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease through an aggressively funded research agenda. To date, the Foundation has funded more than $115 million in research directly or through partnerships.
Source: Dana Barde
The Michael J. Fox Foundation for Parkinson's Research
"While industry plays a vital role in shepherding new therapeutics through the development process toward clinical trials and patients, competitive pressures and tough allocation decisions too often get in the way of making the kinds of 'big bets' necessary for breakthrough developments" said Katie Hood, CEO of The Michael J. Fox Foundation. "By funding industry partners directly, TDI seeks to advance promising treatments that might otherwise get stuck at the pre-clinical stage. Our capital may be comparatively modest, but it can serve as a 'carrot' to leverage companies expertise and infrastructure and speed the development of therapeutics that could have an immense impact on patients' quality of life."
While the Foundation has funded industry researchers since its inception, the Therapeutics Development Initiative was launched in 2006 as part of a larger initiative to capture the attention and imagination of company decision-makers and encourage them to allocate resources to Parkinson's projects. To date, of the approximately $21 million the Foundation has committed in total funding to industry, almost a third (nearly $8 million) has gone to 14 projects under TDI. The current round of awardees will focus on developing and optimizing new treatments targeting alpha-synuclein toxicity; chronic inflammation; trophic factors; and mitochondrial dysfunction.
Christine Bulawa, PhD, of FoldRx Pharmaceuticals Inc., will work to develop a disease-modifying drug that could block the toxicity associated with clumping of the protein alpha-synuclein, a hallmark of PD pathology. Dr. BulawaВЎ's team has identified chemical compounds that protect neurons from alpha-synuclein toxicity and will now work with the compounds in a rodent model of Parkinson's. The researchers hope to identify promising small molecules that, with further optimization, can be developed into drug candidates to be tested in PD patients in clinical trials.
Chronic inflammation plays a role in the death of the dopamine-producing neurons that are lost in Parkinson's disease. Patrick Flood, PhD, of TheraLogics, Inc., and his group will test compounds that specifically target the inflammatory pathway in a PD animal model to determine whether certain drugs can protect against this neuronal loss. The team will assess whether blocking inflammation reverses destruction of dopamine-producing neurons, and actually leads to regeneration of these cells within the brain, to determine the most effective dose and timing for therapeutic intervention.
The blood-brain barrier is a thin layer of tightly packed cells separating the central nervous system from the body's bloodstream. This layer is crucial to protecting the brain from foreign substances, but also poses a major challenge in delivering potentially therapeutic treatments via orally administered drugs. Antonia Orsi, PhD, and her team from Phytopharm have developed a small orally active molecule that crosses the blood-brain barrier. In vivo and in vitro, the molecule increases levels of trophic factors, specialized proteins that potently promote survival of neurons. The team has already demonstrated that the compound can increase the number of dopaminergic neurons in a mouse model of PD. The goal now is to gain greater understanding of the neurorestorative properties of this compound in mice and, if successful, test the compound in a primate model of Parkinson's disease.
Mitochondria are the "energy factories" of body cells. It is believed that mitochondrial function is decreased in people with Parkinson's disease and that mitochondrial toxins induce parkinsonian symptoms in animal models. Rebecca Pruss, PhD, and her colleagues at Trophos are developing unique compounds that improve mitochondrial function and that are currently being evaluated in patients for the treatment of ALS and diabetic neuropathy. Dr. Pruss will test whether these compounds are neuroprotective in an animal model of Parkinson's disease.
Grant abstracts and researcher bios for all projects are available on the Foundation's Web site, michaeljfox/.
About The Michael J. Fox Foundation
The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease through an aggressively funded research agenda. To date, the Foundation has funded more than $115 million in research directly or through partnerships.
Source: Dana Barde
The Michael J. Fox Foundation for Parkinson's Research
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