In China, the incidence of liver cirrhosis is still high. Liver cirrhosis results from fibrosis. If treated properly at fibrosis stage, cirrhosis can be prevented. However, no effective antifibrosis drugs are available at present. Several lines of evidences suggest that oxidative stress plays an important role in the etiopathogenesis of hepatic fibrosis. Melatonin can protect cells, tissues, and organs against oxidative damage induced by a variety of free-radical-generating agents and processes.
A research team led by Professor Jian-Ming Xu from the First Affiliated Hospital of Anhui Medical University, China evaluated the possible fibrosuppressant effect of melatonin in rat. Their study was published on March 28, 2009 in the World Journal of Gastroenterology.
In this study, hepatic fibrosis in rats was successfully induced by subcutaneous injection of sterile CCl4 twice weekly for a total of 12 wk. At the beginning of injection of CCl4, melatonin (2.5, 5, 10 mg/kg body weight) was intraperitoneally administered to the rats daily for 12 wk. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. The serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) were used to evaluate the hepatic injury. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA) and glutathione peroxidase (GPx) in liver homogenates. Serum hyaluronic acid (HA), laminin (LN), and procollagen 3 N-terminal peptide (P3NP) were determined as serum markers of hepatic fibrogenesis.
Their results suggested that treatment with melatonin (10 mg/kg) could decrease the scores of hepatic fibrosis grading, reduced the contents of HA, LN in serum and Hydroxyproline (HYP) in liver, treatment with melatonin (5,10 mg/kg ) could decrease serum levels of ALT, AST and blocked the increase in MDA in rats with hepatic injury caused by CCl4.
Their result indicated melatonin could ameliorate CCl4-induced hepatic fibrosis in rats. The protective effect of melatonin on hepatic fibrosis may be related to its antioxidant activities. This may provide a basis for further studies on the potentially protective effect of melatonin on liver function in cirrhotic patients
Notes:
Reference: Hong RT, Xu JM, Mei Q. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats. World J Gastroenterol 2009; 15(12): 1452-1458
wjgnet/1007-9327/15/1452.asp
Correspondence to: Jian-Ming Xu, Professor, Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Lai-Fu Li
World Journal of Gastroenterology
понедельник, 6 июня 2011 г.
Too Much Of A Charge-Switching Enzyme Causes Symptoms Of Multiple Sclerosis And Related Disorders In Mouse Models
A new study highlights the role of a charge-switching enzyme in nervous system deficits characteristic of multiple sclerosis and other related neurological illness.
Multiple sclerosis (MS) is one of several diseases in which myelin - the insulator for electrical signaling in the nervous system - breaks down and causes severe deficits in brain and nerve function. Much like the rubber insulation on an electrical cord, myelin surrounds long projections from the body of a neuron, and allows signals to travel down the cell with speed and efficiency. Patients with MS and other "de-myelinating" diseases therefore suffer deficits in balance, coordination, and movement, as well as sensory disturbances, from the loss of this neuronal insulation.
A major research initiative in treating these diseases is identifying the molecular factors and changes that lead to myelin breakdown. In a new study published in Disease Models & Mechanisms (DMM), dmm.biologists/, a team of Canadian researchers report on a new mouse model of disease which will help in understanding how demyelination occurs. Previous research had identified that an enzyme known as peptidylarginine deiminase 2, or PAD2, is increased in patients with MS, and that PAD2 switches a charge on a protein key to myelin stability. Therefore, Abdiwahab A. Musse and colleagues at the University of Guelph and the Hospital for Sick Children in Ontario created a genetically modified mouse expressing too much of an enzyme known as PAD2. They found that these mice had significant loss of myelin, and also have behavioral deficits, such as abnormal movement, balance, and coordination.
Not only does this work present a new mouse model to study demyleinating disease, but it also stresses the importance of PAD in maintaining myelin integrity. Their work highlights PAD as a potential therapeutic target, as well as a potential marker for early detection of MS and other diseases characterized by a loss of myelin.
Commentary on this work by researchers Mario Moscarello and Fabrizio Mastronardi will be featured in the DMM Podcast for issue 4/5 of DMM. Podcasts are available via the DMM website at: dmm.biologists>dmm.biologists/.
The report was written by Abdiwahab A. Musse, Dorothee Bienzle, Roberto Poma, and George Harauz at the University of Guelph in Guelph, Ontario, and Zhen Li, Cameron A. Ackerley, Helena Lei, Mario A. Moscarello and Fabrizio G. Mastronardi at the Hospital for Sick Children in Toronto, Ontario. The report is published in the November/December issue of a new research journal, Disease Models & Mechanisms (DMM), published by The Company of Biologists, a non-profit based in Cambridge, UK.
About Disease Models & Mechanisms:
Disease Models & Mechanisms (DMM) is a new research journal publishing both primary scientific research, as well as review articles, editorials, and research highlights. The journal's mission is to provide a forum for clinicians and scientists to discuss basic science and clinical research related to human disease, disease detection and novel therapies. DMM is published by the Company of Biologists, a non-profit organization based in Cambridge, UK.
The Company also publishes the international biology research journals Development, Journal of Cell Science, and The Journal of Experimental Biology. In addition to financing these journals, the Company provides grants to scientific societies and supports other activities including travelling fellowships for junior scientists, workshops and conferences. The world's poorest nations receive free and unrestricted access to the Company's journals.
Source: Donna Perry
The Company of Biologists
Multiple sclerosis (MS) is one of several diseases in which myelin - the insulator for electrical signaling in the nervous system - breaks down and causes severe deficits in brain and nerve function. Much like the rubber insulation on an electrical cord, myelin surrounds long projections from the body of a neuron, and allows signals to travel down the cell with speed and efficiency. Patients with MS and other "de-myelinating" diseases therefore suffer deficits in balance, coordination, and movement, as well as sensory disturbances, from the loss of this neuronal insulation.
A major research initiative in treating these diseases is identifying the molecular factors and changes that lead to myelin breakdown. In a new study published in Disease Models & Mechanisms (DMM), dmm.biologists/, a team of Canadian researchers report on a new mouse model of disease which will help in understanding how demyelination occurs. Previous research had identified that an enzyme known as peptidylarginine deiminase 2, or PAD2, is increased in patients with MS, and that PAD2 switches a charge on a protein key to myelin stability. Therefore, Abdiwahab A. Musse and colleagues at the University of Guelph and the Hospital for Sick Children in Ontario created a genetically modified mouse expressing too much of an enzyme known as PAD2. They found that these mice had significant loss of myelin, and also have behavioral deficits, such as abnormal movement, balance, and coordination.
Not only does this work present a new mouse model to study demyleinating disease, but it also stresses the importance of PAD in maintaining myelin integrity. Their work highlights PAD as a potential therapeutic target, as well as a potential marker for early detection of MS and other diseases characterized by a loss of myelin.
Commentary on this work by researchers Mario Moscarello and Fabrizio Mastronardi will be featured in the DMM Podcast for issue 4/5 of DMM. Podcasts are available via the DMM website at: dmm.biologists>dmm.biologists/.
The report was written by Abdiwahab A. Musse, Dorothee Bienzle, Roberto Poma, and George Harauz at the University of Guelph in Guelph, Ontario, and Zhen Li, Cameron A. Ackerley, Helena Lei, Mario A. Moscarello and Fabrizio G. Mastronardi at the Hospital for Sick Children in Toronto, Ontario. The report is published in the November/December issue of a new research journal, Disease Models & Mechanisms (DMM), published by The Company of Biologists, a non-profit based in Cambridge, UK.
About Disease Models & Mechanisms:
Disease Models & Mechanisms (DMM) is a new research journal publishing both primary scientific research, as well as review articles, editorials, and research highlights. The journal's mission is to provide a forum for clinicians and scientists to discuss basic science and clinical research related to human disease, disease detection and novel therapies. DMM is published by the Company of Biologists, a non-profit organization based in Cambridge, UK.
The Company also publishes the international biology research journals Development, Journal of Cell Science, and The Journal of Experimental Biology. In addition to financing these journals, the Company provides grants to scientific societies and supports other activities including travelling fellowships for junior scientists, workshops and conferences. The world's poorest nations receive free and unrestricted access to the Company's journals.
Source: Donna Perry
The Company of Biologists
Prestigious Early Career Award Received By Clemson Bioengineer
Ning Zhang, assistant professor of bioengineering at Clemson University and the CU-MUSC Bioengineering Program, has received the prestigious 2008 Early Career Translational Research Award from the Wallace H. Coulter Foundation.
The foundation judged Zhang's research on an injectable hydrogel-based system for the treatment of stroke to be a highly promising technology that can progress towards commercial development and clinical practice. Zhang proposed the injectable hydrogel system to assist stem cell therapy for stroke treatment.
"This award exemplifies the strong leadership of Dr. Zhang in translational biomaterials research based on outstanding basic science," said Martine LaBerge, chair of Clemson's bioengineering department. "Our goal as bioengineers is to get potential life-saving treatments such as this from the research lab to the patient in an expedient manner."
The Early Career Translational Research Awards support biomedical engineering research that is translational in nature and encourage and assist eligible biomedical engineering investigators as they establish themselves in academic research careers with two years of funding.
Zhang's research on neurobioengineering has also been recognized by the 2007 Department of Defense Post-Traumatic Stress Disorder/Traumatic Brain Injury Research Program of the Office of the Congressionally Directed Medical Research Programs (CDMRP) with a Concept Award on "Brain Tissue Regeneration After Traumatic Brain Injury."
The Wallace H. Coulter Foundation is a private, nonprofit foundation in Miami dedicated to improving human healthcare by supporting translational research in biomedical engineering. Recipients of the Early Career Translational Research Awards are full-time, tenure-track faculty members with a primary appointment in biomedical engineering. They have received their doctoral degree no more than six years prior to their application, and they held a rank no higher than assistant professor at the time of application.
Wallace H. Coulter was an engineer, inventor and entrepreneur who applied engineering principles to biomedical problems. He founded Coulter Corp., which developed and marketed the first automated blood cell counters and flow cytometers, instruments that revolutionized healthcare diagnostics and therapeutics. Believing that the contributions of engineers to solving biomedical problems were generally under-recognized, Coulter mentored and encouraged young engineers to dream, take risks and be innovative.
Source: Martine LaBerge
Clemson University
The foundation judged Zhang's research on an injectable hydrogel-based system for the treatment of stroke to be a highly promising technology that can progress towards commercial development and clinical practice. Zhang proposed the injectable hydrogel system to assist stem cell therapy for stroke treatment.
"This award exemplifies the strong leadership of Dr. Zhang in translational biomaterials research based on outstanding basic science," said Martine LaBerge, chair of Clemson's bioengineering department. "Our goal as bioengineers is to get potential life-saving treatments such as this from the research lab to the patient in an expedient manner."
The Early Career Translational Research Awards support biomedical engineering research that is translational in nature and encourage and assist eligible biomedical engineering investigators as they establish themselves in academic research careers with two years of funding.
Zhang's research on neurobioengineering has also been recognized by the 2007 Department of Defense Post-Traumatic Stress Disorder/Traumatic Brain Injury Research Program of the Office of the Congressionally Directed Medical Research Programs (CDMRP) with a Concept Award on "Brain Tissue Regeneration After Traumatic Brain Injury."
The Wallace H. Coulter Foundation is a private, nonprofit foundation in Miami dedicated to improving human healthcare by supporting translational research in biomedical engineering. Recipients of the Early Career Translational Research Awards are full-time, tenure-track faculty members with a primary appointment in biomedical engineering. They have received their doctoral degree no more than six years prior to their application, and they held a rank no higher than assistant professor at the time of application.
Wallace H. Coulter was an engineer, inventor and entrepreneur who applied engineering principles to biomedical problems. He founded Coulter Corp., which developed and marketed the first automated blood cell counters and flow cytometers, instruments that revolutionized healthcare diagnostics and therapeutics. Believing that the contributions of engineers to solving biomedical problems were generally under-recognized, Coulter mentored and encouraged young engineers to dream, take risks and be innovative.
Source: Martine LaBerge
Clemson University
TGen And Geisinger Health System Announce Strategic Partnership
The Translational Genomics Research Institute (TGen) and Geisinger Health System have announced the signing of a strategic research agreement that provides for a focused look at the gaps in clinical medicine where biomedical research can make a difference.
One of the first projects will focus on the causes of obesity, diabetes and other metabolic conditions. Researchers plan to look at the possible genetic reasons why so many Americans are overweight, and why diet, exercise and, specifically, bariatric surgery may fail to significantly reduce excess weight in some patients.
TGen, a non-profit biomedical research institute based in Phoenix, will pair its genomic and proteomic research expertise with the clinical excellence and research expertise of Geisinger, a non-profit medical and insurance provider based in Danville, Pa.
Geisinger's strength is its integrated healthcare delivery model, nontransitory population and advanced electronic health record (EHR) with nearly two decades of data. In addition to providing the clinical underpinnings for the study of obesity, the data within the EHR will provide researchers the evidence they need to make discoveries in future projects centered on cancer and other serious diseases.
"Merging Geisinger's wealth of clinical information with our genomic and proteomic expertise should provide researchers a richer framework for exploring the genetic origins of disease, and hopefully lead to improved treatments and outcomes," said Dr. Jeffrey Trent, Ph.D., TGen's President and Research Director.
TGen emphasizes a translational research process intended to quickly turn laboratory discoveries into new drugs and other treatments that can benefit patients, a goal shared by Geisinger.
"Given our unique research structure and a patient population that overwhelmingly supports cutting-edge research, I am confident that this partnership will allow us to test and apply new clinical translation theories to patient care," said Glenn D. Steele, Jr., M.D., Ph.D., Geisinger's President and CEO. "I look forward to the results of this first study, as I am confident we can greatly improve the outcomes for individuals coping with obesity and its many associated complications."
According to 2009 Census data, nearly one-third of the U.S. adult population is overweight and considered obese. The impact of obesity on one's health is great, often leading to a shortened lifespan. A disease, obesity is not always caused by overeating or lack of exercise, and research has shown there is often an underlying genetic component leading to excess weight gain.
David Carey, Ph.D., Director of the Sigfried and Janet Weis Center for Research, located on the campus of the Geisinger Medical Center, agreed that the collaboration should advance patient care. "Identification of patients at risk for chronic metabolic diseases would provide enormous benefit to health care. Geisinger's ability to obtain detailed, electronic health information in real time for a large, stable patient population will significantly accelerate this research effort."
Johanna DiStefano, Ph.D., Director of TGen's Diabetes, Cardiovascular & Metabolic Diseases Division, will lead TGen's efforts to understand the genetic basis of obesity and liver disease. She said research strategies would capitalize on the synergistic strengths of a large multidisciplinary research program in obesity at Geisinger. "I am confident that the long-term results of this collaboration will yield improved diagnostic and therapeutic outcomes for countless individuals suffering from chronic metabolic diseases."
TGen also plans to bring to bear its collaboration with the Partnership for Personalized Medicine (PPM), which includes TGen, Arizona State University's Biodesign Institute and the Fred Hutchinson Cancer Research Center. The PPM's mission is to improve medical outcomes and reduced costs through more effective diagnosis of disease risk, early stage, and matching patients to therapies.
"Working with Geisinger will provide yet another significant opportunity for the Partnership for Personalized Medicine to provide better evidence to meet the specific medical needs of individual patients," said Lee Hartwell, Ph.D., a 2001 Nobel laureate and Executive Committee Chairman of PPM.
The research partnership between TGen and Geisinger will also address some of the nation's other critical health challenges. Preliminary discussions covered such research areas as genetic variations that predispose individuals to disease, congestive heart failure, abdominal aortic aneurysms, and the potential side effects of prescription drugs.
Source:
Steve Yozwiak
The Translational Genomics Research Institute
One of the first projects will focus on the causes of obesity, diabetes and other metabolic conditions. Researchers plan to look at the possible genetic reasons why so many Americans are overweight, and why diet, exercise and, specifically, bariatric surgery may fail to significantly reduce excess weight in some patients.
TGen, a non-profit biomedical research institute based in Phoenix, will pair its genomic and proteomic research expertise with the clinical excellence and research expertise of Geisinger, a non-profit medical and insurance provider based in Danville, Pa.
Geisinger's strength is its integrated healthcare delivery model, nontransitory population and advanced electronic health record (EHR) with nearly two decades of data. In addition to providing the clinical underpinnings for the study of obesity, the data within the EHR will provide researchers the evidence they need to make discoveries in future projects centered on cancer and other serious diseases.
"Merging Geisinger's wealth of clinical information with our genomic and proteomic expertise should provide researchers a richer framework for exploring the genetic origins of disease, and hopefully lead to improved treatments and outcomes," said Dr. Jeffrey Trent, Ph.D., TGen's President and Research Director.
TGen emphasizes a translational research process intended to quickly turn laboratory discoveries into new drugs and other treatments that can benefit patients, a goal shared by Geisinger.
"Given our unique research structure and a patient population that overwhelmingly supports cutting-edge research, I am confident that this partnership will allow us to test and apply new clinical translation theories to patient care," said Glenn D. Steele, Jr., M.D., Ph.D., Geisinger's President and CEO. "I look forward to the results of this first study, as I am confident we can greatly improve the outcomes for individuals coping with obesity and its many associated complications."
According to 2009 Census data, nearly one-third of the U.S. adult population is overweight and considered obese. The impact of obesity on one's health is great, often leading to a shortened lifespan. A disease, obesity is not always caused by overeating or lack of exercise, and research has shown there is often an underlying genetic component leading to excess weight gain.
David Carey, Ph.D., Director of the Sigfried and Janet Weis Center for Research, located on the campus of the Geisinger Medical Center, agreed that the collaboration should advance patient care. "Identification of patients at risk for chronic metabolic diseases would provide enormous benefit to health care. Geisinger's ability to obtain detailed, electronic health information in real time for a large, stable patient population will significantly accelerate this research effort."
Johanna DiStefano, Ph.D., Director of TGen's Diabetes, Cardiovascular & Metabolic Diseases Division, will lead TGen's efforts to understand the genetic basis of obesity and liver disease. She said research strategies would capitalize on the synergistic strengths of a large multidisciplinary research program in obesity at Geisinger. "I am confident that the long-term results of this collaboration will yield improved diagnostic and therapeutic outcomes for countless individuals suffering from chronic metabolic diseases."
TGen also plans to bring to bear its collaboration with the Partnership for Personalized Medicine (PPM), which includes TGen, Arizona State University's Biodesign Institute and the Fred Hutchinson Cancer Research Center. The PPM's mission is to improve medical outcomes and reduced costs through more effective diagnosis of disease risk, early stage, and matching patients to therapies.
"Working with Geisinger will provide yet another significant opportunity for the Partnership for Personalized Medicine to provide better evidence to meet the specific medical needs of individual patients," said Lee Hartwell, Ph.D., a 2001 Nobel laureate and Executive Committee Chairman of PPM.
The research partnership between TGen and Geisinger will also address some of the nation's other critical health challenges. Preliminary discussions covered such research areas as genetic variations that predispose individuals to disease, congestive heart failure, abdominal aortic aneurysms, and the potential side effects of prescription drugs.
Source:
Steve Yozwiak
The Translational Genomics Research Institute
Caltech Scientists Control Complex Nucleation Processes Using DNA Origami Seeds
The construction of complex man-made objects--a car, for example, or even a pizza--almost invariably entails what are known as "top-down" processes, in which the structure and order of the thing being built is imposed from the outside (say, by an automobile assembly line, or the hands of the pizza maker).
"Top-down approaches have been extremely successful," says Erik Winfree of the California Institute of Technology (Caltech). "But as the object being manufactured requires higher and higher precision--such as silicon chips with smaller and smaller transistors--they require enormously expensive factories to be built."
The alternative to top-down manufacturing is a "bottom-up" approach, in which the order is imposed from within the object being made, so that it "grows" according to some built-in design.
"Flowers, dogs, and just about all biological objects are created from the bottom up," says Winfree, an associate professor of computer science, computation and neural systems, and bioengineering at Caltech. Along with his coworkers, Winfree is seeking to integrate bottom-up construction approaches with molecular fabrication processes to construct objects from parts that are just a few billionths of a meter in size that essentially assemble themselves.
In a recent paper in the Proceedings of the National Academy of Sciences (PNAS), Winfree and his colleagues describe the development of an information-containing DNA "seed" that can direct the self-assembled bottom-up growth of tiles of DNA in a precisely controlled fashion. In some ways, the process is similar to how the fertilized seeds of plants or animals contain information that directs the growth and development of those organisms.
"The big potential advantage of bottom-up construction is that it can be cheap"--just as the mold that grows in your kitchen does so for free--"and can be massively parallel, because the objects construct themselves," says Winfree.
But, he adds, while bottom-up approaches have been extremely useful in biology, they haven't played as significant a role in technology, "because we don't have a great grasp on how to design systems that build themselves. Most examples of bottom-up technologies are specific chemical processes that work great for a particular task, but don't easily generalize for constructing more complex structures."
To understand how complexity can be programmed into bottom-up molecular fabrication processes, Winfree and his colleagues study and understand the processes--or algorithms--that generate organization not just in computers but also in the natural world.
"Tasks can be solved by carrying out well-defined rules, and these rules can be carried out by a mindless mechanism such as a computer," he says. "The same set of rules can perform different tasks when given different inputs, and there exist 'universal programs' that can perform any task required of it, as specified in its input. Your laptop is such a universal computer; it can run any software that you download, and in principle, any feasible task could be programmed."
These principles also have been exploited by natural evolution, Winfree says: "Every cell, it appears, is a kind of universal computer that can be instructed in seemingly limitless ways by a DNA genome that specifies what chemical processes to execute, thus building an active organism. The aim of my lab has been to understand algorithms and information within molecular systems."
Winfree's investigations into algorithmic self-assembly earned him a MacArthur "genius" prize in 2000; his collaborator, Paul W. K. Rothemund, a senior research associate at Caltech and a coauthor of the PNAS paper, was awarded the same no-strings-attached grant in 2007 for his work designing scaffolded "DNA origami" structures that self-assemble into nearly arbitrary shapes (such as a smiley face and a map of the Western Hemisphere).
The structures designed by Rothemund, which could eventually be used in smaller, faster computers, were used as the seeds for the programmed self-assembly of DNA tiles described in the current paper.
In the work, the researchers designed several different versions of a DNA origami rectangle, 95 by 75 nanometers, which served as the seeds for the growth of different types of ribbon-like crystals of DNA. The seeds were combined in a test tube with other bits of DNA, called "tiles," heated, and then cooled slowly.
"As it cools, the first origami seed and the individual tiles form, as their component DNA molecules begin sticking to each other and folding into shape--but the tiles and origami don't stick to each other yet," Winfree explains.
"Then, at a lower temperature, the tiles start to stick to each other and to the origami. The critical concept here is that the DNA tiles will only form crystals if the process gets started by a seed, upon which they can grow," he says.
In this way, the DNA ribbons self-assemble themselves, but only into forms such as ribbons with particular widths and ribbons with stripe patterns prescribed by the original seed.
The work, Winfree says, "exhibits a degree of control over information-directed molecular self-assembly that is unprecedented in accuracy and complexity, which makes me feel that we are finally beginning to understand how to program information into molecules and have that information direct algorithmic processes."
Notes:
The paper, "An information-bearing seed for nucleating algorithmic self-assembly," was published in the March 24 issue of the Proceedings of the National Academy of Sciences.
The other authors of the paper are undergraduate Robert D. Barish and visiting scholar Rebecca Schulman. The work was supported by grants from the National Aeronautics and Space Administration's astrobiology program, the National Science Foundation, and the Focus Center Research Program, and a gift from Microsoft Research.
Source:
Kathy Svitil
California Institute of Technology
"Top-down approaches have been extremely successful," says Erik Winfree of the California Institute of Technology (Caltech). "But as the object being manufactured requires higher and higher precision--such as silicon chips with smaller and smaller transistors--they require enormously expensive factories to be built."
The alternative to top-down manufacturing is a "bottom-up" approach, in which the order is imposed from within the object being made, so that it "grows" according to some built-in design.
"Flowers, dogs, and just about all biological objects are created from the bottom up," says Winfree, an associate professor of computer science, computation and neural systems, and bioengineering at Caltech. Along with his coworkers, Winfree is seeking to integrate bottom-up construction approaches with molecular fabrication processes to construct objects from parts that are just a few billionths of a meter in size that essentially assemble themselves.
In a recent paper in the Proceedings of the National Academy of Sciences (PNAS), Winfree and his colleagues describe the development of an information-containing DNA "seed" that can direct the self-assembled bottom-up growth of tiles of DNA in a precisely controlled fashion. In some ways, the process is similar to how the fertilized seeds of plants or animals contain information that directs the growth and development of those organisms.
"The big potential advantage of bottom-up construction is that it can be cheap"--just as the mold that grows in your kitchen does so for free--"and can be massively parallel, because the objects construct themselves," says Winfree.
But, he adds, while bottom-up approaches have been extremely useful in biology, they haven't played as significant a role in technology, "because we don't have a great grasp on how to design systems that build themselves. Most examples of bottom-up technologies are specific chemical processes that work great for a particular task, but don't easily generalize for constructing more complex structures."
To understand how complexity can be programmed into bottom-up molecular fabrication processes, Winfree and his colleagues study and understand the processes--or algorithms--that generate organization not just in computers but also in the natural world.
"Tasks can be solved by carrying out well-defined rules, and these rules can be carried out by a mindless mechanism such as a computer," he says. "The same set of rules can perform different tasks when given different inputs, and there exist 'universal programs' that can perform any task required of it, as specified in its input. Your laptop is such a universal computer; it can run any software that you download, and in principle, any feasible task could be programmed."
These principles also have been exploited by natural evolution, Winfree says: "Every cell, it appears, is a kind of universal computer that can be instructed in seemingly limitless ways by a DNA genome that specifies what chemical processes to execute, thus building an active organism. The aim of my lab has been to understand algorithms and information within molecular systems."
Winfree's investigations into algorithmic self-assembly earned him a MacArthur "genius" prize in 2000; his collaborator, Paul W. K. Rothemund, a senior research associate at Caltech and a coauthor of the PNAS paper, was awarded the same no-strings-attached grant in 2007 for his work designing scaffolded "DNA origami" structures that self-assemble into nearly arbitrary shapes (such as a smiley face and a map of the Western Hemisphere).
The structures designed by Rothemund, which could eventually be used in smaller, faster computers, were used as the seeds for the programmed self-assembly of DNA tiles described in the current paper.
In the work, the researchers designed several different versions of a DNA origami rectangle, 95 by 75 nanometers, which served as the seeds for the growth of different types of ribbon-like crystals of DNA. The seeds were combined in a test tube with other bits of DNA, called "tiles," heated, and then cooled slowly.
"As it cools, the first origami seed and the individual tiles form, as their component DNA molecules begin sticking to each other and folding into shape--but the tiles and origami don't stick to each other yet," Winfree explains.
"Then, at a lower temperature, the tiles start to stick to each other and to the origami. The critical concept here is that the DNA tiles will only form crystals if the process gets started by a seed, upon which they can grow," he says.
In this way, the DNA ribbons self-assemble themselves, but only into forms such as ribbons with particular widths and ribbons with stripe patterns prescribed by the original seed.
The work, Winfree says, "exhibits a degree of control over information-directed molecular self-assembly that is unprecedented in accuracy and complexity, which makes me feel that we are finally beginning to understand how to program information into molecules and have that information direct algorithmic processes."
Notes:
The paper, "An information-bearing seed for nucleating algorithmic self-assembly," was published in the March 24 issue of the Proceedings of the National Academy of Sciences.
The other authors of the paper are undergraduate Robert D. Barish and visiting scholar Rebecca Schulman. The work was supported by grants from the National Aeronautics and Space Administration's astrobiology program, the National Science Foundation, and the Focus Center Research Program, and a gift from Microsoft Research.
Source:
Kathy Svitil
California Institute of Technology
Eating And Weight Gain Not Necessarily Linked, Study Shows
You may not be what you eat after all.
A new study shows that increased eating does not necessarily lead to increased fat. The finding in the much-studied roundworm opens the possibility of identifying new targets for drugs to control weight, the researchers say.
The discovery reveals that the neurotransmitter serotonin, already known to control appetite and fat build-up, actually does so through two separate signaling channels. One set of signals regulates feeding, and a separate set of signals regulates fat metabolism. The worm, known scientifically as Caenorhabdtis elegans, shares half of its genes with humans and is often a predictor of human traits.
The signaling pathways are composed of a series of molecular events triggered by neurons in the brain that ultimately "instruct" the body to burn or store fat.
If the "separate-channel" mechanism is also found in humans, weight-loss drugs might be developed to attack just the fat-deposition channel rather than the hunger-dampening pathway that has met with limited success, says Kaveh Ashrafi, PhD, assistant professor of physiology at UCSF and senior author on the scientific paper reporting the study.
"It's not that feeding isn't important," Ashrafi says. "But serotonin's control of fat is distinct from feeding. A weight-loss strategy that focuses only on eating can only go so far. It may be one reason why diets fail."
The research was reported online June 3 by the journal Cell Metabolism and in the print edition June 4.
The finding does not challenge the view that hunger, feeding and fat are all linked in a feedback loop under the influence of serotonin and other neurotransmitters that act on neurons in the brain. But the discovery shows that this is not the whole story, according to Ashrafi.
Various weight-loss drugs have been developed to boost serotonin and thereby suppress appetite. But the cutback in eating tends to be short-term - often a matter of days, based on animal research, Ashrafi says. Drugs that block the brain's separate fat-deposition signaling pathway might be a boon to controlling obesity, type 2 diabetes, cardiovascular disease and other threats, he adds.
The scientists studied more than 250 genes to identify those that underlie serotonin's effects on fat and feeding. They found that serotonin controls feeding by docking with receptors on neurons that are distinct from those that control fat. In turn, these fat- controlling neurons send signals to sites of fat storage to rev up metabolism.
It is widely believed that environments that encourage excessive food intake and little physical activity promote development of obesity. However, extensive studies have revealed that body weight is not merely a passive consequence of environmental conditions but that a physiological system coordinates the complex mechanisms that regulate food intake and energy expenditure, Ashrafi says.
This physiological system is thought to involve genes that operate in various tissues such as fat, muscle, and brain. In fact, the genetic contribution to body weight is estimated to be between 40 and 70 percent. The molecular mechanisms that link excess fat to various diseases such as type 2 diabetes are not understood.
To help decipher the complex relationships between behavioral and metabolic pathways that control body weight, Ashrafi and his team began analyzing serotonin-induced regulation of fat and feeding in the microscopic C. elegans worm. They took advantage of a powerful and relatively new technique known as RNA interference, or RNAi, which allowed them to inactivate hundreds of genes one at a time to determine the effect of these gene inactivations on serotonin's actions on fat regulation.
"Obesity and thinness are not solely determined by feeding behavior," the scientists conclude in their paper. "Rather, feeding behavior and fat metabolism are coordinated but independent responses of the nervous system to the perception of nutrient availability."
Lead author on the paper is Supriya Srinivasan, PhD, a postdoctoral fellow in Ashrafi's lab. Co-author at UCSF is Leila Sadegh, BS, staff research assistant.
Other co-authors are Ida C. Elle, BS, graduate student; Anne G.L. Christensen, BS, staff research assistant; and Nils J. Faergeman, PhD, associate professor, all at the University of Southern Denmark.
Research support includes the National Institutes of Health, the Sandler Opportunity Fund and the Richard and the Susan Smith Family Foundation Pinnacle Program Project Award.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.
Source: Wallace Ravven
University of California - San Francisco
A new study shows that increased eating does not necessarily lead to increased fat. The finding in the much-studied roundworm opens the possibility of identifying new targets for drugs to control weight, the researchers say.
The discovery reveals that the neurotransmitter serotonin, already known to control appetite and fat build-up, actually does so through two separate signaling channels. One set of signals regulates feeding, and a separate set of signals regulates fat metabolism. The worm, known scientifically as Caenorhabdtis elegans, shares half of its genes with humans and is often a predictor of human traits.
The signaling pathways are composed of a series of molecular events triggered by neurons in the brain that ultimately "instruct" the body to burn or store fat.
If the "separate-channel" mechanism is also found in humans, weight-loss drugs might be developed to attack just the fat-deposition channel rather than the hunger-dampening pathway that has met with limited success, says Kaveh Ashrafi, PhD, assistant professor of physiology at UCSF and senior author on the scientific paper reporting the study.
"It's not that feeding isn't important," Ashrafi says. "But serotonin's control of fat is distinct from feeding. A weight-loss strategy that focuses only on eating can only go so far. It may be one reason why diets fail."
The research was reported online June 3 by the journal Cell Metabolism and in the print edition June 4.
The finding does not challenge the view that hunger, feeding and fat are all linked in a feedback loop under the influence of serotonin and other neurotransmitters that act on neurons in the brain. But the discovery shows that this is not the whole story, according to Ashrafi.
Various weight-loss drugs have been developed to boost serotonin and thereby suppress appetite. But the cutback in eating tends to be short-term - often a matter of days, based on animal research, Ashrafi says. Drugs that block the brain's separate fat-deposition signaling pathway might be a boon to controlling obesity, type 2 diabetes, cardiovascular disease and other threats, he adds.
The scientists studied more than 250 genes to identify those that underlie serotonin's effects on fat and feeding. They found that serotonin controls feeding by docking with receptors on neurons that are distinct from those that control fat. In turn, these fat- controlling neurons send signals to sites of fat storage to rev up metabolism.
It is widely believed that environments that encourage excessive food intake and little physical activity promote development of obesity. However, extensive studies have revealed that body weight is not merely a passive consequence of environmental conditions but that a physiological system coordinates the complex mechanisms that regulate food intake and energy expenditure, Ashrafi says.
This physiological system is thought to involve genes that operate in various tissues such as fat, muscle, and brain. In fact, the genetic contribution to body weight is estimated to be between 40 and 70 percent. The molecular mechanisms that link excess fat to various diseases such as type 2 diabetes are not understood.
To help decipher the complex relationships between behavioral and metabolic pathways that control body weight, Ashrafi and his team began analyzing serotonin-induced regulation of fat and feeding in the microscopic C. elegans worm. They took advantage of a powerful and relatively new technique known as RNA interference, or RNAi, which allowed them to inactivate hundreds of genes one at a time to determine the effect of these gene inactivations on serotonin's actions on fat regulation.
"Obesity and thinness are not solely determined by feeding behavior," the scientists conclude in their paper. "Rather, feeding behavior and fat metabolism are coordinated but independent responses of the nervous system to the perception of nutrient availability."
Lead author on the paper is Supriya Srinivasan, PhD, a postdoctoral fellow in Ashrafi's lab. Co-author at UCSF is Leila Sadegh, BS, staff research assistant.
Other co-authors are Ida C. Elle, BS, graduate student; Anne G.L. Christensen, BS, staff research assistant; and Nils J. Faergeman, PhD, associate professor, all at the University of Southern Denmark.
Research support includes the National Institutes of Health, the Sandler Opportunity Fund and the Richard and the Susan Smith Family Foundation Pinnacle Program Project Award.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.
Source: Wallace Ravven
University of California - San Francisco
Protein Isolated That May Be 'Boon' To Medicine
Scientists at UC Santa Barbara have isolated a unique protein that appears to have a dual function and could lead to a "boon in medicine." The findings are published in the August issue of the Journal of Cell Biology.
The protein that the researchers studied, named mDpy-30, affects both the expression of genes and the transport of proteins. "We first found that this protein has a dual location in the cell," said Dzwokai Ma, senior author and assistant professor in UCSB's Department of Molecular, Cellular and Developmental Biology. "That spurred us to investigate this protein further, because location is always linked to function."
Proteins that are most sensitive to mDpy-30 are pivotal to the movement of a cell, according to the current study and unpublished results from the Ma lab. "Indeed, we have obtained preliminary evidence that mDpy-30 is an important regulator of cell movement," said Ma. "The movement of a cell is essential to myriad biological functions such as neural networking, proper immunological function, and wound healing. Consequently, when these processes go awry, they can result in the development or progression of human disease, including cancer metastasis."
What remains enigmatic, Ma added, is the particular role of mDpy-30 in protein transport regulation, and whether or how this function is coordinated with gene expression during cell movement. "Further study could lead to a boon in medicine," he said.
First authors from UCSB who contributed equally to the paper, are: Zhuojin Xu, Qiang Gong, and Bin Xia. Additional co-authors are Benjamin Groves, Mark Zimmerman, Brian Matsumoto, and Chris Mugler, of UCSB; Dezhi Mu of Sichuan University, Chengdu, China; and Matthew Seaman of the University of Cambridge, Cambridge, U.K.
Source:
Gail Gallessich
University of California - Santa Barbara
The protein that the researchers studied, named mDpy-30, affects both the expression of genes and the transport of proteins. "We first found that this protein has a dual location in the cell," said Dzwokai Ma, senior author and assistant professor in UCSB's Department of Molecular, Cellular and Developmental Biology. "That spurred us to investigate this protein further, because location is always linked to function."
Proteins that are most sensitive to mDpy-30 are pivotal to the movement of a cell, according to the current study and unpublished results from the Ma lab. "Indeed, we have obtained preliminary evidence that mDpy-30 is an important regulator of cell movement," said Ma. "The movement of a cell is essential to myriad biological functions such as neural networking, proper immunological function, and wound healing. Consequently, when these processes go awry, they can result in the development or progression of human disease, including cancer metastasis."
What remains enigmatic, Ma added, is the particular role of mDpy-30 in protein transport regulation, and whether or how this function is coordinated with gene expression during cell movement. "Further study could lead to a boon in medicine," he said.
First authors from UCSB who contributed equally to the paper, are: Zhuojin Xu, Qiang Gong, and Bin Xia. Additional co-authors are Benjamin Groves, Mark Zimmerman, Brian Matsumoto, and Chris Mugler, of UCSB; Dezhi Mu of Sichuan University, Chengdu, China; and Matthew Seaman of the University of Cambridge, Cambridge, U.K.
Source:
Gail Gallessich
University of California - Santa Barbara
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