"You are what you eat." Can these pithy words explain the evolution of the human species?
Yes, says Richard Wrangham of Harvard University, who argues in a new book that the invention of cooking -- even more than agriculture, the eating of meat, or the advent of tools -- is what led to the rise of humanity.
Wrangham's book, "Catching Fire: How Cooking Made Us Human," is published by Basic Books. In it, he makes the case that the ability to harness fire and cook food allowed the brain to grow and the digestive tract to shrink, giving rise to our ancestor Homo erectus some 1.8 million years ago.
"Cooking is the signature feature of the human diet, and indeed, of human life -- but we have no idea why," says Wrangham, the Ruth Moore Professor of Biological Anthropology in Harvard's Faculty of Arts and Sciences. "It's the development that underpins many other changes that have made humans so distinct from other species."
Drawing on a wide body of research, Wrangham makes the case that cooking makes eating faster and easier, and wrings more caloric benefit from food. Moreover, he writes, cooking is vitally important to supporting the outsize human brain, which consumes a quarter of the body's energy.
By freeing humans from having to spend half the day chewing tough raw food -- as most of our primate relatives do -- cooking allowed early humans to devote themselves to more productive activities, ultimately allowing the development of tools, agriculture, and social networks. Cooked food is also softer, meaning the body uses less energy merely digesting what it takes in.
Since physical remnants of fire tend to degrade rapidly, archaeological evidence of fire and cooking dates back only about 800,000 years. Wrangham looked to biological evidence, which shows that around 1.8 million years ago, Homo erectus arose with larger brains and bodies and smaller guts, jaws, and teeth -- changes consistent with the switch to a more tender and energetically rich diet of cooked food.
"Cooking is what makes the human diet 'human,' and the most logical explanation for the advances in brain and body size over our ape ancestors," Wrangham says. "It's hard to imagine the leap to Homo erectus without cooking's nutritional benefits."
While others have posited that meat-eating enabled the rise of Homo erectus some 1.8 million years ago, Wrangham says those theories don't mesh with that species' smaller jaws and teeth. Instead, he claims meat enabled the shift from Australopithecines to Homo habilis -- a species about the size of a chimp, but with a bigger brain -- more than half a million years earlier.
Wrangham says the adoption of cooking had profound impacts on human families and relationships, making hearth and home central to humanity and driving humans into paired mating and perhaps even traditional male-female household roles.
He writes that the advent of cooking permitted a new distribution of labor between men and women: Men entered into relationships to have someone to cook for them, freeing them up for socializing and other pursuits and bolstering their social standing. Women benefited from men's protection, safeguarding their food from thieves. Homo sapiens remains the only species in which theft of food is uncommon even when it would be easy.
"To this day, cooking continues in every known human society," Wrangham says. "We are biologically adapted to cook food. It's part of who we are and affects us in every way you can imagine: biologically, anatomically, socially."
Source:
Steve Bradt
Harvard University
четверг, 20 октября 2011 г.
понедельник, 17 октября 2011 г.
Double Trouble With Insecticide-Resistant Mosquitoes
Mosquitoes harbouring two insecticide-resistance genes have been found to survive unexpectedly well in an insecticide-free environment where carrying such genes would normally be expected to be a burden. As outlined in research published by the open access journal BMC Evolutionary Biology, this results from the genes interacting with one another to the advantage of the host Culex quinquefasciatus mosquitoes and to the detriment of pest management strategies affecting human health.
The research team, led by Dr Vincent Corbel and colleagues from the UniversitГ© Montpellier II, Genetics and Evolution of Infectious Diseases and The Research Institute for Development (IRD) in France compared the survival rates or evolutionary fitness of one strain of the mosquito that carried two resistance genes (ace-1R and KdrR) for two different insecticides to mosquitoes that only had one insecticide-resistance gene, a French research team discovered that the survival cost of having both genes was far lower than the cost of having just ace-1R.
"We know from evolutionary theory that mutations such as these are likely to be costly to their owners in environments where they have not been selected for" explained Dr Corbel. "We've found that in C. quinquefasciatus the cost of having the ace-1R mutation in the absence of insecticides is counterbalanced when the mosquito also has the KdrR mutation. Mosquitoes with both mutations will also be harder to control as they are resistant to two different types of insecticide."
The authors also found evidence that resistance alleles interact with one another in the presence of insecticides. For instance, synergism (that is, a more than an additive effect) in toxicity was observed when a pyrethroid insecticide and a carbamate insecticide were applied simultaneously to the strain sharing both mutations (the insecticide had a greater activity and more of the mosquitoes died), whereas antagonism (that is, a less than an additive effect) was noted with Culex mosquitoes carrying only ace-1R.
Resistance to so-called xenobiotics (antibiotics, insecticides and herbicides) is a problem affecting the control of organisms of medical or economic importance. In C. quinquefasciatus insecticide resistance mutations interacted to positively and negatively influence the mosquitoes' fitness. Costs were associated with both resistance genes in an insecticide-free environment. The KdrR form of the gene, or allele, however, compensated for the costs associated with the ace-1R allele, suggesting that mosquitoes with both genes in the wild could be more prevalent. Females with both alleles were more likely to mature than those with just the ace-1R mutation."
"It is important to identify genetic interactions such as this and how they influence the fitness of multiply resistant organisms in order to better structure management strategies" says Dr Corbel. "We have found in this case that resistance genes do interact and even compensate. We will have to be very careful in how we use insecticides in future as our results have major implications for pest and health management."
1. Costs and benefits of multiple resistance to insecticides for Culex quinquefasciatus mosquitoes
Claire Berticat, Julien Bonnet, Stephane Duchon, Philip Agnew, Mylene Weill and Vincent Corbel
BMC Evolutionary Biology (in press)
Article available at journal website: biomedcentral/bmcevolbiol/
All articles are available free of charge, according to BioMed Central's open access policy.
2. Culex quinquefasciatus is an important carrier of West Nile virus in North America and bancraftian filariasis in Africa. 4 strains of C. quinquefasciatus were used in this study: SLAB, SR, BC, BCSR. All share the same genetic background and cytoplasm and only differ in their genotype at ace-1R and KdrR ace-1R and KdrR confer resistance to carbamate and pyrethroid insecticides respectively
3. BMC Evolutionary Biology is an open access journal publishing original peer-reviewed research articles in all aspects of molecular and non-molecular evolution of all organisms, as well as phylogenetics and palaeontology. BMC Evolutionary Biology (ISSN 1471-2148) is indexed/tracked/covered by PubMed, MEDLINE, BIOSIS, CAS, Zoological Record, Thomson Scientific (ISI) and Google Scholar.
4. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
The research team, led by Dr Vincent Corbel and colleagues from the UniversitГ© Montpellier II, Genetics and Evolution of Infectious Diseases and The Research Institute for Development (IRD) in France compared the survival rates or evolutionary fitness of one strain of the mosquito that carried two resistance genes (ace-1R and KdrR) for two different insecticides to mosquitoes that only had one insecticide-resistance gene, a French research team discovered that the survival cost of having both genes was far lower than the cost of having just ace-1R.
"We know from evolutionary theory that mutations such as these are likely to be costly to their owners in environments where they have not been selected for" explained Dr Corbel. "We've found that in C. quinquefasciatus the cost of having the ace-1R mutation in the absence of insecticides is counterbalanced when the mosquito also has the KdrR mutation. Mosquitoes with both mutations will also be harder to control as they are resistant to two different types of insecticide."
The authors also found evidence that resistance alleles interact with one another in the presence of insecticides. For instance, synergism (that is, a more than an additive effect) in toxicity was observed when a pyrethroid insecticide and a carbamate insecticide were applied simultaneously to the strain sharing both mutations (the insecticide had a greater activity and more of the mosquitoes died), whereas antagonism (that is, a less than an additive effect) was noted with Culex mosquitoes carrying only ace-1R.
Resistance to so-called xenobiotics (antibiotics, insecticides and herbicides) is a problem affecting the control of organisms of medical or economic importance. In C. quinquefasciatus insecticide resistance mutations interacted to positively and negatively influence the mosquitoes' fitness. Costs were associated with both resistance genes in an insecticide-free environment. The KdrR form of the gene, or allele, however, compensated for the costs associated with the ace-1R allele, suggesting that mosquitoes with both genes in the wild could be more prevalent. Females with both alleles were more likely to mature than those with just the ace-1R mutation."
"It is important to identify genetic interactions such as this and how they influence the fitness of multiply resistant organisms in order to better structure management strategies" says Dr Corbel. "We have found in this case that resistance genes do interact and even compensate. We will have to be very careful in how we use insecticides in future as our results have major implications for pest and health management."
1. Costs and benefits of multiple resistance to insecticides for Culex quinquefasciatus mosquitoes
Claire Berticat, Julien Bonnet, Stephane Duchon, Philip Agnew, Mylene Weill and Vincent Corbel
BMC Evolutionary Biology (in press)
Article available at journal website: biomedcentral/bmcevolbiol/
All articles are available free of charge, according to BioMed Central's open access policy.
2. Culex quinquefasciatus is an important carrier of West Nile virus in North America and bancraftian filariasis in Africa. 4 strains of C. quinquefasciatus were used in this study: SLAB, SR, BC, BCSR. All share the same genetic background and cytoplasm and only differ in their genotype at ace-1R and KdrR ace-1R and KdrR confer resistance to carbamate and pyrethroid insecticides respectively
3. BMC Evolutionary Biology is an open access journal publishing original peer-reviewed research articles in all aspects of molecular and non-molecular evolution of all organisms, as well as phylogenetics and palaeontology. BMC Evolutionary Biology (ISSN 1471-2148) is indexed/tracked/covered by PubMed, MEDLINE, BIOSIS, CAS, Zoological Record, Thomson Scientific (ISI) and Google Scholar.
4. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
Source: Charlotte Webber
BioMed Central
пятница, 14 октября 2011 г.
Merkel Cell Originates From Skin, Not The Neural Crest, Case Western Reserve University Discovers
Case Western Reserve University School of Medicine assistant professor of pediatrics, neurosciences and otolaryngology, Stephen M. Maricich, M.D., Ph.D., and his team found that Merkel cells originate in the skin, not the neural crest lineage, as previously speculated.
The study, "Mammalian Merkel Cells are Descended from the Epidermal Lineage", was recently published in the online version of Developmental Biology and is slated its future print edition.
"Merkel cells," discovered by Friedrich Sigmund Merkel in 1875, are found in multiple regions of the skin and make contact with specialized never fibers, participating in the perception of touch.
"A real mystery surrounding Merkel cells was their developmental site of origin. Conflicting evidence suggested that these cells arose from either the skin or neural crest lineages, but there was no definitive proof of either origin," said lead author, Dr. Maricich.
Using genetically engineered mouse lines, the researchers were able to delete Atoh1, a gene essential to the formation of Merkel cells, from different areas of developing embryos. This "conditional deletion" of Atoh1 in the neural crest did not affect the Merkel cell population, however using this same technique in the skin lineage resulted in the loss of all Merkel cells.
"Knocking out Atoh1 in the neural crest line caused other problems for developing embryos, but Merkel cells were completely unaffected. However, loss of Atoh1 expression in the skin deleted all the Merkel cells," said Dr. Maricich. "This showed us that we had specifically targeted the Merkel cells and that Atoh1 expression by skin cells is necessary to their development."
The researchers also fate mapped the cells, a technique used to trace developmental fates of embryonic tissues. This analysis further supported their conditional knockout findings.
"The techniques used in this study will help neuroscientists to further explore the function of Merkel cells, including the behavioral consequences when only Merkel cells have been deleted," said Ellen Lumpkin, Ph.D., a study co-author and assistant professor of neuroscience, molecular physiology and biophysics and molecular and human genetics at the Baylor College of Medicine.
"It is thought that Merkel cells give rise to Merkel cell carcinoma, a rare but aggressive form of skin cancer that responds poorly to current treatments," said Dr. Maricich. "In addition to solving a 130 year-old mystery, our data may be relevant to the understanding of Merkel cell carcinoma, and may provide important clues in the search for novel therapeutic targets."
Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Both are of the National Institutes of Health.
Source:
Christina DeAngelis
Case Western Reserve University
The study, "Mammalian Merkel Cells are Descended from the Epidermal Lineage", was recently published in the online version of Developmental Biology and is slated its future print edition.
"Merkel cells," discovered by Friedrich Sigmund Merkel in 1875, are found in multiple regions of the skin and make contact with specialized never fibers, participating in the perception of touch.
"A real mystery surrounding Merkel cells was their developmental site of origin. Conflicting evidence suggested that these cells arose from either the skin or neural crest lineages, but there was no definitive proof of either origin," said lead author, Dr. Maricich.
Using genetically engineered mouse lines, the researchers were able to delete Atoh1, a gene essential to the formation of Merkel cells, from different areas of developing embryos. This "conditional deletion" of Atoh1 in the neural crest did not affect the Merkel cell population, however using this same technique in the skin lineage resulted in the loss of all Merkel cells.
"Knocking out Atoh1 in the neural crest line caused other problems for developing embryos, but Merkel cells were completely unaffected. However, loss of Atoh1 expression in the skin deleted all the Merkel cells," said Dr. Maricich. "This showed us that we had specifically targeted the Merkel cells and that Atoh1 expression by skin cells is necessary to their development."
The researchers also fate mapped the cells, a technique used to trace developmental fates of embryonic tissues. This analysis further supported their conditional knockout findings.
"The techniques used in this study will help neuroscientists to further explore the function of Merkel cells, including the behavioral consequences when only Merkel cells have been deleted," said Ellen Lumpkin, Ph.D., a study co-author and assistant professor of neuroscience, molecular physiology and biophysics and molecular and human genetics at the Baylor College of Medicine.
"It is thought that Merkel cells give rise to Merkel cell carcinoma, a rare but aggressive form of skin cancer that responds poorly to current treatments," said Dr. Maricich. "In addition to solving a 130 year-old mystery, our data may be relevant to the understanding of Merkel cell carcinoma, and may provide important clues in the search for novel therapeutic targets."
Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Both are of the National Institutes of Health.
Source:
Christina DeAngelis
Case Western Reserve University
вторник, 11 октября 2011 г.
Cancer Surgery Revolutionized By Tumor Painting
A tumor paint developed by researchers at Seattle Children's Hospital Research Institute and Fred Hutchinson Cancer Research Center will help surgeons see where a tumor begins and ends more precisely by illuminating the cancerous cells. The study, published in Cancer Research, shows that the tumor paint can help surgeons distinguish between cancer cells and normal brain tissue in the operating room. The paint is a scorpion-derived peptide called chlorotoxin that is linked to the molecular beacon Cy5.5.Until now there has been no way to allow surgeons to see tumors 'live' during surgery.
Chlorotoxin:Cy5.5 is a fluorescent molecular beacon that emits photons in the near infrared spectrum. This illumination gives surgeons a better chance of removing all of the cancerous cells during surgery without injuring surrounding healthy tissue. This is particularly significant in the brain, where approximately 80% of malignant cancers recur at the edges of the surgical site. Current technology, such as magnetic resonance imaging (MRI) can distinguish tumors from healthy tissue only if more than 1 million cancer cells are present. But Cy5.5 can identify tumors with as few as 2000 cancer cells, making it 500 times more sensitive than MRI.
"My greatest hope is that tumor paint will fundamentally improve cancer therapy," said James M. Olson, MD, PhD, of Seattle Children's Hospital and The Hutchison Center who is the senior author of the study. "By allowing surgeons to see cancer that would be undetectable by other means, we can give our patients better outcomes."
Olson led the team that included neurosurgeons, engineers and biologists. The bioconjugate, Chlorotoxin:Cy5.5 which, when injected, emits a near-infrared light, was created in his laboratory at the Hutchinson Center. In mouse models, the team demonstrated that they could light up brain tumors as small as 1 millimeter in diameter without lighting up the surrounding normal brain tissue. In a prostate cancer model, as few as 200 cancer cells traveling in a mouse lymph channel could be detected.
Chlorotoxin:Cy5.5 is applicable to many cancers, but is especially helpful to surgeons operating on brain tumors. Not only would it reveal whether they'd left behind any bits of tumor, it would also help them avoid removing normal tissue. Chlorotoxin:Cy5.5 activates within hours and it begins binding to cancer cells within minutes. The Chlorotoxin:Cy5.5 signal lasts for 14 days, illuminating cancer cells. Contrast agents currently in use only last for a few minutes.
"I feel fortunate to be working with gifted scientists to bring this revolutionary imaging technique from the laboratory to the bedside," said Richard Ellenbogen, MD, Pediatric Neurosurgeon, Seattle Children's Hospital and co-investigator on the study. "This development has the potential to save lives and make brain tumor resection safer."
Surgery remains a primary form of cancer therapy. Despite advances in surgical tools, surgeons currently rely on color, texture or blood supply to differentiate tumor from normal tissue, a distinction that is often subtle and imperfect. The limitations of this method contribute to cancer growth or patient mortality that is potentially preventable. The tumor painting technique combines a visual guide for the surgeon with the potential for significant improvement in accuracy and safety.
Tumor painting has been successfully tested in mice and the pilot safety trials are complete. Olson and his team are preparing the necessary toxicity studies before seeking approval from the Food and Drug Administration to begin clinical trials. Chlorotoxin:Cy5.5 could be used in operating rooms in as little as 18 months. All clinical studies will have consenting adult participants.
Olson and his team believe that Chlorotoxin:Cy5.5 has the potential to be used in the future as a non-invasive screening tool for early detection of skin, cervical, esophageal, colon and lung cancers. It is also useful in identifying positive lymph nodes which could mean a significant advancement for breast, prostate and testicular cancers.
Children's and the Hutchison Center's role as leading research institutions is underscored by their membership in the Pediatric Brain Tumor Consortium (PBTC), a group of 10 medical centers selected by the National Cancer Institute (NCI). The consortium's members were chosen by the NCI based on their experience, dedication to research and quality of patient care.
Other Children's and Hutchison Center researchers on the team include Mandana Veiseh, PhD; Patrik Gabikian, S-Bahram Bahrami, PhD; Omid Veiseh, Miqin Zhang, Robert C. Hackman, MD; Ali C. Ravanpay, Mark R. Stroud, PhD; Yumiko Kusuma, Stacey J. Hansen, Deborah Kwok, Nina M. Munoz, PhD; Raymond W. Sze, MD; William M. Grady, MD; and Norman M. Greenberg, PhD.
About Seattle Children's Hospital Research Institute, Seattle, Wash.
At the forefront of pediatric research, the Seattle Children's Hospital Research Institute at Children's Hospital and Regional Medical Center in Seattle conducts research under nine major centers and is internationally recognized for its discoveries in cancer, genetics, health services, immunology, pathology, infectious disease and vaccines. Consistently ranked as one of the best children's hospitals in the country by U.S. News & World Report, Children's serves as the pediatric referral center for Washington, Alaska, Montana and Idaho. Children's has been delivering superior patient care for 100 years, including advancing new discoveries and treatments in pediatric research, and serving as a primary teaching, clinical and research site for the Department of Pediatrics at the University of Washington School of Medicine. For more information about the Institute visit research.seattlechildrens/.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc/.
Source: Jennifer Seymour
Children's Hospital and Regional Medical Center of Seattle
Chlorotoxin:Cy5.5 is a fluorescent molecular beacon that emits photons in the near infrared spectrum. This illumination gives surgeons a better chance of removing all of the cancerous cells during surgery without injuring surrounding healthy tissue. This is particularly significant in the brain, where approximately 80% of malignant cancers recur at the edges of the surgical site. Current technology, such as magnetic resonance imaging (MRI) can distinguish tumors from healthy tissue only if more than 1 million cancer cells are present. But Cy5.5 can identify tumors with as few as 2000 cancer cells, making it 500 times more sensitive than MRI.
"My greatest hope is that tumor paint will fundamentally improve cancer therapy," said James M. Olson, MD, PhD, of Seattle Children's Hospital and The Hutchison Center who is the senior author of the study. "By allowing surgeons to see cancer that would be undetectable by other means, we can give our patients better outcomes."
Olson led the team that included neurosurgeons, engineers and biologists. The bioconjugate, Chlorotoxin:Cy5.5 which, when injected, emits a near-infrared light, was created in his laboratory at the Hutchinson Center. In mouse models, the team demonstrated that they could light up brain tumors as small as 1 millimeter in diameter without lighting up the surrounding normal brain tissue. In a prostate cancer model, as few as 200 cancer cells traveling in a mouse lymph channel could be detected.
Chlorotoxin:Cy5.5 is applicable to many cancers, but is especially helpful to surgeons operating on brain tumors. Not only would it reveal whether they'd left behind any bits of tumor, it would also help them avoid removing normal tissue. Chlorotoxin:Cy5.5 activates within hours and it begins binding to cancer cells within minutes. The Chlorotoxin:Cy5.5 signal lasts for 14 days, illuminating cancer cells. Contrast agents currently in use only last for a few minutes.
"I feel fortunate to be working with gifted scientists to bring this revolutionary imaging technique from the laboratory to the bedside," said Richard Ellenbogen, MD, Pediatric Neurosurgeon, Seattle Children's Hospital and co-investigator on the study. "This development has the potential to save lives and make brain tumor resection safer."
Surgery remains a primary form of cancer therapy. Despite advances in surgical tools, surgeons currently rely on color, texture or blood supply to differentiate tumor from normal tissue, a distinction that is often subtle and imperfect. The limitations of this method contribute to cancer growth or patient mortality that is potentially preventable. The tumor painting technique combines a visual guide for the surgeon with the potential for significant improvement in accuracy and safety.
Tumor painting has been successfully tested in mice and the pilot safety trials are complete. Olson and his team are preparing the necessary toxicity studies before seeking approval from the Food and Drug Administration to begin clinical trials. Chlorotoxin:Cy5.5 could be used in operating rooms in as little as 18 months. All clinical studies will have consenting adult participants.
Olson and his team believe that Chlorotoxin:Cy5.5 has the potential to be used in the future as a non-invasive screening tool for early detection of skin, cervical, esophageal, colon and lung cancers. It is also useful in identifying positive lymph nodes which could mean a significant advancement for breast, prostate and testicular cancers.
Children's and the Hutchison Center's role as leading research institutions is underscored by their membership in the Pediatric Brain Tumor Consortium (PBTC), a group of 10 medical centers selected by the National Cancer Institute (NCI). The consortium's members were chosen by the NCI based on their experience, dedication to research and quality of patient care.
Other Children's and Hutchison Center researchers on the team include Mandana Veiseh, PhD; Patrik Gabikian, S-Bahram Bahrami, PhD; Omid Veiseh, Miqin Zhang, Robert C. Hackman, MD; Ali C. Ravanpay, Mark R. Stroud, PhD; Yumiko Kusuma, Stacey J. Hansen, Deborah Kwok, Nina M. Munoz, PhD; Raymond W. Sze, MD; William M. Grady, MD; and Norman M. Greenberg, PhD.
About Seattle Children's Hospital Research Institute, Seattle, Wash.
At the forefront of pediatric research, the Seattle Children's Hospital Research Institute at Children's Hospital and Regional Medical Center in Seattle conducts research under nine major centers and is internationally recognized for its discoveries in cancer, genetics, health services, immunology, pathology, infectious disease and vaccines. Consistently ranked as one of the best children's hospitals in the country by U.S. News & World Report, Children's serves as the pediatric referral center for Washington, Alaska, Montana and Idaho. Children's has been delivering superior patient care for 100 years, including advancing new discoveries and treatments in pediatric research, and serving as a primary teaching, clinical and research site for the Department of Pediatrics at the University of Washington School of Medicine. For more information about the Institute visit research.seattlechildrens/.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit fhcrc/.
Source: Jennifer Seymour
Children's Hospital and Regional Medical Center of Seattle
суббота, 8 октября 2011 г.
54 Million Americans Have Pre-Diabetes
Periodontal diseases may contribute to the progression to pre-diabetes, according to a new study that appears in the March issue of the Journal of Periodontology.
Pre-diabetes is a condition in which blood glucose levels are higher than normal, but not high enough to be diagnosed as diabetes. The American Diabetes Association estimates 54 million people in the United States have pre-diabetes, and a significant portion of those people will develop Type 2 diabetes within 10 years.
Researchers from Denmark investigated if having periodontal diseases can influence pre-diabetes and contribute to the progression of diabetes. They found that having periodontal disease can cause someone to develop pre-diabetic characteristics, and probably disturb the glucose regulation of a non-diabetic who has pre-diabetic characteristics, contributing to the progression of Type 2 diabetes. The study, conducted with rat models known to exhibit pre-diabetes characteristics, is believed to be the first to evaluate the relationship between periodontitis and pre-diabetes.
"This study found that having periodontal diseases can alter the metabolic conditions which would probably lead to the progression to pre-diabetic characteristics and Type 2 diabetes," said Dr. Carla Pontes Andersen, Department of Periodontology at the University of Copenhagen.
"We have known that people with diabetes are more susceptible to periodontal diseases and have more severe disease," said Dr. Preston D. Miller, Jr., President of the American Academy of Periodontology. "This breakthrough research shows having periodontal disease may aggravate pre-diabetes which is a precursor for diabetes. These findings underscore the importance of taking good care of your teeth and gums: it may be a simple way to prevent diabetes, or to prevent the progression of diabetes."
To asses your periodontal health visit perio/ and click on "Assess your gum disease risk". To check if you may be at risk of developing diabetes, visit diabetes/risk-test.jsp.
Visit the AAP website, perio/ for a referral to a periodontist and free brochure titled Diabetes & Periodontal Diseases.
The American Academy of Periodontology is an 8,000-member association of dental professionals specializing in the prevention, diagnosis and treatment of diseases affecting the gums and supporting structures of the teeth and in the placement and maintenance of dental implants. Periodontics is one of nine dental specialties recognized by the American Dental Association.
Contact: Kerry Gutshall
American Academy of Periodontology
Pre-diabetes is a condition in which blood glucose levels are higher than normal, but not high enough to be diagnosed as diabetes. The American Diabetes Association estimates 54 million people in the United States have pre-diabetes, and a significant portion of those people will develop Type 2 diabetes within 10 years.
Researchers from Denmark investigated if having periodontal diseases can influence pre-diabetes and contribute to the progression of diabetes. They found that having periodontal disease can cause someone to develop pre-diabetic characteristics, and probably disturb the glucose regulation of a non-diabetic who has pre-diabetic characteristics, contributing to the progression of Type 2 diabetes. The study, conducted with rat models known to exhibit pre-diabetes characteristics, is believed to be the first to evaluate the relationship between periodontitis and pre-diabetes.
"This study found that having periodontal diseases can alter the metabolic conditions which would probably lead to the progression to pre-diabetic characteristics and Type 2 diabetes," said Dr. Carla Pontes Andersen, Department of Periodontology at the University of Copenhagen.
"We have known that people with diabetes are more susceptible to periodontal diseases and have more severe disease," said Dr. Preston D. Miller, Jr., President of the American Academy of Periodontology. "This breakthrough research shows having periodontal disease may aggravate pre-diabetes which is a precursor for diabetes. These findings underscore the importance of taking good care of your teeth and gums: it may be a simple way to prevent diabetes, or to prevent the progression of diabetes."
To asses your periodontal health visit perio/ and click on "Assess your gum disease risk". To check if you may be at risk of developing diabetes, visit diabetes/risk-test.jsp.
Visit the AAP website, perio/ for a referral to a periodontist and free brochure titled Diabetes & Periodontal Diseases.
The American Academy of Periodontology is an 8,000-member association of dental professionals specializing in the prevention, diagnosis and treatment of diseases affecting the gums and supporting structures of the teeth and in the placement and maintenance of dental implants. Periodontics is one of nine dental specialties recognized by the American Dental Association.
Contact: Kerry Gutshall
American Academy of Periodontology
среда, 5 октября 2011 г.
Cell Death In The Colon Influenced By Vitamin D And Calcium
Researchers at Emory University are learning how vitamins and minerals in the diet can stimulate or prevent the appearance of colon cancer.
Emory investigators will present their findings on biological markers that could influence colon cancer risk in three abstracts at the American Association for Cancer Research meeting in San Diego, April 12-16, 2008.
In a clinical study of 92 patients, supplementing diet with calcium and vitamin D appeared to increase the levels of a protein called Bax that controls programmed cell death in the colon. More Bax might be pushing pre-cancerous cells into programmed cell death, says Emory researcher Veronika Fedirko, who will present her team's results (abstract 464).
Previous studies have shown that calcium and vitamin D tend to reduce colon cancer risk.
"We were pleased that the effects of calcium and vitamin D were visible enough in this small study to be significant and reportable," Fedirko says. "We will have to fully evaluate each marker's strength as we accumulate more data."
The studies of colorectal biopsy samples are part of a larger effort to identify a portfolio of measurements that together can gauge someone's risk of getting colon cancer, says Roberd Bostick, MD, MPH, professor of epidemiology at Emory's Rollins School of Public Health.
"We want to have the equivalent of measuring cholesterol or high blood pressure, but for colon cancer instead of heart disease," Bostick says. "These measurements will describe the climate of risk in the colon rather than spotting individual tumors or cells that may become tumors."
More about Bostick's plans for developing non-invasive blood or urine tests for colon cancer risk is available in an Emory Health Sciences Magazine article.
Another abstract from Bostick and his colleagues (565) demonstrates in a 200-patient case-control study that high levels of calcium and vitamin D together are associated with increased levels of E-cadherin, which moderates colon cells' movement and proliferation.
A third abstract on the same case-control study (5504) shows that high levels of iron in the diet are linked to low levels of APC, a protein whose absence in colon cancer cells leads to their runaway growth.
Bostick and his colleagues are participating in a ten-year multi-center study of the effects of increased vitamin D and calcium and biomarker-guided treatment of colon cancer recurrence. The study involves almost 2,500 people nationwide who have regular colonoscopies.
The Bostick team's research is funded by the National Cancer Institute and the Wilson and Anne Franklin Foundation.
Source: Ashante Dobbs
Emory University
Emory investigators will present their findings on biological markers that could influence colon cancer risk in three abstracts at the American Association for Cancer Research meeting in San Diego, April 12-16, 2008.
In a clinical study of 92 patients, supplementing diet with calcium and vitamin D appeared to increase the levels of a protein called Bax that controls programmed cell death in the colon. More Bax might be pushing pre-cancerous cells into programmed cell death, says Emory researcher Veronika Fedirko, who will present her team's results (abstract 464).
Previous studies have shown that calcium and vitamin D tend to reduce colon cancer risk.
"We were pleased that the effects of calcium and vitamin D were visible enough in this small study to be significant and reportable," Fedirko says. "We will have to fully evaluate each marker's strength as we accumulate more data."
The studies of colorectal biopsy samples are part of a larger effort to identify a portfolio of measurements that together can gauge someone's risk of getting colon cancer, says Roberd Bostick, MD, MPH, professor of epidemiology at Emory's Rollins School of Public Health.
"We want to have the equivalent of measuring cholesterol or high blood pressure, but for colon cancer instead of heart disease," Bostick says. "These measurements will describe the climate of risk in the colon rather than spotting individual tumors or cells that may become tumors."
More about Bostick's plans for developing non-invasive blood or urine tests for colon cancer risk is available in an Emory Health Sciences Magazine article.
Another abstract from Bostick and his colleagues (565) demonstrates in a 200-patient case-control study that high levels of calcium and vitamin D together are associated with increased levels of E-cadherin, which moderates colon cells' movement and proliferation.
A third abstract on the same case-control study (5504) shows that high levels of iron in the diet are linked to low levels of APC, a protein whose absence in colon cancer cells leads to their runaway growth.
Bostick and his colleagues are participating in a ten-year multi-center study of the effects of increased vitamin D and calcium and biomarker-guided treatment of colon cancer recurrence. The study involves almost 2,500 people nationwide who have regular colonoscopies.
The Bostick team's research is funded by the National Cancer Institute and the Wilson and Anne Franklin Foundation.
Source: Ashante Dobbs
Emory University
воскресенье, 2 октября 2011 г.
Genome Mapping Technique Speeds Process Of Finding Specific Genes
A Purdue University scientist was part of a global team that has demonstrated a specialized mapping technique that could speed work in genomic fields by quickly finding genetic associations that shape an organism's observable characteristics.
Using plants from 93 different Arabidopsis thaliana populations, a team led by the Gregor Mendel Institute of Plant Biology in Austria was able to find genetic associations among multiple phenotypes, or traits, suggesting that the same genes or closely related genes controlled those traits. David E. Salt, a Purdue professor of plant biology and co-author of a Nature paper on the study released Wednesday (March 24), said the ability to find these types of genetic links could speed scientists' ability to find and isolate genes and understand their function.
"This may show that multiple phenotypes are being controlled by a specific region of the genome," Salt said. "It helps us understand the mechanisms."
A traditional search for a gene responsible for a particular characteristic requires using plants that have been phenotyped, or identified by characteristics. They are then crossed with others, and the offspring are phenotyped.
Scientists then check for similarities in offsprings' genes with the desired trait. The process can be painstaking and time consuming because many thousands of individuals may need to be checked, Salt said.
Genome-wide association mapping compares the sequence of DNA in genomes of many individual plants or animals to find similarities that narrow the scope of the search for a particular gene.
"We can look for a region in the genome that is in common among the individuals," Salt said. "For plant biologists, it's a much more efficient way of getting to genes. And for animal biologists, where making test crosses is more difficult, this is critical."
In this study, specific differences in DNA, called single nucleotide polymorphisms, or SNPs, were compared at 250,000 sites across the genomes of many individuals. The genomes were matched up against specific traits for each individual in order to find SNPs that are associated with the trait of interest. If scientists were looking for plants that produce high seed yields, for example, they would compare the genomes of plants that have a range of seed yields. The places where the genomes match in individuals with high seed yields are possible locations of sought-after genes.
Genome-wide association mapping is a faster process because fewer plants - usually in the hundreds - need to be grown and phenotyped. Finding genetic associations among multiple phenotypes could reveal more information about how those characteristics might be connected.
Of the 107 phenotypes used in the research, Salt was responsible for phenotyping the plants for 18 characteristics, which focused on nutrient and micronutrient content. He said the next step in the research would be to test those associations to determine the genes responsible for particular plant characteristics.
The National Institutes of Health funded the research.
Writer: Brian Wallheimer
Source:
Brian Wallheimer
Purdue University
Using plants from 93 different Arabidopsis thaliana populations, a team led by the Gregor Mendel Institute of Plant Biology in Austria was able to find genetic associations among multiple phenotypes, or traits, suggesting that the same genes or closely related genes controlled those traits. David E. Salt, a Purdue professor of plant biology and co-author of a Nature paper on the study released Wednesday (March 24), said the ability to find these types of genetic links could speed scientists' ability to find and isolate genes and understand their function.
"This may show that multiple phenotypes are being controlled by a specific region of the genome," Salt said. "It helps us understand the mechanisms."
A traditional search for a gene responsible for a particular characteristic requires using plants that have been phenotyped, or identified by characteristics. They are then crossed with others, and the offspring are phenotyped.
Scientists then check for similarities in offsprings' genes with the desired trait. The process can be painstaking and time consuming because many thousands of individuals may need to be checked, Salt said.
Genome-wide association mapping compares the sequence of DNA in genomes of many individual plants or animals to find similarities that narrow the scope of the search for a particular gene.
"We can look for a region in the genome that is in common among the individuals," Salt said. "For plant biologists, it's a much more efficient way of getting to genes. And for animal biologists, where making test crosses is more difficult, this is critical."
In this study, specific differences in DNA, called single nucleotide polymorphisms, or SNPs, were compared at 250,000 sites across the genomes of many individuals. The genomes were matched up against specific traits for each individual in order to find SNPs that are associated with the trait of interest. If scientists were looking for plants that produce high seed yields, for example, they would compare the genomes of plants that have a range of seed yields. The places where the genomes match in individuals with high seed yields are possible locations of sought-after genes.
Genome-wide association mapping is a faster process because fewer plants - usually in the hundreds - need to be grown and phenotyped. Finding genetic associations among multiple phenotypes could reveal more information about how those characteristics might be connected.
Of the 107 phenotypes used in the research, Salt was responsible for phenotyping the plants for 18 characteristics, which focused on nutrient and micronutrient content. He said the next step in the research would be to test those associations to determine the genes responsible for particular plant characteristics.
The National Institutes of Health funded the research.
Writer: Brian Wallheimer
Source:
Brian Wallheimer
Purdue University
четверг, 29 сентября 2011 г.
Opening The Gate To The Cell's Recycling Center
In cells, as in cities, disposing of garbage and recycling anything that can be reused is an essential service. In both city and cell, health problems can arise when the process breaks down.
New research by University of Michigan cell biologist Haoxing Xu and colleagues reveals key details about how the cell's garbage dump and recycling center, the lysosome, functions. These insights, which may lead to better understanding of conditions such as amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and Charcot-Marie-Tooth (CMT) disease, suggest new avenues of treatment for these and other diseases that cause nerves and muscles to malfunction.
The research, published this week in the online, multidisciplinary journal Nature Communications, focused on gateways called calcium channels in the lysosome membrane. Calcium channels, which also are found in the membranes surrounding muscle and nerve cells, are made of proteins that respond to signals in the form of electrical impulses. When the proper signal comes along, the proteins open the channel, allowing calcium to pass through. The calcium, in turn, triggers some vital process such as muscle contraction or the release of a hormone or neurotransmitter (a chemical messenger involved in nerve transmission).
Scientists know a lot about the workings of calcium channels in the surfaces of muscle and nerve cells, but understanding what goes in the lysosome - a tiny pouch hidden inside the cell - has been a challenge, said Xu. Consequently, the exact identity of the protein involved and how it becomes activated have remained a mystery.
To explore the channel and its workings, Xu's group modified a technique known as the patch clamp, in which a scaled-down pipette and electrodes are attached to a cell membrane to record the activity of one or more proteins making up the channel. With their modification, which they call the lysosome patch clamp, the researchers determined that a protein called TRPML1 serves as the calcium channel in lysosomes and that a lipid known as PI(3,5)P2 carries the signal that activates the protein.
This particular protein and lipid aren't obscure characters previously unknown to science. A mutation in the gene that produces TRPML1 is known to cause Type IV mucolipidosis (ML4), a genetic disorder that affects mainly Jews of Eastern European background and results in mental retardation, poor vision and diminished motor abilities. And mutations in the enzymes needed to make PI(3,5) P2 cause a variety of neurodegenerative diseases including ALS and CMT.
The protein TRPML1 also is of interest because of the unusual way it does its work.
"While other channel proteins are in the 'passenger' seats of the membrane traffic, TRPML1 is in the 'driver' seat," said Xu, an assistant professor of molecular, cellular and developmental biology. This suggests that manipulating TRPML1 channel activity using channel activators or inhibitors could affect membrane traffic.
"If you can activate the channel, it might be possible to overcome the membrane traffic defects caused by the disease-causing mutations. Luckily, small-molecule chemicals that can stimulate TRPML1 channel activity are already available, " Xu said.
He and collaborator Miriam Meisler, a human genetics professor at the U-M Medical School, have experiments underway to see if they can prevent or reverse the course of disease in a mouse model of ALS by increasing activity of the TRPML1 channel.
If the strategy is successful, Xu hopes to explore its use in treating other neurological diseases.
"If the system we're studying turns out to be compromised in more common diseases, the method of increasing channel activity could have important implications for their treatment," he said.
Xu's coauthors on the Nature Communications paper are postdoctoral fellows Xian-ping Dong, Xiping Cheng and Yanling Zhang; graduate students Dongbiao Shen, Xiang Wang, and Qi Zhang; and undergraduate students Taylor Dawson and Xinran Li, all at U-M; Lois Weisman, who is the Sarah Winans Newman Collegiate Professor in the Life Sciences at U-M; and Markus Delling of Children's Hospital Boston.
The research was funded by the U-M Department of Molecular, Cellular & Developmental Biology; the U-M Biological Sciences Scholars Program; the U-M Initiative on Rare Disease Research, the Michigan Alzheimer's Disease Research Center, the National Multiple Sclerosis Society and the National Institutes of Health.
Source:
Nancy Ross-Flanigan
University of Michigan
New research by University of Michigan cell biologist Haoxing Xu and colleagues reveals key details about how the cell's garbage dump and recycling center, the lysosome, functions. These insights, which may lead to better understanding of conditions such as amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and Charcot-Marie-Tooth (CMT) disease, suggest new avenues of treatment for these and other diseases that cause nerves and muscles to malfunction.
The research, published this week in the online, multidisciplinary journal Nature Communications, focused on gateways called calcium channels in the lysosome membrane. Calcium channels, which also are found in the membranes surrounding muscle and nerve cells, are made of proteins that respond to signals in the form of electrical impulses. When the proper signal comes along, the proteins open the channel, allowing calcium to pass through. The calcium, in turn, triggers some vital process such as muscle contraction or the release of a hormone or neurotransmitter (a chemical messenger involved in nerve transmission).
Scientists know a lot about the workings of calcium channels in the surfaces of muscle and nerve cells, but understanding what goes in the lysosome - a tiny pouch hidden inside the cell - has been a challenge, said Xu. Consequently, the exact identity of the protein involved and how it becomes activated have remained a mystery.
To explore the channel and its workings, Xu's group modified a technique known as the patch clamp, in which a scaled-down pipette and electrodes are attached to a cell membrane to record the activity of one or more proteins making up the channel. With their modification, which they call the lysosome patch clamp, the researchers determined that a protein called TRPML1 serves as the calcium channel in lysosomes and that a lipid known as PI(3,5)P2 carries the signal that activates the protein.
This particular protein and lipid aren't obscure characters previously unknown to science. A mutation in the gene that produces TRPML1 is known to cause Type IV mucolipidosis (ML4), a genetic disorder that affects mainly Jews of Eastern European background and results in mental retardation, poor vision and diminished motor abilities. And mutations in the enzymes needed to make PI(3,5) P2 cause a variety of neurodegenerative diseases including ALS and CMT.
The protein TRPML1 also is of interest because of the unusual way it does its work.
"While other channel proteins are in the 'passenger' seats of the membrane traffic, TRPML1 is in the 'driver' seat," said Xu, an assistant professor of molecular, cellular and developmental biology. This suggests that manipulating TRPML1 channel activity using channel activators or inhibitors could affect membrane traffic.
"If you can activate the channel, it might be possible to overcome the membrane traffic defects caused by the disease-causing mutations. Luckily, small-molecule chemicals that can stimulate TRPML1 channel activity are already available, " Xu said.
He and collaborator Miriam Meisler, a human genetics professor at the U-M Medical School, have experiments underway to see if they can prevent or reverse the course of disease in a mouse model of ALS by increasing activity of the TRPML1 channel.
If the strategy is successful, Xu hopes to explore its use in treating other neurological diseases.
"If the system we're studying turns out to be compromised in more common diseases, the method of increasing channel activity could have important implications for their treatment," he said.
Xu's coauthors on the Nature Communications paper are postdoctoral fellows Xian-ping Dong, Xiping Cheng and Yanling Zhang; graduate students Dongbiao Shen, Xiang Wang, and Qi Zhang; and undergraduate students Taylor Dawson and Xinran Li, all at U-M; Lois Weisman, who is the Sarah Winans Newman Collegiate Professor in the Life Sciences at U-M; and Markus Delling of Children's Hospital Boston.
The research was funded by the U-M Department of Molecular, Cellular & Developmental Biology; the U-M Biological Sciences Scholars Program; the U-M Initiative on Rare Disease Research, the Michigan Alzheimer's Disease Research Center, the National Multiple Sclerosis Society and the National Institutes of Health.
Source:
Nancy Ross-Flanigan
University of Michigan
понедельник, 26 сентября 2011 г.
Heart Attack Damage May Be Lessened By Novel Compound
A novel drug designed to lessen muscle damage from a heart attack has passed initial safety tests at the Duke Clinical Research Institute. Results of the study, available online and to be published in the February 19 issue of the journal Circulation, reflect the first time the drug has been tested in humans.
The drug, known as KAI-9803, blocks the activity of an enzyme called delta protein kinase C that triggers cell and tissue death in the aftermath of percutaneous coronary intervention, or PCI. PCI is a set of procedures including balloon angioplasty and stent placement that clear and prop open clogged coronary blood vessels that lead to a heart attack - a process known as reperfusion.
Although the trial (known as DELTA-MI) was not designed to demonstrate the efficacy of KAI-9803, researchers say early data suggest it appears to be a promising compound.
"We've needed something like this for a long time," says Dr. Matthew Roe, a cardiologist at Duke and the lead investigator of the trial.
Roe says many people may not realize that the heart suffers damage at two major points in a heart attack: first, when a blockage in a coronary artery prevents blood and oxygen from getting to the heart, and then again when the patient undergoes PCI and normal blood flow is restored through reperfusion.
"We may not be able to intervene in the first stage of a heart attack, but we think there may be ways to limit damage caused by reperfusion injury," he says.
Researchers randomized 154 patients who had suffered heart attacks and were eligible for PCI into either one of four dosing levels of KAI-9803 or a placebo. Patients underwent PCI - with physicians injecting the drug directly into their coronary blood vessels during the procedure.
"The goal of the treatment is to flood the heart damaged by the heart attack with the drug immediately before blood flow is restored and then again, immediately afterwards," says Roe. "We believe that bathing the area with this novel compound may block the damaging cascade of events that are triggered specifically by delta protein kinase C when blood is restored to the heart muscle," he says.
Earlier studies in animals showed that KAI-9803 lessened damage to the heart muscle and quickly restored its pumping function.
"We designed the DELTA MI trial to find out if KAI-9803 is safe for humans, and we accomplished that goal; we did not see any serious side effects," says Roe. "We also found, however, many promising signs of beneficial drug activity such as lessened damage to the heart muscle and improvement in electrical conductivity in the heart that corresponded to restoration of blood flow to the heart muscle. As a result, we feel this drug has the potential to be helpful in reducing the impact of a heart attack in humans."
The study, funded by KAI Pharmaceuticals, included contributions from researchers in 48 institutions throughout the U.S., Canada, Brazil and Europe.
Source: Michelle Gailiun
Duke University Medical Center
The drug, known as KAI-9803, blocks the activity of an enzyme called delta protein kinase C that triggers cell and tissue death in the aftermath of percutaneous coronary intervention, or PCI. PCI is a set of procedures including balloon angioplasty and stent placement that clear and prop open clogged coronary blood vessels that lead to a heart attack - a process known as reperfusion.
Although the trial (known as DELTA-MI) was not designed to demonstrate the efficacy of KAI-9803, researchers say early data suggest it appears to be a promising compound.
"We've needed something like this for a long time," says Dr. Matthew Roe, a cardiologist at Duke and the lead investigator of the trial.
Roe says many people may not realize that the heart suffers damage at two major points in a heart attack: first, when a blockage in a coronary artery prevents blood and oxygen from getting to the heart, and then again when the patient undergoes PCI and normal blood flow is restored through reperfusion.
"We may not be able to intervene in the first stage of a heart attack, but we think there may be ways to limit damage caused by reperfusion injury," he says.
Researchers randomized 154 patients who had suffered heart attacks and were eligible for PCI into either one of four dosing levels of KAI-9803 or a placebo. Patients underwent PCI - with physicians injecting the drug directly into their coronary blood vessels during the procedure.
"The goal of the treatment is to flood the heart damaged by the heart attack with the drug immediately before blood flow is restored and then again, immediately afterwards," says Roe. "We believe that bathing the area with this novel compound may block the damaging cascade of events that are triggered specifically by delta protein kinase C when blood is restored to the heart muscle," he says.
Earlier studies in animals showed that KAI-9803 lessened damage to the heart muscle and quickly restored its pumping function.
"We designed the DELTA MI trial to find out if KAI-9803 is safe for humans, and we accomplished that goal; we did not see any serious side effects," says Roe. "We also found, however, many promising signs of beneficial drug activity such as lessened damage to the heart muscle and improvement in electrical conductivity in the heart that corresponded to restoration of blood flow to the heart muscle. As a result, we feel this drug has the potential to be helpful in reducing the impact of a heart attack in humans."
The study, funded by KAI Pharmaceuticals, included contributions from researchers in 48 institutions throughout the U.S., Canada, Brazil and Europe.
Source: Michelle Gailiun
Duke University Medical Center
пятница, 23 сентября 2011 г.
Embryonic Pathway Delivers Stem Cell Traits
Studies of how cancer cells spread have led to a surprising discovery about the creation of cells with adult stem cell characteristics, offering potentially major implications for regenerative medicine and for cancer treatment.
Some cancer cells acquire the ability to migrate through the body by re-activating biological programs that have lain dormant since the embryo stage, as the lab of Whitehead Member Robert Weinberg has helped to demonstrate in recent years. Now scientists in the Weinberg lab have shown that both normal and cancer cells that are induced to follow one of these pathways may gain properties of adult stem cells, including the ability to self-renew.
In a paper published online by Cell former postdoctoral researcher Sendurai Mani and his colleagues demonstrated in mice and in human cells that cells that have undergone an "epithelial-to-mesenchymal" (EMT) transition acquire several important characteristics of stem cells. Conversely, the researchers also showed that naturally existing normal stem cells as well as tumor-seeding cancer stem cells show characteristics of the post-EMT cells, including the acquisition of mesenchymal cell traits, which are usually associated with connective tissue cells.
Epithelial cells, which make up most of the human body, bind together in sheet-like structures. In embryonic development, the EMT process breaks up cell-cell adhesion in the epithelial layer, and converts epithelial cells into more loosely associated mesenchymal cells. In the context of cancer development, some cancer cells within a primary cancer may undergo an EMT, migrate through the body to their end destination, and there resume their epithelial form through a reverse process (the mesenchymal-to-epithelial transition).
Mani and his colleagues have identified FOXC2, one of the key genes involved in invasion and metastasis. In addition, FOXC2 appears to program the metastatic ability of some breast cancers.
Mani knew that during embryonic development, FOXC2 expression is restricted to mesoderm and mesoderm-derived cells when they are in an undifferentiated state, and its expression disappears once these cells differentiate. Similarly, his experiments showed that epithelial cells that undergo EMT express FOXC2, but that expression is lost when they revert back to an epithelial state.
In collaboration with Andrea Richardson and Jeffery Kutok, pathologists at Boston's Brigham and Women's Hospital, Mani went on to study FOXC2 expression in normal human breast tissue. It turned out that such cells were located precisely where researchers expect to find mammary epithelial stem cells.
As he pondered these findings and the earlier results about FOXC2's role in metastasis, Mani wondered: Just what were these cells generated by EMT that expressed FOXC2"
Were they simply fibroblasts, the most common cells in normal connective tissue" Or were they actually stem cells"
"I asked Mai-Jing Liao, another postdoc in the Weinberg lab, to check whether the cells generated by EMT would have any stem cell properties," recalls Mani, now an assistant professor in the department of molecular pathology at the University of Texas's M. D. Anderson Cancer Center in Houston. "He said, 'You must be out of your mind, but it won't take more than half an hour to check.'"
Much to Liao's surprise, when he examined cells that had undergo an EMT, his tests did highlight surface proteins that are key markers for stem cells.
The researchers found that the cells that underwent the EMT process were mesenchymal-like in appearance and demonstrated stem-cell surface markers. The cells also displayed an increased ability to grow in suspension, forming structures called mammospheres - another trait of mammary stem cells. Some cells in the resulting mammospheres showed, in turn, stem cell markers, indicating they could differentiate into two kinds of mammary cells. And cells in the mammospheres retained their stem cell properties even after the EMT induction process was stopped.
Furthermore, when the Weinberg lab scientists isolated stem-cell-like cells from cultured human mammary epithelial cells or from mouse breast tissue, their properties were very similar to the EMT-induced cells. Working with Kornelia Polyak of Dana-Farber Cancer Institute and Harvard Medical School, Mani found that this was also true with normal and tumor cells obtained from human patients.
"This for us is a very exciting discovery, not only because of its unexpectedness but because it offers a route by which one could in principle generate unlimited numbers of stem cells committed to create a specific cell type," says Weinberg, who is also a professor of biology at Massachusetts Institute of Technology. "One could imagine, for example, that if one takes skin cells and induces them to undergo an EMT, they could become skin stem cells."
Importantly, the researchers also demonstrated that inducing the EMT process can produce cells with many characteristics of cancer stem cells. (Beginning in 2003, scientists in various labs have identified these self-renewing, tumor-seeding cells in a number of solid tumors.)
This finding could help to answer a key question about metastasis: When tumor cells spread into different sites, how do they multiply enough to form a dangerous new tumor"
"If you take a population of human cancer cells that normally form a tumor very inefficiently and induce an EMT, their tumor-initiating abilities increase by about a hundred-fold, so that it takes about 10,000 cells rather than a million cells to form a tumor," says Wenjun Guo, co-lead author on the paper and postdoctoral researcher in the Weinberg lab. "This suggests cancer stem cells are using pre-existing normal stem cell machinery to propagate their own self-renewal and therefore their tumor-initiating ability."
Mani is continuing his research on the EMT/cancer stem cell connection and its role in cancer metastasis at the M. D. Anderson Cancer Center. Researchers in the Weinberg lab will investigate the EMT process with other cell lines. They also will attempt to give final proof in mice that the process creates completely defined stem cells, by taking cells from mouse mammary fat pads, inducing an EMT for some of the cells, returning the resulting cells to the fat pad, and seeing if they can regenerate the mammary gland.
This research was supported by the Breast Cancer Research Foundation, the MIT Ludwig Center for Molecular Oncology and the National Cancer Institute. Mani was supported by a Department of Defense postdoctoral fellowship.
Full citation:
Cell/, online publication May 15, Print Edition, Volume 133 (4)
"The epithelial-mesenchymal transition generates cells with properties of stem cells"
Sendurai A. Mani (1,3,9,10), Wenjun Guo (1,9), Mai-Jing Liao (1,9), Elinor Ng Eaton (1), Ayyakkannu Ayyanan (4), Alicia Zhou (1), Mary Brooks (1), Ferenc Reinhard (1), Cheng Cheng Zhang (1), Michail Shipitsin (5,6), Lauren L. Campbell (5,7), Kornelia Polyak (5,6,7), Cathrin Brisken(4), Jing Yang (1,8), Robert A. Weinberg (1,2,).
1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142
2. Department of Biology and MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge MA 02139
3. Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, 7435 Fannin St, Houston, TX 77054
4. Ecole polytechnique fГ©dГ©rale de Lausanne (EPFL) ISREC - Swiss Institute for Experimental Cancer Research, CH-1066, Epalinges, Switzerland
5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115
6. Department of Medicine, Harvard Medical School, Boston, MA 02115
7. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115
8. Department of Pharmacology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0636
9. These authors contributed equally to this work
Source: Cristin Carr
Whitehead Institute for Biomedical Research
Some cancer cells acquire the ability to migrate through the body by re-activating biological programs that have lain dormant since the embryo stage, as the lab of Whitehead Member Robert Weinberg has helped to demonstrate in recent years. Now scientists in the Weinberg lab have shown that both normal and cancer cells that are induced to follow one of these pathways may gain properties of adult stem cells, including the ability to self-renew.
In a paper published online by Cell former postdoctoral researcher Sendurai Mani and his colleagues demonstrated in mice and in human cells that cells that have undergone an "epithelial-to-mesenchymal" (EMT) transition acquire several important characteristics of stem cells. Conversely, the researchers also showed that naturally existing normal stem cells as well as tumor-seeding cancer stem cells show characteristics of the post-EMT cells, including the acquisition of mesenchymal cell traits, which are usually associated with connective tissue cells.
Epithelial cells, which make up most of the human body, bind together in sheet-like structures. In embryonic development, the EMT process breaks up cell-cell adhesion in the epithelial layer, and converts epithelial cells into more loosely associated mesenchymal cells. In the context of cancer development, some cancer cells within a primary cancer may undergo an EMT, migrate through the body to their end destination, and there resume their epithelial form through a reverse process (the mesenchymal-to-epithelial transition).
Mani and his colleagues have identified FOXC2, one of the key genes involved in invasion and metastasis. In addition, FOXC2 appears to program the metastatic ability of some breast cancers.
Mani knew that during embryonic development, FOXC2 expression is restricted to mesoderm and mesoderm-derived cells when they are in an undifferentiated state, and its expression disappears once these cells differentiate. Similarly, his experiments showed that epithelial cells that undergo EMT express FOXC2, but that expression is lost when they revert back to an epithelial state.
In collaboration with Andrea Richardson and Jeffery Kutok, pathologists at Boston's Brigham and Women's Hospital, Mani went on to study FOXC2 expression in normal human breast tissue. It turned out that such cells were located precisely where researchers expect to find mammary epithelial stem cells.
As he pondered these findings and the earlier results about FOXC2's role in metastasis, Mani wondered: Just what were these cells generated by EMT that expressed FOXC2"
Were they simply fibroblasts, the most common cells in normal connective tissue" Or were they actually stem cells"
"I asked Mai-Jing Liao, another postdoc in the Weinberg lab, to check whether the cells generated by EMT would have any stem cell properties," recalls Mani, now an assistant professor in the department of molecular pathology at the University of Texas's M. D. Anderson Cancer Center in Houston. "He said, 'You must be out of your mind, but it won't take more than half an hour to check.'"
Much to Liao's surprise, when he examined cells that had undergo an EMT, his tests did highlight surface proteins that are key markers for stem cells.
The researchers found that the cells that underwent the EMT process were mesenchymal-like in appearance and demonstrated stem-cell surface markers. The cells also displayed an increased ability to grow in suspension, forming structures called mammospheres - another trait of mammary stem cells. Some cells in the resulting mammospheres showed, in turn, stem cell markers, indicating they could differentiate into two kinds of mammary cells. And cells in the mammospheres retained their stem cell properties even after the EMT induction process was stopped.
Furthermore, when the Weinberg lab scientists isolated stem-cell-like cells from cultured human mammary epithelial cells or from mouse breast tissue, their properties were very similar to the EMT-induced cells. Working with Kornelia Polyak of Dana-Farber Cancer Institute and Harvard Medical School, Mani found that this was also true with normal and tumor cells obtained from human patients.
"This for us is a very exciting discovery, not only because of its unexpectedness but because it offers a route by which one could in principle generate unlimited numbers of stem cells committed to create a specific cell type," says Weinberg, who is also a professor of biology at Massachusetts Institute of Technology. "One could imagine, for example, that if one takes skin cells and induces them to undergo an EMT, they could become skin stem cells."
Importantly, the researchers also demonstrated that inducing the EMT process can produce cells with many characteristics of cancer stem cells. (Beginning in 2003, scientists in various labs have identified these self-renewing, tumor-seeding cells in a number of solid tumors.)
This finding could help to answer a key question about metastasis: When tumor cells spread into different sites, how do they multiply enough to form a dangerous new tumor"
"If you take a population of human cancer cells that normally form a tumor very inefficiently and induce an EMT, their tumor-initiating abilities increase by about a hundred-fold, so that it takes about 10,000 cells rather than a million cells to form a tumor," says Wenjun Guo, co-lead author on the paper and postdoctoral researcher in the Weinberg lab. "This suggests cancer stem cells are using pre-existing normal stem cell machinery to propagate their own self-renewal and therefore their tumor-initiating ability."
Mani is continuing his research on the EMT/cancer stem cell connection and its role in cancer metastasis at the M. D. Anderson Cancer Center. Researchers in the Weinberg lab will investigate the EMT process with other cell lines. They also will attempt to give final proof in mice that the process creates completely defined stem cells, by taking cells from mouse mammary fat pads, inducing an EMT for some of the cells, returning the resulting cells to the fat pad, and seeing if they can regenerate the mammary gland.
This research was supported by the Breast Cancer Research Foundation, the MIT Ludwig Center for Molecular Oncology and the National Cancer Institute. Mani was supported by a Department of Defense postdoctoral fellowship.
Full citation:
Cell/, online publication May 15, Print Edition, Volume 133 (4)
"The epithelial-mesenchymal transition generates cells with properties of stem cells"
Sendurai A. Mani (1,3,9,10), Wenjun Guo (1,9), Mai-Jing Liao (1,9), Elinor Ng Eaton (1), Ayyakkannu Ayyanan (4), Alicia Zhou (1), Mary Brooks (1), Ferenc Reinhard (1), Cheng Cheng Zhang (1), Michail Shipitsin (5,6), Lauren L. Campbell (5,7), Kornelia Polyak (5,6,7), Cathrin Brisken(4), Jing Yang (1,8), Robert A. Weinberg (1,2,).
1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142
2. Department of Biology and MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge MA 02139
3. Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, 7435 Fannin St, Houston, TX 77054
4. Ecole polytechnique fГ©dГ©rale de Lausanne (EPFL) ISREC - Swiss Institute for Experimental Cancer Research, CH-1066, Epalinges, Switzerland
5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115
6. Department of Medicine, Harvard Medical School, Boston, MA 02115
7. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115
8. Department of Pharmacology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0636
9. These authors contributed equally to this work
Source: Cristin Carr
Whitehead Institute for Biomedical Research
вторник, 20 сентября 2011 г.
New 'test tubes' far smaller than the width of a hair
Using a water droplet 1 trillion times smaller than a liter of club soda as a sort of nanoscale test tube, a University of Washington scientist is conducting chemical analysis and experimentation at unprecedented tiny scales.
The method captures a single cell, or even a small subcellular structure called an organelle, within a droplet. It then employs a powerful laser microscope to study the contents and examine chemical processes, and a laser beam is used to manipulate the cell or even just a few molecules, combining them with other molecules to form new substances.
This nanoscale "laboratory" is so minuscule that it covers just 1 percent of the width of a human hair, said Daniel Chiu, a UW associate chemistry professor who is developing the unique method.
"Anything you can do in the test tube we hope to be able to do in the droplet. We just don't need a lot of cells. We don't even need one cell, just a few molecules," Chiu said.
The new approach makes it easier to get a wide range of information about a cell. Researchers typically use microscopy to see how proteins move within a cell and collect spatial information, but that provides very little biochemical information, Chiu said. Likewise, they can use large amounts of material in a test tube to understand biochemical processes, but that doesn't provide the fine detail of microscopy.
"The cell is very small but it is very complex," Chiu said. "It has many hundreds of thousands of proteins. It is probably the ultimate nanomachine."
The new method, employing a process called microfluidics, allows researchers to perform chemical analysis and to study structure and form at the same time.
The tiny droplet is contained in a microfluidic device, which is far too small to be seen with the naked eye and is mounted on a platform about the size of a dime so researchers can carry it from one place to another. The device has water in one channel and oil in an adjoining channel. The target - a cell, an organelle or just a few molecules - is placed at the interface between the oil and water using a laser beam, so the target is encapsulated as the water droplet is formed.
Once the droplet captures its target, it is held fast while researchers use lasers to manipulate it and conduct analysis and experimentation.
"If you have 10 molecules that you're interested in, you can combine those with other molecules to make new molecules," Chiu said. "You can control their reactivity, move them and combine them if they are confined in a droplet. As soon as you put them in a test tube, they're diffused and you lose the ability to see them."
Chiu presents his work Monday during a session of the American Chemical Society's fall meeting in Washington, D.C.
The new method allows researchers to address specific biological questions that cannot be answered by testing in large quantities in the test tube, such as how organelles within a cell differ from each other, or how different proteins are expressed within the same cell, Chiu said.
"At this point it is still limited to fundamental biological studies," he said. "It provides finer, higher resolution than working with standard test tubes. There are things you cannot find out in bulk, and every cell and organelle is different."
Currently Chiu is focused on continuing development of the process, essentially creating a nanoscale test tube. But he believes the process holds great promise for future chemical and biological research.
"We're still trying to develop the process and to understand the chemistry at this small scale, which could be very different from chemistry at the macro scale," he said.
For more information, contact Chiu at (206) 543-1655 or chiuchem.washington
Vince Stricherz
vincesu.washington
206-543-2580
University of Washington
uwnews
The method captures a single cell, or even a small subcellular structure called an organelle, within a droplet. It then employs a powerful laser microscope to study the contents and examine chemical processes, and a laser beam is used to manipulate the cell or even just a few molecules, combining them with other molecules to form new substances.
This nanoscale "laboratory" is so minuscule that it covers just 1 percent of the width of a human hair, said Daniel Chiu, a UW associate chemistry professor who is developing the unique method.
"Anything you can do in the test tube we hope to be able to do in the droplet. We just don't need a lot of cells. We don't even need one cell, just a few molecules," Chiu said.
The new approach makes it easier to get a wide range of information about a cell. Researchers typically use microscopy to see how proteins move within a cell and collect spatial information, but that provides very little biochemical information, Chiu said. Likewise, they can use large amounts of material in a test tube to understand biochemical processes, but that doesn't provide the fine detail of microscopy.
"The cell is very small but it is very complex," Chiu said. "It has many hundreds of thousands of proteins. It is probably the ultimate nanomachine."
The new method, employing a process called microfluidics, allows researchers to perform chemical analysis and to study structure and form at the same time.
The tiny droplet is contained in a microfluidic device, which is far too small to be seen with the naked eye and is mounted on a platform about the size of a dime so researchers can carry it from one place to another. The device has water in one channel and oil in an adjoining channel. The target - a cell, an organelle or just a few molecules - is placed at the interface between the oil and water using a laser beam, so the target is encapsulated as the water droplet is formed.
Once the droplet captures its target, it is held fast while researchers use lasers to manipulate it and conduct analysis and experimentation.
"If you have 10 molecules that you're interested in, you can combine those with other molecules to make new molecules," Chiu said. "You can control their reactivity, move them and combine them if they are confined in a droplet. As soon as you put them in a test tube, they're diffused and you lose the ability to see them."
Chiu presents his work Monday during a session of the American Chemical Society's fall meeting in Washington, D.C.
The new method allows researchers to address specific biological questions that cannot be answered by testing in large quantities in the test tube, such as how organelles within a cell differ from each other, or how different proteins are expressed within the same cell, Chiu said.
"At this point it is still limited to fundamental biological studies," he said. "It provides finer, higher resolution than working with standard test tubes. There are things you cannot find out in bulk, and every cell and organelle is different."
Currently Chiu is focused on continuing development of the process, essentially creating a nanoscale test tube. But he believes the process holds great promise for future chemical and biological research.
"We're still trying to develop the process and to understand the chemistry at this small scale, which could be very different from chemistry at the macro scale," he said.
For more information, contact Chiu at (206) 543-1655 or chiuchem.washington
Vince Stricherz
vincesu.washington
206-543-2580
University of Washington
uwnews
суббота, 17 сентября 2011 г.
How Cancer Cells Survive A Chemotherapy Drug
What separates the few cancer cells that survive chemotherapy - leaving the door open to recurrence - from those that don't? Weizmann Institute scientists developed an original method for imaging and analyzing many thousands of living cells to reveal exactly how a chemotherapy drug affects each one.
For research student Ariel Cohen, together with Naama Geva-Zatorsky and Eran Eden in the lab of Prof. Uri Alon of the Institute's Molecular Cell Biology Department, the question posed an interesting challenge. To approach it, they needed a method that would allow them to cast a wide net on the one hand - to sift through the numerous cellular proteins that could conceivably affect survival - but that would let them zoom in on the activities of individual cells in detail, on the other. Letting the computer take over the painstaking work of searching for anomalies enabled the team to look at the behavior of over 1000 different proteins. Even so, it took several years to complete the project, which entailed tagging the specific proteins in each group of cancer cells with a fluorescent gene and capturing a series of time-lapse images over 72 hours. A second, fainter fluorescent marker was added to outline the cells, so the computer could identify them. A chemotherapy drug was introduced 24 hours into this period, after which the cells began the process of either dying or defending themselves against the drug.
The team's efforts have produced a comprehensive library of tagged cells, images and data on cancer cell proteins - a virtual goldmine of ready material for further cancer research. And they succeeded in pinpointing two proteins that seem to play a role in cancer cell survival.
Although most of the proteins behaved similarly in all the cells, the researchers found that a small subset of them - around five percent - could act unpredictably, even when the cells and drug exposure were identical. The scientists called these proteins bimodal, as they acted in one of two ways.
The team then asked whether any of the bimodal proteins they had identified were those that occasionally promote cell survival. They found two molecules that seem to fit the bill. One of them, known by the letters DDX5, is a multitasking protein that, among other things, plays a role in initiating the production of other proteins. The other, RFC1, also plays varied roles, including directing the repair of damaged DNA. When the researchers blocked the production of these proteins in the cancer cells, the drug became much more efficient at wiping out the growth.
Cohen: 'This method gave us tremendous insight into how a cell responds to a drug. By conducting an unbiased study - we started with no preconceived notions of which proteins were involved - we were able to pinpoint possible new drug targets and to see how certain activities might boost the effectiveness of current drugs.'
Prof. Uri Alon's research is supported by the Kahn Family Foundation for Humanitarian Support and Keren Isra - Pa'amei Tikva.
For the scientific paper, please see: sciencemag/cgi/reprint/322/5907/1511.pdf
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
Source: Yivsam Azgad
Weizmann Institute of Science
For research student Ariel Cohen, together with Naama Geva-Zatorsky and Eran Eden in the lab of Prof. Uri Alon of the Institute's Molecular Cell Biology Department, the question posed an interesting challenge. To approach it, they needed a method that would allow them to cast a wide net on the one hand - to sift through the numerous cellular proteins that could conceivably affect survival - but that would let them zoom in on the activities of individual cells in detail, on the other. Letting the computer take over the painstaking work of searching for anomalies enabled the team to look at the behavior of over 1000 different proteins. Even so, it took several years to complete the project, which entailed tagging the specific proteins in each group of cancer cells with a fluorescent gene and capturing a series of time-lapse images over 72 hours. A second, fainter fluorescent marker was added to outline the cells, so the computer could identify them. A chemotherapy drug was introduced 24 hours into this period, after which the cells began the process of either dying or defending themselves against the drug.
The team's efforts have produced a comprehensive library of tagged cells, images and data on cancer cell proteins - a virtual goldmine of ready material for further cancer research. And they succeeded in pinpointing two proteins that seem to play a role in cancer cell survival.
Although most of the proteins behaved similarly in all the cells, the researchers found that a small subset of them - around five percent - could act unpredictably, even when the cells and drug exposure were identical. The scientists called these proteins bimodal, as they acted in one of two ways.
The team then asked whether any of the bimodal proteins they had identified were those that occasionally promote cell survival. They found two molecules that seem to fit the bill. One of them, known by the letters DDX5, is a multitasking protein that, among other things, plays a role in initiating the production of other proteins. The other, RFC1, also plays varied roles, including directing the repair of damaged DNA. When the researchers blocked the production of these proteins in the cancer cells, the drug became much more efficient at wiping out the growth.
Cohen: 'This method gave us tremendous insight into how a cell responds to a drug. By conducting an unbiased study - we started with no preconceived notions of which proteins were involved - we were able to pinpoint possible new drug targets and to see how certain activities might boost the effectiveness of current drugs.'
Prof. Uri Alon's research is supported by the Kahn Family Foundation for Humanitarian Support and Keren Isra - Pa'amei Tikva.
For the scientific paper, please see: sciencemag/cgi/reprint/322/5907/1511.pdf
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
Source: Yivsam Azgad
Weizmann Institute of Science
среда, 14 сентября 2011 г.
Humanized Mouse Infected With HIV Vaginally And Rectally Allows Testing
The "humanized mouse" developed by Dr. J. Victor Garcia-Martinez has allowed the University of Texas Southwestern physician-scientist to conduct HIV/AIDS studies that would have been impossible without such a small animal model of HIV infection. The virus only infects humans and chimpanzees, which are protected as endangered species.
But because the new mouse model is a chimera, with a human immune system, it can be infected. Last year, using these humanized mice, a team of scientists led by Dr. Garcia-Martinez demonstrated that antiretroviral drugs given before and after exposure to HIV could prevent vaginal transmission of the virus. That suggests the possibility that women at high risk of HIV infection might one day be able to take a pill on a regular basis. And, since the drugs tested are already available, having gone through the long and complex approval process, that day might be sooner rather than later.
On Sunday, April 19, Dr. Garcia-Martinez tells fellow scientists attending Experimental Biology 2009 in New Orleans that the team is now using the mouse model to obtain evidence that these same approaches apply to protecting men.
Dr. Garcia-Martinez's presentation, updating improvements in the humanized mouse and in the progress of this and other work using the mouse model of human HIV/AIDS infection, is part of the scientific program of the American Society for Biochemistry and Molecular Biology.
First created in 2006, by Dr. Garcia and colleagues at UT Southwestern and the University of Minnesota, the humanized mouse used in these studies represented a new frontier in the preclinical testing of experimental drugs. Early mice models of disease were created by breeding mice that were immunodeficient in order that they would not reject grafts of human tissue. The big advance in the mouse created by Dr. Garcia-Martinez's group is that the mouse develops a human immune system, thanks to transfer of fetal human liver and thymic tissue cells that repopulate the bone marrow, which produces more cells.
The problem with using animals other than humans and chimpanzees for HIV/AIDS studies had been that the other animals, including ordinary mice, never become infected even when exposed to massive amounts of the virus. But the Garcia-Martinez mouse model (called BLT for bone marrow-liver-thymus) can easily be infected with HIV by both rectal and vaginal transmission, since both areas of the mouse body contain human cells.
With a long term-goal to investigate novel approaches to prevent HIV transmission, the team began with male to female infection. Women are at higher risk of infection during heterosexual sex with an infected partner, and women worldwide account for more than half of the estimated 11,000 newly acquired infections every day, with a majority of those transmissions occurring via the vaginal route. However, says Dr. Garcia-Martinez, male to male sexual contact accounts for a high proportion of the HIV/AIDS cases in the United States and rates of such transmission continue to rise, despite extensive educational campaigns.
Dr. Garcia-Martinez believes these statistics clearly reflect an urgent need to devise and implement potential interventions that could prevent both vaginal and rectal HIV-1 transmission especially among high-risk populations. The humanized mouse model provides an increasingly effective tool to move in that direction.
Work in his laboratory is funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Source:
Sylvia Wrobel
Federation of American Societies for Experimental Biology
But because the new mouse model is a chimera, with a human immune system, it can be infected. Last year, using these humanized mice, a team of scientists led by Dr. Garcia-Martinez demonstrated that antiretroviral drugs given before and after exposure to HIV could prevent vaginal transmission of the virus. That suggests the possibility that women at high risk of HIV infection might one day be able to take a pill on a regular basis. And, since the drugs tested are already available, having gone through the long and complex approval process, that day might be sooner rather than later.
On Sunday, April 19, Dr. Garcia-Martinez tells fellow scientists attending Experimental Biology 2009 in New Orleans that the team is now using the mouse model to obtain evidence that these same approaches apply to protecting men.
Dr. Garcia-Martinez's presentation, updating improvements in the humanized mouse and in the progress of this and other work using the mouse model of human HIV/AIDS infection, is part of the scientific program of the American Society for Biochemistry and Molecular Biology.
First created in 2006, by Dr. Garcia and colleagues at UT Southwestern and the University of Minnesota, the humanized mouse used in these studies represented a new frontier in the preclinical testing of experimental drugs. Early mice models of disease were created by breeding mice that were immunodeficient in order that they would not reject grafts of human tissue. The big advance in the mouse created by Dr. Garcia-Martinez's group is that the mouse develops a human immune system, thanks to transfer of fetal human liver and thymic tissue cells that repopulate the bone marrow, which produces more cells.
The problem with using animals other than humans and chimpanzees for HIV/AIDS studies had been that the other animals, including ordinary mice, never become infected even when exposed to massive amounts of the virus. But the Garcia-Martinez mouse model (called BLT for bone marrow-liver-thymus) can easily be infected with HIV by both rectal and vaginal transmission, since both areas of the mouse body contain human cells.
With a long term-goal to investigate novel approaches to prevent HIV transmission, the team began with male to female infection. Women are at higher risk of infection during heterosexual sex with an infected partner, and women worldwide account for more than half of the estimated 11,000 newly acquired infections every day, with a majority of those transmissions occurring via the vaginal route. However, says Dr. Garcia-Martinez, male to male sexual contact accounts for a high proportion of the HIV/AIDS cases in the United States and rates of such transmission continue to rise, despite extensive educational campaigns.
Dr. Garcia-Martinez believes these statistics clearly reflect an urgent need to devise and implement potential interventions that could prevent both vaginal and rectal HIV-1 transmission especially among high-risk populations. The humanized mouse model provides an increasingly effective tool to move in that direction.
Work in his laboratory is funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Source:
Sylvia Wrobel
Federation of American Societies for Experimental Biology
воскресенье, 11 сентября 2011 г.
ECCO Urges MEPs To Think Of Patients' Interests When They Vote On A Review Of A Directive On The Protection Of Animals Used For Scientific Purposes
The European CanCer Organisation - has urged members of the European Parliament not to forget the interests of patients when they take a crucial vote on amendments to the EU Directive on the protection of animals used for scientific purposes (Review of Directive 86/609/EEC).
President of ECCO, Professor Alexander M.M. Eggermont, has written to the members of the European Parliament Agriculture Committee, who will be voting on the issue tomorrow, highlighting ECCO's concerns about several of the amendments that are being proposed.
"ECCO's primary mission is to improve human health, and to win the fight against cancer. We hope that MEPs will not forget this in their understandable desire to protect laboratory animals," writes Prof Eggermont. "We would like to point out that some of the contents of the revised Directive, as well as some amendments proposed by Committee members, could affect the lives of millions of European cancer patients in the years to come.
"We are particularly concerned about two areas:
- the proposed restrictions of the use of non-human primates in medical research
- amendments which would severely limit, if not stop entirely, essential medical research, making the administrative procedures hugely cumbersome
"Because non-human primates are our nearest animal 'relation', their use in medical research is a difficult issue which raises considerable moral concerns. However, there are areas where their use is essential. The Directive proposal to limit the use of primates to research that 'is undertaken with a view to the avoidance, prevention, diagnosis or treatment of life-threatening or debilitating clinical conditions in human beings' may prevent these animals being used in some areas of fundamental research where the primary aim is to gain new knowledge. It is not always possible to demonstrate the relevance of such knowledge to particular diseases or conditions at the time the work is proposed.
"Perhaps most worrying of all are several amendments which, if passed, would raise the regulatory hurdles so high that it seems likely that essential research could be held up for years. Introducing such lengthy administrative procedures will not improve animal welfare, but will greatly affect European medical research. We are particularly concerned about amendment 311, proposed by Mr [Neil] Parish, which calls for all applications for research projects involving animals to be subject to public consultation, in order that regulatory authorities may have 'access to the widest range of views on which to base decisions'. While this may seem as though it will bring about a welcome increase in transparency, medical researchers know from experience that the vast majority of views transmitted will come through organised write-in campaigns from animal rights groups, and collecting and collating them all will add months to the already lengthy process of authorisation.
"On behalf of European patients, doctors, and researchers, we ask you most sincerely to allow us to continue to work to reduce the burden of cancer and not to put unnecessary barriers in our way," concludes Prof Eggermont.
Notes
ECCO - the European CanCer Organisation - exists to uphold the right of all European cancer patients to the best possible treatment and care and to promote interaction between all organisations involved in cancer research, education, treatment and care at the European level
Source
European CanCer Organisation
President of ECCO, Professor Alexander M.M. Eggermont, has written to the members of the European Parliament Agriculture Committee, who will be voting on the issue tomorrow, highlighting ECCO's concerns about several of the amendments that are being proposed.
"ECCO's primary mission is to improve human health, and to win the fight against cancer. We hope that MEPs will not forget this in their understandable desire to protect laboratory animals," writes Prof Eggermont. "We would like to point out that some of the contents of the revised Directive, as well as some amendments proposed by Committee members, could affect the lives of millions of European cancer patients in the years to come.
"We are particularly concerned about two areas:
- the proposed restrictions of the use of non-human primates in medical research
- amendments which would severely limit, if not stop entirely, essential medical research, making the administrative procedures hugely cumbersome
"Because non-human primates are our nearest animal 'relation', their use in medical research is a difficult issue which raises considerable moral concerns. However, there are areas where their use is essential. The Directive proposal to limit the use of primates to research that 'is undertaken with a view to the avoidance, prevention, diagnosis or treatment of life-threatening or debilitating clinical conditions in human beings' may prevent these animals being used in some areas of fundamental research where the primary aim is to gain new knowledge. It is not always possible to demonstrate the relevance of such knowledge to particular diseases or conditions at the time the work is proposed.
"Perhaps most worrying of all are several amendments which, if passed, would raise the regulatory hurdles so high that it seems likely that essential research could be held up for years. Introducing such lengthy administrative procedures will not improve animal welfare, but will greatly affect European medical research. We are particularly concerned about amendment 311, proposed by Mr [Neil] Parish, which calls for all applications for research projects involving animals to be subject to public consultation, in order that regulatory authorities may have 'access to the widest range of views on which to base decisions'. While this may seem as though it will bring about a welcome increase in transparency, medical researchers know from experience that the vast majority of views transmitted will come through organised write-in campaigns from animal rights groups, and collecting and collating them all will add months to the already lengthy process of authorisation.
"On behalf of European patients, doctors, and researchers, we ask you most sincerely to allow us to continue to work to reduce the burden of cancer and not to put unnecessary barriers in our way," concludes Prof Eggermont.
Notes
ECCO - the European CanCer Organisation - exists to uphold the right of all European cancer patients to the best possible treatment and care and to promote interaction between all organisations involved in cancer research, education, treatment and care at the European level
Source
European CanCer Organisation
четверг, 8 сентября 2011 г.
Gene In Breast Cancer Pathway Identified
Scientists at Albert Einstein College of Medicine of Yeshiva University have discovered how a gene crucial in triggering the spread of breast cancer is turned on and off. The findings could help predict whether breast tumors will metastasize and also reveal potential drug targets for preventing metastasis. The study will appear in the May 20th online edition of the Journal of Cell Science.
A few years ago, Einstein scientists discovered a gene called ZBP1 (zipcode binding protein 1), which helps cells to move, grow and organize spatially. "ZBP1 is very active in the developing embryo but largely silent in adult tissues," says Robert H. Singer, Ph.D., professor and co-chair of anatomy and structural biology and co-director of the Gruss-Lipper Biophotonics Center at Einstein. He is one of ZBP1's discoverers and leader of the current study.
Researchers have subsequently found that ZBP1 is reactivated in several types of cancer, including breast, colorectal, and non-small cell lung cancers; but the gene is silenced in metastasizing cancer cells, as was shown by Dr. Singer and another Einstein scientist, John Condeelis, Ph.D., who also is co-chair of anatomy and structural biology and co-director of the Gruss-Lipper Biophotonics Center at Einstein. The purpose of the current study was to find how the ZBP1 gene is activated and silenced and how it influences the spread of breast cancer.
After examining mouse, rat, and human breast cancer cells, Dr. Singer and his team found that ZBP1 silencing occurs when a methyl group (CH3) attaches to ZBP1's promoter region (the segment of a gene where gene expression is initiated). The attachment of CH3 prevents the promoter from binding to a protein called beta-catenin. And without beta-catenin, the ZBP1 gene is effectively silenced.
The study also showed that the silencing of ZBP1 increases cancer cells' ability to migrate and promotes the proliferation of metastatic cells.
The findings have important implications for forecasting breast cancer outcomes. According to the researchers, signs of ZBP1 silencing in breast cancer cells would indicate that a breast tumor is likely to spread - information that would help in choosing a treatment strategy.
The study also points to potential targets for drug treatment. "If you could turn on this protein in cancer cells, or prevent it from being turned off, you could seriously reduce the ability of the cells to metastasize," says Dr. Singer.
The research team is investigating whether the ZBP1 gene in cancer cells could be reactivated - and the cells prevented from metastasizing - by selectively removing CH3 from the ZBP1 promoter.
The paper, "Increased proliferation and migration of breast metastatic cells results from ZBP1 repression by blocking beta-catenin promoter binding," is published in the May 20, 2009, online edition of the Journal of Cell Science. Wei Gu, M.D., Ph.D., instructor in anatomy and structural biology at Einstein, is the lead author. Feng Pan, Ph.D., now at NYU School of Medicine, is a co-author.
Source:
Deirdre Branley
Albert Einstein College of Medicine
A few years ago, Einstein scientists discovered a gene called ZBP1 (zipcode binding protein 1), which helps cells to move, grow and organize spatially. "ZBP1 is very active in the developing embryo but largely silent in adult tissues," says Robert H. Singer, Ph.D., professor and co-chair of anatomy and structural biology and co-director of the Gruss-Lipper Biophotonics Center at Einstein. He is one of ZBP1's discoverers and leader of the current study.
Researchers have subsequently found that ZBP1 is reactivated in several types of cancer, including breast, colorectal, and non-small cell lung cancers; but the gene is silenced in metastasizing cancer cells, as was shown by Dr. Singer and another Einstein scientist, John Condeelis, Ph.D., who also is co-chair of anatomy and structural biology and co-director of the Gruss-Lipper Biophotonics Center at Einstein. The purpose of the current study was to find how the ZBP1 gene is activated and silenced and how it influences the spread of breast cancer.
After examining mouse, rat, and human breast cancer cells, Dr. Singer and his team found that ZBP1 silencing occurs when a methyl group (CH3) attaches to ZBP1's promoter region (the segment of a gene where gene expression is initiated). The attachment of CH3 prevents the promoter from binding to a protein called beta-catenin. And without beta-catenin, the ZBP1 gene is effectively silenced.
The study also showed that the silencing of ZBP1 increases cancer cells' ability to migrate and promotes the proliferation of metastatic cells.
The findings have important implications for forecasting breast cancer outcomes. According to the researchers, signs of ZBP1 silencing in breast cancer cells would indicate that a breast tumor is likely to spread - information that would help in choosing a treatment strategy.
The study also points to potential targets for drug treatment. "If you could turn on this protein in cancer cells, or prevent it from being turned off, you could seriously reduce the ability of the cells to metastasize," says Dr. Singer.
The research team is investigating whether the ZBP1 gene in cancer cells could be reactivated - and the cells prevented from metastasizing - by selectively removing CH3 from the ZBP1 promoter.
The paper, "Increased proliferation and migration of breast metastatic cells results from ZBP1 repression by blocking beta-catenin promoter binding," is published in the May 20, 2009, online edition of the Journal of Cell Science. Wei Gu, M.D., Ph.D., instructor in anatomy and structural biology at Einstein, is the lead author. Feng Pan, Ph.D., now at NYU School of Medicine, is a co-author.
Source:
Deirdre Branley
Albert Einstein College of Medicine
понедельник, 5 сентября 2011 г.
An Advance On New Generations Of Chemotherapy And Antiviral Drugs
Researchers are describing progress toward developing a new generation of chemotherapy agents that target and block uncontrolled DNA replication - a hallmark of cancer, viral infections, and other diseases - more effectively than current drugs in ways that may produce fewer side effects. Their article is scheduled for the Aug. 27 issue of ACS' Biochemistry, a weekly journal.
In the article, Anthony J. Berdis updates and reviews worldwide research efforts to develop drugs that target DNA polymerases, the enzymes responsible for assembling DNA from its component parts. Several promising strategies are already in use that inhibit uncontrolled DNA replication, particularly in anticancer therapy, but most produce severe side effects and are hampered by drug resistance, the researcher notes.
Berdis says that one of the more promising strategies to date involves the use of so-called nucleoside analogues, artificial pieces of DNA that inhibit replication by substituting for natural segments. Most nucleoside analogues directly target the active site of the polymerase enzyme, a non-specific approach that can also harm healthy cells which contain the enzyme. Berdis describes an alternative approach in which the drugs directly target damaged DNA while avoiding healthy DNA, side-stepping the polymerase enzymes of normal cells. The development, which shows promise in preliminary lab studies, could lead to improved nucleoside analogues with fewer side effects, he says. - MTS
"DNA Polymerases as Therapeutic Targets"
Biochemistry, 47 (32), 8253 - 8260, 2008. 10.1021/bi801179f
Download Full Text Article
American Chemical Society
In the article, Anthony J. Berdis updates and reviews worldwide research efforts to develop drugs that target DNA polymerases, the enzymes responsible for assembling DNA from its component parts. Several promising strategies are already in use that inhibit uncontrolled DNA replication, particularly in anticancer therapy, but most produce severe side effects and are hampered by drug resistance, the researcher notes.
Berdis says that one of the more promising strategies to date involves the use of so-called nucleoside analogues, artificial pieces of DNA that inhibit replication by substituting for natural segments. Most nucleoside analogues directly target the active site of the polymerase enzyme, a non-specific approach that can also harm healthy cells which contain the enzyme. Berdis describes an alternative approach in which the drugs directly target damaged DNA while avoiding healthy DNA, side-stepping the polymerase enzymes of normal cells. The development, which shows promise in preliminary lab studies, could lead to improved nucleoside analogues with fewer side effects, he says. - MTS
"DNA Polymerases as Therapeutic Targets"
Biochemistry, 47 (32), 8253 - 8260, 2008. 10.1021/bi801179f
Download Full Text Article
American Chemical Society
пятница, 2 сентября 2011 г.
Do Angry Men Get Noticed?
By comparing how quickly human facial expressions of different types are detected in a crowd of neutral faces, researchers have demonstrated that male angry faces are a priority for visual processing - particularly for male observers. The findings are reported by Mark Williams of the Massachusetts Institute of Technology and Jason Mattingley of the University of Melbourne, Australia, and appear in the June 6th issue of Current Biology.
In evolutionary terms, it makes sense that our attention is attracted by threat in the environment. It has long been hypothesized that facial expressions that signal potential threat, such as anger, may capture attention and therefore "stand out" in a crowd. In fact, there are specific brain regions that are dedicated to processing threatening facial expressions. Given the many differences between males and females, with males being larger and more physically aggressive than females, one might also suspect differences in the way in which threat is detected from individuals of different genders.
In the new work, Williams and Mattingley show that angry male faces are found more rapidly than angry female faces by both men and women. In addition, men find angry faces of both genders faster than women, whereas women find socially relevant expressions (for example, happy or sad) more rapidly. The work suggests that although males are biased toward detecting threatening faces, and females are more attuned to socially relevant expressions, both sexes prioritize the detection of angry male faces; in short, angry men get noticed. The advantage for detecting angry male faces is consistent with the notion that human perceptual processes have been shaped by evolutionary pressures arising from the social environment.
Heidi Hardman
hhardmancell
Cell Press
cellpress/
In evolutionary terms, it makes sense that our attention is attracted by threat in the environment. It has long been hypothesized that facial expressions that signal potential threat, such as anger, may capture attention and therefore "stand out" in a crowd. In fact, there are specific brain regions that are dedicated to processing threatening facial expressions. Given the many differences between males and females, with males being larger and more physically aggressive than females, one might also suspect differences in the way in which threat is detected from individuals of different genders.
In the new work, Williams and Mattingley show that angry male faces are found more rapidly than angry female faces by both men and women. In addition, men find angry faces of both genders faster than women, whereas women find socially relevant expressions (for example, happy or sad) more rapidly. The work suggests that although males are biased toward detecting threatening faces, and females are more attuned to socially relevant expressions, both sexes prioritize the detection of angry male faces; in short, angry men get noticed. The advantage for detecting angry male faces is consistent with the notion that human perceptual processes have been shaped by evolutionary pressures arising from the social environment.
Heidi Hardman
hhardmancell
Cell Press
cellpress/
вторник, 30 августа 2011 г.
NIST Chemical Microscopy Shows Potential For Cell Diagnostics
A paper by researchers at the National Institute of Standards and Technology (NIST) may breathe new life into the use of a powerful - but tricky - diagnostic technique for cell biology. The paper,* appearing this week in the Biophysical Journal, demonstrates that with improved hardware and better signal processing, a powerful form of molecular vibration spectroscopy can quickly deliver detailed molecular maps of the contents of cells without damaging them. Earlier studies have suggested that to be useful, the technique would need power levels too high for cells.
The technique, "B-CARS,"** is one of several variations on Raman spectroscopy, which measures the frequencies associated with different modes of vibration of atoms and their bonds in a molecule. The exact mix of these frequencies is an extremely discriminating "fingerprint" for any particular molecule, so Raman spectroscopy has been used as a chemical microscope, able to detail the structure of complex objects by mapping the chemical composition at each point in a three-dimensional space.
In the biosciences, according to NIST chemist Marcus Cicerone, Raman spectroscopy has been used to detect microscopic cellular components such as mitochondria, detect how stem cells differentiate into new forms and distinguish between subtly different cell and tissue types. It can, for example, detect minor differences between various precancerous and cancerous cells, potentially providing valuable medical diagnostic information. Even better, it does this without the need to add fluorescent dyes or other chemical tags to identify specific proteins.
The catch, says Cicerone, is speed. The usual method, spontaneous Raman scattering takes a long time to gather enough data to generate a single spectrum - as much as seven minutes for fine detail - and that's for each point in the image. "Seven minutes or even five seconds per spectrum is not feasible when we need a million spectra for an image," he observes. CARS, which uses a pair of lasers to pump up the vibrational states and increase signal, is part of the answer. The current breakthroughs for a broadband CARS instrument developed at NIST since 2004, says Cicerone, gets the same information in 50 milliseconds per pixel.
The new catch is power. Recent papers have argued that to get the necessary data, the lasers used in CARS must run at power levels above the damage threshold for living cells, making the technique nearly useless for clinical purposes. Not quite, according to the NIST team. Their paper describes a combination of improved hardware to gather spectra over a very broad range of wavelengths, and a clever mathematical technique that effectively amplifies the useable signal by examining a portion of signal normally ignored as background interference. The result, says Cicerone, pushes their minimum power level below the damage threshold while retaining the speed of CARS. "We have all the information that you have in a Raman spectrum but we get it 5 to 100 times faster," he says, adding that some obvious modifications should push that higher, opening the door to more widespread use of vibrational spectroscopy in both biology and clinical diagnosis.
Notes:
* S.H. Parekh, Y.J. Lee, K.A. Aamer and M.T. Cicerone. Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy. Biophysical Journal. V. 99, Oct. 13, 2010.
** For "broadband coherent anti-Stokes Raman scattering"
Source:
Michael Baum
National Institute of Standards and Technology (NIST)
The technique, "B-CARS,"** is one of several variations on Raman spectroscopy, which measures the frequencies associated with different modes of vibration of atoms and their bonds in a molecule. The exact mix of these frequencies is an extremely discriminating "fingerprint" for any particular molecule, so Raman spectroscopy has been used as a chemical microscope, able to detail the structure of complex objects by mapping the chemical composition at each point in a three-dimensional space.
In the biosciences, according to NIST chemist Marcus Cicerone, Raman spectroscopy has been used to detect microscopic cellular components such as mitochondria, detect how stem cells differentiate into new forms and distinguish between subtly different cell and tissue types. It can, for example, detect minor differences between various precancerous and cancerous cells, potentially providing valuable medical diagnostic information. Even better, it does this without the need to add fluorescent dyes or other chemical tags to identify specific proteins.
The catch, says Cicerone, is speed. The usual method, spontaneous Raman scattering takes a long time to gather enough data to generate a single spectrum - as much as seven minutes for fine detail - and that's for each point in the image. "Seven minutes or even five seconds per spectrum is not feasible when we need a million spectra for an image," he observes. CARS, which uses a pair of lasers to pump up the vibrational states and increase signal, is part of the answer. The current breakthroughs for a broadband CARS instrument developed at NIST since 2004, says Cicerone, gets the same information in 50 milliseconds per pixel.
The new catch is power. Recent papers have argued that to get the necessary data, the lasers used in CARS must run at power levels above the damage threshold for living cells, making the technique nearly useless for clinical purposes. Not quite, according to the NIST team. Their paper describes a combination of improved hardware to gather spectra over a very broad range of wavelengths, and a clever mathematical technique that effectively amplifies the useable signal by examining a portion of signal normally ignored as background interference. The result, says Cicerone, pushes their minimum power level below the damage threshold while retaining the speed of CARS. "We have all the information that you have in a Raman spectrum but we get it 5 to 100 times faster," he says, adding that some obvious modifications should push that higher, opening the door to more widespread use of vibrational spectroscopy in both biology and clinical diagnosis.
Notes:
* S.H. Parekh, Y.J. Lee, K.A. Aamer and M.T. Cicerone. Label-free cellular imaging by broadband coherent anti-Stokes Raman scattering microscopy. Biophysical Journal. V. 99, Oct. 13, 2010.
** For "broadband coherent anti-Stokes Raman scattering"
Source:
Michael Baum
National Institute of Standards and Technology (NIST)
суббота, 27 августа 2011 г.
Preventing Cancer Without Killing Cells
Inducing senescence in aged cells may be sufficient to guard against spontaneous cancer development, according to a paper published online this week in EMBO reports. It was previously unknown whether cellular senescence or programmed cell death apoptosis was the more important safeguard mechanism for suppressing tumours arising from dysfunctional telomeres.
Aged cells have abnormal chromosomes with dysfunctional telomeres shorter ends that can promote tumorigenesis in the absence of the tumour suppressor p53, and may be related to the higher incidence of cancer in older individuals. However, in the presence of p53, dysfunctional telomeres can induce a permanent arrest of cell growth, known as senescence. Sandy Chang and colleagues studied mutant mice with dysfunctional telomeres and copies of the p53 gene that cannot initiate p53-dependent apoptosis but can execute p53-mediated senescence.
The authors found that activating the senescence pathway was sufficient to suppress spontaneous tumorigenesis. Their findings suggest that, by halting cellular proliferation, p53-mediated senescence may act as an important tumour suppressor mechanism in aged cells.
EUROPEAN MOLECULAR BIOLOGY ORGANIZATION (EMBO)
Postfach 1022.40
D-69012 Heidelberg
embo
Aged cells have abnormal chromosomes with dysfunctional telomeres shorter ends that can promote tumorigenesis in the absence of the tumour suppressor p53, and may be related to the higher incidence of cancer in older individuals. However, in the presence of p53, dysfunctional telomeres can induce a permanent arrest of cell growth, known as senescence. Sandy Chang and colleagues studied mutant mice with dysfunctional telomeres and copies of the p53 gene that cannot initiate p53-dependent apoptosis but can execute p53-mediated senescence.
The authors found that activating the senescence pathway was sufficient to suppress spontaneous tumorigenesis. Their findings suggest that, by halting cellular proliferation, p53-mediated senescence may act as an important tumour suppressor mechanism in aged cells.
EUROPEAN MOLECULAR BIOLOGY ORGANIZATION (EMBO)
Postfach 1022.40
D-69012 Heidelberg
embo
среда, 24 августа 2011 г.
Obesity Battle Aided By Red Wine's Resveratrol
Resveratrol, a compound present in grapes and red wine, reduces the number of fat cells and may one day be used to treat or prevent obesity, according to a new study. The results were presented at The Endocrine Society's 90th Annual Meeting in San Francisco.
Past research found that resveratrol protected laboratory mice that were fed a high-calorie diet from the health problems of obesity, by mimicking the effects of calorie restriction. Researchers at the University of Ulm in Germany wanted to know if resveratrol could mimic the effects of calorie restriction in human fat cells by changing their size or function. The German team used a strain of human fat cell precursors, called preadipocytes. In the body, these cells develop into mature fat cells, according to the study's lead author, Pamela Fischer-Posovszky, PhD, a pediatric endocrinology research fellow in the university's Diabetes and Obesity Unit.
In the cell-based study, they found that resveratrol inhibited the pre-fat cells from increasing and prevented them from converting into mature fat cells. Also, resveratrol hindered fat storage. Most interesting, according to Fischer-Posovszky, was that resveratrol reduced production of certain cytokines (interleukins 6 and 8), substances that may be linked to the development of obesity-related disorders, such as diabetes and clogged coronary arteries. Also, resveratrol stimulated formation of a protein known to decrease the risk of heart attack. Obesity decreases this substance, called adiponectin.
The new finding is consistent with the theory that the resveratrol in red wine explains the French paradox, the observation that French people eat a relatively high-fat diet but have a low death rate from heart disease.
"Resveratrol has anti-obesity properties by exerting its effects directly on the fat cells," Fischer-Posovszky said. "Thus, resveratrol might help to prevent development of obesity or might be suited to treating obesity."
Fischer-Posovszky cautioned that, while the health benefits of resveratrol seem promising, there is not sufficient knowledge about the effects of long-term treatment. One small study found that a single dose of up to 5 grams of resveratrol (much higher than the amount in a bottle of red wine) caused no serious ill effects in healthy volunteers, she pointed out. However, she said another study theorized that resveratrol may stimulate the growth of human breast cancer cells, possibly because resveratrol's chemical structure is similar to a phytoestrogen, an estrogen-like substance found in some plants.
This study was partly funded by the German Research Association (Deutsche Forschungsgemeinschaft) and the Ministry of Science, Research and Arts (Ministerium fuer Wissenschaft, Forschung und Kunst), Baden-Wuerttemberg.
Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at endo-society/.
Source: Aaron Lohr
The Endocrine Society
Past research found that resveratrol protected laboratory mice that were fed a high-calorie diet from the health problems of obesity, by mimicking the effects of calorie restriction. Researchers at the University of Ulm in Germany wanted to know if resveratrol could mimic the effects of calorie restriction in human fat cells by changing their size or function. The German team used a strain of human fat cell precursors, called preadipocytes. In the body, these cells develop into mature fat cells, according to the study's lead author, Pamela Fischer-Posovszky, PhD, a pediatric endocrinology research fellow in the university's Diabetes and Obesity Unit.
In the cell-based study, they found that resveratrol inhibited the pre-fat cells from increasing and prevented them from converting into mature fat cells. Also, resveratrol hindered fat storage. Most interesting, according to Fischer-Posovszky, was that resveratrol reduced production of certain cytokines (interleukins 6 and 8), substances that may be linked to the development of obesity-related disorders, such as diabetes and clogged coronary arteries. Also, resveratrol stimulated formation of a protein known to decrease the risk of heart attack. Obesity decreases this substance, called adiponectin.
The new finding is consistent with the theory that the resveratrol in red wine explains the French paradox, the observation that French people eat a relatively high-fat diet but have a low death rate from heart disease.
"Resveratrol has anti-obesity properties by exerting its effects directly on the fat cells," Fischer-Posovszky said. "Thus, resveratrol might help to prevent development of obesity or might be suited to treating obesity."
Fischer-Posovszky cautioned that, while the health benefits of resveratrol seem promising, there is not sufficient knowledge about the effects of long-term treatment. One small study found that a single dose of up to 5 grams of resveratrol (much higher than the amount in a bottle of red wine) caused no serious ill effects in healthy volunteers, she pointed out. However, she said another study theorized that resveratrol may stimulate the growth of human breast cancer cells, possibly because resveratrol's chemical structure is similar to a phytoestrogen, an estrogen-like substance found in some plants.
This study was partly funded by the German Research Association (Deutsche Forschungsgemeinschaft) and the Ministry of Science, Research and Arts (Ministerium fuer Wissenschaft, Forschung und Kunst), Baden-Wuerttemberg.
Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at endo-society/.
Source: Aaron Lohr
The Endocrine Society
воскресенье, 21 августа 2011 г.
Transgenic Mouse Models In Drug Metabolism And Transport: Free AAPS Webinar
The second part of a two-session series to discuss issues from basic research and drug development perspectives
WHO:
The American Association of Pharmaceutical Scientists (AAPS) is a professional, scientific society of approximately 12,000 members employed in industry, academia, government and other research institutes worldwide. Founded in 1986, AAPS provides a dynamic international forum for the exchange of knowledge among scientists to enhance their contributions to public health. AAPS offers timely scientific programs, on-going education, information resources, opportunities for networking, and professional development.
WHAT:
AAPS is pleased to present the complimentary eLearning Webinar on Transgenic Mouse Models in Drug Metabolism and Transport (Session II). This module is organized by the AAPS Pharmacokinetics, Pharmacodynamics and Drug Metabolism Section. This Webinar will be conducted by Xinxin Ding, Ph.D.
WHY:
The purpose of this free Webinar is to educate participants on how animal models allow direct examination of the role that a specific metabolizing enzyme or transporter plays in the disposition, clearance, efficacy, and toxicity of a particular drug or xenobiotic in a whole body system. Participants will gain understanding of the powerful insight these models provide into potential clinical outcomes associated with specific new therapeutics.
WHEN:
October 27, 2009
10:00 AM to 11:30 AM EDT
HOW:
For additional information about the workshop, and to register, visit aapspharmaceutica/webinars/transgenicmodels2.
Session I of this Webinar is archived at mediaserver.aapspharmaceutica/meetings/webinars/archives.pdf.
Source:
Joseph Catapano
American Association of Pharmaceutical Scientists
WHO:
The American Association of Pharmaceutical Scientists (AAPS) is a professional, scientific society of approximately 12,000 members employed in industry, academia, government and other research institutes worldwide. Founded in 1986, AAPS provides a dynamic international forum for the exchange of knowledge among scientists to enhance their contributions to public health. AAPS offers timely scientific programs, on-going education, information resources, opportunities for networking, and professional development.
WHAT:
AAPS is pleased to present the complimentary eLearning Webinar on Transgenic Mouse Models in Drug Metabolism and Transport (Session II). This module is organized by the AAPS Pharmacokinetics, Pharmacodynamics and Drug Metabolism Section. This Webinar will be conducted by Xinxin Ding, Ph.D.
WHY:
The purpose of this free Webinar is to educate participants on how animal models allow direct examination of the role that a specific metabolizing enzyme or transporter plays in the disposition, clearance, efficacy, and toxicity of a particular drug or xenobiotic in a whole body system. Participants will gain understanding of the powerful insight these models provide into potential clinical outcomes associated with specific new therapeutics.
WHEN:
October 27, 2009
10:00 AM to 11:30 AM EDT
HOW:
For additional information about the workshop, and to register, visit aapspharmaceutica/webinars/transgenicmodels2.
Session I of this Webinar is archived at mediaserver.aapspharmaceutica/meetings/webinars/archives.pdf.
Source:
Joseph Catapano
American Association of Pharmaceutical Scientists
четверг, 18 августа 2011 г.
Cooked Ham With A 39 Day Shelf Life, UK
Cooked ham could soon be given a 39 day shelf life, according to scientists
speaking today Tuesday 4 September 2007 at the Society for General
Microbiology's 161st Meeting at the University of Edinburgh, UK, which runs from 3-6
September 2007.
Traditional cooked ham has a maximum shelf life of three to four weeks (21-28
days), including the time from processing to shoppers buying the sliced meat in a
supermarket. Currently cooked ham has 55% of the UK cooked meat market, and to
maintain and expand this market processors are looking at new technologies to
extend shelf life and open up new European markets for pork products.
"Many dairy products such as cheeses and yoghurts and some fermented meat
products already use lactic acid producing bacteria to protect and preserve their
products, and we know these are acceptable to consumers in terms of taste", says
Roisin Lagan from the College of Agriculture, Food & Rural Enterprise in
Cookstown, County Tyrone, Northern Ireland. "We investigated the possibility of
extending the shelf life of cooked and sliced ham by treating it with a protective
culture of Lactobacillus sakei, a common lactic acid producing bacterium".
When the commercially cured and then Lactobacillus treated meat was tasted by an
untrained panel of consumers it was rated as tastier, with a better texture and
overall more acceptability than the same conventionally treated ham. Chemical
studies showed that the bacteria treated ham was drier and slightly more acidic than
the conventionally preserved version of the meat.
The food scientists then looked at the shelf life of the new product and found that
the lactic acid bacteria culture helped to prevent other types of bacteria from
growing on the treated ham, protecting it from possible contamination by food
poisoning bacteria or ones which would taint it by destroying its flavour and texture.
"This means that we have found a reliable and cost effective way of developing a
tasty ham product with a maximum shelf life of 39 days when stored at 4°C" says
Roisin Lagan. "This in turn will allow processors to have longer production runs
leading to less wastage, thus reducing the environmental impact of storing and
processing food waste. The increased shelf life will allow UK companies to compete
more effectively on a global scale. Consumers will be assured a reliable, safe
cooked ham product".
Dr Lagan is presenting the poster 'Shelf life extension of cooked ham using a bioprotective
culture' at 1030 on Tuesday 04 September 2007 in the Plenary session of the 161st
Meeting of the Society for General Microbiology at the University of Edinburgh, 03 - 06
September 2007.
Full programme details of this meeting can be found on the Society's website here. Hard copies are available
on request from the SGM.
The Society for General Microbiology is the largest microbiology society in Europe, and
has over 5,500 members worldwide. The Society provides a common meeting ground for
scientists working in research and in fields with applications in microbiology including
medicine, veterinary medicine, pharmaceuticals, industry, agriculture, food, the
environment and education.
The SGM represents the science and profession of microbiology to government, the media
and the general public; supporting microbiology education at all levels; and encouraging
careers in microbiology.
sgm.ac.uk
speaking today Tuesday 4 September 2007 at the Society for General
Microbiology's 161st Meeting at the University of Edinburgh, UK, which runs from 3-6
September 2007.
Traditional cooked ham has a maximum shelf life of three to four weeks (21-28
days), including the time from processing to shoppers buying the sliced meat in a
supermarket. Currently cooked ham has 55% of the UK cooked meat market, and to
maintain and expand this market processors are looking at new technologies to
extend shelf life and open up new European markets for pork products.
"Many dairy products such as cheeses and yoghurts and some fermented meat
products already use lactic acid producing bacteria to protect and preserve their
products, and we know these are acceptable to consumers in terms of taste", says
Roisin Lagan from the College of Agriculture, Food & Rural Enterprise in
Cookstown, County Tyrone, Northern Ireland. "We investigated the possibility of
extending the shelf life of cooked and sliced ham by treating it with a protective
culture of Lactobacillus sakei, a common lactic acid producing bacterium".
When the commercially cured and then Lactobacillus treated meat was tasted by an
untrained panel of consumers it was rated as tastier, with a better texture and
overall more acceptability than the same conventionally treated ham. Chemical
studies showed that the bacteria treated ham was drier and slightly more acidic than
the conventionally preserved version of the meat.
The food scientists then looked at the shelf life of the new product and found that
the lactic acid bacteria culture helped to prevent other types of bacteria from
growing on the treated ham, protecting it from possible contamination by food
poisoning bacteria or ones which would taint it by destroying its flavour and texture.
"This means that we have found a reliable and cost effective way of developing a
tasty ham product with a maximum shelf life of 39 days when stored at 4°C" says
Roisin Lagan. "This in turn will allow processors to have longer production runs
leading to less wastage, thus reducing the environmental impact of storing and
processing food waste. The increased shelf life will allow UK companies to compete
more effectively on a global scale. Consumers will be assured a reliable, safe
cooked ham product".
Dr Lagan is presenting the poster 'Shelf life extension of cooked ham using a bioprotective
culture' at 1030 on Tuesday 04 September 2007 in the Plenary session of the 161st
Meeting of the Society for General Microbiology at the University of Edinburgh, 03 - 06
September 2007.
Full programme details of this meeting can be found on the Society's website here. Hard copies are available
on request from the SGM.
The Society for General Microbiology is the largest microbiology society in Europe, and
has over 5,500 members worldwide. The Society provides a common meeting ground for
scientists working in research and in fields with applications in microbiology including
medicine, veterinary medicine, pharmaceuticals, industry, agriculture, food, the
environment and education.
The SGM represents the science and profession of microbiology to government, the media
and the general public; supporting microbiology education at all levels; and encouraging
careers in microbiology.
sgm.ac.uk
понедельник, 15 августа 2011 г.
Common Field Mice Confirm Genetic Change Happens Fast
While looks can be deceiving, heredity is revealing, and two scientists who've studied the genetic makeup of a common field mouse report that what's most revealing to them is how fast both genes and morphology can change.
Oliver Pergams, visiting research assistant professor of biological sciences at the University of Illinois at Chicago, and Robert Lacy, population geneticist and conservation biologist at the Chicago Zoological Society, compared the genetic makeup of 115 white-footed mice in the Volo Bog State Natural Area northwest of Chicago using mitochondrial DNA taken from collection samples as old as 150 years and mice collected in recent years.
They found a new type of mouse replaced the old type in Volo Bog between 1976 and 2001.
"The new mice were genetically very different," says Pergams. Structural changes were readily apparent. "Looking at size and shape, the new mice were much bigger and a little flatter."
Pergams and Lacy report the findings in Molecular Ecology, Volume 17, now online, and in print in late December.
Pergams and UIC biological sciences professor Mary Ashley reported in 2001 on similar morphological changes in size and shape over the past century of two widely disparate habitats and species -- deer mice on three different California Channel Islands, and black rats from two Galapagos Islands. While Pergams found these coincidental changes surprising, he said it is too soon to say if this is somehow related to world climate change.
Pergams said the Volo Bog change is best explained by the old mice being replaced by new mice migrating from distinct neighboring populations that are better adapted to survival in the protected bog, which is now surrounded by suburban residential communities.
"This was likely helped by the large environmental changes occurring over the 1976-2001 time period. Replacement with better-adapted genotypes from external populations may be a common way evolution works in an increasingly human-impacted world," Pergams said.
Lacy studies and compares changes of Volo Bog mice both in the wild and in subsequent generations of their offspring raised in his laboratory.
"It was surprising to us to see how fast genetic and physical change could occur even in the wild population," he said.
Pergams said a lesson of the surprisingly fast replacement of the mouse types is not to assume that animal populations are constant. He also said there's a message for environmentalists.
"Humans are changing the global environment at unprecedented rates," he said. "Plants and animals react to these massive environmental changes either by going extinct or [by] adapting very rapidly."
Source: Paul Francuch
University of Illinois at Chicago
Oliver Pergams, visiting research assistant professor of biological sciences at the University of Illinois at Chicago, and Robert Lacy, population geneticist and conservation biologist at the Chicago Zoological Society, compared the genetic makeup of 115 white-footed mice in the Volo Bog State Natural Area northwest of Chicago using mitochondrial DNA taken from collection samples as old as 150 years and mice collected in recent years.
They found a new type of mouse replaced the old type in Volo Bog between 1976 and 2001.
"The new mice were genetically very different," says Pergams. Structural changes were readily apparent. "Looking at size and shape, the new mice were much bigger and a little flatter."
Pergams and Lacy report the findings in Molecular Ecology, Volume 17, now online, and in print in late December.
Pergams and UIC biological sciences professor Mary Ashley reported in 2001 on similar morphological changes in size and shape over the past century of two widely disparate habitats and species -- deer mice on three different California Channel Islands, and black rats from two Galapagos Islands. While Pergams found these coincidental changes surprising, he said it is too soon to say if this is somehow related to world climate change.
Pergams said the Volo Bog change is best explained by the old mice being replaced by new mice migrating from distinct neighboring populations that are better adapted to survival in the protected bog, which is now surrounded by suburban residential communities.
"This was likely helped by the large environmental changes occurring over the 1976-2001 time period. Replacement with better-adapted genotypes from external populations may be a common way evolution works in an increasingly human-impacted world," Pergams said.
Lacy studies and compares changes of Volo Bog mice both in the wild and in subsequent generations of their offspring raised in his laboratory.
"It was surprising to us to see how fast genetic and physical change could occur even in the wild population," he said.
Pergams said a lesson of the surprisingly fast replacement of the mouse types is not to assume that animal populations are constant. He also said there's a message for environmentalists.
"Humans are changing the global environment at unprecedented rates," he said. "Plants and animals react to these massive environmental changes either by going extinct or [by] adapting very rapidly."
Source: Paul Francuch
University of Illinois at Chicago
пятница, 12 августа 2011 г.
Why Are Men More Susceptible To Alcoholism?
Alcohol is one of the most commonly abused substances, and men are up to twice as likely to develop alcoholism as women. Until now, the underlying biology contributing to this difference in vulnerability has remained unclear.
A new study published in Biological Psychiatry reveals that dopamine may be an important factor.
Researchers from Columbia and Yale studied male and female college-age social drinkers in a laboratory test of alcohol consumption. After consuming an alcoholic or non-alcoholic drink, each participant underwent a specialized positron emission tomography (PET) scan, an imaging technique that can measure the amount of alcohol-induced dopamine release.
Dopamine has multiple functions in the brain, but is important in this context because of its pleasurable effects when it is released by rewarding experiences, such as sex or drugs.
Despite similar consumptions of alcohol, the men had greater dopamine release than women. This increase was found in the ventral striatum, an area in the brain strongly associated with pleasure, reinforcement and addiction formation.
"In men, increased dopamine release also had a stronger association with subjective positive effects of alcohol intoxication," explained Dr. Nina Urban, corresponding author for this study. "This may contribute to the initial reinforcing properties of alcohol and the risk for habit formation."
Dr. Anissa Abi-Dargham, senior author on this project, notes that "another important observation from this study is the decline in alcohol-induced dopamine release with repeated heavy drinking episodes. This may be one of the hallmarks of developing tolerance or transitioning into habit."
These findings indicate that the ability of alcohol to stimulate dopamine release may play an important and complex role in its rewarding effects and abuse liability in humans. This identification of an in vivo neurochemical mechanism that could help explain the sex difference in alcoholism is an exciting step forward in alcoholism research.
Sources: Elsevier, AlphaGalileo Foundation.
A new study published in Biological Psychiatry reveals that dopamine may be an important factor.
Researchers from Columbia and Yale studied male and female college-age social drinkers in a laboratory test of alcohol consumption. After consuming an alcoholic or non-alcoholic drink, each participant underwent a specialized positron emission tomography (PET) scan, an imaging technique that can measure the amount of alcohol-induced dopamine release.
Dopamine has multiple functions in the brain, but is important in this context because of its pleasurable effects when it is released by rewarding experiences, such as sex or drugs.
Despite similar consumptions of alcohol, the men had greater dopamine release than women. This increase was found in the ventral striatum, an area in the brain strongly associated with pleasure, reinforcement and addiction formation.
"In men, increased dopamine release also had a stronger association with subjective positive effects of alcohol intoxication," explained Dr. Nina Urban, corresponding author for this study. "This may contribute to the initial reinforcing properties of alcohol and the risk for habit formation."
Dr. Anissa Abi-Dargham, senior author on this project, notes that "another important observation from this study is the decline in alcohol-induced dopamine release with repeated heavy drinking episodes. This may be one of the hallmarks of developing tolerance or transitioning into habit."
These findings indicate that the ability of alcohol to stimulate dopamine release may play an important and complex role in its rewarding effects and abuse liability in humans. This identification of an in vivo neurochemical mechanism that could help explain the sex difference in alcoholism is an exciting step forward in alcoholism research.
Sources: Elsevier, AlphaGalileo Foundation.
вторник, 9 августа 2011 г.
The Beauty Of Nature And How Size Matters Could Impact On Sustainable Energy
The beauty of nature is partly due to the uniformity of leaf and flower size in individual plants, and scientists have discovered how plants arrive at these aesthetic proportions.
Researchers at the John Innes Centre in Norwich have discovered that cells at the margins of leaves and petals play a particularly important role in setting their size.
"The remarkable uniformity of leaves and flowers helps us to tell different species apart, such as daisies and marguerites, which look very similar otherwise. We are now uncovering how the genetic blueprint of a species tightly controls the size of leaves and flowers", says Dr. Michael Lenhard, who led the research.
The cells at the margins seem to secrete a mobile growth signal that keeps the cells throughout the leaf dividing. The more of this signal is produced, the larger the leaves and flowers get.
Surprisingly, this signal seems to be distinct from the classical and well-studied plant hormones that are known to influence growth and development.
"As the signal only seems to come in from the margins, we suggest it gets diluted as the leaf or petal grows. Once the concentration falls below a certain threshold, the cells in the leaf or petal stop dividing. This would be a simple way of measuring the size of a growing organ", says Dr. Lenhard. "It's a bit like adding more and more tonic to a gin and tonic until you can no longer taste the gin."
Strikingly, animals seem to use the same principle of dilution for measuring size, for example of the wings in a fly, although the molecules used are very different.
Efforts are under way to use this discovery to increase leaf growth in biofuel crops for the generation of sustainable energy and to boost the yield of fruits and seeds.
This research was performed in collaboration with Dr Christian Fleck and his group at the Physics Department, University of Freiburg, Germany, and was funded by the Deutsche Forschungsgemeinschaft and the BBSRC. It will be published in Developmental Cell on 3 December, 12:00 PM Noon Eastern Time US.
Source: Dr. Michael Lenhard
Norwich BioScience Institutes
Researchers at the John Innes Centre in Norwich have discovered that cells at the margins of leaves and petals play a particularly important role in setting their size.
"The remarkable uniformity of leaves and flowers helps us to tell different species apart, such as daisies and marguerites, which look very similar otherwise. We are now uncovering how the genetic blueprint of a species tightly controls the size of leaves and flowers", says Dr. Michael Lenhard, who led the research.
The cells at the margins seem to secrete a mobile growth signal that keeps the cells throughout the leaf dividing. The more of this signal is produced, the larger the leaves and flowers get.
Surprisingly, this signal seems to be distinct from the classical and well-studied plant hormones that are known to influence growth and development.
"As the signal only seems to come in from the margins, we suggest it gets diluted as the leaf or petal grows. Once the concentration falls below a certain threshold, the cells in the leaf or petal stop dividing. This would be a simple way of measuring the size of a growing organ", says Dr. Lenhard. "It's a bit like adding more and more tonic to a gin and tonic until you can no longer taste the gin."
Strikingly, animals seem to use the same principle of dilution for measuring size, for example of the wings in a fly, although the molecules used are very different.
Efforts are under way to use this discovery to increase leaf growth in biofuel crops for the generation of sustainable energy and to boost the yield of fruits and seeds.
This research was performed in collaboration with Dr Christian Fleck and his group at the Physics Department, University of Freiburg, Germany, and was funded by the Deutsche Forschungsgemeinschaft and the BBSRC. It will be published in Developmental Cell on 3 December, 12:00 PM Noon Eastern Time US.
Source: Dr. Michael Lenhard
Norwich BioScience Institutes
суббота, 6 августа 2011 г.
Improved Quality Of Life For Women On Continuous Oral Contraceptives
Continuous oral contraceptives may be more effective than the standard 28-day birth control pills in suppressing the ovary, according to researchers. They say that the continuous pill also causes a significant improvement in pain and behavioral changes.
"We have provided a biological proof of concept that both the ovary and the lining of the uterus are suppressed better and quicker with the continuous pill than with the cyclic pill. And there is no harmful effect on the lining of the uterus either," said Richard Legro, M.D., professor of obstetrics and gynecology, Penn State College of Medicine and lead author of the study.
Standard 28-day birth control pills mimic a woman's natural menstrual cycle, while preventing pregnancy. A standard dose includes 21 hormone pills to suppress growth in the endometrium, the lining of the uterus, and seven placeholder placebo pills.
Continuous oral contraceptives may be more effective in treating several medical conditions, where continuous ovarian suppression is desired, such as acne, hirsutism, premenstrual syndrome, endometriosis and polycystic ovary syndrome. But there have been few detailed studies of ovarian function on the pill to demonstrate this effect.
Legro and his colleagues compared the effectiveness of continuous oral contraceptives with that of the cyclical pills. The researchers monitored 62 healthy women, randomly assigned to receive either cyclical or continuous birth control pills, for six months with both researchers and participants blinded to the study group.
"We monitored vaginal bleeding, quality of life, and ovarian and endometrial suppression," said Legro, whose team's findings appeared in a recent issue of the Journal of Clinical Endocrinology and Metabolism.
The researchers found a significant decrease in moderate to heavy bleeding days among women who received the continuous birth control regimen. Women in the continuous group also had a significant decline in circulating and urinary estrogen levels, total ovarian volume and lead follicle size - all biomarkers that indicate the ovary is less active - and reported less pain and behavioral changes compared to women in the cyclic group.
However, results from the study also indicate greater breakthrough bleeding, or spotting, among women in the continuous group. Legro says that while greater breakthrough bleeding may be a truly objectionable side effect for many women, it does not seem to affect their quality of life.
"That is one of the unique things of this study. The quality of life did not necessarily decrease as it was counterbalanced by improvements in other areas such as pain and mood swings," the Penn State researcher added.
According to Legro, the study suggests that there may be diverse mechanisms of breakthrough bleeding depending on whether a woman is using either a cyclical or continuous regimen of birth control pills.
In the case of cyclic pills, the ovary comes back into the equation during the pill free interval leading to a rebound increased secretion of ovarian hormones, which in turn contributes to some breakthrough bleeding, he explained.
"Breakthrough bleeding in the continuous group, in our opinion, is most likely due to the fact that the pill does too good of a job in suppressing the ovary and the lining of the uterus gets a little bit thin and fragile so that from time to time there is a little bit of bleeding," added Legro, whose work is funded by the National Institutes of Health.
The study provides a physical reason for continuous oral contraceptive pills to treat such chronic medical conditions such as polycystic ovary syndrome, endometriosis and premenstrual syndrome, where additional suppression of the ovary or the endometrium is desired, and Legro noted that other chronic conditions such as hypertension or diabetes are treated continuously, not three weeks out of four. Further studies showing a favorable risk benefit ratio of continuous oral contraceptives on these disorders are the next step.
Other researchers on the paper are Jaimey G. Pauli, M.D.; Allen R. Kunselman, senior research assistant; Richard J. Zaino, M.D., professor of anatomic pathology; Laurence M. Demers, M.D., distinguished professor emeritus; Carol L. Gnatuk, M.D.; and William C. Dodson, M.D., all at Penn State College of Medicine; and Juliana W. Meadows, Ph.D., and James Kesner, Ph.D., both at the National Institute for Occupational Safety and Health, Cincinnati, Ohio.
Source: Amitabh Avasthi
Penn State
"We have provided a biological proof of concept that both the ovary and the lining of the uterus are suppressed better and quicker with the continuous pill than with the cyclic pill. And there is no harmful effect on the lining of the uterus either," said Richard Legro, M.D., professor of obstetrics and gynecology, Penn State College of Medicine and lead author of the study.
Standard 28-day birth control pills mimic a woman's natural menstrual cycle, while preventing pregnancy. A standard dose includes 21 hormone pills to suppress growth in the endometrium, the lining of the uterus, and seven placeholder placebo pills.
Continuous oral contraceptives may be more effective in treating several medical conditions, where continuous ovarian suppression is desired, such as acne, hirsutism, premenstrual syndrome, endometriosis and polycystic ovary syndrome. But there have been few detailed studies of ovarian function on the pill to demonstrate this effect.
Legro and his colleagues compared the effectiveness of continuous oral contraceptives with that of the cyclical pills. The researchers monitored 62 healthy women, randomly assigned to receive either cyclical or continuous birth control pills, for six months with both researchers and participants blinded to the study group.
"We monitored vaginal bleeding, quality of life, and ovarian and endometrial suppression," said Legro, whose team's findings appeared in a recent issue of the Journal of Clinical Endocrinology and Metabolism.
The researchers found a significant decrease in moderate to heavy bleeding days among women who received the continuous birth control regimen. Women in the continuous group also had a significant decline in circulating and urinary estrogen levels, total ovarian volume and lead follicle size - all biomarkers that indicate the ovary is less active - and reported less pain and behavioral changes compared to women in the cyclic group.
However, results from the study also indicate greater breakthrough bleeding, or spotting, among women in the continuous group. Legro says that while greater breakthrough bleeding may be a truly objectionable side effect for many women, it does not seem to affect their quality of life.
"That is one of the unique things of this study. The quality of life did not necessarily decrease as it was counterbalanced by improvements in other areas such as pain and mood swings," the Penn State researcher added.
According to Legro, the study suggests that there may be diverse mechanisms of breakthrough bleeding depending on whether a woman is using either a cyclical or continuous regimen of birth control pills.
In the case of cyclic pills, the ovary comes back into the equation during the pill free interval leading to a rebound increased secretion of ovarian hormones, which in turn contributes to some breakthrough bleeding, he explained.
"Breakthrough bleeding in the continuous group, in our opinion, is most likely due to the fact that the pill does too good of a job in suppressing the ovary and the lining of the uterus gets a little bit thin and fragile so that from time to time there is a little bit of bleeding," added Legro, whose work is funded by the National Institutes of Health.
The study provides a physical reason for continuous oral contraceptive pills to treat such chronic medical conditions such as polycystic ovary syndrome, endometriosis and premenstrual syndrome, where additional suppression of the ovary or the endometrium is desired, and Legro noted that other chronic conditions such as hypertension or diabetes are treated continuously, not three weeks out of four. Further studies showing a favorable risk benefit ratio of continuous oral contraceptives on these disorders are the next step.
Other researchers on the paper are Jaimey G. Pauli, M.D.; Allen R. Kunselman, senior research assistant; Richard J. Zaino, M.D., professor of anatomic pathology; Laurence M. Demers, M.D., distinguished professor emeritus; Carol L. Gnatuk, M.D.; and William C. Dodson, M.D., all at Penn State College of Medicine; and Juliana W. Meadows, Ph.D., and James Kesner, Ph.D., both at the National Institute for Occupational Safety and Health, Cincinnati, Ohio.
Source: Amitabh Avasthi
Penn State
среда, 3 августа 2011 г.
Hepatitis C Virus Channels Efforts Into Cell Survival
Researchers at the University of Leeds have discovered a previously unknown mechanism that allows the hepatitis C virus (HCV) to remain in the body for decades.
A study published in the Proceedings of the National Academy of Sciences (PNAS) shows that the virus blocks the actions of a specific ion channel in the cell membrane that would usually trigger apoptosis - the cell's self-destruct programme - and in doing so, has evolved another way of protecting itself from being eliminated from the body.
Apoptosis occurs naturally in the body to allow the removal of unhealthy cells or the replacement of worn-out cells. One of the ways in which apoptosis can be triggered in a cell is to reduce its potassium levels. This can happen when the cell is exposed to oxidative stress that activates a specific ion channel (which acts as a pore in the cell membrane) causing it to open and allow out potassium ions.
However, the research team has discovered that a protein made by HCV, known as NS5A, is able to block the activation of this ion channel in liver cells, enabling these cells to resist cell death for longer.
"For a virus to persist in the body over a long time, it has to find a way of manipulating the host cell so that it becomes resistant to apoptosis," says lead researcher Professor Mark Harris of the University's Faculty of Biological Sciences. "We know of many ways that viruses have evolved to do this, but this is the first observation of a virus preventing cell death by manipulating an ion channel."
HCV affects some 170 million people globally and only around half of these will respond to treatment. Many sufferers will be asymptomatic - some for twenty or even thirty years - but the virus remains in the liver, and its long-tem damage can ultimately cause cirrhosis or cancer.
"Cells in the liver are often exposed to high levels of oxidative, and other, stresses as they work to detoxify the blood of foreign compounds such as drugs and alcohol, and to remove chemicals produced by our own bodies," says Professor Harris. "In addition, the virus itself causes oxidative stress as it replicates in the cells. The research shows that the virus has evolved another way of protecting itself from this natural process, and to avoid elimination from the body for longer."
The research team believes that continued research may offer a potential target for drug development, perhaps through combination therapy.
"We need to find out exactly how the blocking action works, but it's possible that two drugs could be coupled together, one to prevent the virus from blocking the ion channel and another to induce stress to force apoptosis," says Professor Harris.
"It's a very exciting discovery, and ideally we'd like to expand our investigations to see whether other viruses that cause long term or chronic infections - such as HIV - have evolved the same ability."
The research was funded by the Medical Research Council.
Source:
Clare Elsley
University of Leeds
A study published in the Proceedings of the National Academy of Sciences (PNAS) shows that the virus blocks the actions of a specific ion channel in the cell membrane that would usually trigger apoptosis - the cell's self-destruct programme - and in doing so, has evolved another way of protecting itself from being eliminated from the body.
Apoptosis occurs naturally in the body to allow the removal of unhealthy cells or the replacement of worn-out cells. One of the ways in which apoptosis can be triggered in a cell is to reduce its potassium levels. This can happen when the cell is exposed to oxidative stress that activates a specific ion channel (which acts as a pore in the cell membrane) causing it to open and allow out potassium ions.
However, the research team has discovered that a protein made by HCV, known as NS5A, is able to block the activation of this ion channel in liver cells, enabling these cells to resist cell death for longer.
"For a virus to persist in the body over a long time, it has to find a way of manipulating the host cell so that it becomes resistant to apoptosis," says lead researcher Professor Mark Harris of the University's Faculty of Biological Sciences. "We know of many ways that viruses have evolved to do this, but this is the first observation of a virus preventing cell death by manipulating an ion channel."
HCV affects some 170 million people globally and only around half of these will respond to treatment. Many sufferers will be asymptomatic - some for twenty or even thirty years - but the virus remains in the liver, and its long-tem damage can ultimately cause cirrhosis or cancer.
"Cells in the liver are often exposed to high levels of oxidative, and other, stresses as they work to detoxify the blood of foreign compounds such as drugs and alcohol, and to remove chemicals produced by our own bodies," says Professor Harris. "In addition, the virus itself causes oxidative stress as it replicates in the cells. The research shows that the virus has evolved another way of protecting itself from this natural process, and to avoid elimination from the body for longer."
The research team believes that continued research may offer a potential target for drug development, perhaps through combination therapy.
"We need to find out exactly how the blocking action works, but it's possible that two drugs could be coupled together, one to prevent the virus from blocking the ion channel and another to induce stress to force apoptosis," says Professor Harris.
"It's a very exciting discovery, and ideally we'd like to expand our investigations to see whether other viruses that cause long term or chronic infections - such as HIV - have evolved the same ability."
The research was funded by the Medical Research Council.
Source:
Clare Elsley
University of Leeds
воскресенье, 31 июля 2011 г.
Lateral Excitation Of Bridges By Balancing Pedestrians
On its opening day, the London Millennium Bridge experienced unexpected large oscillations due to crowd loading. It has generally been thought this was due to pedestrians synchronising their footsteps with the bridge motion. However, this is not supported by more recent measurements on other bridges. In contrast with previous research, this study considers the basic way humans maintain balance. This gives the surprising result that pedestrians walking randomly, keeping balance as normal, can cause large bridge oscillations. This finally seems to explain the initiation of the Millennium Bridge 'wobble' and gives new insight for designing bridges to avoid vibration problems.
Proceedings of the Royal Society A: Physical Sciences
Proceedings A has an illustrious history of publishing pioneering and influential research articles across the entire range of the physical and mathematical sciences. These have included Maxwell's electromagnetic theory, the Braggs' first account of X-ray crystallography, Dirac's relativistic theory of the electron, and Watson and Crick's detailed description of the structure of DNA.
Proceedings of the Royal Society A: Physical Sciences
Proceedings of the Royal Society A: Physical Sciences
Proceedings A has an illustrious history of publishing pioneering and influential research articles across the entire range of the physical and mathematical sciences. These have included Maxwell's electromagnetic theory, the Braggs' first account of X-ray crystallography, Dirac's relativistic theory of the electron, and Watson and Crick's detailed description of the structure of DNA.
Proceedings of the Royal Society A: Physical Sciences
четверг, 28 июля 2011 г.
In Fat-Free Mice Liver Fat Reduced By Fat-Free Diet, Researchers Report
Researchers at UT Southwestern Medical Center have uncovered crucial clues about a paradoxical disease in which patients with no body fat develop many of the health complications usually found in obese people.
The findings in mice, appearing online today in Cell Metabolism, have led to the initiation of a National Institutes of Health-funded clinical trial to determine whether eating an extremely low-fat diet could prevent many of the metabolic complications brought on by lipodystrophy.
Lipodystrophies are metabolic disorders characterized by the selective loss of fat tissues and complications of insulin resistance. Scientists speculate that the condition could be caused by the failure of stem cells to become fat cells.
"These patients don't have fatty tissue, even inside their abdomen," said Dr. Abhimanyu Garg, professor of internal medicine at UT Southwestern and senior author of the study. "They basically lack all the fat we see in a typical person, but their livers are loaded with fat. That's a big problem because too much fat in the liver leads to liver damage.
"We cannot do anything to reverse fat loss, but our findings might lead to the development of new therapies for the metabolic complications of lipodystrophy, such as diabetes, fatty liver and high triglycerides," said Dr. Garg, an investigator in the Center for Human Nutrition.
Dr. Garg has been studying patients with lipodystrophies for more than 20 years. He and colleagues at UT Southwestern have led the way in identifying gene mutations responsible for several forms of lipodystrophy and in identifying novel therapeutic approaches for these patients.
In this study, researchers genetically engineered mice to lack a specific enzyme called AGPAT2, which is also lacking in humans with generalized lipodystrophy. Under normal conditions, AGPAT2 is involved in the production of fat in body fat cells. In 2002 Dr. Garg's lab found that the AGPAT2 gene is mutated in patients with congenital generalized lipodystrophy.
"We generated this mouse model to learn why humans with this type of lipodystrophy develop metabolic complications," Dr. Garg said.
The researchers found that mice without the AGPAT2 enzyme used a novel, previously uncharacterized pathway to synthesize fat in their liver. Dietary fat also contributed to fat accumulation in the liver. Typically, particles called chylomicrons carry dietary fat throughout the body and release it in peripheral tissues so that it can either be stored in adipose tissue for later use or immediately burned as energy by muscles. Normally, adipose tissue provides fatty acids for fat synthesis in the liver. In these lipodystrophic mice, however, the adipose tissue did not release the excess fatty acids and the dietary fat accumulated in the liver.
What is surprising about this, Dr. Garg said, is that the amount of fat stored in the liver dropped substantially when researchers put the lipodystrophic mice on a fat-free diet. "Just eliminating the dietary fat reduced liver triglycerides by approximately 50 percent," he said.
In addition to establishing a clinical trial, Dr. Garg said the next step is to study the stem cells from the mice with lipodystrophy in order to determine why their stem cells become bone and muscle but not fat.
Other UT Southwestern researchers involved in the research were Dr. Victor CortГ©s, lead author of the study and postdoctoral researcher in molecular genetics; Dr. David Curtis, surgery resident; Dr. Xinli Shao, research scientist in immunology; Dr. Vinay Parameswara, instructor of internal medicine; Dr. Jimin Ren, instructor in radiology at the Advanced Imaging Research Center; Dr. Victoria Esser, associate professor of internal medicine; Dr. Robert Hammer, professor of biochemistry; Dr. Anil Agarwal, associate professor of internal medicine; and Dr. Jay Horton, professor of internal medicine.
The research was funded by the NIH, Southwestern Medical Foundation and the Perot Foundation. Dr. CortГ©s is supported by a postdoctoral fellowship from Pontificia Universidad CatГіlica de Chile and a presidential fellowship from the Chilean government.
Source: Kristen Holland Shear
UT Southwestern Medical Center
The findings in mice, appearing online today in Cell Metabolism, have led to the initiation of a National Institutes of Health-funded clinical trial to determine whether eating an extremely low-fat diet could prevent many of the metabolic complications brought on by lipodystrophy.
Lipodystrophies are metabolic disorders characterized by the selective loss of fat tissues and complications of insulin resistance. Scientists speculate that the condition could be caused by the failure of stem cells to become fat cells.
"These patients don't have fatty tissue, even inside their abdomen," said Dr. Abhimanyu Garg, professor of internal medicine at UT Southwestern and senior author of the study. "They basically lack all the fat we see in a typical person, but their livers are loaded with fat. That's a big problem because too much fat in the liver leads to liver damage.
"We cannot do anything to reverse fat loss, but our findings might lead to the development of new therapies for the metabolic complications of lipodystrophy, such as diabetes, fatty liver and high triglycerides," said Dr. Garg, an investigator in the Center for Human Nutrition.
Dr. Garg has been studying patients with lipodystrophies for more than 20 years. He and colleagues at UT Southwestern have led the way in identifying gene mutations responsible for several forms of lipodystrophy and in identifying novel therapeutic approaches for these patients.
In this study, researchers genetically engineered mice to lack a specific enzyme called AGPAT2, which is also lacking in humans with generalized lipodystrophy. Under normal conditions, AGPAT2 is involved in the production of fat in body fat cells. In 2002 Dr. Garg's lab found that the AGPAT2 gene is mutated in patients with congenital generalized lipodystrophy.
"We generated this mouse model to learn why humans with this type of lipodystrophy develop metabolic complications," Dr. Garg said.
The researchers found that mice without the AGPAT2 enzyme used a novel, previously uncharacterized pathway to synthesize fat in their liver. Dietary fat also contributed to fat accumulation in the liver. Typically, particles called chylomicrons carry dietary fat throughout the body and release it in peripheral tissues so that it can either be stored in adipose tissue for later use or immediately burned as energy by muscles. Normally, adipose tissue provides fatty acids for fat synthesis in the liver. In these lipodystrophic mice, however, the adipose tissue did not release the excess fatty acids and the dietary fat accumulated in the liver.
What is surprising about this, Dr. Garg said, is that the amount of fat stored in the liver dropped substantially when researchers put the lipodystrophic mice on a fat-free diet. "Just eliminating the dietary fat reduced liver triglycerides by approximately 50 percent," he said.
In addition to establishing a clinical trial, Dr. Garg said the next step is to study the stem cells from the mice with lipodystrophy in order to determine why their stem cells become bone and muscle but not fat.
Other UT Southwestern researchers involved in the research were Dr. Victor CortГ©s, lead author of the study and postdoctoral researcher in molecular genetics; Dr. David Curtis, surgery resident; Dr. Xinli Shao, research scientist in immunology; Dr. Vinay Parameswara, instructor of internal medicine; Dr. Jimin Ren, instructor in radiology at the Advanced Imaging Research Center; Dr. Victoria Esser, associate professor of internal medicine; Dr. Robert Hammer, professor of biochemistry; Dr. Anil Agarwal, associate professor of internal medicine; and Dr. Jay Horton, professor of internal medicine.
The research was funded by the NIH, Southwestern Medical Foundation and the Perot Foundation. Dr. CortГ©s is supported by a postdoctoral fellowship from Pontificia Universidad CatГіlica de Chile and a presidential fellowship from the Chilean government.
Source: Kristen Holland Shear
UT Southwestern Medical Center
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