One of the nation's foremost vascular biologists, Dr. Timothy T. Hla, has been appointed as the new director of the Center for Vascular Biology and professor of pathology and laboratory medicine at Weill Cornell Medical College.
Founded in 1995, Weill Cornell's Center for Vascular Biology is dedicated to biomedical research into vascular disease -- specifically atherosclerosis and thrombosis -- and the contributing role of the vascular system in a wide range of diseases.
Previously leading the Center was its founding director, Dr. David P. Hajjar, executive vice provost and senior executive vice dean; dean of the Graduate School of Medical Sciences; and the Frank H.T. Rhodes Distinguished Professor of Cardiovascular Biology and Genetics and professor of biochemistry and pathology at Weill Cornell Medical College. After 15 years as director, Dr. Hajjar elected to step down in order to focus on comprehensive Medical College initiatives and responsibilities.
"Vascular biology is a tremendously fertile area for research. By better understanding the role of blood vessels in disease, we will improve our ability to develop new treatments for conditions from cancer to arthritis to heart disease," Dr. Hajjar says. "An accomplished researcher, administrator and teacher, Timothy Hla is uniquely qualified to lead this effort at Weill Cornell. Notably, he has made significant contributions to vascular biology across areas including the molecular basis of angiogenesis, the biology of the COX-2 pathway, sphingolipids as mediators in health and disease, and lipid mediators."
Dr. Hla's research into COX-2 has furthered scientific understanding of how this pathway is a molecular determinant of cancer progression and potentially a key component of the link between inflammation and cancer. He was the first to demonstrate exaggerated COX-2 expression in human chronic inflammatory disorders -- specifically rheumatoid arthritis. He subsequently discovered that COX-2 is over-expressed in human colorectal cancer tissues, and demonstrated that COX-2 over-expression in the mammary glands of transgenic mice results in invasive mammary cancer development.
As a postdoctoral fellow, Dr. Hla worked to clone mRNAs that arise during in vitro angiogenesis. During these efforts, he was able to clone the DNA for the orphan receptor EDG-1 (endothelial differentiation gene-1) -- the first-ever example of this kind of receptor in mammalian cell differentiation. And, in searching for EDG-1's binding site, he identified a platelet-derived lipid molecule called sphingosine-1-phosphate (S1P) -- a major discovery that brought together the fields of vascular biology and sphingolipid signaling. This research established S1P as an extracellular lipid mediator that acts in the extracellular environment to communicate between cells by binding to cell surface receptors. S1P receptor modulators are now in Phase III clinical trials to control inflammation in the treatment of multiple sclerosis.
Following the identification of the S1P receptor, Dr. Hla turned his attention to characterizing the signaling properties of S1P receptors and their actions on vascular cells, demonstrating the mechanisms behind formation of a stable vessel. He also showed that S1P signaling is important to tumor angiogenesis.
Dr. Hla's investigative studies have been well funded by the National Institutes of Health (NIH) and other granting agencies. Currently, Dr. Hla serves as principal investigator on two NIH-sponsored R01 awards. He was also granted a MERIT award from the NIH in 2006. In addition, his project grant was renewed by the NIH -- work that he will be continuing at Weill Cornell.
Dr. Hla has contributed significantly to a number of professional organizations and to the editorial boards of leading scientific journals. He has served on the council and as secretary-treasurer of the North American Vascular Biology Organization, and has served as a co-organizer of the 2003, 2005 and 2007 FASEB summer research conferences on lysophospholipids. He serves as editor-in-chief of the publications Prostaglandins and Other Lipid Mediators. He has also served as a member of the editorial boards of the Journal of Biological Chemistry, Vascular Pharmacology, The FASEB Journal, and Arthrosclerosis, Thrombosis and Vascular Biology.
Originally from Burma, Dr. Hla received his Ph.D. in biochemistry from George Washington University in 1988. Upon completion of a postdoctoral fellowship in the Laboratory of Molecular Biology at the American Red Cross, he was appointed Scientist I/assistant professor in the Department of Molecular Biology at George Washington University in 1991. He was promoted to Scientist II/associate professor in 1994. In 1996, Dr. Hla was recruited to the University of Connecticut School of Medicine, where he was appointed associate professor. Dr. Hla was appointed director of the Cell Biology Graduate Program in 1997, and director of the school's Center for Vascular Biology in 1998. He was promoted to professor of cell biology and of genetics and developmental biology in 2000.
"I very much look forward to collaborating with my new colleagues at Weill Cornell as we pursue a number of promising avenues for research," says Dr. Hla. "Specifically, we will be looking at the role of S1P signaling in regulating tumor development and the various ways by which COX-2 promotes cancer and angiogenesis. The longstanding strength in research areas of vascular biology, angiogenesis and hematology/oncology will allow us to branch into fruitful avenues in both basic and clinical research."
The Center for Vascular Biology
Under the direction of Dr. David P. Hajjar, the Center for Vascular Biology at Weill Cornell Medical College has made major contributions -- elucidating the biology of cells of the artery wall, the blood cells with which they interact, and the principal cellular and genetic changes that take place in arteries that predispose them to the formation of plaque and blood clots. Researchers at the Center have studied the interactions between blood cells and vessels, testing the hypothesis that mediators -- substances including nitrogen oxides, reactive oxygen species and growth factors -- regulate blood-vessel cell activity and plaque formation, and that atherosclerosis acts like a blood clot, forming a "response to injury."
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston, making Weill Cornell one of only two medical colleges in the country affiliated with two U.S. News Honor Roll hospitals.
Source: NewYork-Presbyterian Hospital
четверг, 26 мая 2011 г.
Cell Death Receptor Links Cancer Susceptibility And Inflammation
For over 10 years, Wafik S. El-Deiry, MD, PhD, Professor of Medicine, Genetics, and Pharmacology at the University of Pennsylvania School of Medicine, has been pursuing a cancer-targeting molecule called TRAIL and its molecular partners. TRAIL is normally produced by immune cells and curtails tumor spread by binding to a specialized receptor on a tumor's surface.
"However, in cancer patients who often have suppressed immunity, and for reasons we still don't understand, there isn't enough TRAIL being produced, so tumors are not suppressed," explains El-Deiry, who is also Co-Program Leader of the Radiation Biology Program for the Abramson Cancer Center at Penn.
Most recently, El-Deiry and colleagues demonstrated for the first time a link between TRAIL's receptor and cancer susceptibility, as reported online December 13, 2007 in the Journal of Clinical Investigation in advance of the January 2008 print issue. Unexpectedly, they also found a connection via Trail between inflammation and cancer susceptibility.
Mice engineered without the TRAIL receptor on their cells versus healthy controls developed larger and more tumors in their livers and other organs after being challenged with a chemical carcinogen or radiation. The team also bred TRAIL receptor knock-out mice with mice genetically engineered to get B-cell lymphomas that metastasize to the liver. Their offspring displayed more liver tumors compared to controls. "This is the first direct in vivo evidence that loss of the tumor death-inducing TRAIL receptor confers cancer susceptibility," says El-Deiry.
When intact, TRAIL and its receptor decrease the influx of inflammatory cells and molecules that can lead to cancer. New models of cancer have suggested a link between inflammation and cancer in the last five years, and El-Deiry is in the early stages of trying to understand this connection with respect to the TRAIL pathway.
For example, in this study, the mice without the TRAIL receptor that were irradiated developed chronic pneumonia, an inflammatory response, as well tumors, evidence pointing to the connection between cancer and inflammation via TRAIL. "One benefit of this work is that it provides a new and unanticipated model implicating a TRAIL pathway deficiency in the chronic toxicity of radiation therapy," he notes. Inflammation is a common late and serious side-effect of radiation treatment in people.
El-Deiry and his team are now looking within tumor tissue for inflammatory molecules as clues to how cancer and inflammation are coupled. "Our work with TRAIL and its receptor in mouse models represents a new way to look at cancer susceptibility and its potential therapy in humans as well as new ways to decrease debilitating radiation side-effects experienced by cancer patients," says El-Deiry.
Co-authors in addition to El-Deiry are Niklas Finnberg from Penn and Andres J.P. Klein-Szanto from Fox Chase Cancer Center, Philadelphia. This research was funded in part by the National Cancer Institute.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S. News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, comprised of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 300 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.
University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn
"However, in cancer patients who often have suppressed immunity, and for reasons we still don't understand, there isn't enough TRAIL being produced, so tumors are not suppressed," explains El-Deiry, who is also Co-Program Leader of the Radiation Biology Program for the Abramson Cancer Center at Penn.
Most recently, El-Deiry and colleagues demonstrated for the first time a link between TRAIL's receptor and cancer susceptibility, as reported online December 13, 2007 in the Journal of Clinical Investigation in advance of the January 2008 print issue. Unexpectedly, they also found a connection via Trail between inflammation and cancer susceptibility.
Mice engineered without the TRAIL receptor on their cells versus healthy controls developed larger and more tumors in their livers and other organs after being challenged with a chemical carcinogen or radiation. The team also bred TRAIL receptor knock-out mice with mice genetically engineered to get B-cell lymphomas that metastasize to the liver. Their offspring displayed more liver tumors compared to controls. "This is the first direct in vivo evidence that loss of the tumor death-inducing TRAIL receptor confers cancer susceptibility," says El-Deiry.
When intact, TRAIL and its receptor decrease the influx of inflammatory cells and molecules that can lead to cancer. New models of cancer have suggested a link between inflammation and cancer in the last five years, and El-Deiry is in the early stages of trying to understand this connection with respect to the TRAIL pathway.
For example, in this study, the mice without the TRAIL receptor that were irradiated developed chronic pneumonia, an inflammatory response, as well tumors, evidence pointing to the connection between cancer and inflammation via TRAIL. "One benefit of this work is that it provides a new and unanticipated model implicating a TRAIL pathway deficiency in the chronic toxicity of radiation therapy," he notes. Inflammation is a common late and serious side-effect of radiation treatment in people.
El-Deiry and his team are now looking within tumor tissue for inflammatory molecules as clues to how cancer and inflammation are coupled. "Our work with TRAIL and its receptor in mouse models represents a new way to look at cancer susceptibility and its potential therapy in humans as well as new ways to decrease debilitating radiation side-effects experienced by cancer patients," says El-Deiry.
Co-authors in addition to El-Deiry are Niklas Finnberg from Penn and Andres J.P. Klein-Szanto from Fox Chase Cancer Center, Philadelphia. This research was funded in part by the National Cancer Institute.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S. News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
The Abramson Cancer Center (ACC) of the University of Pennsylvania is a national leader in cancer research, patient care, and education. The pre-eminent position of the Cancer Center is reflected in its continuous designation as a Comprehensive Cancer Center by the National Cancer Institute for 30 years, one of 39 such Centers in the United States. The ACC is dedicated to innovative and compassionate cancer care. The clinical program, comprised of a dedicated staff of physicians, nurse practitioners, nurses, social workers, physical therapists, nutritionists and patient support specialists, currently sees over 50,000 outpatient visits, 3400 inpatient admissions, and provides over 25,000 chemotherapy treatments, and more than 65,000 radiation treatments annually. Not only is the ACC dedicated to providing state-of-the-art cancer care, the latest forms of cancer prevention, diagnosis, and treatment are available to our patients through clinical themes that developed in the relentless pursuit to eliminate the pain and suffering from cancer. In addition, the ACC is home to the 300 research scientists who work relentlessly to determine the pathogenesis of cancer. Together, the faculty is committed to improving the prevention, diagnosis and treatment of cancer.
University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn
B-Cell Development And Yin And Yang 1
A new paper in Genes & Development reveals how a protein called Yin Yang 1 regulates early B cell development.
B cells are the antibody-producing cells of the body, which form the basis for the body's recognition of foreign pathogens. B cells undergo a multi-staged maturation process, whereby variable segments of their genome are recombined in various different ways to produce the diversity of antigen recognition that underlies the immune system.
In their upcoming paper, Dr. Yang Shi (Harvard Medical School) and colleagues demonstrate that Yin Yang 1 (YY1) plays a crucial role in regulating VH to DHJH recombination, an essential event for the differentiation of pro-B cell to pre-B cell.
"VHDHJH recombination is a fascinating, but incompletely understood process, which is initiated with the movement of the IgH locus from the periphery to the center of the nucleus where the locus undergoes contraction and recombination. YY1 represents the second transcription factor demonstrated to control IgH locus contraction, thus offering a unique opportunity to investigate molecular mechanisms that control this important process," explains Dr. Shi.
Contact: Heather Cosel
Cold Spring Harbor Laboratory
B cells are the antibody-producing cells of the body, which form the basis for the body's recognition of foreign pathogens. B cells undergo a multi-staged maturation process, whereby variable segments of their genome are recombined in various different ways to produce the diversity of antigen recognition that underlies the immune system.
In their upcoming paper, Dr. Yang Shi (Harvard Medical School) and colleagues demonstrate that Yin Yang 1 (YY1) plays a crucial role in regulating VH to DHJH recombination, an essential event for the differentiation of pro-B cell to pre-B cell.
"VHDHJH recombination is a fascinating, but incompletely understood process, which is initiated with the movement of the IgH locus from the periphery to the center of the nucleus where the locus undergoes contraction and recombination. YY1 represents the second transcription factor demonstrated to control IgH locus contraction, thus offering a unique opportunity to investigate molecular mechanisms that control this important process," explains Dr. Shi.
Contact: Heather Cosel
Cold Spring Harbor Laboratory
A Potential Sugar Fix For Tumors
Researchers at the Duke School of Medicine apparently have solved the riddle of why cancer cells like sugar so much, and it may be a mechanism that could lead to better cancer treatments.
Jonathan Coloff, a graduate student in Assistant Professor Jeffrey Rathmell's laboratory in the Duke Department of Pharmacology and Cancer Biology, has found that the tumor cells use glucose sugar as a way to avoid programmed cell death. They make use of a protein called Akt, which promotes glucose metabolism, which in turn regulates a family of proteins critical for cell survival, the researchers shared during an April 15 presentation at the American Association of Cancer Research Annual Meeting in San Diego.
In normal cells, growth factors regulate metabolism and cell survival. Removing these factors leads to loss of glucose uptake and metabolism and cell death. Cancer cells, however, maintain glucose metabolism and resist cell death, even when deprived of growth factors.
To study how Akt might affect these processes, Coloff and colleagues introduced a cancer-causing form of Akt called myrAkt, into cells that depend on growth factor to survive. The mutant form of Akt allowed cells to maintain glucose usage and survive even when no growth factors were present, allowing them to bypass a normal safeguard used by cells to prevent cancer development.
The death of normal cells after growth factors are removed is partly accomplished by two proteins called Mcl-1 and Puma. But the cancer-causing version of Akt prevents these two proteins from accomplishing their tasks, allowing the cell to survive when it shouldn't.
Once glucose was withdrawn from the environment, however, Akt was no longer able to maintain regulation of the key targeted proteins Mcl-1 and Puma, and the cells died.
"Akt's dependence on glucose to provide an anti-cell-death signal could be a sign of metabolic addiction to glucose in cancer cells, and could give us a new avenue for a metabolic treatment of cancer," said Dr. Rathmell.
Source: Mary Jane Gore
Duke University Medical Center
Jonathan Coloff, a graduate student in Assistant Professor Jeffrey Rathmell's laboratory in the Duke Department of Pharmacology and Cancer Biology, has found that the tumor cells use glucose sugar as a way to avoid programmed cell death. They make use of a protein called Akt, which promotes glucose metabolism, which in turn regulates a family of proteins critical for cell survival, the researchers shared during an April 15 presentation at the American Association of Cancer Research Annual Meeting in San Diego.
In normal cells, growth factors regulate metabolism and cell survival. Removing these factors leads to loss of glucose uptake and metabolism and cell death. Cancer cells, however, maintain glucose metabolism and resist cell death, even when deprived of growth factors.
To study how Akt might affect these processes, Coloff and colleagues introduced a cancer-causing form of Akt called myrAkt, into cells that depend on growth factor to survive. The mutant form of Akt allowed cells to maintain glucose usage and survive even when no growth factors were present, allowing them to bypass a normal safeguard used by cells to prevent cancer development.
The death of normal cells after growth factors are removed is partly accomplished by two proteins called Mcl-1 and Puma. But the cancer-causing version of Akt prevents these two proteins from accomplishing their tasks, allowing the cell to survive when it shouldn't.
Once glucose was withdrawn from the environment, however, Akt was no longer able to maintain regulation of the key targeted proteins Mcl-1 and Puma, and the cells died.
"Akt's dependence on glucose to provide an anti-cell-death signal could be a sign of metabolic addiction to glucose in cancer cells, and could give us a new avenue for a metabolic treatment of cancer," said Dr. Rathmell.
Source: Mary Jane Gore
Duke University Medical Center
Study Findings Have Implications For Development Of Pain Relieving Drugs
Morphine and other opioids are widely used to treat both acute and chronic pain yet their benefits are often limited because some people experience side effects or do not respond to them efficiently.
Now, new research from the University of North Carolina at Chapel Hill's Center for Neurosensory Disorders, based within the School of Dentistry, has identified genetic variants that offer insight into individual responses to morphine. Researchers said long-term implications of the findings may include the development of drugs with greater pain-relieving effects and fewer side effects, as well as the development of genetic tests predicting individual responses to these medications.
Up to one-third of people treated with opioids develop substantial side effects, said Luda Diatchenko, M.D., Ph.D., an associate professor in the center and the study's co-senior author. In addition, there is more than a 10-fold difference in the responses some patients show a very good response and others show a very poor response to the same amount.
The study, which appeared in the March 15, 2009, issue of the journal Human Molecular Genetics, identifies new variations in the gene that produces the OPRM1 receptor, the primary biological target for opioid analgesics such as morphine. The research also provides evidence that the receptor carries many more genetic variations than previously thought.
"Genetic variations in this receptor play a crucial role in individual responsiveness to these drugs, but we currently have very little understanding of its genetic structures and molecular and cellular mechanisms," Diatchenko said.
She added that collaboration with the National Institutes of Health's National Center for Biotechnology Information had provided crucial insights into these mechanisms. Bioinformatics is an emerging field combining information technology and biology.
"Bioinformatics has become one of the driving forces of modern biomedical science," said Svetlana Shabalina, Ph.D., a senior scientist at the National Center for Biotechnology Information and the other study co-senior author. "Bioinformatic tools are indispensable for the identification of underlying genetic causes in complex disorders. We expect many important discoveries in this field."
"The outcomes of these studies are very exciting and are likely to lead to new diagnostic tests that will permit clinicians to predict a patient's risk for inadequate or adverse responses to opioids," said William Maixner, D.D.S., Ph.D., co-author of the study, director of the Center for Neurosensory Disorders and professor of endodontics and pharmacology in the UNC schools of dentistry and medicine, respectively. "The outcomes may also enable the development of a new class of opioids that are safer and more effective than those currently available," he said.
The study was funded by grants from the National Institutes of Health.
Other study authors from the UNC School of Dentistry are Pavel Gris, Ph.D.; Josee Gauthier and Inna E. Tchivileva, M.D. Additional study authors are Dmitri V. Zaykin, Ph.D., and Kyoko Shibata, Ph.D., of the National Institute of Environmental Health Sciences; Aleksey Y. Ogurtsov, Ph.D., of the National Center for Biotechnology Information; Inna Belfer, M.D., Ph.D., of the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism and the University of Pittsburgh; Bikashkumar Mishra, M.D., and Carly Kiselycznyk, Ph.D. of the NIDCR and NIAAA; Margaret R. Wallace, Ph.D., of the University of Florida College of Medicine; Roland Staud, M.D., and Roger B. Fillingim, Ph.D., of the University of Florida College of Dentistry; Nikolay A. Spiridonov, Ph.D., of the U.S. Food and Drug Administration; Mitchell B. Max, M.D., Ph.D., of the NIDCR and University of Pittsburgh; and David Goldman, M.D., of the NIAAA.
Source: University of North Carolina at Chapel Hill
Now, new research from the University of North Carolina at Chapel Hill's Center for Neurosensory Disorders, based within the School of Dentistry, has identified genetic variants that offer insight into individual responses to morphine. Researchers said long-term implications of the findings may include the development of drugs with greater pain-relieving effects and fewer side effects, as well as the development of genetic tests predicting individual responses to these medications.
Up to one-third of people treated with opioids develop substantial side effects, said Luda Diatchenko, M.D., Ph.D., an associate professor in the center and the study's co-senior author. In addition, there is more than a 10-fold difference in the responses some patients show a very good response and others show a very poor response to the same amount.
The study, which appeared in the March 15, 2009, issue of the journal Human Molecular Genetics, identifies new variations in the gene that produces the OPRM1 receptor, the primary biological target for opioid analgesics such as morphine. The research also provides evidence that the receptor carries many more genetic variations than previously thought.
"Genetic variations in this receptor play a crucial role in individual responsiveness to these drugs, but we currently have very little understanding of its genetic structures and molecular and cellular mechanisms," Diatchenko said.
She added that collaboration with the National Institutes of Health's National Center for Biotechnology Information had provided crucial insights into these mechanisms. Bioinformatics is an emerging field combining information technology and biology.
"Bioinformatics has become one of the driving forces of modern biomedical science," said Svetlana Shabalina, Ph.D., a senior scientist at the National Center for Biotechnology Information and the other study co-senior author. "Bioinformatic tools are indispensable for the identification of underlying genetic causes in complex disorders. We expect many important discoveries in this field."
"The outcomes of these studies are very exciting and are likely to lead to new diagnostic tests that will permit clinicians to predict a patient's risk for inadequate or adverse responses to opioids," said William Maixner, D.D.S., Ph.D., co-author of the study, director of the Center for Neurosensory Disorders and professor of endodontics and pharmacology in the UNC schools of dentistry and medicine, respectively. "The outcomes may also enable the development of a new class of opioids that are safer and more effective than those currently available," he said.
The study was funded by grants from the National Institutes of Health.
Other study authors from the UNC School of Dentistry are Pavel Gris, Ph.D.; Josee Gauthier and Inna E. Tchivileva, M.D. Additional study authors are Dmitri V. Zaykin, Ph.D., and Kyoko Shibata, Ph.D., of the National Institute of Environmental Health Sciences; Aleksey Y. Ogurtsov, Ph.D., of the National Center for Biotechnology Information; Inna Belfer, M.D., Ph.D., of the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism and the University of Pittsburgh; Bikashkumar Mishra, M.D., and Carly Kiselycznyk, Ph.D. of the NIDCR and NIAAA; Margaret R. Wallace, Ph.D., of the University of Florida College of Medicine; Roland Staud, M.D., and Roger B. Fillingim, Ph.D., of the University of Florida College of Dentistry; Nikolay A. Spiridonov, Ph.D., of the U.S. Food and Drug Administration; Mitchell B. Max, M.D., Ph.D., of the NIDCR and University of Pittsburgh; and David Goldman, M.D., of the NIAAA.
Source: University of North Carolina at Chapel Hill
Memory Impairment Common In People With A History Of Cancer
People with a history of cancer have a 40 percent greater likelihood of experiencing memory problems that interfere with daily functioning, compared with those who have not had cancer, according to results of a new, large study.
The findings, believed to be one of the first culled from a nationwide sample of people diagnosed with different cancers, mirror findings of cancer-related memory impairment in smaller studies of certain cancers, such as breast and prostate cancer. Results were presented at the Third AACR Conference on The Science of Cancer Health Disparities.
"The findings show that memory impairment in cancer patients is a national problem that we must pay special attention to," said Pascal Jean-Pierre, Ph.D., M.P.H., assistant professor at the University of Miami Miller School of Medicine, department of pediatrics, and the Sylvester Comprehensive Cancer Center.
He added that while there is no curative treatment yet for memory impairment ongoing studies are testing therapies physicians can still help these patients.
"One of the most important parts of cancer treatment is management of symptoms, such as impairments in attention, memory and fatigue, in order to improve a patient's quality of life. This study suggests these memory issues are more common than had been recognized before, and should be assessed in all patients with a history of cancer," Jean-Pierre said.
Jean-Pierre and colleagues used data from the National Health and Nutrition Examination Survey (NHANES), a population-based survey sponsored by the U.S. Centers for Disease Control and Prevention designed to collect information on the health and nutrition in U.S. households. Their sample included 9,819 people, aged 40 years and older, from diverse educational and racial-ethnic backgrounds. Within that group, 1,305 participants reported they had cancer or a history of cancer.
All participants had a physical exam and responded to a survey, which included the question: "Are you limited in any way because of difficulty remembering or because you experience periods of confusion?"
Fourteen percent of participants who had cancer reported memory impairment compared to 8 percent of participants who did not have cancer. Those with cancer were 40 percent more likely to have memory issues than other participants impairments that interfered with daily functioning.
"The findings indicate that cancer is, therefore, a key independent predictor of memory problems in the sample studied," said Jean-Pierre.
He calls the condition "cancer related cognitive dysfunction," suggesting that it goes beyond the "chemobrain" label that has been attached primarily to women treated with chemotherapy for their breast cancer who reported problems in cognitive function (e.g., attention and memory).
"These memory issues can be related to treatment, such as chemotherapy, radiation, and hormone therapies, or to the tumor biology itself, which could change brain chemistry and neurobehavioral function," said Jean-Pierre.
Source: American Association for Cancer Research (AACR)
The findings, believed to be one of the first culled from a nationwide sample of people diagnosed with different cancers, mirror findings of cancer-related memory impairment in smaller studies of certain cancers, such as breast and prostate cancer. Results were presented at the Third AACR Conference on The Science of Cancer Health Disparities.
"The findings show that memory impairment in cancer patients is a national problem that we must pay special attention to," said Pascal Jean-Pierre, Ph.D., M.P.H., assistant professor at the University of Miami Miller School of Medicine, department of pediatrics, and the Sylvester Comprehensive Cancer Center.
He added that while there is no curative treatment yet for memory impairment ongoing studies are testing therapies physicians can still help these patients.
"One of the most important parts of cancer treatment is management of symptoms, such as impairments in attention, memory and fatigue, in order to improve a patient's quality of life. This study suggests these memory issues are more common than had been recognized before, and should be assessed in all patients with a history of cancer," Jean-Pierre said.
Jean-Pierre and colleagues used data from the National Health and Nutrition Examination Survey (NHANES), a population-based survey sponsored by the U.S. Centers for Disease Control and Prevention designed to collect information on the health and nutrition in U.S. households. Their sample included 9,819 people, aged 40 years and older, from diverse educational and racial-ethnic backgrounds. Within that group, 1,305 participants reported they had cancer or a history of cancer.
All participants had a physical exam and responded to a survey, which included the question: "Are you limited in any way because of difficulty remembering or because you experience periods of confusion?"
Fourteen percent of participants who had cancer reported memory impairment compared to 8 percent of participants who did not have cancer. Those with cancer were 40 percent more likely to have memory issues than other participants impairments that interfered with daily functioning.
"The findings indicate that cancer is, therefore, a key independent predictor of memory problems in the sample studied," said Jean-Pierre.
He calls the condition "cancer related cognitive dysfunction," suggesting that it goes beyond the "chemobrain" label that has been attached primarily to women treated with chemotherapy for their breast cancer who reported problems in cognitive function (e.g., attention and memory).
"These memory issues can be related to treatment, such as chemotherapy, radiation, and hormone therapies, or to the tumor biology itself, which could change brain chemistry and neurobehavioral function," said Jean-Pierre.
Source: American Association for Cancer Research (AACR)
Bone Implicated As Therapeutic Target For Type 2 Diabetes
Bones are typically thought of as calcified, inert structures, but researchers at Columbia University Medical Center have now identified a surprising and critically important novel function of the skeleton. They've shown for the first time that the skeleton is an endocrine organ that helps control our sugar metabolism and weight and, as such, is a major determinant of the development of type 2 diabetes.
The research, published in Cell, demonstrates that bone cells release a hormone called osteocalcin, which controls the regulation of blood sugar (glucose) and fat deposition through synergistic mechanisms previously not recognized. Usually, an increase in insulin secretion is accompanied by a decrease in insulin sensitivity. Osteocalcin, however, increases both the secretion and sensitivity of insulin, in addition to boosting the number of insulin-producing cells and reducing stores of fat.
In this published research, authors show that an increase in osteocalcin activity prevents the development of type 2 diabetes and obesity in mice. This discovery potentially opens the door for novel therapeutic avenues for the prevention and treatment of type 2 diabetes.
"The discovery that our bones are responsible for regulating blood sugar in ways that were not known before completely changes our understanding of the function of the skeleton and uncovers a crucial aspect of energy metabolism," said Gerard Karsenty, M.D., Ph.D., chair of the department of Genetics and Development at Columbia University Medical Center, Paul Marks Professor in the Basic Sciences, and senior author of the paper. "These results uncover an important aspect of endocrinology that was unappreciated until now."
Karsenty and his colleagues had previously shown that leptin, a hormone released by fat cells, acts upon and ultimately controls bone mass. They reasoned that bones must in turn communicate with fat, so they searched bone-forming cells for molecules that could potentially send signals back to fat cells.
The researchers found that osteocalcin, a protein made only by bone-forming cells (osteoblasts), was not a mere structural protein, but rather a hormone with totally unanticipated and crucial functions. Osteocalcin directs the pancreas' beta cells, which produce the body's supply of insulin, to produce more insulin. At the same time, osteocalcin directs fat cells to release a hormone called adiponectin, which improves insulin sensitivity. This discovery showed for the first time that one hormone has a synergistic function in regulating insulin secretion and insulin sensitivity, and that this coordinating signal comes from the skeleton. Additionally, osteocalcin enhances the production of insulin-producing beta cells, which is considered one of the best, but currently unattainable, strategies to treat diabetes.
People with type 2 diabetes have been shown to have low osteocalcin levels, suggesting that altering the activity of this molecule could be an effective therapy. That hypothesis is supported by the Columbia research, which showed that mice with high levels of osteocalcin activity were prevented from gaining weight or becoming diabetic even when they ate a high fat diet. Analysis of mice lacking the osteocalcin protein showed that they had type 2 diabetes, increased fat mass, a decrease in insulin and adiponectin expression, and decreased beta-cell proliferation.
This research was supported by the National Institutes of Health, the American Diabetes Association, the Japan Society for the Promotion of Science, and the Pennsylvania Department of Health.
The researchers are now examining the role of osteocalcin in the regulation of blood sugar in humans and are continuing investigations into the relationship between osteocalcin and the appearance of type 2 diabetes and obesity.
Source: Susan Craig
Columbia University Medical Center
The research, published in Cell, demonstrates that bone cells release a hormone called osteocalcin, which controls the regulation of blood sugar (glucose) and fat deposition through synergistic mechanisms previously not recognized. Usually, an increase in insulin secretion is accompanied by a decrease in insulin sensitivity. Osteocalcin, however, increases both the secretion and sensitivity of insulin, in addition to boosting the number of insulin-producing cells and reducing stores of fat.
In this published research, authors show that an increase in osteocalcin activity prevents the development of type 2 diabetes and obesity in mice. This discovery potentially opens the door for novel therapeutic avenues for the prevention and treatment of type 2 diabetes.
"The discovery that our bones are responsible for regulating blood sugar in ways that were not known before completely changes our understanding of the function of the skeleton and uncovers a crucial aspect of energy metabolism," said Gerard Karsenty, M.D., Ph.D., chair of the department of Genetics and Development at Columbia University Medical Center, Paul Marks Professor in the Basic Sciences, and senior author of the paper. "These results uncover an important aspect of endocrinology that was unappreciated until now."
Karsenty and his colleagues had previously shown that leptin, a hormone released by fat cells, acts upon and ultimately controls bone mass. They reasoned that bones must in turn communicate with fat, so they searched bone-forming cells for molecules that could potentially send signals back to fat cells.
The researchers found that osteocalcin, a protein made only by bone-forming cells (osteoblasts), was not a mere structural protein, but rather a hormone with totally unanticipated and crucial functions. Osteocalcin directs the pancreas' beta cells, which produce the body's supply of insulin, to produce more insulin. At the same time, osteocalcin directs fat cells to release a hormone called adiponectin, which improves insulin sensitivity. This discovery showed for the first time that one hormone has a synergistic function in regulating insulin secretion and insulin sensitivity, and that this coordinating signal comes from the skeleton. Additionally, osteocalcin enhances the production of insulin-producing beta cells, which is considered one of the best, but currently unattainable, strategies to treat diabetes.
People with type 2 diabetes have been shown to have low osteocalcin levels, suggesting that altering the activity of this molecule could be an effective therapy. That hypothesis is supported by the Columbia research, which showed that mice with high levels of osteocalcin activity were prevented from gaining weight or becoming diabetic even when they ate a high fat diet. Analysis of mice lacking the osteocalcin protein showed that they had type 2 diabetes, increased fat mass, a decrease in insulin and adiponectin expression, and decreased beta-cell proliferation.
This research was supported by the National Institutes of Health, the American Diabetes Association, the Japan Society for the Promotion of Science, and the Pennsylvania Department of Health.
The researchers are now examining the role of osteocalcin in the regulation of blood sugar in humans and are continuing investigations into the relationship between osteocalcin and the appearance of type 2 diabetes and obesity.
Source: Susan Craig
Columbia University Medical Center
Elastic Interactions Of Membrane Proteins
Cellular survival relies crucially on the ability to receive and communicate signals from and to the outside world. A major part of this regulation and communication is performed by proteins within the membrane of a cell. How these proteins work is an important topic in biology, and one which these scientists have excellently clarified by computational techniques.
Tristan Ursell and colleagues have examined the elasticity of the membrane, which changes thickness to accommodate the proteins embedded within it. Proteins respond to stimuli by altering their shape to perform specific tasks, such as channel proteins, which allow the flow of ions in only one formation. Ursell created a physical model which shows that the membrane itself can communicate structural and hence formational information between membrane proteins. Hence, proteins can "talk" and "respond" to each other using the membrane as a generic "voice."
This is an exciting development, published in PLoS Computational Biology, which shows that the membrane's elastic forces can ultimately dictate the formation, organization, and therefore effects, of the proteins within it.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: compbiol.plosjournals/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0030081
CITATION: Ursell T, Huang K, Peterson E, Phillips R (2007) Cooperative gating and spatial organization of membrane proteins through elastic interactions. PLoS Comput Biol 3(4): e81. doi:10.1371/journal.pcbi.0030081
Contact: Rob Phillips
Public Library of Science
Tristan Ursell and colleagues have examined the elasticity of the membrane, which changes thickness to accommodate the proteins embedded within it. Proteins respond to stimuli by altering their shape to perform specific tasks, such as channel proteins, which allow the flow of ions in only one formation. Ursell created a physical model which shows that the membrane itself can communicate structural and hence formational information between membrane proteins. Hence, proteins can "talk" and "respond" to each other using the membrane as a generic "voice."
This is an exciting development, published in PLoS Computational Biology, which shows that the membrane's elastic forces can ultimately dictate the formation, organization, and therefore effects, of the proteins within it.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: compbiol.plosjournals/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0030081
CITATION: Ursell T, Huang K, Peterson E, Phillips R (2007) Cooperative gating and spatial organization of membrane proteins through elastic interactions. PLoS Comput Biol 3(4): e81. doi:10.1371/journal.pcbi.0030081
Contact: Rob Phillips
Public Library of Science
Researchers Unravel Mystery Behind Long Lasting Memories
A new study by researchers at Wake Forest University School of Medicine may reveal how long-lasting memories form in the brain.
The researchers hope that the findings, now available online and scheduled to appear in an upcoming issue of Neuroscience, may one day help scientists develop treatments to prevent and treat conditions such as post-traumatic stress disorder.
"Although many things are known about memories that form from repeat experiences, not much is known with regard to how some memories form with just one exposure," said Ashok Hegde, Ph.D., an associate professor of neurobiology and anatomy and the lead investigator on the study.
Scientists do know that people tend to remember extremely happy or sad occasions vividly because of the emotional connection, Hegde said. Extreme emotions trigger the release of a chemical in the brain called norepinephrine, which is related to adrenaline. That norepinephrine somehow helps memories last a long time some even a lifetime.
For example, he said, when a person asks, "Where were you when the 9/11 attacks happened?" most people can recall immediately where they were and what they were doing when they heard the news. They remember the moment as if it just happened because a national tragedy arouses emotion and emotion somehow makes memories last for a long time, Hegde explained.
For the current study, Hegde and colleagues looked at how norepinephrine helps female mice remember the scent of their male partners after being exposed to it just once during mating.
The researchers studied the neural circuitry in the accessory olfactory bulb, the part of the brain where memory of the male partner's scent is stored. They found that norepinephrine, released in mice while mating, activates an enzyme called Protein Kinase C (PKC), specifically, the "alpha" isoform of PKC, in the accessory olfactory bulb. The PKC enzyme has about a dozen forms, or isoforms, that exist in the brains of mammals, including humans.
"The fact that PKC-alpha is activated through the release of norepinephrine is an important discovery," Hegde said. "It explains how strong memories form for specific sensory experiences."
In female mice, the information about the partner's scent is carried by a chemical called glutamate and the fact that mating has occurred is conveyed by the release of norepinephrine, Hegde explained. Previous studies have found that glutamate and norepinephrine together, but not individually, cause strong memory formation for the male's scent.
"No one knew how this happened," Hegde said. "Our findings indicate that the PKC-alpha enzyme tells the nerve cells in the brain that these two chemicals have arrived together. PKC-alpha is like the bouncer who lifts the rope blocking the entrance to an exclusive club for strong memories when glutamate and norepinephrine arrive together. If they arrive alone, they can't get past the velvet rope."
Hegde explained that, when memory is stored in the brain, the connections between nerve cells, called synapses, change. Strong memories are formed when synapses become stronger through structural changes that occur at the synapse. PKC-alpha works with glutamate and norepinephrine to create those changes.
Hegde said that the next step in this line of research is to learn exactly how PKC-alpha can turn genes on in nerve cells. Understanding the precise sequence of molecules that are activated by PKC-alpha will help researchers block the function of these molecules and test whether they block memory formation. This future research will not only explain strong pleasant memories, but also how strong unpleasant memories form in instances like post-traumatic stress disorder.
The current study was funded by the National Institutes of Health, Edward Mallinckrodt Foundation and the Whitehall Foundation.
Co-researchers were Chenghai Dong, M.D., Ph.D., and Dwayne Godwin, Ph.D., both of the School of Medicine, and Peter Brennan, Ph.D., of the University of Bristol, United Kingdom.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,056 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Wake Forest University Baptist Medical Center
The researchers hope that the findings, now available online and scheduled to appear in an upcoming issue of Neuroscience, may one day help scientists develop treatments to prevent and treat conditions such as post-traumatic stress disorder.
"Although many things are known about memories that form from repeat experiences, not much is known with regard to how some memories form with just one exposure," said Ashok Hegde, Ph.D., an associate professor of neurobiology and anatomy and the lead investigator on the study.
Scientists do know that people tend to remember extremely happy or sad occasions vividly because of the emotional connection, Hegde said. Extreme emotions trigger the release of a chemical in the brain called norepinephrine, which is related to adrenaline. That norepinephrine somehow helps memories last a long time some even a lifetime.
For example, he said, when a person asks, "Where were you when the 9/11 attacks happened?" most people can recall immediately where they were and what they were doing when they heard the news. They remember the moment as if it just happened because a national tragedy arouses emotion and emotion somehow makes memories last for a long time, Hegde explained.
For the current study, Hegde and colleagues looked at how norepinephrine helps female mice remember the scent of their male partners after being exposed to it just once during mating.
The researchers studied the neural circuitry in the accessory olfactory bulb, the part of the brain where memory of the male partner's scent is stored. They found that norepinephrine, released in mice while mating, activates an enzyme called Protein Kinase C (PKC), specifically, the "alpha" isoform of PKC, in the accessory olfactory bulb. The PKC enzyme has about a dozen forms, or isoforms, that exist in the brains of mammals, including humans.
"The fact that PKC-alpha is activated through the release of norepinephrine is an important discovery," Hegde said. "It explains how strong memories form for specific sensory experiences."
In female mice, the information about the partner's scent is carried by a chemical called glutamate and the fact that mating has occurred is conveyed by the release of norepinephrine, Hegde explained. Previous studies have found that glutamate and norepinephrine together, but not individually, cause strong memory formation for the male's scent.
"No one knew how this happened," Hegde said. "Our findings indicate that the PKC-alpha enzyme tells the nerve cells in the brain that these two chemicals have arrived together. PKC-alpha is like the bouncer who lifts the rope blocking the entrance to an exclusive club for strong memories when glutamate and norepinephrine arrive together. If they arrive alone, they can't get past the velvet rope."
Hegde explained that, when memory is stored in the brain, the connections between nerve cells, called synapses, change. Strong memories are formed when synapses become stronger through structural changes that occur at the synapse. PKC-alpha works with glutamate and norepinephrine to create those changes.
Hegde said that the next step in this line of research is to learn exactly how PKC-alpha can turn genes on in nerve cells. Understanding the precise sequence of molecules that are activated by PKC-alpha will help researchers block the function of these molecules and test whether they block memory formation. This future research will not only explain strong pleasant memories, but also how strong unpleasant memories form in instances like post-traumatic stress disorder.
The current study was funded by the National Institutes of Health, Edward Mallinckrodt Foundation and the Whitehall Foundation.
Co-researchers were Chenghai Dong, M.D., Ph.D., and Dwayne Godwin, Ph.D., both of the School of Medicine, and Peter Brennan, Ph.D., of the University of Bristol, United Kingdom.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children's Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university's School of Medicine and Piedmont Triad Research Park. The system comprises 1,056 acute care, rehabilitation and long-term care beds and has been ranked as one of "America's Best Hospitals" by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America's Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.
Source: Wake Forest University Baptist Medical Center
Algebra Adds Value To Mathematical Biology Education
As mathematics continues to become an increasingly important component in undergraduate biology programs, a more comprehensive understanding of the use of algebraic models is needed by the next generation of biologists to facilitate new advances in the life sciences, according to researchers at Sweet Briar College and the Virginia Bioinformatics Institute (VBI) at Virginia Tech.
In the paper, "Mathematical Biology Education: Beyond Calculus," which is featured in the July 31, 2009 issue of Science, VBI Professor Reinhard Laubenbacher and Sweet Briar College Mathematical Sciences Professor Raina Robeva highlight algebraic models as one of the diverse mathematical tools needed in the professional development of up-and-coming life scientists. Despite this critical need, the authors explain, algebraic models have played a less substantial role in undergraduate curricula than other methods.
Future generations of biologists will routinely use mathematical and computational approaches to develop and frame hypotheses, design experiments, and analyze results. Sound mathematical models are essential for this purpose and are currently used in the field of systems biology to understand complex biological networks. Two types of mathematical models, in particular, have been successfully used in biology to reproduce network structure and dynamics: Continuous-time models derived from differential equations (DE models) focus on the kinetics of biochemical reactions, while discrete-time algebraic models built from functions of finite-state variables focus on the logic of the connections of network variables. According to Laubenbacher and Robeva, while DE models have been included more often in undergraduate curricula integrating mathematics and biology, algebraic models should also be viewed as an important training component for students at all education levels.
"Discrete-time algebraic models created from finite-state variables, such as Boolean networks, are increasingly being used to model a variety of biochemical networks, including metabolic, gene regulatory, and signal transduction networks," says Laubenbacher. "Often, researchers do not have enough of the information required to build detailed quantitative models. Algebraic models need less information about the system to be modeled, making them useful for instances where quantitative information may be missing. All the work that goes into building them can then be used to construct detailed kinetic models, when additional information becomes available. In addition, algebraic models are much more intuitive than differential equations models, which makes them more easily accessible to life scientists."
Using algebraic models is a relatively quick, easy and reliable way for students to integrate mathematical modeling into their life sciences coursework. Creating algebraic models of biochemical networks requires only a modest mathematical background, which is usually provided in a college algebra course. Without the complexities involved in teaching students how to construct more complicated models, algebraic models make the introduction of mathematical modeling into life sciences courses more accessible for faculty members as well.
According to Robeva, "The exciting thing about algebraic models from an educational perspective is that they highlight aspects of modern-day biology and can easily fit in both the biology and mathematics curricula. At the introductory level, they provide a quick path for introducing biology students to constructing and using mathematical models in the context of contemporary problems such as gene regulation. At the more advanced level, the general study and analysis of such models often require sophisticated mathematical theories. This makes them perfect for inclusion into mathematics courses, where the biology can provide a meaningful framework for many of the abstract structures. As educators, we should actively be looking for the best ways to seize this opportunity for advancing mathematical biology."
Source:
Susan Bland
Virginia Tech
In the paper, "Mathematical Biology Education: Beyond Calculus," which is featured in the July 31, 2009 issue of Science, VBI Professor Reinhard Laubenbacher and Sweet Briar College Mathematical Sciences Professor Raina Robeva highlight algebraic models as one of the diverse mathematical tools needed in the professional development of up-and-coming life scientists. Despite this critical need, the authors explain, algebraic models have played a less substantial role in undergraduate curricula than other methods.
Future generations of biologists will routinely use mathematical and computational approaches to develop and frame hypotheses, design experiments, and analyze results. Sound mathematical models are essential for this purpose and are currently used in the field of systems biology to understand complex biological networks. Two types of mathematical models, in particular, have been successfully used in biology to reproduce network structure and dynamics: Continuous-time models derived from differential equations (DE models) focus on the kinetics of biochemical reactions, while discrete-time algebraic models built from functions of finite-state variables focus on the logic of the connections of network variables. According to Laubenbacher and Robeva, while DE models have been included more often in undergraduate curricula integrating mathematics and biology, algebraic models should also be viewed as an important training component for students at all education levels.
"Discrete-time algebraic models created from finite-state variables, such as Boolean networks, are increasingly being used to model a variety of biochemical networks, including metabolic, gene regulatory, and signal transduction networks," says Laubenbacher. "Often, researchers do not have enough of the information required to build detailed quantitative models. Algebraic models need less information about the system to be modeled, making them useful for instances where quantitative information may be missing. All the work that goes into building them can then be used to construct detailed kinetic models, when additional information becomes available. In addition, algebraic models are much more intuitive than differential equations models, which makes them more easily accessible to life scientists."
Using algebraic models is a relatively quick, easy and reliable way for students to integrate mathematical modeling into their life sciences coursework. Creating algebraic models of biochemical networks requires only a modest mathematical background, which is usually provided in a college algebra course. Without the complexities involved in teaching students how to construct more complicated models, algebraic models make the introduction of mathematical modeling into life sciences courses more accessible for faculty members as well.
According to Robeva, "The exciting thing about algebraic models from an educational perspective is that they highlight aspects of modern-day biology and can easily fit in both the biology and mathematics curricula. At the introductory level, they provide a quick path for introducing biology students to constructing and using mathematical models in the context of contemporary problems such as gene regulation. At the more advanced level, the general study and analysis of such models often require sophisticated mathematical theories. This makes them perfect for inclusion into mathematics courses, where the biology can provide a meaningful framework for many of the abstract structures. As educators, we should actively be looking for the best ways to seize this opportunity for advancing mathematical biology."
Source:
Susan Bland
Virginia Tech
Montreal Researcher, Physician And Teacher Phil Gold To Be Inducted Into The Canadian Medical Hall Of Fame
Prof. Heather Munroe-Blum, Principal and Vice-Chancellor of McGill University, and the Hon. Arthur T. Porter, Director General and CEO of the McGill University Health Centre (MUHC), welcome the news that Dr. Phil Gold is to be inducted into The Canadian Medical Hall of Fame. In 1965, Dr. Gold co-discovered the carcinoembryonic antigen (CEA), the first clinically useful human tumour marker that revolutionized the diagnosis and management of cancer. At a ceremony in April 2010, Dr. Gold and five other distinguished inductees will join the ranks of the existing 76 laureates who have pushed the boundaries of knowledge to improve human health.
"When we talk about our institution's role in transforming health care, we often mention such luminaries as Dr. Wilder Penfield, Sir William Osler and Dr. Maude Abbott who have helped put the MUHC on the world map," noted the Hon. Arthur T. Porter. "These pioneers' contributions to medicine will always be emblematic of our rich heritage but today I wish to underscore another facet of their impact, namely how they and all those who have followed in their footsteps inspire new generations to pursue excellence. Dr. Gold is one of these remarkable individuals. I am honoured to call him both a colleague and a friend."
Dr. Gold was born in Montreal and has remained faithful to his native city for most of his life. A brilliant mind with a distinguished record of scientific achievement in immunology and cancer, Dr. Gold is Professor of Medicine, Physiology and Oncology in the Faculty of Medicine at McGill and Executive Director of the Clinical Research Centre at the Montreal General Hospital, which is part of the Research Institute of the MUHC. He is known to many as a down-to-earth, caring physician, an inspirational leader and a gifted teacher - the latter being clearly of great importance to him: "I am very honoured to be included among the pantheon of great physicians in the Medical Hall of Fame," said Dr. Gold. "Many of them were my teachers and colleagues; from my perspective, the most important thing I've ever done is teach."
Dr. Gold's passion for teaching resonates with Prof. Munroe-Blum: "This has been a great year for McGill. We're very proud that faculty members, scholars and alumni have earned two Nobel Prizes, three Killam Prizes and two Steacie Memorial Fellowships. These awards and Dr. Gold's distinction as the latest inductee in The Canadian Medical Hall of Fame speak volumes to the quality of our professoriate and our commitment to attracting the best from Canada and around the world to support graduate students and the excellence of our programs."
In 1965, Dr. Gold and his colleague, Dr. Samuel Freedman, published a seminal paper on their concept-shifting discovery of CEA, the tumour marker that is found in 70% of cancer patients. This marker was developed into a blood test that remains the most frequently used test in oncology around the world today, in addition to being the standard against which other human tumour markers are measured. Through this work, Dr. Gold is credited for developing the field of Human Tumour Marker Biology. His subsequent demonstration that CEA was in embryonic and fetal tissue initiated the field of oncodevelopmental biology.
The impact of the CEA discovery, along with other work in the division of clinical immunology and allergy at the Montreal General Hospital, led to the establishment of the McGill Cancer Centre in 1974. Thirty-five years later, Dr. Gold's original dream of creating a first-rate cancer centre by centralizing the efforts of McGill University and its affiliated hospitals has been realized through the Research Institute of the MUHC and the Goodman Cancer Centre at McGill.
"The relevance of Dr. Gold's discovery over four decades ago stands today as an indelible testament to the value of research," added Dr. Vassilios Papadopoulos, Director of the Research Institute (RI) and Associate Director General of Research at the MUHC. "He is a trusted friend to his colleagues, an invaluable contributor to many RI committees and a role model for young investigators. I am thrilled that we have thirty-five Cancer Axis investigators at the Research Institute to further Dr. Gold's dream. With our new Comprehensive Cancer Centre and the Centre for Innovative Medicine at the Glen Campus, we will be even better positioned to push the boundaries of new knowledge."
Dr. Gold has received numerous international awards and been elected to many prestigious scientific organizations. He was made a Companion of the Order of Canada (1986), an Officer of the Ordre national du QuГ©bec (1990), and a member of the Academy of Great Montrealers (1986). He received the Gairdner Foundation International Award (with Dr. Freedman, 1978) and the F.N.G. Starr Award from the Canadian Medical Association (1986).
Dr. Gold's fellow Canadian Medical Hall of Fame inductees include Dr. Alan C. Burton MBE, Dr. William A. Cochrane OC, Dr. James C. Hogg OC, Dr. Vera Peters OC and Dr. Calvin R. Stiller CM O. Ont. More than 500 of Canada's leading citizens will come together to celebrate the formal induction of the incoming laureates on April 13, 2010 in Calgary. Eighteen of the current seventy-six laureates have ties to McGill and/or the MUHC.
McGill University, founded in Montreal, Que., in 1821, is Canada's leading post-secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 33,000 students. McGill attracts students from more than 160 countries around the world. Almost half of McGill students claim a first language other than English - including 6,000 francophones - with more than 6,200 international students making up almost 20 per cent of the student body.
Source:
Julie Robert
McGill University Health Centre
"When we talk about our institution's role in transforming health care, we often mention such luminaries as Dr. Wilder Penfield, Sir William Osler and Dr. Maude Abbott who have helped put the MUHC on the world map," noted the Hon. Arthur T. Porter. "These pioneers' contributions to medicine will always be emblematic of our rich heritage but today I wish to underscore another facet of their impact, namely how they and all those who have followed in their footsteps inspire new generations to pursue excellence. Dr. Gold is one of these remarkable individuals. I am honoured to call him both a colleague and a friend."
Dr. Gold was born in Montreal and has remained faithful to his native city for most of his life. A brilliant mind with a distinguished record of scientific achievement in immunology and cancer, Dr. Gold is Professor of Medicine, Physiology and Oncology in the Faculty of Medicine at McGill and Executive Director of the Clinical Research Centre at the Montreal General Hospital, which is part of the Research Institute of the MUHC. He is known to many as a down-to-earth, caring physician, an inspirational leader and a gifted teacher - the latter being clearly of great importance to him: "I am very honoured to be included among the pantheon of great physicians in the Medical Hall of Fame," said Dr. Gold. "Many of them were my teachers and colleagues; from my perspective, the most important thing I've ever done is teach."
Dr. Gold's passion for teaching resonates with Prof. Munroe-Blum: "This has been a great year for McGill. We're very proud that faculty members, scholars and alumni have earned two Nobel Prizes, three Killam Prizes and two Steacie Memorial Fellowships. These awards and Dr. Gold's distinction as the latest inductee in The Canadian Medical Hall of Fame speak volumes to the quality of our professoriate and our commitment to attracting the best from Canada and around the world to support graduate students and the excellence of our programs."
In 1965, Dr. Gold and his colleague, Dr. Samuel Freedman, published a seminal paper on their concept-shifting discovery of CEA, the tumour marker that is found in 70% of cancer patients. This marker was developed into a blood test that remains the most frequently used test in oncology around the world today, in addition to being the standard against which other human tumour markers are measured. Through this work, Dr. Gold is credited for developing the field of Human Tumour Marker Biology. His subsequent demonstration that CEA was in embryonic and fetal tissue initiated the field of oncodevelopmental biology.
The impact of the CEA discovery, along with other work in the division of clinical immunology and allergy at the Montreal General Hospital, led to the establishment of the McGill Cancer Centre in 1974. Thirty-five years later, Dr. Gold's original dream of creating a first-rate cancer centre by centralizing the efforts of McGill University and its affiliated hospitals has been realized through the Research Institute of the MUHC and the Goodman Cancer Centre at McGill.
"The relevance of Dr. Gold's discovery over four decades ago stands today as an indelible testament to the value of research," added Dr. Vassilios Papadopoulos, Director of the Research Institute (RI) and Associate Director General of Research at the MUHC. "He is a trusted friend to his colleagues, an invaluable contributor to many RI committees and a role model for young investigators. I am thrilled that we have thirty-five Cancer Axis investigators at the Research Institute to further Dr. Gold's dream. With our new Comprehensive Cancer Centre and the Centre for Innovative Medicine at the Glen Campus, we will be even better positioned to push the boundaries of new knowledge."
Dr. Gold has received numerous international awards and been elected to many prestigious scientific organizations. He was made a Companion of the Order of Canada (1986), an Officer of the Ordre national du QuГ©bec (1990), and a member of the Academy of Great Montrealers (1986). He received the Gairdner Foundation International Award (with Dr. Freedman, 1978) and the F.N.G. Starr Award from the Canadian Medical Association (1986).
Dr. Gold's fellow Canadian Medical Hall of Fame inductees include Dr. Alan C. Burton MBE, Dr. William A. Cochrane OC, Dr. James C. Hogg OC, Dr. Vera Peters OC and Dr. Calvin R. Stiller CM O. Ont. More than 500 of Canada's leading citizens will come together to celebrate the formal induction of the incoming laureates on April 13, 2010 in Calgary. Eighteen of the current seventy-six laureates have ties to McGill and/or the MUHC.
McGill University, founded in Montreal, Que., in 1821, is Canada's leading post-secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 33,000 students. McGill attracts students from more than 160 countries around the world. Almost half of McGill students claim a first language other than English - including 6,000 francophones - with more than 6,200 international students making up almost 20 per cent of the student body.
Source:
Julie Robert
McGill University Health Centre
Scientists Speed Up Menopause, Causing Infertility In Crop-Destroying Pests
When scientist Loretta Mayer set out to alleviate diseases associated with menopause, she didn't realize her work could lead to addressing world hunger and feeding hundreds of millions of people.
The Northern Arizona University researcher and her colleagues at NAU and the University of Arizona identified a nontoxic chemical technology that when applied to rodents, caused infertility in rats, which feast on crops intended for human consumption.
"This environmentally neutral approach, that has never been available before, will reduce the damage rice-field rats cause in countries that depend on rice as a main food supply," Mayer said.
Rodents consume or damage up to 50 percent of pre-harvest rice crops. Due to the large-scale cultivation of rice worldwide, if rice production were to increase by 10 percent, "this would feed about 380 million people a year," Mayer said. "We can easily increase rice production by 10 percent by reducing rodent fertility in half."
She said this noninvasive approach is more humane than poison, which takes several days to kill rodents and seeps into groundwater, harming other animals and possible food sources.
The sterilization technology derived from Mayer's research, done by Patricia Hoyer and and Glenn Sipes at UofA, investigated potential damage caused to ovarian follicles in women exposed to certain chemicals in industrial settings. Of particular interest was a chemical compound known as 4-vinylcyclohexene diepoxide, or VCD, typically used in manufacturing rubber tires, polyesters and plastics.
She found that low, nontoxic doses of VCD in mice sped the menopausal process and rendered them infertile. She dubbed this new animal model of accelerated menopause "mouseopause."
Mayer and her colleagues have developed a product called ContraPest that incorporates the chemical sterilization treatment into bait. The bait is put into strategically placed stations that lure rodents into cages too small to attract or affect other animals. "No rat or mice I know can resist a little hole," she said.
ContraPest is being tested in Indonesia - the largest producer of rice in the world, and is currently being registered for rodent-population control in Australia.
"We are testing it in Indonesia, and then our next target site will be in the Philippines. From the Philippines we go to Vietnam," Mayer said.
Scientists adapt the product to different rodent species at SenesTech, the Flagstaff-based company that grew out of Mayer's work on the NAU campus. Named after the word senescence, meaning approaching an advanced age, the young company hopes to create a number of beneficial products.
Mayer and her team of researchers also are adapting the technology platform for population management of other animals. They are formulating a product, ChemSpay, for use in population management of wild animals such as deer, coyotes, foxes, raccoons, horses, buffalo and elk as well as cats and dogs.
"What we are doing right now is we are preparing the translation of this technology to dogs and cats. We have already completed six months of study in dogs. This could have a tremendous impact on reducing the number of animals in shelters," said Mayer noting that not only is the method a cost-effective way to avoid surgical spaying, there's a global impact to canine management most people don't realize.
"Dogs are huge vectors of disease throughout the world," she said. "In India, every two seconds someone is bitten by a dog. The tragedy is that every 30 minutes someone dies from rabies. If you continue to vaccinate against rabies, you won't be able to make a dent. You have to combine rabies vaccinations with fertility control."
She hopes to address rabies problems on the rise in West Africa, India and China.
Australia hopes to put the technology to use in managing its kangaroo, wallaby and camel populations. New Zealand, Spain and the United Kingdom also are in line to put ChemSpay to use.
She said luring students to the research team was easy. "We want them involved with hands-on research and field experience," she said. "The first question I ask interested students is if they have empty passport pages they are ready to fill."
Biology graduate student Anna Mae Burd recently returned from training international colleagues in the Philippines. She is initiating field tests in Indonesia with graduate student Nyo Me Htwe. Me Htwe has been working by the side of Mayer's partner, NAU researcher and SenesTech's chief scientific officer Cheryl Dyer adapting the bait to different rodent species.
LAUNCH YOUTUBE VIDEO
youtube/watch?v=CXYsvvdGhyM
Source:
Diane Rechel
Northern Arizona University
The Northern Arizona University researcher and her colleagues at NAU and the University of Arizona identified a nontoxic chemical technology that when applied to rodents, caused infertility in rats, which feast on crops intended for human consumption.
"This environmentally neutral approach, that has never been available before, will reduce the damage rice-field rats cause in countries that depend on rice as a main food supply," Mayer said.
Rodents consume or damage up to 50 percent of pre-harvest rice crops. Due to the large-scale cultivation of rice worldwide, if rice production were to increase by 10 percent, "this would feed about 380 million people a year," Mayer said. "We can easily increase rice production by 10 percent by reducing rodent fertility in half."
She said this noninvasive approach is more humane than poison, which takes several days to kill rodents and seeps into groundwater, harming other animals and possible food sources.
The sterilization technology derived from Mayer's research, done by Patricia Hoyer and and Glenn Sipes at UofA, investigated potential damage caused to ovarian follicles in women exposed to certain chemicals in industrial settings. Of particular interest was a chemical compound known as 4-vinylcyclohexene diepoxide, or VCD, typically used in manufacturing rubber tires, polyesters and plastics.
She found that low, nontoxic doses of VCD in mice sped the menopausal process and rendered them infertile. She dubbed this new animal model of accelerated menopause "mouseopause."
Mayer and her colleagues have developed a product called ContraPest that incorporates the chemical sterilization treatment into bait. The bait is put into strategically placed stations that lure rodents into cages too small to attract or affect other animals. "No rat or mice I know can resist a little hole," she said.
ContraPest is being tested in Indonesia - the largest producer of rice in the world, and is currently being registered for rodent-population control in Australia.
"We are testing it in Indonesia, and then our next target site will be in the Philippines. From the Philippines we go to Vietnam," Mayer said.
Scientists adapt the product to different rodent species at SenesTech, the Flagstaff-based company that grew out of Mayer's work on the NAU campus. Named after the word senescence, meaning approaching an advanced age, the young company hopes to create a number of beneficial products.
Mayer and her team of researchers also are adapting the technology platform for population management of other animals. They are formulating a product, ChemSpay, for use in population management of wild animals such as deer, coyotes, foxes, raccoons, horses, buffalo and elk as well as cats and dogs.
"What we are doing right now is we are preparing the translation of this technology to dogs and cats. We have already completed six months of study in dogs. This could have a tremendous impact on reducing the number of animals in shelters," said Mayer noting that not only is the method a cost-effective way to avoid surgical spaying, there's a global impact to canine management most people don't realize.
"Dogs are huge vectors of disease throughout the world," she said. "In India, every two seconds someone is bitten by a dog. The tragedy is that every 30 minutes someone dies from rabies. If you continue to vaccinate against rabies, you won't be able to make a dent. You have to combine rabies vaccinations with fertility control."
She hopes to address rabies problems on the rise in West Africa, India and China.
Australia hopes to put the technology to use in managing its kangaroo, wallaby and camel populations. New Zealand, Spain and the United Kingdom also are in line to put ChemSpay to use.
She said luring students to the research team was easy. "We want them involved with hands-on research and field experience," she said. "The first question I ask interested students is if they have empty passport pages they are ready to fill."
Biology graduate student Anna Mae Burd recently returned from training international colleagues in the Philippines. She is initiating field tests in Indonesia with graduate student Nyo Me Htwe. Me Htwe has been working by the side of Mayer's partner, NAU researcher and SenesTech's chief scientific officer Cheryl Dyer adapting the bait to different rodent species.
LAUNCH YOUTUBE VIDEO
youtube/watch?v=CXYsvvdGhyM
Source:
Diane Rechel
Northern Arizona University
Steroids Cause The Same Tissue Changes As Tendon Injury
Patients who get a steroid injection in their shoulder for rotator cuff pain relief or improved shoulder function should not return to their regular activities or start physical therapy for a few weeks, a Loyola University Health System study shows.
"Steroid injection temporarily produces a molecular response in the tissue that is similar to that of a tendon injury, possibly making it more vulnerable to damage during this time," said senior study investigator Dr. John Callaci, assistant professor, department of orthopedic surgery and rehabilitation, Loyola University Chicago Stritch School of Medicine, Maywood, Ill.
"This is especially important because steroids often give patients rapid pain relief," said Callaci. "If a patient returns to rigorous activities right after a steroid injection, the weakened tissue may not be able to sustain itself."
He cautioned that these findings should not preclude people from having a steroid injection or physicians from administering steroids. "The study gives us a better understanding of what is happening on the molecular level," he said.
Loyola presented the findings here today at the 53rd annual meeting of the Orthopaedic Research Society.
"We found that steroid injections cause a tendon to behave in a way where it thinks it has been acutely injured," noted Callaci. "Steroids rapidly provide anti-inflammatory and pain relief. That is why steroids are so popular, but physical therapy also can produce some of the same effects. It just takes longer."
For the study, Callaci and colleagues examined the global gene expression profiles in rotator cuff tendons following injury or exposure to corticosteroid. The researchers used gene array analysis of the complete rat genome to characterize the molecular response of rat rotator cuff tendon tissue to injury, injection of corticosteroids, and the presence of both injury and corticosteroid.
Results of the study shows that 2,000 genes were changed by injury; 1,000 genes were changed by steroids. A significant number, 750, of the changed genes overlapped between the two groups.
"Not only did gene expression overlap but so did some biological pathways," said Callaci. "Acute injury of the rat rotator cuff tendon significantly modulated the expression of genes in 26 different biological pathways and steroids affected 13 pathways. Twelve of the 13 overlap with the injured pathways.
"The implication of an overlapping pathway is that you have pathways that are modulated after an injury suggesting the tendon is doing things to try to heal itself," said Callaci. "That might suggest there might be a temporary period of vulnerability or weakness in a tendon. It thinks it is being injured and it produces things that normally it produces after injury, which might cause some temporary instability."
Loyola currently is conducting a biomechanical study to determine if the steroids change strength, stress, strain or elasticity of tendons. "We are investigating the biological basis of how tendons heal and how steroids may modulate that healing," said Callaci.
"We want to see if there are actual differences in biomechanical properties right after steroid injection," he said. "If you have a tendon injury already and you're given steroids, how is that modulating the healing response? Do you get more scar formation or do other things change? These are the questions we are researching now."
Co-authors of the study with Callaci are principal investigator Dr. Anthony S. Wei, who did his research at Loyola and now is at Washington University Medical Center in St. Louis; Dr. Benjamin Sears, Loyola resident, Dr. Dainius Juknelis, research associate, Dr. Frederick Wezeman, professor of orthopaedic surgery and rehabilitation, Loyola University Chicago Stritch School of Medicine, director, musculoskeletal biology research laboratory, Loyola University Health System, and associate dean, Loyola University Chicago Graduate School at Loyola University Medical Center, Maywood, Ill.; and Dr. Pietro Tonino, associate professor of orthopaedic surgery, department of orthopaedic surgery and rehabilitation, Loyola University Chicago Stritch School of Medicine and chief of sports medicine.
For more information on Loyola University Health System, log onto loyolamedicine
Funding for the study was provided by a gift from Mr. and Mrs. Charles R Walgreen III and a research grant from the Mid America Orthopaedic Association.
The 53rd Annual Meeting of the Orthopaedic Research Society at the San Diego Convention Center, 111 W. Harbor Drive, San Diego, runs through February 14, 2007.
Loyola University Health System, a wholly owned subsidiary of Loyola University Chicago (LUC), includes the private teaching hospital at Loyola University Medical Center (LUMC), 14 specialty and primary care centers in the western and southwestern suburbs, the Loyola Ambulatory Surgery Center at Oakbrook and the Loyola Oakbrook Terrace Imaging Center; and serves as co-owner-operator of RML Specialty Hospital, a long-term acute hospital specializing in ventilation weaning and other medically complex patients in suburban Hinsdale, Ill. Loyola is nationally recognized for its specialty care and groundbreaking research in cancer, neurological disorders, neonatology and the treatment of heart disease. The 61-acre medical center campus in Maywood, Ill., includes the 523-licensed bed Loyola University Hospital with a Level I trauma center, the region's largest burn unit, one of the Midwest's most comprehensive organ transplant programs, the Russo Surgical Pavilion and the Ronald McDonald® Children's Hospital of LUMC. Also on campus are Loyola's Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, Loyola Outpatient Center and LUC Stritch School of Medicine. The medical school includes the Cardiovascular Institute, Oncology Institute, Burn & Shock Trauma Institute, Neuroscience Institute and the Neiswanger Institute for Bioethics and Health Policy.
Loyola University Health System
2160 S. First Ave.
Maywood, IL 60153
United States
luhs
"Steroid injection temporarily produces a molecular response in the tissue that is similar to that of a tendon injury, possibly making it more vulnerable to damage during this time," said senior study investigator Dr. John Callaci, assistant professor, department of orthopedic surgery and rehabilitation, Loyola University Chicago Stritch School of Medicine, Maywood, Ill.
"This is especially important because steroids often give patients rapid pain relief," said Callaci. "If a patient returns to rigorous activities right after a steroid injection, the weakened tissue may not be able to sustain itself."
He cautioned that these findings should not preclude people from having a steroid injection or physicians from administering steroids. "The study gives us a better understanding of what is happening on the molecular level," he said.
Loyola presented the findings here today at the 53rd annual meeting of the Orthopaedic Research Society.
"We found that steroid injections cause a tendon to behave in a way where it thinks it has been acutely injured," noted Callaci. "Steroids rapidly provide anti-inflammatory and pain relief. That is why steroids are so popular, but physical therapy also can produce some of the same effects. It just takes longer."
For the study, Callaci and colleagues examined the global gene expression profiles in rotator cuff tendons following injury or exposure to corticosteroid. The researchers used gene array analysis of the complete rat genome to characterize the molecular response of rat rotator cuff tendon tissue to injury, injection of corticosteroids, and the presence of both injury and corticosteroid.
Results of the study shows that 2,000 genes were changed by injury; 1,000 genes were changed by steroids. A significant number, 750, of the changed genes overlapped between the two groups.
"Not only did gene expression overlap but so did some biological pathways," said Callaci. "Acute injury of the rat rotator cuff tendon significantly modulated the expression of genes in 26 different biological pathways and steroids affected 13 pathways. Twelve of the 13 overlap with the injured pathways.
"The implication of an overlapping pathway is that you have pathways that are modulated after an injury suggesting the tendon is doing things to try to heal itself," said Callaci. "That might suggest there might be a temporary period of vulnerability or weakness in a tendon. It thinks it is being injured and it produces things that normally it produces after injury, which might cause some temporary instability."
Loyola currently is conducting a biomechanical study to determine if the steroids change strength, stress, strain or elasticity of tendons. "We are investigating the biological basis of how tendons heal and how steroids may modulate that healing," said Callaci.
"We want to see if there are actual differences in biomechanical properties right after steroid injection," he said. "If you have a tendon injury already and you're given steroids, how is that modulating the healing response? Do you get more scar formation or do other things change? These are the questions we are researching now."
Co-authors of the study with Callaci are principal investigator Dr. Anthony S. Wei, who did his research at Loyola and now is at Washington University Medical Center in St. Louis; Dr. Benjamin Sears, Loyola resident, Dr. Dainius Juknelis, research associate, Dr. Frederick Wezeman, professor of orthopaedic surgery and rehabilitation, Loyola University Chicago Stritch School of Medicine, director, musculoskeletal biology research laboratory, Loyola University Health System, and associate dean, Loyola University Chicago Graduate School at Loyola University Medical Center, Maywood, Ill.; and Dr. Pietro Tonino, associate professor of orthopaedic surgery, department of orthopaedic surgery and rehabilitation, Loyola University Chicago Stritch School of Medicine and chief of sports medicine.
For more information on Loyola University Health System, log onto loyolamedicine
Funding for the study was provided by a gift from Mr. and Mrs. Charles R Walgreen III and a research grant from the Mid America Orthopaedic Association.
The 53rd Annual Meeting of the Orthopaedic Research Society at the San Diego Convention Center, 111 W. Harbor Drive, San Diego, runs through February 14, 2007.
Loyola University Health System, a wholly owned subsidiary of Loyola University Chicago (LUC), includes the private teaching hospital at Loyola University Medical Center (LUMC), 14 specialty and primary care centers in the western and southwestern suburbs, the Loyola Ambulatory Surgery Center at Oakbrook and the Loyola Oakbrook Terrace Imaging Center; and serves as co-owner-operator of RML Specialty Hospital, a long-term acute hospital specializing in ventilation weaning and other medically complex patients in suburban Hinsdale, Ill. Loyola is nationally recognized for its specialty care and groundbreaking research in cancer, neurological disorders, neonatology and the treatment of heart disease. The 61-acre medical center campus in Maywood, Ill., includes the 523-licensed bed Loyola University Hospital with a Level I trauma center, the region's largest burn unit, one of the Midwest's most comprehensive organ transplant programs, the Russo Surgical Pavilion and the Ronald McDonald® Children's Hospital of LUMC. Also on campus are Loyola's Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, Loyola Outpatient Center and LUC Stritch School of Medicine. The medical school includes the Cardiovascular Institute, Oncology Institute, Burn & Shock Trauma Institute, Neuroscience Institute and the Neiswanger Institute for Bioethics and Health Policy.
Loyola University Health System
2160 S. First Ave.
Maywood, IL 60153
United States
luhs
Genome Biology And Evolution: After Dinosaurs, Mammals Rise But Their Genomes Get Smaller
Evidence buried in the chromosomes of animals and plants strongly suggests only one group -- mammals -- have seen their genomes shrink after the dinosaurs' extinction. What's more, that trend continues today, say Indiana University Bloomington scientists in the first issue of a new journal, Genome Biology and Evolution.
The scientists' finding might seem counter-intuitive, given that the last 65 million years have seen mammals expand in diversity and number, not to mention dominance in a wide variety of ecological roles. But it is precisely their success in numbers that could have led to the contraction of their genomes.
"Larger population sizes make natural selection more efficient," said IU Bloomington evolutionary biologist Michael Lynch, who led the study. "If we are correct, we have shown how to bring ancient genomic information together with the paleontological record to learn more about the past."
And the present. Lynch says the data he and his colleagues analyzed suggest human genomes are still undergoing a contraction -- though you shouldn't expect to see noticeable changes in our chromosomes for a few million years yet.
Lynch's group examined the genomes of seven mammals, eight non-mammalian animals and three plants, specifically with regard for the long terminal repeat (LTR) sequences of transposable elements, a curious sort of "jumping" genetic sequence initially dropped into genomes by viruses. IU School of Informatics (Bloomington) bioinformaticians Mina Rho and Haixu Tang oversaw the survey of mammalian and non-mammalian genomes.
Transposable elements often lose their functionality soon after insertion but nevertheless are disturbingly common. In the human genome, for example, transposable elements constitute as much as 45 percent of an individual's total DNA. Long terminal repeat sequences, part of that figure, make up about 8 percent of humans' total DNA.
LTRs come in a range of sizes and ages, and it is the age distribution of LTRs that interested Lynch and his colleagues.
"This study started out as independent observations in the literature," Lynch said. "The data we saw suggested a bulge in age distribution of transposable elements in humans and mouse."
Left enough time, Lynch says, transposable elements are eventually lost from the genome, sometimes by accident and sometimes, perhaps, as the result of natural selection against excess DNA. An LTR is far more likely to survive a few years of cell divisions -- and the chance of obliteration via a DNA replication error -- than 10 million years of cell divisions. Plotting the full range of 17 species' LTRs, young and old, Lynch and his colleagues usually saw a descending curve with lots of new transposable elements and a dramatic drop-off in the number of older elements.
But not in most mammals. In humans, macaques, cows, dogs and mouse, Lynch's group observed a hill-shaped curve, with a peak of middle-aged LTRs and drop-offs both in the number of older and younger LTRs. The shape of the curve is consistent with previously published data for other types of so-called "junk" DNA elements.
The depressed numbers of very young LTRs, Lynch says, strongly suggests a contraction in overall genome sizes of the lineages of the mammals the scientists studied. That could come about in one of two ways, he says. One possibility is an increase in the efficiency of natural selection that accompanies population growth.
"We think that's the most likely explanation," Lynch said. "Another possibility is that natural selection was just stronger, but we doubt it. For that to be the case, natural selection would have to act in the same way on several lineages around the globe simultaneously."
Mo Zhou, Xiang Gao and Sun Kim also contributed to the report. It was funded with grants from the National Institutes of Health, the National Science Foundation and the Indiana METACyt Initiative, an Indiana University program seeded by the Lilly Foundation.
Source:
David Bricker
Indiana University
The scientists' finding might seem counter-intuitive, given that the last 65 million years have seen mammals expand in diversity and number, not to mention dominance in a wide variety of ecological roles. But it is precisely their success in numbers that could have led to the contraction of their genomes.
"Larger population sizes make natural selection more efficient," said IU Bloomington evolutionary biologist Michael Lynch, who led the study. "If we are correct, we have shown how to bring ancient genomic information together with the paleontological record to learn more about the past."
And the present. Lynch says the data he and his colleagues analyzed suggest human genomes are still undergoing a contraction -- though you shouldn't expect to see noticeable changes in our chromosomes for a few million years yet.
Lynch's group examined the genomes of seven mammals, eight non-mammalian animals and three plants, specifically with regard for the long terminal repeat (LTR) sequences of transposable elements, a curious sort of "jumping" genetic sequence initially dropped into genomes by viruses. IU School of Informatics (Bloomington) bioinformaticians Mina Rho and Haixu Tang oversaw the survey of mammalian and non-mammalian genomes.
Transposable elements often lose their functionality soon after insertion but nevertheless are disturbingly common. In the human genome, for example, transposable elements constitute as much as 45 percent of an individual's total DNA. Long terminal repeat sequences, part of that figure, make up about 8 percent of humans' total DNA.
LTRs come in a range of sizes and ages, and it is the age distribution of LTRs that interested Lynch and his colleagues.
"This study started out as independent observations in the literature," Lynch said. "The data we saw suggested a bulge in age distribution of transposable elements in humans and mouse."
Left enough time, Lynch says, transposable elements are eventually lost from the genome, sometimes by accident and sometimes, perhaps, as the result of natural selection against excess DNA. An LTR is far more likely to survive a few years of cell divisions -- and the chance of obliteration via a DNA replication error -- than 10 million years of cell divisions. Plotting the full range of 17 species' LTRs, young and old, Lynch and his colleagues usually saw a descending curve with lots of new transposable elements and a dramatic drop-off in the number of older elements.
But not in most mammals. In humans, macaques, cows, dogs and mouse, Lynch's group observed a hill-shaped curve, with a peak of middle-aged LTRs and drop-offs both in the number of older and younger LTRs. The shape of the curve is consistent with previously published data for other types of so-called "junk" DNA elements.
The depressed numbers of very young LTRs, Lynch says, strongly suggests a contraction in overall genome sizes of the lineages of the mammals the scientists studied. That could come about in one of two ways, he says. One possibility is an increase in the efficiency of natural selection that accompanies population growth.
"We think that's the most likely explanation," Lynch said. "Another possibility is that natural selection was just stronger, but we doubt it. For that to be the case, natural selection would have to act in the same way on several lineages around the globe simultaneously."
Mo Zhou, Xiang Gao and Sun Kim also contributed to the report. It was funded with grants from the National Institutes of Health, the National Science Foundation and the Indiana METACyt Initiative, an Indiana University program seeded by the Lilly Foundation.
Source:
David Bricker
Indiana University
Early Environmental Exposure May Accelerate Age-Related Neurodegeneration
Exposure to iron during the first weeks of life in combination with exposure later in life to a common herbicide may contribute to the subsequent degeneration of brain cells associated with the onset of Parkinson's disease (PD), according to a new study in mice. The findings also showed that a compound that protects cells in the body from damage from certain forms of oxygen, a kind of antioxidant, could suppress such neural degeneration.
Previous studies indicated that both early exposure to iron and later exposure to the herbicide paraquat independently increase oxidative stress - an environment in which damage from levels of reactive oxygen is more likely - in dopamine-producing regions of the brain, areas that are affected by PD. Julie Andersen, PhD, and her team at the Buck Institute for Age Research found that feeding iron to newborn mice made them more susceptible to paraquat, which increases levels of harmful forms of oxygen and damages dopamine-producing neurons as they grew older. The study appears in The Journal of Neuroscience.
"The importance of the study is that it points to a possible role of common mechanisms triggered by iron and paraquat as important in PD, and suggests that therapies that block their effects would be worth testing in patients," says Marie-Francoise Chesselet, MD, PhD, of UCLA, who did not participate in the study.
Ten-day-old mice were fed iron for a week. At ages from two months to two years, they were then exposed to paraquat for three weeks. By examining their brains, Andersen and her team found that by the time the mice were a year old, early iron consumption exacerbated damage to brain cells caused by paraquat exposure. The effect was even more pronounced at two years of age, the human equivalent of 60 - 70 years.
A subset of mice that received the antioxidant at the same time that they were exposed to paraquat exhibited reduced levels of dopamine-producing neuron death, suggesting they were protected from oxidative damage. Aging is the single major risk factor for PD, but the findings from Andersen and her colleagues show that exposure during the neonatal period may play a crucial role in the development of late-onset PD.
Future studies are likely to explore the role of antioxidants in helping to prevent and treat symptoms of PD, says Andersen. "The present findings suggest that antioxidants may be a viable therapeutic approach for neurodegenerative diseases associated with oxidative stress, such as PD."
The work was supported by a grant from the National Institutes of Health.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 36,500 basic scientists and clinicians who study the brain and nervous system.
Contact: Sara Harris
Society for Neuroscience
Previous studies indicated that both early exposure to iron and later exposure to the herbicide paraquat independently increase oxidative stress - an environment in which damage from levels of reactive oxygen is more likely - in dopamine-producing regions of the brain, areas that are affected by PD. Julie Andersen, PhD, and her team at the Buck Institute for Age Research found that feeding iron to newborn mice made them more susceptible to paraquat, which increases levels of harmful forms of oxygen and damages dopamine-producing neurons as they grew older. The study appears in The Journal of Neuroscience.
"The importance of the study is that it points to a possible role of common mechanisms triggered by iron and paraquat as important in PD, and suggests that therapies that block their effects would be worth testing in patients," says Marie-Francoise Chesselet, MD, PhD, of UCLA, who did not participate in the study.
Ten-day-old mice were fed iron for a week. At ages from two months to two years, they were then exposed to paraquat for three weeks. By examining their brains, Andersen and her team found that by the time the mice were a year old, early iron consumption exacerbated damage to brain cells caused by paraquat exposure. The effect was even more pronounced at two years of age, the human equivalent of 60 - 70 years.
A subset of mice that received the antioxidant at the same time that they were exposed to paraquat exhibited reduced levels of dopamine-producing neuron death, suggesting they were protected from oxidative damage. Aging is the single major risk factor for PD, but the findings from Andersen and her colleagues show that exposure during the neonatal period may play a crucial role in the development of late-onset PD.
Future studies are likely to explore the role of antioxidants in helping to prevent and treat symptoms of PD, says Andersen. "The present findings suggest that antioxidants may be a viable therapeutic approach for neurodegenerative diseases associated with oxidative stress, such as PD."
The work was supported by a grant from the National Institutes of Health.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 36,500 basic scientists and clinicians who study the brain and nervous system.
Contact: Sara Harris
Society for Neuroscience
Four Days Of REM Sleep Deprivation Contributes To A Reduction Of Cell Proliferation In Rats
Four days' exposure to a REM sleep deprivation procedure reduces cell proliferation in the part of the forebrain that contributes to long-term memory of rats, according to a study published in the February 1 issue of the journal SLEEP.
The study, authored by Dennis McGinty, PhD, of the V.A. Greater Los Angeles Healthcare System, focused on male Sprague-Dawley rats. REM sleep deprivation was achieved by a brief treadmill movement initiated by automatic online detection of REM sleep. A yoked-control (YC) rat was placed in the same treadmill and experienced the identical movement regardless of the stage of the sleep-wake cycle.
According to the results, REM sleep was reduced by 85 percent in REM sleep deprived rats and by 43 percent in YC rats. Cell proliferation was reduced by 63 percent in REM sleep deprived rats compared with YC rats. Across all animals, cell proliferation exhibited a positive correlation with the percentage of REM sleep.
"Several studies have shown that sleep contributes to brain plasticity in general, and to adult neurogenesis, in particular," said Dr. McGinty. "Neurogenesis is a concrete example of brain plasticity, suppression of adult neurogenesis is thought to be important in pathologies such as depression. One current question has to do with the relative contribution of the two sleep states, non-REM and REM, which have very different, even opposite, physiological properties. This study showed that REM sleep has a critical role in facilitating brain plasticity. The study does not exclude an equally important role for non-REM sleep. In other recent work, we have shown that sleep fragmentation can also suppress adult neurogenesis. How sleep affects the molecular mechanisms underlying neurogenesis remains to be explored."
It is recommended that older adults get between seven and eight hours of nightly sleep.
The American Academy of Sleep Medicine (AASM) offers the following tips on how to get a good night's sleep:
* Follow a consistent bedtime routine.
* Establish a relaxing setting at bedtime.
* Get a full night's sleep every night.
* Avoid foods or drinks that contain caffeine, as well as any medicine that has a stimulant, prior to bedtime.
* Do not bring your worries to bed with you.
* Do not go to bed hungry, but don't eat a big meal before bedtime either.
* Avoid any rigorous exercise within six hours of your bedtime.
* Make your bedroom quiet, dark and a little bit cool.
* Get up at the same time every morning.
Those who suspect that they might be suffering a sleep disorder are encouraged to consult with their primary care physician or a sleep specialist.
SLEEP is the official journal of the Associated Professional Sleep Societies, LLC, a joint venture of the AASM and the Sleep Research Society.
SleepEducation, a patient education Web site created by the AASM, provides information about various sleep disorders, the forms of treatment available, recent news on the topic of sleep, sleep studies that have been conducted and a listing of sleep facilities.
Article: "Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat."
Source: Jim Arcuri
American Academy of Sleep Medicine
The study, authored by Dennis McGinty, PhD, of the V.A. Greater Los Angeles Healthcare System, focused on male Sprague-Dawley rats. REM sleep deprivation was achieved by a brief treadmill movement initiated by automatic online detection of REM sleep. A yoked-control (YC) rat was placed in the same treadmill and experienced the identical movement regardless of the stage of the sleep-wake cycle.
According to the results, REM sleep was reduced by 85 percent in REM sleep deprived rats and by 43 percent in YC rats. Cell proliferation was reduced by 63 percent in REM sleep deprived rats compared with YC rats. Across all animals, cell proliferation exhibited a positive correlation with the percentage of REM sleep.
"Several studies have shown that sleep contributes to brain plasticity in general, and to adult neurogenesis, in particular," said Dr. McGinty. "Neurogenesis is a concrete example of brain plasticity, suppression of adult neurogenesis is thought to be important in pathologies such as depression. One current question has to do with the relative contribution of the two sleep states, non-REM and REM, which have very different, even opposite, physiological properties. This study showed that REM sleep has a critical role in facilitating brain plasticity. The study does not exclude an equally important role for non-REM sleep. In other recent work, we have shown that sleep fragmentation can also suppress adult neurogenesis. How sleep affects the molecular mechanisms underlying neurogenesis remains to be explored."
It is recommended that older adults get between seven and eight hours of nightly sleep.
The American Academy of Sleep Medicine (AASM) offers the following tips on how to get a good night's sleep:
* Follow a consistent bedtime routine.
* Establish a relaxing setting at bedtime.
* Get a full night's sleep every night.
* Avoid foods or drinks that contain caffeine, as well as any medicine that has a stimulant, prior to bedtime.
* Do not bring your worries to bed with you.
* Do not go to bed hungry, but don't eat a big meal before bedtime either.
* Avoid any rigorous exercise within six hours of your bedtime.
* Make your bedroom quiet, dark and a little bit cool.
* Get up at the same time every morning.
Those who suspect that they might be suffering a sleep disorder are encouraged to consult with their primary care physician or a sleep specialist.
SLEEP is the official journal of the Associated Professional Sleep Societies, LLC, a joint venture of the AASM and the Sleep Research Society.
SleepEducation, a patient education Web site created by the AASM, provides information about various sleep disorders, the forms of treatment available, recent news on the topic of sleep, sleep studies that have been conducted and a listing of sleep facilities.
Article: "Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat."
Source: Jim Arcuri
American Academy of Sleep Medicine
Compound Found In Red Wine Neutralizes Toxicity Of Proteins Related To Alzheimer's
An organic compound found in red wine - resveratrol - has the ability to neutralize the toxic effects of proteins linked to Alzheimer's disease, according to research led by Rensselaer Professor Peter M. Tessier. The findings, published in the May 28 edition of the Journal of Biological Chemistry, are a step toward understanding the large-scale death of brain cells seen in certain neurodegenerative diseases.
"We've shown how resveratrol has very interesting selectivity to target and neutralize a select set of toxic peptide isoforms," Tessier said. "Because resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms."
Isoforms are different packing arrangements of a particular peptide. Deformations of a particular peptide - the AОІ1-42 peptide - have been linked to Alzheimer's disease. Improperly folded peptides have been shown to collect in accumulations called "plaques" within the brain. Those plaques are often found near areas of cell death in diseased brains.
It is not clear that resveratrol is able to cross the blood-brain barrier, Tessier said. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging.
In their research, Tessier and his co-authors generated A peptides packed together in five unique isoforms, or "arrangements" (monomer, soluble oligomer, non-toxic oligomer, fibrillar intermediates and amyloid fibrils). In their experiments, three of these arrangements were toxic to human cells, two were not.
Next, the researchers introduced resveratrol.
The resveratrol reacted with the toxic arrangements of the AОІ1-42 peptide, neutralizing their toxicity.
It did not affect the non-toxic arrangements.
"The surprise is that this molecule can target some of these packing arrangements that are toxic and rearrange them into packing arrangements that are not toxic. For those forms that are non-toxic, it doesn't change them," Tessier said.
Intriguingly, Tessier said, one of the toxic arrangements (the soluble oligomer) and one of the non-toxic arrangements (the non-toxic oligomer) were indistinguishable by various methods. And yet the resveratrol only affected the toxic arrangement.
The point, Tessier concludes, is that the seemingly identical non-toxic and toxic arrangements must have some distinguishing feature yet to be discovered, raising questions for future study.
"We have two things that look very similar, but one is toxic and the other isn't," Tessier said. "What is it that makes the bad one bad and the good one good?"
The research produced several other findings, Tessier said, including reliable methods of generating the arrangements Tessier's team produced, and formation of one arrangement which had previously been unknown.
Last week, Tessier was named as a 2010 Pew Scholar in the Biomedical Sciences by the Pew Charitable Trusts.The distinction includes an award of $240,000 over four years and inclusion into a select community of scientists that includes three Nobel Prize winners, three MacArthur Fellows, and two recipients of the Albert Lasker Medical Research Award, according to the Pew Charitable Trusts.
Tessier was also recently awarded a five-year, $411,872 Faculty Early Career Development Award (CAREER) from the National Science Foundation (NSF) for research in the related field of protein thermodynamics and aggregation.
The CAREER Award is given to faculty members at the beginning of their academic careers and is one of NSF's most competitive awards, placing emphasis on high-quality research and novel education initiatives.
Tessier joined the Rensselaer faculty in 2007 following a postdoctoral fellowship at the Massachusetts Institute of Technology's Whitehead Institute for Biomedical Research. He received his bachelor's degree in chemical engineering from the University of Maine, and went on to earn his doctoral degree in chemical engineering from the University of Delaware.
Source:
Rensselaer Polytechnic Institute (RPI)
"We've shown how resveratrol has very interesting selectivity to target and neutralize a select set of toxic peptide isoforms," Tessier said. "Because resveratrol picks out the clumps of peptides that are bad and leaves alone the ones that are benign, it helps us to think about the structural differences between the peptide isoforms."
Isoforms are different packing arrangements of a particular peptide. Deformations of a particular peptide - the AОІ1-42 peptide - have been linked to Alzheimer's disease. Improperly folded peptides have been shown to collect in accumulations called "plaques" within the brain. Those plaques are often found near areas of cell death in diseased brains.
It is not clear that resveratrol is able to cross the blood-brain barrier, Tessier said. However, the molecule has garnered interest in recent years for its potential impact on cancer and aging.
In their research, Tessier and his co-authors generated A peptides packed together in five unique isoforms, or "arrangements" (monomer, soluble oligomer, non-toxic oligomer, fibrillar intermediates and amyloid fibrils). In their experiments, three of these arrangements were toxic to human cells, two were not.
Next, the researchers introduced resveratrol.
The resveratrol reacted with the toxic arrangements of the AОІ1-42 peptide, neutralizing their toxicity.
It did not affect the non-toxic arrangements.
"The surprise is that this molecule can target some of these packing arrangements that are toxic and rearrange them into packing arrangements that are not toxic. For those forms that are non-toxic, it doesn't change them," Tessier said.
Intriguingly, Tessier said, one of the toxic arrangements (the soluble oligomer) and one of the non-toxic arrangements (the non-toxic oligomer) were indistinguishable by various methods. And yet the resveratrol only affected the toxic arrangement.
The point, Tessier concludes, is that the seemingly identical non-toxic and toxic arrangements must have some distinguishing feature yet to be discovered, raising questions for future study.
"We have two things that look very similar, but one is toxic and the other isn't," Tessier said. "What is it that makes the bad one bad and the good one good?"
The research produced several other findings, Tessier said, including reliable methods of generating the arrangements Tessier's team produced, and formation of one arrangement which had previously been unknown.
Last week, Tessier was named as a 2010 Pew Scholar in the Biomedical Sciences by the Pew Charitable Trusts.The distinction includes an award of $240,000 over four years and inclusion into a select community of scientists that includes three Nobel Prize winners, three MacArthur Fellows, and two recipients of the Albert Lasker Medical Research Award, according to the Pew Charitable Trusts.
Tessier was also recently awarded a five-year, $411,872 Faculty Early Career Development Award (CAREER) from the National Science Foundation (NSF) for research in the related field of protein thermodynamics and aggregation.
The CAREER Award is given to faculty members at the beginning of their academic careers and is one of NSF's most competitive awards, placing emphasis on high-quality research and novel education initiatives.
Tessier joined the Rensselaer faculty in 2007 following a postdoctoral fellowship at the Massachusetts Institute of Technology's Whitehead Institute for Biomedical Research. He received his bachelor's degree in chemical engineering from the University of Maine, and went on to earn his doctoral degree in chemical engineering from the University of Delaware.
Source:
Rensselaer Polytechnic Institute (RPI)
Protein And MicroRNA Block Cellular Transition Vital To Metastasis
Like a bounty hunter returning escapees to custody, a cancer-fighting gene converts organ cells that change into highly mobile stem cells back to their original, stationary state, researchers report online at Nature Cell Biology.
This newly discovered activity of the p53 gene offers a potential avenue of attack on breast cancer stem cells thought to play a central role in progression and spread of the disease, according to scientists at The University of Texas MD Anderson Cancer Center.
Long known for monitoring DNA damage and forcing defective cells to kill themselves, p53 also activates bits of RNA that block two proteins, the researchers found. This prevents conversion of epithelial-differentiated cells, which line or cover an organ, into cells that resemble mesenchymal stem cells when stimulated by the TGF-B(beta) growth factor.
Mesenchymal cells are mobile adult stem cells that can reproduce themselves and differentiate into a variety of cell types
"Blocking this conversion from epithelial cell to a mesenchymal cell type is important because that change plays an essential role in cancer metastasis," said senior author Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology.
Cancer treatment potential
"We found that p53 activates the micro RNA miR-200c, which forces cells that have taken on stem cell traits to revert to epithelial form," Hung said. "Activating this pathway has therapeutic potential to target tumor-initiating cells that have stem cell characteristics."
Research has shown that about 80 percent of all solid tumors begin in the epithelial cells. However, 90 percent of cancer deaths are caused by metastasis, the progression and spread of the disease to other organs.
The epithelial-to-mesenchymal transition (EMT) and its opposite process play important roles in embryonic development. Research has connected EMT activation to cancer progression and metastasis. Recent studies tie EMT to gain of stem cell traits in normal and transformed cells.
Cell status depends on p53, miR-200c levels
A series of experiments established that the p53 protein activates the miR-200c gene to produce the microRNA and that expression of the protein and miR-200c moved up and down together.
-- Knockout experiments in normal breast epithelial cells consistently showed that p53 expression stifled the EMT transition.
-- Cells with reduced p53 changed into mesenchymal-like cells.
-- When miR-200c was overexpressed in cells with low levels of p53, the cells took on epithelial characteristics, indicating that p53 uses the microRNA to block or reverse the transition to mesenchymal-type cells.
-- Mutated p53 failed to produce miR-200c, increasing stem cells in the cell culture.
-- Tissue array analysis of gene expression in 106 human breast tumor samples showed that low p53 expression correlated with higher expression of two genes associated with EMT. Increased p53 raised levels of miR-200c and the expression of a gene associated with epithelial status.
Mutations of p53 occur in more than half of cancers and loss of p53 activity correlates with poor prognosis in several cancer types. Restoring functions lost by p53 mutation by re-expressing miR-200c might be a good therapeutic strategy for treatment of p53-deficient tumors, Hung said.
Research was funded by grants from the National Cancer Institute, including those for MD Anderson's Specialized Program in Research Excellence (SPORE) for breast cancer and MD Anderson's cancer center support grant; the National Breast Cancer Foundation, Inc.; the Breast Cancer Research Foundation; the MD Anderson-China Medical University and Hospital Sister Institution Fund; the National Science Council of Taiwan and the Cancer Research Center of Excellence, Taiwan Department of Health.
Source: University of Texas M. D. Anderson Cancer Center
This newly discovered activity of the p53 gene offers a potential avenue of attack on breast cancer stem cells thought to play a central role in progression and spread of the disease, according to scientists at The University of Texas MD Anderson Cancer Center.
Long known for monitoring DNA damage and forcing defective cells to kill themselves, p53 also activates bits of RNA that block two proteins, the researchers found. This prevents conversion of epithelial-differentiated cells, which line or cover an organ, into cells that resemble mesenchymal stem cells when stimulated by the TGF-B(beta) growth factor.
Mesenchymal cells are mobile adult stem cells that can reproduce themselves and differentiate into a variety of cell types
"Blocking this conversion from epithelial cell to a mesenchymal cell type is important because that change plays an essential role in cancer metastasis," said senior author Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology.
Cancer treatment potential
"We found that p53 activates the micro RNA miR-200c, which forces cells that have taken on stem cell traits to revert to epithelial form," Hung said. "Activating this pathway has therapeutic potential to target tumor-initiating cells that have stem cell characteristics."
Research has shown that about 80 percent of all solid tumors begin in the epithelial cells. However, 90 percent of cancer deaths are caused by metastasis, the progression and spread of the disease to other organs.
The epithelial-to-mesenchymal transition (EMT) and its opposite process play important roles in embryonic development. Research has connected EMT activation to cancer progression and metastasis. Recent studies tie EMT to gain of stem cell traits in normal and transformed cells.
Cell status depends on p53, miR-200c levels
A series of experiments established that the p53 protein activates the miR-200c gene to produce the microRNA and that expression of the protein and miR-200c moved up and down together.
-- Knockout experiments in normal breast epithelial cells consistently showed that p53 expression stifled the EMT transition.
-- Cells with reduced p53 changed into mesenchymal-like cells.
-- When miR-200c was overexpressed in cells with low levels of p53, the cells took on epithelial characteristics, indicating that p53 uses the microRNA to block or reverse the transition to mesenchymal-type cells.
-- Mutated p53 failed to produce miR-200c, increasing stem cells in the cell culture.
-- Tissue array analysis of gene expression in 106 human breast tumor samples showed that low p53 expression correlated with higher expression of two genes associated with EMT. Increased p53 raised levels of miR-200c and the expression of a gene associated with epithelial status.
Mutations of p53 occur in more than half of cancers and loss of p53 activity correlates with poor prognosis in several cancer types. Restoring functions lost by p53 mutation by re-expressing miR-200c might be a good therapeutic strategy for treatment of p53-deficient tumors, Hung said.
Research was funded by grants from the National Cancer Institute, including those for MD Anderson's Specialized Program in Research Excellence (SPORE) for breast cancer and MD Anderson's cancer center support grant; the National Breast Cancer Foundation, Inc.; the Breast Cancer Research Foundation; the MD Anderson-China Medical University and Hospital Sister Institution Fund; the National Science Council of Taiwan and the Cancer Research Center of Excellence, Taiwan Department of Health.
Source: University of Texas M. D. Anderson Cancer Center
Why A Mother's High-Fat Diet Contributes To Obesity In Her Children
New research published online in The FASEB Journal (fasebj) suggests that pregnant women should think twice about high-fat foods. In a study from the University of Cincinnati and the Medical College of Georgia, scientists found that female mice fed high fat diets were more likely to have oversized offspring (a risk factor for overweight and obesity) because fat causes the placenta to go into "overdrive" by providing too many nutrients to the fetus. This information also suggests that the reverse may be true as well - high fat diets may help prevent undersized babies.
"Our model may one day lead to dietary recommendations for mothers who are entering pregnancy overweight or obese," said Helen N. Jones, Ph.D., first author of the study. "We hope this research will ultimately help reduce the number of babies suffering from birth injuries, decrease C-section rates, and lower the risk of babies becoming overweight or obese later in life."
To reach their conclusion, the researchers fed one group of mice a normal diet and another group a higher fat diet for eight weeks. Then the mice were mated. At the end of each mouse's pregnancy the offspring were delivered by c-section and weighed along with their placentas. The scientists then took blood from the mothers and measured the ability of the placenta to transport nutrients to the babies.
"It's no secret that big women tend to have big babies," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but now we know that there's more at play than genetics. Cutting back on fatty foods during pregnancy might decrease the chance of having a baby that becomes overweight in the future."
According to the U.S. Centers for Disease Control and Prevention, about one-third of adult men and women, and 16.3 percent of children and youth in the United States are obese. Obesity increases the risk of many diseases and health conditions, including: hypertension, osteoarthritis (breakdown of cartilage and its underlying bone in a joint), dyslipidemia (high total cholesterol, high levels of triglycerides), type 2 diabetes, coronary heart disease, stroke, gallbladder disease, sleep apnea and respiratory problems, and some cancers.
The FASEB Journal (fasebj) is published by the Federation of American Societies for Experimental Biology (FASEB) and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 21 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances health and welfare by promoting progress and education in biological and biomedical sciences through service to its member societies and collaborative advocacy.
Source: Cody Mooneyhan
Federation of American Societies for Experimental Biology
"Our model may one day lead to dietary recommendations for mothers who are entering pregnancy overweight or obese," said Helen N. Jones, Ph.D., first author of the study. "We hope this research will ultimately help reduce the number of babies suffering from birth injuries, decrease C-section rates, and lower the risk of babies becoming overweight or obese later in life."
To reach their conclusion, the researchers fed one group of mice a normal diet and another group a higher fat diet for eight weeks. Then the mice were mated. At the end of each mouse's pregnancy the offspring were delivered by c-section and weighed along with their placentas. The scientists then took blood from the mothers and measured the ability of the placenta to transport nutrients to the babies.
"It's no secret that big women tend to have big babies," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but now we know that there's more at play than genetics. Cutting back on fatty foods during pregnancy might decrease the chance of having a baby that becomes overweight in the future."
According to the U.S. Centers for Disease Control and Prevention, about one-third of adult men and women, and 16.3 percent of children and youth in the United States are obese. Obesity increases the risk of many diseases and health conditions, including: hypertension, osteoarthritis (breakdown of cartilage and its underlying bone in a joint), dyslipidemia (high total cholesterol, high levels of triglycerides), type 2 diabetes, coronary heart disease, stroke, gallbladder disease, sleep apnea and respiratory problems, and some cancers.
The FASEB Journal (fasebj) is published by the Federation of American Societies for Experimental Biology (FASEB) and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 21 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances health and welfare by promoting progress and education in biological and biomedical sciences through service to its member societies and collaborative advocacy.
Source: Cody Mooneyhan
Federation of American Societies for Experimental Biology
Can Genetic Information Be Controlled By Light?
DNA, the molecule that acts as the carrier of genetic information in all forms of life, is highly resistant against alteration by ultraviolet light, but understanding the mechanism for its photostability presents some puzzling problems. A key aspect is the interaction between the four chemical bases that make up the DNA molecule. Researchers at Kiel University have succeeded in showing that DNA strands differ in their light sensitivity depending on their base sequences. Their results are reported by Nina Schwalb and colleagues in the current issue of the journal Science appearing on October 10, 2008.
It has been known for many years that the individual bases that code the genetic information contained in DNA show a high degree of photostability, as the energy that they take up from UV radiation is immediately released again. Surprisingly, however, it is found that in DNA, which consists of many bases, those mechanisms are ineffective or only partially effective. It seems that the deactivation of UV-excited DNA molecules must instead occur by some completely different mechanisms specific to DNA, which are not yet understood. Through measurements by a variety of methods on DNA molecules with different base sequences, the research group led by Professor Friedrich Temps at the Institute of Physical Chemistry of Kiel University has now been able to confirm and clarify that assumption.
According to Professor Temps, "DNA achieves its high degree of photostability through its complex double-helix structure. The interactions between bases that are stacked one above another within a DNA strand, and the hydrogen bonds between the base pairs of the two complementary single strands in the double-helix play key roles. Through the different interactions that we have observed the DNA acts to some extent as its own sun-protection".
Nina Schwalb investigated many different base combinations in synthetically-produced DNA molecules. Using a femtosecond pulsed laser spectroscope, she measured the characteristic energy release for each combination. She was able to measure the time for which the molecules continued to fluoresce, and thus how long they stored the light energy. She found that for some base combinations these fluorescence 'lifetimes' were only about 100 femtoseconds, whereas for others they were up to a thousand times longer. A femtosecond is one millionth of a billionth of a second.
Commenting on the conclusions from her research, Nina Schwalb says: "We have investigated the photophysical properties and have found that different base combinations have widely different fluorescence lifetimes. This could lead to the development of a new diagnostic method whereby laser light could be used to directly recognise certain genetic sequences without, for example, having to mark the DNA with dyes as in the method used at present".
One might also envisage linking the photophysical properties to genetic characteristics. When these mechanisms are better understood, it might in the long term become possible to repair gene mutations using laser radiation.
"In the field of nano-electronics it has already been shown that synthetically produced DNA can be used as 'nano-wires'. On the basis of the different reaction times of the molecules it might one day become possible to use laser pulses to 'switch' specific molecules. It might even be possible under some circumstances to make transistors from DNA that would work through the hydrogen bonds," explains Professor Temps.
This release is available in German.
The work of Nina Schwalb is being supported by the German Research Foundation (DFG) as part of the project "Ultrafast Photodynamics of DNA".
Source: Nina Schwalb
Kiel University
It has been known for many years that the individual bases that code the genetic information contained in DNA show a high degree of photostability, as the energy that they take up from UV radiation is immediately released again. Surprisingly, however, it is found that in DNA, which consists of many bases, those mechanisms are ineffective or only partially effective. It seems that the deactivation of UV-excited DNA molecules must instead occur by some completely different mechanisms specific to DNA, which are not yet understood. Through measurements by a variety of methods on DNA molecules with different base sequences, the research group led by Professor Friedrich Temps at the Institute of Physical Chemistry of Kiel University has now been able to confirm and clarify that assumption.
According to Professor Temps, "DNA achieves its high degree of photostability through its complex double-helix structure. The interactions between bases that are stacked one above another within a DNA strand, and the hydrogen bonds between the base pairs of the two complementary single strands in the double-helix play key roles. Through the different interactions that we have observed the DNA acts to some extent as its own sun-protection".
Nina Schwalb investigated many different base combinations in synthetically-produced DNA molecules. Using a femtosecond pulsed laser spectroscope, she measured the characteristic energy release for each combination. She was able to measure the time for which the molecules continued to fluoresce, and thus how long they stored the light energy. She found that for some base combinations these fluorescence 'lifetimes' were only about 100 femtoseconds, whereas for others they were up to a thousand times longer. A femtosecond is one millionth of a billionth of a second.
Commenting on the conclusions from her research, Nina Schwalb says: "We have investigated the photophysical properties and have found that different base combinations have widely different fluorescence lifetimes. This could lead to the development of a new diagnostic method whereby laser light could be used to directly recognise certain genetic sequences without, for example, having to mark the DNA with dyes as in the method used at present".
One might also envisage linking the photophysical properties to genetic characteristics. When these mechanisms are better understood, it might in the long term become possible to repair gene mutations using laser radiation.
"In the field of nano-electronics it has already been shown that synthetically produced DNA can be used as 'nano-wires'. On the basis of the different reaction times of the molecules it might one day become possible to use laser pulses to 'switch' specific molecules. It might even be possible under some circumstances to make transistors from DNA that would work through the hydrogen bonds," explains Professor Temps.
This release is available in German.
The work of Nina Schwalb is being supported by the German Research Foundation (DFG) as part of the project "Ultrafast Photodynamics of DNA".
Source: Nina Schwalb
Kiel University
How Sunlight Causes Skin Cells To Turn Cancerous
Most skin cancers are highly curable, but require surgery that can be painful and scarring.
A new study by Loyola University Health System researchers could lead to alternative treatments that would shrink skin cancer tumors with drugs. The drugs would work by turning on a gene that prevents skin cells from becoming cancerous, said senior author Mitchell Denning, Ph.D.
The study was published Jan. 15, 2010 in the Journal of Biological Chemistry.
More than 1 million people in the United States are diagnosed with skin cancer each year. In the new study, researchers examined a type of skin cancer, called squamous cell carcinoma, that accounts for between 200,000 and 300,000 new cases per year.
Squamous cell carcinoma begins in the upper part of the epidermis, the top layer of the skin. Most cases develop on areas that receive lots of sun, such as the face, ear, neck, lips and backs of hands. There are various surgical treatments, including simple excision, curettage and electrodessication (scraping with a surgical tool and treating with an electric needle) and cryosurgery (freezing with liquid nitrogen). Removing large skin cancers can require skin grafts and be disfiguring.
Sunlight can damage a skin cell's DNA. Normally, a protein called protein kinase C (PKC) is activated in response to the damage. If the damage is too great to repair, the PKC protein directs the cell to die.
Healthy cells grow and divide in a cell-division cycle. At several checkpoints in this cycle, the cell stops to repair damaged DNA before progressing to the next step in the cycle. The new study found that the PKC gene is responsible for stopping the cell at the checkpoint just before the point when the cell divides. In squamous cell carcinoma, the PKC gene is turned off. The cell proceeds to divide without first stopping to repair its DNA, thus producing daughter tumor cells.
Denning said a class of drugs called protein kinase inhibitors potentially could shrink tumors by turning the PKC gene back on. Several such drugs have been approved by the Food and Drug Administration for other cancers. Denning is pursuing grant funding to test such drugs on animal models.
Denning is a professor in the Department of Pathology at Loyola University Chicago Stritch School of Medicine. The lead author of the study is Edward LaGory, a doctoral student at Stritch. A third co-author is Leonid Sitailo, Ph.D., a research assistant professor at Stritch.
Source: Loyola University Health System
A new study by Loyola University Health System researchers could lead to alternative treatments that would shrink skin cancer tumors with drugs. The drugs would work by turning on a gene that prevents skin cells from becoming cancerous, said senior author Mitchell Denning, Ph.D.
The study was published Jan. 15, 2010 in the Journal of Biological Chemistry.
More than 1 million people in the United States are diagnosed with skin cancer each year. In the new study, researchers examined a type of skin cancer, called squamous cell carcinoma, that accounts for between 200,000 and 300,000 new cases per year.
Squamous cell carcinoma begins in the upper part of the epidermis, the top layer of the skin. Most cases develop on areas that receive lots of sun, such as the face, ear, neck, lips and backs of hands. There are various surgical treatments, including simple excision, curettage and electrodessication (scraping with a surgical tool and treating with an electric needle) and cryosurgery (freezing with liquid nitrogen). Removing large skin cancers can require skin grafts and be disfiguring.
Sunlight can damage a skin cell's DNA. Normally, a protein called protein kinase C (PKC) is activated in response to the damage. If the damage is too great to repair, the PKC protein directs the cell to die.
Healthy cells grow and divide in a cell-division cycle. At several checkpoints in this cycle, the cell stops to repair damaged DNA before progressing to the next step in the cycle. The new study found that the PKC gene is responsible for stopping the cell at the checkpoint just before the point when the cell divides. In squamous cell carcinoma, the PKC gene is turned off. The cell proceeds to divide without first stopping to repair its DNA, thus producing daughter tumor cells.
Denning said a class of drugs called protein kinase inhibitors potentially could shrink tumors by turning the PKC gene back on. Several such drugs have been approved by the Food and Drug Administration for other cancers. Denning is pursuing grant funding to test such drugs on animal models.
Denning is a professor in the Department of Pathology at Loyola University Chicago Stritch School of Medicine. The lead author of the study is Edward LaGory, a doctoral student at Stritch. A third co-author is Leonid Sitailo, Ph.D., a research assistant professor at Stritch.
Source: Loyola University Health System
Human Fertilisation And Embryology Bill Published, UK
Health Minister Dawn Primarolo published the Human
Fertilisation and Embryology Bill to reform the regulation of human
embryology and ensure that Britain remains a world leader in medical
research.В The Bill will not however alter the model of regulation or
the basic foundations of the existing law.
The Bill updates current regulation of assisted reproduction and
embryo research in the light of developments in technology and
society's attitudes. It will ensure regulation is fit for purpose,
and help maintain the UK's position as a world leader in reproductive
technologies and research.
The main elements of the Bill are:
- ensuring that the creation and use of all human embryos outside the
body - whatever the process used in their creation - are subject to
regulation;
- a ban on selecting the sex of offspring for non-medical reasons;
- retention of a duty to take account of "the welfare of the child"
when providing fertility treatment, but removal of the reference to
"the need for a father";
- provisions to recognise same-sex couples as legal parents of
children conceived through the use of donated sperm, eggs or embryos;
- altering restrictions on the use of HFEA-collected data to make it
easier to do follow-up research;
- provisions increasing the scope of legitimate embryo research
activities, including regulation of "inter-species embryos" (embryos
combining human and animal genetic material).
Dawn Primarolo said:
"The UK is a world leader and a good place to do research. This Bill
will allow legitimate medical and scientific use of human
reproductive technologies for research to flourish in this country,
while giving the public confidence that they are being used and
developed sensibly with appropriate controls in place.
"I believe this Bill will provide clarity and assurance to patients,
researchers, the medical profession, and the public for years to
come."
The Bill needs to move through both the House of Lords and then the
Commons. It will then receive Royal Assent. It is expected to be in
force from early 2009.
Notes:
1. On 17 May, the government published draft legislation for
pre-legislative scrutiny to revise and update the Human Fertilisation
and Embryology Act 1990. This was set out in the Human Tissue and
Embryos (draft) Bill.
2. The Joint Committee scrutiny report was published on 1 August.
The way ahead for the Bill was set out in the Government's response
to the Scrutiny Committee report published on 8 October.
3. The current legislation, the Human Fertilisation and Embryology
Act 1990, is based largely on consideration and debate that took
place in the 1980s.
4. The bill sets out what will be permitted within the law, it is not
a commitment to what will be provided by the NHS.
5. Main elements of the Bill
Bill Proposals - main elements
-Current Position
Ensuring that the creation and use of all human embryos outside the
body - whatever the process used in their creation - are subject to
regulation.
-Current law refers to fertilisation - sperm and egg.
A ban on selecting the sex of offspring for non-medical reasons.
-Currently subject to HFEAВ guidance i.e. only allowed for medical
reasons
Retention of a duty to take account of "the welfare of the child"
when providing fertility treatment, but removal of the reference to
"the need for a father".
-Currently take account of the welfare of the child, including the
need for a father.
Provisions to recognise same-sex couples as legal parents of children
conceived through the use of donated sperm, eggs or embryos.
-Currently, only the partner who has given birth to the child is
regarded as a legal parent.
Altering restrictions on the use of HFEA-collected data to make it
easier to do follow-up research.
-Currently, the HFEA has legal restrictions on what data can be
released from the register.
Provisions increasing the scope of legitimate embryo research
activities, including regulation of "inter-species embryos".
-The current law (the 1990 Act) bans "mixing of human and animal
gametes". It refers to human embryos only.
6. The Government's response to the Report from the Joint Committee
on the Human Tissues and Embryos (draft) Bill is available at
dh.uk
Fertilisation and Embryology Bill to reform the regulation of human
embryology and ensure that Britain remains a world leader in medical
research.В The Bill will not however alter the model of regulation or
the basic foundations of the existing law.
The Bill updates current regulation of assisted reproduction and
embryo research in the light of developments in technology and
society's attitudes. It will ensure regulation is fit for purpose,
and help maintain the UK's position as a world leader in reproductive
technologies and research.
The main elements of the Bill are:
- ensuring that the creation and use of all human embryos outside the
body - whatever the process used in their creation - are subject to
regulation;
- a ban on selecting the sex of offspring for non-medical reasons;
- retention of a duty to take account of "the welfare of the child"
when providing fertility treatment, but removal of the reference to
"the need for a father";
- provisions to recognise same-sex couples as legal parents of
children conceived through the use of donated sperm, eggs or embryos;
- altering restrictions on the use of HFEA-collected data to make it
easier to do follow-up research;
- provisions increasing the scope of legitimate embryo research
activities, including regulation of "inter-species embryos" (embryos
combining human and animal genetic material).
Dawn Primarolo said:
"The UK is a world leader and a good place to do research. This Bill
will allow legitimate medical and scientific use of human
reproductive technologies for research to flourish in this country,
while giving the public confidence that they are being used and
developed sensibly with appropriate controls in place.
"I believe this Bill will provide clarity and assurance to patients,
researchers, the medical profession, and the public for years to
come."
The Bill needs to move through both the House of Lords and then the
Commons. It will then receive Royal Assent. It is expected to be in
force from early 2009.
Notes:
1. On 17 May, the government published draft legislation for
pre-legislative scrutiny to revise and update the Human Fertilisation
and Embryology Act 1990. This was set out in the Human Tissue and
Embryos (draft) Bill.
2. The Joint Committee scrutiny report was published on 1 August.
The way ahead for the Bill was set out in the Government's response
to the Scrutiny Committee report published on 8 October.
3. The current legislation, the Human Fertilisation and Embryology
Act 1990, is based largely on consideration and debate that took
place in the 1980s.
4. The bill sets out what will be permitted within the law, it is not
a commitment to what will be provided by the NHS.
5. Main elements of the Bill
Bill Proposals - main elements
-Current Position
Ensuring that the creation and use of all human embryos outside the
body - whatever the process used in their creation - are subject to
regulation.
-Current law refers to fertilisation - sperm and egg.
A ban on selecting the sex of offspring for non-medical reasons.
-Currently subject to HFEAВ guidance i.e. only allowed for medical
reasons
Retention of a duty to take account of "the welfare of the child"
when providing fertility treatment, but removal of the reference to
"the need for a father".
-Currently take account of the welfare of the child, including the
need for a father.
Provisions to recognise same-sex couples as legal parents of children
conceived through the use of donated sperm, eggs or embryos.
-Currently, only the partner who has given birth to the child is
regarded as a legal parent.
Altering restrictions on the use of HFEA-collected data to make it
easier to do follow-up research.
-Currently, the HFEA has legal restrictions on what data can be
released from the register.
Provisions increasing the scope of legitimate embryo research
activities, including regulation of "inter-species embryos".
-The current law (the 1990 Act) bans "mixing of human and animal
gametes". It refers to human embryos only.
6. The Government's response to the Report from the Joint Committee
on the Human Tissues and Embryos (draft) Bill is available at
dh.uk
The Time It Takes To Reassemble The World
A few glimpses are enough to perceive a seamless and richly detailed visual world. But instead of "photographic snapshots", information about the color, shape and motion of an object is pulled apart and sent through individual nerve cells, or neurons, to the visual center in the brain. How the brain puts the scene back to together has been hotly debated ever since neurons were discovered over a century ago.
A novel experimental design allowed researchers at the Salk Institute for Biological Studies to scrutinize this process, called conjunction, stopwatch in hand. They found that individual features of an object are permanently joined together by a computational process that takes time, 1/100th of a second to be exact. Their findings are reported in the Jan. 24 issue of the Journal of Neuroscience.
"The question of how the brain integrates different signals is fundamental to our understanding of sensory processing, and a range of different theories have been advanced," says John Reynolds, Ph.D., an assistant professor in the Systems Neurobiology Laboratory who led the study. "Our finding that a very small, but consistent, amount of time is required to compute a very simple conjunction is important because it places very tight limits on the amount of time that is available for the mechanisms that mediate this computation to operate."
To measure the time required for integration, Clara BodelГіn, Ph.D., a mathematician in Reynolds' laboratory, painstakingly designed pairs of simple images-for example, a red vertical stripe pattern or a green horizontal pattern-which, when presented quickly enough, cancel one another and become invisible.
After securing the last eight computer monitors in the world that could actually present the stimuli quick enough to exceed the limits of perception (newer LCD monitors don't refresh the screen fast enough) and painstakingly calibrating the monitors to precisely control the activity of individual photoreceptors in the eye, the Salk researchers were ready to inch closer to answering an age-old and much-debated question: How do neurons communicate to give rise to our coherent perception of the world?
At very high presentation rates, the stimuli were literally invisible. But when BodelГіn slowed the presentation rate, human observers could tell an image's orientation. Interestingly, when presentation rate was lowered even further, the test subjects could distinguish color and orientation but were unable to say which image - the vertical or horizontal one - was red or green. In other words, the brain could "see" both form and color but could not see how they were combined.
Only after slowing presentation of the stimuli further could the observers accurately report color and orientation of individual objects, indicating that computing the overall meaning of all this visual input is a time-consuming process. Thus, the features of the stimulus were available to perception before they were "bound" together. Binding of features, however, required more time.
"Nobody knew whether a separate computation step was necessary to integrate individual attributes of objects and, if so, how long it would take," explains BodelГіn. "The fact that it takes time to reliably perceive the combination of color and orientation points to the existence of a distinct integration mechanism. We can now start to test different hypotheses about the nature of this mechanism," she adds.
"The question how the brain synthesizes visual information is of tremendous importance from a basic science standpoint," explains Reynolds and adds that "it also has important practical implications for understanding and ultimately treating disorders of perception, such as visual agnosia, a debilitating condition in which the patient cannot 'see' complex visual stimuli."
By precisely measuring this fleeting visual computation, BodelГіn and her colleagues have taken an important first step in understanding the mechanisms that fail in patients who suffer from this disorder.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Contact: Gina Kirchweger
Salk Institute
A novel experimental design allowed researchers at the Salk Institute for Biological Studies to scrutinize this process, called conjunction, stopwatch in hand. They found that individual features of an object are permanently joined together by a computational process that takes time, 1/100th of a second to be exact. Their findings are reported in the Jan. 24 issue of the Journal of Neuroscience.
"The question of how the brain integrates different signals is fundamental to our understanding of sensory processing, and a range of different theories have been advanced," says John Reynolds, Ph.D., an assistant professor in the Systems Neurobiology Laboratory who led the study. "Our finding that a very small, but consistent, amount of time is required to compute a very simple conjunction is important because it places very tight limits on the amount of time that is available for the mechanisms that mediate this computation to operate."
To measure the time required for integration, Clara BodelГіn, Ph.D., a mathematician in Reynolds' laboratory, painstakingly designed pairs of simple images-for example, a red vertical stripe pattern or a green horizontal pattern-which, when presented quickly enough, cancel one another and become invisible.
After securing the last eight computer monitors in the world that could actually present the stimuli quick enough to exceed the limits of perception (newer LCD monitors don't refresh the screen fast enough) and painstakingly calibrating the monitors to precisely control the activity of individual photoreceptors in the eye, the Salk researchers were ready to inch closer to answering an age-old and much-debated question: How do neurons communicate to give rise to our coherent perception of the world?
At very high presentation rates, the stimuli were literally invisible. But when BodelГіn slowed the presentation rate, human observers could tell an image's orientation. Interestingly, when presentation rate was lowered even further, the test subjects could distinguish color and orientation but were unable to say which image - the vertical or horizontal one - was red or green. In other words, the brain could "see" both form and color but could not see how they were combined.
Only after slowing presentation of the stimuli further could the observers accurately report color and orientation of individual objects, indicating that computing the overall meaning of all this visual input is a time-consuming process. Thus, the features of the stimulus were available to perception before they were "bound" together. Binding of features, however, required more time.
"Nobody knew whether a separate computation step was necessary to integrate individual attributes of objects and, if so, how long it would take," explains BodelГіn. "The fact that it takes time to reliably perceive the combination of color and orientation points to the existence of a distinct integration mechanism. We can now start to test different hypotheses about the nature of this mechanism," she adds.
"The question how the brain synthesizes visual information is of tremendous importance from a basic science standpoint," explains Reynolds and adds that "it also has important practical implications for understanding and ultimately treating disorders of perception, such as visual agnosia, a debilitating condition in which the patient cannot 'see' complex visual stimuli."
By precisely measuring this fleeting visual computation, BodelГіn and her colleagues have taken an important first step in understanding the mechanisms that fail in patients who suffer from this disorder.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Contact: Gina Kirchweger
Salk Institute
In Stanford Study Mathematical Innovation Turns Blood Draw Into Information Gold Mine
Scientists at the Stanford University School of Medicine have devised a software algorithm that could enable a common laboratory device to virtually separate a whole-blood sample into its different cell types and detect medically important gene-activity changes specific to any one of those cell types.
In a study to be published online March 7 in Nature Methods, the scientists reported that they had successfully used the new technique to pinpoint changes in one cell type that flagged the likelihood of kidney-transplant recipients rejecting their new organs. Without the software, these gene-activity flags would have gone unnoticed. The authors believe that the use of the new algorithm may have applications beyond kidney rejection, allowing doctors to better identify the onset of cancers, genetic disorders and a variety of other problems.
The lab device, called a microarray, is a standard research tool. But until the development of this algorithm, scientists and physicians have not been able to use it to derive such medically useful information from whole-blood samples. Part of the problem is that the information is obscured by the whole-blood samples' complex, multiple-component composition.
"Drawing blood is one of the most common diagnostic tests in clinical practice," said one of the investigators, Atul Butte, MD, PhD, assistant professor of pediatrics and of medical informatics. "We'd love to be able to use microarrays to find changes in the blood that indicate trouble somewhere in the body. But distinguishing one type of cell from another can be critical to doing that."
Butte is a senior author of the paper, along with Mark Davis, PhD, director of the Stanford Institute for Immunity, Transplantation and Infection. The two lead authors are postdoctoral scholar Shai Shen-Orr, PhD, and Robert Tibshirani, PhD, professor of health research and policy and of statistics.
The potential for extracting important information from a blood sample has mushroomed since the advent of the microarray about 15 years ago. A microarray is a man-made, thumbnail-sized grid of DNA on whose surface reside tens of thousands of tiny sensors that can distinguish among different short sequences of nucleic acids - the genetic material of all life. Such a chip can be immersed in an extract from living cells, such as blood; then, whenever a sensor on the chip detects a matching nucleic-acid sequence, it transmits a fluorescent signal recording the sequence's presence.
By using microarrays to measure how actively a gene is being "expressed," research scientists can detect medically important alterations in a tissue. As they get steadily cheaper and easier to work with, microarrays are also at the threshold of widespread use as clinical diagnostic devices.
Still, whole blood poses a complication when used as a sample in microarray analyses. "Any 7-year-old can look at a blood sample under a microscope and see it's a mix of a huge number of different kinds of cells," said Butte, who is also director of the Center for Pediatric Bioinformatics at Lucile Packard Children's Hospital. A single sample contains dozens of cell types, at different levels of maturity or at different stages of activation. A gene-expression change that, in one cell type, means something has gone terribly wrong may in another cell type be completely benign, or even a sign of needed activation. But a microarray has no way of knowing which kind of cell in the mix a particular nucleic-acid snippet came from.
To make things more difficult, the composition of samples drawn from two different patients - or even of two samples drawn at different times from the same patient - varies dramatically.
Imagine that a public-opinion analyst, new on the job, were to conduct two national voter-preference surveys before and after a politician's speech, to see if that speech improved or impaired the popularity of a piece of legislation. But the rookie analyst has neglected to ask those surveyed which party they lean toward or what state they come from, so doesn't realize the first survey sample had a Democrat-to-Republican ratio of 30:70, while in the second, the ratio was reversed. The analyst might mistakenly infer a huge swing in pre- and post-speech preferences, when in fact the only real change was in the samples' compositions. Meanwhile, a vehement change in support among residents of a small but election-swinging state might go undetected.
In the same way, comparing a gene-expression pattern based on one person's whole-blood sample to another person's, or even the same person's blood over time, isn't very informative with a typical microarray run. Medically significant changes in gene-expression patterns can go unnoticed in those tests, while those that reflect changes in the composition of the sample may trigger false alarms.
While ways of separating whole blood into its constituent cell types do exist, these methods are too tedious, time-consuming and costly for routine clinical diagnostics and, for similar reasons, pose a challenge for research on large groups of subjects.
So the investigators devised an algorithm - in this case, a very large number of fairly simple equations. They believed that the simultaneous solution for all these equations enabled the assigning of gene-expression changes to particular cell types in patients' blood samples.
To test their algorithm's accuracy, the researchers obtained whole blood samples from 24 pediatric kidney-transplant patients. Fifteen of the 24 patients were experiencing symptoms of acute transplant rejection, while nine were in stable condition.
Because complete blood counts had been routinely performed on these patients, the frequencies within each sample of five important blood-cell types - monocytes, lymphocytes, neutrophils, basophils and eosinophils - were known.
Analyzing patients' whole blood samples via microarrays without resorting to the new algorithm, the investigators couldn't distinguish any gene-expression pattern differences between the two patient groups. But when they used the new algorithm, they found hundreds of differences in gene expression. Those differences could be used to tell which patients were rejecting their transplants and which were not. Of equal importance, this method let the researchers see that these changes were largely confined to one particular cell type: the monocytes. Only the new virtual-separation technique made fingering this cellular culprit possible.
"It was like a giant arrow pointing to the biological source of the rejection problem," said Davis, the Burton and Marion Avery Family Professor of Immunology and a Howard Hughes Medical Institute investigator.
Other Stanford co-authors were Dale Bodian, PhD; Trevor Hastie, PhD; Purvesh Khatri, PhD; Nicholas Perry; and Minnie Sarwal, MD, PhD. None of the co-authors has any financial stake in the new software technology. They intend to distribute it to the academic and nonprofit investigator communities free of charge and, perhaps, to license it to for-profit companies in order to speed its dissemination.
The study was supported by the National Institute of Allergy and Infectious Diseases, the National Heart Lung, and Blood Institute and the National Cancer Institute, all arms of the National Institutes of Health.
Source:
Bruce Goldman
Stanford University Medical Center
In a study to be published online March 7 in Nature Methods, the scientists reported that they had successfully used the new technique to pinpoint changes in one cell type that flagged the likelihood of kidney-transplant recipients rejecting their new organs. Without the software, these gene-activity flags would have gone unnoticed. The authors believe that the use of the new algorithm may have applications beyond kidney rejection, allowing doctors to better identify the onset of cancers, genetic disorders and a variety of other problems.
The lab device, called a microarray, is a standard research tool. But until the development of this algorithm, scientists and physicians have not been able to use it to derive such medically useful information from whole-blood samples. Part of the problem is that the information is obscured by the whole-blood samples' complex, multiple-component composition.
"Drawing blood is one of the most common diagnostic tests in clinical practice," said one of the investigators, Atul Butte, MD, PhD, assistant professor of pediatrics and of medical informatics. "We'd love to be able to use microarrays to find changes in the blood that indicate trouble somewhere in the body. But distinguishing one type of cell from another can be critical to doing that."
Butte is a senior author of the paper, along with Mark Davis, PhD, director of the Stanford Institute for Immunity, Transplantation and Infection. The two lead authors are postdoctoral scholar Shai Shen-Orr, PhD, and Robert Tibshirani, PhD, professor of health research and policy and of statistics.
The potential for extracting important information from a blood sample has mushroomed since the advent of the microarray about 15 years ago. A microarray is a man-made, thumbnail-sized grid of DNA on whose surface reside tens of thousands of tiny sensors that can distinguish among different short sequences of nucleic acids - the genetic material of all life. Such a chip can be immersed in an extract from living cells, such as blood; then, whenever a sensor on the chip detects a matching nucleic-acid sequence, it transmits a fluorescent signal recording the sequence's presence.
By using microarrays to measure how actively a gene is being "expressed," research scientists can detect medically important alterations in a tissue. As they get steadily cheaper and easier to work with, microarrays are also at the threshold of widespread use as clinical diagnostic devices.
Still, whole blood poses a complication when used as a sample in microarray analyses. "Any 7-year-old can look at a blood sample under a microscope and see it's a mix of a huge number of different kinds of cells," said Butte, who is also director of the Center for Pediatric Bioinformatics at Lucile Packard Children's Hospital. A single sample contains dozens of cell types, at different levels of maturity or at different stages of activation. A gene-expression change that, in one cell type, means something has gone terribly wrong may in another cell type be completely benign, or even a sign of needed activation. But a microarray has no way of knowing which kind of cell in the mix a particular nucleic-acid snippet came from.
To make things more difficult, the composition of samples drawn from two different patients - or even of two samples drawn at different times from the same patient - varies dramatically.
Imagine that a public-opinion analyst, new on the job, were to conduct two national voter-preference surveys before and after a politician's speech, to see if that speech improved or impaired the popularity of a piece of legislation. But the rookie analyst has neglected to ask those surveyed which party they lean toward or what state they come from, so doesn't realize the first survey sample had a Democrat-to-Republican ratio of 30:70, while in the second, the ratio was reversed. The analyst might mistakenly infer a huge swing in pre- and post-speech preferences, when in fact the only real change was in the samples' compositions. Meanwhile, a vehement change in support among residents of a small but election-swinging state might go undetected.
In the same way, comparing a gene-expression pattern based on one person's whole-blood sample to another person's, or even the same person's blood over time, isn't very informative with a typical microarray run. Medically significant changes in gene-expression patterns can go unnoticed in those tests, while those that reflect changes in the composition of the sample may trigger false alarms.
While ways of separating whole blood into its constituent cell types do exist, these methods are too tedious, time-consuming and costly for routine clinical diagnostics and, for similar reasons, pose a challenge for research on large groups of subjects.
So the investigators devised an algorithm - in this case, a very large number of fairly simple equations. They believed that the simultaneous solution for all these equations enabled the assigning of gene-expression changes to particular cell types in patients' blood samples.
To test their algorithm's accuracy, the researchers obtained whole blood samples from 24 pediatric kidney-transplant patients. Fifteen of the 24 patients were experiencing symptoms of acute transplant rejection, while nine were in stable condition.
Because complete blood counts had been routinely performed on these patients, the frequencies within each sample of five important blood-cell types - monocytes, lymphocytes, neutrophils, basophils and eosinophils - were known.
Analyzing patients' whole blood samples via microarrays without resorting to the new algorithm, the investigators couldn't distinguish any gene-expression pattern differences between the two patient groups. But when they used the new algorithm, they found hundreds of differences in gene expression. Those differences could be used to tell which patients were rejecting their transplants and which were not. Of equal importance, this method let the researchers see that these changes were largely confined to one particular cell type: the monocytes. Only the new virtual-separation technique made fingering this cellular culprit possible.
"It was like a giant arrow pointing to the biological source of the rejection problem," said Davis, the Burton and Marion Avery Family Professor of Immunology and a Howard Hughes Medical Institute investigator.
Other Stanford co-authors were Dale Bodian, PhD; Trevor Hastie, PhD; Purvesh Khatri, PhD; Nicholas Perry; and Minnie Sarwal, MD, PhD. None of the co-authors has any financial stake in the new software technology. They intend to distribute it to the academic and nonprofit investigator communities free of charge and, perhaps, to license it to for-profit companies in order to speed its dissemination.
The study was supported by the National Institute of Allergy and Infectious Diseases, the National Heart Lung, and Blood Institute and the National Cancer Institute, all arms of the National Institutes of Health.
Source:
Bruce Goldman
Stanford University Medical Center
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