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St. Jude study shows genes play an unexpected role in their own activation

06-22-2007 · EurekAlert!

Investigators at St. Jude Children's Research Hospital have discovered how a single molecular "on switch" triggers gene activity that might cause effects ranging from learning and memory capabilities to glucose production in the liver.

Keywords: jude, study, shows, genes, play, unexpected, role, activation, show, gene

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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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Scientists identify a candidate gene for osteoporosis
03-28-2007 · EurekAlert!
Researchers report the identification of a gene that may play a role in susceptibility to osteoporosis -- the crippling disease that leads to bone fractures, especially of the hip and spine. The study, conducted by scientists at the Musculoskeletal Diseases Center of the Jerry L. Pettis Memorial Veteran's Affairs Medical Center at Loma Linda, shows convincing evidence that a gene called DARC negatively regulates bone density in mice.
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Genes influence age-related hearing loss
11-14-2007 · EurekAlert!
A new Brandeis University study of twins shows that genes play a significant role in the level of hearing loss that often appears in late middle age. The research, in the Journal of Gerontology: Medical Sciences, examined genetic and environmental factors affecting hearing loss in the frequency range of speech recognition.
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University of Washington researchers play leading role in major study of human genome function
06-13-2007 · EurekAlert!
Scientists at the University of Washington and other members of an international consortium have completed a multi-year research effort that dramatically boosts understanding of how the human genome functions. While previous studies of the human genome have focused mainly on genes, this study provides insight into non-gene sequences and "regulatory elements" that control genes and may play a role in many common diseases.
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Provider influence and patient barriers affect use of colorectal cancer screening
02-11-2008 · EurekAlert!
A new study shows that health care providers play a key role in the likelihood their patients are screened for colorectal cancer.
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Nature and nurture are both to blame for depression, study says
01-15-2008 · EurekAlert!
Depression is one of the most common forms of psychopathology. Studies suggest that the neurotransmitter dopamine may play a role in the risk for depression. Early negative interpersonal environments (i.e., rejecting parents) have also been implicated. New research investigated whether a gene associated with dopamine interacted with maternal parenting style to predict episodes of depression.
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Genes play important role in risk for dependence on illicit and licit drugs
11-05-2007 · EurekAlert!
The genes that play a role in illegal drug abuse are not entirely the same as those involved in dependence on legal substances like alcohol and nicotine, and caffeine addiction appears to be genetically independent of all the others, according to a study led by Virginia Commonwealth University researchers.
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Glucocorticoid plays key role in skin abnormalities induced by psychological stress
12-01-2006 · EurekAlert!
A new study shows how psychological stress induces abnormalities in skin structure and function that could initiate or worsen skin disorders such as psoriasis and atopic dermatitis. The study provides a link for understanding the roles psychological stress and glucocorticoid, a type of steroid, play in skin disorders and shows that blocking glucocorticoid can prevent skin abnormalities induced by psychological stress.
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Sour taste make you pucker? It may be in your genes
07-11-2007 · EurekAlert!
Scientists at the Monell Chemical Senses Center report that genes play a large role in determining individual differences in sour taste perception. The findings may help researchers identify the still-elusive taste receptor that detects sourness in foods and beverages, just as recent gene studies helped uncover receptors for sweet and bitter taste.
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Hepatitis C helicase unwinds DNA in a spring-loaded, 3-step process
07-26-2007 · EurekAlert!
The process by which genes are duplicated is mysterious and complex, involving a cast of characters with diverse talents and the ability to play well with others in extremely close quarters. A key player on this stage is an enzyme called a helicase. Its job is to unwind DNA or RNA so that another enzyme, a polymerase, can faithfully copy each nucleotide in the genetic code.A study to appear in Science sheds new light on how the hepatitis C helicase plays this role.
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