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Study led by Scripps Research scientist reveals little-known cell networks vital to circadian rhythm

05-03-2007 · EurekAlert!

In a wide-ranging systems biology study of circadian rhythm, a multi-institutional collaboration led by Scripps Research Institute Professor Steve Kay has uncovered some little-known cellular mechanisms for sustaining circadian rhythm and limiting the impact of genetic clock mutations in mammals. The new findings could have important implications for future circadian studies, and point researchers toward new ways to manipulate human circadian rhythm at the molecular level to treat diseases such as bipolar disorder.

Keywords: study, led, scripps, research, scientist, reveals, little-known, cell, networks, vital, circadian, rhythm, scripp, reveal, little, known, network

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Study of malaria parasites reveals new parasitic states
11-28-2007 · EurekAlert!
Although malaria parasites have undergone extensive laboratory study, relatively little is known about how they behave in humans to cause disease. Newly published data from a study of malaria-infected human blood reveal two biological states of the parasite Plasmodium falciparum not observed under laboratory conditions. This information may help scientists develop new strategies for treating malaria.
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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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Undergraduate research shows leaderless honeybee organizing
06-11-2007 · EurekAlert!
A new finding by an undergraduate scientist and a senior bee researcher gives new insight on the organization of honeybee colonies, which exhibit behavior rivaling human cultures in social complexity. The study reveals that major colony management activities are directed anonymously by hive workers using a nonspecific signal that modulates worker and queen behavior, and may have implications important for understanding other complex phenomena, from brain activity to terrorist networks.
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Scientists discover novel way to remove iron from ferritin
11-02-2007 · EurekAlert!
A new study led by Children's Hospital Oakland Research Institute senior scientist, Elizabeth Theil, PhD, is the first to suggest that a small protein or heptapeptide could be used to accelerate the removal of iron from ferritin. The results of this study may help scientists develop new medications that dramatically improve the removal of excess iron in patients diagnosed with blood diseases such as B-Thalassemia (Cooley's anemia) or sickle cell disease.
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Scripps Research study reveals new function of protein kinase pathway in tumor suppression
01-25-2007 · EurekAlert!
Scientists at the Scripps Research Institute have discovered a surprising new function of a well-known signaling pathway that, when activated, can inhibit tumor development. This finding may lead to the development of drugs that can serve as an effective cancer therapy by artificially activating this pathway in cancer cells.
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First high-res 3D structures of mammalian HSP90 protein solved
10-12-2007 · EurekAlert!
Dr. Dan Gewirth, Hauptman-Woodward senior research scientist, has just solved the structure of the first mammalian GRP94 protein implicated in immune diseases such as sepsis, AIDS and certain cancers. His work is being published today in a cover article in Molecular Cell. Gewirth's study confirms his hypothesis that this protein -- GRP94 -- is from the same family as the better known HSP90 proteins.
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Study says normal but out-of-control enzyme may be culprit that signals some cells to become cancer
07-31-2007 · EurekAlert!
Working with human colorectal cancer cells, a University of Minnesota team, led by cancer biologists Zigang Dong and Ann Bode, has found the potential culprit among a network of enzymes that relay signals inside cells to regulate such functions as cell growth, cancer development and programmed cell death. The work suggests that drugs designed to disable the enzyme, known as TOPK, could have anticancer benefits. The study appears in the July issue of the journal Gastroenterology.
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Bits of 'junk' RNA aid master tumor-suppressor gene
08-23-2007 · EurekAlert!
A University of Michigan study reveals that the p53 gene, a key protector mutated in half of all cancers, gets help in its vital job of stifling tumors from a trio of little-known micro RNA genes. Drugs that mimic their benefits could become important tools in cancer therapy someday.
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Networking around the clock
04-05-2007 · EurekAlert!
A Brandeis University study published in Cell this week shows for the first time experimentally that the circadian cells in fruit flies function as a network that enables the insects to adapt their behavior according to seasonal changes. This discovery leads the way to understanding how mammals, and presumably humans, adjust physiology and behavior to environmental changes such as short winter days and long summer ones.
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Parkinson's protein protects neurons from stress induced cell death
05-21-2007 · EurekAlert!
Parkinson's disease, also known as shaking palsy, is one of the most frequent diseases of the nervous system. In a collaborative effort the groups of Dr. Konstanze Winklhofer (Ludwig-Maximilians-University Munich) and Dr. Daniel Krappmann (GSF -- Research Center for Environment and Health, Neuherberg) have now been able to reveal a novel function for the Parkin protein.
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