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Hemophilia A Mice Benefit From Gene Therapy
Hemophilia A is an inherited bleeding disease caused by a lack of the blood clotting protein Factor VIII. It had been hoped that gene therapy would provide a breakthrough in treatment, but the most common gene therapy approach has had little clinical success. However, a team of researchers, at the University of Minnesota Medical School, Minneapolis, has now developed a new approach to target genes specifically to mouse liver sinusoidal endothelial cells (the cells that are the main of Factor VIII) and used it to provide long-term expression of Factor VIII in hemophilia A mice, markedly reducing their disease. They hope that their data might prove to be a step toward successful human clinical trials in individuals with hemophilia A.

RA Individuals From Lower GDP Countries Keep Working Despite Worse Symptoms Than Richer Countries
Individuals diagnosed with rheumatoid arthritis (RA) in lower gross domestic product (GDP) countries (GDP below $11,000) are more likely to continue working despite higher disease activity and functional disability scores compared to their counterparts in higher GDP countries (GDP >$24,000) according to a new multinational study presented today at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark.
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Genome Sequencing Of Schistosomiasis Parasites Could Promote Drug Development
Researchers have sequenced the genomes of two parasites that cause bilharzia or schistosomiasis - a disease transmitted by water-borne snails that affects more than 200 million people worldwide - "revealing potential weaknesses that could be exploited by drug developers," Nature reports (Smith, 7/15).
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Methane-Producing Molecule Can Also Repair DNA

The Archaea are single-celled organisms and a domain unto themselves, quite apart from the so called eukaryotes, being bacteria and higher organisms. Many species live under extreme conditions, and carry out unique biochemical processes shared neither with bacteria nor with eukaryotes. Methanogenic archaeans, for example, can produce methane gas out of carbon dioxide and hydrogen. The underlying chemical reaction, a reduction, involves the cofactor known as F0 or F420 which is the tiny molecule deazaflavin. It has previously been found only in methanogenic bacteria, and has accordingly been considered the signature molecule for those species. A research group working with Professor Thomas Carell, however, has now shown that this cofactor is also common in eukaryotes, where it performs an entirely different function: deazaflavin is involved in DNA repair processes. (PNAS Early Edition online, 1 July 2009) Catalysts assist in chemical reactions without undergoing any alteration of their own. In the cells of living organisms, proteins perform this important function. They carry out the metabolism fundamental to all living processes. Proteins are instrumental in cellular respiration, they for instance reduce oxygen to water and oxidize food into carbon dioxide. This releases the energy that makes life possible at all. Proteins cannot perform these functions on their own. They depend on small helper molecules. Such molecules are stored inside special pockets in the proteins and carry out essential metabolic functions. The living organism itself produces many of these helpers. Others - like vitamins - must be obtained from food. Severe vitamin deficiencies are a harsh reminder of how essential these molecules are. Methanogenic bacteria have quite an exceptional task to accomplish: They have to produce methane. In terms of chemistry, this is no mean feat. Methane production is currently one of the most hotly pursued goals for the purposes of renewable energy. It is also a serious greenhouse gas. Enzymatic methane production involves the tiny molecule deazaflavin, known as cofactor F0 or cofactor F420. This cofactor is stored inside special proteins of methanogenic bacteria, and is essential for methane biosynthesis. Cofactor F0/F420 is a small molecule that, until now, has only been found in methanogenic bacteria. It is regarded as the signature molecule for such species. "We have now shown that this picture is not entirely true," Carell says. "This cofactor is significantly more widespread in the biosphere than previously assumed. Most importantly, it also occurs in higher organisms, the so-called eukaryotes. But in these, it performs a completely different task." As the researchers were able to demonstrate, the cofactor is involved in DNA repair processes. Specifically, repair of UV damage to the DNA molecule. Plants and many other organisms that are exposed to intense sunlight must cope with an enormous degree of damage to their genes. To repair those mutations, they need the help of complex enzymes. These photolyases in turn require cofactor FAD - aka vitamin B2 - to accomplish this function. It has long been suspected that these crucial enzymes require yet another cofactor to provide the energy that DNA repair requires. "We have now shown that, in many organisms, this cofactor is F0/F420," Carell reports. "This molecule has been conclusively detected in DNA repair enzymes of Drosophila melanogaster, the fruit fly. Not long ago, another research group even postulated that F0/F420 is co-responsible for DNA repair in plants. Our view of cofactor F420 as a signature molecule for methanogenic species has therefore radically changed: this cofactor is widespread and it is essential for both methane synthesis and for DNA repair." Notes: Professor Thomas Carell is speaker of the "Center for Integrated Protein Science Munich (CiPSM)" center of excellence which supported this research. Publication: "The archaeal cofactor F0 is a light-harvesting antenna chromophore in eukaryotes", Andreas F. Glas, Melanie J. Maul, Max Cryle, Thomas R. M. Barends, Sabine Schneider, Emine Kaya, Ilme Schlichting, and Thomas Carell Professor Thomas Carell Ludwig-Maximilians-Universität MÃønchen


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