But some rare metabolic diseases, such as hypolipidemia and Tangier disease, seem to work in reverse--they severely limit the amount of fat and cholesterol that makes it into the bloodstream. Researchers from the Carnegie Institution and the University of Pennsylvania have found a specific gene that could be responsible for such conditions; when the gene is disrupted, so is the ability to absorb lipids (fatty substances that include cholesterol) through the intestine.
Zebrafish larvae with a lethal mutation affecting fat metabolism (ffr) look the same as normal larvaes (wt) under normal magnification (left). However, when the embryos ingest lipid molecules labeled with...
In their latest research, published in the April 4 issue of the journal Cell Metabolism, Steve Farber of Carnegie’s Department of Embryology and Michael Pack, of the University of Pennsylvania School of Medicine describe their efforts to locate a gene called fat free within the genome of the zebrafish. These fish have become popular research organisms because their embryos are transparent, allowing studies that are not possible with traditional model organisms, such as mice and rats. Farber and Pack found that, despite the distant evolutionary relation between humans and zebrafish, the fat free gene in zebrafish is quite similar to a pair of human genes.
The researchers also explore the physical effects of a specific mutation of the gene, seeking to explain why larval fish with the mutation exhibit an impaired ability to absorb cholesterol. These fish die when they are about a one-and-a-half weeks old because of this defect, even though they look normal and swallow properly.
"There is a lot we still don’t know about how animals absorb, transport, and otherwise manage lipids," Farber said. "The fact that just one gene can have such a huge effect is encouraging, because it might reveal a means for treatment of human disease."
The scientists began by looking for structural defects in the mutants’ digestive organs. Their livers have abnormalities in the cells and ducts that produce bile--a salty, somewhat soapy fluid that helps lipid digestion. Certain pancreatic cells are also flawed, interfering with the production of digestive enzymes necessary for the breakdown of complex lipid molecules.
More importantly, the mutants also have defects in the cells that line the intestine, where fat and cholesterol absorption takes place. Normally, globules of lipid pass into these cells in small sacs called vesicles. These vesicles connect with the Golgi apparatus, a labyrinth of membranes filled with enzymes that modify the fats, and then new vesicles transport the fats out of the cell and into the bloodstream. The researchers found that this process is disrupted in the fat free mutants, preventing fats from reaching the bloodstream, and thereby depriving the animal of needed lipids.
Farber and Pack used a strategy called positional cloning both to locate fat free in the zebrafish genome and to determine its sequence. They found that the gene shares 75 percent of its sequence with a human gene called ANG2 (Another New Gene 2), which up to this time has had no known function. It also shares parts of its sequence with a gene called COG8, which is known to affect the Golgi apparatus. They also found that a change in only one base--one "letter" in the DNA code--results in the lethal mutation in zebrafish.
"This gene is absolutely necessary for cholesterol absorption--without it, the animals die," Farber said. This is encouraging for Pack, a physician-scientist in Penn’s Department of Medicine, "If we can understand this process in zebrafish, perhaps we can take what we learn and apply it to similar genes in humans, which could in turn lead to treatment for lipid metabolism disorders."
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Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
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Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
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Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
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Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
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