BioUpdates for June, 2001

Seeing into the Future

Is it a Bird? Is it a Plane? No, it’s a Dinosaur!

The Ever Changing World of Proteins

Very Bad Cholesterol



Seeing into the Future

Experiments by researchers from the University of Florida, Cornell University, and the University of Pennsylvania are offering hope for combating the genetic disease Leber congenital amaurosis (LCA) that results in retinal degeneration and blindness. Using gene therapy on dogs born blind, suffering from a condition similar to LCA, the researchers succeeded in restoring vision to all three dogs. The experiment represents the biggest advance in the treatment of retinal degeneration and is particularly significant for two reasons. Firstly, it is the first time with this type of blindness that an eye’s function has been restored rather than simply halting further degeneration. Secondly, it is the first study to show gene therapy can be used effectively with eyes similar in size to the human eye. The experiment involved treating the right eyes of three blind Briard puppies with one injection of a virus carrying the corrective genes, while leaving the left eye untreated to act as a means of control. Although the experiment was to allow three months before testing the vision of the puppies, it became evident that their vision was being restored much sooner. Formal tests at the 3-month mark clearly indicated the restoration of sight to the right eye. Using mazes researchers observed the dogs bumping into objects on their left side while avoiding obstacles on their right. Much has to done to investigate potential negative effects of the treatment and it will be some years before trials on people can begin. However, the team is expressing cautious optimism. They not only see a bright future ahead for gene therapy as a means of treating the form of LCA caused by the mutated RPE65 gene, but also for treating other forms of LCA as well as other retinal degenerative conditions.

References:

Acland, G.M. et al (2001) Gene therapy restores vision in a canine model of childhood blindness. Nature Genetics 28 (May): 92-95

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Nature Genetics

http://www.nature.com/ng/

Search archive for article. Registration may be required to view abstract.

University of Pennsylvania Vision Research Center

http://vrc.med.upenn.edu/

Foundation for Fighting Blindness

http://www.blindness.org/

Although diplomatic relations between the US and China might not exactly be at an all-time high, paleontologists from both countries continue to enjoy fruitful relationships. While politicians wrangle over surveillance aircraft, researchers from the Chinese Academy of Geological Sciences and the American Museum of Natural History have just reported in Nature on a major dinosaur discovery. In spring 2000 scientists unearthed a specimen of a dromaeosaur, a two-legged theropod, with its full body covering intact. A discovery that "radically modifies our vision of these extinct animals" and sheds new light on theories concerning the origin of birds, strengthening the case of those who claim birds evolved from dinosaurs. The specimen displayed a covering of downy fibers, tufts resembling primitive feathers and branched structures similar to the barbs of contemporary bird feathers. Previous "feathered" dinosaur fossils have not provided a clear picture, but this discovery provides indisputable evidence that a feather like covering did exist in non-avian dinosaurs, indicating that feathers initially developed before flight probably as a method of keeping warm, with later adaptations leading to warm-bloodedness and flight. The researchers even speculate that such body coverings were needed by the young of larger species of theropods such as Tyrannosaurus Rex. During the spring of 2001 the specimen is on show at a number of US museums and is also undergoing CAT scan imaging.

References:

Qiang, Ji et al (2001). The distribution of integumentary structures in a feathered dinosaur. Nature 410 (April 26): 1084

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Nature

http://www.nature.com

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American Museum of Natural History

http://www.amnh.org/science/specials/dinobird.html

http://research.amnh.org/vertpaleo/dinobird.html

While some researchers struggle with the complexities of protein folding, Joshua Wand at the University of Pennsylvania is investigating another aspect of proteins; one that could fundamentally shift our understanding of how proteins function. Using nuclear magnetic resonance relaxation imaging Wand and his colleagues have been investigating the internal dynamics of the calmodulin-peptide protein across a range of temperatures. They discovered that the internal dynamics of the protein were much more fluid and variable than previous experiments using crystallographic techniques revealed. This discovery certainly demands a change in how proteins are viewed. A protein’s function is seen as being directly linked to its structure, with each having a different biochemical task. For the most part a protein’s structure has been seen as essentially static but Wand’s observations show that the structure of proteins is not necessarily static but rather entropic, meaning they have the ability to assume multiple states. Wand believes this dynamism is crucial to how proteins work. This notion suggests proteins could perhaps take on different tasks at different times due to variations in temperature, or have periods of activity and inactivity related to temperature changes.

References:

Lee, Andrew and Wand, A. Joshua (2001). Microscopic origins of entropy, heat capacity and the glass transition in proteins. Nature 411 (May 24): 501-504

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Nature

http://www.nature.com

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Untitled

http://cpmcnet.columbia.edu/dept/gsas/biochem/faculty/palmer.html

In a unique study Japanese researchers from the Osaka City University Medical School have identified oxidized low-density lipoprotein (ox-LDL) as a major culprit in causing heart attacks. Ox-LDL is considered more dangerous than LDL because it promotes clogging of blood vessels and the Japanese study certainly seems to confirm these suspicions, and certainly suggests that treatments to lower ox-LDL would reduce the incidence of heart attack and measuring ox-LDL levels would be a strong indicator of an impending heart attack. The researchers examined ox-LDL levels in four groups of 45 patients. Blood levels of ox-LDL were measured in heart attack patients, patients with unstable angina, patients with stable angina in addition to a control group with no heart problems. The results were very clear. Heart attack victims had over 63% more ox-LDL than unstable angina patients. In turn, unstable angina patients had levels over 33% higher than stable angina patients, whose own ox-LDL levels were 53% higher than the control group. Heart attack victim’s ox-LDL levels were 236% higher than those of the control group. In a secondary part of the study, sections of the coronary arteries associated with the unstable and stable angina patients were analyzed for ox-LDL content. Once again results showed significantly higher levels in the unstable angina patients, adding further disrepute to ox-LDL’s plummeting reputation!

References:

Ueda, Makiko et al (2001). Elevated Levels of Oxidized Low Density Lipoprotein Show a Positive Relationship With the Severity of Acute Coronary Syndromes. Circulation 103 (April): 1955-1960

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Circulation (Journal of the American Heart Association)

http://circ.ahajournals.org/cgi/content/abstract/103/15/1955

Abstract of the above reference.