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BioUpdates for January, 2003 by Andrew Tolley Timing is Everything Timing is Everything After a lifelong search, bells are ringing for the husband and wife research team of D. James and Dorothy Morre of Purdue University. Although they have been occupied by other projects, the question of what makes the body "tick" has remained with them since 1962. Now, four decades later they have finally discovered the single protein that dictates the body’s rhythms. Studying how cells grow, they observed a repeating cycle of cell growth that alternated 12 minutes of enlargement with 12 minutes of rest. Working on the assumption that proteins were responsible for this pattern, the team was led to a single dual-functioning cylindrical molecule, an ECTO-NOX protein that facilitates cell growth for 12 minutes and then switches to another function for the next 12 minutes. Confirmation of the protein’s influence was obtained when Morre and James reproduced and manipulated of the protein to create clock cycles of different lengths of time. This very fundamental piece of biological knowledge could have any number of potential applications. Already scientists are talking about using it to counter jet lag, or the ill effects of sleep disorders and space travel, as well as possibly maximizing the impact of treatments with drugs that are sensitive to the timing of their delivery. The list will no doubt grow, but before any applications are possible the researchers remind us that a full understanding of this protein still requires a lot of work. References: Morre, D.J. et al (2002). Biochemical basis for the biological clock. Biochemistry 41(2002): p11941-11945 Visit: Biochemistry http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2002/41/i40/abs/bi020392h.html Abstract of above reference. Maternal Bonds Thanks to the combined efforts of researchers from the University of California at San Francisco, the Nevada Center for Reproductive Medicine, the Lawrence Berkeley National Laboratory and the University of Wisconsin, our understanding of embryonic and fetal development has taken a significant leap forward. The researchers have identified the mechanisms by which the embryo attaches itself to the uterus. Their studies demonstrate that the protein L-selectin that coats the trophoblast--a layer of specialized cells on the surface of the blastocyst (the very early embryo)--binds with carbohydrates on the uterine wall, thus enabling the embryo to attach to the uterus and commence placental development. Examining biopsies from the endometrium taken at different times during a woman’s monthly cycle, the researchers were able to establish that the greatest levels of carbohydrates coincides with greatest receptivity to the blastocyst. Furthermore, examination of L-selectin levels on the blastocyst revealed that the levels of the protein were greatest at time of implantation. Further study indicated that L-selectin levels on trophoblasts remained adequate to bond with the uterus up to the 16th week of pregnancy. This very basic research immediately invites clinical studies. This knowledge may lead to a fuller understanding of the causes of infertility and, perhaps more importantly, shed light on the causes of preeclampsia (life-threatening high blood pressure in pregnant women). It is believed that preeclampsia may result from the failure of placental cells to develop into blood-vessel-like cells that in turn have been linked to trophoblasts not adequately securing themselves to the wall of the uterus. References: Genbacev, Olga D. et al (2003). Trophoblast L-Selectin-Mediated Adhesion at the Maternal-Fetal Interface. Science 299 (Jan 17): 405-408. Asgerally T. Fazleabas and J. Julie Kim (2003). What Makes an Embryo Stick? Science 299 (Jan 17): 355-356. Visit: Science http://www.sciencemag.org/cgi/content/summary/299/5605/355 Abstracts of above references. Getting Down to the Bone (Marrow) Two different studies are both pointing to the potential use of bone marrow stem cells to treat various neurological disorders such as Parkinson’s disease. Led by Dr. Eva Mezey of the National Institute of Neurological Disorders and Strokes, one team, building on research already conducted in mice, has accumulated strong evidence that bone marrow cells can enter the human brain and generate neurons. The team used brain tissue derived from autopsies of four female leukemia patients who had received bone marrow transplants from males. On examination the team identified cells in the brain tissue that contained Y-chromosomes. This strongly suggests that these cells originated from the male bone marrow donors rather than the patients, and gives good reason to conclude that stem cells in bone marrow can develop into brain cells. Although the majority of the new cells in the brain tissue were glia or other non-neuronal cells, a small number of neurons were also identified in clusters in the cerebral cortex and hippocampus. Meanwhile researchers from Cedars-Sinai Medical Center’s Maxine Dunitz Neurosurgical Institute have successfully demonstrated that stem cells from whole adult bone marrow can be differentiated into a variety of central nervous system cells. After culturing bone marrow cells into "spheres" and transferring specific genes, the team could entice the bone marrow cells to develop into astrocytes, neurons, and oligodendroglia. With the promise of culturing central nervous system cells in the laboratory from patient-derived bone marrow, the ethical, practical, and safety controversies that swirl around using embryonic stem cells or a patient’s own brain tissue may be avoidable, perhaps opening the door to new therapies for any number of neurological diseases or injuries. References: Online Edition of Proceedings of the National Academy of Science Mezey, Eva et al (2003). Transplanted bone marrow generates new neurons in human brains PNAS published January 21, 2003, 10.1073/pnas.0336479100 (Neuroscience) Kabos, Peter et al (2002). Generation of Neural Progenitor Cells from Whole Adult Bone Marrow. Experimental Neurology 178 (Dec 2002): p288-293 Visit: Proceedings of the National Academy of Science http://www.pnas.org/cgi/content/abstract/0336479100v1 Abstract of above reference. Science Daily http://www.sciencedaily.com/releases/2003/01/030121080856.htm Press release concerning Mezey’s research. Experimental Neurology at Science Direct Search for Experimental Neurology article at Science Direct. Bones of Contention Conventional thinking in paleontology accepts the notion that birds evolved from dinosaurs, but exactly how this evolution came about remains a major point of debate. Two theories dominate: the first proposes that ground-dwelling animals developed feathers that allowed them to fly, whereas the second proposes that tree-dwelling animals developed gliding structures to facilitate leaping from tree to tree. The lack of concrete evidence for either theory has allowed the debate to persist, but two recent announcements begin to offer answers to some of the questions, while adding weight to both arguments. Dr. Kenneth Dial, a vertebrate morphologist from the University of Montana, has been observing the behavior of partridges and their behavior when moving along inclines. Instead of choosing to fly, the bird uses what is called "wing-assisted incline running" (WAIR), a process that stabilizes the animal as it runs on steep slopes. Dial postulates that this could represent a transitional stage between running and flying with WAIR’s presence in birds today representing an ancestral remnant. Whereas Dial’s work is based on interpretation of animal behavior, Xing Xu of the Chinese Academy of Sciences and his colleagues have just described in Nature a new four-winged dinosaur fossil called Microraptor gui found in China’s Liaoning province. They believe the remains of this small, four-winged dromaeosaur provide convincing evidence of the arboreal theory. They theorize that the four wings indicate that the animal was a glider and that as its successors developed flight they lost the hind wings. The new fossil will no doubt be subject to much examination from both proponents and opponents of the arboreal theory, especially since it is the first major fossil evidence addressing the transition to avian flight. References: Dial, Kenneth P. (2003). Wing-Assisted Incline Running and the Evolution of Flight. Science 299 (Jan 17): p402-404. Xing Xu, et al (2003). Four-winged dinosaurs from China. Nature 421 (Jan 23): p335-340 Prum, Richard O. (2003). Paleontology: Dinosaurs take to the air. Nature 421 (Jan 23): p323-324 Visit: Science http://www.sciencemag.org/cgi/content/abstract/299/5605/402 Abstract of above reference. Nature http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v421/n6921/abs/nature01342_fs.html Abstracts of above references. Heartworming News We usually think of worms as helping the soil. Now, research by scientists from the Medical College of Georgia, Massachusetts General Hospital and Harvard Medical School are uncovering exciting evidence that worms could also help the human heart. Over recent years evidence has accumulated connecting inflammation to cardiovascular disease. In brief, inflammation seems to restrict the free flow of blood through blood vessels and is especially associated with post-operative cardiac complications. The fatty acid Omega-3 is widely known to have an anti-inflammatory effect: the low rates of heart disease among native Alaskans who eat an Omega-3 rich diet is testimony to this fact. Armed with this knowledge and the fact that western diets contain the inflammation-inducing fatty acid, Omega-6, the researchers have been searching for a way to promote Omega-3 and reduce Omega-6. To do this they have turned to the worm C. elegans. Worms require a lot of Omega-3 to develop and acquire the fatty acid by converting Omega-6 to Omega-3 using an enzyme, desaturase fat-1. Researchers have now been mimicking the worm. In laboratory cultures, they have been able to convert Omega-6 to Omega-3 and have also seen a positive effect in a laboratory setting on reducing inflammatory markers on human vascular endothelium. The researcher’s next move is to develop a transgenic mouse that expresses the desaturase fat-1 to discover whether similar results are found in an entire organism. If this provides encouraging results, human clinical trials will no doubt follow. References: Presentation at the American Heart Association Scientific Sessions, November
2002. Visit: American Heart Association Scientific Sessions 2002 http://www.scientificsessions.org/ Medical College of Georgia http://www.mcg.edu/news/2002NewsRel/Meiler.html Press release concerning research. |
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