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BioUpdates for November, 2001

by Andrew Tolley

Complex Complex Carbohydrate Story Comes to an End

More to Flowers than Meets the Human Eye

Virtuous Venom

Peptides: A Dose of One's Own Medicine

Suppressing Genes and Criticism


Complex Complex Carbohydrate Story Comes to an End
Researchers at the University of Georgia's Complex Carbohydrate Research Center have known about the very complex carbohydrate, rhamnogalacturan II and its presence in all higher plants for over 20 years but have never been able to pin down its function. However, that has just changed. A combination of teamwork, toil, and good fortune has made it apparent that RG-II is crucial to normal plant growth because it cross-links with boron to form a structure for the cell wall to accommodate other components correctly. The team found their primary clue while examining mutant dwarf specimens of Arabidopsis. They discovered that although the plants had normal levels of RG-II, only half was cross-linked with boron. Consequently, the plant lacked the structural strength to expand and grow normally. Knowing that the mutant Arabidopsis lacked the enzyme that produces the sugar L-fucose, a component of RG-II, the team suspected that the RG-II would lack L-fucose. This suspicion proved to be correct, indicating that without normal RG-II plant growth was inhibited. Subsequent introduction of L-fucose as a fertilizer allowed normal plant growth, demonstrating that the RG-II molecule could be returned to the shape required to maximize cross-linking with boron. Conversely, boron fertilization produced similar results simply because the additional boron forced even defective RG-II to cross-link.

References:

O'Neill, Matthew A. et al (2001). Requirement of Borate Cross-Linking of Cell Wall Rhamnogalacturonan II for Arabidopsis Growth. Science 294 (Oct 26th): 846

Visit:

Science
http://www.sciencemag.org/cgi/content/abstract/294/5543/846
Abstract of above article.

University of Georgia Complex Carbohydrate Research Center
http://www.ccrc.uga.edu

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More to Flowers than Meets the Human Eye
Even though the colors of flowers tantalize the human eye, what we actually see is far from the view of those creatures with vision in the ultraviolet regions of the spectrum, namely bugs. To bugs more complex patterns appear that enable them to home in on the nectar and assist the plant in the pollination process. The work of two Cornell University biologists, Thomas and Maria Eisner, has illuminated this field of study for many years and now the same couple along with other Cornell researchers has discovered that the chemicals that produce these patterns in the ultraviolet spectrum serve an additional function. The chemicals in question, dearomatized isoprenylated phloroglucinols or DIPs, were examined in the flowering plant Hypericum calycinum for their role as anti-feedants. After isolating the plant's DIPs the researchers tempted caterpillars of the Utheisa ornatrix moth to filter paper discs laced with chemicals from plants the insects eat. Then the same paper discs drenched with DIPs were provided for the caterpillars. The research team observed that most of the caterpillars acknowledged the chemical warning and declined to feed on the DIP laden paper. What is more, those foolish specimens who did not pay attention to the warning met an early demise. It is evident from this study to the Cornell researchers that DIPs appear to have at least a dual evolutionary function. Not only do they facilitate plant reproduction but also protect the plant from the voracious appetite of herbivorous insects. The team is confident that they will discover similar patterns in other flowering plants and that this work will open up new avenues of research concerning natural pest control.

References:

Gronquist, Matthew et al (2001). Attractive and defensive functions of the ultraviolet pigments of a flower (Hypericum calycinum). Proceedings of the National Academy of Sciences 98 (Nov 20th): 13745-13750

Visit:

Proceedings of the National Academy of Sciences
http://www.pnas.org/cgi/content/abstract/98/24/13745
Abstract of above article.

Cornell Institute for Research in Chemical Ecology
http://www.cfe.cornell.edu/circe/aboutcirce.html

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Virtuous Venom
Multiple sclerosis is a debilitating disease leading to paralysis and ultimately death. Over 250,000 people in the U.S. suffer from this currently incurable affliction, but now there is a glimmer of hope from an unlikely source. Researchers from the University of California at Irvine and the University of Marseilles in France have discovered that a component of the venom of Caribbean sea anemone, Stichodactyla helianthus, when used in rat experiments not only halted the progression of paralysis but even reversed the process. An experimental form of multiple sclerosis was induced in laboratory rats. T cells with an unusually high number of ion channels that trigger the cells to attack neurons were activated, bringing on the onset of multiple sclerosis symptoms. However, when the sea anemone venom component ShK was given to the rats the T cell's ion channels were blocked, protecting neurons from attack and halting further paralysis and in some cases leading to recovery without compromising the overall immune system.

The researchers are not making bold promises just yet. They recognize that the effect of ShK is short-lived, limiting its prospects as a therapeutic drug, however their discovery provides a foundation for hope. Learning more about when to administer ShK and in what doses is one avenue of exploration, but perhaps more promising is that ShK now provides a blueprint for the type of chemical compounds researchers should look for in nature or develop synthetically. In a broader sense, the discovery underlines the importance of protecting the world's biodiversity; we only just beginning to realize what a fantastic medical cabinet the planet's ecosystems are.

References:

Beeton, Christine et al (2001). Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proceedings of the National Academy of Sciences 98 (Nov 20th): 13942-13947

Visit:

Proceedings of the National Academy of Sciences
http://www.pnas.org/cgi/content/abstract/98/24/13942
Abstract of above article.

National Multiple Sclerosis Society
http://www.nmss.org/

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Peptides: A Dose of One's Own Medicine
Two recently published works are revealing more information about the role of peptides in innate immunity, the body's initial response to invading pathogens. At the University of North Carolina researchers have isolated from mast cells a previously unknown family of peptide antibiotics in hybrid striped bass, a fish used in aquaculture. The discovery of these antibiotic peptides, now named Pisicidins, is the strongest evidence yet that mast cells actually combat pathogens rather than just signal other cells to attack invading pathogens. The researchers believe it is likely these antibodies are also found in human mast cells. The implications for medicine are significant in number of ways.

Meanwhile at the University of California at San Diego a research team has discovered that specific peptides with antimicrobial properties also act as natural antibodies in mammals. Using laboratory mice to study peptides called cathelicidins, the team is the first to demonstrate the mechanisms by which these peptides aid the immune system's initial response to infection. Comparing mice infected with group A streptococcus, normal mice were able to resist infection more effectively than specimens engineered to lack cathelicidins. A second experiment confirmed the role of the cathelicidins. When the normal mice were exposed to a strain of group A strep resistant to the peptides they developed infections similar to those of the cathelicidin deficient mice in the first experiment. Since these same peptides are present in humans, the UCSD work is also likely to contribute to new antibiotic therapies. In a world where so many bacteria are fast becoming resistant to existing drugs it is vital that new drugs are developed. Knowledge of these peptides may provide models for new drug development. Additionally, if these peptides are absent or depleted in some individuals a broader understanding of why some individuals are more vulnerable than others to disease may also be achieved.

References

Gallo, Richard L. et al (2001). Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414 (Nov 22nd): 454-457

Silphaduang, Umaporn and Noga, Edward J. (2001). Antimicrobials: Peptide antibiotics in mast cells of fish. Nature 414 (Nov 15th): 268-269

Visit:

Nature
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v414/n6861/abs/414268a0_fs.html
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v414/n6862/abs/414454a0_fs.html

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Suppressing Genes and Criticism
Given all the controversy surrounding stem cells the recent work of scientists at the University of Pennsylvania's Center for Animal Transgenesis and Germ Cell Research may diffuse some of the furor. Indeed their discoveries may lead to an avenue of research free of the need for embryonic stem cells and so removing all the ethical issues that have been raised. Examining the stem cells of mouse embryos the team identified a receptor, known as Germ Cell Nuclear Factor or GNCF, as having a role in suppressing the expression of the gene Oct4. Oct4 is believed to be the gene playing the pivotal role in maintaining a stem cell's pluripotency (the potential of a stem cell to later develop into any number of different types of body tissue). Suppressing Oct4 reduces a stem cell's ability to differentiate, making GNCF the equivalent of an on-off switch for stem cell pluripotency. The researchers believe that the complete mechanism is likely to be more complex, involving more components than just GCNF, however they do believe there is now the possibility of halting stem cell development and even the potential to reverse cell development. If this is possible, there may be the potential to convert ordinary adult cells back to embryonic stem cells removing the need for "fresh" embryonic stem cells. If that can happen, the research community will be able to work in a far less controversial environment.

References:

Fuhrmann, Guy et al (2001). Mouse Germline Restriction of Oct4 Expression by Germ Cell Nuclear Factor. Developmental Cell 2001 1: 377-387

Visit:

Developmental Cell
http://www.developmentalcell.com/cgi/content/abstract/1/3/377/
University of Pennsylvania's Center for Animal Transgenesis and Germ Cell Research
http://www.vet.upenn.edu/catgrc/

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