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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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