ScienceWeek

SCIENCE-WEEK - February 22, 2002 - Vol. 6 Number 8
An Email Research Digest Published Weekly Since 1997

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There is no doubt that great revolutions of human
scientific thought will occur in the next century,
and in the century after that, and in thousands of
centuries afterward. So which of our current pet
scientific dogmas will be among the first washed
away by new facts and sudden clarities?
-- Anonymous

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Section 1
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Contents of this Issue (Full reports in Section 2):

Basic Sciences
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1. Neuroscience: The NMDA Receptor
2. Integrins of the Cell Surface
3. Stability of Biomolecules and Gas-Phase Properties
4. Biological Cells: Surface Molecular Recognition
5. On Bioluminescence in Coelenterates
6. Zinc and the Nervous System 
7. Earth's Geomagnetic Field and Nuclear Fission
8. Classical vs. Quantum Phase Transitions
9. Charge Transport by Negatively Charged Excitons
10. 5000 Years of Super-Cyclones Along Great Barrier Reef
11. On Quantum Criticality
12. On Crystal Polymorphism

Praxis
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13. Universities: Grant Reimbursement Fraud and False Claims
14. Lung Cancer, Oncogenes, and Retroviruses (*)
15. On the Anti-Cancer Drug Taxol
16. Cocaine Addiction: Ineffectiveness of Acupuncture Treatment
17. Human Use of Global Photosynthesis
18. Red Wine and Coronary Heart Disease
19. Assembly of a New Class of Microwires
20. El Nino: Fire Damage in Logged Forests
21. On the Synthesis of Pure Enantiomers
22. Acoustic Surgery
23. Applications of Liquid Crystals
24. On Free-Radical Polymerization

Miscellany
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25. Pre- and Postdoctoral Fellowship Profile:
Office of G. de Alba at Smithsonian Tropical Research Institute
26. In Focus:
Genomes, Gene Numbers, and Repetitive Sequences (James D. Watson)
27. New Books


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Section 2
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1. NEUROSCIENCE: ON THE NMDA RECEPTOR
M.B. Kennedy and P. Mazerra (California Institute of Technology,
US) discuss the NMDA receptor, the authors making the following
points:
     1) The N-methyl-D-aspartate (NMDA)-type glutamate receptor
is one of 3 major classes of receptors for glutamate, the
principle excitatory neurotransmitter in the central nervous
system. This receptor plays a key role in learning and in the
formation of memories by acting as a "coincidence detector" that
initiates changes in synaptic strength that lead to the formation
of new neural networks. It is also an important mediator of
several forms of pathological neuronal toxicity.
     2) The NMDA receptor responds at a synapse only when the
presynaptic terminal releases glutamate at the same time that the
postsynaptic neuron is strongly depolarized by the sum of
activating influences impinging on it. In effect, the NMDA
receptor initiates the strengthening of all synapses that
depolarize the same postsynaptic neuron at the same time, and
thus triggers the formation of a new and more stable circuit.
     3) When the NMDA-receptor channel opens, it allows passage
of calcium ions, as well as sodium and potassium ions, into the
cell. The calcium ions trigger a cascade of biochemical signaling
reactions catalyzed by enzymes located just underneath the
postsynaptic membrane. These reactions modify other membrane
channels at the synapse, ultimately leading to a change in the
strength of the electrical signal produced when the synapse is
later activated again.
     4) Like most ligand-gated channels, the NMDA receptor is an
oligomer of 4 to 5 individual subunits that come together in the
membrane to form the channel. One of these subunits (NR1) is
necessary for channel function and is similar in structure to the
subunits of other ligand-gated channels. However, the 4 other
principle subunits (NR2A,B,C,D) are unique among ligand-gated
channels in having long extensions of their carboxyl-terminal
tails that protrude into the cytoplasm beneath the membrane and
serve as anchoring points for signal transducing enzymes.
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Proc. Nat. Acad. Sci. 2001 98:12323
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com
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Related Background:
GLUTAMATE AND NEUROLOGICAL DISEASE
E.A. Cavalheiro and J.W. Olney (University of Sao Paulo, BR)
discuss glutamate and neurological disease. Forty years ago, it
was demonstrated by T. Hayashi that the amino acid glutamate,
when introduced directly into the central nervous system, could
trigger convulsions by an excitatory (depolarizing) action on
nerve cell membranes. At approximately the same time, other
researchers reported that subcutaneous injections of glutamate
can kill neurons in the retina or brain, and that the
neuroexcitatory action of glutamate was responsible for the cell-
killing effect. From these early findings, glutamate gradually
became recognized for its beneficial role as the predominant
excitatory neurotransmitter in the mammalian central nervous
system, and also became recognized for its detrimental potential
as an "excitotoxic" molecule that can destroy neurons throughout
the entire central nervous system. A large family of glutamate
transmitter receptors was then identified, with these receptors
classified as either "ionotropic" or "metabotropic". The
ionotropic subfamily is further divided into 3 subtypes, referred
to as N-methyl-D-aspartate (NMDA) receptors, alpha-amino-3-
hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors, and
kainate receptors. In recent decades, it has been demonstrated
that glutamate excitotoxicity is responsible for neuronal
degeneration in anoxia and in essentially all other acute brain
injury conditions (e.g., stroke, hypoglycemia, epilepsy, and head
trauma), and the excitotoxic action of glutamate has been shown
in many cases to involve abnormal uptake or intracellular
mobilization of calcium ions. There is also substantial evidence
implicating abnormal glutamate signaling and/or excitotoxicity in
the pathogenesis of numerous more chronic central nervous system
diseases, such as Parkinson's and Alzheimer's disease, and also
multiple sclerosis.
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Proc. Nat. Acad. Sci. 2001 98:5947
SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
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Related Background:
DRUG ADDICTION AND THE GLUTAMATE NEUROTRANSMITTER
Dopamine is an important neurotransmitter in the human brain, and
it has been implicated in several serious behavioral pathologies.
There is a dopamine hypothesis of depression, a dopamine
hypothesis of schizophrenia, and dopamine has also been
implicated in the reinforcing effects of psychostimulant drugs of
abuse such as cocaine and amphetamine. Another neurotransmitter,
glutamate, is a major excitatory amino acid neurotransmitter
accounting for an estimated 40 percent of all nerve signals in
the human brain, and involved in phenomena such as neural
development, learning, and memory formation. Glutamate is
ordinarily released under close cellular biochemical control and
reuptake, and in excess amounts it is an intense excitant of
nerve cells and potentially toxic. Glutamate is suspected as an
important contributor to the pathogenesis of a number of
neurodegenerative disorders, including amyotrophic lateral
sclerosis and parkinsonian dementia. The glutamate receptor is
the molecular site that mediates the actions of glutamate
neurotransmitters, and this receptor has been a focus of
intensive research and has been differentiated into N-methyl D-
aspartate (NMDA), kainate, and quisqualate subtypes. Neurons that
release glutamate are called "glutamatergic", and they have been
located in many important areas of the human brain. Until the
past few years, the study of the neurobiological basis of drug
addiction has focused on dopamine, but there is apparent growing
interest in the involvement of glutamate as a key
neurotransmitter. This was the focus of a recent meeting (May
3-5, 1998) at the US National Institutes of Health in Rockville,
Maryland (US), at which evidence was presented that blockade of
glutamate transmission prevents behavioral sensitization in rats
to repeated doses of amphetamine or cocaine. Behavioral
sensitization, also called "reverse tolerance", is the
development of increased sensitivity to the effects of drugs such
as pyschostimulants, and its occurrence in animals is considered
a prime model for human drug abuse. The idea that glutamate
biochemistry and neurophysiology may play a key role in human
drug addiction is apparently exciting many researchers in the
field.
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Science 1998 280:2045
ScienceWeek 1998 17 Jul
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Related Background:
INTRACELLULAR SODIUM AND GAIN CONTROL OF THE NMDA RECEPTOR
It has been known for 50 years [*Note #1] that the influx of
sodium ion into the nerve cell is fundamental to electrical
signalling in the nervous system, the influx essential for such
basic signals as *action potentials and *excitatory postsynaptic
potentials in neurons. During periods of impulse bursting or high
levels of discharge activity, large increases in intracellular
sodium ion concentration are apparently produced in the neuron
cell body and *dendrites, and a central question is what is the
intracellular signalling function, if any, of this increased
postsynaptic intracellular sodium ion concentration?
... ... X.-M. Yu and M.W. Salter (2 installations, CA) now report
that intracellular sodium ion concentration regulates the
function of *NMDA (N-methyl-D-aspartate) receptors, a principle
subtype of *glutamate receptor. The authors report that NMDA-
receptor-mediated whole-cell electric currents and NMDA-receptor
*single channel activity were increased by raising intracellular
sodium ion concentration, and that channel activity decreased
upon lowering intracellular sodium ion concentration. The authors
conclude from this that the activity of NMDA channels tracks
changes in intracellular sodium ion concentration. They report
that the sensitivity of the channel to sodium ion is apparently
set by an enzyme (a *kinase) known to be associated with the
channel. Increasing intracellular sodium ion concentration
selectively increased synaptic responses mediated by NMDA
receptors, but did not increase synaptic responses mediated by
non-NMDA receptors. The authors suggest their results indicate
the change in postsynaptic intracellular sodium ion concentration
that occurs during neuronal activity is a signal for controlling
the gain of excitatory synaptic transmission, and that this
mechanism may be important for NMDA-receptor-dependent
*plasticity and toxicity in the central nervous system.
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Nature 1998 396:469
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Notes:
... ... *Note #1: The first direct evidence in single nerve
fibers that an influx sodium ion electrical current is the major
event during the nerve impulse was provided by A.L. Hodgkin and
B. Katz in 1949. In the 1950s, Hodgkin was joined by A.F. Huxley,
and together they developed a quantitative model to explain the
ion currents involving sodium and potassium. Also in the 1950s,
J.C. Eccles provided the first comparable evidence for the
*excitatory postsynaptic potentials of neuron synapses, and
during the same period B. Katz provided the first evidence for
the role of sodium ion currents during events at the
neuromuscular junction. Hodgkin, Huxley, and Eccles received the
Nobel Prize in Physiology and Medicine in 1963; Katz received the
Nobel Prize in Physiology and Medicine in 1970 (primarily for his
work involving chemical transmitter events at the neuromuscular
junction).
... ... *action potentials: In general, the term "action
potential" refers to the potential change produced by current
flow resulting from a transient increase in sodium ion
permeability, a transient change that is propagated along the
nerve axon to the axon terminal(s). In most vertebrate nerve
cells, the nerve axon is a long extension of the cell, an
extension that can attain lengths as much as a meter, the
extension originating from a cell body approximately 50 microns
in diameter.
... ... *excitatory postsynaptic potentials: Neurotransmitters
are chemical substances released at the terminals of nerve axons
in response to the propagation of an impulse to the end of that
axon. The neurotransmitter substance diffuses into the synapse,
the junction between the presynaptic nerve ending and the
postsynaptic neuron, and at the membrane of the postsynaptic
neuron the transmitter substance interacts with a receptor.
Depending on the type of receptor, the result may be an
excitatory or an inhibitory effect on the postsynaptic nerve
cell. In each case, the effect is associated with a transient
electrical change in the postsynaptic membrane, the excitatory
effect associated with an "excitatory postsynaptic potential", a
transient depolarizing current flow involving an influx of sodium
ions.
... ... *dendrites: The general input extensions of nerve cells
are called "dendrites", and they may also be extensively
branched. In general, dendrites are considered to receive input
and axons to propagate output, but the electrical architecture of
most neurons is complicated, and in many types of nerve cells
activation of the axon produces electrical activity that not only
propagates down the axon but also propagates backward through the
cell body and dendrites.
... ... *NMDA (N-methyl-D-aspartate) receptors and glutamate
receptors: Glutamate is a major excitatory amino acid
neurotransmitter, accounting for an estimated 40 percent of all
nerve signals in the human brain, and involved in phenomena such
as neural development, learning, and memory formation. Glutamate
is ordinarily released under close cellular biochemical control
and reuptake, and in excess amounts it is an intense excitant of
nerve cells and potentially toxic. Glutamate is suspected as an
important contributor to the pathogenesis of a number of
neurodegenerative disorders, including amyotrophic lateral
sclerosis and parkinsonian dementia. The glutamate receptor is
the molecular site that mediates the actions of glutamate
neurotransmitters, and this receptor has been a focus of
intensive research and has been differentiated into N-methyl D-
aspartate (NMDA), kainate, and quisqualate subtypes [see
background material below]. Neurons that release glutamate are
called "glutamatergic", and they have been located in many
important areas of the human brain. 
... ... *single channel activity: (single ion channel activity)
Ion channels are protein channels in cell membranes that allow
ions to pass from extracellular solution to intracellular
solution and vice versa. Most ion channels are selective,
allowing only certain ions to pass, and an individual cell has
ion channels with various ion selectivities. The selectivity of
an ion channel can be "gated", the channel effectively opened or
closed, and ion channels are said to *voltage-gated or *ligand-
gated, depending on how the change in selectivity is provoked.
... ... *kinase: In general, a "kinase" is any enzyme involved in
the transfer of a phosphate group.
... ... *plasticity: In neurobiology, the term "plasticity" is
the name given to the capacity of neural tissue to adjust to
change.
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SCIENCE-WEEK 1999 8 Jan
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Related Background:
CALCIUM SENSING OF METABOTROPIC GLUTAMATE RECEPTORS
L-glutamate (derived from the amino acid, glutamic acid) is
considered the principal excitatory neurotransmitter in the
vertebrate central nervous system, and is one of the
neurotransmitter substances that interact with ion channels that
are switched on or off by specific ligands (i.e., they are
"ligand-gated"). Glutamate is known to act on 3 classes of
receptors, one of which is a slow-acting receptor type coupled to
G-proteins and called "metabotropic". (The G-proteins are
membrane-bound proteins that act as transducers between messenger
molecules interacting with the cell surface and the intracellular
messenger system). Frog oocytes are frog egg cells, and they are
a common laboratory vehicle for expressing the proteins of
genetically engineered material from other species and coupling
this expression with electrophysiological measurements of frog
oocyte membrane behavior. "Transfection" is the uptake of
exogenous (foreign) DNA fragments in solution directly into
animals cells in laboratory culture, and is one method of
introducing foreign genes into cells. ... ... Kubo et al (3
authors Tokyo Metropolitan Institute for Neuroscience, JP) report
investigations of the behavior of rat metabotropic glutamate
receptors as calcium ion sensors in a frog oocyte expression
system, and that some types of these receptors are indeed
activated not only by glutamate but also by extracellular
Ca(sup2+). A single amino acid residue was found to determine the
sensitivity of these receptors to calcium ion, and one of the
receptors caused morphological changes when transfected into
mammalian cells. The authors suggest that in cells under
physiological conditions, the sensing of extracellular calcium
ion by metabotropic glutamate receptors may be an important
aspect of neuron cell regulatory processes.
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Science 1998 13 Mar
ScienceWeek 1998 27 Mar
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Related Background:
SECRETION OF GLUTAMATE BY BRAIN ASTROCYTES
Glial cells are more numerous than neurons in the brain, but
their function has been generally characterized as "metabolic" or
"supportive", without much discussion of details, and more is
known about peripheral glial cells than glial cells in the
central nervous system. Astrocytes are the largest glial cells,
with many extensions radiating outward like a starburst, and at
least one of their functions is apparently to maintain the so-
called "blood-brain barrier" effectively separating neural tissue
from blood. ... Kainic acid, an algal neurotoxin, is a structural
analogue of glutamate, and it has been extensively used in
research, since at high concentrations it selectively destroys
glutamate receptor neurons (glutaminergic neurons). Glutamate is
known to act on 3 classes of receptors, one of them called the
kainate receptor because at low concentrations of kainic acid the
action of glutamate on this receptor is enhanced. The chemistry
of this kainate receptor is not yet well-characterized, mainly
because selective ligands for it are not known. Another class of
glutamate receptor is the AMPA receptor [AMPA = (RS)-alpha-amino-
3-hydroxy-5-methyl-4-isoxazoleproprionic acid], and the third is
NMDA (N-methyl-D-aspartate). These 3 receptors are ionotropic,
i.e., their activation produces changes in membrane ion
permeability. According to another and more recent scheme of
glutamate receptor classification, one receptor type is
AMPA/kainate (ionotropic), another receptor type is NMDA
(ionotropic), and a third receptor type is a slow-acting receptor
type coupled to G-proteins and called metabotropic receptors.
(The G-proteins are membrane-bound proteins that act as
transducers between messenger molecules interacting with the cell
surface and the intracellular messenger system). Prostaglandins
are fatty acids secreted by cells that have hormone-like actions
in the immediate vicinity, and one circumstance that produces
their release is tissue injury.
... ... Bezzi et al (8 authors at 2 installations, IT) report
that coactivation of the AMPA/kainate and metabotropic glutamate
receptors on astrocytes stimulates these cells to release
glutamate through a calcium-dependent process mediated by
prostaglandins. The authors suggest their results reveal a new
pathway of regulated transmitter release from astrocytes, and
that interactions between neurons and astrocytes may play a
critical role in synaptic plasticity and neurotoxicity. They also
suggest that the prostaglandin-mediated glutamate release from
astrocytes may be involved in the pathophysiology of various
brain diseases and injuries.
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Nature 1998 15 Jan
ScienceWeek 1998 30 Jan
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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2. ON INTEGRINS OF THE CELL SURFACE
Membrane proteins are classified into a number of types,
depending on the number of transmembrane domains, the orientation
of the protein, and the presence of other kinds of attachment to
the lipid bilayer. Type 1 membrane proteins are defined as
membrane proteins having a single transmembrane domain with the
C-terminus on the cytoplasmic side of the cell membrane.
... ... J-P. Xiong et al (Harvard University, US) discuss
integrins, the authors making the following points:
     1) Integrins are large heterodimeric cell surface receptors
found in many animal species ranging from sponges to mammals.
These receptors are involved in fundamental cellular processes
such as attachment, migration, proliferation, differentiation,
and survival. Integrins also contribute to the initiation and/or
progression of many common diseases, including neoplasia, tumor
metastasis, immune dysfunction, ischemia-reperfusion injury,
viral infections, osteoporosis, and coagulopathies.
     2) An integrin is approximately 280 angstroms long, and
consists of one alpha subunit (150 to 180 kilodaltons) and one
beta subunit (approximately 90 kilodaltons), both of which are
type 1 membrane proteins. 18 alpha and 8 beta mammalian subunits
are known, which assemble non-covalently into 24 different
heterodimers. Contacts between the alpha and beta subunits
primarily involve their NH(sub2)-terminal halves, which together
form a globular head. The remaining portions form 2 rod-shaped
tails that span the plasma membrane.
     3) Like other receptors, integrins transmit signals to the
cell interior ("outside-in signaling"), signals that regulate
organization of the cytoskeleton, activate kinase signaling
cascades, and modulate the cell cycle and gene expression. Unlike
other receptors, however, ligand binding with integrins is not
generally constitutive but is regulated to reflect the activation
state of the cell. This "inside-out regulation" of integrin
affinity protects the host from pathological integrin-mediated
adhesion. Inside-out and outside-in signaling are associated with
distinct conformational changes in the integrin extracellular
segment. These changes vary with cell type and the state and
nature of the ligand, and are modulated by divalent cations that
are also required for integrin-ligand interaction.
     4) The authors report they have solved the crystal structure
of the extracellular portion of an integrin (alpha-V-beta-3) at
3.1 angstroms resolution. The 12 domains assemble into an ovoid
"head" and two "tails". In the crystal, the integrin is severely
bent at a defined region in its tails, reflecting an unusual
flexibility that may be linked to integrin regulation.
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Science 2001 294:339 
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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3. STABILITY OF BIOMOLECULES AND GAS-PHASE PROPERTIES
R.A. Jockusch et al (University of California Berkeley, US)
discuss gas-phase properties of biomolecules, the authors making
the following points:
     1) Biological processes, including signal transduction,
control of reaction specificity, and macromolecular structure,
depend on electrostatic interactions among the polar and ionic
species ubiquitous in living systems. Proteins and nucleic acids
contain numerous charged functionalities. Free metal ions provide
electrochemical gradients necessary for cellular function, and
they also serve as messengers. Binding of metal ions is crucial
to the function of many enzymes. A dramatic example is the
sequence of events triggered by a small flux of calcium ions.
Calcium coordinates to multiple oxygens in proteins such as
calmodulin, which then undergo a large structural change, become
activated, and in turn activate other proteins, including those
involved in muscle contraction.
     2) The intrinsic stability of biomolecules with charged
functionalities is determined by the gas-phase acidities and
basicities of these groups. Ionic species are further stabilized
in several ways. Counterions provide favorable electrostatic
interactions. Solvation of charges by polar species, especially
water, also provides significant stabilization. Increased
knowledge of these interactions is vital to the understanding and
prediction of biomolecular properties in-vivo. Gas-phase studies 
of simplified systems, such as single amino acids, metal ions,
and/or individual water molecules, provide a means for
investigating these effects individually.
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J. Am. Chem. Soc. 2001 123:12255
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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4. BIOLOGICAL CELLS: SURFACE MOLECULAR RECOGNITION
N.S. Sampson et al (State University of New York Stony Brook, US)
discuss surface molecular recognition in biological cells, the
authors making the following points:
     1) Biological cells display on their surfaces a complex
mixture of receptors and ligands that mediates cell adhesion and
cell communication. In this context, receptors and ligands are
protein molecules that clasp one another, much like a hook and an
eye used in some clothing. Receptors are typically integral to
the cell membrane: part of the molecule is confined to the lipid
bilayer, and the remainder extends beyond the membrane inside and
outside the cell. Ligands may be integral to the membrane of
another cell, part of the matrix outside the cell, or freely
diffusing in the medium outside the cell. Furthermore, these
receptor and ligand proteins are frequently glycosylated, i.e.,
sugar polymers are covalently linked to the proteins. Depending
on the receptor and the ligand, the protein amino acids, sugars,
or both may be the functional moieties involved in cell adhesion
and communication.
     2) The milieu outside a cell is quite complex, consisting of
a) insoluble proteins and glycosaminoglycans that form a matrix,
b) a variety of cells of different types, and c) small water-
soluble molecules. The cell surface-extracellular milieu
interactions are analogous to a complex cellular "Velcro": cells
attach to the matrix and to each other to form the structure of a
tissue. The ligands presented by the milieu can provide an
address code for the cell to adhere or to migrate, or a signal
for a cell to grow, undergo alterations, or die. The signals from
the ligated receptor may be transmitted to the nucleus of the
cell to activate transcription and ultimately synthesis of
various proteins. Alternatively, a receptor ligated to the
extracellular matrix may provide a direct link to the
intracellular cytoskeleton that provides the structural integrity
of the cell and dictates the shape of the cell.
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Proc. Nat. Acad. Sci. 2001 98:12870
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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5. ON BIOLUMINESCENCE IN COELENTERATES
S.H. Haddock et al (Monterey Bay Aquarium Research Institute, US)
discuss bioluminescence in coelenterates, the authors making the
following points:
     1) Bioluminescence of the hydromedusa Aequorea victoria has
been studied more thoroughly than that of any other marine
invertebrate. These jellyfish, readily collected from the waters
of Puget Sound, Washington, have been the source of the first
purified and cloned green-fluorescent protein, and the first
calcium-regulated photoprotein. This photoprotein, aequorin, has
been extensively studied since its discovery nearly 40 years ago.
It is a complex of an apoprotein joined with oxygen and a light-
emitting luciferin called "coelenterazine". Because they are
triggered by calcium ions to produce light, photoproteins have
been widely used as calcium "reporters", and the high level of
interest in these molecules has led to detailed studies of their
chemistry and molecular biology. Photoprotein genes have been
cloned from several species of hydromedusae, and recently the
tertiary structures of two photoproteins have been resolved. If,
however, the gene for apo-aequorin is introduced into an
organism, no light will be emitted unless luciferin is provided
exogenously. As a result, there is great interest in finding the
pathways and genes responsible for the production of luciferin.
     2) Photoproteins similar to aequorin have been found in sea
gooseberries (ctenophores), marine pelagic protozoa
(radiolarians) , and other hydromedusae. In addition,
coelenterazine, the imidazolopyrazine luciferin of these
photoprotein systems, is also used by fish, squid, some
crustaceans, arrow worms (chaetognath), and is found in many non-
luminous organisms as well. But despite its occurrence in a
variety of phyla, and recent interest in its anti-oxidative
properties, there has been little experimental evidence to
indicate the origins of this light-emitting molecule in nature.
There are two examples from crustacea: a) a dietary requirement
for coelenterazine has been demonstrated for the lophogastrid
shrimp Gnathophausia ingens, whereas b) the decapod shrimp
Systellaspis debilis appears to have the ability to synthesize
the molecule.
     3) The authors report that the hydromedusae A. victoria is
unable to produce its own coelenterazine and is dependent on a
dietary supply of this luciferin for bioluminescence. The authors
suggest this evidence regarding the origins of luciferin in
coelenterates (Cnidaria) has implications for the evolution of
bioluminescence and for understanding the extensive use of
coelenterazine among marine organisms. In addition, the authors
suggest that if jellyfish are unable to synthesize their own
luciferin, then the name "coelenterazine" may be a misnomer,
since the only evidence for production of this molecule in the
ocean comes from crustaceans.
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Proc. Nat. Acad. Sci. 2001 98:11148
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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6. ZINC AND THE NERVOUS SYSTEM 
P. Manzerra et al (Washington University St. Louis, US) discuss
zinc and the nervous system, the authors making the following
points:
     1) Zinc is an important trace element functioning in both
catalytic and structural capacities in all mammalian cells. The
central nervous system additionally contains a chelatable pool of
zinc located in synaptic vesicles, predominantly within
glutamatergic nerve terminals throughout the cerebral
hemispheres. This zinc is released into the synaptic cleft with
synaptic activity, reaching concentrations that may routinely
exceed 10 to 20 micromolar and may approach 300 micromolar in
extreme conditions.
     2) The precise role of synaptically released zinc is
unknown, but acute modulation of the activity of several
receptors and channels is likely, including neurotransmitter
receptors, voltage-sensitive cation channels, and Na(+)/K(+)
ATPase. In particular, given its systematic co-release with the
neurotransmitter glutamate, the ability of zinc to inhibit N-
methyl-D-aspartate (NMDA) receptors may figure prominently in its
physiological actions.
     3) Although limited zinc exposure has multiple modulatory
effects potentially relevant to a normal signaling function,
exposure to higher concentrations or for longer durations can
trigger brain cell death more easily in neurons than in
astrocytes. Zinc toxicity has been postulated to contribute to
neuronal loss after prolonged seizures, transient global
ischemia, or traumatic brain injury. Zinc-induced neuronal death
apparently depends on excessive zinc influx across the plasma
membrane via several routes, including voltage- and agonist-gated
calcium ion channels as well as the sodium-calcium exchanger.
Zinc release from intracellular stores or binding sites may also
contribute to neurotoxicity.
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Proc. Nat. Acad. Sci. 2001 98:11055
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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7. EARTH'S GEOMAGNETIC FIELD AND NUCLEAR FISSION
D.F. Hollenbach and J.M. Herndon (Oak Ridge National Laboratory,
US) discuss Earth's geomagnetic field, the authors making the
following points:
     1) The geomagnetic field is evidence of a powerful energy
source at or near the center of the Earth. Traditional
geophysical models of energy sources for the geomagnetic field
invoke the decay energy of naturally occurring long-lived
radionuclides (mainly uranium, thorium, and potassium-40) or are
based upon the assumed ongoing growth of the inner core by
cooling, presumably releasing gravitational potential energy and
latent heat of crystallization. These energy sources, however,
generally are capable of changing only gradually and in only one
direction over time. The Earth's magnetic field, by contrast,
varies in intensity and reverses polarity frequently, but quite
irregularly, with an average interval between reversals of
approximately 200,000 years. Lacking a variable and/or
intermittent energy source, geophysicists have for decades
hypothesized geomagnetic reversals as arising solely from geo-
dynamo instabilities.
     2) Variations in the Earth's magnetic field, however, are
readily understandable strictly from an energy standpoint given
the presence of naturally varying self-sustaining nuclear fission
chain reactions occurring deep within the Earth. Indeed, the
variable and/or intermittent energy output of a deep-Earth
nuclear reactor, serving as the major energy source for
geomagnetic field production, will inevitably lead to variations
in the Earth's magnetic field whether the geomagnetic field
arises from a self-excited dynamo mechanism, as widely believed,
or from some other yet unknown mechanism.
     3) Nuclear fission chain reactions do occur in nature. In
1972, researchers at the French Atomic Energy Establishment at
Pierrelatte discovered the nearly intact remains of a natural
nuclear fission reactor in a 0.5-meter thick seam of uranium ore
located at Oklo in the Republic of Gabon. Subsequently, other
reactor zones were discovered in the region and appear to have
functioned as self-sustained nuclear fission reactors
approximately 1.8 billion years ago.
     4) The authors report that numerical simulations of a
planetary-scale geo-reactor clearly demonstrate that such a geo-
reactor a) would function as a fast-neutron fuel breeder reactor;
b) could, under appropriate conditions, operate over the entire
period of geologic time; and c) would function in such a manner
as to yield variable and/or intermittent output power.
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Proc. Nat. Acad. Sci. 2001 98:11085
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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8. ON CLASSICAL VS. QUANTUM PHASE TRANSITIONS
Piers Coleman (Rutgers University, US) discusses phase
transitions, the author making the following points:
     1) Matter transforms itself into new ordered states through
phase transitions. At a first-order phase transition, such as
boiling or melting, the new phase emerges quickly following a
sharp transition. At a second-order phase transition, the new
order emerges gradually within the material. As the material
passes into the ordered state, it passes through a remarkable
stage known as a "critical point", at which interactions with
infinite range develop within the material.
     2) Surprisingly, the theory of critical phenomena, a triumph
of late 20th century physics, did not involve any quantum
mechanics. It turns out that any temperature above absolute zero
destroys the coherence effects of quantum mechanics over the long
distances where critical phenomena play a role. But quantum phase
transitions have recently been observed in careful experiments.
     3) In 1976, John Hertz predicted the existence of a quantum
phase transition in metals. Hertz proposed that when the
temperature at which a magnetic phase transition occurs in a
metal is reduced to absolute zero, a "quantum critical point"
would develop. In a conventional metal, interactions between
electrons occur over a short range, and the motions of individual
electrons are largely independent. At a quantum critical point,
however, these interactions can grow until they have infinite
range, but they also become infinitely retarded in time, so that
the influence of one moving electron on another electron is felt
long after the moving electron has passed. This causes the
motions of electrons to become highly correlated. so they move
collectively and can no longer be considered as independent
particles. One of the important side effects of such infinite-
range interactions generated between electrons at a quantum phase
transition is apparently the development of unconventional (e.g.,
high-temperature) superconductivity.
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Nature 2001 413:788
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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9. CHARGE TRANSPORT BY NEGATIVELY CHARGED EXCITONS
     An "exciton" is a combination of an electron and a positive
hole, the exciton free to move through a nonmetallic crystal as a
unit. Although it transports energy, the exciton ordinarily has
no net electrical charge. When an electron in an exciton
recombines with a hole, the original atom is restored and the
exciton vanishes. When this occurs, the energy of the exciton may
be converted into light, or the energy may be transferred to an
electron of a neighboring atom with the production of a new
translocatable exciton.
     When a particle is confined to a domain whose dimensions are
of the order of the wavelength of the particle, the states of
motion of the particle become quantized according to the laws of
quantum mechanics. This is the idea of the "quantum well", which
is essentially a one-dimensional confinement domain. The physical
behavior of such a quantum confinement domain exhibits new and
interesting effects that not only test fundamental theories, but
also offers possibilities for important technological
applications.
... ... D. Sanvitto et al (University of Cambridge, UK) discuss
charge transport by excitons, the authors making the following
points:
     1) The "exciton", the bound state resulting from the Coulomb
attraction of an optically excited electron-hole pair, is often
described as the semiconductor analog of the hydrogen atom. In
1958, Lampert speculated on the existence of a class of mobile
excitons, the analogs of the negative hydrogen ion H(-) and
positive hydrogen molecule H(sub2)(+). However, because the
binding energy of the second electron to the electron-hole pair
is quite small, unambiguous observation of a spectral line due to
the negatively charged exciton (which is also called a "trion")
did not follow until the advent of high-quality remotely doped
quantum well structures in which the trion binding energy is
substantially increased. This occurs at a very low excess
electron density at which each photo-excited electron-hole pair
interacts with and binds to a single excess electron.
     2) The authors report transport of electron-hole complexes
in semiconductor quantum wells under applied electric fields.
Negatively charged excitons [X(-)], created by laser excitation
of a high electron mobility transistor, are observed to drift
upon applying a voltage between the source and drain. In
contrast, neutral excitons do not drift under similar conditions.
The X(-) mobility is found to be as high as 6.5 x 10^(4)
centimeters-square per volt per second. The authors suggest the
results demonstrate that X(-) exists as a free particle in the
best-quality samples and that light emission from opto-electronic
devices can be manipulated through exciton drift under applied
electric fields.
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Science 2001 294:837
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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10. 5000 YEARS OF SUPER-CYCLONES ALONG GREAT BARRIER REEF
J. Nott and M. Hayne (James Cook University, AU) discuss super-
cyclones, the authors making the following points:
     1) In tropical intraplate settings that are largely free
from the effects of sizeable earthquakes, tsunamis, volcanic
eruptions, and landslides, tropical cyclones rank as one of the
main hazards affecting both natural and human communities. In
natural communities, disturbance by hazards is one of the most
important mechanisms affecting the evolution and diversity of
species.
     2) Understanding long-term variability in the occurrence of
tropical cyclones that are of extreme intensity is important for
determining their role in ecological disturbances, for predicting
present and future community vulnerability and economic loss, and
for assessing whether changes in the variability of such cyclones
are induced by climate change. Our ability to accurately make
these assessments has been limited by the short (less than 100
years) instrumented record of cyclone intensity.
     3) The authors determined the intensity of prehistoric
tropical cyclones over the past 5000 years from a) ridges of
detrital coral and shell deposited above highest tide, and b)
terraces that have been eroded into coarse-grained alluvial fan
deposits. These features occur along 1500 kilometers of the Great
Barrier Reef and also the Gulf of Carpentaria of Australia.
     4) The authors infer that the deposits were formed by storms
with recurrence intervals of 2 to 3 centuries, and the authors
demonstrate that the cyclones responsible must have been of
extreme intensity (central pressures less than 920 hectopascals).
The authors estimate that the frequency of such "super-cyclones"
is an order of magnitude higher than that previously estimated
(which was once every several millennia), and that the frequency
is sufficiently high to suggest that the character of rainforests
and coral reef communities were probably shaped by these events.
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Nature 2001 413:508
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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11. ON QUANTUM CRITICALITY
S.A. Grigera et al (University of St. Andrews, UK) discuss
quantum criticality, the authors making the following points:
     1) Understanding the behavior of a dense assembly of
interacting or "correlated" electrons in metallic systems remains
one of the outstanding challenges of modern physics. It is a
many-body quantum-mechanical problem of such complexity that it
cannot be solved by direct "first principles" calculation, so it
has been tackled through a series of ingenious alternative
approaches that have been developed over the past 50 years.
     2) A concept that has attracted considerable attention
recently is "quantum criticality", which can be explicitly
produced by depressing the characteristic temperature of a
second-order phase transition toward absolute zero by using some
externally applied control parameter such as chemical composition
or hydrostatic pressure. The physical properties of the system
are then dominated by the critical fluctuations associated with
this quantum critical point or quantum phase transition.
     3) The concept of quantum criticality has generated
considerable excitement for several reasons:
... ... a) It is now generally acknowledged that these
fluctuations can influence the behavior of correlated electron
systems even at very high temperature, up to room temperature and
beyond.
... ... b) Because a whole variety of tuning parameters can
produce a quantum critical point, many materials of scientific
and technological interest may be close to such a point in some
general parameter space.
... ... c) Proximity to a quantum critical point may stabilize
novel ground states in itinerant systems. Examples of these
include unconventional forms of superconductivity and magnetism.
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Science 2001 294:329
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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12. ON CRYSTAL POLYMORPHISM
C.A. Mitchell et al (Eli Lilly & Co., US) discuss crystal
polymorphism, the authors making the following points:
     1) In this context, the term "polymorphism" refers to the
ability of a molecule to adopt different crystal forms. Crystal
polymorphism reflects the delicate balance of forces responsible
for guiding molecular organization in the solid state. Though
often viewed as an annoyance, this phenomenon represents an
opportunity to examine subtle structure-property relationships
and the relationship between molecular conformation and crystal
packing. An elucidation of polymorphism promises molecular-level
control of crystallization and improvement in crystal structure
design and prediction.
     2) Polymorphism also has considerable technological
significance owing to the dependence of crystal properties on
solid-state structure. For example, the discovery and
characterization of the polymorphs of a drug are important for
evaluation of shelf stability (against transformations to other
polymorphs) and bioavailability of the final pharmaceutical
product. Polymorph screening is a particularly important
component of drug development processes because of patent
protection of new crystal forms, regulations that require
polymorph identification and characterization, and the need for
strict monitoring and recording of process conditions to achieve
controlled and reproducible crystallization outcomes.
     3) Despite decades of polymorphism studies, prediction of
all possible polymorphs of a given substance remains difficult.
Furthermore, it is impossible to guarantee that all experimental
parameters that could lead to the discovery of unknown forms have
been exhausted or that polymorphs produced through an ostensibly
reliable process will not disappear at a later time.
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J. Am. Chem. Soc. 2001 123:10830
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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13. UNIVERSITIES AND GRANT REIMBURSEMENT FRAUD AND FALSE CLAIMS
P.E. Kalb and K.G. Koehler (Sidley Austin Brown and Wood, US)
discuss university violations of the False Claims Act in grant
reimbursement cases, the authors making the following points:
     1) Federal officials can prosecute reimbursement fraud under
a variety of statutes, but they most commonly rely on the federal
False Claims Act (FCA), a Civil-War era statute that prohibits
the knowing submission of false or fraudulent claims and false
statements to the government. The term "knowing" is statutorily
defined to include not only actual knowledge of the truth or
falsity of a claim, but also deliberate ignorance or reckless
disregard thereof. The popularity of the FCA as a vehicle for
attacking financial improprieties in the grant reimbursement
process, such as improperly reported costs, inflated costs, or
costs incurred in a manner inconsistent with the grant document
is demonstrated by the following cases:
     2) In a case brought by a whistle-blower, the University of
Minnesota paid $32 million to settle charges that among other
improprieties it falsely represented that it had no grant-related
income and it inflated its billings by improperly charging to
federal grants salaries for employees who did not work on the
intended project and supplies that were not used for the project.
     3) In another whistle-blower case, New York University paid
$15.5 million to settle allegations that its medical center
submitted false information to recover indirect costs and sought
reimbursement for unallowable expenses, including, for example,
entertainment and capital interest expenses.
     4) As part of a $2.6 million settlement, Thomas Jefferson
University settled allegations that it had failed to report that
the principal investigator for a National Cancer Institute grant
had left the country. The Beth Israel Deaconess Medical Center
paid $920,000 to settle similar allegations.
     5) The University of Chicago paid $250,000 to settle
charges, based on the university's self-disclosure, that it
improperly spent federal funds earmarked for the creation of a
specific computer system on other items, such as salaries,
computer maintenance, telephone charges, and equipment.
     6) The University of Connecticut paid $1.3 million to settle
allegations that it received federal funding for a joint
geriatric medical and dental fellowship program that, in fact,
did not contain all the required elements of the dental training
component.
     7) The authors conclude: "Institutions conducting research,
particularly clinical research, must comply with a myriad of
legal rules. Until relatively recently, these rules generally
were laxly enforced. In recent years, however, regulatory
officials, law enforcement officials, and private whistle-blowers
have become increasingly active, and it is highly likely that
their enforcement efforts will continue, at an even greater
level, in years to come. Institutions that fail to take
appropriate prophylactic measures to ensure compliance will do so
at their own risk."
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J. Am. Med. Assoc. 2002 287:85
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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14. LUNG CANCER
M.E. Garber et al (Stanford University, US) discuss lung cancer,
the authors making the following points:
     1) Four main histological subtypes of lung cancer are
regularly distinguished by tumor morphology under the light
microscope. Squamous and small cell tumors account for
approximately 30 percent and 19 percent of all lung cancers,
respectively. These cancers are believed to derive mainly from
epithelial cells that line the larger airways. Adenocarcinomas
comprise 30 percent of all lung cancers, and these tumors are
believed to derive from epithelial cells that line the peripheral
small airways. Finally, 10 percent of lung tumors are classified
as "large cell", a poorly differentiated subtype usually
diagnosed by exclusion of the other 3 types of lung cancer. Like
adenocarcinomas, large cell tumors are preferentially located in
the periphery of the lung.
     2) Patients with non-small cell lung tumors (squamous,
adenocarcinomas, and large cell) are treated differently from
those with small cell tumors. The pathological distinction
between small cell lung cancer and non-small cell lung cancer is
therefore very important. There is a relative consensus among
pathologists on the diagnosis of small cell cancer. These tumors
progress along a typical clinical course that is characterized by
an excellent initial response to chemotherapy and is often
associated with several months of complete regression. This
short-term regression, however, is followed by recurrence,
development of chemo-resistance, and finally death caused by
systemic dissemination. In contrast, the morphological subtyping
of non-small cell lung cancer is more difficult and far less
reliable in predicting patient outcome. Approximately 50 percent
of patients die from metastatic disease even after complete
surgical removal of the primary tumor. The initial tumor
pathologic diagnosis is based on small bronchoscopic biopsy
specimens and may change when surgically removed specimens are
reexamined. Lung tumor heterogeneity is well documented and is
reflected in the morphological classification of mixed tumors
such as adenosquamous carcinoma or combined small cell lung
cancer containing both small cell and non-small cell components.
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Proc. Nat. Acad. Sci. 2001 98:13784
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com
----------
Related Background:
MEDICAL BIOLOGY: NEW DATA ON RETROVIRUSES AND LUNG CANCER
     Whether viruses are classified as "living" or "non-living"
is arbitrary, but in either case one is dealing with a remarkable
entity. As a group, viruses are in the size range 20 to 300
nanometers, compact bundles of genetic information that have
apparently existed for billions of years. They are unable to
replicate except inside a living host cell, and outside the host
cell they are inert. Viruses pass through filters that trap
bacteria, and they can be seen only be electron microscopy. Like
other biological systems, each virus contains molecular genetic
information in the form of nucleic acid, but in viruses this
information comes in the form of DNA or RNA, never both. The
viral genome is transcribed and replicated only with a host cell,
with variations in process dependent on the type of virus and the
type of host cell.
     When viruses are categorized in terms of their genomes,
there are two general types: a) viruses with a DNA genome (DNA
viruses), and b) viruses with an RNA genome (RNA viruses). RNA
viruses are unique: only in these viruses do we find genomes
consisting of RNA; all other biological entities, DNA viruses,
bacteria, plant cells, animal cells, etc., contain DNA genomes.
     There are more than 2500 groups of different viruses now
recognized and at least partially characterized. In each case,
for both DNA and RNA viruses, once it enters the host cell, the
general challenge for the virus is the same: directly or
indirectly, the viral genome must bring about the production of
the *messenger RNAs needed by the host *ribosomes to produce the
specific proteins necessary for replication of the complete
virus.
     With DNA viruses, the DNA viral genome acts as the template
for the production of messenger RNA. With RNA viruses, however,
the process is more complicated.
     In general, with some types of RNA viruses, the RNA genome
("plus-sense"; "positive-strand") can itself act as messenger RNA
for host ribosomes; while other types of RNA viruses, the RNA
genome ("minus-sense"; negative-strand) must first produce a
complementary RNA, which then acts as messenger RNA for the host
ribosomes. The replication process in minus-sense RNA viruses is
complex, since host cells do not carry enzymes that can
polymerize complementary RNA from an RNA template, and such
viruses therefore must carry their own special enzymes ("RNA-
dependent transcriptases") to achieve this synthesis.
     A third and special type of RNA virus is the so-called
"retrovirus", of which there are many versions. Retroviruses are
single-stranded RNA viruses that have an enzyme called reverse
transcriptase, and with this enzyme the viral RNA is used as a
template to produce viral DNA from host-cellular material. This
DNA is then incorporated into the host cell's genome, where it
codes for the production of messenger RNA and the ultimate
synthesis of viral components. The HIV virus, for example, is a
retrovirus.
     As a class, retroviruses are usually spherical, 80 to 110
nanometers in diameter, with an RNA genome of approximately 7000
to 10,000 nucleotide bases. An outstanding characteristic of such
viruses is that if they kill host cells at all it is usually only
after a long latent period (although there are certain important
exception). In addition, these viruses are apparently capable of
altering, or affecting the expression of, host cell genes
involved in cancer (oncogenes).
     The three primary genes of the retrovirus genome are called
"gag", "pol", and "env". The gag gene encodes the protein of the
virus capsid, the protein coat directly encapsulating the viral
genome; the pol gene encodes a reverse transcriptase involved in
replication of the genome; the env gene encodes the protein of
the membrane envelope of the virus when it is outside a host cell
(the membrane envelope of the "virion"). (These 3 genes actually
produce more than 3 different proteins; what these genes encode
for are precursor proteins, each of which is a precursor for
several varieties of proteins with different viral functions. In
addition, different proteins can be produced by splices of
elements from the 3 primary genes.
     Concerning the general structure of the retrovirus, the
internal nucleic acid genome is encapsulated by a protein coat
(the capsid), and the capsid in turn is surrounded by the
external lipoprotein envelope. Beyond this general scheme, there
is no single morphology for retroviruses.
     The protein encoded by the env gene (called the Env protein)
is important in recognition of host-cell surface receptors, with
which it interacts to secure entry of the virus into the host
cell. In addition, after infection the host-cell expresses Env
protein on its own surface, and this evidently prevents
reinfection of that host cell after new viruses are released.
     Perhaps the most important property of retroviruses is their
ability to splice into the host-cell genome pieces of their own
genome, the result either the introduction of new genes into the
host genome or the activation or inactivation of specific nearby
genes of the host genome. In principle, either of these scenarios
can lead to corruption of the growth regulation process of the
host genome, and thus to a line of malignant cells.
     Viruses have been implicated in the etiology of several
types of human cancers, including cervical cancer and liver
cancer. The viruses that have been strongly associated with human
cancers include human papillomaviruses, Epstein-Barr virus,
hepatitis B virus, and a human retrovirus. Many viruses can cause
tumors in animals, either as a result of natural infection or
after experimental inoculation. Animal viruses are studied to
learn how a limited amount of genetic information (only one or a
few viral genes) can profoundly alter the growth behavior of host
cells, and ultimately convert a normal cell into a malignant
cell. For example, classical studies of RNA tumor viruses first
revealed the involvement of cellular *oncogenes in cancer, and
similar studies with DNA tumor viruses first implicated a role
for *tumor suppressor genes in cancer. In the 1980s, these
discoveries revolutionized thinking about the molecular
mechanisms of carcinogenesis.
     Alveolar cell cancer (bronchiolo-alveolar cancer, broncho-
alveolar cancer) is a human lung cancer, a subtype of
*adenocarcinoma, and apparently a lung cancer unrelated to
cigarette smoking. The cause of this disease is unknown.
     "Jaagsiekte" is a contagious lung cancer (ovine pulmonary
carcinoma) of sheep, sometimes also of goats and guinea pigs, the
disease resembling the more benign forms of human alveolar cell
cancer. Jagsiekte in sheep is apparently caused by a retrovirus
(jagsiekte sheep retrovirus), and infected sheep secrete large
amounts of lung fluids from which copious quantities of the virus
may be obtained.
     The term "fibroblasts" refers to a type of connective tissue
cell that secretes the structural proteins (e.g., collagen) that
form certain tissue components. Fibroblasts are easy to maintain
in tissue culture, and they are often used as experimental cell
systems.
     In this context, the term "transformation" refers to the
transformation of a normal cell into a malignant (cancer) cell.
... ... N. Maeda et al (4 authors at University of California
Irvine, US) present a report on cancerous transformation of mouse
fibroblasts by jaagsiekte sheep retrovirus DNA, the authors
making the following points:
     1) The authors point out that animal retrovirus-induced
cancers have played fundamental roles in understanding the
molecular basis of cancer. Jaagsiekte sheep retrovirus is the
causative agent of ovine pulmonary carcinoma, a contagious lung
cancer of sheep (also known as sheep pulmonary adenomatosis).
This retrovirus-induced cancer consists of transformed secretory
*epithelial cells of the lungs, and a characteristic feature of
the tumors is the production of large amounts of fluid secreted
from tumor cells containing infectious virus. The disease closely
resembles human alveolar carcinoma, and is thus an important
model for understanding the latter.
     2) The authors point out that oncogenic retroviruses induce
tumors by two mechanisms. a) Acutely transforming retroviruses
capture a normal host-cell gene (a "protooncogene") and convert
it into a viral oncogene. Such retroviruses typically induce
rapid neoplasms in vivo, and they frequently can transform cells
in culture. b) Retroviruses that lack oncogenes (non-acute
retroviruses) also can induce tumors, although they typically
require longer incubation periods and multiple rounds of
infection in vivo. An important molecular mechanism for these
viruses is insertion in the host-cell genome of viral genetic
material in the vicinity of a protooncogene. This results in
overexpression of the protooncogene.
     3) The authors report their experiments indicate that
jaagsiekte sheep retrovirus DNA (i.e., DNA produced by
transcription of the viral genome) can induce transformation in a
line of mouse fibroblasts (NIH 3T3 cells), and that additional
experiments have localized the transforming activity to the viral
env gene. The authors suggest their results indicate that the
envelope gene carries the transforming potential in this virus,
an unusual case of a transformation potential carried by a viral
structural protein.
... ... In a contiguous independent report, S.K. Rai et al (6
authors at 3 installations, US) report that the envelope (env)
gene of jaagsiekte sheep retrovirus "has the unusual property
that it can induce transformation in rat fibroblasts, and thus is
likely to be responsible for oncogenesis in animals."
... ... In a commentary on the above work, Naomi Rosenberg (Tufts
University, US) points out that more than 50 oncogenes now known
to be involved in human cancers were first discovered and studied
in retroviral models. "Nonetheless, only one retrovirus, human T
cell lymphotrophic virus (HTLV), is oncogenic in humans, and, as
we enter the 21st century, retroviral oncogenesis models may seem
to be of largely historical interest. However, analyses of
jaagsiekte sheep retrovirus by Maeda et al and Rai et al...
reveal that oncogenic retroviruses still hold important secrets
that may be directly relevant to human cancer."
-----------
Proc. Nat. Acad. Sci. 2001 98:4285,4443,4449
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Notes:
... ... *messenger RNAs: (mRNAs) The ribonucleic acid molecules
transcribed from DNA that carry the coded information
specifying the sequence of amino acids in proteins.
... ... *ribosomes: A ribosome (not to be confused with riboZYME)
is a small particle, a complex of various ribonucleic acid
component subunits and proteins that functions as the site of
protein synthesis. In general, ribosomes read the messenger RNA
template to produce specific polypeptide sequences by
polymerizing amino acids.
... ... *oncogenes: There are two general meanings of this term
in current use. The first meaning refers to any of a family of
cellular genes that normally code for proteins involved in cell
growth or regulation, but which may produce malignant processes
when mutated or activated by viruses. The second meaning of the
term "oncogene" refers to viral genes found in certain DNA tumor
viruses, genes that are required for viral replication, but whose
activation produces malignant transformations.
... ... *tumor suppressor genes: Tumor suppressor genes code for
proteins that apparently either prevent cell division or provoke
cell death in defective cells. Thus, deletion or inactivation of
tumor suppressor genes can result in malignant cell replication.
... ... *adenocarcinoma: In general, a tumor of epithelial cells
(see below) in which the cells are in a glandular or gland-like
pattern.
... ... *epithelial cells: In animals, "epithelial cells" compose
the cell layers that form the interface between a tissue and the
external environment, for example, the cells of the skin, the
lining of the intestinal tract, and the lung airway passages.
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SCIENCE-WEEK 2001 20 Jul
-----------
Related Background:
TUMOR VIRUSES AND ONCOGENES
     Viruses, first discovered in 1892 [*Note #1], are infectious
agents that are smaller than biological cells such as bacteria,
their size ranging from about 20 nanometers to about 900
nanometers. Beginning in the 1930s, there was much controversy
about classification, with the central question whether viruses
are a "life" form. The answer, of course, depends on the
definition of "life", and since there are various definitions
possible, the question is ill-defined. In general, a virus is a
self-organizing molecular system capable of using living cells to
replicate itself, the sequence of events in many cases altering
or destroying the cells and thus causing a disease process.
     In addition to disease processes caused by the destruction
of cells, viruses are now known to be etiologic factors in the
development of several types of human tumors, including two of
worldwide significance: cervical cancer and liver cancer. Viruses
have also been strongly associated epidemiologically with other
human cancers, and these viruses include *human papillomavirus,
*Epstein-Barr virus, and *hepatitis B virus.
     Like other viruses, tumor viruses are classified among
different virus families according to the nucleic acid of their
genome and the biophysical characteristics of their virions
(virion = the complete virus particle as it exists outside the
host cell). All known tumor viruses either have a DNA genome or
an RNA genome. In the case of an RNA genome, the RNA genome
generates a DNA "provirus" (a preliminary virus entity) after
infection of cells. All RNA tumor viruses (i.e., tumor viruses
with an RNA genome) belong to the "retrovirus" family.
Retroviruses carry an RNA-directed polymerizing enzyme (reverse
transcriptase) that constructs a DNA copy of the RNA genome of
the virus. This DNA copy (the provirus) becomes integrated into
the DNA of the infected host cell, and it is from this integrated
DNA that all proteins of the virus are translated.
     Tumor viruses are of two general types with respect to tumor
induction, distinguished by (among other things) whether or not
they carry "oncogenes" (i.e., any gene associated with the
causation of cancer). All DNA tumor viruses carry oncogenes,
these oncogenes an integral part of the viral genome and not
derived from host cells. Of RNA tumor viruses, there are two
types: a) the highly oncogenic ("direct-transforming") RNA tumor
viruses (class I RNA tumor viruses) carry an oncogene of host-
cell origin; b) the weakly oncogenic ("slowly transforming") RNA
tumor viruses (class II RNA tumor viruses) do not contain an
oncogene but induce leukemias after long incubation periods by
indirect mechanisms. In this context, the term "transforming"
refers to the transformation of a normal host-cell into a cancer
cell. ... ... George Klein (Karolinska Institute, SE) presents an
essay on the history of the idea of tumor viruses, the author
making the following points:
     1) In 1911, Peyton Rous (1879-1970) demonstrated that fowl
*sarcomas could be transmitted with cell-free filtrates, and the
rapid consensus was that cancer was a viral disease. But when
similar experiments with mouse and rat tumors failed soon after,
it was concluded that tumor viruses occurred only in birds, and
the field fell into disrepute.
     2) The discovery in the 1920s of the Shope papilloma virus,
which causes warts in rabbits, produced little enthusiasm among
researchers because the tumors were largely benign.
     3) In the 1930s, the mouse mammary tumor virus was
discovered, and this virus was called "*milk factor" rather than
"milk virus" to avoid a negative reaction from people in the
medical science community who had relegated tumor viruses to the
cabinet of freaks.
     4) The great change in the climate of opinion concerning
tumor viruses came in the 1950s when Ludvik Gross discovered the
mouse leukemia virus, and Sarah Stewart and Bernice Eddy
identified the *polyomavirus. Within a few years the pendulum had
swung to the opposite extreme. After decades of failed attempts,
viruses that could induce tumors in mammals were now isolated in
quick succession. Tumor virology rapidly became favored by grant-
giving agencies, and the oncogene concept -- that tumor viruses
carry "cancer genes" that can transform some of their target
cells into a cancerous or precancerous state -- was formulated in
the context of this enthusiasm.
     5) The class I RNA tumor viruses can induce tumors because
they have accidentally incorporated from host cells genes that
regulate growth. After entering a new host cell, the viral enzyme
reverse transcriptase copies the viral RNA into provirus DNA
which integrates randomly into the host cell DNA. When the virus
starts to reproduce itself, and the proviral DNA is transcribed
back into RNA, some of the new virus particles may also carry
additional cellular sequences from regions adjacent to the random
integration site of the proviral DNA. These newly replicated
virus particles have the potential to corrupt the DNA of other
host cells when these host cells are subsequently infected.
     6) Class II RNA tumor viruses do not themselves contain
oncogenes, but contribute to malignant tumor development
relatively infrequently when their proviral DNA happens to
integrate into the host DNA near host oncogenes.
     7) By discovering cellular genes that regulate growth and
that can contribute to cancer development after illegitimate
viral activation, the virologists demonstrated the existence of
host oncogenes that when mutated can promote cancer formation
independent of viruses. This discovery once again relegated tumor
virology to a less prominent place and reaffirmed the sovereignty
of cell biology. Cancer is essentially a disease of cellular DNA;
when viruses are involved in cancer, they are involved as one of
many possible DNA-corrupting agents.
     8) All oncogenes have turned out to be *highly conserved
housekeeping genes that participate in the regulation of the
*cell cycle. Their potentially tumorigenic forms drive the cell
towards proliferation. For overt tumor development, additional
genetic changes are required, including loss of *cell-cycle
check-point controls, inhibition of programmed cell death
(apoptosis), and *up-regulation of blood supply (*angiogenesis).
The current oncogene field, therefore, emerged from erroneous
concepts concerning the etiology of cancer, but these concepts,
when combined with several decades of diligent experimentation,
finally produced a valuable outline of the events that cause the
formation of cancerous tumors.
-----------
Nature 1999 400:515
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Notes:
... ... *Note #1: In 1892, a Russian botanist named Dmitri
Ivanovsky (1864-1920) became interested in the cause of a disease
of the valuable tobacco plant, a disease called "mosaic disease".
The name was due to the mosaic patterns the disease produced on
the leaves of the plant. Ivanovsky devised an experiment, mashed
up infected leaves, and forced them through filters designed to
remove all bacteria. He discovered that the liquid that passed
through the filters could still infect healthy tobacco plants.
Ivanovsky concluded, in error, that the infectious agent was
still a bacterium, but that his filters were somehow defective,
and it was this conclusion that he published in a Russian
scientific journal. Six years later, a Dutch botanist named
Martinus Beijerinck (1851-1931) repeated the experiments and
concluded the infectious agent was not a bacterium but the liquid
itself, a poison, and he called it a filterable "virus", the word
"virus" being the Latin word for poison. In the 1930s, an
American biochemist named Wendell Meredith Stanley (1904-1971)
became interested in this mysterious "virus" liquid. He believed
the poison to be a protein. He repeated the filtration
experiments with diseased tobacco leaves, and he isolated a
crystalline substance in high concentration that had all the
infective properties of the so-called virus liquid. In the report
which Stanley published in 1935, he concluded: "Tobacco mosaic
virus is regarded as an autocatalytic protein which, for the
present, may be assumed to require the presence of living cells
for multiplication." For this work, Stanley received the Nobel
Prize in Chemistry in 1946. Although the tobacco mosaic virus,
like all viruses, is much more than just a simple autocatalytic
protein, the first understanding of the true nature of viruses
was now in place. The experiments that had begun in Russia in
1892 culminated 43 years later in the startling realization that
an entire class of infectious agents much smaller than bacteria
existed.
... ... *human papillomavirus: The papillomavirus causes benign
tumors called "warts". The virus in its extracellular form
(virion) is 55 nanometers in diameter, with a circular double-
stranded DNA genome of approximately 8000 nucleotide base pairs.
The virus primarily infects surface *epithelia. There are more
than 70 different types of human papillomaviruses.
... ... *epithelia: In animals, epithelial cells compose the cell
layers that form the interface between a tissue and the external
environment, for example, the cells of the skin, the lining of
the intestinal tract, and the lung airway passages.
... ... *Epstein-Barr virus: The Epstein-Barr virus is a large
ubiquitous herpesvirus that is the causative agent of acute
infectious mononucleosis and a factor in the development of
nasopharyngeal carcinoma, Burkitt's lymphoma, and other
disorders. The virion is approximately 100 nanometers in
diameters, and contains a double-stranded DNA genome consisting
of approximately 172,000 nucleotide base pairs.
... ... *carcinoma: In general, a carcinoma is any malignancy
derived from epithelial tissue.
... ... *hepatitis B virus: The hepatitis B virus is the
causative agent of *serum hepatitis. The virion is 42 nanometers
in diameter, the genome double-stranded DNA with 3200 nucleotide
base pairs.
... ... *serum hepatitis: In general, "hepatitis" is any
inflammation of the liver. "Serum hepatitis" is usually
transmitted by injection of infected blood or blood derivatives,
or by the use of contaminated needles or other instruments.
... ... *sarcomas: A sarcoma is a connective tissue neoplasm,
usually highly malignant.
... ... *milk factor: The prototype of RNA tumor viruses is the
"mouse mammary tumor virus", which occurs in high-mammary-cancer
strains of inbred mice, and is found in particularly large
amounts in lactating mammary tissues and milk. The virus is
readily transferred to suckling mice, in whom the incidence of
subsequent development of carcinoma of the breast is high. The
work of J.J. Bittner (1904-1961) on this virus is classic: In the
1930s, carefully inbred strains of mice were kept for research on
cancer. Some strains were highly resistant to cancer and rarely
developed it, while other strains were so prone to cancer that
almost every individual animal developed the disease. In 1936,
Bittner established that if young mice of a cancer-resistant
strain were transferred to the breast of a foster mother of a
cancer-prone strain, the young mice developed cancer in the
course of their lives. If, on the other hand, young mice of a
cancer-prone strain were fed at the breast of a foster mother of
a cancer-resistant strain, they did not usually develop cancer.
The Bittner "milk factor" was isolated in 1949 and was found to
consist of virus-like particles containing nucleic acid.
... ... *polyomavirus: Papillomaviruses and polyomaviruses are
the two classes of papovaviruses. Like papillomaviruses,
polyomaviruses have a double-stranded DNA genome, but with only
5000 nucleotide base pairs. The polyoma virion is 45 nanometers
in diameter, and the target tissues are internal organs. An
important research tool, the SV40 monkey virus, is a
polyomavirus.
... ... *highly conserved housekeeping genes: The term "highly
conserved" refers to a gene sequence maintained across
evolutionary time. So-called "housekeeping" genes are genes
coding for proteins involved in essential functions such as
metabolic cycles.
... ... *cell cycle: The "cell cycle" is the name given to the
ordered sequence of phases through which a cell passes from one
mitotic cell division to the next.
... ... *cell-cycle check-point controls: So-called "checkpoints"
are points in the cell division cycle where the cycle can be
halted until conditions are suitable for the cell to proceed to
the next stage.
... ... *up-regulation: In general, the term "up-regulation"
refers to an increase in the activity of some entity or process.
... ... *angiogenesis: Angiogenesis, the origin and development
of blood vessels, is an important consideration in the growth of
cancerous tumors, since the tumor provokes directed angiogenesis
into itself (up-regulation of a blood supply) with the end result
that the tumor is supplied with oxygen and nutrients. Without
angiogenesis, tumors can attain only a small size before becoming
self-inhibiting.
-----------
SCIENCE-WEEK 1999 10 Sep
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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15. ON THE ANTI-CANCER DRUG TAXOL
S. Jennewein et al (Washington State University, US) discuss
taxol, the authors making the following points:
     1) Taxol (generic name paclitaxel) is a highly effective
anti-cancer drug used widely in the treatment of various
carcinomas, melanomas, and sarcomas. This structurally complex
taxane diterpenoid (taxoid) was first isolated from the bark of
the Pacific yew tree (Taxus brevifolia). Despite great
difficulties in obtaining sufficient quantities of Taxol for
clinical trials from this source, the unique mode of action of
this drug, as well as its outstanding potency against several
tumor cell lines, ultimately led to the development of Taxol as
one of the most efficacious anti-cancer drugs in current use.
     2) Taxol is presently derived largely by semisynthesis from
the advanced taxoid 10-deacetylbaccatin III, which can be
obtained from needles of the European yew tree, Taxus baccata.
However, approval of Taxol for the treatment of additional types
of cancer, as well as the use of the drug much earlier in the
course of clinical intervention, is very likely to increase the
demand for Taxol and its precursors for semisynthesis.
Additionally, extensive studies on the naturally occurring
taxoids, now numbering over 350, have led to the discovery of
novel structures and to the preparation of new chemical
derivatives with improved biological activity. These "second
generation" taxoid drugs, like Taxol itself, will depend on the
isolation of natural products from the yew tree.
     3) Several elegant total synthetic routes to Taxol and
related taxoids have been developed. However, low yields and high
costs preclude these methods from commercial production, and for
the foreseeable future sourcing must continue to rely on Taxus
species or, potentially, on cell cultures derived therefrom.
Improved biological production methods depend on an understanding
of the biosynthetic pathways leading to Taxol and related taxoids
and on definition of the responsible enzymes and genes. Taxol
biosynthesis involves approximately 20 enzymatic steps from
primary plant metabolism, and several of these steps have now
been defined.
-----------
Proc. Nat. Acad. Sci. 2001 98:13595
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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16. COCAINE ADDICTION: INEFFECTIVENESS OF ACUPUNCTURE TREATMENT
A. Margolin et al (Yale University, US) discuss acupuncture as a
treatment for cocaine addiction, the authors making the following
points:
     1) Cocaine addiction continues to be a serious problem in
the US, with official estimates that in 1998 there were 3.3
million chronic cocaine users. Although several psychological and
behavioral approaches have shown promise, treatment for cocaine
addiction has been impeded by the lack of a generally effective
pharmacologic agent. Partly because of this lack, auricular (ear)
acupuncture as codified by the National Acupuncture
Detoxification Association is now one of the most widely used
treatments for this disorder, with more than 400 substance abuse
clinics in the US and Europe providing this form of treatment.
Auricular acupuncture is also a treatment component in numerous
drug court programs (treatment programs mandated by the justice
system).
     2) The mechanism by which acupuncture may treat cocaine
addiction is unclear. Clinical reports suggest that it has a
calming effect upon patients, decreases craving for cocaine, and
promotes retention of patients in psychosocial treatments.
Research on acupuncture for the treatment of cocaine addiction
has shown mixed results, and the methods used in these studies
have varied.
     3) The authors report a study to investigate the
effectiveness of auricular acupuncture as a treatment for cocaine
addiction. The study involved 620 cocaine-dependent adult
patients, with both needle-insertion controls and relaxation
controls (commercial videos containing relaxing imagery, e.g.,
nature scenes and soft music). Treatments were offered 5 times
weekly for 8 weeks. From their results, the authors conclude that
within the clinical context of this study, acupuncture was not
more effective than a needle insertion or relaxation control in
reducing cocaine use. The authors suggest the study does not
support the use of acupuncture as a stand-alone treatment for
cocaine addiction or in contexts in which patients receive only
minimal concurrent psychosocial treatment.
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J. Am. Med. Assoc. 2002 287:55
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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17. HUMAN USE OF GLOBAL PHOTOSYNTHESIS
S. Rojstaczer et al (Duke University, US) discuss human use of
global photosynthesis, the authors making the following points:
     1) Human use of photosynthesis products is pervasive,
including direct use of plants for food and fiber as well as
indirect use from grazing by domesticated animals. Population
increases have led to speculation and estimates that the human
footprint on the biosphere, in terms of the use of both plants
and fresh water, is approaching the limit of planet
sustainability.
     2) A key measure of human impact on the biosphere and
hydrosphere is human use of terrestrial net primary production,
which represents the net energy (production minus respiration)
created by carbon fixation on land. Previous estimates of global
human appropriation of this biological resource -- which governs
the total amount of food available on Earth -- and its surrogates
have used mean estimates of parameters, the estimates made on the
basis of limited small-scale field studies.
     3) The authors report a study incorporating contemporary
data, many of which are satellite-based, to estimate the human
appropriation of photosynthesis products and quantify the
uncertainty in our knowledge of this appropriation. The authors
report they estimate that humans appropriate 10 to 55 percent of
terrestrial photosynthesis products. This broad range reflects
uncertainty in key parameters and makes it difficult to ascertain
whether we are approaching crisis levels in our use of the
planet's resources. Improved estimates will require high-
resolution global measures within agricultural lands and tropical
forests.
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Science 2001 294:2549
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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18. RED WINE AND CORONARY HEART DISEASE
R. Corder et al (Queen Mary University London, UK) discuss red
wine as a preventative of coronary heart disease, the authors
making the following points:
     1) Statistical evidence of reduced coronary heart disease in
areas of high wine consumption has led to the widespread belief
that wine affords a protective effect. Although moderate drinking
of any alcohol helps to reduce the incidence of coronary heart
disease, there is no clear evidence that red wine confers an
additional benefit.
     2) The concept of the "French paradox" has arisen from
reports that deaths from coronary heart disease are much lower in
France than in the UK, despite a comparable dietary intake of
saturated fats by these populations, and this has been attributed
to the higher consumption of alcohol in France, particularly of
wine. Mechanisms implicated in this phenomenon include increases
in high-density lipoprotein and fibrinolytic activity, and
decreased platelet aggregation, but these changes are modest and
can be caused by ethanol consumption per se. Indeed, the very
existence of the French paradox has been questioned, as it may
simply reflect a time lag in dietary cholesterol intake.
Identification of a specific property of red wine that accounts
for reduction in coronary heart disease could resolve this
controversy as well as provide insight into the health benefits
of a Mediterranean diet.
     3) The authors report a demonstration that red wines
strongly inhibit the synthesis of endothelin-1, a vasoactive
peptide that is crucial in the development of coronary
atherosclerosis, and the authors suggest their findings indicate
the components (apparently polyphenols) specific to red wine may
help prevent coronary heart disease. The most effective red wine
was that made from Cabernet Sauvignon grapes. The authors
examined ethanol-free extracts from 23 red wines, 4 white wines,
one rose wine, and one red-grape juice. Extracts from white wines
and from the rose wine showed little or no inhibition of
endothelin-1 synthesis in cultured bovine aortic endothelial
cells; an extract from the red-grape juice had a small effect.
The authors point out that red-wine extract is also known to
elicit endothelium-dependent vasodilation and lower blood
pressure, which may provide further protection against coronary
heart disease.
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Nature 2001 414:863
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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19. ASSEMBLY OF A NEW CLASS OF MICROWIRES
K.D. Hermanson et al (University of Delaware, US) discuss
microwire assembly, the authors making the following points:
     1) The assembly of colloidal particles holds promise for the
miniaturization of photonic and electrical circuits and their
stacking in the 3rd dimension. Important recent developments in
the field of creating miniaturized electrically functional
structures include the synthesis of electronic elements by
templated growth in membrane channels and their assembly and
characterization, formation of electrical connections and
electronic elements by electrodeposition, and assembly of
prefabricated blocks by capillary forces.
     2) Different types of semiconductor nanowires have been
synthesized by chemical or electrochemical growth, and could be
used in prototypes of electronic devices. Microwires have also
been fabricated by a combination of templating and microfluidics.
In most cases, however, the connection and interfacing of the
small elements remains a challenge. Another challenge is to
assemble structures from suspension, creating "wet" electronic
circuits that can find application in sensors, electrically
readable bioarrays, and biologic-electronic interfaces.
     3) The authors report that a new class of microwires can be
assembled by dielectrophoresis from suspensions of metallic
nanoparticles. The wires are formed in the gaps between planar
electrodes and can grow faster than 50 microns per second to
lengths exceeding 5 millimeters. These wires have good ohmic
conductance and automatically form electrical connections to
conductive islands or particles. The thickness and fractal
dimension of the wires can be controlled, and composite wires
with a metallic core surrounded by a latex shell can be
assembled. The authors suggest that the simple assembly process
and the high surface-to-volume ratio of these wires make them
promising components for wet electronic and bioelectronic
circuits.
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Science 2001 294:1082
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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20. EL NINO: FIRE DAMAGE IN LOGGED FORESTS
F. Siegert et al (Ludwig Maximilians University, DE) discuss El
Nino drought fire damage, the authors making the following
points:
     1) In 1997-1998, fires associated with an exceptional
drought caused by the El Nino/Southern Oscillation (ENSO)
devastated large areas of tropical rainforests worldwide.
Evidence suggests that in tropical rainforest environments
selective logging may lead to an increased susceptibility of
forests to fire. The authors investigated whether this was true
in the 1997-1998 Indonesian fires, the largest fire disaster ever
observed.
     2) During the last three decades, pressure on forests by
logging and massive transmigration has strongly increased on the
island of Borneo. According to official sources, more than 180
million cubic meters of large logs have been harvested from the
forests of East Kalimantan since 1969. Fire became a threat to
the rainforests in East Kalimantan only recently. Undisturbed
tropical rainforest is normally highly resistant to fire because
of low loads of available fuel, low fuel-energy content, and high
humidity even during drought.
     3) The authors report they performed a multiscale analysis
using coarse- and high-resolution optical and radar satellite
imagery assisted by ground and aerial surveys to assess the
extent of the fire-damaged area and the effect on vegetation in
East Kalimantan on the island of Borneo in 1997-1998. A total of
5.2 +- 0.3 million hectares, including 2.6 million hectares of
forest, was found burned with varying degrees of damage. Forest
fires primarily affected recently logged forests. Primary forests
or those logged long ago were less affected. The authors suggest
these results support the hypothesis of positive feedback between
logging and fire occurrence. The fires severely damaged the
remaining forests and significantly increased the risk of
recurrent fire disasters by leaving huge amounts of dead
flammable wood.
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Nature 2001 414:437
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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21. ON THE SYNTHESIS OF PURE ENANTIOMERS
j. Kubota and F. Zaera (University of California Riverside, US)
discuss the synthesis of pure enantiomers, the authors making the
following points:
     1) Chirality is prominent in the biochemistry of living
organisms, since living systems have evolved to favor one
handedness over the other. The use of the wrong enantiomer in
pharmaceutical applications can be deadly: witness the case of
thalidomide, where the analgesic properties of one enantiomer is
offset by the fetal malformations caused by the other enantiomer.
     2) At present, the best way to synthesize enantiomerically
pure chemicals is via homogeneous catalysis. However, since such
processes often require expensive and hard-to-handle metal
complexes that are difficult to separate from the products, the
use of heterogeneous catalysts is much preferred. The most
promising route for that is via the addition of chiral modifiers
to regular catalysts, but such an approach has thus far been
limited by the lack of understanding of the corresponding surface
processes.
     3) One of the few successful examples of chiral-modified
heterogeneous catalysis is the hydrogenation of alpha-ketoesters
on supported platinum catalysts modified with cinchona alkaloids.
Unfortunately, tuning that process for specific applications is
hampered by the fact that small changes in structure or
concentration of the modifier, particle size of the metal
catalyst, nature of the solvent, and reaction conditions all
affect the activity and selectivity of the system in
unpredictable ways. The authors report a spectroscopic study of
the absorption of cinchona from solution onto platinum surfaces,
and conclude that in general, the conditions that favor a flat-
lying adsorption of the aromatic ring of the modifier increase
the activity and enantioselectivity of the platinum catalyst.
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J. Am. Chem. Soc. 2001 123:11115
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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22. ON ACOUSTIC SURGERY
Gail ter Haar (Institute of Cancer Research, UK) discuss acoustic
surgery, the author making the following points:
     1) High-intensity ultrasound fields may be focused on
targets lying deep within the human body, and if sufficient sound
energy is concentrated within the focal volume, the temperature
in that region may be raised to levels at which the constituent
cells are killed. This technique, which is called "focused
ultrasound surgery" or "high-intensity focused ultrasound", has
potential applications in any medical field that may benefit from
the selective destruction of tissue volumes. Recent clinical
interest in the technique has concentrated on treating soft-
tissue cancers and on debulking enlarged prostates (benign
prostatic hyperplasia).
     2) Elevated temperatures (hyperthermia) have been used for
many years to combat disease. In the 1980s, considerable interest
appeared in using hyperthermia in combination with radiotherapy
or chemotherapy for treating cancer. The goal was to raise the
temperature of the tumor and a surrounding margin of normal
tissue from normal body temperature (37 degrees C.) to 42 to 46
degrees C. for about an hour. Radio-frequency, microwave, and
ultrasound energy were investigated for this purpose, and sources
were developed for use outside the body, within body cavities,
and within the tissue themselves. The main disadvantage of these
hypothermia techniques is the requirement of uniform temperature
distributions in a narrow range, which necessitates the
introduction of thermocouples into the target tissue, because
blood flow cooling can lead to local cold spots.
     3) In focused ultrasound surgery, the temperature in the
focal zone is raised to a temperature above 56 degrees C. and is
held for 1 to 3 seconds. The rapid deposition of thermal energy
leads to a peak temperature rise that is independent of cooling
by blood flow -- an important consideration for tissues in which
the vascular pattern is not completely known or predictable.
Early indications from clinical trials demonstrate the very real
possibility that focused ultrasound surgery will offer a
practical alternative to conventional surgery.
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Physics Today 2001 December
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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23. ON APPLICATIONS OF LIQUID CRYSTALS
C. Denniston and J.M. Yeomans (Johns Hopkins University, US)
discuss liquid crystals, the authors making the following points:
     1) In most practical applications of liquid crystals, such
as traditional display devices, defect structures in liquid
crystals destroy the optical properties and are undesirable.
However, novel display designs, such as bistable displays or
multidomain nematics, exploit defect properties. Most attempts to
control the defect motion have made use of bulk electric fields.
     2) Liquid crystals are typically comprised of highly
anisotropic rod-shaped molecules. The "nematic" phase occurs when
the molecules align parallel, giving rise to long-range
orientational order with the direction of alignment indicated by
the so-called "director field". In a typical display device, the
liquid crystal is confined between two plates a few microns
apart, and the director configuration on the plates is fixed.
When an electric field is switched on, the molecules align in the
direction preferred by the field. After switching off the field,
long-range elastic interactions ensure that the molecules
reorient themselves in the direction preferred by the surfaces.
These devices can be used as displays because different liquid-
crystal orientations have different optical properties. The
switching of such traditional liquid-crystal devices is well
understood.
     3) However, there is now considerable interest in developing
bistable devices that can retain a memory of two distinct states
with different liquid-crystal orientations and thus different
optical properties, even when the field is switched off. It has
been demonstrated by both theory and experiment that it is
possible to produce two metastable states with different
orientations of the director field in the bulk by having
different configurations of defects near the surface. However,
the process of switching between these two states is not
understood. The authors describe the physics behind the switching
dynamics of a simple bistable nematic device.
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Phys. Rev. Lett. 2001 87:275505
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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24. ON FREE-RADICAL POLYMERIZATION
A.A. Gridnev and S.D. Ittel (DuPont Performance Coatings, US)
discuss free-radical polymerization, the authors making the
following points:
     1) Although free-radical chain reactions were known shortly
after the turn of the 20th century, it was not until the mid-
1930s that free-radical polymerization was recognized. Today,
free-radical polymerization finds application in the synthesis of
many important classes of polymers, including those polymers
based on methacrylates, styrene, chloroprene, acrylonitrile,
ethylene, and the many copolymers of these vinyl monomers.
     2) Free-radical polymerizations are subject to the many
complications one might expect of radical chemistry, but the
simple underlying mechanism is composed of three primary
processes: initiation, propagation, and termination. Generally,
the initiation occurs by cleavage of an azo or peroxide compound
(the "initiator") to yield the "primary radical". The propagation
or growth reaction occurs when monomers add to the primary
radical or to the radical at the end of the growing polymer
chain. Termination occurs primarily by the bimolecular reaction
of two growing polymer radicals.
     3) The two primary mechanisms observed are radical-radical
combination and disproportionation in which one radical abstracts
a hydrogen atom from another radical to result in one saturated
chain and one olefinic chain end. In addition to these primary
reactions, there are a variety of other reactions that occur.
There may be very low levels of "chain transfer" to monomer, a
reaction that leads to termination of one chain with simultaneous
initiation of another new chain, so that there is no change in
the number of radical species present.
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Chem Revs. 2001 101:3611
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SCIENCE-WEEK 22 Feb 2002 www.scienceweek.com

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25. PRE- AND POSTDOCTORAL FELLOWSHIP PROFILE:
Office of G. de Alba at Smithsonian Tropical Research Institute
---------------------------------------------------------------
     INSTALLATION: Smithsonian Tropical Research Institute
     DEPARTMENT: Education
     GENERAL RESEARCH AREA: Tropical Biology
     HEAD OF THIS SPECIFIC OFFICE: Georgina de Alba
     POSTDOCTORAL FELLOWSHIPS ARE AVAILABLE IN THE FOLLOWING
SPECIFIC RESEARCH PROBLEMS: The Smithsonian Tropical Research
Institute (STRI), a division of the Smithsonian Institution
headquartered in the Republic of Panama, offers fellowships for
research conducted with the advice and guidance of its staff
members. Disciplines include ecology, anthropology, paleontology,
evolution, systematics, behavior, and physiology of tropical
plants and animals.
     SPECIFIC FELLOWSHIPS AND PREVIOUS RESEARCH EXPERIENCE AND
DEGREES REQUIRED:
          a) 10-Week Graduate Student Fellowships: For students
engaged in graduate studies who have completed at least one
semester and have not yet been advanced to candidacy if in a PhD
program to carry out research for 10 weeks under the guidance of
a Smithsonian staff member. Deadline for submitting applications
is January 15, 2003
          b) Predoctoral Fellowships: For investigators who have
completed preliminary course work and examinations for the PhD
and are engaged in dissertation research, to conduct a research
project of 3 to 12 months duration under the guidance of a
Smithsonian staff member. Deadline for submitting applications is
January 15, 2003
          c) Postdoctoral Fellowships: For investigators who have
completed the doctoral degree less than seven years before the
application deadline to conduct research for 3 to 12 months at
the Smithsonian. Deadline for submitting applications is =
January 15, 2003
          d) Senior Postdoctoral Fellowships: For investigators
more than 7 years beyond PhD degree, to conduct research at the
Smithsonian from 3 to 12 months. The stipend will often be
matched by other sources of funding such as a sabbatical salary. 
Deadline for submitting applications is January 15, 2003
          e) Short-term Fellowships: Support is provided to carry
out short-term research projects in the tropics in areas of STRI
research and under the supervision of Institute staff members. 
Projects may be exploratory or complete in themselves and their
usual duration is 3 months.  The  majority of these fellowships
are awarded to graduate students, but awards are occasionally
made to undergraduates and postdoctoral candidates. Deadlines for 
submitting applications are the 15 of February, May, August, and
November.
          f) Latin American Fellowships & Internship Program:
Support is provided for undergraduate students and recent
graduates from the Republic of Panama and other Latin American
nations to enable them to carry out project with the supervision
of STRI staff members (fellowships), or to participate in an
on-going project (internships).
          g) Three-year Tupper Postdoctoral Fellowships in
Tropical Biology: Support is provided for a postdoctoral
investigator to conduct a three year project on a subject related
to STRI research interests. The deadline for submitting
applications is January 15, 2003
     USUAL STARTING STIPEND: Short Term Fellows is $2,100 for
three months. Predocs is $17,500/year. Postdocs is $30,000 /year
     SPECIAL REQUIREMENTS: Depending on the country, an
authorized visa may be a requirement by the Panamanian
government.
     APPROXIMATELY NUMBER OF PEOPLE CURRENTLY WORKING IN THIS
SPECIFIC LABORATORY (FACULTY, STAFF, STUDENTS, POSTDOCS): We have
approximately 40 fellows at the moment. We have 39 staff
scientists. We receive more than 600 visiting scientists per
year.
     CONTACT: Adriana Bilgray fellows@tivoli.si.edu
     FURTHER RELEVANT INFORMATION: Web: www.stri.org

--------------------------------------------------------------
Please note: Postdoctoral Fellowship Profiles are provided to
ScienceWeek by the heads of laboratories, and ScienceWeek does
not charge for their publication. For information about
publishing a Postdoctoral Fellowship Profile, contact Claire
Haller at haller@scienceweek.com

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26. IN FOCUS: GENOMES, GENE NUMBERS, AND REPETITIVE SEQUENCES
"Why organismal complexity fails to correlate with gene numbers
is not fully clear. It may be due in part to RNA splicing events
which generate multiple protein products from single genes;
vertebrate genes give rise to more splicing products than
invertebrate genes. But the quality of respective nervous systems
may be equally relevant. The roundworm, being dumber than the
fruit fly, may need more specific proteins (and therefore genes)
to respond to enemies or changes in its environment -- the fruit
fly's more advanced nervous system lets it respond to potential
enemies and stresses by flying away. Plants, being totally dumb,
must continually evolve new genes to respond to new enemies and
climatic changes. Many more vertebrate genomes need to be
sequenced before we have a sense of how often the generation of
new genes has underlain evolutionary change. We also need to know
why vertebrate genomes contain so many more repetitive sequences
than invertebrates. Most human repetitive sequences appear to
have arisen as the result of the generation and movement of
transposable genetic elements. Conceivably, many of the mutations
that underlie vertebrate evolution arise from transposon
movements into regulatory regions, changing gene expression
patterns. The very high levels of repetitive DNA in amphibians
and lungfish may reflect past needs to evolve fast for survival
in their ever-changing ecological niches."
-----------
James D. Watson: "The Human Genome Revealed"
in: C. Dennis and R. Gallegher (eds.): _The Human Genome_
(Palgrave, New York 2001, p.6) (March 2002)
http://www.amazon.com/exec/obidos/ASIN/0333971434/scienceweek

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27. NEW BOOKS

Ceccarelli: Shaping Science with Rhetoric: The Cases of
Dobzhansky, Schroedinger, and Wilson
http://www.amazon.com/exec/obidos/ASIN/0226099067/scienceweek

Ebenholtz: Oculomotor Systems and Perception
http://www.amazon.com/exec/obidos/ASIN/0521804590/scienceweek

Goodman and Gilman: The Pharmacological Basis of Therapeutics
http://www.amazon.com/exec/obidos/ASIN/0071354697/scienceweek

Wang: The Universality of Physics: A Festschrift in Honor of Deng
Feng Wang
http://www.amazon.com/exec/obidos/ASIN/0306467038/scienceweek

Rossing: The Science of Sound
http://www.amazon.com/exec/obidos/ASIN/0805385657/scienceweek

Hubbell: Shrinking the Cat: Genetic Engineering Before We Knew
About Genes
http://www.amazon.com/exec/obidos/ASIN/0618040277/scienceweek

Garwin et al: Megawatts and Megatons: A Turning Point in the
Nuclear Age?
http://www.amazon.com/exec/obidos/ASIN/0375403949/scienceweek

Kitcher: Science, Truth, and Democracy
http://www.amazon.com/exec/obidos/ASIN/0195145836/scienceweek

Byrd et al: An American Health Dilemma. Voi. 1, A Medical History
of African Americans and the Problem of Race: Beginnings to 1900
http://www.amazon.com/exec/obidos/ASIN/0415924499/scienceweek

Courtwright: Forces of Habit: Drugs and the Making of the Modern
World
http://www.amazon.com/exec/obidos/ASIN/0674004582/scienceweek

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In the text, the affiliation following the names of authors in
sources with more than one author is the affiliation of the lead
author.

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