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ScienceWeek
SCIENCE-WEEK
A Weekly Email Digest of the News of Science
A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.
November 23, 2001 -- Vol. 5 Number 47
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It is impossible to express a really new principle
in terms of a model following old laws.
-- Max Planck (1858-1947)
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. On the Origin of Earth's Moon
2. Ice Nanotubes Inside Carbon Nanotubes
3. Chemistry: On Dendritic Catalysis
4. On ENDOR Spectroscopy
5. Research on Blood Substitutes: Open Science vs. Commerce
6. Point Defects in Two-Dimensional Colloidal Crystals
7. On Cell-Cycle Checkpoints
8. On Immune Cells and Membrane Lipid Rafts
9. Calcitic Micro-Lenses and Photoreception in Brittlestars
10. Old World Sources of First New World Human Inhabitants
11. Evolution of Bacterial Pathogenesis and Symbiosis
12. On the Classical Biogenic Amines
13. In Focus: On Earth's Gravity and the Mantle
14. From PRAXIS: Effects of Commercialization on Research
15. Sources
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Section 2
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1. ON THE ORIGIN OF EARTH'S MOON
R.M. Canup and E. Asphaug (Southwest Research Institute, US)
discuss the origin of the Moon. The Moon is generally believed to
have formed from debris ejected by a large off-center collision
with the early Earth. The impact orientation and size are
constrained by the angular momentum contained in both the spin of
the Earth and the orbit of the Moon, a quantity that has been
nearly conserved over the past 4.5 billion years. Simulations of
potential moon-forming impacts now achieve resolutions sufficient
to study the production of bound debris. However, identifying
impacts capable of yielding the Earth-Moon system has proved
difficult. Previous studies have found that forming the Moon with
an appropriate impact angular momentum required the impact to
occur when the Earth was only about half formed, a more
restrictive and problematic model than that originally envisaged.
The authors report a class of impacts that yield an iron-poor
Moon, as well as the current masses and angular momentum of the
Earth-Moon system. This class of impacts involves a smaller --
and thus more likely -- object than previously considered viable,
and suggests that the Moon formed near the very end of Earth's
accumulation. The authors suggest that it is in retrospect
interesting that the Mars-mass impactor that now appears to be
the most promising Moon-forming candidate is essentially that
originally proposed by A.G. Cameron and W.R. Ward in 1976, a
decade before the first Moon-forming impact simulations.
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NAT 2001 412:708
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Related Background:
ON THE ORIGIN OF THE EARTH AND THE MOON
Two of the central questions in planetary and Earth science
concern the origin of the Earth and Moon. How did these two
bodies form and what forces defined their basic physical
structures? ... ... A.N. Halliday and M.J. Drake (2
installations, CH US) present a short review of current research
in this area, the authors making the following points:
1) Advances in this field have come mainly with progress in
simulating the dynamics of planetary accretion, in measuring
isotopes that act as chronometers for early Solar System
processes, in analysis of noble gas isotopes that yield clues
about the early atmosphere, and in melting experiments at
previously unattainable pressures and temperatures. Although a
general picture may be emerging, many issues remain hotly
debated.
2) Planet formation is believed to begin with sticking and
frictional coagulation of dust particles in a gaseous nebula that
persists in the *circumstellar disk. The particles grow in size
until there is substantial gravitational attraction between
kilometer-sized bodies, and these coalesce further. Major
collisions between small proto-planets eventually result in
objects the size of Earth.
3) The energy of late-stage planet-building impacts would be
colossal, sufficient to melt the entire planet. *Magma oceans
would be formed, and some volatile elements would escape into
space. The most widely accepted theory for the origin of the Moon
is that it coalesced from a ring of debris produced by such a
late-stage collision between two Earth-forming proto-planets.
This "Giant Impact Theory", established over a decade ago,
explains the rotational speed of the Earth-Moon system, a
critical feature that must be reproduced by any satisfactory
model. But in spite of a growing consensus, some researchers are
still opposed to the Giant Impact Theory on both dynamical and
geochemical grounds.
4) All isotopic data are consistent with Earth being fully
formed within 50 to 100 million years after the start of the
Solar System. The isotopic record from Moon rocks is consistent
with the formation of the Moon at about the same time.
5) The authors conclude: "We have recently come a long way
in obtaining hard constraints on the origin of Earth and the
Moon. The issues have changed from discussion of whether or not
there was a giant Moon-forming impact to debate about the
accretion rates of the Earth and the chemical, isotopic, and
physical effects of such catastrophic accretionary scenarios."
... ... In a contiguous short review of the same research area,
Frank A. Podosek (Washington University St. Louis, US) makes the
following points:
1) The age of the Solar System as a whole is easier to
determine than the age of Earth. The age of the Solar System is
reliably inferred from the age of *refractory element-rich
inclusions in meteorites to be approximately 4.57 billion years,
thus providing an upper limit to the age of Earth. These
inclusions are the oldest known objects in the Solar System, and
their content indicates that the Solar System did not exist for
more than approximately 1 million years before the inclusions
formed.
2) In contrast to these ancient extraterrestrial objects,
there are no known terrestrial rocks or minerals whose formation
essentially coincides with the formation of Earth, and therefore
the age of Earth must be inferred indirectly. Several independent
approaches indicate that Earth formed approximately 100 million
years later than the Solar System as a whole.
3) All the various isotopic chronometers are intrinsically
capable of considerably higher precision, but this precision
cannot yet be realized. It is not even clear whether the
chronometers are consistent or in conflict with each other. All
methods rely on models of varying complexity involving
assumptions difficult to verify and parameters difficult to
measure.
4) The author concludes: "For testing the giant impact
scenario in particular, it would be useful to have a quantitative
theory for whether a preexisting atmosphere is lost in the
impact, whether preexisting planetary structures (*core, mantle,
and crust) are re-equilibrated after such an impact, and how much
of the Moon comes from the impactor and how much comes from the
target."
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SCI 1999 283:1861,1863
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Notes:
... ... *circumstellar disk: One of the important discoveries of
the 1980s was the existence of circumstellar disks of dust around
some stars, the disks apparently replenished by unseen parent
bodies such as comets and asteroids.
... ... *Magma: In general, any mass of molten rock.
... ... *refractory: Refractory materials are materials resistant
to decomposition by heat, pressure, or chemical attack. The term
is most commonly applied to heat resistance.
... ... *core, mantle, and crust: Seismic studies indicate the
interior of the Earth consists of three parts: a metallic core, a
dense rocky mantle, and a thin low-density crust. The central
part of the core is solid, but the outer part of the core is
evidently liquid.
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SW 1999 4 Jun
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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Related Background:
AGE AND ORIGIN OF EARTH'S MOON
The most widely accepted theory for the origin of the Earth's
moon is that during the late stages of the Earth's accretion an
impact with another planet at least the size of Mars occurred,
and the impact generated both the hot debris that formed the moon
and the angular momentum of the Earth-moon system. In geology,
the mantle of a planet or moon is the layer that lies between the
crust and the core. Chondrites are a type of stony meteorite
consisting of an agglomeration of millimeter-sized globules
(chondrules) that are thought to be unchanged since the original
condensation out of the nebula from which the sun and solar
system formed, and "chondritic" is the term used to describe a
rock composition similar to that of chondrites, which implies an
age of 4.2 to 4.5 billion years. The term "radiogenic", on the
other hand, is used to describe a rock composition apparently
resulting from varying isotope decays, and the oldest radiogenic
compositions on Earth have been dated at 3.6 to 3.8 billion
years. A hafnium-tungsten chronometer is not an actual instrument
but a method of radiometric age determination using the isotope
ratios of the elements hafnium and tungsten. Hafnium is
lithophilic (silicate-loving), which means it tends to associate
with chondritic materials, while tungsten is siderophilic (metal-
loving), which means it tends to associate with metal cores, and
using these differing affinities of these elements, one can
attempt a construction of the age and origin of the moon by
analysis of moon rock samples and comparisons with Earth rocks.
Lee et al (4 authors at 2 installations, US) report a study of
the age and origin of the moon with the hafnium-tungsten
chronometric method. The tungsten isotopic compositions of 21
lunar samples were found to range from chondritic to slightly
radiogenic. The authors suggest this heterogeneity is probably
the result of late radioactive decay within the moon itself, and
that the moon formed 4.52 to 4.50 billion years ago and its
mantle has since remained poorly mixed.
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SCI 1997 7 Nov
SW 1997 28 Nov 97
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Related Background:
THE ORIGIN OF EARTH'S MOON
The large impact hypothesis of the origin of the Earth's moon is
the current consensus view. The essential idea is that the moon
formed from debris ejected into a disk around Earth by the impact
of a large body. A version of this is that Earth and its moon
were created more or less simultaneously by the collision of two
large planetesimals, the resultant large body becoming Earth, and
the ejected debris formed the moon. What is accepted by nearly
everyone is that an accretion disk of debris was the first stage
of the moon's formation. Shigeru Ida et al (Tokyo Institute of
Technology, JP; University of Colorado Boulder, US) have
evidently now provided the most detailed simulation calculations
of lunar growth in an impact-generated accretion disk. Using
direct N-body simulations, they show that a single dominant moon
can grow from such a disk within a year, but to satisfy the
present angular momentum and mass constraints on the analysis,
the impacting body must have been at least twice as massive as
Mars, and had to provide the resultant system with a few times
more angular momentum than it now possesses. There is presently
no explanation for the subsequent loss of angular momentum, and
the required massive size of the impacting object is also
puzzling. Although this is apparently the best set of simulation
calculations to date, the authors emphasize that further
simulation modeling is needed [*Note #1].
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NAT 1997 25 Sep
SW 1997 10 Oct 97
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Notes:
... ... *Note #1: Accretion is considered an important factor in
the evolution of stars, planets, and comets. The essential idea
is the coalescence of small particles in space as a result of
collisions, and the gradual formation of larger bodies from
smaller ones as a result of gravitational attraction. An
accretion disk is a disk of gas or particles in orbit around an
object, the disk formed by inflowing matter. A simulation of the
sort mentioned in the report involves computational solutions of
the dynamical equations for the history of a chosen mass of
particulate matter initially ejected from a larger body. By
solving the equations for the mathematical model, one can follow
the evolution of the accretion disk and the agglomeration that
forms the final orbiting satellite. The study mentioned here was
first presented at a meeting of the American Astronomical Society
in July, and here is part of the related SCIENCE-WEEK (1 Aug 97)
report: Until the 1980s, there were three extant theories, with
no data available to support or refute any of them. The Fission
Hypothesis proposed that the moon broke away from a rapidly
spinning proto-Earth after the proto-Earth's differentiation, the
moon forming from iron-poor crust. But the moon rocks in hand
have been found to differ chemically from those of Earth. Also,
if the proto-Earth had been spinning fast enough to break up, the
present Earth-moon system should contain a great deal more
angular momentum than is observed. The Fission Hypothesis
therefore had to be abandoned. The Condensation Hypothesis was
based on the idea that the Earth and the moon condensed
simultaneously from the same cloud of material in the solar
nebula. This hypothesis did not survive because analysis of moon
rocks has shown the Earth and the moon have greatly different
densities and compositions. The Capture Hypothesis proposed that
the moon was formed elsewhere in the solar system and later
"captured" by Earth. This hypothesis was always the least popular
because it required too many coincidental events. Thus, after the
mid-1980s, there was no satisfactory theory of the moon's origin.
During the past decade, a new idea gradually developed, the
Large-Impact Hypothesis, the idea of which is that the moon
formed from debris ejected into a disk around the Earth after a
major collision of the Earth with another large body about 4.5
billion years ago, the other body a planet perhaps as large as
Mars. The Large-Impact Hypothesis is at present the consensus
theory in planetary science.
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SW 1997 10 Oct
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2. ICE NANOTUBES INSIDE CARBON NANOTUBES
Fullerenes are large molecules composed entirely of carbon, with
the chemical formula C(n), where n is any even number from 20 to
over 100. They apparently have the structure of a hollow
spheroidal cage with a surface network of carbon atoms connected
in hexagonal and pentagonal rings. Carbon nanotubes are similar
to fullerenes, except their shape is tubular. They were first
discovered by Sumio Iijima in 1991, and they come in both
multi-wall and single-wall versions, with single-wall nanotubes
having a diameter of approximately 1 nanometer and multi-wall
versions having diameters of the order of 10 to 30 nanometers.
There have been rapid developments in understanding the chemistry
and physics of carbon nanotubes, and there is much excitement in
both the materials science and electronics communities concerning
possible applications of these unique structures.
... ... K. Koga et al (Fukuoka University, JP) discuss ordered
ice nanotubes inside carbon nanotubes. Following their discovery,
carbon nanotubes have attracted interest not only for their
unusual electrical and mechanical properties, but also because
their hollow interior can serve as a nanometer-sized capillary,
mold, or template in material fabrication. The ability to
encapsulate a material in a nanotube also offers new
possibilities for investigating dimensionally confined phase
transitions. Particularly intriguing is the conjecture that
matter within the narrow confines of a carbon nanotube might
exhibit a solid-liquid critical point beyond which the
distinction between solid and liquid phases disappears. This
unusual feature, which cannot occur in bulk material, would allow
for the direct and continuous transformation of liquid matter
into a solid. The authors report simulations of the behavior of
water encapsulated in carbon nanotubes that suggest the existence
of a variety of new ice phases not seen in bulk ice, and of a
solid-liquid critical point. Using carbon nanotubes with
diameters ranging from 1.1 nanometers to 1.4 nanometers and
applied axial pressures of 50 megapascals to 500 megapascals, the
authors find that water can exhibit a first-order freezing
transition to hexagonal and heptagonal ice nanotubes, and a
continuous phase transformation into solid-like square or
pentagonal ice nanotubes.
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NAT 2001 412:802
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3. CHEMISTRY: ON DENDRITIC CATALYSIS
D. Astruc and F. Chardac (University of Bordeaux, FR) discuss
dendritic catalysis. The field of dendrimers was developed in the
late 1970s and early 1980s and has exploded during the past
decade. The reason for this, beyond the aesthetic interest in
dendrimers, is their great potential for applications in biology
and materials science. Among the main potential applications of
dendrimers, catalysis is one of the most promising, since
dendrimers offer a unique opportunity to combine the advantages
of homogeneous and heterogeneous catalysis yet maintain the well-
defined molecular features required for a full and detailed
analysis of catalytic events. In general, it is possible to tune
the structure, size, shape, and solubility of dendrimers and
metallodendrimers at will, and to locate catalytic sites at the
core or at the periphery of the molecule. A large number and
variety of metallodendrimers are now known, and it is clear that
structural design innovations of dendrimers have not yet reached
a limit. Researchers have demonstrated that it is possible to
remove the catalyst from the reaction medium after a reaction
carried out in the presence of a metallodendrimer catalyst, with
removal either by precipitation or by ultrafiltration or
ultracentrifugation, and membrane reactors have been developed
for this purpose. Organometallic and inorganic catalysts
supported on organic polymers such as polystyrene or on inorganic
polymers such as silica have been used for some time, but
dendrimers now offer a much better control of the number, shape,
and structure of the catalytic sites and of their micro-
environment.
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CR 2001 101:2991
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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Related Background:
STUDIES OF DENDRIMERS
J.D. Epperson et al (University of South Florida, US) discuss
studies of dendrimer structure. Dendrimers are highly branched
macromolecules with "tree-like" structures and are synthesized by
repetitively linking molecular building blocks AB(subn), with (n)
usually 2 or 3, to a central core. Since both the internal and
external chemical functionalities of dendrimers can be tailored
to alter their physical and chemical properties, several
potential applications are recognized for these polymers,
including catalysis, self-assembly, and molecular recognition and
encapsulation. For example, the incorporation of 2,6-
diamidopyridino H-bonding sites into internal regions of a
polyamido dendrimer facilitates the selective encapsulation of
"guest" molecules such as barbituric acid and azidothymidine
(AZT) into the interior of the dendrimer. Moreover, modification
of the dendritic exterior is being explored to produce dendrimers
for chromatography additives, antibody conjugates, gene therapy,
and electrically conducting materials. The possibility of
entrapping small molecules inside host dendrimers has raised
great interest in the structural and chemical characterization of
these unique macromolecules. However, detailed structural
analysis of dendrimers by means of x-ray crystallography and NMR
spectroscopy have been hindered by the size and fractal nature of
these molecules.
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JACS 2001 123:8583
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SCIENCE-WEEK 12 Oct 2001 http://scienceweek.com
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4. ON ENDOR SPECTROSCOPY
R. Carmieli et al (Weizmann Institute of Science, IL) discuss
ENDOR spectroscopy. X-ray crystallography is by far the most
established and effective method for determining the 3-
dimensional structure of proteins. However, one limitation of
this technique is the difficulty in determining proton positions.
This is particularly problematic in the case of water and the
hydroxyl ion, which cannot be distinguished. Moreover, the
orientation of the OH bond(s) with respect to other protein
residues cannot be determined as long as the proton positions are
unknown. The latter are of significance as they reveal the
presence of hydrogen bonds, which are very important in structure
stabilization and in reactions involving proton transfer. In
metalloproteins or metalloenzymes, water molecules or OH(-)
anions often serve as ligands to the metal ion, and the detailed
characterization of the metal site requires the identification of
all of its ligands, particularly when they differ in the
structural and electronic characteristics that determine the
properties of the site. When the metal center is paramagnetic,
electron-nuclear double resonance (ENDOR) measurements on single
crystals can provide the missing information concerning the exact
location of the protons. ENDOR spectroscopy has been applied
extensively in the past to study metal ion sites in frozen
solutions of metalloproteins and metalloenzymes, and such studies
have led to the identification of ligands and to the
determination of distances between the metal and the magnetic
nuclei.
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JACS 2001 123:8378
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5. RESEARCH ON BLOOD SUBSTITUTES: OPEN SCIENCE VS. COMMERCE
Jean G. Riess (University of California San Diego, US) discusses
blood substitutes. The term "blood substitute" is clearly a
misnomer, since the products under development only transport the
respiratory gases oxygen and carbon dioxide, and for only a
limited period of time. These products provide none of the
complex and interrelated metabolic, regulatory, hemostatic, and
host defense functions of blood. Oxygen carriers are nevertheless
expected to play a pivotal role in easing the increasingly
frequent blood shortages, solve some transfusion-related safety
issues, and in the process, profoundly change patient care and
the practice of transfusion medicine. Further, these carriers may
find therapeutic value in situations where blood is no longer
capable of adequately delivering oxygen to tissues, as in
myocardial infarction or stroke. Therefore the present products
are more accurately described as temporary oxygen carriers, anti-
hypoxic agents, or temporary red blood cell substitutes. Much of
the research on blood substitutes was initiated and driven by the
medical and life sciences research communities, with many
thousands of papers on the subject already published. The
research field is complicated by the fact that commercial, often
venture capital-supported, competition for a market estimated at
several billions of dollars is intense. This means that all
essential information is not available, especially where the
chemistry of the systems under investigation is concerned. It has
happened that extensive animal experimentation was reported on a
product or formulation that was only identified by some
undecipherable code name. It has also happened that untoward
reactions observed during human clinical trials (and the severity
of these reactions) were for a time known only through hearsay
(or through the financial press) before there was mention of them
in the scientific literature.
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CR 2001 101:2797
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6. POINT DEFECTS IN TWO-DIMENSIONAL COLLOIDAL CRYSTALS
A. Pertsinidis and X.S. Ling (Brown University, US) discuss
diffusion of point defects in 2-dimensional colloidal crystals.
Uniform colloidal microspheres dispersed in a solvent will, under
appropriate conditions, self-assemble into ordered crystalline
structures. Using these colloidal crystals as a model system, a
great variety of problems of interest to materials science,
physical chemistry, and condensed matter physics have been
investigated during the past two decades. Recently, it has been
demonstrated that point defects can be created in 2-dimensional
colloidal crystals by manipulating individual particles with
optical tweezers. Direct imaging of these defects verified that
their stable configurations have lower symmetry than the
underlying triangular lattice, as predicted by numerical
simulations for a number of 2-dimensional systems. It was also
observed that point defects can dissociate into pairs of well-
separated dislocations, a topological excitation especially
important in two dimensions. The authors report they used a
similar experimental system to study the dynamics of mono- and
di-vacancies in 2-dimensional colloidal crystals, and that they
see evidence that the excitation of point defects into
dislocation pairs enhances the diffusion of di-vacancies.
Moreover, the hopping of the defects does not follow a pure
random walk, but exhibits surprising memory effects. The authors
suggest their results may be relevant for explaining the dynamics
of other 2-dimensional systems.
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NAT 2001 413:147
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7. ON CELL-CYCLE CHECKPOINTS
Robert T. Abraham (Duke University, US) discusses cell-cycle
checkpoints. The genomes of eukaryote cells are under continuous
assault by environmental agents (e.g., ultraviolet light and
reactive chemicals) as well as assault by the byproducts of
normal intracellular metabolism (e.g., reactive oxygen
intermediates and inaccurately replicated DNA). Whatever the
origin, genetic damage threatens cell survival and in metazoans
leads to organ failure, immunodeficiency, cancer, and other
pathologic consequences. To ensure that cells pass accurate
copies of their genomes on to the next generation, evolution
effectively overlaid the core cell-cycle machinery with a series
of surveillance pathways called "cell-cycle checkpoints". The
overall function of these checkpoints is to detect damaged or
abnormally structured DNA, and to coordinate cell-cycle
progression with DNA repair. Typically, cell-cycle checkpoint
activation slows or arrests cell-cycle progression, thereby
allowing time for appropriate repair mechanisms to correct
genetic lesions before they are passed on to the next generation
of daughter cells. In a broader context, cell-cycle checkpoints
can be envisioned as signal transduction pathways that link the
pace of key cell-cycle phase transitions to the timely and
accurate completion of prior contingent events. Checkpoint
surveillance functions are not confined solely to the happenings
within the nucleus, since extranuclear parameters, such as growth
factor availability nd cell mass accumulation, also govern the
pace of the cell cycle.
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GD 2001 15:2177
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Related Background:
THEORETICAL BIOLOGY: CONTROLLING CELL CYCLE DYNAMICS
During the past few decades, studies of the *cell division cycle
have revealed many of the genes and proteins that drive and
regulate cell division, and methods for the artificial control of
the cell cycle have become apparent. Such manipulations are
typically achieved by introducing mutations into the genes that
regulate the cycle. These mutations, however, usually result in
uncontrolled cell division, or complete suppression of cell
division, or cause the cell to commit fatal errors during the
cell cycle. ... ... T.S. Gardner et al (3 authors at Boston
University, US), using mathematical modeling of cell division
cycle dynamics, report a potential mechanism for the precise
control of the frequency of cell division and regulation of the
size of the dividing cell. The work of the authors involves the
application of a specific biochemical constraint to two already
existing mathematical models of cell cycle dynamics (models by A.
Goldbeter; B. Novak and J.J. Tyson). The authors report that
control of the cell cycle in their application is achieved by
artificially expressing a protein that reversibly binds and
inactivates any one of the cell division cycle proteins. In the
simplest case (the Goldbeter model), the frequency of cell
division cycle oscillations can be increased or decreased by
regulating the rate of synthesis, the binding rate, or the
equilibrium constant of the binding protein. In a more complex
model of cell division (the Novak-Tyson model), the authors
report that the same reversible binding reaction can alter the
mean cell mass in a continuously dividing cell. The authors
suggest that because their control scheme is general and requires
only the expression of a single protein, it provides a practical
means for tuning the characteristics of the cell cycle in vivo.
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PNAS 1998 95:14190
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Notes:
... ... *cell division cycle: (cell cycle) Prior to each cell
division, a cell passes through a series of preparatory stages
that are collectively known as the "cell cycle". The cycle is
considered to begin when two new cells are formed by the division
of a single parent cell, and it ends when one of these new cells
in turn divides to form two more cells. The paramount process is
the transfer of a complete set of genetic instructions to each
new cell. The periodicity of the cycle varies from one type of
cell to another, and within a single type, the periodicity can
also vary in response to ambient conditions. Laboratory methods
are now available to not only control the periodicity of the cell
cycle, but also to synchronize the periodicities of a population
of cultured cells. The obvious oscillatory behavior of biological
cells has for many decades been the focus of much research
involving mathematical modeling.
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SW 1999 15 Jan
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8. ON IMMUNE CELLS AND MEMBRANE LIPID RAFTS
L.M. Pierini and F.R. Maxfield (Cornell University, US) discuss
lipid rafts. To effectively combat invading pathogens, immune
cells must rapidly switch from approximately spherical resting
cells to polarized migratory cells, which then move in a directed
fashion to the site of infection. The dramatic metamorphosis of
leukocytes into polarized cells and their subsequent migration
are two of the most fascinating phenomena in cell biology.
Polarization and migration require the spatial and temporal
control of signal transduction molecules so that substrate
attachment and membrane extension occur at the cell front, while
detachment and membrane retraction happen at the rear. How do
cells coordinate signaling molecules to perform contrasting
functions at opposite poles? It has long been appreciated that
there is polarization in the protein machinery involved in cell
migration. However, it is becoming evident that lipids are also
distributed nonuniformly, and that the distribution of lipids is
an important factor for directional integration. But although it
is now understood that lipids are distributed nonrandomly in the
plasma membrane and that this has important consequences for cell
signaling and other functions, the precise nature of these lipid
inhomogeneities ("microdomains") remains somewhat enigmatic --
partly because the lipid microdomains are apparently in a size
range (10 to 300 nanometers) that is below the resolution of
optical microscopy. In the current view of the plasma membrane,
certain lipids and proteins assemble into dynamic, sub-micron-
sized lateral organizations that function to facilitate signal
transduction events. Regions of the plasma membrane that are
enriched in sphingolipids and cholesterol are thought to exist in
a liquid-ordered phase that confers detergent resistance to these
structures and allows for their ready isolation by flotation on
sucrose density gradients. One model is that signaling molecules
are recruited to these small "rafts" from a largely liquid-
disordered membrane.
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PNAS 2001 98:9471
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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Related Background:
CAVEOLAE IN THE PLASMA MEMBRANE
J-S. Shin and S.N. Abraham (Duke University, US) discuss
invagination in the plasma membrane. Caveolae -- flask-shaped
invaginations in the plasma membrane -- are present on the
surfaces of many types of mammalian cells, including *endothelial
cells, *smooth muscle cells, and *adipocytes. Like *lipid rafts
(their close relatives), caveolae are plasma membrane assemblies
of glycosphingolipids and cholesterol that are associated with
specific molecules, including *signaling proteins. Caveolae often
contain the protein *caveolin and have proteins anchored to
glycosylphosphatidylinositol, a plasma membrane phospholipid. But
exactly why cells have caveolae or lipid rafts has been a puzzle.
They are believed to be involved in cholesterol transport, the
transport of solutes across endothelial cells, tumor suppression,
and signal transduction through immune and *growth factor
receptors. In addition, it seems they have been commandeered by
various species of viruses, parasites, bacteria (and even
bacterial toxins) to enable these pathogens to enter host cells.
Classic endocytosis (cellular uptake of extracellular agents)
depends on *clathrin-coated pits and involves an intracellular
pathway in which *lysosomes fuse with internalized vesicles,
degrading their contents. In contrast, and clearly of benefit to
pathogens, caveolae-dependent endocytosis does not feed into the
lysosome pathway and does not result in degradation of the
contents of caveolar vesicles.
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SCI 2001 293:1447
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Notes:
... ... *endothelial cells: Endothelial cells are flat cells
forming a layer lining blood vessels, lymphatic vessels, the
heart, etc.
... ... *smooth muscle cells: Smooth muscle was originally
differentiated from striated muscle on the basis of microscopic
appearance, but there are important other differences both
functional and molecular. In general smooth muscle is
specialized for slow sustained contractions such as those
involved in the control of the diameters of blood vessels.
... ... *adipocytes: These are fat cells in connective tissue,
each cell containing one or more fat globules that compress the
cytoplasm of the cell into a thin envelope. The fat globules are
essentially energy storage bins.
... ... *lipid rafts: Lateral heterogeneities in the classical
fluid-mosaic model of cell membranes are now thought of as
domains or "rafts" comprising clusterings of various lipids and
*anchored proteins, these rafts dictating the sorting of
associated proteins and/or providing sites for assembling
cytoplasmic signaling molecules.
... ... *signaling proteins: In general, extracellular or
intracellular proteins involved in directed pathways that result
in specific cellular responses.
... ... *caveolin: Dog caveolin has 178 amino acids and a
molecular weight of 20.6 kilodaltons.
... ... *growth factor: In general, in this context, a "growth
factor" is any specific extracellular substance involved in the
replication of cells.
... ... *clathrin: A 180 kilodalton protein (see related
background material below).
... ... *lysosomes: A lysosome is a cytoplasmic membrane-bound
vesicle 5 to 8 nanometers in diameter and containing a variety of
glycoprotein hydrolytic enzymes used to digest foreign material
or defective organelles.
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SCIENCE-WEEK 21 Sep 2001 http://scienceweek.com
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Related Background:
STRUCTURAL MECHANISMS OF ENDOCYTOSIS
The term "endocytosis" refers in general to any process in which
materials are taken into a biological cell by membrane-bound
vesicles that pinch off from the plasma membrane. When the
material taken up consists of large fragments or whole organisms,
the process is called "phagocytosis". "Receptor-mediated
endocytosis" is a specialized type of endocytosis that brings
specific macromolecules into the cell. Many hormones, *growth
factors, *lymphokines, and nutrients, enter the cell in this
manner. During receptor-mediated endocytosis, the external ligand
first binds to its corresponding plasma membrane receptor; the
receptor-ligand complex then becomes concentrated in specific
regions of the plasma membrane, regions called "coated pits".
Each coated pit is an infolding of the plasma membrane whose
cytoplasmic surface is coated with a polyhedral lattice
constructed from the protein clathrin. The clathrin molecule
consists of 3 large polypeptide chains and 3 small polypeptide
chains organized into a 3-pronged structure, a "triskeleton", and
clathrin triskeletons polymerize with one another to form the
polyhedral lattice. After ligand-receptor complexes have become
clustered within a coated pit, the invaginated membrane pinches
off and becomes internalized as a coated vesicle. This coated
vesicle is initially surrounded by a cage of clathrin molecules,
but this clathrin coat is quickly shed, and vesicles soon
accumulate in what is known as the "endosome compartment" of the
cell. Nearly all the details of the above brief description of
receptor-mediated endocytosis were completely unknown several
decades ago; our current picture is a result of intensive
research in many laboratories, research combining electron
microscopy, biochemistry, and molecular biology.
... ... M. Marsh and H.T. McMahon (2 installations, UK) present a
review of recent research on endocytosis, with a focus on
developments in the clathrin-mediated endocytic pathway. The
authors make the following points:
1) The uptake, or endocytosis, of extracellular material
into cells in membrane-bound vesicles has been of great interest
to cell biologists for most of this century. The many functions
in which endocytosis plays a role include *antigen presentation,
nutrient acquisition, *clearance of apoptotic cells, pathogen
entry, receptor regulation, and *synaptic transmission.
2) Concerning clathrin-mediated endocytosis, a high-
resolution 3-dimensional view of the clathrin coat is beginning
to emerge. Clathrin-coated vesicle formation is a complex process
dependent on, and regulated by, the activities of a set of
intracellular proteins that are recruited through various
protein-protein and protein-lipid interactions. *Phosphorylation
and dephosphorylation are apparently key regulators of these
interactions and of the activities of the involved proteins, but
the precise order in which the different components act at each
step of the process remains to be solved.
3) Of all the coat-mediated transport events characterized
so far in cell biology, endocytic clathrin-coated vesicles are
unique in their degree of complexity. This may reflect a need for
a higher order of control to coordinate clathrin-mediated
endocytosis in various important processes: e.g., the rapid
recovery of synaptic vesicles membranes, or cellular responses to
environmental stimuli.
4) The authors conclude: "The developments seen over the
past couple of years will continue; new insights and structures
will be published soon. The challenge for the new century will be
to understand how these structures interact to drive endocytosis.
-----------
SCI 1999 285:215
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Notes:
... ... *growth factors: Growth factors are peptide hormones that
regulate the growth of cells and tissues.
... ... *lymphokines: (interleukins) Hormones secreted by certain
antigen-processing cells of the immune system, the hormones
causing immune cells specific for the antigen to proliferate.
... ... *antigen presentation: In general, "antigen presentation"
refers to the presentation of antigens on the surfaces of
antigen-presenting cells of the immune system. In order for an
antigen to be presented on the surface of such a cell, the
antigen must first by taken up by the cell via endocytosis. [See
report #5, this issue of SW.]
... ... *synaptic transmission: This is a general term referring
to the events mediating the membrane-to-membrane interaction
between a neuron and another neuron, or a neuron and a muscle or
gland cell, or a neuron and a sensory receptor cell. The junction
is called a "synapse", and in many cases junction transmission
involves release and uptake of "transmitter" substances.
... ... *Phosphorylation: In general, the process of introducing
a phosphoric acid group into a molecule. Biochemical
phosphorylation reactions are of importance in the trapping of
energy, in the formation of biosynthetic intermediates during
metabolic processes, and in the control of the activity of many
enzymes and other proteins.
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SW 1999 6 Aug
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9. CALCITIC MICRO-LENSES AND PHOTORECEPTION IN BRITTLESTARS
J. Aizenberg et al (Bell Laboratories, US) discuss calcitic
microlenses in brittlestars. Echinoderms in general, and
especially the brittlestars (Ophiuroidea), exhibit a wide range
of responses to light intensity, from a largely light-indifferent
behavior to pronounced color change and rapid escape behavior.
Photosensitivity in most echinoderms has been attributed to
"diffuse" dermal receptors. The authors report that certain
single calcite crystals used by brittlestars for skeletal
construction are also a component of specialized photosensory
organs, conceivably with the function of a compound eye. The
analysis of arm ossicles in Ophiocoma showed that in light-
sensitive species, the periphery of the labyrinthic calcitic
skeleton extends into a regular array of spherical
microstructures that have a characteristic double lens design.
These structures are absent in light-indifferent species.
Photolithographic experiments in which a photoresist film was
illuminated through the lens array showed selective exposure of
the photoresist under the lens centers. The authors suggest their
results provide experimental evidence that the microlenses are
optical elements that guide and focus the light inside the
tissue. The estimated focal distance (4 to 7 microns below the
lenses) coincides with the location of nerve bundles -- the
presumed primary photoreceptors. The lens array design
effectively minimizes spherical aberration and birefringence and
detects light from a particular direction. The optical
performance is further optimized by phototropic chromatophores
that regulate the dose of illumination reaching the receptors.
The authors suggest these structures represent an example of a
multifunctional biomaterial that fulfills both mechanical and
optical functions.
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NAT 412:819
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10. OLD WORLD SOURCES OF FIRST NEW WORLD HUMAN INHABITANTS
C.L. Brace et al (University of Michigan, US) discuss the origins
of the first New World inhabitants. Genetic and archeological
evidence supports a northeast Asian source for the first human
inhabitants of the Western Hemisphere. Some interpretations have
suggested that the distribution of linguistically identifiable
groups in the New World may have been the result of separate
prehistoric population movements into the Western Hemisphere.
From the sparse archeological evidence and complementary
molecular genetic data from living populations, an initial entry
date of approximately 15,000 years ago can be postulated.
Questions concerning the initial human settlement of the New
World have involved such matters as the initial date of entry,
route of access, whether there was a single or several dissimilar
waves of people, and how these are genetically related both to
living American Indian groups as well as to Asian and Pacific
populations and possibly to other Old World peoples. Issues of
geology, archeology, and legal ownership are all involved. The
authors report a study using human craniofacial data to assess
the similarities and differences between recent and prehistoric
Old World samples, and between these samples and a similar
representation of samples from the New World. The authors suggest
a combination of two different regional populations appears to
have been involved in the initial human expansion into the
Western Hemisphere, the regions in question a mainland East Asian
core located in China north of the Tropic of Capricorn and south
of the Gobi Desert, and a northwestern component originally
running from near Moscow to the Atlantic coast of Europe north of
the Mediterranean Sea. The archeological record indicates that
both of these components had been separate in the Middle
Pleistocene, with the northwestern component expanding eastward
to exploit unoccupied terrain at the northern edge of Asia in the
Middle Paleolithic approximately 200,000 years ago.
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PNAS 2001 98:10017
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11. EVOLUTION OF BACTERIAL PATHOGENESIS AND SYMBIOSIS
H. Ochman and N.A. Moran (University of Arizona, US) discuss the
evolution of bacterial pathogenesis and symbiosis. Bacteria form
intimate and quite often beneficial associations with a variety
of multicellular organisms, and the diversity of these
associations, combined with their agricultural and clinical
importance, have made them a prominent focus of research.
Estimates of bacterial diversity from various environmental
sources show that pathogens represent a very small portion of
microbial species. Potential hosts, especially humans with their
broad geographic distribution and high population densities, are
constantly besieged by bacteria in the environment, but most
bacteria do not cause infections. Not only are pathogenesis and
symbiosis relatively rare among bacterial species, it is a
derived condition within bacteria as a whole, as evident from the
fact that bacteria existed well before their eukaryotic hosts.
Traditionally, evolutionary biologists have viewed mutations
within individual genes as the major source of phenotypic
variation leading to adaptation through natural selection and
ultimately generating diversity among species. Although such
processes must contribute to the initial development of gene
functions and their subsequent fine-tuning, changes in genome
repertoire occurring through gene acquisition and deletion are
the major events underlying the emergence and evolution of
bacterial pathogens and symbionts. Furthermore, pathogens and
symbionts depend on similar mechanisms for interacting with hosts
and show parallel trends in genome evolution.
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SCI 2001 292:1096
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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Related Background:
MEDICAL BIOLOGY: THE SEARCH FOR UNRECOGNIZED PATHOGENS
Molecular biology is the "New Biology" of the 20th century, and
it has impacted virtually every field in biology and applied
biological science. Two important research areas whose character
has completely changed in recent decades are microbiology, the
study of microorganisms, and medical microbiology, the study of
pathogenic microorganisms. ... ... David A. Relman (Stanford
University, US) presents a review of current strategies in
molecular medical microbiology, with a focus on the search for
unrecognized pathogens. The author makes the following points:
1) Considering only human parasitic and *symbiotic microbes
that have been successfully cultivated in the laboratory --
bacteria, viruses, and unicellular *eukaryotes that inhabit the
human body -- the number and variety of relations between microbe
and host are enormous. Yet more than 99 percent of microorganisms
resist cultivation in the laboratory and can only be identified
or characterized by the use of molecular approaches. Since nearly
all available information concerning the composition of microbes
normally resident in the human body (endogenous microbes) and the
role of microbes in infectious human disease has been based on
laboratory cultivation, one must conclude that unrecognized
pathogens may be the cause of many serious diseases that
currently are without convincing etiology.
2) During the past 15 years, the pathogens for the following
infectious diseases were revealed for the first time:
... ... *Peptic ulcer disease: Helicobacter pylori (1984)
... ... *Non-A, Non-B Hepatitis: Hepatitis C virus (1989)
... ... *Bacillary angiomatosis: Bartonella henselae (1990)
... ... *Whipple's disease: Tropheryma whippelii (1991)
... ... *Hantavirus pulmonary syndrome: Sin Nombre virus (1993)
... ... *Kaposi's sarcoma: KS-associated herpesvirus (1994)
With the exception of Helicobacter pylori, all of the above
infectious agents were first identified directly from clinical
specimens using *molecular genotyping.
3) In the detection and identification of human microbial
pathogens, a reliance on laboratory cultivation of the microbe
poses potential pitfalls: a) we are largely ignorant of the
environmental conditions required by some microorganisms for
growth, and we are thus unable to replicate them in the
laboratory; b) *phenotypic traits are difficult to quantitate,
and they can be misleading. In contrast, genotypic traits
generally provide reliable and quantifiable information and
characterization of infectious agents.
4) There are acute and chronic diseases and syndromes over a
wide range of characteristics that deserve to be the focus of
broad cultivation-independent searches for microbial pathogens.
In short, a substantial amount of unexplained illness resembles
infectious disease. Most clinicians, for example, are familiar
with a scenario in which a previously healthy individual develops
an acute life-threatening illness with signs of infection but
with negative diagnostic test results. Evidence indicates that a)
unexplained death or unexplained critical illness occurs in 0.5
to 2.0 persons per 100,000 population in the US per year; b)
broad-range bacterial *ribosomal DNA *PCR analysis has revealed
known disease-causing agents as a probable or definite pathogen
in certain cases; and c) little thought or attention has been
directed at the selection and processing of clinical specimens
appropriate for molecular pathogen discovery.
5) The application of new pathogen discovery methods is
certain to alter our perspective on microbial disease causation.
For example, improvements in microbial detection and
discrimination may generate data that challenge the traditional
association of one microorganism with one diseased host. We
currently accept the concept of polymicrobial disease causation
in the setting of abscess formation; however, the same concept
may apply to other types of disease, including rheumatic or
"autoimmune" disease, and cancer.
-----------
SCI 1999 284:1308
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Notes:
... ... *symbiotic microbes: In biology, symbiosis is an intimate
and protracted association of individuals of different species.
The term is ordinarily used for mutualistic symbiosis, i.e.,
symbiosis of mutual benefit to the organisms involved. In this
context, the bacteria that normally inhabit the human intestine
and which aid in digestion are symbiotic microbes.
... ... *eukaryotes: Eukaryotes are cells containing membrane-
bound organelles such as a nucleus.
... ... *Peptic ulcer disease: Helicobacter pylori: H. pylori is
an actively motile rod-shaped bacterium with multiple flagella
(whip-like extensions involved in locomotion) at one pole.
... ... *Non-A, Non-B Hepatitis: Hepatitis C virus: The hepatitis
C pathogen is a 30 to 60 nanometer spherical virus with a single-
stranded RNA genome containing approximately 10,000 nucleotide
bases.
... ... *Bacillary angiomatosis: Bartonella henselae: The
bacterium B. henselae is the pathogen that causes "cat-scratch"
disease, and is also involved in bacillary angiomatosis, a
disease predominantly of immunosuppressed individuals,
particularly of AIDS patients. Bacillary angiomatosis is
characterized by circumscribed lesions in almost every organ.
... ... *Whipple's disease: Tropheryma whippelii: The bacterial
organism T. whippelii is only tentatively named, since cultures
to isolate the organism have been unsuccessful. The organism is a
bacillus. Whipple's disease is characterized by fever, abdominal
pain, diarrhea, weight loss, and migratory severe pain in the
joints. A unique bacterial ribosomal RNA sequence has been
identified by *PCR from the lesions.
... ... *Hantavirus pulmonary syndrome: Sin Nombre virus:
Hantavirus is classified as a subtype of bunyavirus, which are
spherical particles containing a single-stranded RNA genome 11 to
21 kilobases in size. In general, the bunyaviruses are one of
several pathogens involved in rodent-borne hemorrhagic fevers
worldwide. The virus measures 80 to 120 nanometers. Hantavirus
pulmonary syndrome is newly recognized in the US, the pathogen
transmitted by deer mice, the disease apparently 60 percent
fatal.
... ... *Kaposi's sarcoma: KS-associated herpesvirus: Kaposi's
sarcoma is an ordinarily rare cancer that can be common in humans
with compromised immune systems (for example, in AIDS). KS-
associated herpesvirus has been detected in over 90 percent of
Kaposi's sarcomas. All herpesviruses have a core of double-
stranded DNA, and range from 100 to 200 nanometers in diameter,
depending on the life cycle stage.
... ... *molecular genotyping: In general, the term "genotyping"
refers to the determination of genetic constitution, as
distinguished from determination of physical appearance
(phenotyping). Molecular genotyping refers to determination of
all or part of the genome.
... ... *phenotypic traits: In general, the observed properties
of an organism. Phenotypic traits are produced by the interaction
of the genotype with the environment. In general, categorization
of an organism on the basis of shape and size is phenotyping;
categorization of an organism on the basis of genome analysis is
genotyping.
... ... *ribosomal DNA: A ribosome (not to be confused with
riboZYME) is a small particle, a complex of various ribonucleic
acid (RNA) component subunits and proteins, that functions as the
site of protein synthesis. There is no DNA in ribosomes. The term
"ribosomal DNA" refers to any DNA sequence that codes for
ribosomal RNA.
... ... *PCR analysis: Polymerase chain reaction (PCR): A
technique for isolating and amplifying any specifically desired
DNA sequence. The reaction is facilitated by a heat-stable DNA
polymerase (e.g., Taq, which is obtained from a thermophilic
bacterium) that can withstand the many cycles of heating and
cooling involved in the technique. PCR is considered by many
molecular biologists to be the most important technical advance
in molecular biology in the second half of the 20th century. The
inventor of the technique, Kary Mullis, received the Nobel Prize
for Chemistry in 1993 for his discovery.
-----------
SW 1999 23 Jul
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12. ON THE CLASSICAL BIOGENIC AMINES
R.T. Premont et al (Duke University, US) discuss biogenic amines.
The classical biogenic amines (serotonin, dopamine, and
histamine) play important roles as neuromodulators. These
neurotransmitters are synthesized from precursor amino acids in
specific neurons and stored in vesicles of synaptic terminals for
release into the synaptic cleft in response to neuronal
depolarization. In the extracellular space, the released amines
bind to specific receptor proteins -- primarily of the G protein-
coupled receptor family -- on both presynaptic and postsynaptic
cells, where they modulate intracellular second messenger
pathways to alter to alter the signaling of the fast
neurotransmitter-gated ion channels. After release, amines are
taken back rapidly into the presynaptic neurons via specific
transporters for repackaging into vesicles and re-release, or are
degraded to inactive products. The neurochemistry of biogenic
amines is relatively well understood, including the control of
amine synthesis from precursor amino acids, their storage and
release, and their reuptake versus degradation. Imbalances in the
levels of these amine neuromodulators are thought to underlie
altered brain function in many pathological conditions, including
dystonias, Parkinson's disease, schizophrenia, drug addiction,
and mood disorders. This obvious involvement of biogenic amines
in multiple brain disorders has led to many years of effort to
understand their action and to therapeutic interventions to
correct deficiencies through either activating or inhibiting the
synthesis, storage, signaling, or metabolism of individual
amines.
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PNAS 2001 98:9474
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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13. IN FOCUS: ON EARTH'S GRAVITY AND THE MANTLE
"Studies of the Earth's gravity field have long shown that
despite the difference in densities between the uppermost layers
of rocks under the oceans and under continents, the amount of
mass per unit area under continents very nearly equals that under
the ocean, a condition known as _isostasy_. In the early 1960s,
knowledge of the Earth's gravity field increased significantly.
Observations of the orbits of satellites coming close to the
Earth's surface established that regional variations of gravity
exist over large horizontal distances... [and] these cannot be
accounted for in terms of the near-surface crustal structure. The
analysis of the Earth's gravitational field proceeds by expanding
the external gravitational potential in terms of a series of
spherical harmonics, a form of mathematical analysis used to
describe a pattern on the surface of a sphere. The analysis works
by breaking down the large pattern into a sequence of simple
patterns in a hierarchy of increasing complexity. 'Low-order'
spherical harmonics describe large-scale variations; for example,
order one represents a function that is positive in one
hemisphere and negative in the other. A 'zonal' spherical
harmonic does not vary with latitude; a 'sectoral' harmonic does
not vary with longitude; 'tesseral' harmonics have neither of
these symmetries. If the Earth were fluid, devoid of strength,
certain zonal harmonics would vanish, and the Earth's rotation
and internal distribution of density would determine the
remaining harmonics. The tesseral harmonic and the sectoral
harmonic would also vanish for a fluid Earth. But this does not
happen. A comparison between the observed values and the values
appropriate for a fluid Earth, rotating at the same velocity as
the Earth and having the same radial density distribution as
estimated by seismologists in 1963, provides a measure of the
stresses supporting the deviations from a fluid Earth. The
harmonics indicate an Earth that is not a fluid, but [an Earth
that] has finite strength. A comparison between the observed
gravity field and the field expected from an isostatically
compensated crust shows two striking features. For the low-order
harmonics (those representing large-scale variation), the
gravitational anomaly expected from the continental crust is
small compared with the observed potential and is of opposite
sign. The small magnitude of the crustal contribution indicates
that the mass anomaly that gives rise to the observed values must
come from somewhere else, and the only plausible alternative is
the mantle. The failure of the continental crust to account for
the observed values of gravity requires density inhomogeneities
that extend well below the oceanic and continental upper layers.
The correlation of the large-scale anomalies in the external
potential with the continent ocean structure requires a different
density distribution for the rocks at depth under oceans and
under continents. In short, the mantle under the continents
appears to be different from the mantle under the oceans."
-----------
Gordon J. MacDonald: How Mobile is the Earth?
in: Naomi Oreskes: _Plate Tectonics: The Insider's History of the
Modern Theory of the Earth_
(Westview Press, Cambridge, MA 2002, p.116)
To be published February 2002
For more information or to order:
http://www.amazon.com/exec/obidos/ASIN/0813339812/scienceweek
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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14. FROM PRAXIS:
EFFECTS OF COMMERCIALIZATION ON RESEARCH
G. Laver et al (Australian National University, AU) discuss the
effects of commercialization on research. The authors suggest
that Australian universities are now in a dangerous state, mainly
because they have had little or no increase in real funding since
1996. Lacking a tradition of private endowments, Australian
universities are being encouraged to an unprecedented degree to
seek commercial finance for projects. The authors suggest that
commercialization of basic research will never lead to a
"knowledge nation", and basic research will not flourish in a
commercial environment when profit dictates the direction of
science. The influenza drug Relenza was not invented by a
pharmaceutical company, but resulted from years of curiosity-
driven basic research in publicly-funded institutions in
Australia and other countries. These discoveries were then
commercialized by GlaxoWellcome. The authors state that in their
experience commercialization of university research leads to a
diminution in the free flow of ideas, a focus on more applied
projects, and serious conflicts of interest. To address the
problems inherent in university research driven by commercial
considerations, we need to identify the conditions required for
good science to flourish. Good scientific research is not done by
corporations, or by the strategic teams beloved of politicians
and administrators, but through ideas which develop in the minds
of individual scientists. Of course scientific discoveries made
in universities should be developed for commercial use. The ideal
situation is vastly increased government support for curiosity-
driven basic research and a mechanism to commercialize any
discoveries made in this way.
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NAT 2001 412:765
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PRAXIS 12 Nov 2001 http://scienceweek.com/praxis
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Related Background:
CORPORATE PAYMENTS TO SCIENTISTS FOR LETTERS TO JOURNALS
A blatant instance of corporate pressure in science was recently
revealed when a newspaper, the *St. Paul Pioneer Press* of St.
Paul, Minnesota (US), reported that more than a dozen scientists
received US$156,000 from the tobacco industry to write letters to
scientific journals disputing the carcinogenic effects of second-
hand smoke. The report was based on confidential industry
documents produced in a current litigation. Among the scientific
journals involved were the *Journal of the National Cancer
Institute*, *Journal of the American Medical Association*, *The
Lancet*, and *Pediatrics*. The authors were paid US$2250 to
US$10,000 per letter by the Tobacco Institute, and apparently two
law firms representing the industry revised some letters before
submission to the journals. According to the examined documents,
the strategy of the Tobacco Institute focused on recruiting
scientists "at or near retirement with no dependence on grant-
dispensing bureaucracies." Some of the journal editors involved
are apparently unconcerned, stating that what is important is
whether the content of a letter is solid. However, Richard
Horton, editor of *The Lancet*, says his reaction is one of
"disgust", and that the writing of such letters is "at best
unethical and at worst an example of research misconduct."
Cardiologist Stanton Glantz (University of California San
Francisco, US) says of the tobacco industry letters: "They are
basically building up a record they could use for political and
legal purposes." One now wonders what corporate groups aside from
the tobacco industry have been promoting by generous financial
inducements the writing of letters by scientists to scientific
journals on other scientific topics of legal, political, or
commercial significance.
(Nature 13 Aug 98 394:609) (Science 14 Aug 98 281:895)
(Science-Week 4 Sep 98)
-------------------
Related Background:
NEW STUDY FINDS CORPORATE GIFTS IMPLY CORPORATE CONTROL
Blumenthal et al (2 installations, US) report an anonymous survey
of 2167 scientists working at 50 research-intensive universities
in the US. More than half of the university scientists who
received gifts of research material from pharmaceutical companies
or biotechnology companies report that the donors expect to exert
influence over their work, including review of academic papers
before publication, and retention of patent rights for commercial
discoveries. This is apparently the first study to examine
relations between commercial interests that give gifts of
research materials and the scientists who receive them. Unlike
research grants and contracts, gifts to US scientists are largely
unregulated by universities and are usually dismissed as
insignificant. Christopher Scott, director of research
development for the Stanford University Medical Center, says:
"There has been, in essence, a gray market of research based on
gifts for many, many years."
-----------
JAMA 1998 1 Apr
NYT 1998 1 Apr 98
SW 1998 10 Apr 98
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Related Background:
INTIMIDATION OF RESEARCHERS BY SPECIAL INTEREST GROUPS
A recent issue of the highly respected New England Journal of
Medicine includes a 5 page exchange of letters on the subject of
intimidation of researchers by special interest groups. The
letters concern three different special interest-clinical science
entanglements: 1) a research study of multiple chemical
sensitivity; 2) the public health hazard of a marketed chemical
(tryptophan) product; 3) a clinical investigation of the outbreak
of interstitial lung disease among workers in a nylon flocking
plant. The first situation involves an accusation of attacks
against a researcher by special interests opposed to the
researcher's published results; the second situation involves an
accusation of peer review corruption by a large corporate entity
confronted with a billion-dollar damage suit; the third situation
involves an accusation of censorship and harassment of a medical
specialist by a manufacturing plant, a medical school
administration, and a hospital. These are all complicated
entanglements, and one cannot do full justice to them in a few
hundred words. But all parties on both sides of the issues
present their views, and these 5 pages of letters provide a
textbook illustration of the problems existing at the societal
interfaces of science. The letters are in response to an article
on the subject by Richard A. Deyo et al that appeared in NEJM on
April 14, 1997 (336:1176).
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NEJM 1997 30 Oct
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Related Background:
ACADEMIC JOURNAL REVISITS CORPORATE CORRUPTION OF SCIENCE
*Lingua Franca*, a highly respected general academic journal, has
published a review of some recent history in the arena of
corporate corruption of science and scientific research. The
fundamental problem is simply stated: Some corporations fund
scientific research with expectations, often contractual, of
control of publication and the final wording of conclusions in
the resultant papers. Several prestigious journals still do not
require scientists who report research results to reveal any
connections to interests that might profit from their
conclusions. But most of the scientific community is determined
to put an end to any corruption. The story is still to be played
out. (Lingua Franca June/July 1997)
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PRAXIS 12 Nov 2001 http://scienceweek.com/praxis
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SCIENCE-WEEK 23 Nov 2001 http://scienceweek.com
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15. SOURCES:
------------
AS: American Scientist; CEN: Chemical & Engineering News;
CR: Chemical Reviews; GD: Genes & Development;
GR: Genome Research; JACS: J. Amer. Chemical Society;
JAMA: J. Amer. Medical Association; JCE: J. Chem. Education;
MMWR: CDC Morbidity and Mortality Weekly Report; NAT: Nature;
NATM: Nature Medicine; NEJM: New England J. Medicine;
NS: New Scientist; NYT: New York Times; NYR: New York Review;
PNAS: Proceedings of the National Academy of Sciences;
PRL: Physical Review Letters; PT: Physics Today; PRAX: PRAXIS;
SA: Scientific American; SCI: Science; SW: ScienceWeek;
TS: The Scientist.
In the text, the affiliation following the names of authors is
the affiliation of the lead author.
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