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ScienceWeek
SCIENCE-WEEK - March 1, 2002 - Vol. 6 Number 9
An Email Research Digest Published Weekly Since 1997
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Imagine a survivor of a failed civilization with only
a tattered book on aromatherapy for guidance in arresting
a cholera epidemic. Yet, such a book would more likely
be found amid the debris than a comprehensible medical
text.
-- James Lovelock
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Section 1
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Contents of this Issue (Full reports in Section 2):
[(*) = extensive background material]
Basic Sciences
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1. Spectroscopy of Transition States in Bacteriorhodopsin
2. Materials Science: On Elastic Membranes
3. On Attosecond Measurements
4. On Optical Solitons (*)
5. Earth Sciences: On the North Atlantic Oscillation
6. Liquid Water: Current Research Problems (*)
7. Mechanisms of Commensalism in Microorganisms
8. Body Patterning in Development
9. Neural Circuits in Olfaction (*)
10. Single-Molecule Analysis of Chemotactic Signaling
11. Neuropsychology of Time
12. On Epithelial Cells
Praxis
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13. On the Semiconductor-Electrolyte Interface
14. Carbon Exchange by Terrestrial Ecosystems
15. On High-Resolution Scanning Tunneling Microscopy
16. The Art of Total Synthesis
17. Self-Assembly of Metal Nanostructures on Polymer Scaffolds
18. Conduction of Water Through Hydrophobic Nanotubes
19. Molecular Biology in Historical Research: Genetic
Characterization of the Body Attributed to the Evangelist Luke
20. On the Nocebo Phenomenon (*)
21. Estimating Human Health Risk From UK Sheep BSE Infection
22. On Cryptococcus Neoformans - A Fungal Pathogen
23. Cancer Diagnosis and Gene Expression Signatures
24. On Susceptibility Genes for Major Mental Illnesses
Miscellany
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25. Postdoctoral Fellowship Profile:
Laboratory of Laura Manuelidis, Yale University
26. In Focus: On the First Major Biotechnology Patent
27. New Books
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Section 2
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1. SPECTROSCOPY OF TRANSITION STATES IN BACTERIORHODOPSIN
The term "photoisomerization" refers to the production of an
isomer by radiant energy (photolysis). Bacteriorhodopsin is a
bacterial protein resembling animal rhodopsin ("visual purple"),
the light-sensitive visual pigment found in the retinas of
animals. In bacteria where it is found, bacteriorhodopsin is
inserted into patches of "purple membrane" in the cell surface,
the purple membranes serving as light-operated proton pumps to
translocate protons from the inside to the outside of the cells.
... ... T. Kobayashi et al (University of Tokyo, JP) discuss
real-time spectroscopy, the authors making the following points:
1) Real-time investigations of the rearrangements of bonds
during chemical transformations require femtosecond temporal
resolution, so that the atomic vibrations within the reacting
molecules can be observed. Following the development of lasers
capable of emitting ultrashort laser flashes on this timescale,
chemical reactions involving relatively simple molecules have
been monitored in detail, revealing the transient existence of
intermediate species as reactants are transformed into products.
2) The authors report the direct observation of nuclear
motion in a complex biological system, the retinal chromophore of
bacteriorhodopsin, as it undergoes the trans-cis
photoisomerization that is fundamental to the vision process. By
using visible light pulses of less than 5 femtoseconds in
duration, the authors report they are able to monitor changes in
the vibrational spectra of the transition state and thus
demonstrate that despite photoexcitation of the anti-bonding
molecular orbital involved, isomerization does not occur
instantly, but involves transient formation of a so-called
"tumbling state". The authors suggest their observations thus
agree with growing experimental and ab initio analytical evidence
for a 3-state photoisomerization model, the observations firmly
discounting the initially suggested 2-state model for this
process.
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Nature 2001 414:531
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2. MATERIALS SCIENCE: ON ELASTIC MEMBRANES
Roderic Lakes (University of Wisconsin Madison, US) discusses
elastic membranes, the author making the following points:
1) Elastic materials deform easily when under strain but
return to their original dimensions when the force is removed:
they resist changes to both shape and volume. Rubbery materials,
which easily change shape but not volume, become notably thinner
in cross-section when stretched. This is described by Poisson's
ratio, the ratio of transverse contraction to longitudinal
extension during stretching. For rubber, Poisson's ratio is close
to the theoretical upper limit of 0.5; for most other common
materials, the ratio is between 0.25 and 0.35. Because all these
materials become thinner when stretched, Poisson's ratio is
always positive. The reason for the thinning is that interatomic
bonds tend to align when deformed.
2) A negative Poisson's ratio, which requires a transverse
expansion (thickening) on stretching, is considered
counterintuitive. Indeed, such materials were once thought not to
exist or even to be impossible. But materials with negative
Poisson's ratio do occur, and have been called "anti-rubber"
"auxetic", or "dilational". For example, 2-dimensional honeycomb
structures have been developed with "inverted" cells, which
unfold when stretched. Regular honeycomb lattices, like most
materials, have a positive Poisson's ratio. Similarly, some foam
materials with a 3-dimensional microstructure of "inwardly
bulging" cells also become fatter when stretched. These foams and
honeycombs have such unusual elastic behavior because of
nonuniform unfolding or deformation of the microstructure. Such
materials are usually tougher and more resilient than most
conventional materials.
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Nature 2001 414:503
ScienceWeek 1 Mar 2002 www.scienceweek.com
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3. ON ATTOSECOND MEASUREMENTS
M. Hentschel et al (Technical University of Vienna, AT) discuss
attosecond measurements, the authors making the following points:
1) Experimental access to fast-evolving microscopic
processes requires a short excitation ("pump") pulse, which sets
the process going, and a short probe pulse for taking snapshots
of the evolution of the process. Recent advances in ultrafast
optics have made available laser pulses as short as a few
femtoseconds for this time-resolved (or "pump-probe") measurement
technique. These pulse durations are practically at the limit set
by the laser field oscillation cycle in the visible spectral
range. They allow the tracking of changes in the nuclear
structure of molecules -- such as vibrations, or the breaking and
formation of chemical bonds -- because the characteristic time
scale for atomic motion on an atomic length scale (0.1
nanometers) extends from a few femtoseconds to a few thousand
femtoseconds. But time-domain access to a wide range of electron
dynamics in the atomic shells has been frustrated so far by the
speed of electronic relaxation processes. The wavefunction of
bound electrons following an energetic excitation -- e.g.,
ionization or the creation of an inner-shell vacancy -- tends to
evolve on an attosecond time scale. Until now, insight into these
processes could be gained only indirectly from frequency-domain
measurements of transition linewidths.
2) The authors report they trace electronic dynamics with a
time resolution of approximately 150 attoseconds by using a
subfemtosecond soft x-ray pulse and a few-cycle visible light
pulse. Their measurement indicates an attosecond response of the
atomic system, a soft x-ray pulse duration of 650 +- 150
attoseconds, and an attosecond synchronism of the soft x-ray
pulse with the light field. The authors suggest the demonstrated
experimental tools and techniques "open the door to attosecond
spectroscopy of bound electrons."
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Nature 2001 414:509
ScienceWeek 1 Mar 2002 www.scienceweek.com
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4. ON OPTICAL SOLITONS
J.C. Bronski et al (University of Illinois Urbana, US) discuss
optical solitons, the authors making the following points:
1) Research in optical solitons has its roots in two
advances of the 1960s: a) the development of the mathematical
theory of solitons starting in 1965, and b) the development of
the laser. These seemingly unrelated developments came together
in 1973 with the theoretical prediction of temporal optical
solitons and their experimental realization in 1980.
2) It is easiest to describe an optical soliton in the
spatial domain, where it is simply a self-guided wave. Consider
an optical beam as narrow as 10 optical wavelengths
(approximately 5 microns for visible light). If such beam
propagates in a linear medium, it diffracts and broadens after
even a short distance (e.g., 1 millimeter). In a nonlinear
material, light actually changes the index of refraction of the
medium in which it propagates, leading to self-focusing. This
self-focusing competes with refractive effects, and at sufficient
intensities can lead to the development of a structure for which
diffraction and self-focusing exactly balance -- a soliton.
3) The field of optical solitons has greatly developed over
the past decade, and optical temporal solitons have become a
promising candidate for optical communication networks. At the
same time, optical spatial solitons have become one of the most
exciting research areas in optics and nonlinear science. Until
1995, all optical soliton experiments used a coherent "pulse",
but in 1996 researchers demonstrated the self-trapping of beams
in which the phase varied randomly. This incoherent wave-packet
self-trapped to form a localized nondiffracting beam, an
incoherent soliton. Further experiments demonstrated that white
light, which is both temporally and spatially incoherent, can
also self-trap.
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Proc. Natl. Acad. Sci. 2001 98:12872
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Related Background:
ON WAVE PHENOMENA IN PHYSICS
The idea of "wave" phenomena, the characterization of certain
phenomena as waves, must rank as one of the most important
concepts in both classical and modern physics. In general, a
"wave" is a time-varying quantity that is also a function of
position, a disturbance either continuous or transient,
travelling through a medium as a result of certain properties of
the medium, the resulting displacements of the medium returning
to zero when the disturbance has passed. The chief parameters of
a wave are its speed of propagation, its frequency, its
wavelength, and its amplitude.
... ... J.A. Scales and R. Sneider (2 installations, US NL)
present an essay on waves in physics, the authors making the
following points:
1) The authors note that when scientists (including
physicists) are asked to define a wave, the answers are often
ambiguous. Students may state that a wave is a solution to the
wave equation; professionals may make some ambiguous statement
about propagation velocity; mathematicians tend to give a formal
characterization based on the hyperbolic character of certain
differential equations. The authors suggest that the term "wave"
be defined as an "organized propagating imbalance", with the
caveat: "Just don't ask us to define 'organized'."
2) The authors state that at the simplest levels, the
ubiquity of (classical) waves can be attributed to the desire of
nature for stable equilibria. Whatever the forces that connect
bits of matter together (e.g., electromagnetic or gravitational),
for small perturbations about a stable equilibrium point, the
forces are approximately linear. A linear restoring force implies
harmonic oscillations, and coupled systems of oscillators support
both propagating and standing disturbances. Linearity also
implies superposition, so that periodic solutions can be added
together to obtain finite wave "packets". Thus, for small
perturbations about an equilibrium state in coupled or decoupled
(extended) systems, waves are the natural consequence of the
stability of simple harmonic motion.
3) Wave propagation is in many situations described by a
linear differential equation. In reality, nonlinearity is of
great importance, and this nonlinearity may destroy the waves.
When this happens, organized wave motion changes into turbulent
motion, and in this process it is impossible to state exactly at
which point the wave ceases to be a wave.
4) Heat is the manifestation of microscopic motion.
Computing the classical resonant frequencies of atoms or
molecules in a lattice gives numbers of the order of 10^(13) Hz,
i.e., in the infrared part of the electromagnetic spectrum, so
that when molecules vibrate they produce heat. These lattice
vibrations are called "phonons", and they have both wave-like and
particle-like character. Lattice vibrations are responsible for
the transport of heat in a lattice, and we know that heat is a
diffusive phenomenon. However, if the lattice is cooled to near
absolute zero, the mean free scattering path of the phonons
becomes comparable to the macroscopic size of the sample, and
when this happens, lattice vibrations no longer behave
diffusively but are actually wave-like. By controlling the
temperature of a sample, one can control the extent to which heat
is ballistic (wave-like) or diffusive.
5) Waves have a central role in quantum mechanics, according
to which theory everything has a wave character. Einstein (1879-
1955) used the relation E = hf (energy equals Planck's constant
times frequency) to connect the wave frequency of light with the
energy of discrete light quanta (photons). De Broglie (1875-1960)
extended this to electrons and other entities of matter. For
classical waves, dissipation generally damps the wave motion, and
ultimately everything appears to come to rest. Quantum mechanics
demonstrates that matter waves do not exhibit dissipation: even
the ground state of a harmonic oscillator is in harmonic motion.
Matter waves never come to rest.
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Nature 1999 401:739
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SCIENCE-WEEK 1999 17 Dec
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Related Background:
NEW LINEARIZED WAVE MODEL SIMPLIFIES SOLITON ANALYSIS
A soliton is a solitary localized wave propagating with little or
no change in form in special circumstances in a nonlinear
dispersive medium. It is one of those special mathematical
circumstances that have relevance because there are many
instances in all branches of science where such solitary
propagating waves apparently occur. The mathematical physics of
solitons, however, is extremely complicated, involving nonlinear
differential wave equations with usually intractable solutions.
The result is that until now there has been little physical
understanding of solitons despite the possibility for
mathematical understanding inherent in the relevant equations.
This week Allan W. Snyder and D. John Mitchell (Australian
National University, Canberra AU) presented a heuristic
mathematical model whose basis is the degeneration of the soliton
nonlinear wave equation to a common linear wave equation for a
special set of parameters and parametric relationships. The
result is that for the first time the physical behavior of the
soliton is intuitively apparent, albeit for these special
circumstances. This is a typical mode of breaking through new
conceptual ground in theoretical physics, and physicists are
excited by this development. It will no doubt spur a vigorous
round of experimental and theoretical investigations that may
well bear fruit in new electro-optic technology.
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Science 1997 6 Jun
ScienceWeek 1997 12 Jun
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5. EARTH SCIENCES: ON THE NORTH ATLANTIC OSCILLATION
M.H. Visbeck et al (Columbia University, US) discuss the North
Atlantic Oscillation, the authors making the following points:
1) When the North Atlantic Oscillation (NAO) is in its
positive phase, low-pressure anomalies over the Icelandic region
and throughout the Arctic combine with high-pressure anomalies
across the subtropical Atlantic to produce stronger than average
westerlies across the midlatitudes. During a positive NAO,
conditions are colder and drier than average over the
northwestern Atlantic and Mediterranean regions, whereas
conditions are warmer and wetter than average in northern Europe,
the eastern US, and parts of Scandinavia. Walker and Bliss (1932)
were among the first to recognize and study this pattern of
climate anomalies, which is most pronounced during boreal winter
(December through March).
2) A remarkable feature of the NAO is its trend toward a
more positive phase over the past 30 years, with a magnitude that
seems to be unprecedented in the observational record. Some of
the most pronounced anomalies have occurred since the winter of
1989, when record positive values of the NAO index have been
documented. Moreover, the trend in the NAO accounts for a myriad
of remarkable changes in the climate over the middle and high
latitudes of the Northern Hemisphere, as well as in marine and
terrestrial ecosystems. Among these changes are:
a) Milder winters in Europe downstream and across Asia,
juxtaposed against more severe winters over Eastern Canada and
the northwest Atlantic.
b) Pronounced regional changes in precipitation
patterns, resulting in the advance of some northern European
glaciers and the retreat of the Alpine glaciers.
c) Changes in sea-ice cover in both the Labrador and
Greenland Seas as well as over the Arctic.
d) Pronounced decreases in mean sea level pressure over
the Arctic and changes in the physical properties of Arctic sea
water.
e) Changes in the intensity of convection in the
Labrador and Greenland-Iceland Seas, which in turn influence the
strength and character of the Atlantic meridional overturning
circulation.
f) Stratospheric cooling over the polar cap and total
column ozone losses poleward of 40 degrees N.
g) Changes in the production of zooplankton and the
distribution of fish, and changes in the length of the growing
season over Europe.
All of these changes seem to be strongly related to the
recent trend in the NAO index. Also, regions seemingly far
removed from the Atlantic, such as the Middle East, experience
significant NAO-related impacts.
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Proc. Natl. Acad. Sci. 2001 98:12876
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Related Background:
OCEANOGRAPHY: PATTERNS OF ARCTIC CIRCULATION
Lawrence A. Mysak (McGill University, CA) discusses Arctic
circulation patterns. The North Atlantic Oscillation (NAO) is
perhaps the best known mode of atmospheric variability outside
the tropics. It consists of a north-south fluctuation of air mass
over the North Atlantic sector whose time evolution is
characterized by the NAO index: the standardized winter sea level
pressure difference between the Azores High and the Icelandic
Low. When the NAO index is in a positive mode, a deepened
Icelandic Low causes strong westerlies over the eastern North
Atlantic, strong southerly winds over the Norwegian Sea, and
strong northerly winds over the Labrador Sea. In the negative
mode, the Icelandic Low and the Azores High tend to be weak and
the winds are reduced in the above areas. Another wintertime
oscillation closely associated with the NAO is the Arctic
Oscillation (AO), which consists of fluctuations in air mass
between middle and high latitudes all around the Northern
Hemisphere. The AO index is highly correlated with the NAO Index,
and because the largest north-south air mass exchanges associated
with the AO occur over the North Atlantic sector, the NAO is
regarded as the regional representative of the AO. On decadal and
longer time scales, the NAO and AO indices over the past 50 years
closely resemble a third index -- the vorticity index. This index
characterizes the wind patterns over the central Arctic. When the
vorticity index is positive (corresponding to both the NAO and AO
indices being positive), there is a weak Arctic High, and the
associated winds tend to produce anti-clockwise ice drift motion
in the eastern Arctic (the European Basin). Conversely, when the
vorticity index is negative (corresponding to negative NAO and AO
indices), there is a strong Arctic High and the ice drift motion
is clockwise in the European Basin. In general, it is clear that
i response to atmospheric circulation fluctuations, the Arctic
Ocean current and sea-ice drift patterns vary on a wide range of
time scales.
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Science 2001 293:1269
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SCIENCE-WEEK 28 Dec 2001 http://scienceweek.com
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6. LIQUID WATER: CURRENT RESEARCH PROBLEMS
In general, "ab initio" (from first principles) calculations
utilize experimental data on atomic systems to facilitate the
adjustment of parameters. The excellent performance of ab initio
techniques distinguishes them from their predecessors, the
"semiempirical" methods, with the quantitative predictions of ab
initio techniques usually falling within experimental error when
comparisons are made to experimental measurements.
Contemporary molecular dynamics simulations, which are
extrapolations of statistical mechanics and which originate in
the work of Alder and Wainright in the 1960s, are computer
simulations of molecular systems typically involving hundreds or
sometimes thousands of idealized particles interacting with
physically realistic potentials. Such molecular dynamics
simulations can provide time-dependent properties of a liquid,
but most commonly they are used to produce a set of
configurations and forces which can be averaged to give
equilibrium properties of the system.
... ... F.N. Keutsch and R.L. Saykally (University of California
Berkeley, US) discuss current research on liquid water. The quest
to achieve an accurate description of liquid water has produced
major advances in the last two decades, but despite the
construction of hundreds of model force fields for use in
simulations, the great advances in computational technology, and
the development of powerful ab initio molecular dynamics methods,
we remain unable to accurately calculate the properties of liquid
water (e.g., heat capacity, density, dielectric constant,
compressibility) over significant ranges in various conditions.
We do not yet have a satisfactory molecular description of how a
proton moves in the liquid, we do not fully understand the
molecular nature of the surfaces of either ice or liquid water,
nor do we understand the origin of the intriguing anomalies and
singularities found in the deeply supercooled region. Although it
is clear that the hydrogen bond network and its fluctuations and
rearrangement dynamics determine the properties of the liquid, no
experimental studies exist that reveal detailed information on a
molecular level without considerable interpretation. Moreover,
the reliability of water models for simulating solvation
phenomena and biological processes remains relatively untested. A
general obstacle to resolving these issues is that of correctly
describing the many-body or cooperative nature of the hydrogen
bonding interactions among a collection of water molecules.
Theoretical work has demonstrated that the H-bond is dominated by
electrostatic interactions, balanced by the repulsive electron
exchange, but that dispersion makes an appreciable contribution,
whereas induction (polarization) is the dominant many-body
effect. It has proven notoriously difficult to accurately
parameterize these interactions from ab initio calculations.
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Proc. Natl. Acad. Sci. 2001 98:10533
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Related Background:
BEHAVIOR OF WATER IN THIN FILMS
U. Raviv et al (Weizmann Institute of Science, IL) discuss the
fluidity of water confined to subnanometer films. The fluidity of
water in confined geometries is relevant to processes ranging
from tribology to protein folding, and the molecular mobility of
water in pores and slits has been extensively studied using a
variety of approaches. Studies in which liquid flow is measured
directly suggest that the viscosity of aqueous electrolytes
confined to films of thickness greater than approximately 2 to 3
nanometers remains close to that in the bulk, and this behavior
is similar to that of non-associative organic liquids confined to
films thicker than approximately 7 to 8 molecular layers. The
authors report they observe that the effective viscosity of water
remains within a factor of 3 of its bulk value, even when it is
confined to films in the thickness range (3.5 +- 1) to (0.0 +-
0.4) nanometers. This contrasts markedly with the behavior of
organic solvents, whose viscosity diverges when confined to films
thinner than approximately 5 to 8 molecular layers. The authors
attribute this difference to the fundamentally different
mechanisms of solidification in the two cases. For non-
associative liquids, confinement promotes solidification by
suppressing translational freedom of the molecules. However, in
the case of water, confinement seems primarily to suppress the
formation of the highly directional hydrogen-bonded networks
associated with freezing.
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Nature 2001 413:51
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Related Background:
PHYSICAL CHEMISTRY: A NEW MODEL OF LIQUID WATER
A prominent consideration in the minds of biologists who
work at the level of cells and molecules is that water is the
most prevalent chemical substance in all biological systems, and
that interactions of water with other biological molecules,
particularly with biological macromolecules, are not clearly
defined but are probably of considerable significance.
Of importance in understanding the role of water, not only
in biological interactions, but also in all solute-solute
interactions in aqueous systems, is the unique structure of water
produced by the short-term and long-term interactions of water
molecules with other water molecules, these interactions caused
primarily by a) hydrogen bonding, and b) polar interactions due
to electrostatic asymmetry.
Contemporary "molecular dynamics simulations", which are
extrapolations of statistical mechanics and which originate in
the work of Alder and Wainright in the 1960s, are computer
simulations of molecular systems typically involving hundreds or
sometimes thousands of idealized particles interacting with
physically realistic potentials. Such molecular dynamics
simulations can provide time-dependent properties of a liquid,
but most commonly they are used to produce a set of
configurations and forces which can be averaged to give
equilibrium properties of the system.
... ... J. Higo et al (5 authors at 2 installations, JP) present
a new model of liquid water, the authors making the following
points:
1) The authors point out that in order to understand the
dynamics of solute molecules and biomolecules functioning in
aqueous solutions, it is important to describe the cooperative
motions of solvent water molecules. Although molecular dynamics
analyses have focused on the statistical laws of motions of water
molecules, and on the collective dynamics of hydrogen-bond
network rearrangements, a clear theoretical picture of these
complex motions has not yet been obtained.
2) The authors point out that the study of the structure and
dynamics of the liquid state must involve both cooperative
motions of molecules and random motions of individual molecules.
Cooperativity of motions of water molecules is manifested in the
observed correlation between orientations of neighboring
molecules. On the other hand, each water molecule rapidly
translates and rotates with a 5 to 10 picosecond timescale, which
produces rapid randomization of orientations.
3) The authors propose a framework to describe the two
aspects of water molecule behavior in a unified way, the
framework involving the introduction of a new quantity, "site-
dipole field". The "site dipole" is defined at each spatial
position by the averaged orientation of water molecules that pass
through that position. Although each water molecule randomly
moves and quickly passes through each spatial site, it is
expected that the site-dipole field shows a coherent pattern
because of cooperativity among water molecules. Such coherent
patterns in bulk water should be perturbed by the presence of
solute molecules and give rise to a characteristic site-dipole
structure around solute molecules. The authors demonstrate that
such coherent patterns indeed exist and that the structural
ordering of site dipoles provides a perspective for the
understanding of hydration of biomolecules.
4) The authors report their simulations reveal the presence
of large vortex-like structures of more than 10 angstroms in
size, with such coherent patterns persisting more than 300
picoseconds, although the orientational memory of individual
molecules is quickly lost. A 1 nanosecond molecular dynamics
simulation of systems consisting of two amino acids shows that
the fluctuations of site-dipole field of solvent are pinned
around the amino acids, resulting in a stable dipole bridge
between side chains of amino acids. The dipole bridge forms even
for a side-chain separation of 14 angstroms, which corresponds to
5 layers of water molecules. The formation of the dipole bridge
is sensitive to the side-chain orientations, and thereby suggests
an explanation for specificity in solvent-mediated interactions
between biomolecules.
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Proc. Nat. Acad. Sci. 2001 98:5961
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Related Background:
PHYSICAL CHEMISTRY: ON THE STRUCTURE OF WATER
Water is the most abundant compound on the surface of the
Earth and the principle constituent of all living organisms. The
oceans alone contain 1.4 x 10^(24) grams, or approximately 3.2 x
10^(7) cubic miles of water. Another 0.8 x 10^(24) grams of water
is held within the rocks of the Earth's crust in the form of
water of hydration. The human body is approximately 65 percent
water by weight, with some tissues (e.g., brain and lung)
composed of nearly 80 percent water.
The experiments of Henry Cavendish (1731-1810) and Antoine
Lavoisier (1743-1794) in the 1780s established that water is
composed of hydrogen and oxygen. Although the careful data of
Cavendish was sufficient to prove that two volumes of hydrogen
combine with one volume of oxygen, he did not point this out, and
it was left to Joseph-Louis Gay-Lussac (1778-1850) and Friedrich
Humboldt (1769-1859) to make this discovery in 1805. In 1842,
Jean Dumas (1800-1884) found that the ratio of the combining
weights of hydrogen and oxygen in water is very nearly 2 to 16.
Although water is the most familiar of liquids, it is also a
liquid of peculiar properties. Perhaps the best-known peculiarity
of water is its density maximum at 4 degrees centigrade (at
atmospheric pressure); cooling or heating water from this
temperature reduces its density. An equally striking anomaly is
that as the density of water is increased, water molecules
diffuse more rapidly, but only up to a point known as the
"diffusivity maximum". At higher densities, the diffusivity
decreases with increasing density, similar to what is observed
with normal liquids.
... ... J.R. Errington and P.G. Debenedetti (Princeton
University, US) present a report on the relationship between the
structure of liquid water and its anomalies, the authors making
the following points:
1) The authors point out that in contrast to crystalline
solids, for which a precise framework exists for describing
structure, quantifying structural order in liquids and *glasses
has proved more difficult because even though such systems
possess *short-range order, they lack *long-range crystalline
order. Some progress has been made using model systems of hard
spheres, but it remains difficult to describe accurately liquids
such as water, where directional attractions (hydrogen bonds)
combine with short-range repulsions to determine the relative
orientation of neighboring molecules as well as their
instantaneous separation. This difficulty is particularly
relevant when discussing the anomalous kinetic and thermodynamic
properties of water, which have long been interpreted
qualitatively in terms of underlying structural causes.
2) The authors introduce two measures of order in water: a)
the "translational order parameter" measures the tendency of
pairs of molecules to adopt preferential separations; this
parameter vanishes for an ideal gas, and is large for a crystal.
b) the "orientational order parameter" measures the extent to
which a molecule and its four nearest neighbors adopt a
tetrahedral arrangement, such as exists in hexagonal ice; this
parameter vanishes for an ideal gas, and equals 1 in a perfectly
tetrahedral arrangement.
3) The authors report they have attempted to gain a
quantitative understanding of the structure-property
relationships of water through the study of translational and
orientational order in a model of water. Using *molecular
dynamics simulations, they identify a structurally anomalous
region -- bounded by loci of maximum orientational order (at low
densities) and minimum translational order (at high densities) --
in which order decreases on compression, and where orientational
and translational order are strongly coupled. This region
encloses the entire range of temperature and densities for which
the anomalous diffusivity and thermal expansion coefficient of
water are observed, and enables a quantification of the degree of
structural order required for these anomalies to occur. The
authors also find that these structural, kinetic, and
thermodynamic anomalies constitute a cascade: they occur
consecutively as the degree of order is increased.
4) The authors summarize: "The physical picture that emerges
from this work is the following: In liquid water there occurs a
cascade of anomalies. Structural anomalies, whereby order
decreases upon compression, occur over the broadest range of
densities and temperatures. Diffusive anomalies, whereby the
diffusion coefficient of water increases by compression, occur
entirely inside the region of structural anomalies. Thermodynamic
anomalies, whereby the density decreases upon cooling at constant
pressure, occur entirely inside the region of diffusive
anomalies. All anomalous states share the topological property
that orientational and translational order are strongly coupled."
... ... In a commentary on this work, Srikanth Sastry (Jawaharlal
Nehru Center for Advanced Scientific Research Bangalore, IN)
states: "Errington and Debenedetti's observations raise
interesting questions and open a new line of investigation. The
characterization of structural anomaly in terms of the strong
coupling between translational order and orientational order may
help to identify precise conditions necessary for anomalous
behavior. But at present it isn't clear why this observed
relationship and the nested pattern of structural, dynamic, and
thermodynamic anomalies hold, and whether we should expect to
find them in other liquids as well."
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Nature 2001 409:300,318
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Notes:
... ... *glasses: In this context, the term "glass" refers to an
amorphous solid whose atoms form a random network.
... ... *short-range order: A solid is crystalline if it has
long-range order: once the positions of an atom and its neighbors
are known at one point, the place of each atom is known precisely
throughout the crystal. Most liquids lack long-range order,
although many liquids have short-range order. In this context,
"short range" is defined as the first- or second-nearest
neighbors of a water molecule. However, at distances many
molecules away, the positions of the molecules become
uncorrelated. Fluids such as water have short-range order but
lack long-range order.
... ... *long-range crystalline order: See previous note.
... ... *molecular dynamics simulations: This study was based on
constant temperature and density molecular dynamics simulations
of 256 interacting particles.
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ScienceWeek 2001 9 Feb
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7. ON THE MECHANISMS OF COMMENSALISM IN MICROORGANISMS
Many bacterial species exhibit a type of association with large
eukaryote species called "commensalism". In such an association,
the "commensal" (the bacterium) gains some benefit (e.g., surplus
food), while the other party (the host) suffers no serious
disadvantage. In "mutualism", members of two different species
benefit and neither suffers disadvantage. In "parasitism", one
party gains considerably at the other party's expense. Certain
species of bacteria resident in the human gastrointestinal tract
are examples of mutualism. Other bacterial species, in the
gastrointestinal tract and elsewhere (e.g., in the nostrils) are
examples of commensalism. Many disease states involve an altered
virulence of bacteria once translocated from the part of the body
they normally occupy to some other part. For example, ordinarily
harmless human gastrointestinal bacteria (e.g., Escherichia coli)
transferred from the gastrointestinal tract to an open wound
and/or the blood system can cause serious infection. In other
cases, bacteria that are ordinarily involved in commensalism or
mutualism may undergo mutation into a virulent strain.
... ... C.M. Krinos et al (Harvard University, US) discuss
commensalism, the authors making the following points:
1) The dynamic interactions between a host and its
intestinal microflora that lead to commensalism are unclear.
Bacteria that colonize the intestinal tract do so despite the
development of a specific immune response by the host. The
mechanisms used by commensal organisms to circumvent this immune
response have yet to be established.
2) The authors report a demonstration that the human colonic
microorganism Bacteroides fragilis is able to modulate its
surface antigenicity by producing at least 8 distinct capsular
polysaccharides -- a number greater than any previously reported
for a bacterium -- and is able to regulate the synthesis of these
polysaccharides in an on-off manner by the reversible inversion
of DNA segments containing the promoters for the expression of
the proteins responsible for the various syntheses.
3) The authors suggest that this means of generating surface
diversity allows the organism to exhibit a wide array of distinct
surface polysaccharide combinations, and may have broad
implications for how the predominant human colonic
microorganisms, the Bacteroides species, maintain an ecological
niche in the intestinal tract. As the entity B. fragilis is the
anaerobic species most frequently isolated from clinical
infections, and the capsular polysaccharides are instrumental in
the disease process, the mechanism revealed here ("phase
variation") may also contribute to the pathogenic potential of
this organism.
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Nature 2001 414:555
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8. ON BODY PATTERNING IN DEVELOPMENT
Y. Takahashi et al (Nara Institute of Science and Technology, JP)
discuss body patterning, the authors making the following points:
1) Ontogenesis (the developmental processes of an individual
animal) begins with a fertilized egg, and through proliferation,
this single cell becomes a homogeneous mass of cells. This mass
of cells then becomes subdivided into distinct groups that
eventually will exhibit functional specialization later in
development. If the units fail to be correctly established in
time and space, certain specializations might be entirely missing
from the embryo, or cells might randomly differentiate
(specialize) in the wrong place. Furthermore, cells specializing
in the wrong place may end up dying because they fail to be
properly integrated with the rest of the organism. All of these
outcomes can have dire effects on the body.
2) The progress of organogenesis is governed by patterning
processes that have occurred earlier during development and that
involve the action of cell-cell signaling pathways, growth
factors acting between cells, and transcription factors acting
within cells. In general, both body segmentation and brain
patterning are essential for conferring a highly organized
functional complexity to the body. In both cases, an originally
homogeneous group of cells obtains characteristics to give rise
to particular structures and functions in a precise spatial and
temporal pattern. This produces patterns such as the regular
repetition of skeletal elements and the 3-dimensional
compartments of brain primordium on which the subsequent
complexity of the neuronal network is organized. It is now widely
accepted that similar sets of factors are shared by different
animal species and also by distinct processes in the course of
early patterning of organogenesis. During animal evolution, a
"prepattern" of fundamental organs apparently emerged relatively
early.
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Proc. Nat. Acad. Sci. 2001 98:12338
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9. ON NEURAL CIRCUITS IN OLFACTION
Z. Zou et al (Harvard University, US) discuss olfaction, the
authors making the following points:
1) Mammals perceive an immense variety of volatile chemicals
as having different "odors". The initial event in olfactory
perception is the detection of odorants by odorant receptors on
olfactory sensory neurons in the nose. Signals generated by these
neurons in response to odorants are relayed through the olfactory
bulb of the brain, and then the olfactory cortex, ultimately
reaching the higher cortical areas that are believed to be
important in odor discrimination, as well as limbic areas of the
brain believed to mediate the emotional and physiological effects
of odors.
2) In the olfactory epithelium of the mouse nose, there are
approximately 5 million olfactory sensory neurons, each of which
expresses only one of approximately 1000 different odorant
receptor genes. Each odorant receptor recognizes multiple
odorants, but different odorants are recognized, and thereby
encoded, by different combinations of odorant receptors. The
olfactory epithelium has 4 spatial zones that express non-
overlapping sets of odorant receptors and project axons to 4
corresponding zones in the olfactory bulb. In the nose, neurons
expressing the same odorant receptor are scattered throughout one
zone. But in the olfactory bulb, their axons converge at 2 fixed
locations, where they form synapses with bulb mitral and tufted
relay neurons in only a few of the bulb's 2000 glomeruli. The
result is a stereotyped spatial map in which inputs from
different odorant receptors are targeted to different glomeruli
and bulb neurons. Consistent with patterns of odor-induced
activity, an odorant's receptor code is represented in the nose
by a dispersed ensemble of neurons and in the bulb by a specific
combination of glomeruli.
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Nature 2001 414:173
ScienceWeek 1 Mar 2002 www.scienceweek.com
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Related Background:
NEUROBIOLOGY: ON MECHANISMS OF OLFACTION
In vertebrates, two major sensory systems are dedicated to the
detection of chemicals in the environment: olfaction and taste.
The olfactory system detects airborne molecules; the taste system
detects ingested, water-soluble molecules. In humans, olfaction
provides information about chemicals from food, one's self, other
people, and about a variety of animals, plants, and other aspects
of the environment. Olfactory information can influence feeding
behavior, social interactions, and reproduction. Taste
(gustation) provides information about the quality, quantity, and
safety of ingested food. Three articles in a recent symposium are
devoted to various aspects of the biology of olfaction:
... ... Peter Mombaerts (The Rockefeller University, US) presents
a review of the role of specific proteins as odorant and
chemosensory receptors, the author making the following points:
1) The olfactory systems of various species solve the
problem of general molecular recognition in widely differing
ways. Despite this variety, the molecular receptors are
invariably *G protein-coupled 7-transmembrane proteins, and these
receptor proteins are encoded by the largest gene families known
to exist in a given animal genome. Such receptor gene families
have been identified in vertebrates and two invertebrate species
(the *nematode Caenorhabditis elegans and the fruit fly
*Drosophila melanogaster).
2) The complexity of the odorant receptor repertoire is
estimated in mouse and rat at 1000 genes, or 1 percent of the
genome, surpassing that of the *immunoglobulin and *T cell genes
combined.
3) In rodents, two distinct 7-transmembrane gene families
may encode the chemosensory receptors of the *vomeronasal organ,
which is specialized in the detection of pheromones. Remarkably,
these receptor families have practically no sequence homology
among them.
4) Experiments indicate that vertebrate odorant receptors
may fulfill a dual role, also serving as address molecules that
guide axons of olfactory sensory neurons to their precise target
in the brain.
... ... K. Mori et al (3 authors at 2 installations, JP) present
a review of the coding and processing of odor molecule
information in the olfactory bulb, the authors making the
following points:
1) Olfactory sensory neurons detect a large variety of odor
molecules and send information through their axons to the
olfactory bulb, the first site for the processing of olfactory
information in the brain. The axonal connection is precisely
organized so that signals from 1000 different types of odorant
receptors are sorted out in 1800 specific clusters (glomeruli) in
the mouse olfactory bulb.
2) Individual glomeruli modules presumably represent a
single type of receptor and are thus tuned to specific molecular
features of odorants.
3) Local neuronal circuits in the olfactory bulb mediate
*lateral inhibition among glomerular modules to sharpen the
tuning specificity of output neurons. These circuits also mediate
synchronized oscillatory discharges among specific combinations
of output neurons and may contribute to the integration of
signals from distinct odorant receptors in the *olfactory cortex
of the brain.
... ... Gilles Laurent (California Institute of Technology, US)
presents a review of systems aspects of early olfactory coding,
the author making the following points:
1) Studying a neural code requires asking specific questions
such as the following: What information do the signals carry?
What formats are used? Why are such formats used? Although
superficially unambiguous, such questions involve hidden
difficulties and biases. The author suggests that whereas Shannon
and Weaver (1963) developed information theory to quantify
communication through noisy channels, neuroscientists have found
that brains do more than just convey information about the world.
Sensory circuits apparently evolved to detect selective patterns
relevant for survival, but these circuits also create qualities
that do not exist outside of the brain. Hence, brain codes can be
studied from many different perspectives.
2) To understand coding, the format and information-carrying
features of signals transported from a source to a receiver must
be examined. Although the approach is clear when applied to
traditional communication channels, it is fuzzier when applied to
brain circuits. Neurons propagate signals via transmembrane
voltage changes -- in most cases, *action potentials. As far as
we know, all information carried by one neuron is conveyed by
some aspect or aspects of its "spike" (action potential)
discharge. The study of neural coding thus requires an estimate
of the discharge of the participating neuron, and in this regard
no technique is perfect.
3) Given a defined source and receiver, what forms could
codes take? Because the relevant signals are spikes produced by
individual neurons over time, any neural code is spatiotemporal.
4) Whereas the visual and auditory systems process energy
signals whose propagation in the external environment is
predictable, olfaction must deal with turbulent flow of the
medium (turbulent flow of air).
5) The author concludes: "The study of olfactory coding sits
at the intersection of several established and evolving areas of
modern neuroscience... Traditional concepts transferred literally
from the study of other senses may not always be appropriate for
olfactory codes. The time seems ripe for combining theories that
emphasize global dynamics with experimental approaches that
provide cellular and spike time resolution, as well as behavior."
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Science 1999 286:707,711,723
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Notes:
... ... *G protein-coupled 7-transmembrane proteins: G-proteins
are a family of signal-coupling proteins that act as
intermediaries between activated cell receptors and effectors,
for example, the transduction of chemical messenger (hormone)
signals from the cell surface to the cell interior. The G-protein
is apparently embedded in the cell membrane with parts exposed on
the outside surface and inside surface. So-called "seven-
transmembrane proteins" (seven-transmembrane-domain proteins) are
a type of receptor protein containing, in a single polypeptide
chain, 7 hydrophobic domains that traverse the cell membrane
lipid bilayer.
... ... *nematode Caenorhabditis elegans: Nematodes are an
abundant and ubiquitous phylum of unsegmented roundworms.
Caenorhabditis elegans is a small (1 mm) nematode worm. It is
transparent, hermaphroditic, free-living, and found in soil. It
has a relatively small genome (approximately 3000 genes), and
only a few types of cells in its body. It has a 16-hr
embryogenesis that can be achieved in a petri dish, and is thus
highly suitable for the study of developmental and behavioral
genetics.
... ... *Drosophila melanogaster: A major advantage of this
experimental system is the presence of giant chromosomes in the
insect's salivary glands. (In cells with chromosomes, the
chromosomes are the physical structure into which DNA is
organized and on which genes are carried.) Drosophila also has a
short reproductive cycle (approximately 10 days), and it produces
100 to 400 progeny per mating.
... ... *immunoglobulin: The immunoglobulins are a large
glycoprotein category that includes antibodies as a subset. In
general, an "antibody" is a protein molecule produced by the
immune system of vertebrate organisms, the molecule designed to
specifically interact with a particular chemical entity called an
antigen, the antigen usually a particular surface component of a
foreign organism.
... ... *T cell: (lymphocyte) Lymphocytes are a type of leukocyte
(white blood cell) responsible for the immune response. There are
two classes of lymphocytes: 1) B-cells, which, when presented
with a foreign chemical entity (antigen), change into antibody
producing plasma cells; and, 2) T-cells, which interact directly
with foreign invaders such as bacteria and viruses. Certain types
of T-cells are also involved in B-cell production of antibodies.
The essential point of the text is that since the immune system
of vertebrates is so essential for survival of the organism, the
large number of genes devoted to receptor proteins is an
indication of the importance of sensory receptors in evolution.
... ... *vomeronasal organ: The vomer is a flat bone of
trapezoidal shape forming the inferior and posterior portion of
the nasal septum, and term "vomeronasal" refers to the vomer and
the nasal bone.
... ... *lateral inhibition: In general, a type of neuronal
inhibition in which activity of a neuron inhibits activities of
other neurons in the same locus. The simplest example is an axon
collateral involved in a negative feedback loop to one or more
nearby nerve cells.
... ... *olfactory cortex of the brain: The cerebral cortex is a
thin surface layering of nerve cells of the brain, the region
only several millimeters thick but covering all of the brain
surface. This is the part of the central nervous system most
intimately involved with the so-called "higher faculties",
although the cortex operates in concert with other parts of the
brain. The structure is primitive in lower mammals, and is found
progressively more pronounced and with greater surface area in
primates and man.
... ... *action potentials: (nerve impulses) In general,
transient pulses (e.g., 1 millisecond) of reversed membrane
potential propagated over the long extensions of neurons (axons),
in some cases over relatively large distances (e.g., 1 meter
between spinal motorneurons and peripheral muscle cells). The
physical characteristics of the action potentials in the nervous
systems of diverse animal forms are often quite similar.
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ScienceWeek 1999 17 Dec
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10. SINGLE-MOLECULE ANALYSIS OF CHEMOTACTIC SIGNALING
G-proteins are a family of signal-coupling proteins that act as
intermediaries between activated cell receptors and effectors,
for example, the transduction of hormonal signals from the cell
surface to the cell interior, and certain G-proteins are known to
interact with adenylyl cyclase. The G-protein is apparently
embedded in the cell membrane with parts exposed on the outside
surface and inside surface. The outside moiety is activated by
the first messenger, and the inside moiety activates the second
messenger, the G-protein thus acting as a trans-membrane signal
transducer.
... ... M. Ueda et al (Osaka University, JP) discuss chemotactic
signaling, the authors making the following points:
1) Chemotaxis, the process by which cells move toward
attractive molecules, operates in a range of biological processes
including immunity, neuronal patterning, and morphogenesis. The
cells of the colonial organism Dictyostelium discoideum display a
strong chemotactic response to cyclic adenosine 3',5'-
monophosphate (cAMP; cyclic AMP), the response mediated by a cell
surface receptor and a G-protein-linked signaling pathway. The
signaling downstream of the activated G proteins are initiated
locally in the region of the chemotactic cell facing the higher
concentration of attractant (cell anterior) even though receptors
and G proteins are uniformly distributed on the cell surface.
2) The authors report they used single-molecule imaging
techniques to reveal the binding of individual cAMP molecules to
heterotrimeric guanine nucleotide-binding-protein-coupled
receptors on the surface of living D. discoideum cells. The
binding sites were uniformly distributed and diffused rapidly in
the plane of the cell membrane. The probabilities of individual
association and dissociation events were greater for receptors at
the anterior end of the cell. Agonist-induced receptor
phosphorylation had little effect on any of the monitored
properties, whereas G-protein coupling influenced the binding
kinetics. The authors suggest these observations illustrate the
dynamic properties of receptors involved in gradient sensing and
indicate that these properties may be polarized in chemotactic
cells.
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Science 2001 294:864
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11. ON THE NEUROPSYCHOLOGY OF TIME
P.A. Lewis and V. Walsh (University of Birmingham, UK) discuss
the neuropsychology of time, the authors making the following
points:
1) Immanuel Kant (1724-1804) attempted to explain the
special status of time and space in perception by arguing that
our understanding of the Universe is limited by the way our
brains process information. Specifically, Kant noted that we
perceive all events as occurring in time and space, but it is not
clear whether these dimensions exist in reality or are byproducts
of our mental organization. For the neuroscientist, the question
is slightly different: Allowing that our perceptions are mental
constructs and therefore often differ from, or ignore, physical
reality (e.g., illusions), the question becomes, How do brain
structures and processes shape these perceptions?
2) Within most sensory modalities, there is a clear starting
point, because the dimensions being examined -- size, color,
pitch, pressure, etc. -- can be measured using known receptor
systems. For time, however, it is less clear how to approach the
issue, since we do not appear to have a set of peripheral time
sensors or a primary time area in the brain. So how do we come to
be aware of time, and what mechanisms do we use to measure it?
3) Psychologists and physiologists have been investigating
time measurement since the early 17th century, and approaches
they have used fall into two main categories: a) examination of
the psychophysical properties of temporal estimation data, and b)
investigations aiming to isolate the necessary brain regions
using focal lesions or, more recently, neuroimaging. An important
fundamental concept that has emerged from this work is that of
multiple neural clocks. Measurement of intervals with different
durations, or for different behavioral purposes, appears to draw
upon quite discrete and different mechanisms in many cases.
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Current Biology 2002 12:R9
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12. ON EPITHELIAL CELLS
William M. Bement (University of Wisconsin Madison, US) discusses
epithelial cells, the author making the following points:
1) When isolated, the rates of movement of epithelial cells
compare poorly to even the most indolent of fibroblasts, and when
in their natural state (forming an "epithelium"), epithelial
cells appear completely inert. This view is reinforced by the
fact that epithelia function to maintain a selective barrier
between the outside world and the interior tissues of an
organism, a role that presumably would not benefit from the kind
of wanderlust displayed by other and more lively cell types. In
fact, however, epithelial cells can be very dynamic, and their
ability to move is actually critical for barrier maintenance in
the face of wounding, when translocation of epithelial cells
repairs holes in the epithelial monolayer.
2) However, in contrast to most cells used as models for
cell locomotion, cells that tend to move in isolation, epithelial
cells have the ability to move en masse, while maintaining their
cell-cell junctions, a feature that reflects their role as living
bulwarks against unwanted incursions by ions and pathogens.
3) The danger to epithelial function from wounding is
obvious, but there is another danger that is less obvious but
just as pervasive -- programmed cell death (apoptosis). As is
common with highly differentiated cells, those that comprise the
epithelium have a finite lifespan, and their demise would result
in a breach in the epithelium unless somehow compensated. The
cellular mechanism underlying this compensation has recently been
revealed by Rosenblatt et al (2001): Cells bordering apoptotic
cells assemble a multicellular ring of actin filaments (F-actin)
and myosin-2 around their doomed neighbor well before overt signs
of cell death, and then contract this structure to squeeze the
apoptotic cell into the extracellular space.
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Current Biology 2002 12:R12
Current Biology 2001 11:1847
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13. ON THE SEMICONDUCTOR-ELECTROLYTE INTERFACE
An important aspect of modern photoelectrochemistry is the focus
on control of events at junctions between semiconductors and
electrolyte solutions. Such junctions are electrically complex,
with specific electronic architectures in the interface and in
the two adjoining phases.
... ... Michael Graetzel (Swiss Federal Institute of Technology,
CH) discusses the semiconductor-electrolyte interface, the author
making the following points:
1) When a semiconductor is placed in contact with an
electrolyte, electric current initially flows across the junction
until electronic equilibrium is reached, the state where the
Fermi energy of the electrons in the solid is equal to the redox
potential of the electrolyte. The transfer of electric charge
produces a region on each side of the junction where the charge
distribution differs from the bulk material, and this is known as
the "space charge layer".
2) On the electrolyte side, the space charge layer
corresponds to the familiar "electrolytic double layer", i.e.,
the compact Helmholtz layer followed by the diffuse Gouy-Chapman
layer. On the semiconductor side of the junction, the nature of
the band bending depends on the position of the Fermi level in
the solid. If the Fermi level of the electrode is equal to the
flat bend potential, there is no excess charge on either side of
the junction and the bands are flat. If electrons accumulate at
the semiconductor side, one obtains an accumulation layer. If,
however, the electrons deplete from the solid into the solution,
a depletion layer is formed, leaving behind a positive excess
charge formed by the immobile ionized donor states. Finally,
electron depletion can go so far that the concentration of
electrons at the interface falls below the intrinsic level. As a
consequence, the semiconductor is p-type at the surface and n-
type in the bulk, corresponding to an inversion layer.
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Nature 2001 414:340
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14. ON CARBON EXCHANGE BY TERRESTRIAL ECOSYSTEMS
D.S. Schimel et al (Max Planck Institute for Biogeochemistry
Jena, DE) discuss global carbon exchange, the authors making the
following points:
1) Knowledge of carbon exchange between the atmosphere,
land, and the oceans is important, given that the terrestrial and
marine environments are currently absorbing approximately half of
the carbon dioxide emitted by fossil-fuel combustion. This carbon
uptake is therefore limiting the extent of atmospheric and
climatic change, but its long-term nature remains uncertain.
Nevertheless, high precision atmospheric observations of
concentrations of carbon dioxide and oxygen make it possible to
partition the uptake of atmospheric carbon dioxide between the
land and the ocean with increased confidence.
2) The authors report a survey of the current state of
knowledge of global and regional patterns of carbon exchange by
terrestrial ecosystems. Atmospheric carbon dioxide and oxygen
data confirm that the terrestrial biosphere was largely neutral
with respect to net carbon exchange during the 1980s, but became
a net carbon sink in the 1990s. This recent sink can be largely
attributed to northern extra-tropical areas, and is approximately
split between North American and Eurasia. Tropical land areas,
however, were approximately in balance with respect to carbon
exchange, implying a carbon sink that offset emissions due to
tropical deforestation. The evolution of the terrestrial carbon
sink is largely the result of changes in land use over time, such
as regrowth on abandoned agricultural land and fire prevention,
in addition to responses to environmental changes, such as longer
growing seasons, and fertilization by carbon dioxide and
nitrogen. Nevertheless, there remain considerable uncertainties
as to the magnitude of the sink in different regions and the
contribution of different processes.
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Nature 2001 414:169
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15. ON HIGH-RESOLUTION SCANNING TUNNELING MICROSCOPY
W.A. Hofer et al (University College London, UK) discuss high-
resolution scanning tunneling microscopy, the authors making the
following points:
1) It is currently difficult to avoid the scanning tunneling
microscope (STM) in the imaging, fabrication, or characterization
of nanoscale structures, and STM is certainly the most ubiquitous
tool in surface science. But while the formation of atomic wires
from metal leads and their final breaking is well researched, the
physics of the reverse process -- an STM tip approaching the
surface at very close range -- is far less documented. Even more
importantly, several routes are currently being explored to
fabricate and operate electronic devices on the nanoscale.
2) In chemical methods of nanofabrication, a high precision
of atomic assembly is attainable, even though the exact position
of every atom is not controlled. By contrast, to initiate such a
process, or to craft structures by moving each element into
place, the exact position of the STM tip and the target atoms
must be known. Furthermore, nanoscale research requires a high
degree of knowledge about the electronic, chemical, and transport
properties of potential constituents -- information often
obtained by STM. This information may be misleading if the tip-
sample distance is not correctly estimated. Therefore, as soon as
the work moves from qualitative to quantitative, distance
estimates are of critical importance. The question of distances
has been analyzed to some extent for STM, and for the related
scanning force microscope. What is missing, so far, is a picture
of the interplay between forces, relaxations, and electric
currents.
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Phys. Rev. Lett. 2001 87:236104
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16. THE ART OF TOTAL SYNTHESIS
Istvan E. Marko (Catholic University of Louvain, BE) discusses
total synthesis, the author making the following points:
1) The total synthesis of complex natural products remains
the most difficult, daunting, and challenging endeavor in organic
chemistry. The remarkable synthesis of vitamin B12 by Robert
Woodward (1917-1979) in 1968 and by Albert Eschenmoser in 1977
marks the beginning of modern natural product synthesis. Before
this work, organic synthesis was performed primarily to nail down
the structure of particular molecules. But the structure of
vitamin B12 was known through the pioneering crystallographic
work of Dorothy Crowfoot Hodgkin (1910-1994), and the emphasis
thus shifted to exploring new synthetic routes to make this
complex material from simple starting materials.
2) The Woodward synthesis of vitamin B12 took 11 years and
involved more than 90 separate reactions by over 100 coworkers.
The stereochemical puzzles involved in the synthesis led to the
Woodward-Hoffman rules, which delineate how the electronic
structures of molecules reorganize during reactions. The vitamin
B12 synthesis revolutionized theoretical chemistry, and the
Woodward-Hoffman rules paved the way to the use of orbital theory
by the chemical community.
3) Another milestone in organic chemistry was the discovery
by Derek Barton (1918-1998) in the 1950s that organic molecules
could be assigned a preferred conformation, and that the chemical
and physical properties of a molecule could be interpreted in
terms of that preferred conformation. This discovery helped to
guide synthetic pathways. Retrosynthetic analysis, which entails
going backward from a target molecule to starting materials, was
introduced by Corey and Cheng in 1989, and its relevance
demonstrated by a number of exquisite total syntheses.
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Science 2001 294:1842
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17. SELF-ASSEMBLY OF METAL NANOSTRUCTURES ON POLYMER SCAFFOLDS
W.A. Lopes and H.M. Jaeger (University of Chicago, US) discuss
self-assembly of metal nanostructures, the authors making the
following points:
1) Self-assembly is emerging as an elegant "bottom-up"
method for fabricating nanostructured materials. This approach
becomes particularly powerful when the ease and control offered
by the self-assembly of organic components is combined with the
electronic, magnetic, or photonic properties of inorganic
components.
2) The authors report a demonstration of a versatile
hierarchical approach for the assembly of organic-inorganic
copolymer-metal nanostructures in which one level of self-
assembly guides the next. In a first step, ultrathin diblock
copolymer films form a regular scaffold of highly anisotropic
stripe-like domains. During a second assembly step, differential
wetting guides diffusing metal ions to aggregate selectively
along the scaffold, producing highly organized metal
nanostructures.
3) The authors report that in contrast to the usual
requirement of near-equilibrium conditions for ordering, the
metal arranged on the copolymer scaffold produces the most highly
ordered configurations when the system is far from equilibrium.
The authors delineate two distinct assembly modes of the metal
component -- each mode characterized by different ordering
kinetics and strikingly different current-voltage
characteristics. The authors suggest these results therefore
demonstrate the possibility of guided large-scale assembly of
laterally nanostructured systems.
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Nature 2001 414:735
ScienceWeek 1 Mar 2002 www.scienceweek.com
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18. CONDUCTION OF WATER THROUGH HYDROPHOBIC NANOTUBES
G. Hummer et al (NIH, US) discuss water conduction through
nanotubes, the authors making the following points:
1) Confinement of matter on the nanometer scale can induce
phase transitions not seen in bulk systems. In the case of water,
so-called "drying transitions" occur on this scale as a result of
strong hydrogen-bonding between water molecules, which can cause
the liquid to recede from nonpolar surfaces to form a vapor layer
separating the bulk phase from the surface.
2) The authors report molecular dynamics simulations
demonstrating spontaneous and continuous filling of a nonpolar
carbon nanotube with a 1-dimensional ordered chain of water
molecules. Although the molecules forming the chain are in
chemical and thermal equilibrium with the surrounding bath, the
authors report they observe pulse-like transmission of water
through the nanotube. These transmission bursts result from the
tight hydrogen-bonding network inside the tube, which ensures
that density fluctuations in the surrounding bath lead to
concerted and rapid motion along the tube axis. The authors also
find that a minute reduction in the attraction between the tube
wall and water dramatically affects pore hydration, leading to
sharp two-state transitions between empty and filled states on a
nanosecond timescale.
3) The authors suggest their observations indicate that
carbon nanotubes, with their rigid nonpolar structures, might be
exploited as unique molecular channels for water and protons,
with the channel occupancy and conductivity tunable by changes in
the local channel polarity and solvent conditions.
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Nature 2001 414:188
ScienceWeek 1 Mar 2002 www.scienceweek.com
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19. MOLECULAR BIOLOGY AND HISTORICAL RESEARCH: GENETIC
CHARACTERIZATION OF THE BODY ATTRIBUTED TO THE EVANGELIST LUKE
C. Vernesi et al (University of Ferrara, IT) discuss the
evangelist Luke, the authors making the following points:
1) According to historical sources, the evangelist Luke was
born in Antioch, in the Roman province of Syria, and died in
Thebes (Greece) at age 84 approximately in the year 150 AD. His
body was initially buried in Thebes, but then it was transferred
to Constantinople in the 2nd year of the reign of the emperor
Constantius (338 AD), and eventually to Padua (Italy) at an
unspecified time before 1177, possibly under the reign of Julian
the Apostate ((361-363), or during the iconoclast controversy,
726-846). The availability of samples from the Padua body for DNA
typing provided an opportunity to test the degree to which
molecular biology could confirm history by assigning the remains
of a single individual to a geographical region of origin.
2) The marble sarcophagus containing the body traditionally
attributed to Luke was opened September 17, 1998 by a committee
headed by Vito T. Marin. The sarcophagus contained a leaden
coffin whose size fits into the tomb considered to be Luke's in
Thebes. Inside the coffin, along with various objects (including
two plates with the dates 1463 and 1562, when the coffin was last
opened), was the skeleton of a male individual. Evident signs of
osteoporosis and skeletal deformation showed that the individual
had died at age 70 or more. The pelvis had fused with the coffin,
and complementary marks of larvae of saprophage Diptera on the
pelvis and on the head suggest that the body decomposed in that
coffin.
3) Mitochondrial DNA (mtDNA) extracted from two teeth was
cloned and typed. The sequence determined in multiple clones is
an uncommon variant of a set of alleles common in the
Mediterranean region. The authors also collected and typed modern
samples, and with samples from Anatolia that were already
available in the literature, they could reject the hypothesis
that the body belonged to a Greek rather than to a Syrian
individual. However, the probability of an origin in the area of
modern Turkey was only insignificantly lower than the probability
of a Syrian origin. The authors suggest the genetic evidence is
therefore compatible with the possibility that the body comes
from Syria, but is also compatible with the possibility of a
replacement of the body in Constantinople.
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Proc. Nat. Acad. Sci. 2001 98:13460
ScienceWeek 1 Mar 2002 www.scienceweek.com
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20. ON THE NOCEBO PHENOMENON
A.J. Barsky et al (Harvard University, US) discuss side effects
in medication, the authors making the following points:
1) Almost 3 billion prescriptions are filled each year in
outpatient settings in the US, an increase of 50 percent since
1992. Although many side effects (generally defined as an action
of a drug other than the one for which it is being used) result
directly from the pharmacological activity of these drugs, many
other side effects cannot be attributed to their specific
pharmacological actions. Such nonspecific side effects distress
patients, add to the burden of their illness, and increase the
costs of their care. The consequence may be nonadherence,
discontinuation by physicians of what is otherwise an appropriate
therapy, or prompt attempts to treat these side effects with
additional drugs.
2) The "nocebo phenomenon" may be of relevance in
understanding adverse nonspecific side effects. The nocebo (Latin
for "I will harm") phenomenon refers to symptoms and/or
physiological changes that follow the administration of an inert
and chemically inactive substance that the patient believes to be
an active drug. The term "nocebo"was originally introduced to
distinguish the noxious or distressing effects of a placebo
(Latin for "I will please") from its beneficial therapeutic
effects.
3) The authors report a focused review of the literature,
the review identifying several factors that appear to be
associated with the nocebo phenomenon and/or reporting of
nonspecific side effects while taking active medication: a) the
patient's expectations of adverse effects at the outset of
treatment; b) a process of conditioning, in which the patient
learns from prior experiences to associate medication-taking with
somatic symptoms; c) certain psychological characteristics such
as anxiety, depression, and the tendency to somatize; d)
situational and contextual factors.
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J. Am. Med. Assoc. 2002 287:622
ScienceWeek 1 Mar 2002 www.scienceweek.com
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Related Background:
PLACEBO EFFECT MECHANISM IN PARKINSON'S DISEASE
Parkinson's disease (also called Parkinson disease) is a
slowly progressive degenerative central nervous system disorder,
characterized by decreased movement, muscular rigidity, resting
tremor, and postural instability.
The disease was first described by James Parkinson (1755-
1824) in 1817 and is now known to be associated with degeneration
of one or more specific regions of the brain (dopaminergic neuron
groups such as the *substantia nigra) and resultant loss of
*neural projections to several important brain centers.
Dopaminergic neurons are nerve cells that use dopamine as a
*neurotransmitter substance. Dopamine is found in several major
areas of the brain, and it is the degeneration of so-called
dopamine neurons that is apparently involved in Parkinson's
disease.
One must distinguish "parkinsonism" from Parkinson's
disease. Parkinsonism is a syndrome (a complex of symptoms; in
this context, a complex of various movement symptoms) that may be
caused by Parkinson's disease, but which may also be caused by
infectious, vascular, pharmacological, toxic, metabolic,
structural, and various degenerative disorders. In other words,
not every individual with parkinsonism has Parkinson's disease.
The major differentiating characteristic is the response to the
drug "*levodopa", which is converted by the body into dopamine.
Individuals with parkinsonism who respond to levodopa treatment
receive a diagnosis of Parkinson's disease.
At the present time, Parkinson's disease is the 4th most
common neurodegenerative disease of the elderly. It affects
approximately 1 percent of people older than 65 years, and 0.4
percent of people between 40 and 65 years.
... ... R. de la Fuente-Fernandez et al (University of British
Columbia, CA) discuss the mechanism of the placebo effect in
Parkinson's disease. The simple act of receiving any treatment
(active or not) may in itself have a positive effect because of
expectation of benefit. This is the "placebo effect", a potential
confounder in assessing the efficacy of any therapeutic
intervention. Placebo-controlled studies were designed precisely
to control for such an effect, and it has been assumed that the
placebo response is not mediated directly through any physical or
chemical effect of treatment. In Parkinson's disease the placebo
effect can be prominent, but little is known about its mechanism.
Using positron emission tomography with Parkinson's disease
patients, the authors report in vivo evidence for substantial
release of endogenous dopamine in the striatum (caudate nucleus
and putamen) in response to placebo. The dopamine system is
involved in the regulation of several cognitive, behavioral, and
sensorimotor functions, and particularly in reward mechanisms.
These experiments, however, did not involve a direct reward. The
authors conclude that dopamine release in the nigrostriatal
system is linked to expectation of a reward, in this case the
anticipation of therapeutic benefit. All patients were familiar
with the effect of an active drug (levodopa), and such previous
experience may have enhanced their expectation.
-----------
Science 2001 293:1164
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PRAXIS 10 Sep 2001
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Related Background:
MEDICAL BIOLOGY: A CLINICAL TEST OF THE PLACEBO EFFECT
In general, the term "placebo" (which in Latin means "I will
please") refers to a treatment that has no specific effects on
the condition being treated. Thus, a placebo is often a substance
or preparation without pharmacological activity, e.g., a pill
consisting of milk sugar (lactose) or a liquid consisting of
physiological saline solution. There are currently two general
uses of placebos in clinical medicine: a) an inert substance
administered as a "medicine" for its suggestive effect; b) an
inert compound identical in appearance to material being tested
in experimental research, with the placebo known or not known to
the physician and/or patient, the purpose to distinguish between
drug action and any suggestive effect of the material under
study. It is generally agreed that although a placebo may have no
effect on organic disease, it may have an effect on the patient's
subjective experience of disease
The term "placebo effect" refers to something more complex,
a phenomenon in which a clinically significant response occurs
following administration of a therapeutically inert substance.
Such responses include both therapeutic and side effects of drugs
and are not limited to subjective reports: physiological
functions may be objectively influenced. Placebo effects also
include changes deriving from the nonspecific aspects of a
procedure, for example the treatment setting, patient
expectations, etc.
For more than 50 years, the placebo effect has been
recognized as a distinct phenomenon, with many illustrations of
the effect. For example, in one classic study, 3 out of 4
patients suffering from postoperative wound pain reported
satisfactory pain relief after an injection of sterile saline
solution. Responders were indistinguishable from non-responders,
both in the apparent severity of their pain and in the nature of
their personalities. It has also been found that the placebo
effect in postoperative patients can be blocked by the drug
naloxone, a competitive antagonist of opiate receptors. In
general, a common misunderstanding about the placebo effect is
the view that patients who respond to a therapeutically
meaningless reagent are not suffering real pain but only
"imagining" the pain, and so therefore the pain can be relieved
by a placebo. In general, in the psychological, psychiatric, and
neurobiological communities, the placebo effect is considered to
be quite real. Many others in the medical community, however, are
not convinced.
The general idea that psychological input can effect
physiological processes is well accepted by psychologists,
psychiatrists, and neurobiologists primarily because the pathways
that make such effects possible have been identified. However, in
the 19th century, the noted pathologist Rudolf Virchow (1821-
1902) uttered his famous dictum, "All diseases are diseases of
cells," and this attitude has colored much of biological medicine
since that time. Well, yes, all diseases are indeed ultimately
diseases of cells, but when fear causes sudden death in a cardiac
patient one is confronted with a salient instance of
psychological input producing a massive physiological response
via activation of the autonomic nervous system. Such activation
can produce pathological interactions between cells, including
ultimate tissue injury. In general, to neglect the psychological
input to the nervous system as a factor in pathologic
physiological function is not appropriate, no more appropriate
than the idea that all problems with a personal computer are
independent of user input. The administration of a placebo to a
patient is a psychological input that may or may not produce a
physiological effect depending on the patient and on the
circumstances.
With that said, we now report a very recent study of the
placebo effect that is already being touted in the popular press
as proof that the placebo effect does not exist. The study,
however, does not demonstrate that at all.
... ... A. Hrobjartsson and P.C. Gotzsche (University of
Copenhagen, DK) present an analysis of clinical trials in the
literature, the analysis comparing placebo with no treatment. The
authors make the following points:
1) The authors conducted a systematic review of reports of
clinical trials in which patients were randomly assigned to
either placebo or no treatment. A "placebo" could be
pharmacological (e.g., a tablet), physical (e.g., a
manipulation), or psychological (e.g., a conversation). The
authors identified 130 trials that met their inclusion criteria,
the study involving a total of 8525 patients in trials
investigating 40 different clinical conditions ranging from
anxiety to hyperglycemia.
2) The authors report that as compared with no treatment,
placebo had no significant effect on binary outcome studies,
regardless of whether these outcomes were objective or
subjective. For trials with continuous outcomes, placebo had a
beneficial effect, but the effect decreased with increasing
sample size, indicating a possible bias related to the effects of
small trials. The pooled standardized mean difference was
significant for the trials with subjective outcomes but not for
the trials with objective outcomes. In 27 trials involving the
treatment of pain, placebo had a beneficial effect.
3) The authors conclude: "We found little evidence in
general that placebos had powerful clinical effects. Although
placebos had no significant effects on objective or binary
outcomes, they had possible small benefits in studies with
continuous subjective outcomes and for the treatment of pain.
Outside the setting of clinical trials, there is no justification
for the use of placebos."
-----------
A. Hrobjartsson and P.C. Gotzsche: Is the placebo powerless? An
analysis of clinical trials comparing placebo with no treatment.
(New England J. Med. 24 May 01 344:1594)
QY: Asbjorn Hrobjartsson: a.hrobjartsson@cochrane.dk
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Summary by SCIENCE-WEEK http://scienceweek.com 8Jun01
For more information: http://scienceweek.com/swfr.htm
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Related Background:
MEDICAL BIOLOGY:
ANALYSIS OF A MASS PSYCHOGENIC ILLNESS IN A HIGH SCHOOL
Epidemic hysteria, also called "mass psychogenic illness" or
"mass sociogenic illness" or "transient situational disturbance"
was first described in the Middle Ages, and it has been reported
in a variety of cultures and settings. In general, in an actual
acute situation, mass psychogenic illness may be difficult to
distinguish from a bioterrorist event, a rapidly spreading
infection, or acute exposure to toxic substances. Epidemics of
psychogenic illness often attract intense media attention and may
have profound public health, social, and economic repercussions.
... ... T.F. Jones et al (8 authors at 4 installations, US)
present a detailed analysis of a particular outbreak of mass
psychogenic illness, the authors (who essentially comprised a
medical and environmental team) making the following points:
1) On November 12, 1998, a teacher at Warren County High
School in McMinnville, Tennessee (US) noticed a "gasoline-like"
smell in her classroom, and soon thereafter she had a headache,
nausea, shortness of breath, and dizziness. The school was
evacuated, and 80 students and 19 staff members went to the
emergency room at the local hospital, where 38 persons were
hospitalized overnight. Five days later, after the school had
reopened, another 71 persons went to the emergency room. An
extensive investigation was performed by government agencies.
2) The authors report they were unable to find a medical or
environmental explanation for the reported illnesses. The persons
who reported symptoms on the first day came from 36 classrooms
scattered throughout the school. The high school population
consisted of 1825 students and 140 staff members. The building
was 4 years old and situated on land that had previously been
farmed. The property was located outside the town of McMinnville,
which has a population of approximately 11,000 persons. The
county has one high school and one hospital. The most frequent
symptoms (both in this group and in the group of people who
reported symptoms 5 days later) were headache, dizziness, nausea,
and drowsiness. Blood and urine specimens showed no evidence of
carbon monoxide, volatile organic compounds, pesticides,
polychlorinated biphenyls, paraquat, or mercury. There was no
evidence of toxic compounds in the environment. A questionnaire
administered 1 month later indicated that the reported symptoms
were significantly associated with female sex, seeing another ill
person, knowing that a classmate was ill, and reporting an
unusual odor at the school.
3) The authors conclude: "This illness, attributed to toxic
exposure, had features of mass psychogenic illness -- notably,
widespread subjective symptoms thought to be associated with
environmental exposure to a toxic substance in the absence of
objective evidence of an environmental cause."
4) In a critical commentary on this report in the same
journal, Simon Wessely (Guy's School of Medicine, UK) states:
"One of the less welcome aspects of the Freudian tradition has
been the widespread acceptance of the existence of symptoms that
are, in that destructive phrase, "all in the mind". Yet
psychogenic symptoms are physiologic experiences that are based
on identifiable physiologic processes that cause pain and
suffering. The children at McMinnville High School experienced
genuine symptoms. That the cause of these symptoms was probably
anxiety about toxic exposure, rather than any exposure itself,
does not detract from their reality. By labeling the episode
psychogenic or hysterical, however, that is precisely what we are
doing."
[Editor's note: Wessely's point is that although mental
health professionals are aware that physiologic symptoms in
psychogenic illness are real symptoms that can cause pain and
suffering, the public (and many professionals outside the field
of mental health) has a tendency to consider symptoms of
psychogenic illness as "imagined" and not worthy of attention.
Such symptoms, however, are indeed real, as real as the
psychogenic blushing of an individual's face (an opening of blood
capillary beds in the face), when that individual perceives (or
imagines) a social embarrassment, or as real as the increase in
heart rate that can be produced by a real or imagined physical
threat, or even by merely watching an action film. All the
symptoms in the reported high school case can be shown to be
produced by specific activations of the autonomic nervous system,
activations affecting the vascular system, heart rate,
respiration, etc., and these activations can follow specific
activations of the central nervous system by psychological
anxiety states. The biologic paradigm is simply stated: the
central nervous system receives (perceives) psychological input,
and, in addition to the effect of that input on other central
nervous system activity, that input, if capable of provoking
certain emotional states, is complexed, filtered, and converted
to activation of the autonomic nervous system, which in turn
activates physiologic output by controlling various involuntary
muscle groups and glandular secretions. In summary, the symptoms
of the high school population should be considered as most
definitely real; it was the source of the anxiety that was
evidently imagined.]
-----------
New Engl. J. Med. 13 Jan 00 342:96,129
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ScienceWeek 1 Mar 2002 www.scienceweek.com
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21. ESTIMATING HUMAN HEALTH RISK FROM UK SHEEP BSE INFECTION
H.M. Ferguson et al (Imperial College London, UK) discuss bovine
spongiform encephalopathy risks, the authors making the following
points:
1) At the present time, it is uncertain whether bovine
spongiform encephalopathy (BSE) was transmitted to UK sheep in
the past via feed supplements and whether it is still present.
Well grounded mathematical and statistical models are therefore
essential to integrate the limited and disparate data, to explore
uncertainty, and to define data-collection priorities.
2) The authors report they analyzed the implications of
different scenarios of BSE spread in sheep for relative human
exposure levels and variant Creutzfeldt-Jakob disease (vCJD)
incidence. The authors demonstrate that if BSE entered the sheep
population and a degree of transmission occurred, then ongoing
public health risks from ovine (sheep) spongiform encephalopathy
(OSE) are likely to be greater than those from cattle, but that
any such risk could be reduced by up to 90 percent through
additional restrictions on sheep products entering the food
supply.
3) Extending the analysis to consider absolute risk, the
authors estimate the 95 percent confidence interval for future
vCJD mortality to be 50 to 50,000 human deaths considering
exposure to BSE alone, with the upper bound increasing to 150,000
human deaths with inclusion of exposure from the worst-case OSE
scenario examined.
-----------
Nature 2002 415:420
ScienceWeek 1 Mar 2002 www.scienceweek.com
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22. ON CRYPTOCOCCUS NEOFORMANS - A FUNGAL PATHOGEN
Stuart M. Levitz (Boston University, US) discusses C. neoformans,
the author making the following points:
1) Cryptococcus neoformans is a model organism for the study
of fungal infections. This encapsulated fungus is found
worldwide, particularly in soil samples contaminated by bird
excreta. Despite frequent exposure, immunologically intact
persons rarely get disease from this organism, and the annual
incidence estimated at only 0.001 percent. However, the incidence
rises astronomically in patients with impaired T-cell function.
In persons with AIDS, C. neoformans is one of the 5 most common
causes of life-threatening opportunistic infections.
Meningoencephalitis is the most common clinical presentation of
cryptococcosis, although any organ system can be affected. C.
neoformans is a facultative intracellular parasite of
macrophages, and it seems that the capacity to survive both
inside and outside this phagocyte is critical for the virulence
of the organism.
2) Of the more than 100,000 fungal species that exist on our
planet, fewer than 20 regularly cause serious infections in
humans. Overwhelmingly, those patients afflicted with serious
fungal infections have severely compromised immune systems, e.g.,
from AIDS or neutropenia. Thus, innate and acquired immunity
normally form very effective host defenses against various fungi.
This is true not only in humans, but in all other members of the
animal kingdom studied thus far. In fact there is a remarkable
evolutionary conservation in the pathways leading to antifungal
defenses.
3) The major virulence factor of C. neoformans is its
polysaccharide capsule, and this organism is the only fungus of
medical importance to possess a capsule. Deletion of genes
necessary for capsule formation results in C. neoformans
organisms that are not virulent in mouse models of
cryptococcosis. Moreover, reinsertion of the genes restores
virulence. The major component of the capsule is a high molecular
weight polysaccharide, glucuronoxylomannan, which both coats the
fungus and is shed. In patients with cryptococcosis, shed
glucuronoxylomannan accumulates locally in surrounding tissue,
particularly in macrophages, but also circulates in the blood and
cerebrospinal fluid.
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Proc. Nat. Acad. Sci. 2001 98:14760
ScienceWeek 1 Mar 2002 www.scienceweek.com
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23. CANCER DIAGNOSIS AND GENE EXPRESSION SIGNATURES
S. Ramaswamy et al (Massachusetts Institute of Technology, US)
discuss cancer diagnosis, the authors making the following
points:
1) The optimal treatment of patients with cancer depends on
establishing accurate diagnoses by using a complex combination of
clinical and histopathological data. In some instances, this task
is difficult or impossible because of atypical clinical
presentation or atypical histopathology, and these difficulties
can result in diagnostic confusion, prompting calls for mandatory
second opinions in all surgical pathology cases. In the
aggregate, these are significant limitations that may hinder
patient care, add expense, and confound the results of clinical
trials.
2) To determine whether the diagnosis of multiple common
adult malignancies could be achieved purely by molecular
classification, the authors subjected 218 tumor samples, spanning
14 common tumor types, and 90 normal tissue samples, to
oligonucleotide microarray gene expression analysis. The
expression levels of 16,063 genes and expressed sequence tags
were used to evaluate the accuracy of a multi-class classifier
based on a machine algorithm. Overall classification accuracy was
78 percent, far exceeding the accuracy of random classification
(9 percent). Poorly differentiated cancers resulted in low-
confidence predictions and could not be accurately classified
according to their tissue of origin, indicating that they are
molecularly distinct entities with dramatically different gene
expression patterns compared with their well-differentiated
counterparts. The authors suggest that taken together these
results demonstrate the feasibility of accurate multi-class
molecular cancer classification and indicate a strategy for
future clinical implementation of molecular cancer diagnostics.
-----------
Proc. Nat. Acad. Sci. 2001 98:15149
ScienceWeek 1 Mar 2002 www.scienceweek.com
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24. ON SUSCEPTIBILITY GENES FOR MAJOR MENTAL ILLNESSES
In this context, the term "linkage" refers to gene sequences
(genetic loci) that tend to be inherited together more often than
would be expected by chance. Genetic linkage is a reflection of
the physical location of the loci on the same chromosome segment
or DNA molecule. Loci which are close together are less likely to
be separated by recombination and are therefore more likely to be
inherited together. The distance between linked loci is measured
in terms of the frequency of recombination events occurring
between them. The term "linkage disequilibrium" refers to a
situation in which a particular combination of gene variants
(alleles) at two closely linked loci appears more frequently than
would be expected by chance.
... ... In an editorial, E.S. Gershon et al (University of
Chicago, US) discuss susceptibility genes for major mental
illnesses, the authors making the following points:
1) The discovery of susceptibility genes for bipolar
disorder and schizophrenia is thought to be one of the most
intractable current problems in human genetics. The
epidemiological data argue that a substantial portion of the
genetic variance seen in these disorders results from a limited
number of genes with small effects. This is similar to the
situation for many other common diseases with complex inheritance
patterns. Nevertheless, recent scientific advances in human
genetics, combined with recent findings on bipolar disorder and
schizophrenia and the availability of family samples through the
US National Institute of Mental Health (NIMH), suggest that a
scientific opportunity now exists to identify susceptibility
genes for these disorders.
2) Within the scientific community, many still believe that
we do not have the ability to discover susceptibility genes for
bipolar disorder or schizophrenia. Back in 1997, a NIMH workgroup
recommended "large-scale molecular genetics studies" of bipolar
disorder, schizophrenia, and early-onset major depressive
disorder but did not see the time as ripe for favoring a
particular molecular strategy. These 1997 recommendations were
made in view of then-extant data and technology. The authors
(Gershon et al) suggest it is time to reconsider. The authors
suggest we now have the foundation of understanding and the tools
to embark on innovative and meticulous analysis of human genome
linkage disequilibrium with illness in suitable samples and
through molecular scrutiny of disequilibrium regions.
"Investigators should enter the quest for susceptibility genes
for major mental illnesses, and funding agencies should give new
consideration to programmatic support for the discovery of
susceptibility genes for psychiatric disease. The current
situation represents a stalling of the positional cloning process
at the midpoint and may be impeding scientific progress."
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Science 2001 294:957
ScienceWeek 1 Mar 2002 www.scienceweek.com
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25. POSTDOCTORAL FELLOWSHIP PROFILE:
Laboratory of Laura Manuelidis, Yale University
-----------------------------------------------
INSTALLATION: Yale University Medical School
DEPARTMENT: Section of Neuropathology/Surgery
GENERAL RESEARCH AREA: Creutzfeldt-Jakob Disease &
BSE/Neurodegenerative/viral. Experimental models, NOT service
diagnosis.
HEAD OF THIS SPECIFIC LABORATORY: Laura Manuelidis
POSTDOCTORAL FELLOWSHIPS AVAILABLE IN THE FOLLOWING SPECIFIC
RESEARCH PROBLEMS: Agent-host and cell-specific interactions,
transgenic models, molecular probes.
PREVIOUS RESEARCH EXPERIENCE AND DEGREES REQUIRED: Animal,
molecular, tissue culture-cell biology. More important are
intelligence and ability to learn.
USUAL STARTING STIPEND: Standard NIH, negotiable.
SPECIAL REQUIREMENTS: US citizen. Alternate: In US and/or
with valid visa for 2 or more years commitment.
NUMBER OF PEOPLE CURRENTLY WORKING IN THIS SPECIFIC
LABORATORY (FACULTY, STAFF, STUDENTS, POSTDOCS): Typically 1-2
faculty, 4-5 post docs, 1-2 students.
CONTACT FOR MORE INFORMATION: laura.manuelidis@yale.edu
FURTHER RELEVANT INFORMATION: People who do best in this lab
are self-motivated, sufficiently responsible (and neat and
organized) to work with infectious agents, and are inquisitive.
--------------------------------------------------------------
Please note: Postdoctoral Fellowship Profiles are provided to
ScienceWeek by the heads of laboratories and published without
charge. For information about publishing a profile, contact
Claire Haller at: haller@scienceweek.com
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26. IN FOCUS: ON THE FIRST MAJOR BIOTECHNOLOGY PATENT
"On 2 December 1980 the US Patent Office issued the first major
patent in the new biotechnology, one of three patents
subsequently known as the Cohen-Boyer recombinant DNA cloning
patents. The first patent is based on the 1973-1974 development
by Stanley N. Cohen of Stanford and Herbert W. Boyer of the
University of California San Francisco (UCSF) of a fundamental
process of molecular biology that came to be known as recombinant
DNA technology. The concept arose in November 1972 as the two
scientists brainstormed on a late-evening walk after attending a
scientific conference in Hawaii. Sketching out a research
collaboration over deli sandwiches, Cohen and Boyer agreed to
pool their respective expertise in plasmid biology and bacterial
restriction enzymes in experiments that they began soon after
returning to the mainland. By March 1973, at most four months
after initiating the experiments, Cohen, Boyer, and their
coworkers at Stanford and UCSF knew that their DNA-splicing and
cloning (amplifying) procedure worked. In November they published
a paper entitled "Construction of Biologically Functional
Bacterial Plasmids In Vitro." Years later, Boyer recalled his
emotions at the instant of success: "I think the most exciting
moment was when we did the first experiments with the recombined
plasmid DNA. [Colleague] Bob Helling and I looked at the first
[electrophoresis] gels, and I can remember tears coming to my
eyes, it was so nice. I mean there it was. You could visualize
your results in physical terms, and after that we knew we could
do a lot of things."
-----------
Sally S. Hughes: "Making Dollars Out of DNA"
in: Isis 2001 92:541
-----------
Editor's note: In 1976 Herbert Boyer joined with financier Robert
Swanson to invest $500 each to form the company Genentech, which
went public in 1980. Stanley N. Cohen, Boyer's collaborator,
should not be confused with the Nobel Laureate (1986) Stanley
Cohen, who worked on growth factors.
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27. NEW BOOKS
Milton: The Casimir Effect
http://www.amazon.com/exec/obidos/ASIN/9810243979/scienceweek
Hombein et al: High Altitude: An Exploration of Human Adaptation
http://www.amazon.com/exec/obidos/ASIN/0824703138/scienceweek
Davies et al: Human Physiology
http://www.amazon.com/exec/obidos/ASIN/0443045593/scienceweek
Bromley: A Century of Physics
http://www.amazon.com/exec/obidos/ASIN/0387952470/scienceweek
Hoffmann et al: Computational Statistical Physics: From
Billiards to Monte Carlo
http://www.amazon.com/exec/obidos/ASIN/3540421602/scienceweek
Cochrane: Informing Judgment: Case Studies of Health Policy and
Research in Six Countries
http://www.amazon.com/exec/obidos/ASIN/1887748474/scienceweek
O'Brien: Chemokine Receptors and AIDS
http://www.amazon.com/exec/obidos/ASIN/0824706366/scienceweek
Thorpy et al: Encyclopedia of Sleep and Sleep Disorders
http://www.amazon.com/exec/obidos/ASIN/0816040893/scienceweek
Whalley: The Aging Brain
http://www.amazon.com/exec/obidos/ASIN/0231120249/scienceweek
Lohner et al: Development of Novel Antimicrobial Agents: Emerging
Strategies
http://www.amazon.com/exec/obidos/ASIN/1898486239/scienceweek
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
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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