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ScienceWeek
SCIENCE-WEEK - January 4, 2002 - Vol. 6 Number 1
An Email Research Digest Published Weekly Since 1997
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Science keeps moving us away from the Apes.
Of course, if one wants to be an ape, one
objects to the movement.
-- Anonymous
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. Molecular vs. Macroscopic Hydrophobic Interactions
2. On Chaotic Systems
3. On the Morphological Evolution of Galaxies
4. Generation of a Stable Triplet Carbene
5. On the Detection of Extrasolar Terrestrial Planets
6. On the Standard Model of Planet Formation
7. Evolution and Sexual Reproduction
8. Psychological Depression and the Shrinking Hippocampus
9. On Human Evolution
10. On the History of Eugenics in the US
11. Calcium Ion Regulation in Biological Cells
12. On the Histone Code
13. PostDoctoral Fellowship Profile:
Laboratory of Weiming Xia, Harvard University
14. In Focus: On Inflammation
15. From PRAXIS: Criticism of US Health Insurance Policy
16. This Week in PRAXIS
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Section 2
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1. MOLECULAR VS. MACROSCOPIC HYDROPHOBIC INTERACTIONS
H.S. Ashbaug h and M.E. Paulaitis (Princeton University, US)
discuss hydrophobic interactins. The distinction between
molecular hydrophobic effects, quantified by hydrocarbon-to-water
transfer free energies, and hydrophobic driving forces that
influence self-assembly on larger length scales (e.g., micelle
formation and protein folding) was first noted by C. Tanford in
1979. His observation was based on the large discrepancy between
the measured water-hydrocarbon interfacial tension and the
incremental free energy of hydrophobic hydration per solute
surface area obtained from n-alkane solubility data.
Israelachvili et al (1976) also noted this discrepancy in
proposing an elementary theory of surfactant self-assembly in
aqueous solution. Adopting the phenomenological approach of
linearly correlating free energies of hydrophobic hydration with
solute surface areas, they resolved the discrepancy by defining
n-alkane surface areas with respect to the van der Waals surface,
rather than with respect to the solvent-accessible surface of
these hydrocarbons. Thus, they calculated a hydration free
energy/surface area coefficient from n-alkane solubility data
that was close to the experimental value for the macroscopic
water-hydrocarbon interfacial tension. A more recent example of
the distinction between molecular and macroscopic hydrophobic
interactions is found in measurements of a long-range attractive
force between macroscopic hydrophobic surfaces which cannot be
explained on the basis of molecular hydrophobic effects. The lack
of a definitive interpretation of these measurements underscores
the need for a quantitative theory of hydrophobic phenomena
beyond molecular hydrophobic effects. In general, the need for a
unified and quantitative description of both molecular and
macroscopic hydrophobic phenomena arises because hydrophobic
driving forces play an important role in self-assembly on
intermediate length scales and the fact that quantitative
descriptions of these driving forces are derived from molecular
solubility data, macroscopic interfacial tension measurements, or
interpolation of these quantities.
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J. Am. Chem. Soc. 2001 123:10721
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SCIENCE-WEEK 4 Jan 2002 http://scienceweek.com
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Related Background:
HYDROPHOBIC MOLECULAR INTERACTIONS
T.M. Raschke et al (Stanford University, US) discuss theoretical
studies of hydrophobic molecular interactions. The hydrophobic
interaction, the tendency for nonpolar molecules to aggregate in
solution, is a major driving force in biology, a force that
stabilizes biological structures ranging from native
conformations of proteins to cellular membranes, and the origin
of this effect has been the topic of much investigation, both
experimental and theoretical. In a direct approach to the
physical basis of the hydrophobic effect, the authors performed
nanosecond molecular dynamics simulations on increasing numbers
of hydrocarbon solute molecules in water-filled boxes of
different sizes. The intermittent formation of solute clusters
gives a free energy that is proportional to the loss in exposed
molecular surface area with a constant of proportionality of 45
+- 6 calories per mole per square angstrom. The molecular surface
area is the envelope of the solute cluster that is impenetrable
by solvent and is somewhat smaller than the more traditional
solvent-accessible surface area, which is the area transcribed by
the radius of a solvent molecule rolled over the surface of the
cluster. When a factor relating molecular surface area to solvent
accessible surface area is applied, the proportionality constant
is 24 calories per mole per square angstrom. The authors suggest
this is the first direct calculation of the hydrophobic
interaction from molecular dynamics simulations, and that the
excellent qualitative and quantitative agreement with experiment
demonstrates that simple van der Waals interactions and atomic
point-charge electrostatics account for the most important
driving force in biology.
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Proc. Nat. Acad. Sci. 2001 98:5965
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SCIENCE-WEEK 5 Oct 2001 http://scienceweek.com
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Related Background:
SURFACE TOPOGRAPHY AND HYDROPHOBIC HYDRATION OF BIOMOLECULES
Cheng and Rossky (University of Texas Austin, US) present
computer simulations of the interactions between the polypeptide
mellitin and water. Many biomolecules are characterized by
surfaces containing extended nonpolar regions, and the
aggregation and removal of such surfaces from water is believed
to play a critical role in the biomolecular assembly in cells. A
better understanding of the hydrophobic hydration of biomolecules
may therefore yield new insights into intracellular assembly.
Conventional views hold that the hydration shell of small
hydrophobic solutes is clathrate-like, characterized by local
cage-like hydrogen-bonding structures and a distinct loss in
entropy. The hydration of extended nonpolar planar surfaces,
however, appears to involve structures that are orientationally
inverted relative to clathrate-like hydration shells, with
unsatisfied hydrogen bonds directed toward the hydrophobic
surface. The authors suggest their computer simulations
demonstrate that the two different hydration structures also
exist near a biomolecular surface, and that the two structures
are distinguished by a substantial difference in water-water
interaction enthalpy. The authors further suggest that the strong
influence of surface topography on the structure and free energy
of hydrophobic hydration is likely to hold in general, and will
be particularly important for the many biomolecules whose
surfaces contain convex patches, deep or shallow concave grooves,
and roughly planar areas.
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Nature 1998 392:696
Science-Week 1998 8 May
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Related Background:
PRESSURE DEPENDENCE OF HYDROPHOBIC INTERACTIONS OF PROTEINS
The term "denaturation of proteins" refers to an alteration of
protein folding structure by heat, acid, alkali, mechanical
shaking, etc., the result a change in physical properties such as
solubility. "Hydrophobic aggregates" are aggregates of nonpolar
moieties, the aggregation often resulting from Van der Waals
interactions (i.e., dispersion interactions), and in the case of
many proteins, such aggregates of hydrophobic protein side chains
play an important role in producing particular folding
conformations. Clathrates are molecular compounds formed by the
inclusion of molecules of one type in holes in the lattice of
another type, and clathrate hydrates are clathrates involving
significant hydration as a component of the inclusion compound.
... ... Hummer et al (5 authors at 3 installations, US) report a
model explaining pressure denaturation of proteins by the
pressure destabilization of hydrophobic aggregates, the model
using information theory of hydrophobic interactions, with
clathrate hydrates predicted to form by virtually the same
mechanism that drives pressure denaturation of proteins. The
authors suggest that studies of changes in protein conformation
with pressure will not only elucidate the fundamentals of
conformation thermodynamics, but will also clarify adaptation
processes of barophilic organisms such as those living under
extreme pressures in the deep sea.
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Proc. Nat. Acad. Sci. 1998 95:1552
ScienceWeek 1998 13 Mar
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2. ON CHAOTIC SYSTEMS
Andreas Albrecht (University of California Davis, US) discusses
chaotic systems. Chaotic behavior is well understood from a
classical perspective, and is typically discussed in the context
of a mathematical "phase space" in which there are dimensions for
both position (x) and momentum (p). A particle at a given instant
can be specified as a point in classical phase space, and the
time development of the particle describes a curve or trajectory
in phase space. In chaotic systems, particles that start out in
virtually identical states (i.e., at very close points in phase
space) rapidly evolve into completely different states (i.e.,
distant parts of phase space). Because nothing is ever measured
with absolute precision, one can never realistically talk about
"points" in phase space. Instead, every point (x,p) in phase
space is typically assigned a probability P(x,p). For a well-
specified particle, this probability peaks sharply at a localized
point in phase space. For an ordinary classical object, such as a
single billiard ball, a phase-space probability distribution that
starts out sharply peaked will remain peaked over time; a small
uncertainty in the starting point results in a similar small
degree of ignorance at a later time. Chaotic systems are
dramatically different. A sharply peaked initial distribution
gets torn apart by the chaotic evolution, as neighboring phase-
space trajectories rapidly head off in different directions. A
small amount of ignorance at the beginning rapidly translates
into huge uncertainties later on, as the distribution becomes
highly delocalized.
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Nature 2001 412:687
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Related Background:
CHAOS AND COMPLEXITY
Ilya Prigogine (Free University Brussels, BE), who received
the Nobel Prize in Chemistry in 1977 for his work in
nonequilibrium thermodynamics, was among the first theoreticians
to deal with the applications of the second law of thermodynamics
to complex systems. The second law of thermodynamics effectively
holds that physical systems tend to slide spontaneously and
irreversibly toward a state of disorder (an increase of entropy).
There is no explanation in classical thermodynamics, however, of
how complex systems can arise spontaneously from less ordered
states and maintain themselves in apparent defiance of the
tendency toward entropy. Prigogine has proposed that as long as
systems receive energy and matter from an external source,
nonlinear systems ("dissipative structures") can pass through
periods of instability and then self-organization, resulting in
more complex systems whose characteristics cannot be predicted
except as statistical probabilities. The work of Prigogine has
been influential in a wide variety of fields, ranging from
physical chemistry to biology, and this work has been fundamental
in the new disciplines of chaos theory and complexity theory.
What is called "complexity theory" is a theory that proposes
that certain systems manifest behaviors that are completely
inexplicable by any conventional analysis of the constituent
parts of the system. These behaviors, commonly called "emergent
behaviors", apparently occur in many complex systems involving
living organisms. One example is the idea that human
consciousness is an emergent property of a complex network of
neurons in the brain. The major problem of complexity theory is
how to model such emergent behavior: how to devise mathematical
laws that allow emergent behavior to be explained and predicted.
This effort to establish a solid theoretical foundation for the
description of complex systems has attracted mathematicians,
physicists, biologists, economists, and social scientists.
In the research context, complexity and "chaotic behavior"
are not synonymous. If one focuses attention on the time
evolution of an emergent behavior, e.g., daily changes in
temperature, that behavior may well be completely deterministic
yet indistinguishable from a random process: the behavior is
chaotic. However, although chaos is often associated with complex
systems, not all complex systems manifest chaotic behavior. From
the standpoint of systems theory, it is the interactions of
components that create emergent patterns that are important, and
not any chaotic behavior these may patterns may display.
... ... Massimo Pigliucci (University of Tennessee Knoxville, US)
presents a review of current ideas in chaos and complexity
theory, the author making the following points:
1) The author points out that in common non-scientific usage
the term "chaos" is a synonym for randomness, for completely non-
deterministic and irregular phenomena. In mathematical theory,
however, the term "chaos" refers to a deterministic (i.e., non-
random) phenomenon characterized by special properties that make
the predictability of outcomes very difficult: chaotic behavior
is such that although it does not occur randomly, it has the
appearance of a series of random occurrences.
2) Chaotic dynamics are usually (but not always) a property
of nonlinear systems (i.e., systems whose behavior can be
described by sets of nonlinear equations). However, the converse
is not true: not all nonlinear dynamics generate chaotic
behavior. Typically, a given system of equations can produce both
non-chaotic and chaotic outcomes, depending on the range of
values assumed by the parameters of the equations. In many
systems, one can increase the value of a key parameter and obtain
a progression of outcomes from a steady equilibrium state to
regular oscillations with two equilibria, to more complex cycles
with multiple equilibria, to finally producing the chaotic
condition.
3) Another phenomenon typically associated with chaos is the
so-called "butterfly effect": chaos is analogous to a situation
in which the flapping of a butterfly's wings in Brazil ends up
starting a cascade of events that results in a tornado in Texas.
The term for this is "sensitivity to initial conditions": a small
perturbation of a system can cause a series of effects that
eventually lead to macroscopic consequences later in the time
sequence. Had that perturbation been of a different nature, an
entirely different series of events would have occurred. a more
formal way to describe the butterfly effect is to state that the
predictability of the system decreases exponentially with time:
our predictions of where the system will be are relatively good
for the immediate future, but lose accuracy for slightly longer
intervals of time, and are soon completely useless.
4) In general, a chaotic system is one whose mathematical
function is characterized by at least one of the following: a)
The system has sensitive dependence on initial conditions on its
domain; and/or b) the system has a positive *Lyapunov exponent at
each point in its domain that is not eventually periodic. A
"Lyapunov exponent" is a convenient measure of how fast the
trajectories of the system diverge in *phase space: if the
exponent is negative, the system actually converges at an
equilibrium point; if the exponent is near zero, the system
behaves with periodic regularity; if the exponent is positive,
the system is either chaotic or (for very large positive
exponents) random.
5) Chaos theory is a component of a larger but more vague
theoretical framework called "complexity theory". Essentially,
complexity theory is an attempt to study systems that satisfy two
conditions: a) the system is made of many interacting parts; b)
the interactions result in emergent properties that are not
immediately reducible to a simple sum of the properties of the
individual components. In general, complexity theory uses
nonlinear dynamical modeling to account for the behavior of
orderly complex systems. The dynamics manifested by a given
system depend fundamentally on two parameters: the number of
parts (N) that compose the system, and the average number of
connections (K) among the parts within the system. So-called "NK"
systems then fall into 3 types, depending on the relationship
between N and K:
... ... a) K very small compared to N: Number of connections very
small compared to the total number of parts: Each part behaves
essentially independently of other parts, and the properties of
the system are the properties of the individual parts. Such
systems tend to be static or reach simple dynamic equilibria, and
are sometimes called "sub-critical".
... ... b) K increasing compared to N: The dynamics becomes more
complex and emergent properties appear: Local changes propagate
to distant parts of the system as a consequence of connectivity,
but this propagation usually does not cause global change, since
the ratio of K to N is still relatively small. Such systems are
called "edge of chaos" systems, or "critical systems".
... ... c) K approaches N: Most components of the system are
connected to almost every other component: This creates the
determinate but unstable "supercritical" systems described by
chaos theory.
In terms of Lyapunov exponents: a) subcritical NK systems
have a negative Lyapunov exponent; b) critical NK systems have a
Lyapunov exponent near zero; c) chaotic NK systems are
characterized by a positive Lyapunov exponent.
Most classical mathematics, physics, and biology deal with
subcritical systems; chaos theory and fractal geometry deal with
supercritical systems; complexity theory focuses on critical
systems and the transition between system types. Alleged examples
of critical systems (i.e., systems on the "edge of chaos")
include the evolution of natural populations, the developmental
biology of plants and animals, the stock market, the global
economy, and the dynamics of galaxy clusters.
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Skeptic 2000 vol.8 No.3
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Notes:
... ... *Lyapunov exponent: See related background material
below.
... ... *phase space: See related background material below.
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SCIENCE-WEEK 2001 9 Feb
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Related Background:
THEORETICAL PHYSICS: CHAOS AND NONLINEAR DYNAMICS
In general, a nonlinear dynamical system is a system
described by time-dependent differential equations such that the
rates of change of one or more dependent variables of the system
depend in a nonlinear fashion on the variables themselves.
Certain nonlinear dynamical systems, some of which are of great
scientific interest, exhibit "chaotic dynamics". In this context,
the term "chaos" refers to unpredictable behavior arising in a
system that obeys deterministic laws but exhibits
unpredictability. The essential idea is that in certain systems
small perturbations may produce a cascade of larger
perturbations, so that eventually the behavior of such systems
cannot be predicted from prior states no matter if the systems
appear simple and obey deterministic laws. Examples of chaotic
nonlinear dynamical systems are the weather and populations of
organisms, and instances of chaotic dynamics have now been
documented in most scientific disciplines.
Because the differential equations for many nonlinear
systems are often intractable (i.e., no explicit quantitative
solutions are possible), a focus of theoretical research on
nonlinear systems has been on analysis of the qualitative
behavior of such systems, in particular on analysis of the "phase
space" and "trajectories" in the phase spaces of such systems.
The idea is essentially as follows: If the state of a system
depends upon N variables, the instantaneous state of the system
can be viewed as a point (phase point) in an N-dimensional space
(phase space; system hyperspace), and as the state of the system
changes, its phase point can be viewed as describing a trajectory
in its phase space. Qualitative analysis of the possible families
of solutions of nonlinear differential equations can provide
information about such phase space trajectories, and there are
certain real systems for which qualitative analysis of the phase
space trajectories of the system has revealed significant
properties of the system otherwise difficult to delineate.
... ... J.P. Gollub and M.C. Cross (2 installations, US) present
a commentary on recent research on chaotic nonlinear dynamics,
the authors making the following points:
1) The techniques of nonlinear dynamics are well-developed,
but the impact of this field has been largely confined to
phenomena in which there are only a few important time-dependent
quantities. Unfortunately, this excludes a vast range of
important problems in which the behavior of one point in space
can be quite different (though statistically similar) to that at
another location. A particular example is convective behavior.
2) The traditional approach to studying nonlinear dynamical
behavior is to plot the dynamical variables of the system as a
multidimensional phase space graph indicating how the behavior
changes over time. For example, a simplified model of the Solar
System consisting of the Sun and 9 planets would require a phase
space with as many as 60 dimensions (3 position and 3 momentum
coordinates for each body). In the case of a convecting fluid, a
complete description of the flow pattern requires knowledge of
the velocity and temperature at a very large number of locations,
so the number of dimensions of the phase plot are enormous (from
thousands to millions, depending on the desired spatial
resolution). As a result, the methods of nonlinear dynamics are
cumbersome and progress has been slow, even though many
interesting examples of spatiotemporal chaos have been explored
both experimentally and numerically.
3) Recent research (D.A. Egolf et al: Nature 404:733 2000)
involving numerical studies of an accepted model of thermal
convection indicates that the origin of unpredictable motion in
chaotic thermal convective systems, at least in one particular
form of spatiotemporal chaos, lies in what occurs in small
regions of space and over short time-scales. These local changes
in the organization of the flow affect the surrounding regions in
such a way that the entire future evolution is affected. The
authors state: "This is something akin to Ed Lorenz's famous
remark [E.N. Lorenz: J. Atmos. Sci. 20:130 1963] that the
localized flapping of a butterfly's wings might change the
weather dramatically over the entire world a few weeks later."
Although such sensitivity to localized fluctuations has never
been confirmed as the source of the unpredictability of the
weather, it is apparently the origin of chaotic dynamics in
thermal convection.
4) The authors conclude: "The methods used by Egolf et al
should apply to many other forms of chaos in spatially extended
systems (physical, chemical, and biological) for which reliable
model equations are available, so that the key processes leading
to the complex dynamics can be identified. Applications to areas
as diverse as cardiology and atmospheric dynamics might be
expected eventually. Moreover, it is not unreasonable to imagine
that insight into the processes leading to unpredictability will
also lead to progress in modifying or controlling the dynamics of
these systems."
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Nature 13 Apr 2000 404:710
SCIENCE-WEEK 2000 23 Jun
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Related Background:
EXPERIMENTAL EVIDENCE FOR MICROSCOPIC CHAOS
In the study of physical systems, the term "chaotic behavior" has
a specific meaning: the behavior of a system is said to be
"chaotic" if its final state is so sensitive to the system's
precise initial conditions that the behavior of the system is in
effect unpredictable and cannot be distinguished from a random
process, even though the behavior of the system is strictly
determinate in a mathematical sense. In other words, a
deterministic system characterized by extremely sensitive
instabilities, despite the system being determinate, can exhibit
behavior that is unpredictable, and the system is then called
"chaotic". During the past several decades, the analysis of such
chaotic systems has intrigued both physicists and mathematicians.
In general, in the study of physical systems, the term "phase
space" refers to a multidimensional space, each point of which
(phase point) completely represents the state of the system. For
example, in the study of dynamical systems, each phase point in
the phase space completely represents the values of all the
generalized coordinates and corresponding momenta. As the phase
point of a system moves in the phase space (e.g., changes with
time), the phase point follows a trajectory in the phase space,
and this trajectory is called the "phase point trajectory". In
the mathematical analysis of a particular phase space and its
phase point trajectories, "*Lyapunov exponents" are coefficients
that describe the rates at which nearby phase point trajectories
converge or diverge, and the Lyapunov exponents can be shown to
provide estimates of how long the behavior of a dynamical system
is predictable before chaotic behavior sets in. Chaotic behavior
of a system is characterized by the existence of positive
Lyapunov exponents. ... ... Gaspard et al present the results of
an experimental study of "microscopic chaos". The authors point
out that many macroscopic dynamical phenomena, for example in
hydrodynamics and oscillatory chemical reactions, have been
observed to display erratic or random time evolution, despite the
deterministic character of their dynamics -- a phenomenon known
as "macroscopic chaos". On the other hand, it has been long
supposed that the existence of chaotic behavior in the
microscopic motions of atoms and molecules in fluids or solids is
responsible for their equilibrium and non-equilibrium
properties. But, the authors state, this hypothesis of
microscopic chaos has never been verified experimentally. The
authors now report direct experimental evidence for microscopic
chaos in fluid systems, the study involving the *observation of
brownian motion of a colloidal particle suspended in water. The
authors report finding a positive lower bound on the sum of
positive Lyapunov exponents of the system composed of the
brownian particle and the surrounding fluid. They suggest their
results and quantitative analysis provide strong experimental
evidence for microscopic chaos. They conclude: "On the assumption
that the system is deterministic, and given our knowledge of the
molecular structure of the fluid, this evidence supports, in
particular, the hypothesis that large systems -- which may be
treated by statistical mechanics -- are typically chaotic. The
result also supports the role of dynamical instability in non-
equilibrium fluids."
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Nature 1998 394:865
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Notes:
... ... *Lyapunov: A.M. Lyapunov (1857-1918) developed a general
theory of dynamic stability applicable to both linear and
nonlinear systems. His work was largely buried and forgotten
until it was exhumed nearly 30 years after his death.
... ... *observation of brownian motion: The experiment here
involved a colloidal particle of 2.5 microns diameter moving in
suspension in deionized water at 22 degrees Celsius, with
recorded observations of 145,612 positions over a total time
interval of approximately 2430 seconds, the observations
involving a microscope and video camera, the smallest resolution
stated as 25 nanometers. Particles of this size undergo
sedimentation, which may confound the results with non-Brownian
effects, but the authors report studies of non-sedimenting
smaller particles substantiate their observations, the larger
particle simply allowing tracking observations for a longer time.
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SCIENCE-WEEK 1998 18 Sep
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3. ON THE MORPHOLOGICAL EVOLUTION OF GALAXIES
R.G. Abraham and S. van den Bergh (University of Toronto, CA)
discuss the morphology of galaxies. Nearby galaxies are usually
classified on the basis of a scheme originally proposed by Edwin
Hubble (1889-1953) in 1926. This "tuning fork" classification
system characterizes galaxies with reference to a set of bright
nearby standard galaxies. In Hubble's scheme, galaxies are
divided into ellipticals and spirals. Spiral galaxies are
subdivided into unbarred (S) and barred (SB) categories, which
define the tines of the tuning fork. Along each tine, galaxies
are further subdivided according to the tightness and fine
structure of their spiral arms, which changes monotonically along
the tuning fork in step with the fraction of light in the central
bulge of the galaxy. These subcategories are denoted Sa, Sb, and
Sc (SBa, SBb, SBc in the case of barred spirals). A catch-all
category for irregular galaxies is also included. However, many
galaxies have taken on their familiar appearance relatively
recently, and in the distant Universe, galaxy morphology deviates
significantly (and systematically) from that of nearby galaxies
at redshifts (z) as low as 0.3. This corresponds to a time
approximately 3.5 billion years in the past, which is only
approximately 25 percent of the present age of the Universe.
Beyond z = 0.5 (5 billion years in the past), spiral arms are
less well developed and more chaotic, and barred spiral galaxies
may become rarer. At z = 1, approximately 30 percent of the
galaxy population is sufficiently peculiar that classification by
Hubble's traditional "tuning fork" system is meaningless. On the
other hand, some characteristics of galaxies have not changed
much over time. The space density of luminous disk galaxies has
not changed significantly since z = 1, indicating that although
the general appearance of these galaxies has continuously changed
over time, their overall numbers have been conserved.
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Science 2001 293:1273
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4. GENERATION OF A STABLE TRIPLET CARBENE
H. Tomioka et al (Mie University, JP) discuss carbenes. Most
molecules are held together by covalent bonds -- electron pairs
jointly shared by the two atoms that are linked by the bond. Free
radicals, in contrast, have at least one unpaired electron. In
the case of carbon-based radicals, the carbon atom at the radical
center no longer makes 4 bonds with other atoms as it would do in
its normal and tetravalent state. The presence of unpaired
electrons renders such radicals highly reactive, so they normally
occur only as transient intermediates during chemical reactions.
But the discovery by M. Gomberg in 1900 of triphenylmethyl, the
first relatively stable free radical containing a central
trivalent carbon atom, demonstrated that radicals with suitable
geometrical and electronic structures can be stable. Compounds
containing a divalent carbon atom that uses only 2 of its 4
valence electrons for bonding are usually less stable than
Gomberg-type radicals with trivalent carbon. Although the role of
these so-called "carbenes" in chemical reactions has long been
postulated, they were unambiguously identified only in the 1950s.
More recently, stable carbenes have been prepared, but the
singlet state of these molecules, with the 2 nonbonding valence
electrons paired, means that they are not radicals. Carbenes in
the second possible electronic state, the triplet state, are
radicals: the 2 nonbonding electrons have parallel spins and
occupy different orbitals. The authors report the preparation and
characterization of a triplet carbene whose half-life of 19
minutes at room temperature shows it to be significantly more
stable than previously observed triplet carbenes.
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Nature 2001 412:626
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Related Background:
STABILIZATION OF CARBENES
The term "carbene" refers to chemical species of the type
R(sub2)C, in which the carbon atom has two electrons that do not
form bonds. Methylene is the simplest example. Carbenes are
highly reactive and ordinarily exist only as transient
intermediates in certain organic reactions. In general, carbenes
attack double bonds to give cyclopropane derivatives, and they
also cause insertion reactions in which the carbene group is
inserted between the carbon and hydrogen of a C-H bond. Curt
Wentrup (2001) discusses carbene chemistry. Although stable free
radicals were first prepared in 1900, stable carbenes have long
remained elusive. Carbenes have become well-established synthetic
intermediates, their high reactivity making them versatile
targets for preparative, mechanistic, and theoretical studies.
Now Sole et al (2001) report an important synthetic advance that
enables the preparation of unusually stable yet highly reactive
carbenes, and related carbene species may find future
applications as efficient catalysts. Certain carbenes have been
shown to form exceptionally strong bonds with virtually all the
transition elements and many lanthanides, and carbenes may thus
surpass the ubiquitous phosphine ligands in organometallic
catalytic chemistry.
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Science 2001 292:1846,1901
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5. ON THE DETECTION OF EXTRASOLAR TERRESTRIAL PLANETS
E.B. Ford et al (Princeton University, US) discuss extrasolar
terrestrial planets. The detection of massive planets orbiting
nearby stars has become almost routine, but current techniques
are as yet unable to detect terrestrial planets with masses
comparable to that of Earth. Future space-based observatories to
detect Earth-like planets are being planned. Terrestrial planets
orbiting the habitable zones of stars -- where planetary surface
conditions are compatible with the presence of liquid water --
are of enormous interest because they might have global
environments similar to Earth's and may even harbor life. The
light scattered by such a planet will vary in intensity and color
as the planet rotates, and the resulting light curve will contain
information about the planet's surface and atmospheric
properties. The authors report a model that predicts features
that should be discernible in the light curve obtained by low-
precision photometry. For extrasolar planets similar to Earth,
the authors expect daily flux variations of up to hundreds of
percent, depending sensitively on ice and cloud cover as well as
on seasonal variations. The authors suggest this indicates that
the meteorological variability, composition of the surface (e.g.,
ocean versus land fraction), and rotation period of an Earth-like
planet could be derived from photometric observations. Even
signatures of Earth-like plant life could be constrained, or
possibly with further study, even uniquely determined.
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Nature 2001 412:885
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6. ON THE STANDARD MODEL OF PLANET FORMATION
S.J. Kortenkamp et al (University of Maryland, US) discuss planet
formation. The standard model of planet formation begins with a
protoplanetary disk of gas and dust orbiting a central protostar.
Growth of terrestrial planets in such a disk is usually described
in 3 stages: 1) accretion of dust particles into 10^(12) to
10^(18) grams (kilometer-size) comprising planetesimals in
approximately 10,000 years; 2) gravitational accumulation of
planetesimals via a process called "runaway growth", which
produces 10^(26) to 10^(27) grams (Mercury- to Mars-size)
comprising planetary embryos in approximately 100,000 years; and
3) giant impacts between embryos, resulting in full-size 10^(27)
to 10^(28) grams comprising terrestrial planets in 100 million
years. Farther out in the disk, the density of solids is enhanced
with condensed ices and the embryos may be capable of reaching
approximately 10 Earth-masses in 1 million years. Upon reaching
this mass, the bodies may begin accumulating approximately 100
Earth-masses of disk gas to form giant planets like Jupiter and
Saturn in 10 million years. This is the "core-accretion"
mechanism of giant planet formation, referring to the growth of a
solid core followed by accretion of gas. The standard model of
planet formation was developed to help explain how planets could
have formed around our isolated Sun. However, binary stars are
the most common outcome of the star formation process, and
evidence exists for protoplanetary disks in young multiple-star
systems. The end-state of planet formation in such systems has
also been observed, and nearly 30 percent of the detected
extrasolar planets exist in multiple-star systems. The standard
model of planet formation cannot easily accommodate such systems
and has difficulty explaining the odd orbital characteristics of
most extrasolar giant planets. The authors demonstrate that the
formation of terrestrial-size planets may be insulated from these
problems, enabling mush of the framework of the standard model to
be salvaged for use in complex systems. A type of runaway growth
is identified that allows planetary embryos to form by a
combination of nebular gas drag and perturbations from massive
companions -- be they giant planets, brown dwarfs, or other
stars.
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Science 2001 293:1127
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7. ON EVOLUTION AND SEXUAL REPRODUCTION
Richard E. Lenski (Michigan State University, US) discusses
evolution and sexual reproduction, the author making the
following points:
1) Why have some organisms evolved the capacity for sexual
reproduction, whereas others make do with reproducing asexually?
Since the time of August F. Weismann (1834-1914), most biologists
have been taught that sex produces variation and thereby promotes
evolutionary adaptation. But how does sex achieve this effect,
and under what circumstances is it worthwhile?
2) The traditional explanation for sex is that it
accelerates adaptation by allowing two or more beneficial
mutations that have appeared in different individuals to
recombine within the same individual. Without sexual
recombination, individual clones that possess different
beneficial mutations compete with one another, slowing adaptation
by clonal interference. Sex, according to the traditional
explanation, allows simultaneous improvements at several genetic
loci, whereas multiple adaptations must occur sequentially in
clonal organisms.
3) The above explanation, however, has recently come into
question. First, sex imposes a 50 percent reduction in
reproductive output: If a female can produce viable offspring on
her own, why dilute her genetic contribution to subsequent
generations by mating with a male? Second, the circumstances
under which this kind of model provides sufficient advantage to
offset the cost of sex are restrictive, requiring certain forms
of selection and environmental fluctuations. Third, alternative
models propose that the advantage of sex lies in eliminating
deleterious mutations rather than in combining beneficial
mutations. Still another hypothesis, involves an interplay
between deleterious and beneficial mutations. Finally, empirical
tests of these hypotheses have so far failed to produce a clear
winner, so the field is ripe for significant experiments.
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Science 2001 294:533
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8. PSYCHOLOGICAL DEPRESSION AND THE SHRINKING HIPPOCAMPUS
Robert M. Sapolsky (Stanford University, US) discusses
psychological depression, the author making the following points:
1) Throughout human history, it has been apparent that few
medical maladies are as devastating in their effects as major
depression. And since the 1950s, with the advent of the first
generation of antidepressant drugs, it has been apparent that
depression is a biological disorder. This has generated the
tremendous intellectual challenge of how to understand the
material, reductive bases of a disease of malignant sadness.
2) Both the tragic components and the intellectual challenge
of depression have deepened in the last decade with a series of
high-visibility reports that indicate prolonged major depression
is associated with atrophy within the central nervous system.
Such atrophy is centered in the brain region called the
hippocampus [see background material below]. This structure plays
a critical role in learning and memory, and the magnitude of the
hippocampal volume loss (nearly 20 percent in some reports) helps
explain some well-documented cognitive deficits that accompany
major depression.
3) These findings of hippocampal atrophy raise immediate
questions. First, is it permanent? Tentatively, this appears to
be the case, as the atrophy persists for up to decades after the
depressions are in remission. Next, does the hippocampal atrophy
arise as a result of depression, or does it precede and even
predispose toward depression? There is little evidence for the
latter, and most researchers tacitly assume that this
morphological change is a consequence of the biology underlying
the affective (mood) aspects of the disease.
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Proc. Nat. Acad. Sci. 2001 98:12320
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Related Background:
NEUROBIOLOGY: NEUROGENESIS AND CLINICAL DEPRESSION
The term "depression" as used in clinical psychiatry is a
large basket filled with diagnostic ambiguities, historical
semantic baggage, and shifting therapeutic fashions.
Nevertheless, the clinical syndrome, no matter how foggy its
outlines, is real at its core, affects real people, is a major
cause of psychological dysfunction, and a major cause of suicide.
In the US alone, approximately 200,000 suicide attempts are made
each year; 75 people commit suicide every day; suicide accounts
for 30 percent of the deaths among university students and is the
second leading cause of death among adolescents. What is known is
that clinical depression is involved in over half of all
attempted suicides, a relation that defines the urgency of
research in this area. From the standpoint of clinical
neurobiology, the research problem is clear: clinical depression,
whatever it may be, is a dysfunctional alteration of behavior,
and the task of the clinical neurobiologist is to determine what,
if any, dysfunctional alterations of the brain and/or brain
dynamics are responsible for the clinical syndrome.
The term "neurogenesis" refers to the generation of new
nerve cells. Until a few years ago, neurogenesis was considered
to be totally absent in the adult mammalian brain, but
neurogenesis has now been identified in certain regions of the
brains of several mammalian species, and there is currently much
research devoted to relating brain neurogenesis to various brain
pathologies.
... ... B.L. Jacobs et al (3 authors at 2 installations, US)
present a review of recent research relating clinical depression
and brain neurogenesis, the authors making the following points:
1) The authors point out that many researchers believe that
*stress is the most significant causal agent (with the possible
exception of genetic predisposition) in the etiology of
depression. In addition, nerve cells in the *hippocampal region
of the brain are among the most sensitive to the deleterious
effects of stress. Consequently, a stress-induced decrease in
neurogenesis in the hippocampus may be an important factor in
precipitating episodes of depression. As a corollary, increasing
*serotonin-related neurotransmission is apparently the most
effective treatment for depression, and such treatment also
augments (in animal models) hippocampal neurogenesis. Thus,
serotonin-induced increases in neurogenesis might promote
recovery from depression. Considering all this, the authors
propose that the waxing and waning of neurogenesis in the
hippocampus might trigger the precipitation of and recovery from
episodes of clinical depression.
2) The relation between stress and hippocampal neurogenesis
has been examined in several species. Removing the *adrenal
glands of a rat increases neurogenesis in the *dentate gyrus, and
this effect can be reversed with the *glucocorticoid hormone
corticosterone, which normally is secreted by the adrenal glands.
The circulating level of glucocorticoids apparently suppresses
the birth of neurons in the dentate gyrus under normal
conditions. It has also been demonstrated that systemic
administration of corticosterone to normal animals suppresses
dentate gyrus neurogenesis. In summary, stress apparently
suppresses the rate of dentate-gyrus cell proliferation in adults
of a number of species, and it probably does so through increases
in brain glucocorticoids.
3) The authors point out that they do not exclude other
changes as being important in the etiology and recovery from
depression. For example, besides suppressing neurogenesis,
increased glucocorticoids might mediate additional direct
neuronal effects in various brain structures. Similarly, changes
in serotonin neurotransmission might also exert direct effects in
various brain structures. The authors suggest that all of these
changes, acting in concert, give rise to the complex syndrome of
depression.
-----------
American Scientist 2000 88:340
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Notes:
... ... *stress: See background material below.
... ... *hippocampal region: See background material below.
... ... *serotonin-related neurotransmission: The term
"neurotransmission" refers, in general, to the interactions
between nerve cells. Serotonin is one of a variety of
neurotransmitter substances, i.e., substances involved in the
mechanisms of neurotransmission.
... ... *adrenal glands: Organs that sit on the tops of the
kidneys (one on each kidney). Each adrenal gland has two parts,
adrenal cortex and adrenal medulla. The adrenal cortex secretes
corticosteroid and androgen hormones; the adrenal medulla makes
the hormones epinephrine (adrenalin) and norepinephrine.
... ... *dentate gyrus: The term "dentate gyrus" refers to one of
the two interlocking gyri (folds) composing the hippocampus.
... ... *glucocorticoid hormone corticosterone: See background
material below.
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SCIENCE-WEEK 2000 1 Dec
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Related Background:
NEUROBIOLOGY: NEUROLOGICAL CORRELATES OF LEARNING DEFICITS
PRODUCED BY PRENATAL STRESS
The concept of "stress" has a long and rich history in
psychobiology. Hans Selye (1907-1982) pioneered the idea of a
discrete paradigm describing the linkage between psychological
stress, physiological response (usually involving hormone
secretions), and histopathological consequences. In the medical
community, during the past 50 years, the degree to which any such
paradigm linking psychological events to specific tissue
pathology has been accepted has varied widely from one individual
physician to another. In general, current neurobiological and
psychobiological researchers take the paradigm for granted;
medical practitioners accept or avoid the paradigm, depending on
their training in psychiatry. But what is not disputed by anyone
is that psychological events, particularly psychological "stress"
(in the general sense of the term) can produce physiological
changes that may include changes in the secretions of hormones,
and that such changes, in turn, may affect the behavior of
various parts of the nervous system. (As elementary examples of
physiological changes produced by psychological stress, consider
the change in heart rate produced by a frightening psychological
event, or the alteration of the capillary beds in the skin of the
face (blushing) produced by an embarrassment.)
The central question remains of profound importance: To what
extent can environmental psychological stresses perceived by the
sensory systems produce long-lasting pathological changes in
tissues both neural and non-neural?
But if the question is important (and rather easily stated),
attempts to obtain an answer are confronted with enormous
difficulties because of the limitations of research with human
subjects. Animal models are of prime importance in this field,
and although the extrapolation from an animal model to human
biology in this domain is often uncertain, each piece of
information is a potential nugget in a field where research is
not easy.
The term "corticosterone" refers to a glucocorticoid,
specifically to an important corticosteroid of the normal human
adrenal cortex. Among other things, corticosterone induces
deposition of glycogen in the liver, sodium conservation, and
potassium secretion. It is the principal glucocorticoid in the
rat. (In general, a "glucocorticoid" [glycocorticoid] is any
steroid-like compound capable of significantly influencing
intermediary metabolism.
The term "hippocampus" refers to a region of the cerebral
cortex in the medial part of the temporal lobe. In humans, among
other functions, the hippocampus is apparently involved in
short-term memory, and analysis of the neurological correlates of
learning behavior in animals indicates that the hippocampus is
also involved in memory in other species.
The term "dentate gyrus" refers to one of the two
interlocking gyri (folds) composing the hippocampus.
... ... V. Lemaire et al (4 authors at University of Bordeaux,
FR) present a study of the effects of prenatal stress in rats on
neurological development, the authors making the following
points:
1) There is much evidence from animal studies that during
the period immediately before, during, and immediately after
birth (perinatal period), the development of an organism is
subjected to complex environmental influences. For example,
deleterious life events during pregnancy may induce
neurobiological and behavioral defects in offspring, with some of
these effects involving the hippocampus. Indeed, there is
evidence that prenatal stress results in an enhanced production
of stress hormones by the mother during critical periods of fetal
brain development, and that prenatal stress provokes a longer
corticosterone response to stress in the offspring associated
with a reduction in the number of hippocampal corticosteroid
receptors. Behaviorally, such progeny, from adulthood to
senescence, exhibit memory deficits in a hippocampal dependent
task.
2) The authors report that prenatal stress in rats induced
lifespan reduction of neurogenesis in the dentate gyrus and
produced impairment in hippocampal-related spatial tasks.
Prenatal stress blocked the increase of learning-induced
neurogenesis. The authors suggest their data strengthen
pathophysiological hypotheses that propose an early
neurodevelopmental origin for psychopathological vulnerabilities
in aging.
3) In this study, stress was performed each day of the last
week of pregnancy from day 15 until delivery. Pregnant females
were individually restrained for 45 minutes 3 times a day during
the light phase in plastic transparent cylinders (7 centimeters
diameter, 19 centimeters long) exposed to bright light. Control
pregnant females were left undisturbed in their home cages.
4) The authors conclude: "The major impact of our data lies
in the demonstration that deleterious environmental conditions
occurring early in life have profound effects on neurogenesis in
the dentate gyrus, an index of hippocampal *plasticity, and that
these alterations are associated with impaired performances in a
spatial memory task. Neurogenesis, cell number, and cognitive
capabilities are altered from adulthood to senescence in
prenatally stressed rats... Our results reinforce the hypothesis
that many psychopathological affections have their origin in
early developmental influences. More generally, they show the
heuristic value of accurate animal models to better understand
the mechanisms by which early stress and *epigenetic risk factors
promote learning disabilities in children and in age-related
disorders such as Alzheimer's disease."
-----------
Proc. Nat. Acad. Sci. 2000 97:11032
-----------
Notes:
... ... *plasticity: In neurobiology, the term "plasticity" is
the name given to the capacity of neural tissue to adjust to
change. One variant of this concerns the dependence of the
"wiring" of the nervous system on its input. Another variant
concerns the degree to which one region can under certain
conditions assume the function of another region. Plasticity does
not occur everywhere in the nervous system, but it is often
evident in the cerebral cortex of the brain, the cortex being the
thin layer of cells apparently responsible for higher analysis of
sensory input, language, ideation, and other so-called higher
functions lumped together in the category "cognitive processes".
... ... *epigenetic risk factors: In this context, risk factors
associated with fetal and postnatal development.
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SCIENCE-WEEK 2000 20 Oct
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Related Background:
ON THE NEUROBIOLOGY OF DEPRESSION
Charles B. Nemeroff (Emory University, US), in a review of the
neurobiology of depression, makes the following points: 1) It is
estimated that 5 to 12 percent of men and 10 to 20 percent of
women in the US will suffer from a major depressive episode
sometime in their life. Approximately half of these individuals
will become depressed more than once, and up to 10 percent will
experience manic phases in addition to depressive phases, a
condition known as manic-depressive illness or bipolar disorder.
2) As many as 15 percent of those who suffer from depression or
bipolar disorder commit suicide each year. In 1996, the US
Centers for Disease Control and Prevention listed suicide as the
9th leading cause of death in the US, taking the lives of 30,862
people. Most experts believe this number is a gross under-
estimate. 3) The search for the biological underpinnings of
depression is intensifying, and emerging findings promise to
yield better therapies. 4) The mind does not exist without the
brain. Considerable evidence indicates that regardless of the
initial triggers, the final common pathways to depression involve
biochemical changes in the brain, and it is these changes that
ultimately give rise to deep sadness and the other salient
characteristics of depression 5) Biochemical abnormalities that
are prominent in some depressions may differ from those
predominating in others. 6) There has been no success in
identifying specific genes involved in depression, perhaps
because any genetic predisposition to depression may involve
several genes, each of which makes only a small and hard-to-
detect contribution. 7) Many cases of depression apparently stem
at least in part from disturbances in brain circuits that convey
signals via certain neurotransmitters of the *monoamine class
(e.g., norepinephrine). 8) There is mounting evidence that
chronic overactivity of the hormonal system known as the
hypothalamic-pituitary-adrenal axis in response to stress, in
particular the overproduction of *corticotropin-releasing factor,
contributes to depression. 9) The author proposes a stress-
diasthesis model of mood disorders, the model involving an
interaction between experience (stress) and inborn predisposition
(diasthesis).
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Scientific American June 1998
Science-Week 1998 26 Jun
-------------------
Notes:
... ... *monoamine: The monoamines in this context are a class of
neurotransmitters that includes 3 catecholamines (dopamine,
norepinephrine, epinephrine), an indoleamine (serotonin), a
quaternary amine (acetylcholine), and an ethylamine (histamine).
... ... *corticotropin-releasing factor (CRF): This is a 41-amino
acid hypothalamic polypeptide discovered in 1981, and the
evidence indicates it is a major physiological regulator of the
pituitary-adrenal axis. It controls release of various hormones
from the anterior pituitary. There is considerable evidence that
CRF is also a neurotransmitter in brain areas outside the
hypothalamus. It apparently mediates neuroendocrine, autonomic,
and behavioral responses to stress, and there is evidence that
CRF-containing neurons play a role in the pathophysiology of
anxiety disorders.
-----------
ScienceWeek 1998 26 Jun
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9. ON HUMAN EVOLUTION
Ian Tattersall (American Museum of Natural History, US) discusses
human evolution. When we contemplate the extraordinary abilities
and accomplishments of Homo sapiens, it is certainly hard to
avoid a first impression that there must somehow have been an
element of inevitability in the process by which we came to be
what we are. The product, it's easy to conclude, is so
magnificent that it _must_ stand as the ultimate expression of a
lengthy and gradual process of amelioration and enhancement. How
could we have got this way by accident? If we arrived at our
exalted state through evolution, then evolution must have worked
long and hard at burnishing and improving the breed, must it not?
Yet that seems not to be how evolution works; for natural
selection is not -- it cannot be -- in itself a creative process.
Natural selection can only work to promote or eliminate novelties
that are presented to it by the random genetic changes
(influenced, of course, by what was there before) that lie behind
all biological innovations. Evolution is best described as
opportunistic, simply exploiting or rejecting possibilities as
and when they arise, and in turn, the same possibility may be
favorable or unfavorable, depending on environmental
circumstances (in the broadest definition) at any given moment.
There is nothing inherently directional or inevitable about this
process, which can smartly reverse itself any time the fickle
environment changes.
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Scientific American 2001 December
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10. ON THE HISTORY OF EUGENICS IN THE US
History contains many instances of the ignoble application of
science, and one of the most disastrous examples is that of the
so-called science of "eugenics" in the first half of the 20th
century. Recent major advances in molecular genetics and genetics
biotechnology have produced in some quarters a "genetics
euphoria", with many researchers rushing to establish the
"genetic basis" of various human "behavior traits", the latter
term encompassing, by implication, both "good" and "bad" behavior
traits. Can we expect a proposed therapeutic program to eliminate
genetically based "bad behavior traits"? History suggests extreme
caution is necessary.
... ... Garland E. Allen (Washington University St. Louis, US)
discussed the history of eugenics in the US, the author making
the following points:
1) The term "eugenics" was coined in 1883 by the Victorian
polymath Francis Galton (1822-1911), geographer, statistician,
and first cousin of Charles Darwin (1809-1882). To Galton, the
term meant "truly- or well-born", and referred to a plan to
encourage the "best people" in society to have more children
(positive eugenics) and to discourage or prevent the "worst
elements" of society from having many, if any, children (negative
eugenics). Eugenics became solidified into a movement in various
countries throughout the world in the first three decades of the
20th century, but nowhere more solidly than in the US and, after
World War I, in Germany.
2) During the first three decades of the 20th century,
eugenicists attempted to analyze the inheritance of traits by
using correlation studies between relatives and studies of family
pedigree charts. The basic assumption was that if a trait
recurred in families over several generations, it must be
genetic. For example, the American eugenicist Charles B.
Davenport, director of the Station for Experimental Evolution and
the Eugenics Record Office at Cold Spring Harbor, Long Island,
New York, constructed elaborate pedigrees for Huntington's
chorea, albinism, epilepsy, feeblemindedness, and thalassophilia
or "love of the sea" (which he found to be a Mendelian sex-linked
recessive trait especially prominent in the families of naval
officers). Harry H. Laughlin, superintendent of the Eugenics
Record Office, studied the inheritance of criminality,
feeblemindedness, and many other deleterious traits in different
ethnic and racial groups. He concluded that eastern Europeans,
Mediterraneans, and Russian Jews, among others, harbored a large
number of defective genes in their populations. Such studies,
sprinkled with anecdotes, formed the backbone of eugenic
"science".
3) American eugenicists also worked to establish eugenics-
based legislation in the US. Laughlin was appointed "Expert
Eugenics Witness" to the House Committee on Immigration and
Naturalization in 1921. His prison and hospital data were
critical in convincing the Committee that America's germ plasm
was being weakened by mixing with the lower quality genes coming
from southern and eastern Europe, the Balkans, and Russia. This
led to passage of the Johnson-Reed Act in 1924, which restricted
immigration from these regions. Laughlin and others also lobbied
at the state level for the passage of eugenic sterilization laws,
which would allow individuals in state institutions to be
forcibly sterilized if they were judged to be genetically
defective. More than 35 states passed and used such laws, and by
the 1960s, when most of these laws were beginning to be repealed,
more than 60,000 people in the US had been sterilized for eugenic
purposes. In Germany, the National Socialists (Nazis) used
Laughlin's model as one of the bases of their sweeping
sterilization law of 1933, which ultimately led to the
sterilization of over 400,000 people.
-----------
[Editor's note: The US eugenics movement did not wither away
easily. As late as the 1960s, noted biologist and endocrinologist
Dwight J. Ingle (1907-?), member of the US National Academy of
Sciences and Chairman of the Department of Physiology at the
University of Chicago, founder and long-time editor of the
influential journal _Perspectives in Biology and Medicine_,
continued calling in widely read published articles for the mass
eugenic sterilization of American blacks to prevent "weakening"
of the US Caucasian germ pool. A similar public call for mass
eugenic sterilization of blacks was made during that time and
later by the noted physicist and engineer and Nobel laureate
William B. Shockley (1910-1989) (also a member of the US National
Academy of Sciences). Memoirs concerning Shockley in current
science publications rarely mention his socio-political
activities in the 1960s and later; the journal _Perspectives in
Biology and Medicine_ currently maintains a "Dwight J. Ingle
Memorial Award". In 1980, Shockley revealed that he had
contributed some of his 70-year-old sperm cells for the purpose
of freezing the sperm for eventual use in the insemination of
women of high intelligence. All of which brings to mind a
statement by the biochemist Erwin Chargaff, published in of all
places the journal _Perspectives in Biology and Medicine_ (1973):
"Outside his own ever-narrowing field of specialization, a
scientist is a layman. What members of an academy of science have
in common is a certain form of semiparasitic living." Dwight J.
Ingle was still editor of the journal at the time Chargaff's
statement was published.]
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Science 2001 294:59
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11. CALCIUM ION REGULATION IN BIOLOGICAL CELLS
T.R. Soderling and J.T. Stull (Oregon Health Sciences University,
US) discuss calcium ion regulation. The concentration of free
intracellular calcium ions is highly regulated because calcium
ion is an important cellular signaling molecule. Basal levels of
intracellular calcium ions in most mammalian cells are in the 10
to 50 nanomolar range, and stimulated concentrations are
generally 500 to 1000 nanomoles. Since concentrations of calcium
ions in the extracellular space or intracellular organelles
(endoplasmic and sarcoplasmic reticulum and mitochondria) are in
the millimolar range, the cell has numerous mechanisms for
modulating calcium ion concentration, both temporally and
spatially. Such mechanisms include ligand- and voltage-gated ion
channels, calcium ion pumps, and exchangers in both the plasma
membrane and intracellular calcium-ion storage organelles. These
ion channels, pumps, and exchangers are subject to complex
regulation by cellular signaling pathways. For example, the so-
called L-type calcium ion channel that is primarily activated by
membrane depolarization (i.e., it is voltage-gated) is also
subject to additional modulation via covalent phosphorylation by
protein kinases, which in turn are stimulated by cyclic AMP
(cAMP) or calcium. Temporal and spatial changes in calcium ion
concentration mediate responses of many agonists such as
hormones, growth factors, and neurotransmitters, and mammalian
cells contain a large number of proteins that bind calcium ions
with varying specificity and affinity.
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Chem. Revs. 2001 101:2341
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12. ON THE HISTONE CODE
T. Jenuwein and C.D. Allis (Institute of Molecular Pathology
Vienna, AT) discuss the histone code. In the nuclei of all
eukaryotic cells, genomic DNA is highly folded, constrained, and
compacted by histone and nonhistone proteins in a dynamic polymer
called "chromatin". For example, chromosomal regions that remain
transcriptionally inert are highly condensed in the interphase
nucleus and remain cytologically visible as heterochromatic foci
or as the so-called "Barr body", which is the inactive X
chromosome in female mammalian cells. The distinct levels of
chromatin organization are dependent on the dynamic higher order
structuring of "nucleosomes", which represent the basic repeating
unit of chromatin. Genomic DNA is the ultimate template of our
heredity. Yet despite the justifiable excitement over the human
genome, many challenges remain in understanding the regulation
and transduction of genetic information. It is unclear, for
example, why the apparent number of protein-coding genes in
humans, now estimated at approximately 35,000, only doubles that
of the fruit fly Drosophila melanogaster. Is DNA alone then
responsible for generating the full range of information that
ultimately results in complex eukaryotic organisms such as
ourselves? The authors favor the view that epigenetics, imposed
at the level of DNA-packaging proteins (histones), is a critical
feature of a genome-wide mechanism of information storage and
retrieval that is only beginning to be understood. The authors
propose that a "histone code" exists that may considerably extend
the information potential of the genetic (DNA) code.
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Science 2001 293:1074
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13. POSTDOCTORAL FELLOWSHIP PROFILE:
Laboratory of Weiming Xia, Harvard University
---------------------------------------------
Installation: Brigham and Women's Hospital, Harvard Medical
School, Harvard University
Department: Department of Neurology
General research area: Neuroscience
Head of this specific laboratory: Weiming Xia, Ph.D.
Postdoctoral fellowships are available in the following
research problems: Protein proteolysis and gene expression
profiling in neurodegenerative diseases
Previous research experience and degrees required: Ph.D. or
M.D. in biological or medical science.
Usual starting stipend: $30,000
Special requirements concerning citizenship, etc.: None
Approximately number of people currently working in this
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14. IN FOCUS: ON INFLAMMATION
"Redness and swelling with heat and pain -- _ruber et tumor cum
calore et dolore_ -- have been recognized as the four cardinal
signs of inflammation since the writings of Cornelius Celsus in
the first century of the common era (30 BC to 38 AD). Celsus --
who is sometimes mistaken for Celsius of thermometry -- was
describing the typical reaction of flesh to microbes. Although
all sorts of injuries to humans and beasts will elicit
inflammation, it seems clear that our extensive arsenal of host
defenses has not been stocked by evolution against such recurrent
threats as ionizing radiation, crack cocaine, bombs plastique, or
Katyusha rockets. No, the drab Darwinism of biology suggests that
whereas inflammation may help the individual cope with cuts and
bruises, most of the redness and swelling with heat and pain is
there to make sure that the species is now wiped out by
epidemics. It seems to me that the more we learn about
inflammation, the simpler its message becomes: Our cells and
humors defend the self against invisible armies of the other. We
call our losses 'infection' and our victories 'immunity'. As in
other branches of science, the language we use to describe the
battle of inflammation derives as much from our cultural heritage
-- or the temper of our times -- as from the facts of nature...
The warfare between humans and bacteria was not appreciated as an
order of battle until the microbe hunters of the 19th century
recognized the opposing forces and the territory in dispute. By
1908, when the Nobel Prize was given to Paul Ehrlich [1854-1915]
for his work on humoral immunity (antibodies) and to Elie
Metchnikoff [1845-1916] for his work on cellular immunity
(phagocytosis), it was clear that the body uses these two
strategies in concert to identify and destroy invaders."
-----------
Gerald Weissmann: _Darwin's Audubon: Science and the Liberal
Imagination_
(Perseus Publishing, Cambridge MA 1998, p.25)
(First Paperback Edition December 2001)
http://www.amazon.com/exec/obidos/ASIN/0738205974/scienceweek
-----------
SCIENCE-WEEK 4 Jan 2002 http://scienceweek.com
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15. FROM PRAXIS:
A SHARP CRITICISM OF US HEALTH INSURANCE POLICY
Brian Vastag (J. Am. Med. Assoc., US) discusses US health
insurance. A recent report of the Institute of Medicine says that
the jumble of health insurance schemes in the US "functions more
like a sieve than a safety net". The report paints a bleak
picture of the nation's uninsured. Nearly 18 percent of the US
lacks health coverage -- some 32 million to 42 million people, a
number exceeding the combined populations of Texas, Florida, and
Connecticut. The insurance gap hits working families (those with
at least one worker) particularly hard. A full 80 percent of
uninsured persons under age 65 live in working families; many
survive on low wages from service jobs. Families with two wage
earners fare better, but 10 percent of those families lack health
coverage. While the proportion of uninsured dropped in 1999 and
2000, it is expected to rise again due to ballooning costs. Mary
Sue Coleman, co-chair of the committee that wrote the report and
president of the Iowa Health System and the University of Iowa
(Iowa City) states: "More than the state of the economy, the
rising cost of health care services and insurance premiums,
combined with a hodgepodge of policies and practices, undermines
the affordability for employers, their workers, and the public at
large. In general in the US, millions of adults and children
rarely visit a physician, missing out on care for chronic
illnesses and opportunities for prevention. With nowhere else to
turn, they tend to seek care at emergency departments, often only
after health problems flare and become intolerable.
-----------
J. Am. Med. Assoc. 2001 286:2223
-----------
PRAXIS 31 Dec 2001 http://scienceweek.com/praxis
-----------
SCIENCE-WEEK 4 Jan 2002 http://scienceweek.com
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16. THIS WEEK IN PRAXIS (31 Dec 01):
-------------------------------
1. Anatomy of the Human Genome
2. National Survey of Stress Reactions Following 11 Sep 2001
3. Sharp Criticism of US Health Insurance Policy
4. On Alzheimer's Disease
5. Inhalation Delivery of Proteins
6. DNA Microarray Analysis and Breast Cancer Prognosis
7. New Method for Discovering Unrecognized Viruses
8. On Science and Technology Advice for Congress
9. On Nanowire Nanosensors
10. Determination of Enantiomeric Excess
11. A New Neuroelectronic Interface
12. Molecular Sieve With Adjustable Pores
For information about PRAXIS, see:
http://www.scienceweek.com/praxis
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In the text, the affiliation following the names of authors is
the affiliation of the lead author.
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