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ScienceWeek
SCIENCEWEEK
ScienceWeek - September 20, 2002 Vol. 6 Number 38
An Online Research Digest Published Weekly Since 1997
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Discovery consists of seeing what everybody has seen and
thinking what nobody has thought.
-- Albert Szent-Gyorgyi (1893-1986)
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Section 1
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1. On the Accuracy of Climate Simulations
2. Inorganic Chemistry: On Aurophilicity
3. On Dielectric Black Hole Analogs
4. Neurobiology: On Axon Regeneration
5. Neural Plasticity: The Auditory-Visual System Linkage
6. Paleoanthropology: On the New Hominid Fossil from Chad
7. Stimulated Emission by Three-Photon Excitation
8. On Guiding X-Ray Photons
9. Inorganic Chemistry: On Transition Metal Nitrosyls
10. On Fetal Alcohol Syndrome
11. Obesity and the Risk of Heart Failure
12. On the Treatment of Obesity
13. ScienceWeek Notices and Subscription Information
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Section 2
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1. ON THE ACCURACY OF CLIMATE SIMULATIONS
T.M. Smith et al (National Climatic Data Center, US) discuss
climate simulations, the authors making the following points:
1) It is a fundamental tenet of the scientific method that
theories must be consistent with observations. To test our
understanding of the climate system, we must evaluate how
accurately climate models reproduce not only today's climate
(1), but also the climate of the past. Over the past decade, the
observed climate record has become more complete, allowing the
climatic effects of natural agents and human-related changes in
atmospheric composition (collectively referred to as "climate
forcing") to be estimated. We can now test how well climate
models simulate century-scale variations in the observed climate
record. There have been numerous intercomparisons of various
climate model simulations of 20th-century climate, based on the
best available estimates of the climate forcing (2).
2) A standard assumption in these intercomparisons is that the
model simulations should reproduce as closely as possible
observed climate variability. This assumption must, however, be
viewed with caution. Observational errors, sampling errors, and
time-dependent biases degrade the climate record. Considerable
effort has been spent at minimizing these biases (3,4), yet
problems remain. Consider for example the worldwide record of
sea surface temperatures, which dates back to the 19th century.
At present, several different estimates of time-dependent bias
adjustments and the effects of incomplete and changing spatial
sampling can be used to correct the observational record before
1942 (2-5). Different assumptions and adjustment techniques lead
to additional uncertainty in the climate record.
3) Climate models are not perfect either. Errors evolve in
climate simulations as a result of incomplete physical
understanding and limited knowledge of past (or future) climate
forcing. These errors must be considered along with the
uncertainty related to climate chaos, which occurs because of
nonlinear interactions in the global climate system. Climate
chaos errors can be addressed through repeated runs of a climate
model with the same forcing, but different starting conditions.
These ensemble simulations can then be used to estimate the
magnitude of the uncertainty introduced by a chaotic climate
system (2).
References (abridged):
1. B. A. Wielicki et al., Science 295, 841 (2002)
2. J. T. Houghton et al., Climate Change 2001: The Scientific
Basis. Contribution of Working Group I to the Third Assessment
Report of the Intergovernmental Panel on Climate Change
(Cambridge Univ. Press, Cambridge/New York, 2001)
3. C. K. Folland, D. E. Parker, Q. J. R. Meteorol. Soc. 121, 319
(1995)
4. T. M. Smith, R. W. Reynolds, J. Clim. 15, 73 (2002)
5. T. M. Smith, C. F. Ropelewski, J. Clim. 7, 949 (1994)
Science 2002 296:483
Web Links: climate simulation climate forcing
Related Background:
ON CLIMATE MODELING
Leonard A. Smith (London School of Economics, US) discusses
climate modeling, the author making the following points:
1) The traditional approach to climate modeling is to build the
most complicated model that will fit inside the largest computer
available, run it once, and see what happens. This approach
yields a single "best guess" forecast. Yet even in high school
physics, we learn that an answer without "error bars" is no
answer at all. Although it is a nontrivial task to assign
relevant uncertainty estimates to imperfect models of chaotic
systems undergoing transient changes in forcing, doing so is
conceivable. One alternative to devoting all our resources to
one best guess is to use the same computer resource to perform
an ensemble of model runs. This alternative would, of course,
require the use of simpler models, and a balance between running
different initial conditions (to cope with chaos), different
model parameterizations and parameter values (to identify tuning
issues), and different model structures (to mitigate model
error). A single best guess from a complicated model run without
good uncertainty estimates is impotent, whereas a beautiful set
of ensemble statistics on too simple a model is irrelevant. How
do we go about assigning resources between these two extremes?
And how can we tell which physical phenomena of economic and
social interest our current models might be able to forecast?
2) At best, our models hold only in certain circumstances. This
is true even for our "Laws of Physics". In climate forecasting,
to make any progress, we assume the "rosy scenario" holds: a)
nothing horrible happens that takes the model beyond its range
of validity (e.g., no asteroid collides with the Earth); and b)
no small but crucial feedback mechanism is missing from our
model (i.e., our model has a range of validity). As we are
forced to assume the rosy scenario, we can never make objective
probability statements on the basis of our climate simulations.
What we can do is establish their internal consistency: we can
determine for which phenomena and on which time scales our
models might reflect reality.
Proc. Nat. Acad. Sci. 2002 99:2487
Related Background:
ON GLOBAL CLIMATE MODELS
M. Stute et al (Barnard College, US) discuss global climate
models, the authors making the following points:
1) Global climate is a result of the complex interactions
between the atmosphere, cryosphere (ice), hydrosphere (oceans),
lithosphere (land), and biosphere (life), fueled by the
nonuniform spatial distribution of incoming solar radiation. We
know from climate reconstructions using recorders such as ice
cores, ocean and lake sediment cores, tree rings, corals, cave
deposits, and ground water that the Earth's climate has seen
major changes over its history.
2) An analysis of the temperature variations patched together
from all these data reveals that climate change occurs in cycles
with characteristic periods, for example, 200 million, 100,000,
or 4 to 7 years. For some of these cycles, particular mechanisms
have been identified, for example, climate forcing by changes in
the Earth's orbital parameters or internal oscillations of the
coupled ocean-atmosphere system. However, major uncertainties
remain in our understanding of the interplay of the components
of the climate system.
3) Paleoclimate reconstructions, in particular from ice cores,
also have demonstrated that climate can change over extremely
short periods of time such as a few years. Over the last
century, humans have altered the Earth's surface and the
composition of its atmosphere to the extent that these factors
measurably affect current climate conditions, and there is
concern that perhaps during one human generation we will
gradually change climate conditions or even trigger a rapid and
much more dramatic shift: we might be "poking an angry beast".
4) Major progress in our understanding of climate processes in
the past, present, and future has been made by the development
of numerical models that simulate climate at an increasing level
of detail. Recent breakthroughs in spatial coverage and temporal
resolutions of systems recording today's climate, and
high-resolution reconstruction of past climate conditions from
diverse sources using new past-climate indicators (proxies),
make it possible to validate climate models and thus improve
their reliability for future predictions.
Proc. Nat. Acad. Sci. 2001 98:10529
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2. ON AUROPHILICITY
A. Codina et al (University of La Riojo, ES) discuss
aurophilicity, the authors making the following points:
1) The term "aurophilicity" refers to the tendency of
closed-shell gold(I) atoms to aggregate at distances shorter
than the sum of the van der Waals radii with an interaction
energy that is comparable in strength to hydrogen bonds.(1) It
is important to note that this aggregation is an intrinsic
effect of the metal centers and is not imposed by the ligand
architecture; this has been demonstrated in a large number of
experimental and theoretical reported examples(2) and, in
principle, gold-gold interactions could be used to control
supramolecular structures and their dimensionality.(3)
2) This effect has prompted a number of research groups to seek
similar situations in other closed-shell metal atoms of the same
period or even the same group. Thus, "argentophilicity" or even
"cuprophilicity" are terms coined to describe the analogous
phenomena and have also been theoretically analyzed.(4) These
metallophilic interactions are considered to be responsible for
some physical properties.(5) Nevertheless, in most cases the
formation of polymeric structures6 or the ligand architecture
plays a significant role in the aggregation of the metal centers
and there are few examples of unsupported Ag(I)-Ag(I) or
Cu(I)-Cu(I) interactions; this may indicate that these are
weaker than those of Au(I)-Au(I), leaving the metallophilicity
concept as a matter for discussion.
3) In contrast, hydrogen bonds are well established as
structural motifs for the construction of molecular networks.
These interactions have been widely reviewed, showing that
several organometallic molecules bind into crystal architectures
through intermolecular hydrogen bonds. Indeed, hydrogen bonding
is known as the master-key interaction in crystal engineering
because it combines directionality with strength. On the other
hand, hydrogen bonding has been extensively studied from a
theoretical point of view, giving a rich source of supplementary
information concerning this phenomenon.
References (abridged):
1. (a) Schmidbaur, H.; Graf, W.; Müller, G. Angew. Chem., Int.
Ed. Engl. 1988, 27, 417. (b) Harwell, D. E.; Mortimer, M. D.;
Knobler, C. B.; Anet, F. A. L.; Hawthorne, M. F. J. Am. Chem.
Soc. 1996, 118, 2679. (c) Pyykkö, P.; Zhao, Y. F. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 604. (d) Pyykkö, P.; Li, J.; Runeberg,
N. Chem. Phys. Lett. 1994, 218, 133. (e) Bachman, R. E.;
Fioritto, M. S.; Fetics, S. K.; Cocker, T. M. J. Am. Chem. Soc.
2001, 123, 5376
2. Pyykkö, P. Chem. Rev. 1997, 97, 597
3. Leznoff, D. B.; Xue, B. Y.; Batchelor, R. J.; Einstein, F. W.
B.; Patrick, B. O. Inorg. Chem. 2001, 40, 6026
4. (a) Pyykkö, P.; Runeberg, N.; Mendizabal, F. Chem. Eur. J.
1997, 3, 1451.[ChemPort] (b) Pyykkö, P.; Mendizabal, F. Inorg.
Chem. 1998, 37, 3018. (c) Fernández, E. J.; López-de-Luzuriaga,
J. M.; Monge, M.; Rodríguez, M. A.; Crespo, O.; Gimeno, M. C.;
Laguna, A.; Jones, P. G. Inorg. Chem. 1998, 37, 6002
5. (a) Che, C. M.; Tse, M. C.; Chan, M. C. W.; Cheung, K. K.;
Phillips, D. L.; Leung, K. H. J. Am. Chem. Soc. 2000, 122, 2464.
(b) Che, C. M.; Mao, Z.; Miskowski, V. M.; Tse, M. C.; Chan, C.
K.; Cheung, K. K.; Phillips, D. L.; Leung, K. H. Angew. Chem.,
Int. Ed. 2000, 39, 4084
J. Am. Chem. Soc. 2002 124:6781
Web Links: aurophilicity hydrogen bonding
Related Background Brief:
THE STRUCTURAL AND FUNCTIONAL EQUIVALENCE OF AUROPHILIC AND
HYDROGEN BONDING: EVIDENCE FOR THE FIRST EXAMPLES OF ROTATOR
PHASES INDUCED BY AUROPHILIC BONDING. There has been
considerable interest in the attractive interaction that exists
between closed-shell gold(I) centers.1 This interaction,
commonly referred to as "aurophilicity" or "aurophilic bonding",
has been estimated by both experiment and theory to have a
strength similar to hydrogen bonding (29-46 kJ/mol vs 10-65
kJ/mol). Furthermore, Desiraju and co-workers have shown that,
like hydrogen bonding, aurophilic bonding is distinctly
directional. As might be expected based on this combination of
strength and directionality, the use of aurophilic bonds to
control the supramolecular structure of gold-containing
complexes is becoming increasingly common. The striking
energetic and structural similarities between aurophilic and
hydrogen bonding raises the question: can aurophilic bonding
function as a structural and functional equivalent to hydrogen
bonding? That is, can aurophilic bonding be used to construct
supramolecular architectures that are equivalent to those
created by hydrogen bonding, and will the resulting materials
exhibit physical properties similar to those seen for their
hydrogen bond-based counterparts? R.E. Bachman et al: J. Am.
Chem. Soc. 2001 123:5376.
Related Background Brief:
GOLD-GOLD INTERACTIONS AS CRYSTAL ENGINEERING DESIGN ELEMENTS IN
HETEROBIMETALLIC COORDINATION POLYMERS. Coordination polymers
containing Cu(II) and [Au(CN)2]- units were prepared. Most of
their structures incorporate attractive gold-gold interactions,
thus illustrating that such aurophilic interactions can be
powerful tools for increasing structural dimensionality in
supramolecular systems. [Cu(tren)Au(CN)2][Au(CN)2] (1, tren =
tris(2-aminoethyl)amine) forms a cation/anion pair, which is
weakly linked by hydrogen bonds but not by aurophilic
interactions. [Cu(en)2Au(CN)2][Au(CN)2] (2-Au, en =
ethylenediamine) is a 2-dimensional system composed of a chain
of [Au(CN)2]- anions and another chain of [(en)2Cu-NCAuCN]+
cations; short Au-Au bonds of 3.1405 angstroms connect the
anions. This bond is shorter than that observed in the analogous
silver(I) structure, 2-Ag. The average M-C bond lengths of 1.984
angstroms in 2-Au are significantly shorter than those found in
2-Ag, suggesting that Au(I) is smaller than Ag(I).
Cu(dien)[Au(CN)2]2 (3, dien = diethylenetriamine) forms a
1-dimensional chain of tetranuclear [Au(CN)2]- units that are
bound to [Cu(dien)] centers. Aurophilic interactions of ~3.35
angstroms hold the tetramer together. Cu(tmeda)[Au(CN)2]2 (4,
tmeda = N,N,N',N'-tetramethylethylenediamine) forms a
3-dimensional network by virtue of aurophilic interactions of
3.3450 and 3.5378 angstroms. Altering the Cu:Au stoichiometry
yields Cu(tmeda)[Au(CN)2]1.5(ClO4)0.5, which has an unusual
2-dimensional rhombohedral layer structure (space group R32).
Complex 5 is composed of three mutually interpenetrating
Cu[Au(CN)2]1.5 networks which are interconnected by aurophilic
interactions of 3.4018 and 3.5949 angstroms. Weak
antiferromagnetic coupling is observed in 2 and 5. D.B. Leznoff
et al: Inorganic Chemistry 2001 40:6026.
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3. ON DIELECTRIC BLACK HOLE ANALOGS
R. Schuetzhold et al (University of British Columbia, CA)
discuss black hole analogs, the authors making the following
points:
1) At present we know four fundamental interactions in physics:
the strong and the weak interaction, electromagnetism, and
gravitation. The first three forces are described by quantum
field theories whereas the fourth is governed by the laws of
general relativity -- a purely classical theory. In view of the
success -- and the excellent agreement with experimental data --
of the electroweak standard model (unifying the electromagnetic
and the weak force at high energies) it is conjectured that all
four interactions can be described by an underlying unified
theory above the Planck scale. This fundamental description is
expected to incorporate the four forces as low-energy effective
theories.
2) In spite of various investigations during the last few
decades, a satisfactory and explicit candidate for this
underlying law is still missing. At present we can consistently
consider just quantum fields, e.g., electromagnetism, in the
presence of classical, i.e., externally prescribed,
gravitational fields. This semiclassical treatment is expected
to provide some insight into the structure of the underlying
theory. One of the most striking consequences of this formalism
is the Hawking effect [1] predicting the evaporation of black
holes. However, this prediction is faced with a conceptual
difficulty: Its derivation [1] is based on the assumption that
the semiclassical treatment is valid at arbitrary scales. But
the decomposition into a classical gravitational sector and a
quantum field sector is valid at low energies only
(trans-Planckian problem). The investigation of high-energy
effects requires some knowledge about the underlying theory
including quantum gravity.
3) In order to elucidate this point, Unruh [2] suggested
scenarios which display a close similarity to that of the
Hawking effect with the underlying physical laws being
completely understood -- the sonic black hole analogs. These
analogs are based on the remarkable observation that the
propagation of sound waves in flowing fluids is -- under
appropriate conditions -- equivalent to that of a scalar field
in curved space-times; see, e.g., [2,3]. The acoustic horizon
occurs if the velocity of the fluid exceeds the speed of sound
within the liquid. Many examinations have been devoted to the
topic of black hole analogs after the original proposal by Unruh
[2]; see, e.g., [3-5], as well as references therein. In Garay
et al (2000), the possibility of realizing an acoustic horizon
within a Bose-Einstein condensate is addressed. More generally,
Ref. [4] discusses the simulation of phenomena of curved
space-times within superfluids. These investigations suggest
that Hawking radiation is a mainly kinematic effect and only
weakly sensitive to trans-Planckian physics -- for the class of
models under consideration.
4) In summary: As an alternative to the sonic black hole
analogs, the authors discuss a different scenario for modeling
black hole Schwarzschild geometry in a laboratory -- the
dielectric black hole. The dielectric analog of the horizon
occurs if the velocity of a medium with a finite permittivity
exceeds the speed of light in that medium. The authors address
the relevance for experimental tests of the Hawking effect and
possible implications.
References (abridged):
1. S. W. Hawking, Nature (London) 248, 30 (1974); Commun. Math.
Phys. 43, 199 (1975)
2. W.G. Unruh, Phys. Rev. Lett. 46, 1351 (1981)
3. M. Visser, Classical Quantum Gravity 15, 1767 (1998)
4. G.E. Volovik, Phys. Rep. 351, 195 (2001); U.R. Fischer and
G.E. Volovik, Int. J. Mod. Phys. D 10, 57 (2001)
5. S. Liberati, S. Sonego, and M. Visser, Classical Quantum
Gravity 17, 2903 (2000)
Phys. Rev. Lett. 2002 88:061101
Web Links: black hole
Related Background:
ON ROTATING BLACK HOLES
Since all black holes must have mass, there are 4 possible types
of black hole, each type derived from equations of the general
theory of relativity:
a) A "Schwarzschild black hole" (first derived 1916) has no
charge and no angular momentum.
b) A "Reissner-Nordstrom" black hole (first derived 1918) has
charge but no angular momentum.
c) A "Kerr black hole" (first derived 1963) has angular momentum
but no charge.
d) A "Kerr-Newman black hole" (first derived 1965) has both
charge and angular momentum.
It is currently believed that real black holes are almost
certainly rotating and have very little electric charge, so that
the Kerr solution should be the most applicable.
M.H. van Putten and A. Levinson (Massachusetts Institute of
Technology, US) discuss rotating black holes, the authors making
the following points:
1) Gravitation is a universal force in nature, and it ultimately
leads to black holes as fundamental objects. Supermassive black
holes are believed to form the nuclei of galaxies, and
stellar-mass black hole candidates are found in soft x-ray
transients and galactic microquasars. Rotating black holes,
discovered by Kerr as exact solutions to general relativity
equations, are of great astrophysical interest because their
emissions provide a method for identifying and studying black
holes.
2) Kerr black holes build up angular momentum, and this energy
can be emitted in accord with known principles. Spontaneous
emissions in vacuo are suppressed by canonical angular momentum
barriers, but Kerr black holes -- surrounded by a torus
magnetosphere supported by surrounding matter -- do not behave
this way.
3) The authors report that the rotational energy of a black hole
surrounded by a torus is released through several channels. They
have determined that a minor fraction of the energy is released
in baryon-poor outflows from a differentially rotating open
magnetic flux tube, and a major fraction is released in
gravitational radiation by the torus. The authors associate the
energy emitted in baryon-poor outflows with gamma-ray bursts.
The remaining fraction is released in torus winds, thermal
emissions, and conceivably mega-electronvolt neutrino emissions.
The emitted gravitational radiation can be detected by
gravitational wave experiments, and this provides a method for
identifying Kerr black holes in the Universe.
Science 2002 295:1874
Related Background:
ASTROPHYSICS: BLACK HOLES AS EMPIRICAL OBJECTS
During the life of a star, two opposing forces control the
star's equilibrium: the gravitational force, which drives the
collapse of the star's mass inward to the center of gravity, and
the counteracting outward pressure derived from the nuclear
fusion reactions in the star's core. When the nuclear fuel burns
out, the star begins its death and gravitational collapse
occurs. If the terminal stages of star death (during which large
amounts of stellar material are blown away) leave a remnant star
mass greater than 3 solar masses, the ultimate gravitational
collapse will produce a black hole, a relativistic singularity.
A black hole is a localized region of space from which neither
matter nor radiation can escape. The "trapping" occurs because
the requisite escape velocity, which can be calculated from the
relevant equations, exceeds the velocity of light and is
therefore unattainable. Another view of a black hole is that it
is a mass that has collapsed to such a small volume that its
gravity prevents the escape of all radiation. Space and time
essentially have no meaning in a black hole. The boundary of the
black hole is called the "event horizon", because any event
within the boundary is invisible outside, the invisibility
resulting from the fact that no radiation can escape to be
detected. The radius of the black hole depends upon how much
matter has fallen into the region; it is called the
"Schwarzschild radius", and it is usually a few kilometers.
However, massive black holes are possible and are thought to be
the source of quasars (quasi-stellar objects), which are
extremely luminous sources radiating energy over the entire
spectrum from x-rays to radio waves, and which are apparently
the oldest and most distant objects in the universe. If quasars
indeed involve black holes, the radiation is from material just
outside the black hole, and not from anything within it. Nothing
inside a black hole can get out of it. Other massive black
holes, closer to us than quasars, are apparently the centers of
galaxies, both *galaxies with active centers and galaxies with
dormant centers.
R.Blandford and N. Gehrels (2 installations, US) present a
review of current research on black holes, with a focus on
observable phenomena. The authors make the following points:
1) The term "black hole" was introduced in a lecture by John
Wheeler in 1968, and used to describe a new view of
gravitational collapse, a shift in perspective from that of an
observer at infinity, for whom the black hole is a limiting case
and never forms, to a description of a black hole in terms of
the fate of matter falling into it as the matter crosses the
event horizon.
2) Energy is the key to understanding astrophysical black holes.
For the past three decades, it has become well established
theoretically that black holes can be voracious monsters
devouring all that they encounter. Some black holes are
extremely luminous and easily outshine their stellar and
galactic counterparts that rely on nuclear, as opposed to
gravitational, energy for their power. Since the late 1970s, it
has been well understood that black holes are most likely to be
detected in stellar *binary systems of approximately 10
solar-masses (i.e., 10 times the mass of the Sun, whose mass is
approximately 2 x 10^(30) kilograms), and in galactic nuclei
with masses of the order of 10^(6) to 10^(9) solar masses.
3) The archetype of the stellar black hole is Cygnus X-1, a
powerful x-ray source varying so rapidly that it must be a
compact star. Only 3 types of compact stars are known: *white
dwarfs, *neutron stars, and black holes. But theory indicates
that of compact stars only black holes can have masses greater
than 3 solar-masses. Since application of Kepler's laws to
Cygnus X-1 in 1971 resulted in an estimated mass of 8
solar-masses, this object was established as a black hole.
4) For black holes in active galactic nuclei, dynamical
investigations beginning in the late 1970s, established that
galaxies, such as the giant *elliptical galaxy M87 in the Virgo
Cluster, contain central dark masses (3 x 10^(9) solar-masses in
the case of M87) that appeared to be too compact to be a central
cluster of stars. In 1995, M. Miyoshi et al were able to measure
the orbital speed of the gaseous disk around the nucleus of the
nearby spiral galaxy NGC 4258. The authors demonstrated that the
gas speed obeys Kepler's laws, and that the gaseous disk is
warped. Since the calculated mass and size of the central object
are 4 x 10^(7) solar-masses and half a light year, respectively,
the consensus is that the central object is definitely a black
hole.
5) Concerning our own Galaxy, measurements of motions and
velocities of individual stars in orbit around the center of the
Galaxy indicate the mass of our own black hole has a value of
2.6 x 10^(6) solar-masses.
6) The authors suggest that at the present time we have 15 mass
estimates for black holes in the nuclei of nearby galaxies that
are quite secure. It appears that the majority of nearby
luminous galaxies now contain dormant black holes. However,
during earlier epochs, when the black holes were supplied with
gaseous fuel at a much higher rate, they were able to outshine
their host galaxies, in some cases by factors of thousands.
These ancient objects are the quasars, which we can spot from
distances so large that many of them emitted the light we see
now when the Universe was less than 10 percent of its present
age.
7) In summary, the authors note: "The past five years have seen
a remarkable gain in the sophistication of black hole
observations with telescopes that span the entire
electromagnetic spectrum. No longer is there any serious debate
as to whether black holes exist. We know that they must be quite
common, and we can now study them in increasing detail."
PhysicsToday June 1999
Text Notes:
... ... *galaxies with active centers: Active galactic nuclei
are central regions of galaxies in which considerable energy is
apparently generated by processes other than those operating in
ordinary stars. The energy may result from the accretion of
material into a massive black hole situated at the core of the
galaxy.
... ... *binary systems: Binary stars are a pair of stars
revolving around a common center of mass under the influence of
their mutual gravitational attraction, and apparently the
majority of stars in the universe are binaries and not singlets.
In some cases the binary system is resolvable into two
components, and in other cases the presence of a second star is
inferred by perturbations in the motion or emitted radiation of
the first star. If the binaries are close enough, they may share
stellar material, and this results in a particular kind of
stellar evolution.
... ... *white dwarfs: White dwarf stars are extremely dense and
compact stars that have undergone gravitational collapse. They
are the final stage in the evolution of low-mass stars after
they have lost their outer layers. White dwarf stars are
approximately the size of Earth, but with a mass approximately
that of the Sun.
... ... *neutron stars: If, following its terminal stages, the
remnant mass of a star is between 1.4 and 2 to 3 solar masses,
the star will collapse into a neutron star, a body with a radius
of 10 to 15 kilometers, with a core so dense that its component
protons and electrons have merged into neutrons.
... ... *elliptical galaxy: In 1925, the astronomer Edwin Hubble
introduced a classification scheme for galaxies that is now
widely used. The scheme has 3 main types of galaxy: elliptical,
spiral, and barred spiral, and each is further divided into
morphological subtypes. Elliptical galaxies are apparently
composed of old stars, contain little dust, are the central
dominant galaxies in rich clusters, and many are powerful
sources of radio wavelength radiation. The size of elliptic
galaxies ranges from dwarf ellipticals [10^(8) stars] to
supergiant ellipticals [10^(13) stars]. Elliptical galaxies are
believed to be a stage in the evolution of galaxies, and
different cosmological models make specific predictions about
the number of elliptical galaxies as a function of redshift. In
principle, therefore, observations of elliptical galaxies can be
used to discriminate between models.
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4. ON AXON REGENERATION
M.L. Condic (University of Utah, US) discusses axon
regeneration, the author making the following points:
1) As the central nervous system (CNS) matures in postnatal
life, there is a decline in the ability of neurons to regenerate
axons following injury. Embryonic CNS neurons in many vertebrate
animals will readily regenerate following even the most severe
traumas. For example, full functional recovery is made after a
complete spinal transection in embryonic chicks [1], so long as
the transection occurs before the midpoint of embryonic
development. Following this point, there is a rapid decline in
the ability of CNS neurons to regenerate axons after injury,
culminating in complete regenerative failure by early postnatal
stages.
2) Changes in the CNS environment and the intrinsic properties
of maturing neurons both contribute to the gradual decline in
regenerative potential [2]. Adult central neurons are capable of
regeneration under permissive conditions [3,4], indicating that
the inhibitory environment of the injured adult CNS prevents the
regrowth of axons. Yet even in favorable environments, adult
regeneration is slow, typically well below the rates of axon
extension observed from the same neurons at embryonic stages.
Conversely, embryonic neurons transplanted to adult injury
models regenerate significantly better than adult neurons in the
same non-permissive environment [5]. Even adult peripheral
neurons that are capable of relatively robust axonal
regeneration in the permissive environment of the peripheral
nerve are nonetheless significantly impaired relative to the
regenerative ability of their younger counterparts. So while the
inherent rate of axonal regeneration may be superior for
peripheral neurons compared to central neurons, all neurons
exhibit a similar, cell-autonomous decline in their ability to
regenerate axons between embryonic and adult stages.
3) What is the underlying basis for the gradual decline of
axonal regeneration capability? J.L. Goldberg et al [Science
2002 296:1860] have recently examined the regeneration
capability of retinal neurons at embryonic and postnatal stages.
In agreement with previous work, they found a dramatic,
age-dependent decline in the ability of retinal neurons to
regenerate axons in culture. Surprisingly, this developmental
decline does not appear to be activated by an intrinsic neural
program or induced by target-derived factors, but rather it
requires contact with maturing amacrine cells within the retina.
Amacrine cell membranes are sufficient to shift retinal ganglion
cells in culture from the efficient production of long axons to
the generation of numerous, short processes containing the
dendritic marker MAP-2. This shift from production of axons to
production of dendrites does not spontaneously revert over time
in culture, suggesting that once the change has occurred, it is
quite stable.
References (abridged):
1. Shimizu I., Oppenheim R.W., O'Brien M. and Shneiderman A.
(1990) Anatomical and functional recovery following spinal cord
transection in the chick embryo. J. Neurobiol., 21:918-937
2. Horner P.J. and Gage F.H. (2000) Regenerating the damaged
central nervous system. Nature, 407:963-970
3. Richardson P.M., McGuinness U.M. and Aguayo A.J. (1980) Axons
from CNS neurons regenerate into PNS grafts. Nature, 284:264-265
4. David S. and Aguayo A.J. (1981) Axonal elongation into
peripheral nervous system 'bridges' after central nervous system
injury in adult rats. Science, 214:931-933
5. Nogradi A. and Vrbova G. (1994) The use of embryonic spinal
cord grafts to replace identified motoneuron pools depleted by a
neurotoxic lectin, volkensin. Exp. Neurol., 129:130-141
Current Biology 2002 12:R455
Web Links: axon regeneration
Related Background Brief:
ANATOMICAL AND FUNCTIONAL RECOVERY FOLLOWING SPINAL CORD
TRANSECTION IN THE CHICK EMBRYO. Following complete transection
of the thoracic spinal cord at various times during embryonic
development, chick embryos and post-hatched animals exhibited
various degrees of anatomical and functional recovery depending
upon the age of injury. Transection on embryonic day 2 (E2),
when neurogenesis is still occurring and before descending or
ascending fiber tracts have formed, produced no noticeable
behavioral or anatomical deficits. Embryos hatched on their own
and were behaviorally indistinguishable from control hatchlings.
Similar results were found following transection on E5, an age
when neurogenesis is complete and when ascending and descending
fiber tracts have begun to project through the thoracic region.
Within 48 h following injury on E5, large numbers of nerve
fibers were observed growing across the site of transection. By
E8, injections of horse-radish peroxidase (HRP) administered
caudal to the lesion, retrogradely labeled rostral spinal and
brainstem neurons. Embryos transected on E5 were able to hatch
and could stand and locomote post-hatching in a manner that was
indistinguishable from controls. Following spinal cord
transections on E10, anatomical recovery of the spinal cord at
the site of injury was not quite as complete as after E5
transection. Nonetheless, anatomical continuity was restored at
the site of injury, axons projected across this region, and
rostral spinal and brainstem neurons could be retrogradely
labeled following HRP injections administered caudal to the
lesion. At least part of this anatomical recovery may be
mediated by the regeneration or regrowth of lesioned axons.
Although none of the embryos transected on E10 that survived to
hatching were able to hatch on their own, because several
sham-operated embryos were also unable to hatch, we do not
attribute this deficit to the spinal transection. When
E10-transected embryos were aided in escaping from the shell,
they were able to support their own weight, could stand, and
locomote, and were generally comparable, behaviorally, to
control hatchlings. Repair of the spinal cord following
transection on E15 was considerably less complete compared to
embryos transected on E2, E5, or E10. However, in some cases, a
degree of anatomical continuity was eventually restored and a
few spinal neurons rostral to the lesion could be retrogradely
labeled with HRP. By contrast, labeled brainstem neurons were
never observed following E15 transection. E15 transected embryos
were never able to hatch on their own, and when aided in
escaping from the shell, the hatchlings were never able to
stand, support their own weight, or locomote. I. Shimizu et al:
J Neurobiol 1990 21:918.
Related Background Brief:
NEURONAL CYCLIC AMP CONTROLS THE DEVELOPMENTAL LOSS IN ABILITY
OF AXONS TO REGENERATE. Unlike neonatal axons, mammalian adult
axons do not regenerate after injury. Likewise, myelin, a major
factor in preventing regeneration in the adult, inhibits
regeneration from older but not younger neurons. Identification
of the molecular events responsible for this developmental loss
of regenerative capacity is believed key to devising strategies
to encourage regeneration in adults after injury. The authors
report that the endogenous levels of the cyclic nucleotide,
cAMP, are dramatically higher in young neurons in which axonal
growth is promoted both by myelin in general and by a specific
myelin component, myelin-associated glycoprotein (MAG), than in
the same types of neurons that, when older, are inhibited by
myelin-MAG. Inhibiting a downstream effector of cAMP [protein
kinase A (PKA)] prevents myelin-MAG promotion from young
neurons, and elevating cAMP blocks myelin-MAG inhibition of
neurite outgrowth in older neurons. Of importance is that
developmental plasticity of spinal tract axons in neonatal rat
pups in vivo is dramatically reduced by inhibition of PKA. Thus,
the switch from promotion to inhibition by myelin-MAG, which
marks the developmental loss of regenerative capacity, is
mediated by a developmentally regulated decrease in endogenous
neuronal cAMP levels. D. Cai et al: J Neurosci 2001 21:4731
Related Background Brief:
ROBUST REGENERATION OF ADULT SENSORY AXONS IN DEGENERATING WHITE
MATTER OF THE ADULT RAT SPINAL CORD. The authors have recently
reported that minimally disturbed adult CNS white matter can
support regeneration of adult axons, their study using a novel
microtransplantation technique to inject minute volumes of
dissociated adult rat dorsal root ganglion neurons directly into
adult rat CNS pathways (Davies et al 1997). This atraumatic
injection procedure minimized scarring and allowed considerable
numbers of regenerating adult axons immediate access to the
adult CNS glial terrain where they rapidly extended for long
distances. A critical question remained as to whether
degenerating white matter at acute and chronic stages (up to 3
months) after injury could still support regeneration. To
investigate this, the authors report they have microtransplanted
adult sensory neurons into degenerating white matter of the
adult rat spinal cord several millimeters rostral to a severe
lesion of the dorsal columns. Regeneration of donor sensory
axons in both directions away from the site of transplantation
was robust even within white matter undergoing fulminant
Wallerian degeneration despite intimate contact with myelin.
Along their route, the regrowing axons extended large numbers of
collaterals into the adjacent dorsal horn. However, after
entering the lesion, the rapidly extending growth cones stopped
and became dystrophic within high concentrations of reactive
glial matrix. The authors suggest their results offer compelling
evidence that the major environmental impediment to regeneration
in the adult CNS is the molecular barrier that forms directly at
the lesion site, and that degenerating white matter beyond the
glial scar has a far greater intrinsic ability to support axon
regeneration than previously thought possible. S.J. Davies et
al: J Neurosci 1999 19:5810.
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5. NEURAL PLASTICITY: THE AUDITORY-VISUAL SYSTEM LINKAGE
Andrew J. King (Oxford University, UK) discusses neural
plasticity, the author making the following points:
1) Extensive interactions take place between the different
senses during development. This is evident from the many changes
that have been reported in the remaining sensory systems
following a modality-specific impairment in early life [1]. But
substantial cross-modal plasticity is also observed when the
brain is faced with the task of coordinating information across
the senses. In particular, the more accurate and reliable
spatial information available to the visual system is used to
calibrate the emerging neural representation of auditory space
in the superior colliculus. This ensures that single neurons in
this midbrain structure -- which plays an important role in
controlling the direction of gaze -- respond to multisensory
signals that are linked in space and time, despite
growth-related changes and individual differences in the size
and relative positions of the different sense organs [2].
2) Substantial progress has been made in the last few years in
revealing how visual experience shapes the auditory responses of
neurons in the superior colliculus. In particular, studies in
ferrets [3,4] and barn owls [5] now suggest that the instructive
visual signals originate from topographically organized
projections to the auditory neurons and that these inputs may
provide a template against which auditory spatial tuning is
matched.
3) The superior colliculus has long been the brain area of
choice for investigating the way stimuli in different sensory
modalities are combined and integrated by individual neurons,
both in adult animals and during the course of development [2].
In mammals, the superficial layers of the superior colliculus
contain only visually responsive neurons, whereas visual,
auditory and tactile inputs converge in its deeper layers. For
each sensory modality, stimulus location is represented
topographically within the nucleus. In other words, neurons in a
given region of the superior colliculus respond optimally to
visual or auditory stimuli arising from the same direction in
space, or to stimulation of a corresponding part of the body
surface. This arrangement allows each of the sensory inputs
associated with a particular target or event to be transformed
into appropriate motor signals that are sent to the brainstem
and spinal cord. Although some of the deep-layer neurons respond
to stimuli of only one modality, others receive inputs from at
least two of the sensory systems. The spike discharge rates of
these multisensory neurons can be dramatically altered when the
different stimuli are presented together. Such interactions are
thought to improve the likelihood of detecting and localizing
objects that can be both seen and heard, and, if close by, felt
as well.
4) In summary: Recent studies in owls and ferrets seem to have
identified the origin and nature of the visual signals that
shape the development of the auditory space map in the midbrain,
which ensures that the neural representations of both sensory
modalities share the same topographic organization.
References (abridged):
1. Rauschecker J.P. (1995) Compensatory plasticity and sensory
substitution in the cerebral cortex. Trends Neurosci., 18:36-43
2. King A.J. (1999) Sensory experience and the formation of a
computational map of auditory space in the brain. BioEssays,
21:900-911
3. King A.J., Schnupp J.W.H. and Thompson I.D. (1998) Signals
from the superficial layers of the superior colliculus enable
the development of the auditory space map in the deeper layers.
J. Neurosci., 18:9394-9408
4. Doubell T.P., Baron J., Skaliora I. and King A.J. (2000)
Topographic projection from the superior colliculus to the
nucleus of the brachium of the inferior colliculus: evidence for
convergence of visual and auditory information. Eur. J.
Neurosci., 12:4290-4308
5. Luksch H., Gauger B. and Wagner H. (2000) A candidate pathway
for a visual instructional signal to the barn owl's auditory
system. J. Neurosci. , R, 20:C70
Current Biology 2002 12:R393
Web Link: superior colliculus
Related Background Brief:
COMPENSATORY PLASTICITY AND SENSORY SUBSTITUTION IN THE CEREBRAL
CORTEX. Cats deprived visually from birth show few overt
impairments in their natural behavior. Therefore, they seem well
suited as an animal model for the study of compensatory
plasticity after early vision loss. It can be demonstrated that
binocularly deprived cats show improved abilities of auditory
localization, and at least equal tactile behavior compared to
normal controls. Within the anterior ectosylvian cortex of
binocularly deprived cats, where different sensory modalities
come together, the anterior ectosylvian visual area is
completely taken over by auditory and somatosensory inputs.
Furthermore, the auditory spatial tuning of single units in this
cortical region is sharpened significantly as a result of visual
deprivation. Somatosensory compensation for early loss of vision
can be demonstrated by a hypertrophy of the facial vibrissae,
and a corresponding expansion of their central representation in
the somatosensory cortex of binocularly deprived animals. The
compensatory changes in the cortex can be explained by a
reorganization of sensory representations under the guidance of
sensorimotor feedback rather than by instruction through an
extraneous "supervisory" signal. These processes might form the
neural basis of sensory substitution in blind humans. J.P.
Rauschecker: Trends Neurosci 1995 18:36
Related Background Brief:
TOPOGRAPHICAL PROJECTION FROM THE SUPERIOR COLLICULUS TO THE
NUCLEUS OF THE BRACHIUM OF THE INFERIOR COLLICULUS IN THE
FERRET: CONVERGENCE OF VISUAL AND AUDITORY INFORMATION. The
normal maturation of the auditory space map in the deeper layers
of the ferret superior colliculus (SC) depends on signals
provided by the superficial visual layers, but it is unknown
where or how these signals influence the developing auditory
responses. The authors report that tracer injections in the
superficial layers label axons with en passant and terminal
boutons, both in the deeper layers of the SC and in their
primary source of auditory input, the nucleus of the brachium of
the inferior colliculus (nBIC). Electron microscopy confirmed
that biocytin-labeled SC axons form axodendritic synapses on
nBIC neurons. Injections of biotinylated dextran amine in the
nBIC resulted in anterograde labeling in the deeper layers of
the SC, as well as retrogradely labeled superficial and deep SC
neurons, whose distribution varied systematically with the
rostrocaudal placement of the injection sites in the nBIC.
Topographical order in the projection from the SC to the
ipsilateral nBIC was confirmed using fluorescent microspheres.
The authors demonstrated the existence of functional SC-nBIC
connections by making whole-cell current-clamp recordings from
young ferret slices. Both monosynaptic and polysynaptic EPSPs
were generated by electrical stimulation of either the
superficial or deep SC layers. In addition to unimodal auditory
units, both visual and bimodal visual-auditory units were
recorded in the nBIC in vivo and their incidence was higher in
juvenile ferrets than in adults. The SC-nBIC circuit provides a
potential means by which visual and other sensory or premotor
signals may be delivered to the nBIC to calibrate the
representation of auditory space. T.P. Doubell et al: Eur J
Neurosci 2000 12:4290.
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6. ON THE NEW HOMINID FOSSIL FROM CHAD
Bernard Wood (George Washington University, US) discusses
hominid fossils, the author making the following points:
1) A single fossil can fundamentally change the way we
reconstruct the tree of life. More than 75 years ago, Raymond
Dart's description(1) of the Taung skull from southern Africa
wrought such a transformation with regard to human evolution.
Dart provided hard evidence to support Darwin's prediction that
the roots of human evolutionary history run deepest in Africa. A
fossil cranium recently discovered by Michel Brunet and his
colleagues(2,3) marks a similar turning point in our
understanding of human origins. The new fossils -- the cranium,
a jaw fragment and several teeth -- belong to a primitive human
precursor, or hominid, that is an astonishing 6–7 million years
old. The transformation wrought here is more nuanced than
Dart's, but it is as fundamental. Here we have compelling
evidence that our own origins are as complex and as difficult to
trace as those of any other group of organisms.
2) For almost 150 years(4) it has been suggested that modern
humans are more closely related to the African apes than they
are to the orang-utan. Nowadays, evidence from both bones and
teeth(5), and soft tissues (muscles, nerves, and so on), and
from molecular and DNA analyses, support the view that modern
humans and chimpanzees are particularly closely linked. When the
DNA differences are calibrated by using palaeontological
evidence, they indicate that the hypothetical ancestor of modern
humans and the chimpanzee lived between about 5 and 7 million
years ago.
3) The hominid fossil record outside Africa has stubbornly
failed to break the 2-million-year barrier. Thus, if the
"molecular clock" keeps reasonably good time, between 3 and 5
million years or so of our independent evolution took place on
the African continent. Four regional "windows" provide fossil
evidence relevant to our early evolutionary history. The
southern African window was revealed by Dart in 1925 when the
first (and only) hominid fossil from Taung, near Kimberley, was
recognized; since then, neighboring cave sites have provided a
rich fossil record that stretches back to around 3 to 3.5
million years ago. The East African window comprises sites along
the Eastern, or Gregory, Rift Valley, from close to the Gulf of
Aden in the north to northern Tanzania in the south. The sites
are associated with sedimentary basins or the rivers that fed or
drained them. Two of them, Middle Awash in Ethiopia and Lukeino
in Kenya, have so far provided the oldest evidence of creatures
that are plausible human ancestors.
References (abridged):
1. Dart, R. A. Nature 115, 195-199 (1925)
2. Brunet, M. et al. Nature 418, 145-151 (2002)
3. Vignaud, P. et al. Nature 418, 152-155 (2002)
4. Huxley, T. H. Evidence as to Man's Place in Nature (Williams
& Norgate, London & Edinburgh, 1863)
5. Groves, C. P. in Systematics of the Great Apes (eds Swindler,
D. R. & Erwin, J.) 187-217 (Liss, New York, 1986)
Nature 2002 418:133
Web Links: hominids human origins
Related Background Brief:
SOFT-TISSUE ANATOMY OF THE EXTANT HOMINOIDS: A REVIEW AND
PHYLOGENETIC ANALYSIS. The authors report the results of a
literature search for information about the soft-tissue anatomy
of the extant non-human hominoid genera, Pan, Gorilla, Pongo and
Hylobates, together with the results of a phylogenetic analysis
of these data plus comparable data for Homo. Information on the
four extant non-human hominoid genera was located for 240 out of
the 1783 soft-tissue structures listed in the Nomina Anatomica.
Numerically these data are biased so that information about some
systems (e.g. muscles) and some regions (e.g. the forelimb) are
over-represented, whereas other systems and regions (e.g. the
veins and the lymphatics of the vascular system, the head
region) are either under-represented or not represented at all.
Screening to ensure that the data were suitable for use in a
phylogenetic analysis reduced the number of eligible soft-tissue
structures to 171. These data, together with comparable data for
modern humans, were converted into discontinuous character
states suitable for phylogenetic analysis and then used to
construct a taxon-by-character matrix. This matrix was used in
two tests of the hypothesis that soft-tissue characters can be
relied upon to reconstruct hominoid phylogenetic relationships.
In the first, parsimony analysis was used to identify cladograms
requiring the smallest number of character state changes. In the
second, the phylogenetic bootstrap was used to determine the
confidence intervals of the most parsimonious clades. The
parsimony analysis yielded a single most parsimonious cladogram
that matched the molecular cladogram. Similarly the bootstrap
analysis yielded clades that were compatible with the molecular
cladogram; a (Homo, Pan) clade was supported by 95% of the
replicates, and a (Gorilla, Pan, Homo) clade by 96%. These are
the first hominoid morphological data to provide statistically
significant support for the clades favored by the molecular
evidence. S. Gibbs et al: J Anat 2002 200:3.
Related Background Brief:
HOW RELIABLE ARE HUMAN PHYLOGENETIC HYPOTHESES? Cladistic
analysis of cranial and dental evidence has been widely used to
generate phylogenetic hypotheses about humans and their fossil
relatives. However, the reliability of these hypotheses has
never been subjected to external validation. To rectify this,
the authors applied identical methods to equivalent evidence
from two groups of extant higher primates for whom reliable
molecular phylogenies are available, the hominoids and
papionins. The authors report they found that the phylogenetic
hypotheses based on the craniodental data were incompatible with
the molecular phylogenies for the groups. Given the robustness
of the molecular phylogenies, these results indicate that little
confidence can be placed in phylogenies generated solely from
higher primate craniodental evidence. The corollary of this is
that existing phylogenetic hypotheses about human evolution are
unlikely to be reliable. Accordingly, new approaches are
required to address the problem of hominin phylogeny. Proc Natl
Acad Sci U S A 2000 Apr 25;97(9):5003.
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7. STIMULATED EMISSION BY THREE-PHOTON EXCITATION
G.S. He et al (State University of New York Buffalo, US) discuss
three-photon excitation, the authors making the following points:
1) Multiphoton processes, predicted(1) theoretically in 1931,
were for a long time considered to be mainly of academic
interest. This view changed when it was shown(2,3) that a
two-photon absorption process could, because of a quadratic
dependence of excitation on intensity, produce a spatially
confined excitation useful for three-dimensional data storage
and imaging. Two-photon absorption has received considerable
attention recently because of the development of highly
efficient two-photon-sensitive materials, leading to numerous
technological applications(4,5). These successes have created
interest in exploring applications based on three-photon
excitations. For a three-photon process, a longer excitation
wavelength such as those common in optical communications can be
used. Also, the cubic dependence of the three-photon process on
the input light intensity provides a stronger spatial
confinement, so that a higher contrast in imaging can be
obtained.
2) The authors report the observation of a highly directional
and up-converted stimulated emission as an amplified spontaneous
emission, produced in an organic chromophore solution by a
strong simultaneous three-photon absorption at 1.3 microns. This
achievement suggests opportunities for a three-photon process in
frequency-upconversion lasing, short-pulse optical
communications, and the emerging field of biophotonics. In this
experiment, the gain medium is the organic chromophore
4-[N-(2-hydroxyethyl)-N-(methyl)amino phenyl]-4'-(6-hydroxyhexyl
sulphonyl) stilbene (APSS) dissolved in dimethyl sulphoxide
(DMSO). APSS has been reported to exhibit good properties for
two-photon pumped lasing as well as for optical power limiting,
when excited at a wavelength of 800 nm. The molecular structure
of APSS and its linear absorption spectrum in DMSO have been
shown previously. The authors report that APSS also exhibits a
strong three-photon absorption when excited by ultrashort laser
pulses at 1.3 µm, producing population inversion. This creates
the prospect of developing new three-photon materials with even
more enhanced cross-sections for three-photon absorption.
References (abridged):
1. Göppert-Meyer, M. Elementartakte mit zwei Quantensprüngen.
Ann. Phys. 9, 275-294 (1931)
2. Parthenopoulos, D. A. & Rentzepis, P. M. Three-dimensional
optical storage memory. Science 245, 843-845 (1989)
3. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser
scanning fluorescence microscopy. Science 248, 73-76 (1990)
4. Zhao, C. F., He, G. S., Bhawalkar, J. D., Park, C. K. &
Prasad, P. N. Newly synthesized dyes and their polymer/glass
composites for one- and two-photon pumped solid-state cavity
lasing. Chem. Mater. 7, 1979-1983 (1995)
5. Reinhardt, B. A. et al. Highly active two-photon dyes:
design, synthesis, and characterization toward application.
Chem. Mater. 10, 1863-1874 (1998)
Nature 2002 415:767
Web Links: three-photon excitation
Related Background Brief:
TWO-PHOTON LASER SCANNING FLUORESCENCE MICROSCOPY. Molecular
excitation by the simultaneous absorption of two photons
provides intrinsic three-dimensional resolution in laser
scanning fluorescence microscopy. The excitation of fluorophores
having single-photon absorption in the ultraviolet with a stream
of strongly focused subpicosecond pulses of red laser light has
made possible fluorescence images of living cells and other
microscopic objects. The fluorescence emission increased
quadratically with the excitation intensity so that fluorescence
and photo-bleaching were confined to the vicinity of the focal
plane as expected for cooperative two-photon excitation. This
technique also provides unprecedented capabilities for
three-dimensional, spatially resolved photochemistry,
particularly photolytic release of caged effector molecules. W.
Denk et al: Science 1990 248:73
Related Background Brief:
IMAGING LIVING CELLS AND TISSUES BY TWO-PHOTON EXCITATION
MICROSCOPY. Two-photon excitation microscopy provides attractive
advantages over confocal microscopy for three-dimensionally
resolved fluorescence imaging. Since two-photon excitation
occurs only at the focal point of the microscope, it inherently
provides three-dimensional resolution. This localization of
excitation also minimizes photobleaching and photodamage, which
are the ultimate limiting factors in imaging living cells.
Furthermore, no pinhole is required to attain three-dimensional
discrimination, so the efficiency of fluorescence collection is
increased. These advantages allow experiments on thick living
samples that would not be possible with other imaging
techniques. The cost and complexity of the lasers required for
two-photon excitation microscopy have limited its use, but
appropriate turn-key lasers have now been introduced, and their
cost should decrease. Finally, the recent introduction of
commercial two-photon excitation laser-scanning microscope
systems allows a much larger group of researchers access to this
state-of-the-art methodology. D.W. Piston: Trends Cell Biol 1999
9:66.
Related Background Brief:
TWO-PHOTON MOLECULAR EXCITATION PROVIDES INTRINSIC 3-DIMENSIONAL
RESOLUTION FOR LASER-BASED MICROSCOPY AND MICROPHOTOCHEMISTRY.
With the development of sensitive and specific fluorescent
indicators, modern laser scanning microscopies enable
visualization and measurement of submicron, dynamic processes
inside living cells and tissues. The authors describe the
working principles of new, nonlinear laser microscopies based on
two-photon molecular excitation. In these techniques, a pulsed
laser produces peak photon densities high enough that when
focused into an appropriate medium, excitation by photon energy
combinations can occur. For example, two red photons interacting
simultaneously with a fluorescent molecule can excite within it
a UV electronic transition, one corresponding to twice the
energy of each single photon. Because the amount of two-photon
excitation depends on the square of the local illumination
intensity, this process exhibits a unique localization to the
diffraction-limited spot of the beam focus. Elsewhere along the
beam, excitation of background and photodamage is virtually
nonexistent. Focal point localization of two-photon excitation
lends to all visualization, measurement, and photopharmacology
studies an intrinsic, three-dimensional resolution. The authors
describe some preliminary biological applications, specifically,
imaging of vital DNA stains in developing cells and embryos,
imaging of cellular metabolic activity from NADH
autofluorescence, spatially resolved measurements of cytoplasmic
calcium ion activity, and optically induced micropharmacology
using caged bioeffector molecules. R.M. Williams et al: FASEB J
1994 8:804.
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8. ON GUIDING X-RAY PHOTONS
Till H. Metzger (European Synchrotron Radiation Facility
Grenoble, FR) discusses x-ray photons, the author making the
following points:
1) Almost 150 years ago, James Clerk Maxwell (1831-1879)
formulated the equations that govern electromagnetic wave
propagation. The equations predict that in materials in which
the index of refraction changes in a stepwise fashion, a
discrete set of modes should be observed. The polarization,
shape, and amplitude of these modes or "guided waves" can be
controlled through the design of the waveguide.
2) Guided waves have found many uses, from efficient radiation
sources to communication technology, but x-rays have proven
difficult to control. The art of guiding waves has been
developed at different times for different parts of the
electromagnetic spectrum. Cavity resonators of microwaves and
radar were known long before the invention of lasers and optical
fibers. Hard x-rays are the last frontier, requiring interfaces
perfect enough to support mode propagation and guiding of 0.1-nm
radiation.
3) Such precision seemed impossible to achieve until Spiller and
Segmüller demonstrated that x-rays can propagate in suitable
planar thin-film structures (2). More recently, Feng et al.
introduced the concept of resonant beam couplers (see the first
figure) (3). These structures enable efficient coupling of
x-rays into planar waveguides. A thinned surface cladding is
used, thereby avoiding coupling of the beam through the front
end. The latter would inevitably lead to large losses, because
the diameters of available x-ray beams are orders of magnitude
larger than the guiding layer. The resonant beam coupler
principle has boosted research into x-ray waveguides, leading to
new devices that could produce x-ray beams with submicrometer
diameters (4, 5). Pfeiffer et al (1) now report the first proof
of principle that resonant beam coupling can be realized in two
dimensions. They show that x-ray resonances can be excited in
two-dimensional (2D) channel structures and clarify the
corresponding coupling mechanism.
References (abridged):
1. F. Pfeiffer, C. David, M. Burghammer, C. Riekel, T. Salditt,
Science 297, 230 (2002)
2. E. Spiller, A. Segmüller, Appl. Phys. Lett. 24, 60 (1974)
3. Y. P. Feng et al., Phys. Rev. Lett. 71, 537 (1993)
4. M. J. Zwanenburg et al., Phys. Rev. Lett. 82, 1696 (1999)
5. M. J. Zwanenburg et al., Phys. Rev. Lett. 85, 5154 (2000)
Science 2002 297:205
Web Links: wave guides
Related Background Brief:
NON-DESTRUCTIVE DETERMINATION OF LOCAL STRAIN WITH 100-NANOMETRE
SPATIAL RESOLUTION. Structure sizes of approximately 180 nm are
now standard in microelectronics, and state-of-the-art
fabrication techniques can reduce these to just a few tens of
nanometres. But at these length scales, the strain induced at
interfaces can locally distort the crystal lattice, which may in
turn affect device performance in an unpredictable way. A means
of non-destructively characterizing such strain fields with high
spatial resolution and sensitivity is therefore highly
desirable. One approach is to use Raman spectroscopy, but this
is limited by the intrinsic approximately 0.5-microm resolution
limit of visible light probes. Techniques based on electron-beam
diffraction can achieve the desired nanometer-scale resolution.
But either they require complex sample preparation procedures
(which may alter the original strain field) or they are
sensitive to distortional (but not dilational) strain within
only the top few tens of nanometres of the sample surface.
X-rays, on the other hand, have a much greater penetration
depth, but have not hitherto achieved strain analysis with
sub-micrometer resolution. The authors describe a magnifying
diffraction imaging procedure for X-rays which achieves a
spatial resolution of 100nm in one dimension and a sensitivity
of 10^(-4) for relative lattice variations. The authors
demonstrate the suitability of this procedure for strain
analysis by measuring the strain depth profiles beneath oxidized
lines on silicon crystals. S. Di Fonzo et al: Nature 2000
403:638.
Related Background Brief:
TWO-DIMENSIONAL X-RAY WAVEGUIDES AND POINT SOURCES. X-ray
scattering has had a tremendous impact as an experimental
technique for studying the atomic structure of condensed matter.
However, the technique is usually limited by two important
constraints. First, it is characterized by two extremely opposed
(separated) length scales: the microscopic x-ray wavelength and
the macroscopic cross section of the beam or, equivalently, the
spot size on the sample. The sample therefore must be
homogeneous over the entire length, and the technique probes its
ensemble-averaged structure. Second, the technique is restricted
to static structural information owing to the elastic nature of
the scattering events. X-ray scattering is insensitive to the
dynamic nature of structural assemblies. The authors demonstrate
that resonant coupling of synchrotron beams into suitable
nanostructures can be used for the generation of coherent x-ray
point sources. A two-dimensionally confining x-ray waveguide
structure has been fabricated by e-beam lithography. By shining
a parallel undulator beam onto the structure, a discrete set of
resonant modes can be excited in the dielectric cavity,
depending on the two orthogonal coupling angles between the beam
and the waveguide interfaces. The resonant excitation of the
modes is evidenced from the characteristic set of coupling
angles as well as the observed far-field pattern. The x-ray
nanostructure may be used as coherent x-ray point sources with a
beam cross section in the nanometer range. F. Pfeiffer et al:
Science 2002 297:230.
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9. INORGANIC CHEMISTRY: ON TRANSITION METAL NITROSYLS
L. Andrews and A. Citra (University of Virginia, US) discuss
transition metal nitrosyls, the authors making the following
points:
1) Although the chemistry of nitric oxide (NO) is extremely
important in several areas of chemistry, the interaction of NO
with transition metals is perhaps the most noteworthy. The
reaction of nitric oxide on metal surfaces and in contact with
metal cations in zeolites is important in the development of
effective catalysts that can reduce atmospheric pollution.(1-3)
2) The susceptibility of adsorbed NO to dissociation on metal
substrates depends on the metal position in the periodic table,
which relates to the heat of adsorption.(1) In addition,
transition metal nitrosyl complexes play many roles. Novel
nitrosyl structures may form the basis for information storage
by virtue of long-lived metastable isomers.(4,5) Furthermore,
the interaction of nitric oxide with transition metal centers in
biological systems has also received considerable attention.
Nitric oxide binds to the heme center in metalloproteins and has
been identified as an important messenger molecule in
neurophysical systems. Finally, nitric oxide reacts with
superoxide to form peroxynitrite, which has serious pathological
consequences in the human system.
3) At the heart of these research areas is the fundamental
interaction between NO and transition metal atoms. In the past
this has been classified in terms of the electron count in the
{MNO} subunit in larger complexes, and qualitative molecular
orbital diagrams have been constructed to explain and predict
the properties of such compounds. While these schemes are
useful, they have been surpassed by quantum chemical
calculations, in particular density functional theory, that can
compute the equilibrium and associated properties of transition
metal nitrosyl-containing species, including metal nitrosyl
complexes, and even first principles calculations for nitric
oxide on extended metal surfaces. Such calculations do away with
the assumptions of early bonding models and introduce a number
of new parameters to characterize a nitrosyl complex or an
extended system, namely the structure, energy, and nitrosyl
stretching frequencies. The authors review the experimental
measurement and density functional theory calculation of simple
binary transition metal nitrosyl vibrational frequencies.
References (abridged):
1. Brown, W. A.; King, D. A. J. Phys. Chem. B 2000, 104, 2578
2. Schlogl, R. Angew. Chem. 1993, 105, 402
3. Shelef, M. Chem. Rev. 1995, 95, 209
4. (a) Zollner, H.; Kraser, W.; Woike, T.; Haussuhl, S. Chem.
Phys. Lett. 1989, 161, 497. (b) Woike, Th.; Haussuhl, S. Solid
State Commun. 1993, 86, 333
5. Guida, J. A.; Aymonino, P. J.; Piro, O. E.; Castellano, E. E.
Spectrochim. Acta 1993, 49A, 535. Guida, J. A.; Piro, O. E.;
Aymonino, P. J. Inorg. Chem. 1995, 34, 4113
Chem. Rev. 2002 102:885
Web Links: nitrosyls nitric oxide
Related Background Brief:
NITRIC OXIDE CHEMISORPTION AND REACTIONS ON METAL SURFACES. A
NEW PERSPECTIVE. The authors present a review with 236
references on nitric oxide adsorption on metal surfaces. In the
past it was recognized that the tendency for a metal surface to
dissociate NO depends on its position in the periodic table, but
little was understood about the dissociation process itself.
Recent experimental and theoretical studies have shown that this
view is oversimplified. In addition to the distinction between
molecular and dissociative adsorption on surfaces, the structure
of NO on metal surfaces has also been the subject of detailed
study and debate. The authors suggest it is therefore timely to
update our ideas about NO adsorption and reactivity. The authors
examine the structure of NO on surfaces, in particular the
break-down of vibrational assignments, and how these assignments
can be improved. The NO dissociation process is also discussed
along with the formation and reactions of the NO dimer, (NO)2,
on some metal surfaces. W.A. Brown and D.A. King: J Phys Chem B
2000 104:2578.
Related Background:
BIOCHEMISTRY: NITRIC OXIDE
Endothelial cells are flat cells forming a layer lining blood
vessels, lymphatic vessels, the heart, etc., and the term
"relaxing factor" refers to any chemical entity that promotes
the relaxation of muscle fibers. The discovery of an
endothelial-derived relaxing factor by R.F. Furchgott in 1980
initiated studies that ultimately led to the identification of
nitric oxide as an endogenous signaling molecule. In the
classical pathway described by Furchgott, nitric oxide is
synthesized by vascular endothelial cells and the substance then
diffuses into the underlying smooth muscle cells to mediate
vascular relaxation. Although this pathway plays a major role in
vascular control, subsequent work has revealed that
endothelium-dependent relaxation is not the only mode for nitric
oxide to regulate blood flow. In certain vascular beds,
regulation of vessel tone by nitric oxide does not require the
endothelium but instead relies on neuronal activity,
specifically on neurons involved in the synthesis of nitric
oxide. (This is the basis for the action of sildenafil [Viagra].)
P.C. Ford and I.M. Lorkovic (University of California Santa
Barbara, US) discuss nitric oxide, the authors making the
following points:
1) It is now well established that nitric oxide (nitrogen
monoxide; NO) plays fundamental roles in biochemical
processes.(1,2) Early concerns with the biology of NO were
largely focused on the known toxicities of NO and other reactive
nitrogen oxide species as constituents of air pollution,
including cigarette smoke.(3) However, natural physiological
activities are now known to include roles in blood pressure
control, neurotransmission, and immune response. Subsequent
reports have identified a number of disease states involving NO
imbalances,(2,4) and such observations have stimulated extensive
research activity into the chemistry, biology, and pharmacology
of NO. This has led to renewed interest in the solution-phase
reactions of NO, since understanding the fundamental chemistry
may provide new insights regarding the physiological roles of
this "simple" molecule.
2) The principal targets for NO under bioregulatory conditions
are metal centers, primarily iron proteins.(5) The best
characterized example is the ferro-heme enzyme soluble guanylyl
cyclase. Formation of a nitrosyl complex with Fe(II) leads to
labilization of a trans axial (proximal) histidine ligand in the
protein backbone, and the resulting change in the protein
conformation is believed to activate the enzyme for catalytic
formation of the secondary messenger cyclic-guanylyl
monophosphate (cGMP) from guanylyl triphosphate (GTP). The
enzymatic formation of cGMP leads to relaxation of smooth muscle
tissue of blood vessels, hence lowering blood pressure. Other
reports describe roles of NO as an inhibitor for metalloenzymes
such as cytochrome P450, a cytochrome oxidase, nitrile
hydratase, and catalase, as a substrate for mammalian
peroxidases, and as a contributor to the vasodilator properties
of a salivary ferri-heme protein of blood sucking insects. Heme
centers are also involved in the in vivo generation of NO by
oxidation of arginine catalyzed by nitric oxide synthase enzymes.
3) For bioregulatory purposes, NO concentrations generated are
low, and [NO] values less than 1 micromolar have been reported
to be generated in endothelium cells for blood pressure control.
Thus, reactions with targets such as sGC must be very fast to
compete effectively with other physical and chemical processes
that deplete free NO. However, the NO concentrations produced
during immune response to pathogen invasion are much higher, and
under these conditions, reactive nitrogen species such as
peroxynitrite anion (OONO-) and N(sub2)O(sub3) may have
physiological importance. These biomedical roles place a high
premium on understanding the fundamental chemistry of NO under
conditions relevant to its biological formation and decay.
References (abridged):
1. (a) Moncada, S.; Palmer, R. M. J.; Higgs, E. A. Pharmacol.
Rev. 1991, 43, 109. (b) Feldman, P. L.; Griffith, O. W.; Stuehr,
D. J. Chem. Eng. News 1993, 71 (10), 26. (c) Butler, A. R.;
Williams, D. L. Chem. Soc. Rev. 1993, 233. (d) Methods in Nitric
Oxide Research; Feelisch M., Stamler, J. S., Eds.; John Wiley
and Sons: Chichester, England, 1996 and references therein. (e)
Wink, D. A.; Hanbauer, I.; Grisham, M. B.; Laval, F.; Nims, R.
W.; Laval, J.; Cook, J.; Pacelli, R.; Liebmann, J.; Krishna, M.;
Ford, P. C.; Mitchell, J. B. Curr. Top. Cell. Regul. 1996, 34,
159.
2. Nitric Oxide: Biology and Pathobiology; Ignarro, L. J., Ed.;
Academic Press: San Diego, 2000.
3. Schwartz, S. E.; White, W. H. Trace Atmospheric Constituents.
Properties, Transformation and Fates; J. Wiley & Sons: New York,
1983.
4. Nitric Oxide and Infection; Fang, F. C., Ed.; Kluwer
Academic/Plenum Publishers: New York, 1999.
5. (a) Traylor, T. G.; Sharma, V. S. Biochemistry 1992, 31,
2847. (b) Radi, R. Chem. Res. Toxicol. 1996, 9, 828.
Chem. Rev. 2002 102:993
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10. ON FETAL ALCOHOL SYNDROME
L. Miller et al (Centers for Disease Control and Prevention, US)
discuss fetal alcohol syndrome, the authors making the following
points:
1) Fetal alcohol syndrome is caused by maternal alcohol use
during pregnancy and is one of the leading causes of preventable
birth defects and developmental disabilities in the US. Fetal
alcohol syndrome is diagnosed on the basis of a combination of
growth deficiency (pre- or postnatal), central nervous system
dysfunction, facial dysmorphology, and maternal alcohol use
during pregnancy. Estimates of the prevalence vary from 0.2 to
1.0 per 1,000 live-born infants. This variation is due, in part,
to the small size of the populations studied, varying case
definitions, and different surveillance methods. In addition,
differences have been noted among racial/ethnic populations. To
monitor the occurrence of fetal alcohol syndrome, the Centers
for Disease Control (CDC) collaborated with five states (Alaska,
Arizona, Colorado, New York, and Wisconsin) to develop the Fetal
Alcohol Syndrome Surveillance Network (FASSNet). The authors
report a summary of the results of an analysis of FASSNet data
on children born during 1995-1997, which indicate that FAS rates
in Alaska, Arizona, Colorado, and New York ranged from 0.3 to
1.5 per 1,000 live-born infants and were highest for black and
American Indian/Alaska Native populations.
2) The CDC suggests this report demonstrates that maternal
alcohol use during pregnancy continues to affect children.
Recent data indicate that the prevalence of binge (i.e., >5
drinks on any one occasion) and frequent drinking (i.e., >7
drinks per week or >5 drinks on any one occasion) during
pregnancy reached a high point in 1995 and has not declined.
FASSNet prevalence rates are similar to rates published
previously from population-based prevalence studies, despite
different case definitions and surveillance methods. These data
indicate that children born to mothers in certain racial/ethnic
populations have consistently higher prevalence rates of fetal
alcohol syndrome. For example, prevalence was 3.0 per 1,000
live-born infants for American Indians/Alaska Natives during
1977-1992 compared with 0.2 for other Alaska residents during
the same period. FASSNet findings confirm higher prevalence
rates among black and American Indian/Alaska Native populations.
Alaska health authorities have increased efforts to address this
health problem. Increased awareness of maternal alcohol use and
more complete documentation by Alaska Native health
organizations might result in more vigilant reporting of
potential cases of FAS, which could contribute to high reported
FAS prevalence in this population.
3) The number of children affected adversely by in-utero
exposure to alcohol is probably underestimated for at least four
reasons. First, some fetal alcohol syndrome cases might not be
diagnosed because of the syndromic nature of the condition, the
lack of pathognomonic features, and the negative perceptions of
fetal alcohol syndrome diagnosis. Second, medical records of
children with fetal alcohol syndrome often lack sufficient
documentation to determine case status. For example, 10 children
diagnosed with fetal alcohol syndrome by a clinical geneticist,
dysmorphologist, or developmental pediatrician did not meet the
surveillance case definition for confirmed or probable fetal
alcohol syndrome because documentation in the abstracted medical
records was insufficient or the child did not meet FASSNet
surveillance case definition criteria. However, adding these 10
children to the total case count would change the overall
prevalence only slightly, from 0.43 to 0.45 per 1,000 live-born
infants. Third, some children might not be identified as having
fetal alcohol syndrome until they reach school age, at which
point central nervous system abnormalities and learning
disabilities are recognized more easily. Because only part of
the cohort under surveillance was of school age and education
records were not used in this surveillance system, the actual
number of cases might have been underestimated. Finally, an
unknown number of persons with fetal alcohol syndrome left the
surveillance area before being identified by the surveillance
system. Because of the small numbers and differences in sources
and awareness among clinicians, prevalence rates across
racial/ethnic populations and across states should be compared
with caution.
4) The CDC suggests that ongoing, consistent, population-based
surveillance systems are necessary to measure the occurrence of
fetal alcohol syndrome and the impact of fetal alcohol syndrome
prevention activities. These systems also are useful in
evaluating the need for early intervention and special education
services for children with birth defects such as fetal alcohol
syndrome.
J. Am. Med. Assoc. 2002 288:38
Morbidity & Mortality Weekly Report 2002 51:433
Web Links: fetal alcohol syndrome
Related Background:
ALCOHOL USE IN THE US AMONG WOMEN OF CHILD-BEARING AGE
The term "fetal alcohol syndrome" refers to fetal dysfunction
due to maternal alcohol abuse during pregnancy, and it is the
most common cause of drug-induced fetal dysfunction and fetal
malformations (teratogenesis). The most severe dysfunction
consequence is severe mental retardation due to impaired brain
development. In general, alcohol ingested during pregnancy can
produce a wide spectrum of defects, ranging from spontaneous
abortion to severe behavioral defects without apparent physical
anomalies. The US incidence of fetal alcohol syndrome is
approximately 2.2 per 1000 live births, which exceeds that of
Down syndrome and cerebral palsy. The critical volume of
ingested alcohol that results in fetal alcohol syndrome is
unknown.
The Morbidity and Mortality Weekly Report (Centers for Disease
Control and Prevention, US) discusses alcohol use among women of
child-bearing age, the report making the following points:
1) Prenatal exposure to alcohol is one of the leading
preventable causes of birth defects, mental retardation, and
neurodevelopmental disorders in the United States.(1) One of the
national health objectives for 2010 is to increase the
percentage of pregnant women abstaining from alcohol to 94
percent.(2) During 1991-1995, alcohol use by pregnant women
increased substantially, and alcohol use by nonpregnant women of
childbearing age increased slightly.(3) To characterize trends
in alcohol use among women of childbearing age, CDC analyzed
representative survey data from the Behavioral Risk Factor
Surveillance System (BRFSS) during 1991-1999. This report
summarizes the results of the analysis, which indicate that the
rate of any alcohol use (i.e., at least one drink) during
pregnancy has declined since 1995. However, rates of binge
drinking (i.e., 5 drinks on any one occasion) and frequent
drinking (i.e., 7 drinks per week or 5 drinks on any one
occasion) during pregnancy have not declined, and these rates
also have not declined among nonpregnant women of childbearing
age. The report suggests that health-care providers should
routinely screen women of childbearing age for alcohol use and
counsel them about the adverse effects of alcohol use during
pregnancy.
2) BRFSS is an ongoing, state-based, random-digit–dialed
telephone survey of the noninstitutionalized U.S. civilian
population aged 18 years. Data were analyzed for women aged
18-44 years in all 50 states. Women were asked about their use
of alcohol during the 30 days preceding the survey. Three
alcohol drinking patterns were examined: any use, binge
drinking, and frequent drinking. Information on alcohol use was
obtained every year through 1993 and every other year thereafter.
3) During 1995-1999, a total of 4,695 (4.3 percent) of the
107,141 women aged 18-44 years who were interviewed about their
alcohol use during the month preceding the survey reported that
they were pregnant at the time of the interview. The prevalence
of any alcohol use among pregnant women increased from 12.4
percent in 1991 to 16.3 percent in 1995.(3) Compared with 1995
data, prevalence was lower in 1997 (11.4 percent) and 1999 (12.8
percent). In contrast, the rates of binge drinking and frequent
drinking reported by pregnant women in 1995 remained
substantially unchanged in 1997 and 1999: binge drinking rates
were 2.9 percent in 1995, 1.8 percent in 1997, and 2.7 percent
in 1999, and frequent alcohol use rates were 3.5 percent in
1995, 2.1 percent in 1997, and 3.3 percent in 1999. Among
nonpregnant women who reported any alcohol use, rates remained
stable: 53.2 percent in 1995, 52.8 percent in 1997, and 53.3
percent in 1999. Binge drinking rates among this population were
11.2 percent in 1995, 10.8 percent in 1997, and 12.3 percent in
1999.
4) In comparison with other pregnant women, pregnant women who
reported any alcohol use, binge drinking, and frequent drinking
were more likely to be aged >30 years, employed, and unmarried.
Nonpregnant women who reported any alcohol use, binge drinking,
and frequent drinking had similar employment and marital status
as pregnant women. In addition, nonpregnant women reporting any
alcohol use were more likely to be white and to have higher
education levels than women who did not engage in this behavior;
nonpregnant women who reported binge drinking and frequent
drinking tended to be aged <30 years.
References (abridged):
1. Jacobs EA, Copperman SM, Jeffe A, Kulig J. Fetal alcohol
syndrome and alcohol related neurodevelopmental disorders.
Pediatrics. 2000 106:358-61.
2. US Department of Health and Human Services. Healthy People
2010 (conference ed, in 2 vols). Washington, DC: US Department
of Health and Human Services, 2000.
3. CDC. Alcohol consumption among pregnant and childbearing-aged
womenUnited States, 1991 and 1995. MMWR Morb Mortal Wkly Rep.
1997;46:346-50.
4. US Department of Health and Human Services. Summary of
findings from the 1999 National Household Survey on Drug Abuse.
Washington, DC: US Department of Health and Human Services, 2000.
5. Ebrahim SH, Diekman ST, Floyd LR, Decoufle P.
Pregnancy-related alcohol use among women in the United
States1988-95. Prenat Neonat Med. 1999 4:39-46.
J. Am. Med. Assoc. 2002 287:2069
MMWR 2002 51:273
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11. OBESITY AND THE RISK OF HEART FAILURE
S. Kenchaiah et al (Framingham Heart Study, US) discuss obesity
and heart failure, the authors making the following points:
1) Heart failure is a major health problem that is increasing in
scope.(1) Despite recent therapeutic advances, morbidity and
mortality after the onset of heart failure remain
substantial.(1) Consequently, prevention of heart failure
through identification and management of risk factors and
preclinical phases of the disease is a priority.(2) In this
context, several studies have evaluated body-mass index (the
weight in kilograms divided by the square of the height in
meters) as a risk factor for left ventricular remodeling and
overt heart failure. In these investigations, obesity has been
consistently associated with left ventricular hypertrophy and
dilatation,(3-5) which are known precursors of heart failure.
Whereas extreme obesity has been associated with heart failure,
data are limited regarding the influence of overweight and
lesser degrees of obesity on the risk of heart failure.
Accordingly, the authors investigated the relation of body-mass
index with the risk of heart failure in a community-based sample.
2) The authors investigated the relation between the body-mass
index and the incidence of heart failure among 5881 participants
in the Framingham Heart Study (mean age, 55 years; 54 percent
women). During follow-up (mean, 14 years), heart failure
developed in 496 subjects (258 women and 238 men). After
adjustment for established risk factors, there was an increase
in the risk of heart failure of 5 percent for men and 7 percent
for women for each increment of 1 in body-mass index. As
compared with subjects with a normal body-mass index, obese
subjects had a doubling of the risk of heart failure. For women,
the hazard ratio was 2.12 (95 percent confidence interval, 1.51
to 2.97); for men, the hazard ratio was 1.90 (95 percent
confidence interval, 1.30 to 2.79).
3) The authors conclude that in their large, community-based
sample, increased body-mass index was associated with an
increased risk of heart failure. The authors suggest that given
the high prevalence of obesity in the US, strategies to promote
optimal body weight may reduce the population burden of heart
failure.
References (abridged):
1. American Heart Association. 2002 Heart and stroke statistical
update. Dallas: American Heart Association, 2001
2. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the
evaluation and management of chronic heart failure in the adult:
executive summary: a report of the American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee to Revise the 1995 Guidelines for the
Evaluation and Management of Heart Failure). J Am Coll Cardiol
2001;38:2101-2113
3. Messerli FH, Sundgaard-Riise K, Reisin ED, et al. Dimorphic
cardiac adaptation to obesity and arterial hypertension. Ann
Intern Med 1983;99:757-761
4. Hammond IW, Devereux RB, Alderman MH, Laragh JH. Relation of
blood pressure and body build to left ventricular mass in
normotensive and hypertensive employed adults. J Am Coll Cardiol
1988;12:996-1004
5. Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of
obesity on left ventricular mass and geometry: the Framingham
Heart Study. JAMA 1991;266:231-236
New Engl. J. Med. 2002 347:305
Web Links: obesity and heart disease
Related Background Brief:
DIMORPHIC CARDIAC ADAPTATION TO OBESITY AND ARTERIAL
HYPERTENSION. Cardiovascular function and structure were
evaluated by M-mode echocardiography and systemic hemodynamics
in paired lean and obese patients, either hypertensive or
normotensive. Compared to lean patients, obese patients had
greater left atrial (p less than 0.0001), ventricular (p less
than 0.001), and aortic root (p less than 0.002) diameters;
posterior and septal wall thickness (p less than 0.001); and
ventricular mass, cardiac output, stroke volume, and stroke work
(all p less than 0.0001). Hypertensive patients had increased
posterior wall thickness, end diastolic wall stress, stroke work
(p less than 0.01), and a lower radius to posterior wall
thickness ratio indicating concentric hypertrophy (p less than
0.001) when compared to normotensive patients. Cardiac
adaptation to obesity consists of left ventricular dilatation
and hypertrophy (eccentric hypertrophy) irrespective of arterial
pressure levels. In contrast, essential hypertension solely
produces concentric hypertrophy. Both obesity and hypertension
increase left ventricular stroke work by disparate hemodynamic
mechanisms; their presence in the same patient will tax the
heart and increase the long-term risk of congestive failure.
F.H. Messerli et al: Ann Intern Med 1983 99:757.
Related Background Brief:
RELATION OF BLOOD PRESSURE AND BODY BUILD TO LEFT VENTRICULAR
MASS IN NORMOTENSIVE AND HYPERTENSIVE EMPLOYED ADULTS. Left
ventricular muscle mass is increased in the presence of large
body size, high blood pressure and obesity, but the relative
contributions to ventricular mass of these and other factors
have not been elucidated. Accordingly, echocardiographic left
ventricular mass in unmedicated employed adults (162
normotensive, 145 borderline hypertension and 317 with
established essential hypertension) was related to height,
weight, lean body mass, body mass index, systolic and diastolic
blood pressure, age, gender, race and 24 h urinary sodium and
potassium excretion. In the total population, body mass index,
systolic blood pressure and height were the most significant (p
less than 0.0001) independent correlates of left ventricular
mass, whereas gender and age made smaller contributions. In each
normotensive and hypertensive subgroup, body mass index and
height remained highly significant independent predictors of
left ventricular mass, systolic blood pressure became a weaker
predictor (0.001 less than p less than 0.02) and only among
patients with established hypertension was diastolic blood
pressure a weak independent determinant (p less than 0.05) of
ventricular mass. The increase in left ventricular mass
attributable to obesity was due to eccentric hypertrophy because
end-diastolic relative wall thickness was similar in obese and
non-obese subjects in each blood pressure group. Thus obesity,
as measured by body mass index, is as important a potential
determinant of left ventricular muscle mass as is systolic blood
pressure and it is of greater statistical significant in an
adult employed population than is diastolic blood pressure,
height, gender, age or dietary sodium intake. I.W. Hammond et
al: J Am Coll Cardiol 1988 12:996.
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12. ON THE TREATMENT OF OBESITY
Jules Hirsch (Rockefeller University, US) discusses treatment of
obesity, the author making the following points:
1) Obesity must be ranked among the most intractable of our
health problems. In 1999, the Centers for Disease Control and
Prevention reported (1) that obesity, defined as a body mass
index =>30, had risen in the adult United States population from
12.0% in 1991 to 17.9% in 1998. At this time we have little
evidence for abatement of the "epidemic," although warnings from
health officials and physicians are numerous and most
individuals consider obesity both unsightly and hazardous.
Treatments with many different diets, behavior modification,
nutrition counseling, over-the-counter drugs, and dietary
supplements are the basis for a lucrative industry that has
hardly made a dent in the problem. How can we understand the
intractability of this national nuisance?
2) The unwanted weight of the obese is that of triglyceride
stored in adipose tissue. Storage of this calorically dense
substance is held to account by the simple thermodynamic
expression, delta(E) = Q - W. One cannot increase energy
storage (E) without an inequality between what you eat (Q) and
what you burn (W). But there is some surprising arithmetic in
the account ledger of calories. Consider the all-too-common case
of Mr. X who joined the ranks of the obese by gradually
accumulating 75,000 kcal (1 kcal = 4.18 kJ) in his adipose depot
over the first 5 years of happy marriage. The extra 75,000 kcal
is just a ripple in the vast stream of 4 million or 5 million
kilocalories that flux in and out of Mr. X's body over 5 years.
In fact, his excess intake averages only 40 kcal per day or
about 1.5% of what normal or non-obese intake might be. Our
choices of foods and the amount we eat at any meal are likely to
be determined by the time of day, social context, level of
culinary excellence, and just caprice. This being the case, it
is all the more amazing that just a bite or two less at each
meal, to create the small deficit in Q needed for the slow
abatement of obesity, is such a difficult behavior to sustain
over time. In some way, seemingly random variations in food
intake are shaped over long periods of time so as to maintain
the level of caloric storage, whether obese or normal. This
speaks for the existence of a regulatory system that senses the
level of caloric storage and makes long-term adjustments of food
intake and/or caloric expenditure.
3) Studies of adipose tissue histology many years ago showed
that the number of adipocytes, like the level of fat storage,
remains quite constant, but adipocytes readily enlarge or shrink
with overfeeding and underfeeding (3). This response of cell
size to nutritional alterations led the author to wonder whether
something related to cell size might generate a signal to
hypothalamic centers involved in the control of food intake,
thereby constituting a system for maintaining a fixed weight of
adipose tissue at either normal or excess levels (4).
4) The advent of molecular genetics brought powerful new tools
for addressing this issue. Various genetically based obesities
in mice and rats had been under study in many different ways
without uncovering the mechanism for obesity; however,
positional cloning found the molecular defect in the obese ob/ob
mouse (5). The inability of the adipocyte of ob/ob mice to
secrete leptin, a novel peptide, is the central abnormality in
this genetic form of obesity; defects in the detection of leptin
by central nervous system receptors are the basis for a number
of other genetic obesities in rats and mice. Along with leptin,
the adipocyte elaborates and secretes adipsin, adiponectin,
resistin, and such a remarkable number of other substances that
reviews have appeared on the "adipocyte as an endocrine organ".
Which adipocyte product, other than leptin, senses energy
storage is a lively area for research, but it is likely that
more than one signal from adipose tissue can up- or
down-regulate a group of food intake-controlling neuropeptides
found in the arcuate nucleus of the ventro-medical hypothalamus.
References (abridged):
1. Nokdad, A. H. , Serdula, M. K. , Dietz, W. H. , Bowman, B.
A. , Marks, J. S. & Koplan, J. P. (1999) J. Am. Med. Assoc. 282,
1519-1522
2. Thupari, J. N. , Landree, L. E. , Ronnett, G. V. & Kuhajda,
F. P. (2002) Proc. Natl. Acad. Sci. USA 99, 9498-9502
3. Hirsch, J. (1971) in Advances in Internal Medicine, ed.
Stollerman, G. H. (Yearbook Medical Publishers, Chicago), Vol.
17, pp. 289-300
4. Hirsch, J. (1972) Adv. Psychosom. Med. 7, 229-242
5. Zhang, Y. , Proenca, R. , Maffei, M. , Barone, M. , Leopold,
L. & Friedman, J. M. (1994) Nature (London) 372, 425-432
Proc. Nat. Acad. Sci. 2002 99:9096
Web Links: leptin adipocytes
Related Background Brief:
C75 INCREASES PERIPHERAL ENERGY UTILIZATION AND FATTY ACID
OXIDATION IN DIET-INDUCED OBESITY. C75, a known inhibitor of
fatty acid synthase is postulated to cause significant weight
loss through decreased hypothalamic neuropeptide Y (NPY)
production. Peripherally, C75, an -methylene--butyrolactone,
reduces adipose tissue and fatty liver, despite high levels of
malonyl-CoA. To investigate this paradox, the authors studied
the effect of C75 on fatty acid oxidation and energy production
in diet-induced obese (DIO) mice and cellular models.
Whole-animal calorimetry showed that C75-treated DIO mice had a
50% greater weight loss, and a 32.9% increased production of
energy because of fatty acid oxidation, compared with paired-fed
controls. Etomoxir, an inhibitor of carnitine
O-palmitoyltransferase-1 (CPT-1), reversed the increased energy
expenditure in DIO mice by inhibiting fatty acid oxidation. C75
treatment of rodent adipocytes and hepatocytes and human breast
cancer cells increased fatty acid oxidation and ATP levels by
increasing CPT-1 activity, even in the presence of elevated
concentrations of malonyl-CoA. Studies in human cancer cells
showed that C75 competed with malonyl-CoA, as measured by CPT-1
activity assays. Thus, C75 acts both centrally to reduce food
intake and peripherally to increase fatty acid oxidation,
leading to rapid and profound weight loss, loss of adipose mass,
and resolution of fatty liver. The pharmacological stimulation
of CPT-1 activity is a novel finding. The dual action of the C75
class of compounds as fatty acid synthase inhibitors and CPT-1
agonists has therapeutic implications in the treatment of
obesity and type II diabetes. J. W. Thupari et al: Proc. Nat.
Acad. Sci. 2002 99:9498.
Related Background:
ON THE HORMONE GHRELIN
D.E. Cummings et al (University of Washington, US) discuss the
hormone ghrelin, the authors making the following points:
1) Obesity represents a global epidemic(1) and is a leading
cause of illness and death worldwide.(2,3) Weight reduction
achieved by dieting, exercise, or medical therapy often elicits
compensatory changes in appetite and energy expenditure(4,5)
that make weight loss of more than 5 to 10 percent unlikely to
be sustained. In contrast, gastric bypass surgery, in which most
of the stomach and duodenum are bypassed with the use of a
gastrojejunal anastomosis, typically causes substantial,
long-term weight loss. The operation appears to undermine the
normal compensatory physiologic responses to energy deficit.
This effect is unlikely to result from gastric restriction
alone, and it has been proposed that a disruption of gut-derived
factors that regulate eating behavior is involved, although no
such factors have been identified.
2) Ghrelin is a recently discovered orexigenic hormone that is
secreted primarily by the stomach and duodenum and has been
implicated in both meal-time hunger and the long-term regulation
of body weight. In humans, plasma ghrelin levels rise shortly
before and fall shortly after every meal, a pattern that is
consistent with a role in the urge to begin eating. If
circulating ghrelin participates in long-term regulation of body
weight, its level should increase with weight loss as part of
the compensatory response to an energy deficit. In contrast,
gastric bypass may disrupt ghrelin secretion by isolating
ghrelin-producing cells from direct contact with ingested
nutrients, which normally regulate ghrelin levels, and this
effect may contribute to the efficacy of the procedure in
reducing weight.
3) To test these hypotheses, the authors determined the 24-hour
plasma ghrelin profiles in subjects before and after
diet-induced weight loss, and compared these values with those
in subjects who had lost weight after proximal gastric bypass
surgery. The authors report that the increase in plasma ghrelin
level with diet-induced weight loss is consistent with the
hypothesis that ghrelin has a role in the long-term regulation
of body weight. Gastric bypass is associated with markedly
suppressed ghrelin levels, possibly contributing to the
weight-reducing effect of the procedure.
4) In summary: 24-hour plasma ghrelin levels increase in
response to diet-induced weight loss, suggesting that ghrelin
may play a part in the adaptive response that limits the amount
of weight that may be lost by dieting. We also found that
ghrelin levels are abnormally low after gastric bypass, raising
the possibility that this operation reduces weight in part by
suppressing ghrelin production. These data suggest that ghrelin
antagonists may someday be considered in the treatment of
obesity.
References (abridged):
1. Taubes G. As obesity rates rise, experts struggle to explain
why. Science 1998;280:1367-1368
2. Kopelman PG. Obesity as a medical problem. Nature
2000;404:635-643
3. Lew EA. Mortality and weight: insured lives and the American
Cancer Society Studies. Ann Intern Med 1985;103:1024-1029
4. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy
expenditure resulting from altered body weight. N Engl J Med
1995;332:621-628. [Erratum, N Engl J Med 1995;333:399.]
5. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG.
Central nervous system control of food intake. Nature
2000;404:661-671
New Engl. J. Med. 2002 346:1623
Web Links: ghrelin hormone
Related Background:
ON CHILDHOOD OBESITY
Albert P. Rocchini (University of Michigan, US) discusses
childhood obesity, the author making the following points: 1)
Childhood obesity has reached epidemic proportions. Worldwide,
approximately 22 million children under 5 years of age are
overweight, and during the past 3 decades, the number of
overweight children in the US has more than doubled. In 1983,
18.6 percent of preschool children in the US were defined as
overweight, and 8.5 percent were defined as obese. By the year
2000, 22 percent of preschool children were overweight and 10
percent were obese. Data indicate that the prevalence of
overweight has increased by 21.5 among non-Hispanic black
children, 21.8 percent among Hispanic children, and 12.3 percent
among non-Hispanic white children. Similar increases in the
prevalence of obesity have been observed worldwide, and
childhood obesity is the most serious and prevalent nutritional
disorder in the US. 2) Obesity has a substantial effect on
cardiovascular risk. Childhood obesity is directly linked to
abnormalities in blood pressure, lipid, lipoprotein, and insulin
levels in adults, as well as to the risk of both coronary artery
disease and diabetes. It has been documented that 80 percent of
obese adolescents have elevated systolic blood pressure,
diastolic blood pressure, or both. Furthermore, 97 percent of
such adolescents have 4 or more of the following cardiovascular
risk factors: elevated serum triglyceride levels (more than 100
milligrams per deciliter), low levels of high-density
lipoprotein cholesterol, increased total cholesterol levels
(more than 200 milligrams per deciliter), elevated systolic
blood pressure, diastolic blood pressure, or both, diminished
maximal oxygen consumption, and a strong history in the
immediate family of coronary heart disease, myocardial
infarction, angina pectoris, or high blood pressure.
New Engl. J. Med. 2002 346:854
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