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ScienceWeek
SCIENCEWEEK
ScienceWeek - October 4, 2002 Vol. 6 Number 40
An Online Research Digest Published Weekly Since 1997
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I should like to find a way of discouraging unnecessary
publications, but I have not found a solution, save the radical
one... that all scientific papers be published anonymously.
-- Erwin Chargaff (1905-2002)
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Section 1
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1. On the Atmosphere of Saturn's Moon Titan
2. On Relaxation Processes in Supercooled Liquids
3. On Amines and Perfect Reactions
4. Calcium Ion Storage and Dendrite Neuropeptide Release
5. On Grammar vs. Language in Neurolinguistics
6. On the Evolution of Dinoflagellates
7. On Quantum Cloning
8. On Supramolecular Assembly on Surfaces
9. Scanning Tunneling Microscopy at High Pressures
10. Embryonic stem Cells and Parkinson's Disease
11. Infections and Susceptibility to Autoimmune and Allergic
Diseases
12. On Human Use of the Biosphere
13. ScienceWeek Notices and Subscription Information
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Section 2
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1. ON THE ATMOSPHERE OF SATURN'S MOON TITAN
P. Rannou et al (University of Paris, FR) discuss Saturn's moon
Titan, the authors making the following points:
1) Titan, the largest moon of Saturn, is the only satellite in
the Solar System with a dense atmosphere. Titan's atmosphere is
mainly nitrogen with a surface pressure of 1.5 atmospheres and a
temperature of 95 kelvins(1). A seasonally varying(2) haze,
which appears to be the main source of heating and cooling that
drives atmospheric circulation(3,4), shrouds the moon. The haze
has numerous features that have remained unexplained. There are
several layers(5), including a "polar hood", and a pronounced
hemispheric asymmetry(2). The upper atmosphere rotates much
faster than the surface of the moon, and there is a significant
latitudinal temperature asymmetry at the equinoxes.
2) Earth-based observations have long indicated the presence of
CH4 in Titan's atmosphere and the possibility of a rich organic
chemistry. The complexity of Titan's atmospheric photochemistry
was confirmed by Voyager observations in 1980 which revealed the
presence of nine gaseous organic molecules other than CH4. In
addition, laboratory simulations using gas mixtures identical to
Titan's atmosphere have shown that the solid organic material
produced in the laboratory has the same optical properties as
the haze determined from Titan's geometric albedo. Radiative
transfer calculations show that this haze is the dominant
absorber of sunlight in Titan's atmosphere, particularly in the
ultraviolet and blue regions of the spectrum, with the result
that only 10% of the solar flux at the top of Titan's atmosphere
reaches the surface. A significant fraction of sunlight (40%) is
absorbed by the haze in the stratosphere, creating an
anti-greenhouse effect. In addition, the haze is also the
dominant source of infrared cooling in the stratosphere, and
therefore it is not surprising that the stratospheric
circulation is dominated by radiative balance due to the haze.
3) The authors describe a numerical simulation of Titan's
atmosphere, which appears to explain the observed features of
the haze. The critical new factor in the model is the coupling
of haze formation with atmospheric dynamics, which includes a
component of strong positive feedback between the haze and the
winds.
References (abridged):
1. Lellouch, E. et al. Titan's atmosphere and hypothesis ocean:
a re-analysis of the Voyager 1 radio-occultation and IRIS 7.7-m
data. Icarus 79, 328-349 (1989)
2. Sromovsky, L. A. et al. Implication of Titan's north-south
brightness asymmetry. Nature 292, 698-702 (1981)
3. Hourdin, F. et al. Numerical simulation of the general
circulation of the atmosphere of Titan. Icarus 117, 358-374
(1995)
4. Tokano, T., Neubauer, F. M., Laube, M. & McKay, C. P.
Seasonal variation of Titan's atmospheric structure simulated by
a general circulation model. Icarus 47, 493-520 (1999)
5. Rages, K. & Pollack, J. B. Vertical distribution of
scattering haze in Titan's upper atmosphere. Icarus 55, 50-62
(1983)
Nature 2002 418:853
Web Links: moon Titan moons of Saturn
Related Background Brief:
NUMERICAL SIMULATION OF THE GENERAL CIRCULATION OF THE
ATMOSPHERE OF TITAN. The authors report the atmospheric
circulation of Titan was investigated with a general circulation
model. The representation of the large-scale dynamics is based
on a grid point model developed and used at Laboratoire de
Meteorologie Dynamique for climate studies. The code also
includes an accurate representation of radiative heating and
cooling by molecular gases and haze as well as a parametrization
of the vertical turbulent mixing of momentum and potential
temperature. Long-term simulations of the atmospheric
circulation are presented. Starting from a state of rest, the
model spontaneously produces a strong superrotation with
prograde equatorial winds (i.e., in the same sense as the
assumed rotation of the solid body) increasing from the surface
to reach 100 m/sec near the 1-mbar pressure level. Those
equatorial winds are in very good agreement with some indirect
observations, especially those of the 1989 occultation of Star
28-Sgr by Titan. On the other hand, the model simulates
latitudinal temperature contrasts in the stratosphere that are
significantly weaker than those observed by Voyager 1 which, the
authors suggest, may be partly due to the nonrepresentation of
the spatial and temporal variations of the abundances of
molecular species and haze. The authors present diagnostics of
the simulated atmospheric circulation underlying the importance
of the seasonal cycle and a tentative explanation for the
creation and maintenance of the atmospheric superrotation based
on a careful angular momentum budget. F. Hourdin et al: Icarus
1995 117:358.
Related Background Brief:
THE THERMAL STRUCTURE OF TITAN'S ATMOSPHERE. The authors report
they have developed a radiative-convective model of the thermal
structure of Titan's atmosphere. The model computes the solar
and infrared radiation in a series of spectral intervals with
vertical resolution. Sources of opacity in the visible and near
infrared include stratospheric haze particles, methane cloud
particles, and gaseous methane; sources of opacity in the
thermal infrared include the pressure-induced opacity of N2,
CH4, and H2, the permitted transitions of C2H2 and C2H6, and
particulate opacity. The haze properties are determined with a
simple microphysics model. The model contains a minimum of free
parameters and the authors attempt to determine these by fits to
independent data sets. The authors find that gas and haze
opacity alone, with the temperatures fixed by Voyager
observations, produces a model that is within a few percent of
radiative convective balance everywhere in the atmosphere. In a
self-consistent computation of temperatures, the authors find
that their model calculation for the surface temperature is, in
general, colder than the observed value by 5-10 kelvins. The
presence or absence of methane condensation clouds only slightly
alters the results. Good agreement can be obtained by adjusting
the parameters in the model. The model parameters in these
optimized cases are typically within 15% of the baseline values
and within the limits allowed by observations. The authors
conclude that the most important factors controlling Titan's
thermal structure are absorption of sunlight by the
stratospheric haze and the pressure-induced gas opacity in the
infrared. Within the uncertainties of the model, these effects
can explain the observed temperature profile. Condensation
clouds play a minor role, if any. C.P. McKay et al: Icarus 1989
80:23.
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2. ON RELAXATION PROCESSES IN SUPERCOOLED LIQUIDS
S. Hensel-Bielowka and M. Paluch (University of Silesia, PL)
discuss relaxation processes in supercooled liquids, the authors
making the following points:
1) In the supercooled region the molecular dynamics of liquids
slow down dramatically, and some characteristic relaxation
processes can be observed. The major (alpha) relaxation process,
reflecting structural rearrangement, is characterized by a
broad, asymmetric absorption spectrum, along with deviation from
an Arrhenius dependency of relaxation times on temperature or
pressure.
2) For many liquids another relaxation process, called the
secondary or beta relaxation, is found near and below the glass
transition temperature. The maximum of the secondary relaxation
peak occurs at frequencies higher than the alpha peak, and above
Tg both relaxations tend to bifurcate. First observations of the
beta relaxation were made in polymers, corresponding to the
motion of side groups in polymers containing flexible pendant
dipoles, or more generally local mode motions [1]. However, from
the work of Johari and Goldstein [2], who observed the beta
relaxation in rigid small molecules, this process is considered
to be a near universal and intrinsic feature of the deeply
supercooled and glassy states.
3) However, despite much debate, there is no general agreement
about the origin of the secondary relaxation in supercooled
liquids. It is still unknown if this process has an
intermolecular or intramolecular origin, or whether it reflects
small [3,4] or relatively large-angle jumps [5]. Another open
issue is whether all molecules contribute to the relaxation, or
only those residing in regions of density lower than the bulk.
The latter idea was put forward by Johari (1973) and Goldstein
(1969), who referred to regions retaining motional degrees of
freedom as "islands of mobility." On the other hand, the former
idea can be found in many models. One of the most general
concepts is embodied in the "coupling model" of Ngai [1979], who
suggests that the secondary relaxation is a spatially uniform
feature, with temporary fluctuations of density responsible for
the motions underlying this process. This view, in which
statistically all molecules contribute to the observed response,
finds support in the work of Wagner and Richert on sorbitol
[1998] and of Vogel and Roessler on toluene [4].
References (abridged):
1. G. Williams and D. C. Watts, Trans. Faraday Soc. 67, 1971.
(1971).
2. G. P. Johari and M. Goldstein, J. Chem. Phys. 53, 2372 (1970).
3. S. Kaufmann et al., J. Chem. Phys. 93, 197 (1990).
4. M. Vogel and E. Roessler, J. Phys. Chem. B 104, 4285 (2000).
5. A. Arbe et al., Phys. Rev. E 54, 3853 (1996).
Phys. Rev. Lett. 2002 89:025704
Web Links: supercooled liquids relaxation in liquids
Related Background
DIFFUSION IN GLASSES AND SUPERCOOLED LIQUIDS
In general, "ergodicity" is a property of dynamic systems
containing a random variable (stochastic systems): a system is
said to be ergodic if it tends in probability to a limiting form
which is independent of the initial conditions. The term "mode
coupling theory" (MCT) refers to a theory that describes the
transition of super-cooled liquids to a non-ergodic state. The
transition of the super-cooled liquid to the glass state
represents a critical slowing down of the particle motions,
leading to structural arrest. A characteristic property of the
arrested state is that it has the static structure of a liquid.
Apart from the parameters describing the microscopic motion, the
static structure factor is the only input to the theory, which
aims to give a complete description of the dynamical properties
of the system.
H.R. Schober (Institute for Solid-State Research Julich, DE)
discusses diffusion in glasses, the author making the following
points:
1) Diffusion in glasses and their melts has been studied
intensively for many years. These efforts are stimulated both by
the technological importance of glassy and amorphous materials
and by the desire to understand the physics of disordered
systems in general and the liquid to glass transition in
particular. Despite this effort there is still no agreement on
the nature of diffusion on an atomic level or on its change at
temperatures near the glass transition. This holds even for
simple densely packed glasses such as binary metallic glasses.
2) In a hot liquid, diffusion is by flow, whereas, in the glass
well below the transition temperature, it will be mediated by
hopping processes. One key question is the transition between
the two regimes. For fragile glasses, such as most polymers and
amorphous metallic glasses, so-called "mode coupling theory"
predicts an arrest of the homogeneous viscous flow in the
undercooled melt at a temperature (Tc) well above the glass
transition temperature. Hopping processes will suppress the
predicted singularities and will become the dominant diffusion
process near Tc.
3) The nature of the hopping process is another issue of
controversy. Is it by a vacancy mechanism, similar to diffusion
in the crystalline state, or is it via a collective process
inherent to the disordered structure? Investigations are
hampered by the fact that glasses are thermodynamically not in
equilibrium, and one observes aging of the system. The diffusion
coefficient of a glass that has been relaxed for a long time
will be considerably lower than the diffusion coefficient of an
“as quenched” glass.
4) The author reports a molecular dynamics simulation involving
a calculation of the pressure dependence of the diffusion
coefficient in a binary Lennard-Jones glass (i.e., a system
described by a Lennard-Jones potential approximation). Four
temperature regimes are observed. The apparent activation volume
drops from high values in the hot liquid to a plateau value. It
rises steeply near the critical temperature of mode coupling
theory, but in the glassy state one finds again small values
similar to those in the liquid. The peak of the activation
volume at the critical temperature is in agreement with the
prediction of mode coupling theory.
References (abridged):
1. H. Mehrer, Defect Diffus. Forum 129-130, 57 (1996).
2. W. Frank, Defect Diffus. Forum 143-147, 695 (1997).
3. Y. Loirat, J.L. Bocquet, and Y. Limoge, J. Non-Cryst. Solids
265, 252 (2000).
4. F. Faupel, K. Ratzke, H. Ehmler, P. Klugkist, V. Zollmer, C.
Nagel, A. Rehmet, and A. Heesemann, Mater. Res. Soc. Symp. Proc.
664, L2.1.1 (2001).
5. F. Faupel, W. Frank, M.-P. Macht, H. Mehrer, V. Naundorf, K.
Ratzke, S.K. Sharma, H.R. Schober, and H. Teichler, Rev. Mod.
Phys. (to be published).
Phys. Rev. Lett.2002 88:145901
MATERIALS SCIENCE: SUPERCOOLED LIQUIDS
The term "supercooling" refers to the cooling of a liquid to
below its freezing point without the occurrence of a change from
the liquid state to the solid state. A metastable state occurs,
with the particles of the liquid losing energy but not falling
into place in the lattice of a solid crystal.
A "glass" is a disordered material that lacks the periodicity of
a crystal but behaves mechanically as a solid, and the most
common method of making a glass is by cooling a viscous liquid
fast enough to avoid crystallization, i.e., supercooling the
liquid into the glassy state. This method has been used in one
form or another since at least 4000 B.C., when the Egyptians
made artificial glass in the form of a colored opaque glaze on
beads. But despite the ancient history of glass, the molecular
mechanisms involved in liquids acquiring amorphous rigidity upon
cooling are not fully understood.
P.G. Debenedetti and F.H. Stillinger (2 installations, US)
present a review of current research on supercooled liquids and
the glass transition, the authors making the following points:
1) The authors point out that the glassy state is ubiquitous in
nature and of great importance in technology. It is crucial in
the processing of foods, the commercial stabilization of labile
biochemicals, and the preservations of insect life under
extremes of cold or dehydration. Window glass, composed mostly
of sand, lime, and soda, is the best known example of an
engineered amorphous solid. Optical fibers are made of extremely
pure amorphous silica, occasionally carefully doped. Most
engineering plastics are amorphous solids, as are some metallic
glasses and alloys of interest because of their special magnetic
properties and corrosion resistance. The silicon used in many
photovoltaic cells is amorphous, and it is possible that most
water in the Universe may be glassy. Most of the above examples
of artificial glasses involve supercooling of a liquid to take
advantage of viscous retardation of *nucleation and
crystallization. Quantitative understanding of the extraordinary
viscous slow-down that accompanies supercooling and glass
formation is a major scientific challenge.
2) The authors point out that upon cooling below the freezing
point of a liquid, molecular motion slows down. If the liquid is
cooled sufficiently fast, crystallization can be avoided, and
eventually molecules will rearrange so slowly that they cannot
adequately sample energy configurations in the available time
allowed by the cooling rate. The structure of the liquid
therefore appears "frozen" on the laboratory timescale (e.g.,
minutes). This falling out of equilibrium occurs across a narrow
transformation range where the characteristic molecular
relaxation time becomes of the order of 100 seconds, and the
rate of change of volume with respect to temperature decreases
abruptly (but continuously) to a value comparable to that of a
crystalline solid. The resulting material is a glass.
3) The authors suggest a useful approach to relating the complex
phenomenology of supercooling to molecular scale events is to
focus attention on the "energy landscape" of the liquid, i.e.,
the multidimensional surface generated by the potential energy
of the system as a function of molecular coordinates. In
general, the term "energy landscape" refers to the potential
energy function (P) of an N-body system, with
P = P(r[sub1], r[sub2], ..., r[subN])
where the vectors r[subi] comprise position, orientation, and
vibration coordinates. Important aspects of the complex behavior
of viscous liquids close to the glass transition can be
explained qualitatively from the energy landscape perspective.
Making this descriptive picture quantitative and predictive is a
major challenge that will require investigating how basic
landscape features depend on molecular architecture and, for a
given substance or mixture, on density. The authors conclude:
"Establishing a coherent theoretical perspective on supercooled
liquids and glasses is important. We believe that the landscape
formation offers the natural technical tools for accomplishing
this task."
Nature 2001 410:259
Text Notes:
... ... *nucleation: At the microscopic level, the first stage
of the phase transition liquid-to-solid (crystallization) is the
"nucleation" stage. In this stage, the random motions of the
atoms or molecules apparently create a local situation atypical
of the average properties of the substance. Such locally
atypical regions, initially merely a few atoms in size, are
known as nuclei, embryos, or seeds. The process of nucleus
formation is believed to occur at all temperatures, although the
rate of formation is strongly temperature-dependent.
Alternatively, some small irregularity within the substance,
e.g., an impurity, may provide a locally anomalous region
capable of supporting a nucleus. In general, this first stage of
crystallization, nucleation, is extremely difficult to directly
visualize, since the scale is microscopic and the event may be
initiated anywhere in the volume of a freezing liquid.
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3. ON AMINES AND PERFECT REACTIONS
John F. Hartwig (Yale University, US) discusses amines and
perfect reactions, the author making the following points:
1) Amines pervade our body and the world around us. They are
found on the termini and side chains of amino acids, are
components of common pharmaceuticals, and are behind the stench
of rotting fish. They link the monomer units in most carpeting,
help foam our shampoo, and soften our clothes. Fifteen to 20
billion kilograms of ammonia are produced per year, and amines
are produced from ammonia in similarly staggering amounts.
2) Amines are derivatives of ammonia that contain three single
bonds between nitrogen and carbon or hydrogen. There are several
classic methods to prepare amines, but most of them are
inappropriate for large-scale production. For example, the
reactions of amines with alkyl halides are taught in
introductory organic chemistry courses. But the large amounts of
halide by-product, the need for blocking groups to address poor
selectivity, and the cost of the alkyl halide reagent make this
method unsuitable for commodity chemical production.
3) Instead, amines are generally produced from alcohols with a
solid-acid catalyst by elimination of water (3). The alcohols in
these reactions are often produced from alkene hydrocarbons,
which contain a reactive carbon-carbon double bond. A synthetic
route to amines directly from alkenes would eliminate the need
for the alcohol intermediate, thereby avoiding the cost and
energy consumption of the separation and purification of the
alcohol. This is what Seayad et al (2) report. The yields are
not yet 100%, but the reaction transcends the criteria typically
assigned to the "perfect reaction."
4) A perfect reaction is generally thought to occur with
inexpensive reagents, run with fast rates, form 100% yield of
product, require no added heat, and generate no waste (4-5).
Because impure reactants usually form even less pure products,
synthetic chemists are usually taught to start with clean
reagents. Seayad et al (2) report on a synthetic method that may
ultimately make the production of amines cleaner and more
efficient. The remarkable feature of the reaction reported by
Seayad et al is that predominantly a single terminal amine is
made from a mixture of alkenes.
References (abridged):
1. P. J. Chenier, Survey of Industrial Chemistry (VCH, Weinheim,
Germany, ed. 2, 1992).
2. A. Seayad et al., Science 297, 1676 (2002).
3. K. S. Hayes, Appl. Catal. A 221, 187 (2001).
4. B. M. Trost, Science 254, 1471 (1991).
5. P. A. Wender, Chem. Rev. 96, 1 (1996).
Science 2002 297:1653
Web Links: amines synthesis of amines
Related Background Brief:
INTERNAL OLEFINS TO LINEAR AMINES. Linear aliphatic amines are
used for the production of solvents, fine chemicals,
agrochemicals, pharmaceutical intermediates, and vulcanization
accelerators. They are also sold as catalysts for the production
of polymers, especially polyurethanes. Fatty amines are useful
as fabric softeners, corrosion inhibitors, and emulsifiers as
well as in ore flotation. Important industrial methods for their
synthesis include reductive amination of the corresponding
aldehydes and hydrogenation of the respective nitriles, which
are both available from terminal olefins. In addition, a number
of less atom-efficient methods -- such as classical nucleophilic
substitution reactions of alkyl halides, or less general methods
like hydroamination of olefins -- have been developed on
laboratory scales. Thus, there is considerable interest in
developing versatile and direct preparation routes to amines
using economically more attractive feedstock. The authors report
the selective synthesis of linear amines from internal olefins
or olefin mixtures was achieved through a catalytic one-pot
reaction consisting of an initial olefin isomerization followed
by hydroformylation and reductive amination. Key to the success
is the use of specially designed phosphine ligands in the
presence of rhodium catalysts. This reaction constitutes an
economically attractive and environmentally favorable synthesis
of linear aliphatic amines. A. Seayad et al: Science 2002
297:1676.
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4. Calcium Ion Storage and Dendrite Neuropeptide Release
M. Ludwig et al (University of Edinburgh, UK) discuss dendrite
neuropeptide release, the authors making the following points:
1) Information in neurons flows from synapses, through the
dendrites and cell body (soma), and, finally, along the axon as
spikes of electrical activity that will ultimately release
neurotransmitters from the nerve terminals. However, the
dendrites of many neurons also have a secretory role,
transmitting information back to afferent nerve terminals(1-4).
In some central nervous system neurons, spikes that originate at
the soma can travel along dendrites as well as axons, and may
thus elicit secretion from both compartments(1).
2) Neurons in the supraoptic nucleus (SON) of the hypothalamus
project axons to the posterior pituitary, where oxytocin and
vasopressin are secreted from axonal nerve terminals into the
systemic circulation. These peptides are also released in large
amounts from dendrites in the SON(5), but secretion at these two
sites is not consistently correlated. Suckling evokes oxytocin
release in the SON before significant peripheral secretion,
whereas after osmotic stimulation, SON oxytocin release lags
behind peripheral secretion. During lactation, in response to
suckling, oxytocin cells discharge with brief, intense bursts;
these bursts release boluses of oxytocin into the circulation
that result in milk let-down from the mammary glands. The
bursting activity can be blocked by central administration of
oxytocin antagonists, thus central as well as peripheral
oxytocin is essential for milk let-down. It has been proposed
that suckling evokes dendritic oxytocin release that acts in a
positive feedback manner to evoke bursting.
3) The authors report that in hypothalamic oxytocin neurons,
agents that mobilize intracellular Ca2+ induce oxytocin release
from dendrites without increasing the electrical activity of the
cell body, and without inducing secretion from the nerve
terminals. Conversely, electrical activity in the cell bodies
can cause the secretion of oxytocin from nerve terminals with
little or no release from the dendrites. Finally, mobilization
of intracellular Ca2+ can also prime the releasable pool of
oxytocin in the dendrites. This priming action makes dendritic
oxytocin available for release in response to subsequent spike
activity. Priming persists for a prolonged period, changing the
nature of interactions between oxytocin neurons and their
neighbors.
References (abridged):
1. Hausser, M., Stuart, G., Racca, C. & Sakmann, B. Axonal
initiation and active dendritic propagation of action potentials
in substantia nigra neurons. Neuron 15, 637-647 (1995)
2. Zilberter, Y., Kaiser, K. M. M. & Sakmann, B. Dendritic GABA
release depresses excitatory transmission between layer 2/3
pyramidal and bitufted neurons in rat neocortex. Neuron 24,
979-988 (1999)
3. Isaacson, J. S. & Strowbridge, B. W. Olfactory reciprocal
synapses--dendritic signaling in the CNS. Neuron 20, 749-761
(1998)
4. Isaacson, J. S. Mechanisms governing dendritic -aminobutyric
acid (GABA) release in the rat olfactory bulb. Proc. Natl Acad.
Sci. USA 98, 337-342 (2001)
5. Pow, D. V. & Morris, J. F. Dendrites of hypothalamic
magnocellular neurons release neurohypophysial peptides by
exocytosis. Neuroscience 32, 435-439 (1989)
Nature 2002 418:85
Web Links: dendrite neuropeptide release
Related Background Brief:
AXONAL INITIATION AND ACTIVE DENDRITIC PROPAGATION OF ACTION
POTENTIALS IN SUBSTANTIA NIGRA NEURONS. The site of action
potential initiation in substantia nigra neurons was
investigated by using simultaneous somatic and dendritic
whole-cell recording in brain slices. In many dopamine neurons,
action potentials were observed first at the dendritic recording
site. Anatomical reconstruction showed that in these neurons,
the axon emerged from the dendrite from which the recording had
been made. Action potentials showed little attention in the
dendritic tree, which in dopamine neurons was shown to be due to
recruitment of dendritic sodium channels and may be related to
the dendritic release of dopamine. The authors conclude that in
substantia nigra neurons, the site of action potential
initiation, and thus the final site of synaptic integration, is
in the axon. As the axon can originate from a dendrite, up to
240 microns away from the soma, synaptic input to the
axon-bearing dendrite may be privileged with respect to its
ability to influence action potential initiation. M. Hausser et
al: Neuron 1995 15:637.
Related Background Brief:
MECHANISMS GOVERNING DENDRITIC GAMMA-AMINOBUTYRIC ACID (GABA)
RELEASE IN THE RAT OLFACTORY BULB. In the olfactory bulb,
synaptic transmission between dendrites plays an important role
in the processing of olfactory information. Glutamate released
from the dendrites of principal mitral cells excites the
dendritic spines of granule cells, which in turn release
gamma-aminobutyric acid (GABA) back onto mitral cell dendrites.
Slow N-methyl-d-aspartate (NMDA) receptors on granule dendrites
are particularly effective in driving this reciprocal
dendrodendritic inhibition (DDI), raising the possibility that
calcium influx through NMDA receptors may trigger GABA
exocytosis directly. In this study, the author demonstrates that
NMDA receptor activation is not an absolute requirement and that
DDI can be evoked solely by
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
receptors when granule cell excitability is increased or under
conditions that slow AMPA receptor kinetics. In physiological
extracellular Mg(2+), DDI elicited by photolysis of caged
calcium in mitral dendrites is blocked by cadmium and toxins to
N- and P/Q-type voltage-gated calcium channels. DDI is largely
unaffected after granule dendrites have been loaded with the
slow calcium chelator EGTA, suggesting a tight coupling between
the site of calcium influx and the release machinery governing
GABA exocytosis. The author suggests these results indicate that
voltage-gated calcium channels play an essential role in
dendritic GABA release during reciprocal feedback inhibition in
the olfactory bulb. J.S. Isaacson: Proc. Nat. Acad. Sci 2001
98:337.
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5. On Grammar vs. Language in Neurolinguistics
Massimo Piatelli-Palmarini (University of Arizona, US) discusses
grammar vs. language, the author making the following points:
1) Two styles of explaining the science of mind and behavior
have been competing for as long as anyone cares to remember:
empiricist, centering on habit formation, statistical learning,
imitation and association; and rationalist, focusing on the
projection of internally represented rules. Despite relentless
effort, the former has delivered rather meager results, whereas
the latter, with its pivotal concept of an internally
represented grammar, has produced the solid "conceptual
cognitive revolution".
2) For a rationalist cognitive scientist, a grammar is a finite
mental object, systematically assigning abstract structures to
all the well-formed expressions of a language --that is, to each
member of a set that, for natural languages (such as Chinese or
Italian), is infinite and discrete. Infinite, because every
speaker of a language can produce and understand an unlimited
number of new grammatical sentences. Discrete, because
continuous modification of a sentence to change it into another
is impossible. No sentence could be halfway between "It's a good
car, but they don't sell it" and "It's a good car, but they
don't tell it."
3) A grammar capable of generating complex structures for all
well-formed sentences of a natural language must have recursive
rules, because phrasal constituents can contain other phrasal
constituents of the same or higher kinds ("The young doctor's
three beautiful sisters" is a noun phrase containing another
noun phrase; "The spy who came in from the cold" is a noun
phrase containing a sentence). Moreover, structural rules of
sentence formation can be applied recursively to embed relative
clauses embedding other relative clauses, without limit (as in
"This is the cat that killed the rat that ate the malt that lay
in the house that Jack built"). Because such grammars are
finite, whereas the languages they generate are infinite and
contingently shaped by use, it is advantageous, and
methodologically cogent, to consider the concept of grammar as
primary, and that of language as derived.
4) Since the mid-1950s, powerful formal criteria, derived from
analysis of the artificial languages of mathematics and computer
programming, have been applied to the study of natural languages
to determine principles by which a given class of grammars can
generate a given target language. A universal ('Chomsky')
hierarchy of grammars (automata) was established: the most
powerful class contains as a subclass the immediately less
powerful one, and so on. In tune with the dominant
empiricist–inductivist tradition of the 1950s, the first
grammars to be explored at the lowest level in the hierarchy
were probabilistic and finite-state. From a very large corpus of
ascertained utterances of the language, one can compute the
conditional probability that a word (or string of words) will
follow another.
References:
1. Wasow, T. in Foundations of Cognitive Science (ed. Posner,
M.) 161–205 (MIT Press, Cambridge, Massachusetts, 1991)
2. Chomsky, N. The Minimalist Program (MIT Press, Cambridge,
Massachusetts, 1995)
3. Pullum, G. K. & Scholtz, B. C. Nature 413, 367 (2001)
Nature 2002 416:129
Web Links: neurolinguistics Chomsky
Related Background Brief:
MORE THAN WORDS. In the popular view, a language is merely a
fixed stock of words. Purists worry about foreign loanwords;
conservatives decry slang; and groundless claims that there are
hundreds of Eskimo words for snow are constantly made in popular
writing, as if nothing matters about languages but their
lexicons. But the popular view cannot be right, because (as
linguist Paul Postal has observed) membership in the word stock
of a natural language is open. Consider this example: "GM's new
Zabundra makes even the massive Ford Expedition look
economical." If English had an antecedently given set of words,
then this expression would not be an English sentence at all,
because 'Zabundra' is not a word (we just invented it). Yet the
sentence is not just grammatical English, it is readily
interpretable (it clearly implies that the Zabundra is a large,
fuel-hungry sports utility vehicle produced by General Motors).
Similar points could be made regarding word borrowing, personal
names, scientific nomenclature, onomatopoeisis, acronyms, loaned
words, and so on; English is not a fixed set of words. A more
fundamental reason that a language cannot just be a word stock
is that expressions have syntactic structure. For example, in
most languages, the order of words can be significant: "Mohammed
will come to the mountain" contains the same words as "The
mountain will come to Mohammed", but the expressions are very
different. Geoffrey K. Pullum: Nature 2001 413:367.
Related Background:
ON THE ACQUISITION OF LANGUAGE BY CHILDREN
J.R. Saffran et al (University of Wisconsin Madison, US) discuss
the acquisition of language by children, the authors making the
following points:
1) Before infants can begin to map words onto objects in the
world, they must determine which sound sequences are words. To
do so, infants must uncover at least some of the units that
belong to their native language from a largely continuous stream
of sounds in which words are seldom surrounded by pauses.
Despite the difficulty of this reverse-engineering problem,
infants successfully segment words from fluent speech from
approximately 7 months of age.
2) How do infants learn the units of their native language so
rapidly? One fruitful approach to answering this question has
been to present infants with miniature artificial languages that
embody specific aspects of natural language structure. Once an
infant has been familiarized with a sample of this language, a
new sample, or a sample from a different language, is presented
to the infant. Subtle measures of surprise (e.g., duration of
looking toward the new sounds) are then used to assess whether
the infant perceives the new sample as more of the same or
something different. In this fashion, we can ask what the infant
extracted from the artificial language, which can lead to
insights regarding the learning mechanisms underlying the
earliest stages of language acquisition.
3) Syllables that are part of the same word tend to follow one
another predictably, whereas syllables that span word boundaries
do not. In a series of experiments, it has been found that
infants can detect and use the statistical properties of
syllable co-occurrence to segment novel words. More
specifically, infants do not detect merely how frequently
syllable pairs occur, but rather the probabilities with which
one syllable predicts another. Thus, infants may find word
boundaries by detecting syllable pairs with low transitional
probabilities. What makes this finding astonishing is that
infants as young as 8 months begin to perform these computations
with as little as 2 minutes of exposure. By soaking up the
statistical regularities of seemingly meaningless acoustic
events, infants are able to rapidly structure linguistic input
into relevant and ultimately meaningful units.
Proc. Nat. Acad. Sci. 2001 98:12874
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6. ON THE EVOLUTION OF DINOFLAGELLATES
C.W. Morden and A.R. Sherwood (University of Hawaii, US) discuss
dinoflagellates, the authors making the following points:
1) It is well established that chloroplasts in green and red
algae are derived from a primary endosymbiotic event between a
cyanobacterium and a eukaryotic organism 1 billion years ago
(1,2). Although these two groups account for many of the world's
photosynthetic species, most other major taxonomic groups of
photosynthetic organisms (stramenopiles -- including diatoms,
phaeophytes, chrysophytesand haptophytes) have plastids derived
from a photosynthetic eukaryote implying a secondary
endosymbiosis (1,2). Still other groups, such as the
dinoflagellates, have more complicated associations believed to
be derived from tertiary endosymbioses involving the engulfment
of a secondary endosymbiont. Each endosymbiotic event has
characteristic structural changes associated with it, the most
notable of which is the addition of two membranes surrounding
the plastid (the inner representing the cell membrane of the
engulfed organism and the outer representing the phagocytosis
vacuole membrane) (2). Dinoflagellates, although believed to be
tertiary endosymbionts, have only 3 membranes surrounding their
plastids (1,2), suggesting that the acquisition of too many
membranes may be functionally unstable and can cause some to be
lost.
2) Dinoflagellates are fascinating organisms that have intrigued
researchers for many years. They are most well known for toxic
blooms associated with red tides and symbiotic relationships
with corals (zooxanthellae) (2). They contain an astounding
array of unique features that has been the impetus for continued
evolutionary studies. One is their close phylogenetic link with
apicomplexans, organisms that are best known for causing some of
our most deadly infectious diseases (3,4). Another is the
diverse array of light harvesting pigments within the group.
Peridinin is a xanthophyll found exclusively in dinoflagellates
and, together with chl-a (ubiquitous among photosynthetic
organisms), makes up the light harvesting complex found in most
species. Dinoflagellates with other combinations of plastid
pigments are also known, including chl-b (also in green algae),
fucoxanthin, chl-c1 and -c2 (also in stramenopiles and
haptophytes) and chl-c1 and phycobilins (also in cryptophytes),
and are believed to be the products of further endosymbioses
with species from those groups (5). Yoon et al (Proc. Nat. Acad.
Sci. 2002 99:11724) provide new evidence that implicates
dinoflagellate plastids containing fucoxanthin and chl-c1 and
-c2 (derived from a haptophyte ancestor) as being ancestral to
those with peridinin. This new paradigm in the relationship of
these species forces us to rethink many aspects of
dinoflagellate evolution.
3) In many respects, the findings by Yoon et al (2002) allow a
more parsimonious view of dinoflagellate evolution. Previously
long-held theories suggested that primitive dinoflagellates were
heterotrophic and the addition of a peridinin-containing plastid
occurred relatively recently, which was borne out by the fact
that approximately 50% of dinoflagellate species are
heterotrophic (1) and that many photosynthetic dinoflagellates
have retained heterotrophic behavior. However, recent studies
have demonstrated that photosynthetic dinoflagellates are
clearly ancestral, and that heterotrophy has been independently
derived numerous times within the group. Fucoxanthin and chl-c1
and -c2 are the predominant form of light harvesting pigments
among stramenopiles and haptophytes. With the finding that
haptophytes are the sister group to dinoflagellates in
phylogenetic analyses and that dinoflagellates with fucoxanthin
and chl-c1 and -c2 are apparently ancestral to the
peridinin-containing species, there is no need to hypothesize an
independent origin of these pigments nor a later endosymbiosis
of a haptophyte in dinoflagellates.
References (abridged):
1. Van Den Hoek, C. , Mann, D. G. & Jahns, H. M. (1995) Algae:
An Introduction of Phycology (Cambridge Univ. Press, Cambridge,
U.K.).
2. Graham, L. E. & Wilcox, L. W. (2000) Algae (Prentice-Hall,
Englewood Cliffs, NJ).
3. McFadden, G. I. , Reith, M. E. , Munholland, J. &
Lang-Unnasch, N. (1996) Nature (London) 381, 482.
4. Fast, N. M. , Kinninger, J. C. , Roos, D. S. & Keeling, P.
J. (2001) Mol. Biol. Evol. 18, 418-426.
5. Wilcox, L. W. & Wedemeyer, G. J. (1984) J. Phycol. 20,
236-242.
Proc. Nat. Acad. Sci. 2002 99: 11558
Web Links: dinoflagellates plastids
Related Background Brief:
DINOFLAGELLATE NUCLEAR SSU RRNA PHYLOGENY SUGGESTS MULTIPLE
PLASTID LOSSES AND REPLACEMENTS. Dinoflagellates are a
trophically diverse group of protists with photosynthetic and
non-photosynthetic members that appears to incorporate and lose
endosymbionts relatively easily. To trace the gain and loss of
plastids in dinoflagellates, the authors report they have
sequenced the nuclear small subunit rRNA gene of 28
photosynthetic and four non-photosynthetic species, and produced
phylogenetic trees with a total of 81 dinoflagellate sequences.
Patterns of plastid gain, loss, and replacement were plotted
onto this phylogeny. With the exception of the apparently
early-diverging Syndiniales and Noctilucales, all
non-photosynthetic dinoflagellates are very likely to have had
photosynthetic ancestors with peridinin-containing plastids. The
same is true for all dinoflagellates with plastids other than
the peridinin-containing plastid: their ancestors have replaced
one type of plastid for another, in some cases most likely
through a non-photosynthetic intermediate. Eight independent
instances of plastid loss and three of replacement can be
inferred from existing data, but as more non-photosynthetic
lineages are characterized these numbers will surely grow. J.F.
Saldarriaga et al: J Mol Evol 2001 53:204.
Related Background Brief:
ON DINOFLAGELLATE EVOLUTION. The author presents a broad
overview of the diversity of living dinoflagellates in a
hypothetical evolutionary context. Ultrastructural and some
physiological information is included. Five principal
organizational types: prorocentroid, dinophysoid, gonyaulacoid,
peridinioid and gymnodinoid, are taken to represent lineages,
and the developments within each summarized. Thecal evolution is
discussed party with the aid of a model developed to determine
probable plate homologies in the gonyaulacoids and peridinioids.
Both primitive and highly specialized features are drawn
attention to, particularly with regard to the nucleus and
ocelli. The parallelism between the latter and metazoan eyes is
extraordinary, considering that the dinoflagellate organelles
are made of subcellular components. The roles of various types
of cysts within the lifecycle of dinoflagellates are discussed.
The compatibility of the hypothetical events proposed by the
author with the fossil record is briefly considered, and some
indications of the phyletic position of dinoflagellates are
reviewed. The conclusions summarize the principal developments
that appear to have arisen within the group. The relative
primitiveness of the desmokonts is affirmed. A new combination,
Plectodinium miniatum (Kofoid and Swezy) comb. nov. is proposed,
as well as the recognition of a new order, the Gonyaulacales
ord. nov. F.J. Taylor: Biosystems 1980;13:65.
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7. ON QUANTUM CLONING
S. Fasel et al (University of Geneva, CH) discuss quantum
cloning, the authors making the following points:
1) Classical information can be copied at will. Not so for the
information content of a quantum state: one cannot devise a
process that takes N copies of an arbitrary quantum state as an
input and produces M > N copies of the same quantum state
deterministically. This is the content of the no-cloning theorem
of quantum mechanics [1], which is at the heart of quantum
information theory (in particular, it guarantees the security of
quantum cryptography). To go beyond this no-go theorem, one can
weaken the requirements and ask that the M copies are not
identical to the input state, but as close as possible to it
[2,3]. The physical device that performs this operation is
called a quantum cloning machine. A device that copies equally
well all the possible input states is called a universal quantum
cloning machine.
2) In recent years, communication through optical fibers has
become widespread, and everybody knows that a light signal can
be amplified. But light can (should) be described quantum
mechanically, therefore the standard amplification devices used
in telecom cannot beat the no-cloning theorem.
3) It is not difficult to understand why some noise will always
be produced by the amplifier: the amplification of light is
achieved through stimulated emission, and it is well known that
in this case spontaneous emission will always be present as
well. But it has been noticed recently [4] that the
amplification based on stimulated emission leads to optimal
cloning. To see this, we describe the amplifier as an ensemble
of atoms initially in the excited state that can emit photons
polarized along any direction with equal cross section. The
atoms are irradiated with a photon of suitable energy, polarized
along a direction V. At the exit of the amplifier, we select the
cases in which one and only one additional photon has been
emitted and analyze the output in the (H, V) basis. If p is the
probability that the additional photon is polarized along H
(spontaneous emission), then the probability that the additional
photon is polarized along V is 2p because of stimulated
emission. Now, if we pick one photon of the output at random,
the probability of this photon to be in the same state as the
input photon (namely, V) is called "fidelity of the cloner". In
the case that we are considering, the fidelity is 5/6, which is
indeed the optimal fidelity for a 1 --> 2 universal cloning
machine [2]. This easy reasoning has been extended to any
amplification process N --> M in Ref. [4].
References (abridged):
1. W.K. Wootters and W.H. Zurek, Nature (London) 299, 802
(1982); P. W. Milonni and M. L. Hardies, Phys. Lett. A 92, 321
(1982).
2. V. Buzek and M. Hillery, Phys. Rev. A 54, 1844 (1996).
3. N. Gisin and S. Massar, Phys. Rev. Lett. 79, 2153 (1997); D.
Bruss et al., Phys. Rev. Lett. 81, 2598 (1998).
4. C. Simon et al., Phys. Rev. Lett. 84, 2993 (2000); J. Kempe
et al., Phys. Rev. A 62, 032302 (2000).
Phys. Rev. Lett. 2002 89:107901
Web Links: quantum cloning
Related Background:
ON QUANTUM CRYPTOGRAPHY
N. Gisin et al (University of Geneva, CH) discuss quantum
cryptography, the authors making the following points:
1) Electrodynamics was discovered and formalized in the 19th
century. The 20th century was then profoundly affected by its
applications. A similar adventure may be underway for quantum
mechanics, discovered and formalized during the last century,
Indeed, although the laser and semiconductor are already common,
applications of the most radical predictions of quantum
mechanics have only recently been conceived, and their full
potential remains to be explored by the physicists and engineers
of the 21st century.
2) The most peculiar characteristics of quantum mechanics are
the existence of indivisible quanta and of entangled systems.
Both of these lie at the root of quantum cryptography, which
could very well be the first commercial application of quantum
physics at the single-quantum level. In addition to quantum
mechanics, the 20th century has been marked by two other major
scientific revolution: information theory and relativity. The
status of the latter is well recognized. It is less well known
that the concept of information, currently measured in bits, and
the formalization of relevant probabilities are quite recent,
although they have a tremendous impact on our daily life. It is
fascinating to realize that quantum cryptography lies at the
intersection of quantum mechanics and information theory, and
that, moreover, the tension between quantum mechanics and
relativity --- the famous Einstein-Rosen-Podolsky (EPR) paradox
--- is closely connected to the security of quantum cryptography.
3) The idea of quantum cryptography was first proposed in the
1970s by Stephen Wiesner and in the 1980s by Charles H. Bennett
and Gilles Brassard. However, this idea is so simple that any
first-year student since the infancy of quantum mechanics could
actually have discovered it. Nevertheless, it is only now that
the field is mature enough and information security important
enough that physicists are ready to consider quantum mechanics
not only as a strange theory that produces paradoxes but also as
a tool for new engineering. Apparently, information theory,
classical cryptography, quantum physics, and quantum optics
first had to develop into mature sciences. It is certainly not a
coincidence that quantum cryptography and, more generally,
quantum information were developed by a community including many
computer scientists and more mathematically oriented young
physicists: broader interests than traditional physics were
needed.
Rev. Mod. Phys. 2002 74:145
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8. ON SUPRAMOLECULAR ASSEMBLY ON SURFACES
G.M. Credo et al (North Carolina State University, US) discuss
supramolecular assembly, the authors making the following points:
1) Metal-molecule-metal junctions have been used to elucidate
single-molecule properties in organic monolayers that are
applicable in molecular electronics. For example, pore-based
sandwich structures(1,2), mechanical break junctions(3), and Hg
drop electrode top contacts(4,5) have been used to characterize
the current-voltage properties of organic monolayers. Studies
have also employed scanning tunneling microscopy (STM) and
conducting atomic force microscopy (cAFM) to probe the
current-voltage properties of molecular junctions with more
limited contact areas. In particular, reports of STM studies on
redox-active molecular monolayers have described the use of
electroactive moieties in molecular junctions to facilitate
nonlinear current-voltage behavior. In a recent example, the
nonlinear current-voltage phenomenon of negative differential
resistance (NDR) was observed in an electroactive,
ferrocene-terminated self-assembled monolayer (SAM). The
identification of nonlinear current-voltage properties such as
NDR for individual molecules expands the potential applicability
of molecule-scale components from use as conductive wires to
multistate molecular switches.
2) Chemical self-assembly is an attractive method for reversibly
constructing well-defined supramolecular systems with properties
defined by their molecular components. In particular, hydrogen
bonding is a familiar construction motif in natural systems and
has been used to assemble functional nanostructures, such as
metal nanoparticle-based networks. Applying these concepts,
noncovalent self-assembly provides a potential method to install
and subsequently remove electroactive functionality in molecular
electronics systems. To explore this possibility, the authors
report they patterned a footprint region for molecular assembly
on a surface featuring a recognition-element-terminated thiol.
The authors then used moieties featuring complementary
recognition to tune the current-voltage properties of the
patterned region. In the current work, the authors used an STM
tip to pattern and probe molecular assemblies and independently
verified the hydrogen bond-mediated assembly process using bulk
electrochemical and spectroscopic techniques.
3) In summary: The authors report that molecules capable of
complementary hydrogen bonding were used to control the
noncovalent self-assembly and electronic properties of a
chemically well-defined surface mesostructure. In this work, the
authors patterned a footprint region for molecular assembly on a
surface and used moieties featuring complementary recognition to
tune the current-voltage properties of the patterned region.
With the appropriate functionalities on the complementary
moieties, the authors were able to increase and decrease the
observed conductance in surface-bound mesoscale structures
imaged by scanning tunneling microscopy (STM).
References (abridged):
1. Chen, J.; Wang, W.; Reed, M. A.; Rawlett, A. M.; Price, D.
W.; Tour, J. M. Appl. Phys. Lett. 2000, 77, 1224-1226.
2. Chen, J.; Reed, M. A.; Rawlett, A. M.; Tour, J. M. Science
1999, 286, 1550-1552.
3. Reed, M. A.; Zhou, C.; Muller, C. J.; Burgin, T. P.; Tour, J.
M. Science 1997, 278, 252-254.
4. (a) Holmlin, E. E.; Haag, R.; Chabinyc, M. L.; Ismagilov, R.
F.; Cohen, A. E.; Rampi, M. A.; Terfort, A.; Whitesides, G. M.
J. Am. Chem. Soc. 2001, 123, 5075-5085. (b) Holmlin, R. E.;
Ismagilov, R. F.; Haag, R.; Mujica, V.; Ratner, M. A.; Rampi, M.
A.; Whitesides, G. M. Angew. Chem., Intl. Ed. 2001, 2316-2320.
5. Selzer, Y.; Salomon, A.; Ghabboun, J.; Cahen, D. Angew.
Chem., Int. Ed. 2002, 41, 827-830.
J. Am. Chem. Soc. 2002 124:9036
Web Links: supramolecules negative differential resistance
Related Background Brief:
ELECTRON TRANSPORT THROUGH THIN ORGANIC FILMS IN
METAL-INSULATOR-METAL JUNCTIONS BASED ON SELF-ASSEMBLED
MONOLAYERS. The authors describe an experimentally simple system
for measuring rates of electron transport across organic thin
films having a range of molecular structures. The system uses a
metal-insulator-metal junction based on self-assembled
monolayers (SAMs); it is particularly easy to assemble. The
junction consists of a SAM supported on a silver film (Ag-SAM-1)
in contact with a second SAM supported on the surface of a drop
of mercury (Hg-SAM-2) -- that is, a Ag-SAM(1)SAM(2)-Hg junction.
SAM-1 and SAM-2 can be derived from the same or different
thiols. The current that flowed across junctions with SAMs of
aliphatic thiols or aromatic thiols on Ag and a SAM of
hexadecane thiol on Hg depended both on the molecular structure
and on the thickness of the SAM on Ag: the current density at a
bias of 0.5 V ranged from 2 x 10^(-10) A/cm^(2) for
HS(CH(2))(15)CH(3) on Ag to 1 x 10^(-6) A/cm^(2) for
HS(CH(2))(7)CH(3) on Ag, and from 3 x 10^(-6) A/cm^(2) for
HS(Ph)(3)H (Ph = 1,4-C(6)H(4)) on Ag to 7 x 10^(-4) A/cm^(2) for
HSPhH on Ag. The current density increased roughly linearly with
the area of contact between SAM(1) and SAM(2), and it was not
different between Ag films that were 100 or 200 nm thick. The
current-voltage curves were symmetrical around V = 0. The
current density decreased with increasing distance between the
electrodes according to the relation I = I(0)e(-beta d(Ag,Hg)),
where d(Ag,Hg) is the distance between the electrodes, and beta
is the structure-dependent attenuation factor for the molecules
making up SAM(1). At an applied potential of 0.5 V, beta was
0.87 +/- 0.1 A^(-1) for alkanethiols, 0.61 +/- 0.1 A^(-1) for
oligophenylene thiols, and 0.67 +/- 0.1 A^(-1) for benzylic
derivatives of oligophenylene thiols. The values of beta did not
depend significantly on applied potential over the range of 0.1
to 1 V. These junctions provide a test bed with which to screen
the intrinsic electrical properties of SAMs made up of molecules
with different structures; information obtained using these
junctions will be useful in correlating molecular structure and
rates of electron transport. R.E. Holmlin et al: J Am Chem Soc
2002 124:8762.
Related Background:
SUPRAMOLECULAR CHEMISTRY
S.T. Nguyen et al (Northwestern University, US) discuss
supramolecular chemistry. For over 100 years, chemistry has
focused primarily on understanding the behavior of molecules and
their construction from constituent atoms, and our current level
of understanding of molecules and chemical construction
techniques has given us the confidence to tackle the
construction of virtually any molecule, be it biological or
designed, organic or inorganic, monomeric or macromolecular in
origin. During the last few decades, chemists have extended
their investigations beyond atomic and molecular chemistry into
the realm of "supramolecular chemistry". Terms such as
"molecular self-assembly", "hierarchical order", and
"nanoscience" are often associated with this area of research.
In general, supramolecular chemistry is the study of
interactions between, rather than within, molecules -- in other
words, chemistry using molecules rather than atoms as building
blocks. Whereas traditional chemistry deals with the
construction of individual molecules (1 to 100 angstroms length
scale) from atoms, supramolecular chemistry deals with the
construction of organized molecular "arrays" with much larger
length scales (1 to 100 nanometers). In classical molecular
chemistry, strong association forces such as covalent and ionic
bonds are used to assemble atoms into discrete molecules and
hold them together. In contrast, the forces used to organize and
hold together supramolecular assemblies are weaker non-covalent
interactions, such as hydrogen bonding, polar attractions, van
der Waals forces, and hydrophilic-hydrophobic interactions.
Proc. Nat. Acad. Sci. Sci. 2001 98:11849
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9. SCANNING TUNNELING MICROSCOPY AT HIGH PRESSURES
B.L. Hendriksen and J.W. Frenken (Leiden University, NL) discuss
high-pressure scanning tunneling microscopy, the authors making
the following points:
1) Much of the present-day fundamental understanding of
heterogeneous catalysis has been obtained by studying simplified
model catalysts at well-defined, but strongly nonrealistic
conditions, such as ultrahigh vacuum (UHV) or very low gas
pressures [1]. Yet, there lies an enormous pressure gap of at
least 9 orders of magnitude between the low pressures used in
model experiments (lO^(-9) bar) and the pressures applied in
practical catalysis (>1 bar). It has been suggested that the
presence of reactants at a high pressure can have a dramatic
effect on the surface structure and composition, and thereby the
performance of a catalyst [2-5].
The scanning tunneling microscope (STM) makes it possible to
determine the surface stmcture on an atomic scale, not only in
UHV, but also at elevated pressures. Insertion of a STM inside a
flow reactor should make it possible to determine simultaneously
(changes of) the surface structure and the catalytic activity of
a single crystal surface. However, the detection of the small
quantities of reaction product from the typical small surface
area of the model catalyst requires a reactor volume smaller
than the size of a typical STM. For this reason, the authors
have developed a dedicated, high-pressure, high-temperature
scanning tunneling microscope.
3) The STM is combined with a flow reactor in such a way that
only the STM tip is inside the gold-plated high-pressure cell.
The rest of the STM is separated from the reactor cell by a tiny
flexible 0-ring, which serves as a leak tight seal, but allows
the scanning motion. In this way, the authors report they have
reduced the reactor volume to only 500 microliters, and avoided
exposure of the entire STM to the reactants. The STM can operate
at pressures from vacuum to 5 bars at temperatures of 300-425
kelvins and a flow of 0-10 ml/min, which corresponds to 1/3 of
the reactor volume per second. As the authors operate this
so-called "Reactor-STM" in a flow mode, they can image the
surface and simultaneously determine the reaction rate by means
of on-line mass analysis with a quadrupole mass spectrometer of
the gas leaving the reactor. With this instrument, the authors
report they can directly observe the effects of controlled
changes in the gas mixture. The Reactor-STM is integrated in a
standard UHV system, which allows state-of-the-art surface
preparation and prereaction and postreaction analysis by
traditional surface science diagnostics [e.g., low-energy
electron diffraction (LEED) and Auger electron spectroscopy
(AES)].
4) In summary: The authors report they have used a novel,
high-pressure high-temperature scanning tunneling microscope,
which is set up as a flow reactor, to determine simultaneously
the surface structure and the reactivity of a Pt(ll0) model
catalyst at semirealistic reaction conditions for CO oxidation.
By controlled switching from a CO-rich to an O2-rich flow and
vice versa, they authors can reversibly oxidize and reduce the
platinum surface. The formation of the surface oxide has a
dramatic effect on the CO2 production rate. The results show
that there is a strict one-to-one correspondence between the
surface structure and the catalytic activity, and suggest a
reaction mechanism which is not observed at low pressures.
References (abridged):
1. G.A. Somorjai, Introduction to Surface Chemistry and
Catalysis (Wiley, New York, 1994).
2. M. Flytzani-Stephanopoulos, S. Wong, and L. D. Schmidt, J.
Catal. 49, 51 (1977).
3. A.K. Galwey, P. Gray, J. F. Griffiths, and S.M. Hasko, Nature
(London) 313, 668 (1985).
4. J. Wilson and C. de Groot, J. Phys. Chem. 99, 7860 (1995).
5. K. F. Peters, P. Seadman, H. Isem, J. Alvarez, and S. Ferrer,
Surf. Sci. 467, 10 (2000).
Phys. Rev. Lett. 2002 89:046101
Web Links: scanning tunneling microscope reactions at high
pressure
Related Background:
SCANNING TUNNELING AND ATOMIC FORCE MICROSCOPY
J.B. Pethica and R. Edgell (University of Oxford, UK) discuss
scanning tunneling and atomic force microscopy, the authors
making the following points:
1) The invention of the scanning tunneling microscope (STM)
sparked a revolution in atom imaging in the 1980s, and the
technique has since become a mainstream tool. In the STM, a
sharp metallic tip is scanned across a surface, causing a
current of electrons to tunnel between the tip and the surface.
By keeping this current -- and hence the gap between the STM tip
and the surface -- constant, the tip will naturally follow the
contours of the atomic landscape and generate an image. On
conducting surfaces, such as metals and semiconductors, the STM
can easily resolve single atoms, but insulators have presented a
much bigger challenge for the technique.
2) Atomic force microscopy (AFM) is a closely related technique
that does not rely on electron tunneling. AFM works by measuring
chemical, electrostatic, or magnetic forces between the
microscope tip and the sample. The tip is usually mounted at the
end of a flexible cantilever whose oscillation frequency changes
whenever the surface exerts a force on the tip. This versatile
technique can be used to study process ranging from biomolecule
mechanics to the growth of thin films. Insulators have also
presented a difficulty for AFM measurements.
3) Now a new report by Barth and Reichling (2001) describes
atomic resolution AFM images of alumina (aluminum oxide), a true
insulator. The surfaces of insulators are in many ways as
important as those of conductors, yet they remain largely
unexplored, and this new work opens another route to the study
of such surfaces. Both STM and AFM are key tools for
nanotechnology, and scanning microscopes will be vital methods
in the future of atom engineering.
Nature 2001 414:27,54
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10. EMBRYONIC STEM CELLS AND PARKINSON'S DISEASE
L.M. Bjorklund et al (Harvard University, US) discuss embryonic
stem cells, the authors making the following points:
1) Parkinson's disease (PD) is a degenerative disorder
characterized by a loss of midbrain dopamine (DA) neurons with a
subsequent reduction in striatal DA (1). Pharmacological
treatment with L-DOPA works initially, but reduced efficacy and
development of motor complications requires treatment
alternatives such as deep brain stimulation and fetal DA neuron
transplantation (2). There is evidence both from animal models
and clinical investigations showing that fetal DA neurons can
produce symptomatic relief (3-5). Technical and ethical
difficulties in obtaining sufficient and appropriate donor fetal
brain tissue have limited the application of this new therapy.
2) Previous work showed that DA neurons can be produced in vitro
from ventral mesencephalic (VM) precursor cells. A problem using
expanded fetal VM precursors is the low in vivo survival rate of
3-5% of the grafted DA neurons, which eliminates the actual gain
by in vitro cell number expansion compared with fresh
(unexpanded) fetal day-12 VM.
3) Embryonic stem (ES) cells have many characteristics required
for an optimal cell source for cell-replacement therapy. ES
cells are self-renewing and multipotent cells derived from the
inner cell mass of the preimplantation blastocyst. The authors
have shown previously that mouse ES cells transplanted to normal
mice or 6-hydroxydopamine (OHDA)-lesioned rats can differentiate
spontaneously into tyrosine hydroxylase (TH)-positive and
serotonin (5HT)-positive neurons. This differentiation is likely
not caused by a specific inductive signal from the host brain,
because similar neuronal differentiation occurs after placement
in the kidney capsule. In the previous study, grafts frequently
showed heterogeneous morphology and often became very large,
disrupting the cytoarchitecture at the implantation site, which
prevented the possibility for functional integration. Because
neurons develop from ES cells even when implanted outside the
central nervous system and ectoderm develops into neural tissue
when cell-to-cell communication is disrupted by dissociation of
the cells, the authors hypothesized that dilution of ES cells
into single-cell suspensions of low ES cell concentrations would
result in neuronal development. A low cell concentration
decreases ES cell-to-cell contact and increases the influence
from the adult host striatum, which in contrast to adult
neurogenic regions may restrict cell migration and
proliferation, thus allowing default differentiation into
neurons in this paradigm.
4) In summary: Although implantation of fetal dopamine (DA)
neurons can reduce parkinsonism in patients, current methods are
rudimentary, and a reliable donor cell source is lacking. The
authors report a demonstration that transplanting low doses of
undifferentiated mouse embryonic stem (ES) cells into the rat
striatum results in a proliferation of ES cells into fully
differentiated DA neurons. ES cell-derived DA neurons caused
gradual and sustained behavioral restoration of DA-mediated
motor asymmetry. Behavioral recovery paralleled in vivo positron
emission tomography and functional magnetic resonance imaging
data demonstrating DA-mediated hemodynamic changes in the
striatum and associated brain circuitry. The authors suggest
these results demonstrate that transplanted ES cells can develop
spontaneously into DA neurons. Such DA neurons can restore
cerebral function and behavior in an animal model of Parkinson's
disease.
References (abridged):
1. Olanow, C. W. & Tatton, W. G. (2000) Annu. Rev. Neurosci. 22,
123-144
2. Olanow, C. W. & Obeso, J. A. (2000) Ann. Neurol. 47, 167-178
3. Freed, C. R. , Greene, P. E. , Breeze, R. E. , Tsai, W. Y. ,
DuMouchel, W. , Kao, R. , Dillon, S. , Winfield, H. , Culver, S.
, Trojanowski, J. Q. , Eidelberg, D. & Fahn, S. (2001) N. Engl.
J. Med. 344, 710-719
4. Hauser, R. A. , Freeman, T. B. , Snow, B. J. , Nauert, M. ,
Gauger, L. , Kordower, J. H. & Olanow, C. W. (1999) Arch.
Neurol. (Chicago) 56, 179-187
5. Piccini, P. , Brooks, D. J. , Bjorklund, A. , Gunn, R. N. ,
Grasby, P. M. , Rimoldi, O. , Brundin, P. , Hagell, P. ,
Rehncrona, S. , Widner, H. & Lindvall, O. (1999) Nat. Neurosci.
2, 1137-1140
Proc. Nat. Acad. Sci. 2002 99:2344
Web Links: Parkinson's disease embryonic stem cells
Related Background Brief:
ETIOLOGY AND PATHOGENESIS OF PARKINSON'S DISEASE. Parkinson's
disease (PD) is an age-related neurodegenerative disorder that
affects approximately 1 million persons in the United States. It
is characterized by resting tremor, rigidity, bradykinesia or
slowness, gait disturbance, and postural instability.
Pathological features include degeneration of dopaminergic
neurons in the substantia nigra pars compacta coupled with
intracytoplasmic inclusions known as Lewy bodies.
Neurodegeneration and Lewy bodies can also be found in the locus
ceruleus, nucleus basalis, hypothalamus, cerebral cortex,
cranial nerve motor nuclei, and central and peripheral
components of the autonomic nervous system. Current treatment
consists of a dopamine replacement strategy using primarily the
dopamine precursor levodopa. While levodopa provides benefit to
virtually all PD patients, after 5–10 years of treatment the
majority of patients develop adverse events in the form of
dyskinesia (involuntary movements) and fluctuations in motor
response. Further, disease progression is associated with the
development of dementia, autonomic dysfunction, and postural
instability, which do not respond to levodopa therapy.
Accordingly, research efforts have been directed toward
understanding the etiology and pathogenesis of PD in the hope of
developing a more effective therapy that will slow or halt the
natural progression of PD. C. W. Olanow and W. G. Tatton: Annu.
Rev. Neurosci. 1999 22:123.
Related Background Brief:
TRANSPLANTATION OF EMBRYONIC DOPAMINE NEURONS FOR SEVERE
PARKINSON'S DISEASE. Transplantation of human embryonic dopamine
neurons into the brains of patients with Parkinson's disease has
proved beneficial in open clinical trials. However, whether this
intervention would be more effective than sham surgery in a
controlled trial is not known. The authors randomly assigned 40
patients who were 34 to 75 years of age and had severe
Parkinson's disease (mean duration, 14 years) to receive a
transplant of nerve cells or undergo sham surgery; all were to
be followed in a double-blind manner for one year. In the
transplant recipients, cultured mesencephalic tissue from four
embryos was implanted into the putamen bilaterally. In the
patients who underwent sham surgery, holes were drilled in the
skull but the dura was not penetrated. The primary outcome was a
subjective global rating of the change in the severity of
disease, scored on a scale of –3.0 to 3.0 at one year, with
negative scores indicating a worsening of symptoms and positive
scores an improvement. The mean (±SD) scores on the global
rating scale for improvement or deterioration at one year were
0.0±2.1 in the transplantation group and –0.4± 1.7 in the
sham-surgery group. Among younger patients (60 years old or
younger), standardized tests of Parkinson's disease revealed
significant improvement in the transplantation group as compared
with the sham-surgery group when patients were tested in the
morning before receiving medication (P=0.01 for scores on the
Unified Parkinson's Disease Rating Scale; P=0.006 for the Schwab
and England score). There was no significant improvement in
older patients in the transplantation group. Fiber outgrowth
from the transplanted neurons was detected in 17 of the 20
patients in the transplantation group, as indicated by an
increase in 18F-fluorodopa uptake on positron-emission
tomography or postmortem examination. After improvement in the
first year, dystonia and dyskinesias recurred in 15 percent of
the patients who received transplants, even after reduction or
discontinuation of the dose of levodopa. The authors conclude
that human embryonic dopamine-neuron transplants survive in
patients with severe Parkinson's disease and result in some
clinical benefit in younger but not in older patients. C.R.
Freed et al: New Engl. J. Med. 2001 344:710.
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11. INFECTIONS AND SUSCEPTIBILITY TO AUTOIMMUNE AND ALLERGIC
DISEASES
Jean-Francois Bach (INSERM, Necker Hospital, FR) discusses
autoimmune and allergic diseases, the author making the
following points:
1) Infectious agents can induce autoimmune diseases in several
experimental settings, some of which have clinical counterparts.
A variety of mechanisms have been invoked to explain these
observations, including molecular mimicry and an increase in the
immunogenicity of autoantigens caused by inflammation in the
target organ.(1) Paradoxically, infectious agents can also
suppress allergic and autoimmune disorders. The author
summarizes the evidence that the main factor in the increased
prevalence of these diseases in industrialized countries is the
reduction in the incidence of infectious diseases in those
countries over the past three decades. This concept is not new.
In 1966, for example, Leibowitz et al. suggested that the risk
of multiple sclerosis is increased among persons who spent their
childhood in a home with a high level of sanitation.(2) About 20
years later, Strachan observed that the risk of allergic
rhinitis was inversely linked to birth order and the size of the
family. He proposed that infections within households in early
childhood have a role in preventing allergic rhinitis.(3) Since
then, numerous epidemiologic and experimental studies have
sought to clarify and extend this so-called "hygiene hypothesis"
concerning asthma and other allergic diseases and autoimmune
disorders.
2) In general, epidemiologic data provide strong evidence of a
steady rise in the incidence of allergic and autoimmune diseases
in developed countries over the past three decades. The
incidence of many diseases of these two general types has
increased: asthma,(4) rhinitis,(5) and atopic dermatitis,
representing allergic diseases, and multiple sclerosis,
insulin-dependent diabetes mellitus (type 1 diabetes) --
particularly in young children -- and Crohn's disease,
representing autoimmune diseases. The prevalence of asthma, hay
fever, and atopic dermatitis doubled in Swedish schoolchildren
between 1979 and 1991, and in Lower Saxony, Germany, the
incidence of multiple sclerosis also doubled from 1969 to 1986.
The incidence of Crohn's disease more than tripled in northern
Europe from the 1950s to the 1990s. The incidence of these
disorders apparently began to increase in the 1950s and
continues to do so today, although the incidence of some of
these diseases may have plateaued.
3) Concomitantly, there has been an obvious decrease in the
incidence of many infectious diseases in developed countries as
a result of antibiotics, vaccination, or more simply, improved
hygiene and better socioeconomic conditions. Intestinal
infections are notable, because their frequency has decreased in
developed countries as compared with less-developed countries,
particularly among children. Moreover, the age at which
colonization of the intestinal flora occurs differs among
countries: intestinal colonization with gram-negative bacteria,
for instance, occurs later in developed than in less-developed
countries, both quantitatively and qualitatively. The high
prevalence of parasitic infections, notably with plasmodia and
schistosoma in southern countries, contrasts with the absence of
these diseases in developed countries. Furthermore, the
frequency of infestation by minor parasites such as Enterobius
vermicularis (pinworms) over the past decade has decreased in
developed countries.
4) Clinical implications: The relation between the reduction in
the incidence of infectious diseases and the increase in the
incidence of allergic and autoimmune diseases, on the one hand,
and the apparent protective effect of infections against
immune-mediated diseases, on the other hand, have clear clinical
implications. A major problem with these correlations is that
the infections contributing to protection or susceptibility are
ill defined. Moreover, certain infectious agents can trigger
allergic or autoimmune diseases.
References (abridged):
1. Olson JK, Croxford JL, Miller SD. Virus-induced autoimmunity:
potential role of viruses in initiation, perpetuation, and
progression of T-cell-mediated autoimmune disease. Viral Immunol
2001;14:227-250.
2. Leibowitz U, Antonovsky A, Medalie JM, Smith HA, Halpern L,
Alter M. Epidemiological study of multiple sclerosis in Israel.
II. Multiple sclerosis and level of sanitation. J Neurol
Neurosurg Psychiatry 1966;29:60-68.
3. Strachan DP. Hay fever, hygiene, and household size. BMJ
1989;299:1259-1260.
4. Woolcock AJ, Peat JK. Evidence for the increase in asthma
worldwide. CIBA Found Symp 1997;206:122-34.
5. Upton MN, McConnachie A, McSharry C, et al. Intergenerational
20 year trends in the prevalence of asthma and hay fever in
adults: the Midspan family study surveys of parents and
offspring. BMJ 2000;321:88-92.
New Engl. J. Med. 2002 347:911
Web Links: autoimmune diseases
Related Background:
ALLERGIC DISEASES AND THE HYGIENE HYPOTHESIS
M. Yazdanbakhsh et al (Leiden University, NL) discuss allergic
diseases, the authors making the following points:
1) There has been a significant increase in the prevalence of
allergic diseases over the past 2 to 3 decades. Currently, more
than 130 million people suffer from asthma, and the numbers are
increasing (1); nevertheless, there is a considerably lower
prevalence of allergic diseases in developing countries (2).
There are also clear differences in the prevalence of allergies
between rural and urban areas within one country. For example,
in Ethiopia, asthma is more prevalent in urban areas than in
rural villages (3), and asthma is more common in residents of
urban Germany than in farmers living in rural Bavaria (4). To
explain these observations, environmental factors associated
with more industrialized and urban living have been studied
intensively, but there is little consistent evidence to suggest
that obvious risk factors, such as increased exposure to indoor
allergens, pollution, or changes in diet and breastfeeding,
could account for the rise in atopic diseases. However, another
category of environmental factors, childhood infections, shows
an overwhelming and consistent negative association with atopy
and allergic diseases. Allergic sensitization is overrepresented
among first-born but is less frequent in children from large
families (5) and those attending day care, suggesting that a
frequent exchange of infections may have a protective effect (5).
2) Atopy, characterized by raised immunoglobulin (Ig)E levels,
underlies allergic diseases such as asthma, rhinoconjunctivitis,
and eczema. The interaction of an environmental allergen with
the innate immune system, its uptake by antigen-presenting
cells, and the subsequent T cell priming leads to the
stimulation of cytokines such as interleukin (IL)-4, IL-5, and
IL-13. These cytokines interact with their receptors to
stimulate IgE production and increased numbers of eosinophils
and mast cells; all of these components are capable of
precipitating inflammation in the respiratory tract.
3) Exposure to food and orofecal pathogens, such as hepatitis A,
Toxoplasma gondii, and Helicobacter pylori, reduces the risk of
atopy by >60%. Studies of gut commensals indicate differences in
the rate of microbial colonization, as well as the bacterial
type involved (clostridia versus lactobacilli) in children with
and without a predisposition to allergy. On the basis of these
data, it has been proposed that the lack of intense infections
in industrialized countries owing to improved hygiene,
vaccination, and use of antibiotics may alter the human immune
system such that it responds inappropriately to innocuous
substances. This so-called "hygiene hypothesis" (5) has been
given an immunological framework in which the balance between
type 1 immune responses (TH1, associated with bacterial and
viral infections and autoimmune diseases) and type 2 immune
responses (TH2, associated with helminth infections and allergic
diseases) is pivotal. It has been postulated that limited
exposure to bacterial and viral pathogens during early childhood
results in an insufficient stimulation of TH1 cells, which in
turn cannot counterbalance the expansion of TH2 cells and
results in a predisposition to allergy.
4) In summary: The increase of allergic diseases in the
industrialized world has often been explained by a decline in
infections during childhood. The immunological explanation has
been put into the context of the functional T cell subsets known
as T helper 1 (TH1) and T helper 2 (TH2) that display polarized
cytokine profiles. It has been argued that bacterial and viral
infections during early life direct the maturing immune system
toward TH1, which counterbalance proallergic responses of TH2
cells. Thus, a reduction in the overall microbial burden will
result in weak TH1 imprinting and unrestrained TH2 responses
that allow an increase in allergy.The authors suggest this
notion is contradicted by observations that the prevalence of
TH1-autoimmune diseases is also increasing and that TH2-skewed
parasitic worm (helminth) infections are not associated with
allergy. More recently, elevations of anti-inflammatory
cytokines, such as interleukin-10, that occur during long-term
helminth infections have been shown to be inversely correlated
with allergy. The authors suggest thst the induction of a robust
anti-inflammatory regulatory network by persistent immune
challenge offers a unifying explanation for the observed inverse
association of many infections with allergic disorders.
References (abridged):
1. M. R. Sears, Lancet 350, 1015 (1997)
2. The International Study of Asthma and Allergies in Childhood
Steering Committee, Lancet 351, 1225 (1998)
3. H. Yemaneberhan, et al., Lancet 350, 85 (1997)
4. O. S. von Ehrenstein, et al., Clin. Exp. Allergy 30, 187
(2000)
5. D. P. Strachan, Br. Med. J. 299, 1259 (1989)
Science 2002 296:490
Web Links: allergic diseases hygiene hypothesis
Related Background:
MEDICAL BIOLOGY: ON THE BIOLOGY OF ALLERGY AND ALLERGIC DISEASES
The term "allergy" refers to a hypersensitive reaction by the
body to foreign substances (antigens) that in similar amounts
and circumstances are harmless within the bodies of people who
do not manifest such a reaction. Antigens that provoke an
allergic reaction are called "allergens", and these include
various pollens, drugs, lints, bacteria, foods, dyes and other
chemicals.
The term "antibodies" refers to proteins produced by the immune
system, these proteins binding to and destroying or neutralizing
antigens. Lymphocytes (lymph cells, lympho-leukocytes) are a
type of leukocyte (white blood cell) involved in the immune
response. There are two classes of such lymphocytes: 1) the
"B-cells", which after a cascade of immune system events
involving a specific antigen change into proliferating specific
antibody producing blood-plasma cells; 2) the "T-cells", one
subclass of which (cytotoxic T-cells) interacts directly with
foreign invaders such as bacteria and viruses, while the other
subclass of T-cells (helper T-cells) is involved in the
proliferation of antibody-specific B-cells.
There are several types of allergic reactions. So-called "type 1
reactions" include hay fever, insect venom allergy, and asthma,
and they involve a class of antibodies known as immunoglobulin E
(IgE). IgE molecules are bound to *mast cells, which are located
in loose connective tissue. When enough antigen has bound with
the IgE antibodies, the mast cells release granules of
*histamine and *heparin, and produce other substances such as
*leukotrienes. These chemicals dilate blood vessels and
constrict bronchial air passages. Histamine is apparently
responsible for the visible symptoms of an allergic attack:
e.g., running nose, wheezing, and tissue swelling. The
predisposition of a person to type 1 allergic reactions is
apparently genetically determined.
A.B. Kay (Imperial College School of Medicine London, UK)
presents a review of allergy and allergic diseases, the author
making the following points concerning the biology of allergy:
1) The author points out that the term "allergy" was introduced
in 1906 by Clemens P. Pirquet [von Cesenatico] (1874- 1929), who
used the term to describe both protective immunity and
hypersensitivity reactions, but over time, the term has come to
be used exclusively for hypersensitivity reactions. The term
"atopy" (from the Greek _atopos_, meaning out of place) is often
used to describe IgE-mediated diseases. Persons with atopy have
a hereditary predisposition to produce IgE antibodies against
common environmental allergens and have one or more "atopic
diseases": allergic rhinitis, asthma, or atopic eczema. Some
allergic diseases, such as *contact dermatitis and
*hypersensitivity pneumonitis, develop via IgE-independent
mechanisms and can be considered non-atopic allergic conditions.
2) The author points out that everyone inhales aero- allergens
derived from pollen, house-dust mites, and cat dander. In
general, adults and children without atopy mount a low-grade
immune response to these aero-allergens, producing several types
of immunoglobulin antibodies, but not IgE antibodies. Persons
with atopy, by contrast, have an exaggerated immune response to
these aero-allergens, the response characterized by the
production of allergen-specific IgE antibodies, and such persons
have elevated serum levels of IgE antibodies and positive
reactions to extracts of common aero-allergens in skin-prick
tests. In general, the immunopathological hallmark of allergic
disease is the infiltration of affected tissue by a specific
type (type 2) of T-helper cells. The types of T-helper cells are
distinguished on the basis of the types of *cytokines they
produce when activated.
3) In utero, T cells of the fetus are primed by common
environmental allergens that cross the placenta, with the immune
response of virtually all newborn infants dominated by type 2
T-helper cells. It has been proposed that during subsequent
development the normal (i.e., non-atopic) infant's immune system
shifts in favor of a type 1 T-helper cell-mediated response to
inhaled allergens, whereas in the potentially atopic infant
there is a further increase in type 2 T-helper cells that were
primed in utero. Microbes are probably the chief stimuli of
protective type 1 T-helper cell immunity.
4) The author suggests the marked increase in the prevalence of
atopic disease in western Europe, the US, and Australasia during
recent years indicates the importance of environmental
influences. An informative example is the change in the
incidence of seasonal allergic rhinitis and asthma after the
reunification of Germany. These disorders were less common in
East Germany than in West Germany before reunification, whereas
since reunification, the prevalence of atopy and hay fever, but
not asthma, has increased among children who spent their early
childhood in East Germany. The author suggests this phenomenon
raises the possibility that a Western lifestyle accounts for the
increase in prevalence. Perhaps in Western countries the
developing immune system is deprived of the microbial antigens
that stimulate type 1 T-helper cells, because the environment is
relatively clean and the use of antibiotics for minor illnesses
in early life is widespread. The author suggests the results of
epidemiological studies seaport this theory.
New Engl. J. Med. 2001 344:30
Text Notes:
... ... *mast cells: Mast cells are white blood cells
(leukocytes) containing dense granules of various substances,
with mast cells often associated with connective tissue.
... ... *histamine: A local hormone that acts as a powerful
stimulant of gastric secretion, constriction of bronchial smooth
muscle, and dilation of blood vessels.
... ... *heparin: The heparins are polymers of O- and N-linked
sulfated glucosamines and hexuronic acids (iduronic and
glucouronic) joined by glycoside linkages, and they are the most
acidic organic acids in the human body. When administered as
pharmacological agents, the heparins have anticoagulant
activity, but they are not ordinarily present in blood, and
their normal function has been a mystery. Mast cells are one of
the two types of cells (the other type being basophils) that
synthesize heparin.
... ... *leukotrienes: In general, a "leukotriene" is a member
of a family of pharmacologically active substances that are
products of eicosanoid metabolism (usually, arachidonic acid),
some of which contain a peptide moiety based on cysteine. The
leukotrienes are classified as "local hormones", i.e., hormones
that are not stored, but which are synthesized in response to
specific stimuli. They are formally derived from eicosanoic acid
and contain a set of 3 conjugated double bonds (thus the suffix
"-triene"). They were originally discovered in association with
leukocytes (thus the prefix "leuko-")
... ... *contact dermatitis: In general, a skin rash resulting
from exposure to either an irritating (e.g., an acid) or
allergic substance.
... ... *hypersensitivity pneumonitis: A chronic progressive
form of pneumonia resulting from exposure to any of a variety of
antigens.
... ... *cytokines: In general, a cytokine is any substance that
promotes cell growth and cell division.
Related Background Brief:
INCREASING INCIDENCE OF MULTIPLE SCLEROSIS IN SOUTH LOWER
SAXONY, GERMANY. In the epidemiological area of South Lower
Saxony the prevalence of multiple sclerosis increased from
51/100,000 in 1969 to 99 in 1986. The mean annual incidence
increased from 2.6 for the period from 1964-1974 to 4.6 for
1975-1985. This trend is significant (p = 0.0068). Diagnostic
criteria, methods of case finding and analysis of the data
remained stable. Minor necessary changes as for example due to
new data protection laws and new handling of early cases by
practicing physicians can hardly explain this significant
increase. In consideration of similar reports from all over the
world biological exogenous factors are suspected but remain to
be identified. S. Poser et al: Neuroepidemiology 1989;8(4):207.
Related Background Brief:
ScienceWeek http://www.scienceweek.com
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12. ON HUMAN USE OF THE BIOSPHERE
M. Wackernagel et al (Redefining Progress, US) discuss human use
of the biosphere, the authors making the following points:
1) The human economy depends on the planet's natural capital,
which provides all ecological services and natural resources.
Drawing on natural capital beyond its regenerative capacity
results in depletion of the capital stock. Through comprehensive
resource accounting that compares human demand to the biological
capacity of the globe, it should be possible to detect this
depletion to help prepare a path toward sustainability.
2) The authors report a study to develop such an accounting
framework, and to measure the extent of humanity's current
demand on the planet's bioproductive capacity. The authors
report they build on many earlier attempts to create
comprehensive measures of human impact on the biosphere. For
example, Vitousek et al. (1) used consumption estimates to
calculate humanity's appropriation of the biosphere's Net
Primary Productivity (NPP). They concluded that the human
economy co-opted organic material equivalent to 40% of the NPP
of terrestrial ecosystems in 1980. Odum developed a conceptual
basis for accounting for energy flows through ecosystems and
human economies, but did not produce overall accounts (2).
Fischer-Kowalski and Huettler (3) advanced the concept of
"societal metabolism," using material flow analysis as a macro
indicator for the environmental performance of societies. The
Global Environment Outlook 2000 (4) and World Resources
2000-2001 (5) describe human impacts on various ecosystem types
in detail, but both reports lack an aggregated summary of the
impacts. Others have analyzed the integrity of subcomponents of
the biosphere, such as carbon cycles, freshwater use, and the
nitrogen cycle, have assigned approximate monetary values to the
ecological services that humanity depends on, or established
frameworks for monetary natural capital accounts for nations.
3) In summary: Sustainability requires living within the
regenerative capacity of the biosphere. In an attempt to measure
the extent to which humanity satisfies this requirement, the
authors use existing data to translate human demand on the
environment into the area required for the production of food
and other goods, together with the absorption of wastes. The
authors suggest that human demand may well have exceeded the
biosphere's regenerative capacity since the 1980s. According to
this preliminary and exploratory assessment, humanity's load
corresponded to 70% of the capacity of the global biosphere in
1961, and grew to 120% in 1999.
References (abridged):
1. Vitousek, P. M. , Ehrlich, P. R. , Ehrlich, A. H. & Matson,
P. A. (1986) BioScience 34, 368-373.
2. Odum, H. T. (1996) Environmental Accounting: EMERGY and
Environmental Decision-Making (Wiley, New York).
3. Fischer-Kowalski, M. & Huettler, W. (1998) J. Ind. Ecol. 2,
107-137.
4. United Nations Environment Program & Stockholm Environment
Institute. (1999) Global Environment Outlook 2000 (Oxford Univ.
Press, New York).
5. World Resources Institute, United Nations Development
Program, United Nations Environment Program & World Bank. (2000)
World Resources 2000-2001, People and Ecosystems: The Fraying
Web of Life (Oxford Univ. Press, New York).
Proc. Nat. Acad. Sci. 2002 99:9266
Web Links: global ecology human use of biosphere
Related Background:
HUMAN USE OF GLOBAL PHOTOSYNTHESIS
S. Rojstaczer et al (Duke University, US) discuss human use of
global photosynthesis, the authors making the following points:
1) Human use of photosynthesis products is pervasive, including
direct use of plants for food and fiber as well as indirect use
from grazing by domesticated animals. Population increases have
led to speculation and estimates that the human footprint on the
biosphere, in terms of the use of both plants and fresh water,
is approaching the limit of planet sustainability.
2) A key measure of human impact on the biosphere and
hydrosphere is human use of terrestrial net primary production,
which represents the net energy (production minus respiration)
created by carbon fixation on land. Previous estimates of global
human appropriation of this biological resource -- which governs
the total amount of food available on Earth -- and its
surrogates have used mean estimates of parameters, the estimates
made on the basis of limited small-scale field studies.
3) The authors report a study incorporating contemporary data,
many of which are satellite-based, to estimate the human
appropriation of photosynthesis products and quantify the
uncertainty in our knowledge of this appropriation. The authors
report they estimate that humans appropriate 10 to 55 percent of
terrestrial photosynthesis products. This broad range reflects
uncertainty in key parameters and makes it difficult to
ascertain whether we are approaching crisis levels in our use of
the planet's resources. Improved estimates will require
high-resolution global measures within agricultural lands and
tropical forests.
Science 2001 294:2549
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